Takafumi Misaki, Fumiko Murao, Kayo Shinomiya, Akihiro Tani, Masayuki Yamada and Yoshinori Mitamura : A Case of Osteopetrosis with Orbital Inflammation Secondary to Maxillary Osteomyelitis., Case Reports in Ophthalmology, Vol.15, No.1, 92-99, 2024.
(Summary)
This is a rare case of maxillary osteomyelitis associated with osteopetrosis, causing orbital inflammation.
Takaaki Sugisawa, Hiroto Ishikawa, Kazutaka Uchida, Yoshio Takesue, Junya Mori, Takamasa Kinoshita, Shohei Morikawa, Fumiki Okamoto, Tomoko Sawada, Masahito Ohji, Takayuki Kanda, Masaru Takeuchi, Akiko Miki, Sentaro Kusuhara, Tetsuo Ueda, Nahoko Ogata, Masahiko Sugimoto, Mineo Kondo, Shigeo Yoshida, Tadahiko Ogata, Kazuhiro Kimura, Yoshinori Mitamura, Tatsuya Jujo, Hitoshi Takagi, Hiroto Terasaki, Taiji Sakamoto, Yuki Komuku and Fumi Gomi : Risk Factors for Legal Blindness in 77 Japanese Patients with Endogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST., Ocular Immunology and Inflammation, Vol.31, No.7, 1505-1512, 2023.
(Summary)
Endogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatments, as well as other advances in medical knowledge and technology.
(Keyword)
Humans / Blindness / Cohort Studies / East Asian People / Endophthalmitis / Eye Infections, Bacterial / Retrospective Studies / Risk Factors / Visual Acuity
Hirotaka Yokouchi, Daisuke Nagasato, Yoshinori Mitamura, Mariko Egawa, Hitoshi Tabuchi, Sonoko Misawa, Satoshi Kuwabara and Takayuki Baba : Alterations in choroidal vascular structures due to serum levels of vascular endothelial growth factor in patients with POEMS syndrome., Scientific Reports, Vol.13, No.1, 2023.
(Summary)
A higher serum vascular endothelial growth factor (VEGF) level can cause choroidal thickening in the choroid of patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. We aimed to determine whether fluctuations in serum VEGF levels affect choroidal vascular structures in patients with POEMS syndrome. This retrospective observational case series examined 17 left eyes of 17 patients with POEMS syndrome. Enhanced depth imaging optical coherence tomography (EDI-OCT) images were obtained, and serum VEGF levels were measured at baseline and 6 months after transplantation with dexamethasone (n = 6), thalidomide (n = 8), or lenalidomide (n = 3). EDI-OCT images were binarized using ImageJ software, and we calculated the areas of the whole choroid and the luminal and stromal areas. Subsequently, we determined whether the choroidal vascular structure had changed significantly between baseline and 6 months after treatment. Six months after treatment, serum VEGF levels and the whole choroid, luminal, and stromal areas had decreased significantly compared to the baseline values (all, P < 0.001). The mean luminal area to the whole choroidal area ratio at 6 months after treatment was 0.70 ± 0.03, which was significantly smaller than the ratio at baseline (0.72 ± 0.03; P < 0.001). Whole choroid and luminal area fluctuations were significantly positively correlated with fluctuations in serum VEGF levels (r = 0.626, P = 0.007 and r = 0.585, P = 0.014, respectively). Choroidal thickening induced by VEGF might be caused by increases in the choroidal vessel lumen area. These results may offer insights into the pathogenesis of POEMS syndrome and the role of serum VEGF in choroidal vascular structure, which may apply to other ocular diseases.
Daisuke Nagasato, Takahiro Sogawa, Mao Tanabe, Hitoshi Tabuchi, Shogo Numa, Akio Oishi, Hanako Ikeda Ohashi, Akitaka Tsujikawa, Tadao Maeda, Masayo Takahashi, Nana Ito, Gen Miura, Terumi Shinohara, Mariko Egawa and Yoshinori Mitamura : Estimation of Visual Function Using Deep Learning From Ultra-Widefield Fundus Images of Eyes With Retinitis Pigmentosa., JAMA Ophthalmology, Vol.141, No.4, 305-313, 2023.
(Summary)
Results of this study suggest that the visual function estimation in patients with retinitis pigmentosa from ultra-widefield fundus autofluorescence images using deep learning might help assess disease progression objectively. Findings also suggest that deep learning models might monitor the progression of retinitis pigmentosa efficiently during follow-up.
Masahiko Shimura, Shigehiko Kitano, Nahoko Ogata, Yoshinori Mitamura, Hideyasu Oh, Haruka Ochi, Shino Ohsawa and Akito Hirakata : Efficacy, durability, and safety of faricimab with extended dosing up to every 16 weeks in Japanese patients with diabetic macular edema: 1-year results from the Japan subgroup of the phase 3 YOSEMITE trial., Japanese Journal of Ophthalmology, Vol.67, No.3, 264-279, 2023.
(Summary)
Consistent with global results, faricimab up to Q16W offered durable vision gains and improved anatomic and disease-specific outcomes among Japanese patients with DME.
(Keyword)
Humans / Angiogenesis Inhibitors / Diabetes Mellitus / Diabetic Retinopathy / East Asian People / Intravitreal Injections / Japan / Macular Edema / Receptors, Vascular Endothelial Growth Factor / Recombinant Fusion Proteins / Treatment Outcome / Visual Acuity
Tomo Nishi, Tetsuo Ueda, Yuutaro Mizusawa, Kayo Shinomiya, Yoshinori Mitamura, Naoki Kimura, Fumi Gomi, Akiko Miki, Makoto Nakamura, Takamasa Kinoshita, Shumpei Obata, Masahito Ohji, Takuya Tsuji, Shigeo Yoshida and Nahoko Ogata : Effect of foveal morphology on visual acuity in 4-6-year-old children with retinopathy of prematurity: a J-CREST study., Scientific Reports, Vol.12, No.1, 2022.
(Summary)
Laser therapy is the most effective treatment considered for retinopathy of prematurity (ROP). We compared the foveal morphology of the retina in eyes with a history of ROP to that of full-term children. This cross-sectional comparative study included 74 patients with a history of ROP, aged 4-6 years. Among them, 41 underwent laser treatment for ROP. The clinical findings and retinal morphology in these patients were compared to that of 33 patients who had spontaneous ROP regression and 30 age-matched full-term controls. All the patients with ROP had 20/40 or better best-corrected visual acuity (BCVA). The foveal thickness was significantly thicker in laser-treated ROP eyes than in regressed ROP eyes and controls. The outer nuclear layer was significantly thicker, and the inner segment (IS) of the photoreceptors and the inner retinal layer were significantly thicker in the laser-treated ROP eyes than that in the control eyes. In the patients with ROP and controls, better BCVA was associated positively with deeper foveal depression, which was associated with a later gestational age. Our results suggest that prematurity and laser treatment affect the foveal morphology and BCVA.
Takeshi Kimura, Takashi Araki, Tsutomu Yasukawa, Aki Kato, Soichiro Kuwayama, Takamasa Kinoshita, Fumiki Okamoto, Tomoya Murakami, Yoshinori Mitamura, Taiji Sakamoto, Hiroto Terasaki, Sentaro Kusuhara, Akiko Miki, Yoshihiro Takamura, Mineo Kondo, Hisashi Matsubara, Tetsuo Ueda, Hiroki Tsujinaka and Fumi Gomi : Differences in clinical characteristics and treatment outcomes of submacular hemorrhage caused by age-related macular degeneration and retinal macroaneurysms: A multicenter survey from the Japan Clinical Retina Study (J-CREST) group., PLoS ONE, Vol.17, No.9, 2022.
(Summary)
The characteristics of, and treatment strategy for, SMH were different between the underlying diseases. Anti-vascular endothelial growth factor treatment with or without expansile gas was mainly chosen for SMH in tnAMD and PCV, whereas vitrectomy with gas was the most common treatment for RAM, and the higher rate for vitrectomy might result in the greater BCVA improvement in the RAM group than in the other groups. Final BCVA was better in PCV, RAM, and tnAMD, in that order, because patients with PCV were younger and had better baseline BCVA.
The recommended treatment for SMHs secondary to nAMD exceeding 2 disc area and with BCVA below 20/40 is vitrectomy or pneumatic displacement for visual improvement.
Daisuke Nagasato, Yuki Muraoka, Mao Tanabe, Naomi Nishigori, Rie Osaka, Yoshinori Mitamura, Hitoshi Tabuchi, Shin Kadomoto, Tomoaki Murakami, Sotaro Ooto, Kiyoshi Suzuma and Akitaka Tsujikawa : Foveal Thickness Fluctuation in Anti-VEGF Treatment for Branch Retinal Vein Occlusion: A Long-term Study., Ophthalmology. Retina, Vol.6, No.7, 567-574, 2022.
(Summary)
Foveal thickness fluctuation was significantly associated with visual acuity and foveal photoreceptor status. Thus, the morphologic and functional prognoses of eyes with BRVO may improve with the identification of the characteristics of eyes with greater FTF and consequently controlling the FTF more strictly.
Hayato Tanaka, Daisuke Nagasato, Shunsuke Nakakura, Toshihiko Nagasawa, Hiroyuki Wakuda, Akihiro Kurusu, Yoshinori Mitamura and Hitoshi Tabuchi : Branch retinal vein occlusion post severe acute respiratory syndrome coronavirus 2 vaccination., Taiwan Journal of Ophthalmology, Vol.12, No.2, 202-205, 2022.
(Summary)
In this article, we report two patients who experienced the first onset of branch retinal vein occlusion (BRVO) 3 days after the administration of the BNT162b2 (Pfizer-BioNTech) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Case 1: A 50-year-old woman without any history of retinal disease developed vision loss in her right eye 3 days after receiving the first dose of the SARS-CoV-2 mRNA vaccine. Case 2: A 56-year-old woman without any history of retinal disease developed vision loss in her right eye 3 days after receiving the first dose of the SARS-CoV-2 mRNA vaccine. Case 1: Temporal superior BRVO and secondary macular edema (ME) were observed in the patient's right eye. Her best-corrected visual acuity (BCVA) was 20/25. Case 2: Temporal inferior BRVO and secondary ME were observed in the patient's right eye. Her BCVA was 13/20. Case 1: Three doses of intravitreal ranibizumab (IVR) were administered. Case 2: Three doses of IVR were administered. Case 1: ME resolved and BCVA improved to 20/20. Case 2: ME resolved and BCVA improved to 20/20. Both the cases showed a possible association between the SARS-CoV-2 vaccination and the first onset of BRVO.
In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME.
Hiroki Sano, Kazuhiko Namekata, Masanori Niki, Kentaro Senba, Fumiko Murao, Takayuki Harada and Yoshinori Mitamura : Ocular expression of cyclin-dependent kinase 5 in patients with proliferative diabetic retinopathy., Journal of Diabetes Investigation, Vol.13, No.4, 628-637, 2022.
(Summary)
Cdk5 activation is involved in PDR pathogenesis through PPARγ expression, and inhibition of Cdk5-mediated PPARγ phosphorylation might be a new therapeutic target for treatment of PDR.
Keisuke Minami, Mariko Egawa, Keisuke Kajita, Fumiko Murao and Yoshinori Mitamura : A Case of Vogt-Koyanagi-Harada Disease-Like Uveitis Induced by Nivolumab and Ipilimumab Combination Therapy., Case Reports in Ophthalmology, Vol.12, No.3, 952-960, 2021.
(Summary)
Nivolumab and ipilimumab are widely used immune checkpoint inhibitors (ICPIs) for the treatment of metastatic melanoma. ICPIs cause an array of side effects called immune-related adverse events (IRAEs) due to activation of an immune response. ICPI-uveitis can cause irreversible vision loss if untreated. There are few reports of recurrent Vogt-Koyanagi-Harada (VKH) disease-like uveitis induced by nivolumab and ipilimumab. We report a case of VKH disease-like uveitis recurrence after resuming ICPIs. A 73-year-old man with advanced melanoma was referred to our clinic with visual loss 25 days after starting nivolumab/ipilimumab. His corrected visual acuity was 0.5 in the right eye and 0.02 in the left eye. Enhanced-depth imaging optical coherence tomography (EDI-OCT) showed marked choroid thickening. The patient was diagnosed with VKH disease-like uveitis due to IRAEs. Subtenon injection of triamcinolone acetonide was performed, and nivolumab/ipilimumab was suspended, but serous retinal detachment (SRD) markedly worsened and choroidal detachment appeared. With 2 courses of steroid pulse therapy and oral steroids, SRD disappeared, and corrected visual acuity recovered in both eyes. Five months after the first injection, exacerbation of melanoma was observed, and nivolumab and oral steroids were restarted. Six weeks later, an increase in choroidal thickness was observed with EDI-OCT and diagnosed as a recurrence of VKH disease-like uveitis. Monitoring for the recurrence of VKH disease-like uveitis during the administration of ICPIs, even after uveitis is treated, is essential. Assessment of choroidal thickness with EDI-OCT may be useful for detecting early signs of VKH disease-like uveitis.
Mineo Kondo, Hidetaka Noma, Masahiko Shimura, Masahiko Sugimoto, Yoshitsugu Matsui, Kumiko Kato, Yoshitsugu Saishin, Masahito Ohji, Hiroto Ishikawa, Fumi Gomi, Kensaku Iwata, Shigeo Yoshida, Sentaro Kusuhara, Hiromasa Hirai, Nahoko Ogata, Takao Hirano, Toshinori Murata, Kotaro Tsuboi, Motohiro Kamei, Takamasa Kinoshita, Soichiro Kuwayama, Yoshio Hirano, Manami Ohta, Kazuhiro Kimura, Kei Takayama, Masaru Takeuchi, Yoshihiro Takamura, Fumiki Okamoto, Yoshinori Mitamura, Hiroto Terasaki, Taiji Sakamoto and J-Crest On Behalf Of Japan Clinical Retina Study Group : Background Factors Affecting Visual Acuity at Initial Visit in Eyes with Central Retinal Vein Occlusion: Multicenter Study in Japan., Journal of Clinical Medicine, Vol.10, No.23, 2021.
(Summary)
The results indicate that an older age, a known strong factor, and the right eye were significantly associated with poorer BCVA at the initial visit to the hospital. These results suggest that functional and/or anatomical differences between the right and left eyes may be involved in these results.
Kayo Shinomiya, Takashi Fujikado, Akiko Kitora, Satoe Okamoto, Akiko Iwata, Yoko Oogushi and Yoshinori Mitamura : Depth Perception with a Newly Developed Microscope Stereotest., Clinical Ophthalmology, Vol.15, 3901-3908, 2021.
(Summary)
Depth perception under the microscope is more accurate under the binocular than in the monocular condition, indicating the potential role of stereopsis. Anisometropia deteriorates depth perception, suggesting that refractive error should be corrected during microscopic work, such as during ophthalmic surgery.
Tomoko Sawada, Tsutomu Yasukawa, Hiroko Imaizumi, Hisashi Matsubara, Kazuhiro Kimura, Hiroto Terasaki, Hiroto Ishikawa, Tomoya Murakami, Masaru Takeuchi, Yoshinori Mitamura, Mariko Yamashita, Yoshihiro Takamura, Toshinori Murata, Jiro Kogo and Masahito Ohji : Ten-year changes in visual acuity at baseline and at 2 years after treatment in a Japanese population with age-related macular degeneration., Graefe's Archive for Clinical and Experimental Ophthalmology, Vol.259, No.5, 1191-1198, 2021.
(Summary)
Baseline BCVA with treatment-naïve nAMD tended to become better during the study period. BCVA at 1 year improved in the era of anti-VEGF; BCVA at 2 years improved in patients who underwent initial treatment in 2012 or later; and CRST decreased in each year during the study period.
Yoshinori Mitamura, Tserennadmid Enkhmaa, Hiroki Sano, Masanori Niki, Fumiko Murao, Mariko Egawa, Shozo Sonoda and Taiji Sakamoto : Changes in choroidal structure following intravitreal aflibercept therapy for retinal vein occlusion., The British journal of Ophthalmology, Vol.105, No.5, 704-710, 2021.
(Summary)
RVO induces substantial oedema of the choroidal stromal area that is detectable by binarisation of EDI-OCT images. This stromal oedema likely stems from high intraocular vascular endothelial growth factor levels. Changes in choroidal structure may be used to assess severity and prognosis of RVO.
Ryoh Funatsu, Hiroto Terasaki, Hideki Shiihara, Sumihiro Kawano, Mariko Hirokawa, Yasushi Tanabe, Tomoharu Fujiwara, Yoshinori Mitamura, Taiji Sakamoto and Shozo Sonoda : Quantitative evaluations of vortex vein ampullae by adjusted 3D reverse projection model of ultra-widefield fundus images., Scientific Reports, Vol.11, No.1, 2021.
(Summary)
The purpose of this study was to determine the number and location of vortex vein ampullae (VVA) in normal eyes. This was an observational retrospective study. Montage images of one on-axis and two off-axis ultra-widefield images of 74 healthy eyes were enhanced, and reverse projected onto a 3D model eye. The number and distance between the optic disc to each VVA in the four sectors were compared. The significance of correlations between these values and age, sex, visual acuity, refractive error, and axial length was determined. The mean number of VVA was 8.10/eye with 1.84, 2.12, 2.19 and 1.95 in upper lateral, lower lateral, upper nasal, and lower nasal sectors, respectively. The mean number of VVA/eye was significantly greater in men at 8.43 than women at 7.76 (P = 0.025). The mean distance between the optic disc and VVA was 14.15 mm, and it was 14.04, 15.55, 13.29 and 13.66 mm in the upper lateral, lower lateral, upper nasal and lower nasal sectors, respectively (all P < 0.05). The number and location of VVA can be obtained non-invasively, and the number was significantly higher in men than women. This technique can be used to determine whether these values are altered in a retinochoroidal disease.
Toshihiko Nagasawa, Hitoshi Tabuchi, Hiroki Masumoto, Shoji Morita, Masanori Niki, Zaigen Ohara, Yuki Yoshizumi and Yoshinori Mitamura : Accuracy of Diabetic Retinopathy Staging with a Deep Convolutional Neural Network Using Ultra-Wide-Field Fundus Ophthalmoscopy and Optical Coherence Tomography Angiography., Journal of Ophthalmology, Vol.2021, 2021.
(Summary)
The combination of Optos and OCTA imaging with DCNN could detect DR at desirable levels of accuracy and may be useful in clinical practice and retinal screening. Although the combination of multiple imaging techniques might overcome their individual weaknesses and provide comprehensive imaging, artificial intelligence in classifying multimodal images has not always produced accurate results.
Hiroto Ishikawa, Kazutaka Uchida, Yoshio Takesue, Junya Mori, Takamasa Kinoshita, Shohei Morikawa, Fumiki Okamoto, Tomoko Sawada, Masahito Ohji, Takayuki Kanda, Masaru Takeuchi, Akiko Miki, Sentaro Kusuhara, Tetsuo Ueda, Nahoko Ogata, Masahiko Sugimoto, Mineo Kondo, Shigeo Yoshida, Tadahiko Ogata, Kazuhiro Kimura, Yoshinori Mitamura, Tatsuya Jujo, Hiroto Terasaki, Taiji Sakamoto, Takaaki Sugisawa, Yuki Komuku and Fumi Gomi : Clinical Characteristics and Outcomes in 314 Japanese Patients with Bacterial Endophthalmitis: A Multicenter Cohort Study from J-CREST., Pathogens, Vol.10, No.4, 2021.
(Summary)
were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye pain, bacterial identification, and poor BCVA at baseline were risk factors for final visual impairment.
Daisuke Nagasato, Yoshinori Mitamura, Mariko Egawa, Fumiko Murao, Toshihiko Nagasawa, Natsumi Komori, Shozo Sonoda, Taiji Sakamoto and Hitoshi Tabuchi : Changes in Choroidal Component Ratio and Circulation After Coffee Intake in Healthy Subjects., Investigative Ophthalmology & Visual Science, Vol.62, No.3, 2021.
(Summary)
Coffee-induced choroidal thinning may result mainly from a reduction in the choroidal vessel lumen, and this vessel lumen reduction correlated with an increased choroidal blood flow velocity after coffee intake. These coffee-induced changes in choroidal component ratio and circulation should be considered when evaluating choroids.
Masakazu Morioka, Yoshihiro Takamura, Kazuki Nagai, Shigeo Yoshida, Junya Mori, Masaru Takeuchi, Tomoko Sawada, Kumiko Sone, Hisashi Fukuyama, Sentaro Kusuhara, Tsutomu Yasukawa, Tomoya Murakami, Hitoshi Tabuchi, Daisuke Nagasato, Takao Hirano, Tetsuo Ueda, Tatsuya Jujo, Hirofumi Sasajima, Yoshinori Mitamura, Kunihiro Ishikawa and Masaru Inatani : Incidence of endophthalmitis after intravitreal injection of an anti-VEGF agent with or without topical antibiotics., Scientific Reports, Vol.10, No.1, 2020.
(Summary)
Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard treatment modality in various types of retinal diseases. However, endophthalmitis remains the most serious complication. Despite the lack of evidence that antibiotics prevent endophthalmitis, topical antibiotics are still used routinely in Japan. We conducted a retrospective multicenter study by analyzing records from patients who underwent IVI of anti-VEGF agents with or without antibiotic treatment. In the analysis of a total of 147,440 eyes, the incidence of endophthalmitis was 0.007%: 0.005% with no use of antibiotics, 0.009% with antibiotic pretreatment, 0.012% with posttreatment, and 0.005% with pre- and posttreatment. There was no statistically significant difference among the four groups (chi-square test, p = 0.57). Most facilities used masks, sterilized gloves, and drapes. Nine of the 10 eyes that developed endophthalmitis received topical antibiotics, and all infected eyes underwent IVI with aflibercept, not the prefilled syringe delivery system. In four patients who received multiple IVI, the detection of causative bacteria revealed resistance to used antibiotics. Data from this large population, treated with or without antibiotics, suggests that antibiotic prophylaxis does not reduce the rate of endophthalmitis after IVI.
(Keyword)
Angiogenesis Inhibitors / Anti-Bacterial Agents / Antibiotic Prophylaxis / Endophthalmitis / Humans / Incidence / Intravitreal Injections / Public Health Surveillance / Retinal Diseases / Surveys and Questionnaires / Vascular Endothelial Growth Factor A
Daisuke Nagasato, Yuki Muraoka, Rie Osaka, Yuko Iida-Miwa, Yoshinori Mitamura, Hitoshi Tabuchi, Shin Kadomoto, Tomoaki Murakami, Sotaro Ooto, Kiyoshi Suzuma and Akitaka Tsujikawa : Factors associated with extremely poor visual outcomes in patients with central retinal vein occlusion., Scientific Reports, Vol.10, No.1, 2020.
(Summary)
Here, we examined prognostic factors for extremely poor visual outcomes in patients with central retinal vein occlusion (CRVO) in actual practices. We included 150 consecutive eyes with treatment-naïve acute CRVO from four different facilities and observed them for over 24 months. Macular edema (ME) was treated with one or three monthly anti-vascular endothelial growth factor injections (1 or 3 + pro re nata). According to the final Snellen visual acuity (VA), we divided the patients into very poor VA (< 20/200) and control (≥ 20/200) groups and examined risk factors for poor final visual outcomes. The baseline Snellen VA was hand motion to 20/13. The mean number of anti-VEGF injections for ME was 5.3 ± 3.7 during the follow-up period. In total, 49 (32.7%) patients exhibited a very poor final VA; this group comprised significantly older patients with a significantly poorer baseline VA (P < 0.01 for both) than the control group. Comorbid internal carotid artery disease and diabetic retinopathy were significantly associated with a poor final VA. In actual clinical practice, visual outcomes may be extremely poor despite ME treatment in certain patients with CRVO, with advanced age, poor baseline VA, and comorbid internal carotid artery disease and diabetic retinopathy being significant risk factors.
Daisuke Nagasato, Hitoshi Tabuchi, Hiroki Masumoto, Takanori Kusuyama, Yu Kawai, Naofumi Ishitobi, Hiroki Furukawa, Shouto Adachi, Fumiko Murao and Yoshinori Mitamura : Prediction of age and brachial-ankle pulse-wave velocity using ultra-wide-field pseudo-color images by deep learning., Scientific Reports, Vol.10, No.1, 2020.
(Summary)
This study examined whether age and brachial-ankle pulse-wave velocity (baPWV) can be predicted with ultra-wide-field pseudo-color (UWPC) images using deep learning (DL). We examined 170 UWPC images of both eyes of 85 participants (40 men and 45 women, mean age: 57.5 ± 20.9 years). Three types of images were included (total, central, and peripheral) and analyzed by k-fold cross-validation (k = 5) using Visual Geometry Group-16. After bias was eliminated using the generalized linear mixed model, the standard regression coefficients (SRCs) between actual age and baPWV and predicted age and baPWV from the UWPC images by the neural network were calculated, and the prediction accuracies of the DL model for age and baPWV were examined. The SRC between actual age and predicted age by the neural network was 0.833 for all images, 0.818 for central images, and 0.649 for peripheral images (all P < 0.001) and between the actual baPWV and the predicted baPWV was 0.390 for total images, 0.419 for central images, and 0.312 for peripheral images (all P < 0.001). These results show the potential prediction capability of DL for age and vascular aging and could be useful for disease prevention and early treatment.
(Keyword)
Adult / Aged / Ankle Brachial Index / Color Perception / Deep Learning / Female / Humans / Hypertension / Male / Middle Aged / Pulse Wave Analysis
Fumiko Murao, Takamasa Kinoshita, Takashi Katome, Hiroki Sano, Masanori Niki and Yoshinori Mitamura : Suspected Gentamicin-Induced Retinal Vascular Occlusion after Vitrectomy., Case Reports in Ophthalmology, Vol.11, No.2, 473-480, 2020.
(Summary)
Retinal vascular occlusion after ocular surgery is a rare but serious complication. A history of cardiovascular diseases, retrobulbar anesthesia injection, high intraocular pressure during the perioperative period, and drug toxicity have been reported as possible causative factors. We report here two cases of multiple retinal vascular occlusions after the subconjunctival injection of gentamicin at the end of uncomplicated 25-gauge vitrectomy. Case 1 was a 61-year-old man who developed a macular hole in the right eye. Phacovitrectomy with gas tamponade was performed. On postoperative day (POD) 1, dot hemorrhage was observed on the temporal side of the optic disk. On POD10, macular whitening, retinal hemorrhage, and multiple occlusion of retinal arteries and veins were observed. Case 2 was a 51-year-old woman who was diagnosed with rhegmatogenous retinal detachment in the right eye and underwent phacovitrectomy with gas tamponade. On POD3, macular whitening with cotton wool spots and retinal hemorrhage were observed with macular ischemia owing to occlusion of retinal arteries and veins. In both cases, subconjunctival injection of gentamicin given at the end of surgery was the most suspected cause of retinal vascular occlusion.
Hideki Shiihara, Shozo Sonoda, Hiroto Terasaki, Naoko Kakiuchi, Takehiro Yamashita, Eisuke Uchino, Fumiko Murao, Hiroki Sano, Yoshinori Mitamura and Taiji Sakamoto : Quantitative analyses of diameter and running pattern of choroidal vessels in central serous chorioretinopathy by en face images., Scientific Reports, Vol.10, No.1, 9591, 2020.
(Summary)
This study was to investigate the choroidal vessels in eyes with central serous chorioretinopathy (CSC) quantitatively. We studied 41 CSC eyes and their fellow eyes, and 41 normal eyes of 41 age-adjusted individuals. En-face optical coherence tomography image of the top 25% slab of Haller's layer was analyze. The mean vessel area, vessel length, and vessel diameter were calculated. The running pattern of the vessels was quantified and used to determine the degree of symmetry, the "symmetry index". The vessel area of CSC eyes was not significantly different from that of fellow eyes but significantly larger than that of normal eyes. The vessel length of CSC eyes was not significantly different from fellow eyes but significantly shorter than that of normal eyes. The mean vessel diameter was larger in CSC eyes than in the fellow eyes and the normal eye. The symmetry index was not significantly different in CSC eyes from that of their fellow eyes but was smaller than that of normal eyes. The quantitative analysis showed that eyes with CSC had larger choroidal vessels and asymmetrical vessels running in Haller's layer.
Tomo Nishi, Tetsuo Ueda, Yuutaro Mizusawa, Kentaro Senba, Kayo Shinomiya, Yoshinori Mitamura, Shozo Sonoda, Eisuke Uchino, Taiji Sakamoto and Nahoko Ogata : Effect of optical correction on choroidal structure in children with anisohypermetropic amblyopia., PLoS ONE, Vol.15, No.4, 2020.
(Summary)
The aim of this study was to assess the effect of wearing optical correction on the choroidal structure in eyes of children with anisohypermetropic amblyopia. This study was conducted at the Nara Medical University Hospital and at the Tokushima University Hospital. Twenty-nine anisohypermetropic amblyopic eyes and their fellow eyes of 29 amblyopic patients (mean age, 5.7 ± 1.7 years, range 3- to 8-years) and twenty eyes of 20 age-similar control children (4.9 ± 0.8 years, range 4- to 6-years) were studied. All patients wore optical correction and 15 patients had both optical correction and patching. The values at the baseline were compared to that at one year later. The binarization method was used to determine the total, luminal, and stromal areas of the choroid in the enhanced depth imaging optical coherence tomographic images. The best-corrected visual acuity (BCVA) of the amblyopic eyes was significantly improved after the one-year period. A large luminal area was characteristic of the amblyopic eye at the baseline, and it was significantly reduced after the optical treatment. The stromal area widened significantly in the amblyopic and fellow eyes after one year whereas there were no significant changes in the choroid of the control eyes after one year. After one-year of optical correction, the luminal/stromal ratios in the amblyopic and fellow eyes were decreased and were then not significantly different from that of the normal control eyes. There was a significant and positive correlation between the improvement of the BCVA and the stromal area at the baseline (r = 0.64, P = 0.001). Wearing corrective lenses on the amblyopic eyes improves the BCVA, and the choroidal structure of the amblyopic eye becomes closer to that of the control eyes. The narrowed luminal area is a specific response of the amblyopic eye associated with the correction of the refractive error. The larger stromal area in the amblyopic eyes at the baseline is a predictive factor for improvements of the BCVA.
Takahiro Sogawa, Hitoshi Tabuchi, Daisuke Nagasato, Hiroki Masumoto, Yasushi Ikuno, Hideharu Ohsugi, Naofumi Ishitobi and Yoshinori Mitamura : Accuracy of a deep convolutional neural network in the detection of myopic macular diseases using swept-source optical coherence tomography., PLoS ONE, Vol.15, No.4, 2020.
(Summary)
This study examined and compared outcomes of deep learning (DL) in identifying swept-source optical coherence tomography (OCT) images without myopic macular lesions [i.e., no high myopia (nHM) vs. high myopia (HM)], and OCT images with myopic macular lesions [e.g., myopic choroidal neovascularization (mCNV) and retinoschisis (RS)]. A total of 910 SS-OCT images were included in the study as follows and analyzed by k-fold cross-validation (k = 5) using DL's renowned model, Visual Geometry Group-16: nHM, 146 images; HM, 531 images; mCNV, 122 images; and RS, 111 images (n = 910). The binary classification of OCT images with or without myopic macular lesions; the binary classification of HM images and images with myopic macular lesions (i.e., mCNV and RS images); and the ternary classification of HM, mCNV, and RS images were examined. Additionally, sensitivity, specificity, and the area under the curve (AUC) for the binary classifications as well as the correct answer rate for ternary classification were examined. The classification results of OCT images with or without myopic macular lesions were as follows: AUC, 0.970; sensitivity, 90.6%; specificity, 94.2%. The classification results of HM images and images with myopic macular lesions were as follows: AUC, 1.000; sensitivity, 100.0%; specificity, 100.0%. The correct answer rate in the ternary classification of HM images, mCNV images, and RS images were as follows: HM images, 96.5%; mCNV images, 77.9%; and RS, 67.6% with mean, 88.9%.Using noninvasive, easy-to-obtain swept-source OCT images, the DL model was able to classify OCT images without myopic macular lesions and OCT images with myopic macular lesions such as mCNV and RS with high accuracy. The study results suggest the possibility of conducting highly accurate screening of ocular diseases using artificial intelligence, which may improve the prevention of blindness and reduce workloads for ophthalmologists.
(Keyword)
Adult / Aged / Blindness / Choroid / Choroidal Neovascularization / Datasets as Topic / Deep Learning / Diagnosis, Differential / Female / Humans / Image Interpretation, Computer-Assisted / Macula Lutea / Male / Mass Screening / Middle Aged / Myopia / ROC Curve / Retinoschisis / Severity of Illness Index / Tomography, Optical Coherence
Masahiko Shimura, Shigehiko Kitano, Daisuke Muramatsu, Harumi Fukushima, Yoshihiro Takamura, Makiko Matsumoto, Masahide Kokado, Jiro Kogo, Mariko Sasaki, Yuki Morizane, Takuya Utsumi, Takashi Koto, Shozo Sonoda, Takao Hirano, Hiroto Ishikawa, Yoshinori Mitamura, Fumiki Okamoto, Takamasa Kinoshita, Kazuhiro Kimura, Masahiko Sugimoto, Kenji Yamashiro, Yukihiko Suzuki, Taiichi Hikichi, Noriaki Washio, Tomohito Sato, Kishiko Ohkoshi, Hiroki Tsujinaka, Sentaro Kusuhara, Mineo Kondo, Hitoshi Takagi, Toshinori Murata and Taiji Sakamoto : Real-world management of treatment-naïve diabetic macular oedema: 2-year visual outcome focusing on the starting year of intervention from STREAT-DMO study., The British journal of Ophthalmology, Vol.104, No.12, 1755-1761, 2020.
(Summary)
For recent years, treatment patterns for DMO have been gradually but certainly changed; as a result, better visual gain, suppression of worsened eyes and better final BCVA have been obtained. Anti-VEGF therapy has become the first-line therapy and its injection frequency has been increasing.
Shohei Morikawa, Fumiki Okamoto, Yoshifumi Okamoto, Yoshinori Mitamura, Hiroto Ishikawa, Kozo Harimoto, Tetsuo Ueda, Taiji Sakamoto, Kazuhiko Sugitani, Osamu Sawada, Junya Mori, Yoshihiro Takamura and Tetsuro Oshika : Clinical characteristics and visual outcomes of work-related open globe injuries in Japanese patients., Scientific Reports, Vol.10, No.1, 2020.
(Summary)
Work-related OGIs showed better visual outcomes than other OGIs. Initial visual acuity, wound length, and the presence of proliferative vitreoretinopathy are predictors of visual outcomes in patients with work-related OGIs.
Our real-world evidence from a large sample of Japanese patients who received STTA showed that the incidence of IOP elevation after STTA was 14.7%, and was associated with younger age, higher baseline IOP, and steroid dose. Thus, IOP should be monitored, especially in patients with younger age, higher baseline IOP, and higher incidences of DME and uveitis.
Mariko Egawa, Yoshinori Mitamura, Masanori Niki, Hiroki Sano, Gen Miura, Akihiro Chiba, Shuichi Yamamoto, Shozo Sonoda and Taiji Sakamoto : CORRELATIONS BETWEEN CHOROIDAL STRUCTURES AND VISUAL FUNCTIONS IN EYES WITH RETINITIS PIGMENTOSA, Retina, Vol.39, No.12, 2399-2409, 2019.
(Summary)
To investigate the choroidal structures in the enhanced depth imaging optical coherence tomographic images in eyes with retinitis pigmentosa (RP) and to determine correlations between the choroidal structures and visual functions. The enhanced depth imaging optical coherence tomographic images of 100 eyes with typical RP and 60 age-, sex-, and axial length-matched normal eyes were binarized using ImageJ. The cross-sectional luminal and stromal areas of the inner and outer subfoveal choroid of 1,500-µm width were measured. The inner choroid included the choriocapillaris and medium vessel layer, and the outer choroid included the larger vessel layer. In the inner choroid, the luminal area and the ratio of luminal/total choroidal area (L/C ratio) were significantly smaller in RP than in controls (P = 0.010, P < 0.001, respectively), whereas the stromal area was not significantly different (P = 0.114). The inner choroidal L/C ratio was significantly correlated with the best-corrected visual acuity, mean deviation, foveal sensitivity, width of the ellipsoid zone, and central foveal thickness in RP after adjusting for the axial length, age, and sex (all P < 0.005). The significant correlations between the inner choroidal structures and the visual functions and retinal structures indicate that the choroidal structures are altered in association with the progression of RP.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Masahiko Shimura, Shigehiko Kitano, Daisuke Muramatsu, Harumi Fukushima, Yoshihiro Takamura, Makiko Matsumoto, Masahide Kokado, Jiro Kogo, Mariko Sasaki, Yuki Morizane, Osamu Kotake, Takashi Koto, Shozo Sonoda, Takao Hirano, Hiroto Ishikawa, Yoshinori Mitamura, Fumiki Okamoto, Takamasa Kinoshita, Kazuhiro Kimura, Masahiko Sugimoto, Kenji Yamashiro, Yukihiko Suzuki, Taiichi Hikichi, Noriaki Washio, Tomohito Sato, Kishiko Ohkoshi, Hiroki Tsujinaka, Sentaro Kusuhara, Mineo Kondo, Hitoshi Takagi, Toshinori Murata and Taiji Sakamoto : Real-world management of treatment-naïve diabetic macular oedema in Japan: two-year visual outcomes with and without anti-VEGF therapy in the STREAT-DME study., The British journal of Ophthalmology, Vol.104, No.9, 1209-1215, 2019.
(Summary)
Following 2-year real-world management of treatment-naïve DME in Japan, BCVA improved by 2 letters. Eyes treated by anti-VEGF monotherapy showed a better visual prognosis than eyes receiving combination therapy. Despite treatment for DME being selected by specialists in consideration of medical and social factors, a satisfactory visual prognosis was not obtained, but final BCVA remained >20/40 in half of all eyes.
Daisuke Nagasato, Hitoshi Tabuchi, Hiroki Masumoto, Hiroki Enno, Naofumi Ishitobi, Masahiro Kameoka, Masanori Niki and Yoshinori Mitamura : Automated detection of a nonperfusion area caused by retinal vein occlusion in optical coherence tomography angiography images using deep learning., PLoS ONE, Vol.14, No.11, 2019.
(Summary)
We aimed to assess the ability of deep learning (DL) and support vector machine (SVM) to detect a nonperfusion area (NPA) caused by retinal vein occlusion (RVO) with optical coherence tomography angiography (OCTA) images. The study included 322 OCTA images (normal: 148; NPA owing to RVO: 174 [128 branch RVO images and 46 central RVO images]). Training to construct the DL model using deep convolutional neural network (DNN) algorithms was provided using OCTA images. The SVM used a scikit-learn library with a radial basis function kernel. The area under the curve (AUC), sensitivity and specificity for detecting an NPA were examined. We compared the diagnostic ability (sensitivity, specificity and average required time) between the DNN, SVM and seven ophthalmologists. Heat maps were generated. With regard to the DNN, the mean AUC, sensitivity, specificity and average required time for distinguishing RVO OCTA images with an NPA from normal OCTA images were 0.986, 93.7%, 97.3% and 176.9 s, respectively. With regard to SVM, the mean AUC, sensitivity, and specificity were 0.880, 79.3%, and 81.1%, respectively. With regard to the seven ophthalmologists, the mean AUC, sensitivity, specificity and average required time were 0.962, 90.8%, 89.2%, and 700.6 s, respectively. The DNN focused on the foveal avascular zone and NPA in heat maps. The performance of the DNN was significantly better than that of SVM in all parameters (p < 0.01, all) and that of the ophthalmologists in AUC and specificity (p < 0.01, all). The combination of DL and OCTA images had high accuracy for the detection of an NPA, and it might be useful in clinical practice and retinal screening.
Takamasa Kinoshita, Hiroko Imaizumi, Miho Shimizu, Junya Mori, Akira Hatanaka, Shuichiro Aoki, Hirotomo Miyamoto, Masanori Iwasaki, Fumiko Murao, Masanori Niki, Hiroki Sano, Shozo Sonoda, Taiji Sakamoto and Yoshinori Mitamura : Systemic and Ocular Determinants of Choroidal Structures on Optical Coherence Tomography of Eyes with Diabetes and Diabetic Retinopathy., Scientific Reports, Vol.9, No.1, 2019.
(Summary)
Knowledgeof the choroidal structures in eyes with diabetes and diabetic retinopathy (DR) should provide information on the pathogenesis of DR. A prospective study was performed to determine the systemic and ocular factors that affect the choroidal structures in eyes with diabetes. Two-hundred consecutive diabetic subjects consisted of 160 treatment-naïve patients with different stages of DR and 40 patients with proliferative DR with prior panretinal photocoagulation (PRP). All underwent blood and urine tests and enhanced depth imaging optical coherence tomography (EDI-OCT). The cross-sectional EDI-OCT images of the subfoveal choroid were binarized to measure the total choroidal area (TCA), luminal area, and stromal area. Multivariate regression analyses were performed to determine the systemic and ocular factors that were significantly correlated with the choroidal structures. The subfoveal choroidal thickness, TCA, luminal area, and stromal area were larger at more advanced stage of DR, and smaller in eyes with PRP than those without (P < 0.001). The TCA and stromal area were significantly and positively correlated with the degree of albuminuria (P = 0.034, P = 0.025, respectively). The choroidal lumen and stroma may increase as the stages of DR progress and decrease after PRP. Albuminuria may be associated with the choroidal stromal edema.
Hiroki Masumoto, Hitoshi Tabuchi, Shunsuke Nakakura, Hideharu Ohsugi, Hiroki Enno, Naofumi Ishitobi, Eiko Ohsugi and Yoshinori Mitamura : Accuracy of a deep convolutional neural network in detection of retinitis pigmentosa on ultrawide-field images., PeerJ, Vol.7, e6900, 2019.
(Summary)
Evaluating the discrimination ability of a deep convolution neural network for ultrawide-field pseudocolor imaging and ultrawide-field autofluorescence of retinitis pigmentosa. In total, the 373 ultrawide-field pseudocolor and ultrawide-field autofluorescence images (150, retinitis pigmentosa; 223, normal) obtained from the patients who visited the Department of Ophthalmology, Tsukazaki Hospital were used. Training with a convolutional neural network on these learning data objects was conducted. We examined the -fold cross validation ( = 5). The mean area under the curve of the ultrawide-field pseudocolor group was 0.998 (95% confidence interval (CI) [0.9953-1.0]) and that of the ultrawide-field autofluorescence group was 1.0 (95% CI [0.9994-1.0]). The sensitivity and specificity of the ultrawide-field pseudocolor group were 99.3% (95% CI [96.3%-100.0%]) and 99.1% (95% CI [96.1%-99.7%]), and those of the ultrawide-field autofluorescence group were 100% (95% CI [97.6%-100%]) and 99.5% (95% CI [96.8%-99.9%]), respectively. Heatmaps were in accordance with the clinician's observations. Using the proposed deep neural network model, retinitis pigmentosa can be distinguished from healthy eyes with high sensitivity and specificity on ultrawide-field pseudocolor and ultrawide-field autofluorescence images.
To evaluate the clinical characteristics and visual outcomes of patients with traffic accident-related open globe injuries, and to examine preoperative factors influencing the visual prognosis after pars plana vitrectomy, as compared with common open globe injuries. Patients with open globe injuries, who underwent pars plana vitrectomy, were identified. Patients' demographic and clinical data were entered into a computerized database for review and analysis; data included age, sex, initial visual acuity, duration between onset of injury and surgery, information about the type and cause of injury, wound location and length, presence of ocular complications, and final visual acuity. Of the 355 open globe injuries, 14 were sustained during a traffic-related accident; the average age was 50.4 years (range: 20-85) and most (78.6%) were men. Of these 14 patients, 9 (64.3%) presented with rupture and 5 (35.7%) with laceration. Injuries were caused while driving (6 eyes; 42.9%), riding a bicycle (5 eyes; 35.7%), involved in car accident while walking (2 eyes; 14.3%), and riding a motorbike (1 eye; 7.1%). Initial visual acuity was significantly related to final visual acuity (P = 0.003, R = 0.80). The final visual acuity in patients with traffic accident-related open globe injuries was significantly better than that of the total group (P = 0.01). Traffic accident-related open globe injuries had better visual outcomes than common open globe injuries. Visual outcomes in patients with traffic accident-related open globe injuries were related to the initial visual acuity. No eyes developed endophthalmitis in patients with traffic accident-related open globe injuries.
Araki Takashi, Ishikawa Hiroto, Iwahashi Chiharu, Niki Masanori, Yoshinori Mitamura, Sugimoto Masahiko, Kondo Mineo, Takamasa Kinoshita, Nishi Tomo, Ueda Tetsuo, Kato Aki, Yasukawa Tsutomu, Takamura Yoshihiro and Gomi Fumi : Central serous chorioretinopathy with and without steroids: a multicenter survey, PLoS ONE, Vol.14, No.2, e0213110, 2019.
(Summary)
We investigated the rates of the use of steroids in Japanese central serous chorioretinopathy (CSC) cases and differences in the characteristics of CSC with and without steroids. A total of 538 eyes of 477 patients diagnosed with CSC, with 3 months or more of follow-up between April 2013 and June 2017 at 8 institutions. Patients with CSC with more than 3 months of follow-up were identified by OCT and fluorescein angiography at 8 institutions. Data collected included patient demographics, history of corticosteroid medication and smoking, spherical errors, findings of angiography, subfoveal choroidal thickness, and changes through the follow-up period. Differences in these findings were analyzed in cases with and without corticosteroid treatment. Among the 477 patients (344 men,133 women), 74 (15.5%) (39 men, 35 women) underwent current or prior steroid treatment. Cases with steroids were higher age (p = 0.0403) and showed no male prevalence, more bilateral involvement (p < 0.0001), and the affected eyes had multiple pigment epithelial detachment (p <0.0001), more fluorescein leakage sites (p < 0.0001), greater choroidal thickness (p = 0.0287) and a higher recurrence rate (p = 0.0412). Steroids can cause severer CSC through an effect on choroidal vessels and an impairment of retinal pigment epithelium.
Ingen Shu, Hiroto Ishikawa, Hiroki Nishikawa, Shohei Morikawa, Fumiki Okamoto, Taiji Sakamoto, Masahiko Sugimoto, Mineo Kondo, Masanori Iwasaki, Takamasa Kinoshita, Toshi Toibana, Yoshinori Mitamura, Yoshihiro Takamura, Ryosuke Motohashi, Masahiko Shimura, Yutaka Sakurai, Masaru Takeuchi and Fumi Gomi : Scleral buckling versus vitrectomy for young japanese patients with rhegmatogenous retinal detachment in the era of microincision surgery: real-world evidence from a multicentre study in Japan., Acta Ophthalmologica, Vol.97, No.5, e736-e741, 2019.
(Summary)
Scleral buckling (SB) and PPV were chosen with almost equal frequency for young patients with RRD. Clinical outcomes for SB and PPV exhibited a similar PARR. The incidence of cataract formation after PPV may constitute an important limitation of the procedure.
Masanori Niki and Yoshinori Mitamura : Clinical preferences and trends of anti-vascular endothelial growth factor treatments for diabetic macular edema in Japan, Journal of Diabetes Investigation, Vol.10, No.2, 475-483, 2019.
(Summary)
To determine the current clinical preferences of anti-vascular endothelial growth factor (VEGF) treatment protocols for diabetic macular edema (DME) in Japan. This was a descriptive cross-sectional study. Answers to a questionnaire consisting of 16 questions were obtained from 176 of 278 (63.3%) surveyed ophthalmologists. The results showed that 81.2% preferred intravitreal injections of anti-VEGF antibodies as the first-line therapy. The most important indicators for beginning anti-VEGF therapy were: the best-corrected visual acuity in 44.3% and the retinal thickness in 30.7%. In the loading phase, 53.4% preferred a single injection, and in the maintenance phase, 75.0% preferred the pro re nata regimen. Financial limitation (85.8%) was reported as the most important difficulty in the treatment. For combination therapy with anti-VEGF treatment, panretinal photocoagulation, focal photocoagulations and a sub-Tenon steroid injection were preferred. The contraindications for anti-VEGF therapy were: prior cerebral infarction (72.7%). Regarding the use of both approved anti-VEGF agents in Japan, ranibizumab and aflibercept, 39.8% doctors used them appropriately. Our results present the current clinical preferences of anti-VEGF treatment for DME in Japan. The best-corrected visual acuity and the retinal thickness are important indicators to institute this therapy. The majority of the ophthalmologists use anti-VEGF treatment as first-line therapy and prefer the 1 + pro re nata regimen.
Naoko Kakiuchi, Shozo Sonoda, Hiroto Terasaki, Hideki Shiihara, Mariko Egawa, Yoshinori Mitamura and Taiji Sakamoto : Choroidal vasculature from ultra-widefield images without contrast dye and its Application to Vogt-Koyanagi-Harada Disease, Ophthalmology. Retina, Vol.3, No.2, 161-169, 2019.
(Summary)
To develop a method to obtain ultra-widefield choroidal vessel images with a fundus camera without using dye, and its application in Vogt-Koyanagi-Harada (VKH) disease. Experimental study and case series. Patients with unilateral retinal disorders and those with VKH disease who had undergone ultra-widefield imaging were studied. Indocyanine green angiography (ICGA) and the 635-nm wavelength Optos ultra-widefield fundus photography (Optos, United Kingdom) images (Optos) were processed by KagoEye 3 software. The 2 types of images were overlapped. The degree of overlapped blood vessel areas of the ICGA image was taken as the matching ratio. The matching ratio was obtained for the peripheral, posterior pole, and overall areas. In addition, changes in the fundus findings were followed up with Optos image analysis in patients with VKH disease. The degree of visibility of the choroidal vessels was evaluated for 5 stages. The clarity scores and the longitudinal findings were compared. The matching ratios between the ICGA images and the Optos images processed by KagoEye3 software were determined. Initially, 10 healthy eyes were studied. The matching ratios for the overall area, the peripheral area, and the posterior pole area of the ICGA image and the Optos image were 64.09%, 74%, and 63.10%, respectively. The correlations between the choroidal blood vessel matching ratio and the ocular axial length and refractive error were not significant, but the matching ratio was correlated significantly with the age. The average clarity score in 12 VKH disease patients was 1.6 ± 0.85 before treatment, which was significantly improved to 4.2 ± 0.75 after 1 month (P < 0.05). Many hyporeflective spotty lesions were observed on the Optos images, which coincided with hyperfluorescent dots on the ICGA images. The lesions gradually disappeared and the vortex vein became visible after treatment. The ultra-widefield Optos images processed by KagoEye3 software can exaggerate images of the choroidal vessels in widefield fundus images without using dye. Because this method is noninvasive, it is applicable to a variety of diseased and healthy eyes.
Sano Hiroki, Namekata Kazuhiko, Kimura Atsuko, Shitara Hiroshi, Guo Xiaoli, Harada Chikako, Yoshinori Mitamura and Harada Takayuki : Differential effects of N-acetylcysteine on retinal degeneration in two mouse models of normal tension glaucoma, Cell Death & Disease, Vol.10, No.2, 75, 2019.
(Summary)
N-acetylcysteine (NAC) is widely used as a mucolytic agent and as an antidote to paracetamol overdose. NAC serves as a precursor of cysteine and stimulates the synthesis of glutathione in neural cells. Suppressing oxidative stress in the retina may be an effective therapeutic strategy for glaucoma, a chronic neurodegenerative disease of the retinal ganglion cells (RGCs) and optic nerves. Here we examined the therapeutic potential of NAC in two mouse models of normal tension glaucoma, in which excitatory amino-acid carrier 1 (EAAC1) or glutamate/aspartate transporter (GLAST) gene was deleted. EAAC1 is expressed in retinal neurons including RGCs, whereas GLAST is mainly expressed in Müller glial cells. Intraperitoneal administration of NAC prevented RGC degeneration and visual impairment in EAAC1-deficient (knockout; KO) mice, but not in GLAST KO mice. In EAAC1 KO mice, oxidative stress and autophagy were suppressed with increased glutathione levels by NAC treatment. Our findings suggest a possibility that systemic administration of NAC may be available for some types of glaucoma patients.
Nagasato Daisuke, Tabuchi Hitoshi, Ohsugi Hideharu, Masumoto Hiroki, Enno Hiroki, Ishitobi Naofumi, Sonobe Tomoaki, Kameoka Masahiro, Niki Masanori and Yoshinori Mitamura : Deep-learning classifier with ultrawide-field fundus ophthalmoscopy for detecting branch retinal vein occlusion, International Journal of Ophthalmology, Vol.12, No.1, 94-99, 2019.
(Summary)
To investigate and compare the efficacy of two machine-learning technologies with deep-learning (DL) and support vector machine (SVM) for the detection of branch retinal vein occlusion (BRVO) using ultrawide-field fundus images. This study included 237 images from 236 patients with BRVO with a mean±standard deviation of age 66.3±10.6y and 229 images from 176 non-BRVO healthy subjects with a mean age of 64.9±9.4y. Training was conducted using a deep convolutional neural network using ultrawide-field fundus images to construct the DL model. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) were calculated to compare the diagnostic abilities of the DL and SVM models. For the DL model, the sensitivity, specificity, PPV, NPV and AUC for diagnosing BRVO was 94.0% (95%CI: 93.8%-98.8%), 97.0% (95%CI: 89.7%-96.4%), 96.5% (95%CI: 94.3%-98.7%), 93.2% (95%CI: 90.5%-96.0%) and 0.976 (95%CI: 0.960-0.993), respectively. In contrast, for the SVM model, these values were 80.5% (95%CI: 77.8%-87.9%), 84.3% (95%CI: 75.8%-86.1%), 83.5% (95%CI: 78.4%-88.6%), 75.2% (95%CI: 72.1%-78.3%) and 0.857 (95%CI: 0.811-0.903), respectively. The DL model outperformed the SVM model in all the aforementioned parameters (<0.001). These results indicate that the combination of the DL model and ultrawide-field fundus ophthalmoscopy may distinguish between healthy and BRVO eyes with a high level of accuracy. The proposed combination may be used for automatically diagnosing BRVO in patients residing in remote areas lacking access to an ophthalmic medical center.
Akiko Miki, Yoichi Sakurada, Koji Tanaka, Kentaro Semba, Yoshinori Mitamura, Mitsuko Yuzawa, Atsushi Tajima, Masahiro Nakatochi, Ken Yamamoto, Keitaro Matsuo, Issei Imoto and Shigeru Honda : Genome-wide association study to identify a new susceptibility locus for central serous chorioretinopathy in the Japanese population, Investigative Ophthalmology & Visual Science, Vol.59, No.13, 5542-5547, 2018.
(Summary)
Central serous chorioretinopathy (CSC) is a retinal disorder that often affects the vision of middle-aged people yet the molecular mechanisms of CSC remain unknown. This study was conducted to identify genetic factors influencing individual differences in susceptibility to CSC. A two-stage genome-wide association study (GWAS) was conducted with a total of 320 unrelated Japanese idiopathic CSC cases and 3245 population-based controls. In a discovery stage, 137 unrelated Japanese idiopathic CSC cases and 1174 population-based controls were subjected to GWAS, followed by a replication study using an additional 183 individuals with idiopathic CSC and 2071 population-based volunteers. The results of the discovery and replication stages were combined to conduct a meta-analysis. In the two-stage GWAS, rs11865049 located at SLC7A5 in chromosome 16q24.2 was identified as a novel disease susceptibility locus for CSC, as evident from the discovery and replication results using meta-analysis (combined P = 9.71 × 10-9, odds ratio = 2.10). The results of the present study demonstrated that SLC7A5 might be the potential candidate gene associated with CSC, indicating a previously unidentified molecular mechanism of CSC.
(Keyword)
Adult / Aged / Asian Continental Ancestry Group / Central Serous Chorioretinopathy / Chromosomes, Human, Pair 16 / Disease Susceptibility / female / Genetic Predisposition to Disease / Genome-Wide Association Study / Humans / Japan / Large Neutral Amino Acid-Transporter 1 / male / Middle Aged / Polymorphism, Single Nucleotide / Tomography, Optical Coherence
Daisuke Nagasato, Hitoshi Tabuchi, Hideharu Ohsugi, Hiroki Masumoto, Hiroki Enno, Naofumi Ishitobi, Tomoaki Sonobe, Masahiro Kameoka, Masanori Niki, Ken Hayashi and Yoshinori Mitamura : Deep neural network-based method for detecting central retinal vein occlusion using ultrawide-field fundus ophthalmoscopy, Journal of Ophthalmology, Vol.2018, 1875431, 2018.
(Summary)
The aim of this study is to assess the performance of two machine-learning technologies, namely, deep learning (DL) and support vector machine (SVM) algorithms, for detecting central retinal vein occlusion (CRVO) in ultrawide-field fundus images. Images from 125 CRVO patients (=125 images) and 202 non-CRVO normal subjects (=238 images) were included in this study. Training to construct the DL model using deep convolutional neural network algorithms was provided using ultrawide-field fundus images. The SVM uses scikit-learn library with a radial basis function kernel. The diagnostic abilities of DL and the SVM were compared by assessing their sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic curve for CRVO. For diagnosing CRVO, the DL model had a sensitivity of 98.4% (95% confidence interval (CI), 94.3-99.8%) and a specificity of 97.9% (95% CI, 94.6-99.1%) with an AUC of 0.989 (95% CI, 0.980-0.999). In contrast, the SVM model had a sensitivity of 84.0% (95% CI, 76.3-89.3%) and a specificity of 87.5% (95% CI, 82.7-91.1%) with an AUC of 0.895 (95% CI, 0.859-0.931). Thus, the DL model outperformed the SVM model in all indices assessed ( < 0.001 for all). Our data suggest that a DL model derived using ultrawide-field fundus images could distinguish between normal and CRVO images with a high level of accuracy and that automatic CRVO detection in ultrawide-field fundus ophthalmoscopy is possible. This proposed DL-based model can also be used in ultrawide-field fundus ophthalmoscopy to accurately diagnose CRVO and improve medical care in remote locations where it is difficult for patients to attend an ophthalmic medical center.
Toshihiko Nagasawa, Hitoshi Tabuchi, Hiroki Masumoto, Masanori Niki, Hideharu Ohsugi and Yoshinori Mitamura : Accuracy of deep learning, a machine learning technology, using ultra-wide-field fundus ophthalmoscopy for detecting idiopathic macular holes, PeerJ, Vol.6, e5696, 2018.
(Summary)
We aimed to investigate the detection of idiopathic macular holes (MHs) using ultra-wide-field fundus images (Optos) with deep learning, which is a machine learning technology. The study included 910 Optos color images (715 normal images, 195 MH images). Of these 910 images, 637 were learning images (501 normal images, 136 MH images) and 273 were test images (214 normal images and 59 MH images). We conducted training with a deep convolutional neural network (CNN) using the images and constructed a deep-learning model. The CNN exhibited high sensitivity of 100% (95% confidence interval CI [93.5-100%]) and high specificity of 99.5% (95% CI [97.1-99.9%]). The area under the curve was 0.9993 (95% CI [0.9993-0.9994]). Our findings suggest that MHs could be diagnosed using an approach involving wide angle camera images and deep learning.
Eiko Ohsugi, Yoshinori Mitamura, Kayo Shinomiya, Masanori Niki, Hiroki Sano, Toshihiko Nagasawa, Shimizu Yukiko, Nagasato Daisuke and Tabuchi Hitoshi : Changes in choroidal thickness in healthy pediatric individuals: A longitudinal study, International Journal of Ophthalmology, Vol.11, No.7, 1179-1184, 2018.
(Summary)
To investigate the changes in the choroidal thickness in healthy pediatric children in a longitudinal study, and to determine the ocular and systemic parameters that were significantly correlated with the changes in the choroidal thickness. This study included 64 eyes of 34 healthy Japanese children with a mean age (±SD) of 4.4 (±0.4)y (range, 3.6-5.8y) at baseline. Swept-source optical coherence tomography (SS-OCT) was used to record images of the retina and choroid at the baseline and after a mean follow-up period of about 1.5y. The 3D raster scan protocol was used to construct the choroidal thickness map. Mean choroidal thickness was calculated for each of the nine sectors of the Early Treatment Diabetic Retinopathy Study grid. Best-corrected visual acuity, axial length, body height, and weight were also measured. Changes in measurements were defined as the baseline values subtracted from the values at the final visit. A generalized estimating equation was used to eliminate the effect of within-subject intereye correlations. The mean central choroidal thickness was significantly reduced during the follow-up period (baseline, 301.8±8.6 µm; final visit, 286.6±8.0 µm, <0.001). The decrease in the choroidal thickness was greatest in the central sector, followed by the sectors of the inner and outer rings. The inner and outer rings had diameters of 1 to 3 mm and 3 to 6 mm, respectively. The changes in the choroidal thickness in the central, inner ring, and outer ring sectors were significantly and negatively correlated with the age, baseline body height, baseline body weight, and elongation of the axial length. These results indicate that the choroidal thickness among preschool-aged Japanese children decreased significantly during the follow-up period. The choroidal thinning is significantly associated with the elongation of axial length. These characteristics should be considered in the evaluation of choroidal thickness in younger children with retinochoroidal disorders.
Kei Akaiwa, Namekata Kazuhiko, Azuchi Yuriko, Hiroki Sano, Guo Xiaoli, Kimura Atsuko, Harada Chikako, Yoshinori Mitamura and Harada Takayuki : Topical ripasudil suppresses retinal ganglion cell death in a mouse model of normal tension glaucoma, Investigative Ophthalmology & Visual Science, Vol.59, No.5, 2080-2089, 2018.
(Summary)
To assess if ripasudil has a neuroprotective effect using mice with excitatory amino acid carrier 1 (EAAC1) deletion (EAAC1 knockout [KO] mice), a mouse model of normal tension glaucoma. Topical administration (5 μL/day) of two different concentrations of ripasudil (0.4% and 2%) were applied to EAAC1 KO mice from 5 to 12 weeks old. Optical coherence tomography, multifocal electroretinograms, the measurement of intraocular pressure (IOP), and histopathology analyses were performed at 5, 8, and 12 weeks old. Retrograde labeling of retinal ganglion cells (RGCs), immunoblot, and immunohistochemical analyses of phosphorylated p38 mitogen-activated protein kinase (MAPK) in the retina were performed at 8 weeks old. Topical ripasudil ameliorated retinal degeneration and improved visual function in EAAC1 KO mice at both 8 and 12 weeks old. Ripasudil reduced IOP and strongly suppressed the phosphorylation of p38 MAPK that stimulates RGC death in EAAC1 KO mice. These results suggest that, in addition to IOP reduction, ripasudil prevents glaucomatous retinal degeneration by neuroprotection, which is achieved by suppressing cell-death signaling pathways.
Farouk Mohameud, Takeshi Naito, Kayo Shinomiya and Yoshinori Mitamura : Observation of Ciliary Body Changes during Accommodation Using Anterior OCT., The Journal of Medical Investigation : JMI, Vol.65, No.1,2, 60-63, 2018.
(Summary)
To evaluate the anatomical changes in the ciliary body (CB) during naturally stimulated accommodation in children using anterior segment optical coherence tomography (OCT). This study was a prospective, observational, noncomparative case series included 18 eyes of 9 children (8 males and 1 female) aged from 4 to 10 years. Ciliary body thickness (CBT) was measured temporally by Anterior OCT at 1, 2 and 3 mm posterior to the scleral spur. Measurements were performed in the accommodated state and the unaccommodated state (with cycloplegia). The mean CBT significantly increased by accommodation at 1 mm posterior to the scleral spur from 751 42 to 818 40 μm (P 0.001) and significantly decreased at 2 and 3 mm from 506 66 to 445 59 μm and from 290 54 to 240 50 μm respectively (P 0.001). During accommodation, the anterior portion of the ciliary body thickens, while the posterior portion decreases in thickness. These findings imply that the circular ciliary muscles are mainly involved in accommodation and not the longitudinal muscles. J. Med. Invest. 65:60-63, February, 2018.
Nishi Tomo, Ueda Tetsuo, MIzusawa Yuutaro, Kentaro Senba, Kayo Shinomiya, Yoshinori Mitamura, Sakamoto Taiji and Ogata Nahoko : Effect of optical correction on subfoveal choroidal thickness in children with anisohypermetropic amblyopia., PLoS ONE, Vol.12, No.12, e0189735, 2017.
(Summary)
The purpose of this study was to determine the effect of optical correction on the best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (CT) in the eyes of children with anisohypermetropic amblyopia. Twenty-four anisohypermetropic amblyopic eyes and their fellow eyes of 24 patients and twenty-three eyes of 23 age-matched control children were studied. After one year of optical correction, the BCVA in the anisohypermetropic amblyopic eyes was significantly improved. Before the treatment, the mean subfoveal CT in the amblyopic eyes was 351.9 ± 59.4 μm which was significantly thicker than that of control eyes at 302.4 ± 63.2 μm. After the treatment, the amount of change in the subfoveal CT in the amblyopic and fellow eyes was greater than that in the control eyes. The amblyopic and fellow eyes with thicker choroids had a greater thinning of the choroid whereas eyes with thinner choroids had a greater thickening of the choroid. We conclude that wearing corrective lenses improves the visual acuity, and induces changes of the subfoveal CT in eyes with anisohypermetropic amblyopia.
MicroRNAs have broad roles in tumorigenesis and cell differentiation through regulation of target genes. Notch signaling also controls cell differentiation and tumorigenesis. However, the mechanisms through which Notch mediates microRNA expression are still unclear. In this study, we aimed to identify microRNAs regulated by Notch signaling. Our analysis found that microRNA-449a (miR-449a) was indirectly regulated by Notch signaling. Although miR-449a-deficient mice did not show any Notch-dependent defects in immune cell development, treatment of miR-449a-deficient mice with azoxymethane (AOM) or dextran sodium sulfate (DSS) increased the numbers and sizes of colon tumors. These effects were associated with an increase in intestinal epithelial cell proliferation following AOM/DSS treatment. In patients with colon cancer, miR-449a expression was inversely correlated with disease-free survival and histological scores and was positively correlated with the expression of MLH1 for which loss-of function mutations have been shown to be involved in colon cancer. Colon tissues of miR-449a-deficient mice showed reduced Mlh1 expression compared with those of wild-type mice. Thus, these data suggested that miR-449a acted as a key regulator of colon tumorigenesis by controlling the proliferation of intestinal epithelial cells. Additionally, activation of miR-449a may represent an effective therapeutic strategy and prognostic marker in colon cancer.
Kei Akaiwa, Namekata Kazuhiko, Azuchi Yuriko, Guo Xiaoli, Harada Chikako, Yoshinori Mitamura and Harada Takayuki : Edaravone suppresses retinal ganglion cell death in a mouse model of normal tension glaucoma., Cell Death & Disease, Vol.8, No.7, e2934, 2017.
(Summary)
Glaucoma, one of the leading causes of irreversible blindness, is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino-acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs. Loss of EAAC1 leads to RGC degeneration without elevated intraocular pressure (IOP) and exhibits glaucomatous pathology including glutamate neurotoxicity and oxidative stress. In the present study, we found that edaravone, a free radical scavenger that is used for treatment of acute brain infarction and amyotrophic lateral sclerosis (ALS), reduces oxidative stress and prevents RGC death and thinning of the inner retinal layer in EAAC1-deficient (KO) mice. In addition, in vivo electrophysiological analyses demonstrated that visual impairment in EAAC1 KO mice was ameliorated with edaravone treatment, clearly establishing that edaravone beneficially affects both histological and functional aspects of the glaucomatous retina. Our findings raise intriguing possibilities for the management of glaucoma by utilizing a widely prescribed drug for the treatment of acute brain infarction and ALS, edaravone, in combination with conventional treatments to lower IOP.
Akiko Iwata, Kayo Shinomiya, Yoko Oogushi, Mariko Egawa and Yoshinori Mitamura : Review of retinopathy of prematurity in Tokushima University Hospital, Folia japonica de ophthalmologica clinica, Vol.10, No.6, 486-489, 2017.
Hideki Shiihara, Taiji Sakamoto, Hiroto Terasaki, Takehiro Yamashita, Naoya Yoshihara, Fumiki Okamoto, Nahoko Ogata, Toshifumi Yamashita, Shozo Sonoda and Yoshinori Mitamura : Effect of fluid-air exchange on reducing residual silicone oil after silicone oil removal., Graefe's Archive for Clinical and Experimental Ophthalmology, 2017.
(Summary)
Our purpose was to determine the effect of fluid-air exchange on the amount of silicone oil (SO) droplets remaining in the vitreous cavity after removal of the main body of the SO. This was a retrospective comparative study of 56 eyes of 56 patients that had undergone vitrectomy with SO tamponade. Fluid-air exchange was performed during surgery in 30 eyes [Air Ex(+) group] and was not done in 26 eyes [Air Ex(-) group]. All of the eyes were examined by ultrasonography, and the images were converted to binarized image. The amount of residual SO droplets/vitreal area in the images was expressed as the, "silicone oil index (SOI)". The correlations between SOI and clinical findings were determined. The SOI was significantly correlated with the axial length (AL, R = 0.444, P = 0.023). The SOI in the Air Ex(+) group was significantly higher (7.4 2.6%) than in the Air Ex(-) group (4.9 3.4%; P = 0.004). Multiple linear regression analyses showed that the SOI was independently and significantly correlated with the AL and the Air Ex(+) group (P = 0.003, P = 0.006, respectively). Fluid-air exchange during vitrectomy to remove residual SO is not effective. Our findings indicate that it may increase the amount of residual SO droplets.
Takamasa Kinoshita, Yoshinori Mitamura, Kayo Shinomiya, Mariko Egawa, Akiko Iwata, Akiko Fujihara, Kentaro Senba, Yoko Oogushi, Kei Akaiwa, Eisuke Uchino, Taiji Sakamoto and Shozo Sonoda : Diurnal variations in luminal and stromal areas of choroid in normal eyes, The British journal of Ophthalmology, Vol.101, No.3, 360-364, 2017.
(Summary)
To determine the diurnal variations of the luminal and stromal areas of the choroid in normal eyes. This was a prospective observational study of 38 eyes of 38 normal subjects. The blood pressure, heart rate, intraocular pressure and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded every 3 hours between 6:00 and 21:00 hours. The horizontal EDI-OCT images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), total cross-sectional choroidal area, the luminal areas, stromal areas and the ratio of luminal area to total choroidal area (L/C ratio) were determined. There were significant diurnal variations in the CCT, total choroidal area, luminal area and L/C ratio with the maximum values at 6:00 hours and the minimum values at 15:00 hours (p<0.001 for the CCT, p=0.011 for the total choroidal area, p<0.001 for the luminal area and p=0.014 for the L/C ratio). There was no significant variation in the stromal area (p=0.216). The range of fluctuation in the CCT was significantly correlated with that in the luminal area and the total choroidal area (p<0.001). However, there was no significant correlation between the fluctuation range in the CCT and that in the stromal area (p=0.095). There was no statistical relationship between the systemic parameters and the choroidal parameters. The changes in the luminal area are most likely responsible for the diurnal change in the CCT and subfoveal choroidal area. UMIN000019060, Pre-results.
Khulood Mohammed Sayed, Mahmoud M. Farouk, Takashi Katome, Toshihiko Nagasawa, Takeshi Naito and Yoshinori Mitamura : Corneal topographic changes and surgically induced astigmatism following combined phacoemulsification and 25-gauge vitrectomy., International Journal of Ophthalmology, Vol.10, No.1, 72-76, 2017.
(Summary)
To evaluate corneal topographic changes and surgically induced astigmatism (SIA) after combined phacoemulsification and 25-gauge transconjunctival sutureless vitrectomy (25-G TSV). A retrospective study on 96 eyes of 87 patients who underwent combined phacoemulsification and 25-G TSV. The different topographic parameters and SIA were analyzed pre- and postoperatively. There was no significant changes in corneal topographic parameters at different follow up periods. Only surface regularity index changed significantly in the 2(nd) postoperative week and then returned to baseline values thereafter. Mean SIA gradually decreased to reach 0.12 D by the 6(th) postoperative month. Corneal surface and astigmatic changes are insignificant in either early or late postoperative periods following combined phacoemulsification and 25-G TSV. The SIA was the minimum among previous reports on sutureless vitrectomy alone or combined with phacoemulsification. Improvement of SIA did not stop at the 3(rd) postoperative month but it continued till the 6(th) month postoperatively.
Erina Daizumoto, Yoshinori Mitamura, Hiroki Sano, Kei Akaiwa, Masanori Niki, Chihiro Yamanaka, Takamasa Kinoshita, Mariko Egawa, Shozo Sonoda and Taiji Sakamoto : Changes of choroidal structure after intravitreal aflibercept therapy for polypoidal choroidal vasculopathy., The British journal of Ophthalmology, Vol.101, No.1, 56-61, 2017.
(Summary)
To quantify the changes of the choroidal structure in the enhanced depth imaging optical coherence tomographic (EDI-OCT) images after intravitreal aflibercept (IVA) injections for polypoidal choroidal vasculopathy (PCV). Retrospective, observational case series. Forty eyes of 40 treatment-naive patients who underwent IVA for PCV were examined by EDI-OCT before, and 3 months and 12 months after IVA. The EDI-OCT images were binarised by ImageJ software. The cross-sectional luminal and stromal areas of the inner and outer subfoveal choroid of 1500 m width were quantified. The stromal but not the luminal area of the inner choroid was significantly decreased at 3 months and 12 months after the IVA (stromal area, both p<0.001; luminal area, both p>0.050). On the other hand, the luminal but not the stromal area of the outer choroid was significantly decreased at 3 months and 12 months (luminal area, both p<0.001; stromal area, both p>0.050). The Pachychoroid Index, ratio of luminal/stromal area (L/S ratio) of the outer choroid divided by the L/S ratio of the inner choroid, was significantly decreased at 3 months and 12 months (both p<0.050). The Pachychoroid Index was increased and returned almost to the baseline level after recurrences and decreased again after successful re-treatment. The baseline Pachychoroid Index was significantly correlated with the presence of a dry macula, thinner fovea and better visual acuity at 12 months (all p<0.050). The binarisation of the EDI-OCT images can be used to quantify the activity of PCV and to predict the prognosis after IVA.
Takamasa Kinoshita, Junya Mori, Natsuki Okuda, Hiroko Imaizumi, Masanori Iwasaki, Miho Shimizu, Hirotomo Miyamoto, Kei Akaiwa, Kentaro Semba, Shozo Sonoda, Taiji Sakamoto and Yoshinori Mitamura : Effects of Exercise on the Structure and Circulation of Choroid in Normal Eyes., PLoS ONE, Vol.11, No.12, e0168336, 2016.
(Summary)
To determine the effects of dynamic exercise on the circulation and the luminal and stromal areas of the choroid in normal eyes. This was a prospective interventional study of 38 eyes of 38 normal subjects enrolled by invitation. The systolic and diastolic blood pressures, heart rate, intraocularpressure, mean ocular perfusion pressure (MOPP), choroidal blood velocity, and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded before, and immediately after mild dynamic exercise. The same measurements were recorded after 10 min of rest. The choroidal blood velocity was measured bylaser speckle flowgraphy, and the mean blur rate was used for the evaluations. The horizontal EDI-OCT images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), total cross sectional choroidal area, luminal areas, stromal areas, and the ratio of luminal area to total choroidal area (L/C ratio) were determined from these images. The systolic and diastolic blood pressures, heart rate, MOPP, and the mean blur rate were significantly increased immediately after the exercise and significantly decreased 10 minutes after the exercise. There wereno significant changes in the mean CCT, the mean total choroidal area, the mean luminal and stromal areas, and the mean L/C ratio after the exercise. Our results suggest that a rest period is needed before measurements of blood flow velocity but not necessary for the EDI-OCT imaging to determine the choroidal thickness and area.
Tomo Nishi, Tetsuo Ueda, Yuutaro Mizusawa, Kayo Shinomiya, Kentaro Senba, Yoshinori Mitamura, Shozo Sonoda, Eisuke Uchino, Taiji Sakamoto and Nahoko Ogata : Choroidal structure in children with anisohypermetropic amblyopia determined by binarization of optical coherence tomographic images, PLoS ONE, Vol.11, No.10, e0164672, 2016.
(Summary)
To compare the choroidal structure of the subfoveal area in the eyes of children with anisohypermetropic amblyopia to that of the fellow eyes and to age-matched controls using a binarization method of the images obtained by enhanced depth imaging optical coherence tomography (EDI-OCT). This study was performed at Nara Medical University Hospital, Tokushima University Hospital, and Kagoshima University Hospital, Japan. Forty amblyopic eyes with anisohypermetropic amblyopia and their fellow eyes (5.9 ± 2.1 years, mean ± standard deviation), and 103 age-matched controls (6.7 ± 2.4 years) were studied. The control eyes were divided into myopic, emmetropic, and hyperopic eyes. The total choroidal area, luminal area and stromal area of the subfoveal choroid were measured by the binarization method. The luminal/stromal ratio and the axial length of the amblyopic eyes were compared to that of the control eyes. The total choroidal area in the amblyopic eyes was significantly larger than that of the fellow eyes (P = 0.005). The luminal/stromal ratio was significantly larger in the amblyopic eyes than that of the fellow eyes (P<0.001) and the control hyperopic eyes (P<0.001). There was a significant negative correlation between the luminal/stromal ratio and the axial length in the control eyes (r = -0.30, P = 0.001), but no significant correlation was found in the amblyopic eyes. The choroidal structure of the amblyopic eyes was different from that of the fellow and the control hyperopic eyes. The choroidal changes are related to amblyopia.
佐埜 弘樹, Takashi Katome, Yoko Oogushi, Masayuki Inoue, Takeshi Naito and Yoshinori Mitamura : Review of four cases of spontaneous closure of macular hole, Japanese Journal of Clinical Ophthalmology, Vol.70, No.10, 1625-1631, 2016.
Takamasa Kinoshita, Yoshinori Mitamura, Terumi Mori, Kei Akaiwa, Kentaro Senba, Mariko Egawa, Junya Mori, Shozo Sonoda and Taiji Sakamoto : Changes in choroidal structures in eyes with chronic central serous chorioretinopathy after half-dose photodynamic therapy, PLoS ONE, Vol.11, No.9, e0163104, 2016.
(Summary)
To determine the structural changes in the choroid after half-dose photodynamic therapy (hPDT) in eyes with chronic central serous chorioretinopathy (CSC). This was a retrospective interventional study of 29 eyes of 29 patients who underwent hPDT for chronic CSC with serous retinal detachment (SRD) and were followed for ≥3 months. Enhanced depth imaging optical coherence tomographic (EDI-OCT) images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), the cross sectional subfoveal choroidal area, the hyporeflective and hyperreflective areas of the inner, outer, and whole choroid were determined at the baseline, and at 1, 3, and 12 months after the hPDT. The SRDs were resolved in 26 (89.7%) eyes at 3 months after the hPDT. The mean CCT (P = 0.001), the total choroidal area (P = 0.001), and the hypo-reflective area (P = 0.003) of the whole choroid were significantly decreased from the baseline at 3 months. The hyperreflective area of whole choroid was not significantly changed during the study period (P = 0.083). The hyperreflective but not the hyporeflective area of the inner choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively). The hyporeflective but not the hyperreflective area of the outer choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively). The hyperreflective area of the inner choroid and hyporeflective area of the outer choroid were significantly decreased after hPDT for chronic CSC. Because the hyperreflective and hyporeflective area correspond to the choroidal stroma and vessels, respectively, the decreased CCT and subfoveal choroidal area after hPDT may be attributed to a decrease in the exudative changes in the inner choroidal stroma and the reduction of the dilation of the outer choroidal vessels.
(Keyword)
Adult / Aged / Aged, 80 and over / Central Serous Chorioretinopathy / Choroid / Chronic Disease / Female / Fluorescein Angiography / Humans / Indocyanine Green / Male / Middle Aged / Photochemotherapy / Tomography, Optical Coherence
赤岩 慶, Kayo Shinomiya, Yoko Oogushi, Teruyoshi Kageji, Akiko Abe and Yoshinori Mitamura : A case of metastatic orbital tumor with severe pain, Japanese Journal of Clinical Ophthalmology, Vol.70, No.8, 1319-1324, 2016.
Akiko Fujihara, Yoshinori Mitamura, Naoki Inomoto, Hiroki Sano, Kei Akaiwa and Kentaro Senba : Optical coherence tomographic parameters predictive of visual outcome after anti-vascular endothelial growth factor therapy for retinal vein occlusion, Clinical Ophthalmology, Vol.10, 1305-1313, 2016.
(Summary)
To determine the optical coherence tomography (OCT) parameters that are predictive of visual outcome after anti-VEGF therapy for a retinal vein occlusion (RVO). Fifty-seven eyes with macular edema (ME) secondary to a central or branch RVO treated with bevacizumab or ranibizumab were studied. Spectral-domain OCT and microperimetry were performed before, 1, 3, and 6 months after the treatment and at the final visit. Central retinal thickness (CRT), macular volume (MV), integrity of the external limiting membrane (ELM), ellipsoid zone (EZ), and foveal bulge (FB), and photoreceptor outer segment (PROS) length were determined. The mean follow-up period was 17.8±11.5 months. In 46 of the 57 eyes, a resolution of the ME was achieved. The pretreatment CRT and MV, presence of intact ELM, EZ, and FB, and PROS length at the time of ME resolution were significantly correlated with the best-corrected visual acuity and retinal sensitivity at the final visit (P<0.050). Multiple regression analyses showed that the pretreatment MV had the highest correlation with the posttreatment best-corrected visual acuity and retinal sensitivity (P<0.050). The CRT, MV, ELM, EZ, FB, and PROS length are predictive factors for the visual outcome after anti-VEGF therapy for RVO.
Shozo Sonoda, Taiji Sakamoto, Nobuhiro Kuroiwa, Noboru Arimura, Hiroki Kawano, Naoya Yoshihara, Takehiro Yamashita, Eisuke Uchino, Takamasa Kinoshita and Yoshinori Mitamura : Structural Changes of Inner and Outer Choroid in Central Serous Chorioretinopathy Determined by Optical Coherence Tomography., PLoS ONE, Vol.11, No.6, e0157190, 2016.
(Summary)
To determine the structural changes of the choroid in eyes with central serous chorioretinopathy (CSC) by enhanced depth imaging optical coherence tomography (EDI-OCT). A retrospective comparative study was performed at two academic institutions. Forty eyes with CSC, their fellow eyes, and 40 eyes of age-matched controls were studied. Subfoveal cross sectional EDI-OCT images were recorded, and the hypo reflective and hyperreflective areas of the inner and outer choroid in the EDI-OCT images were separately measured. The images were analyzed by a binarization method to determine the sizes of the hyporeflective and hyperreflective areas. In the inner choroid, the hyperreflective area was significantly larger in the CSC eyes (35,640±10,229 μm2) than the fellow eyes (22,908±8,522 μm2) and the control eyes (20,630±8,128 μm2; P<0.01 vs control for both, Wilcoxon signed-rank test). In the outer choroid, the hyporeflective area was significantly larger in the CSC eyes (446,549±121,214 μm2) than the control eyes (235,680±97,352 μm2, P<0.01). The average ratio of the hyporeflective area to the total choroidal area was smaller in the CSC eyes (67.0%) than the fellow eyes (76.5%) and the control eyes (76.7%) in the inner choroid (P<0.01, both). However, the ratio was larger in the CSC eyes (75.2%) and fellow eyes (71.7%) than in the control eyes (64.7%) in the outer choroid (P<0.01, both). The larger hyperreflective area in the inner choroid is related to the inflammation and edema of the stroma of the choroid in the acute stage of CSC. The larger hyporeflective areas in the outer choroid is due to a dilatation of the vascular lumens of the larger blood vessels. These are the essential characteristics of eyes with CSC regardless of the onset.
Kayo Shinomiya, 赤岩 慶, Yoko Oogushi, Akiko Fujihara and Yoshinori Mitamura : Effectiveness of 16 gauge sheath in the treatment of dacryolith in the lacrimal sac, Japanese Journal of Clinical Ophthalmology, Vol.70, No.5, 709-712, 2016.
Daisuke Nagasato, Yoshinori Mitamura, Kentaro Senba, Kei Akaiwa, Toshihiko Nagasawa, Yuki Yoshizumi, Hitoshi Tabuchi and Yoshiaki Kiuchi : Correlation between optic nerve head circulation and visual function before and after anti-VEGF therapy for central retinal vein occlusion: prospective, interventional case series., BMC Ophthalmology, Vol.16, 36, 2016.
(Summary)
To determine the correlation between the optic nerve head (ONH) circulation determined by laser speckle flowgraphy and the best-corrected visual acuity or retinal sensitivity before and after intravitreal bevacizumab or ranibizumab for central retinal vein occlusion. Thirty-one eyes of 31 patients were treated with intravitreal bevacizumab or ranibizumab for macular edema due to a central retinal vein occlusion. The blood flow in the large vessels on the ONH, the best-corrected visual acuity, and retinal sensitivity were measured at the baseline, and at 1, 3, and 6 months after treatment. The arteriovenous passage time on fluorescein angiography was determined. The venous tortuosity index was calculated on color fundus photograph by dividing the length of the tortuous retinal vein by the chord length of the same segment. The blood flow was represented by the mean blur rate (MBR) determined by laser speckle flowgraphy. To exclude the influence of systemic circulation and blood flow in the ONH tissue, the corrected MBR was calculated as MBR of ONH vessel area - MBR of ONH tissue area in the affected eye divided by the vascular MBR - tissue MBR in the unaffected eye. Pearson's correlation tests were used to determine the significance of correlations between the MBR and the best-corrected visual acuity, retinal sensitivity, arteriovenous passage time, or venous tortuosity index. At the baseline, the corrected MBR was significantly correlated with the arteriovenous passage time and venous tortuosity index (r = -0.807, P < 0.001; r = -0.716, P < 0.001; respectively). The corrected MBR was significantly correlated with the best-corrected visual acuity and retinal sensitivity at the baseline, and at 1, 3, and 6 months (all P < 0.050). The corrected MBR at the baseline was significantly correlated with the best-corrected visual acuity at 6 months (r = -0.651, P < 0.001) and retinal sensitivity at 6 months (r = 0.485, P = 0.005). The pre-treatment blood flow velocity of ONH can be used as a predictive factor for the best-corrected visual acuity and retinal sensitivity after anti-VEGF therapy for central retinal vein occlusion. UMIN000009072. Date of registration: 10/15/2012.
Mariko Egawa, Yoshinori Mitamura, Kei Akaiwa, Kentaro Senba, Takamasa Kinoshita, Eisuke Uchino, Shozo Sonoda and Taiji Sakamoto : Changes of choroidal structure after corticosteroid treatment in eyes with Vogt-Koyanagi-Harada disease., The British journal of Ophthalmology, Vol.100, No.12, 1646-1650, 2016.
(Summary)
To report the changes of the choroidal structure in the enhanced depth imaging optical coherence tomographic (EDI-OCT) images after high-dose corticosteroid treatment for acute Vogt-Koyanagi-Harada (VKH) disease. Retrospective, observational case series. Thirty-four eyes of 17 patients with acute VKH disease were examined by EDI-OCT before, and 1, 4 and 52 weeks after the treatment. The EDI-OCT images were binarised by ImageJ, a publicly accessible software. The luminal, stromal and total choroidal areas and ratio of luminal/stromal area (L/S ratio) were measured in the subfoveal choroid of 1500 µm width. The area of the peripapillary atrophy (PPA) was measured in the fundus photographs at 1 and 52 weeks. For statistical analyses, a generalised estimating equation method was used to eliminate the effect of within-subject intereye correlations. Before treatment, the EDI-OCT images could not be binarised because of poor image quality in most of the cases. After treatment, the luminal, stromal and total choroidal areas were significantly decreased during the follow-up period (all p<0.05). The L/S ratio significantly fluctuated over time (p=0.0201), and was significantly lower at 4 weeks than at 1 week (p=0.0158). The L/S ratio at 1 week was significantly correlated with increase in the PPA area, subsequent chronic recurrences and total dose of corticosteroid (p<0.0001, p=0.0006, p=0.0037, respectively). The L/S ratio measured by binarisation of EDI-OCT images was predictive factor for the progression of PPA, subsequent chronic recurrences and total dose of corticosteroid, and may serve as a marker for degree of choroidal inflammation in the VKH disease.
(Keyword)
Adult / Aged / Aged, 80 and over / Choroid / Dose-Response Relationship, Drug / Female / Fluorescein Angiography / Follow-Up Studies / Fundus Oculi / Glucocorticoids / Humans / Male / Middle Aged / Optic Disk / Retrospective Studies / Time Factors / Tomography, Optical Coherence / Treatment Outcome / Uveomeningoencephalitic Syndrome / Visual Acuity
Akiko Iwata, Kayo Shinomiya, 冨田 真知子, 木虎 亜希子, 岡本 里江 and Yoshinori Mitamura : A case of X-pattern exotropia undergoing recession of both lateral rectus muscles, Folia japonica de ophthalmologica clinica, Vol.9, No.1, 11-14, 2016.
Takamasa Kinoshita, Hiroko Imaizumi, Hirotomo Miyamoto, Takashi Katome and Yoshinori Mitamura : DETECTION OF CHOROIDAL FOLDS IN PATIENTS WITH VOGT-KOYANAGI-HARADA DISEASE BY RETROMODE SCANNING LASER OPHTHALMOSCOPY., Retinal Cases & Brief Reports, Vol.10, No.2, 160-164, 2016.
(Summary)
To determine whether the choroidal folds in patients with Vogt-Koyanagi-Harada disease can be detected by retromode of a scanning laser ophthalmoscopy (SLO) with infrared laser light source. The authors examined two patients with Vogt-Koyanagi-Harada disease at the acute stage by retromode imaging scanning laser ophthalmoscopy with an infrared laser before and after steroid treatment. The retromode imaging by scanning laser ophthalmoscopy clearly and noninvasively delineated the choroidal folds in both cases. The folds disappeared after steroid treatment and reappeared with recurrences of uveitis. The retromode imaging by scanning laser ophthalmoscopy can detect the choroidal folds and should be useful for detecting and monitoring the choroidal folds in Vogt-Koyanagi-Harada disease.
Mariko Egawa, Yoshinori Mitamura, Hiroki Sano, Kei Akaiwa, Masanori Niki, Kentaro Senba, Shozo Sonoda and Taiji Sakamoto : Changes of choroidal structure after treatment for primary intraocular lymphoma: retrospective, observational case series., BMC Ophthalmology, Vol.15, 136, 2015.
(Summary)
We report changes of choroidal structure determined by binarization of enhanced depth imaging optical coherence tomographic (EDI-OCT) images after treatment for primary intraocular lymphoma (PIOL). Five eyes of four patients with PIOL were examined by EDI-OCT before and 6 months after intravitreal methotrexate injections. In addition, 15 eyes of 15 normal individuals controlled by age and refractive error were examined by EDI-OCT. Binarization of the EDI-OCT images was performed using publicly accessible software (ImageJ). The examined area of the subfoveal choroid was 1,500 m wide, and the dark areas that represented the luminal areas were traced by the Niblack method. Wilcoxon signed rank test was used to determine the significance of changes in the subfoveal choroidal thickness, interstitial area, and luminal area. Mann-Whitney U test was used to compare the parameters in the eyes with pretreatment PIOL and normal control eyes. The subfoveal choroidal thickness was significantly decreased after treatment (P = 0.0431). In the binarized images, the interstitial area was significantly decreased after treatment (P = 0.0431), while the luminal area was not significantly changed (P = 0.8927). After delayed onset of PIOL, increased interstitial area, thickened choroid and unchanged luminal area were observed in one eye. The interstitial area and choroidal thickness were significantly increased in the eyes with pretreatment PIOL compared with the normal control eyes (P = 0.0207, P = 0.0495, respectively), while the luminal area was not significantly different (P = 0.2752). After treatment for PIOL, the EDI-OCT images showed a thinner choroid, and binarization of the EDI-OCT images showed significantly decreased interstitial areas compared with the luminal areas. The binarized EDI-OCT images can provide useful information on choroidal structure in eyes with PIOL, and combining these images with intraocular interleukin levels or fundus autofluorescence images should provide valuable information for determining the PIOL activity.
Takamasa Kinoshita, Hiroko Imaizumi, Hirotomo Miyamoto, Takashi Katome, Kentaro Senba and Yoshinori Mitamura : Two-year results of metamorphopsia, visual acuity, and optical coherence tomographic parameters after epiretinal membrane surgery., Graefe's Archive for Clinical and Experimental Ophthalmology, Vol.254, No.6, 1041-1049, 2015.
(Summary)
To determine the 2-year results of metamorphopsia, visual acuity, and optical coherence tomographic (OCT) parameters after epiretinal membrane (ERM) removal, and to evaluate the correlations among them. We studied 75 eyes of 75 patients with an ERM who underwent vitrectomy and membrane peeling. The best-corrected visual acuity (BCVA), metamorphopsia scores, and OCT parameters were measured at the baseline, and 1, 3, 6, 9, 12, 18, and 24 months postoperatively. M-CHARTS were used to quantify the degree of metamorphopsia. The mean BCVA, degree of metamorphopsia, and all of the OCT parameters except the photoreceptor outer segment (PROS) length improved significantly from that at the baseline at 24 months (P < 0.001). However, they were not significantly different from those at 12 months. The better BCVA at 24 months was correlated with the longer PROS length at the baseline (P < 0.01). The degree of metamorphopsia at 24 months was significantly correlated with that at baseline (P < 0.01). A postoperative follow-up period of 12 months may be sufficient to assess the improvements induced by the ERM surgery. The preoperative PROS length was the prognostic factor for the postoperative BCVA. The preoperative degree of metamorphopsia was the prognostic factor for the postoperative degree of metamorphopsia, suggesting that surgery for ERM should be performed before development of severe metamorphopsia.
Mariko Egawa, Masayuki Inoue, Yuki Hayashi, Yoshinori Mitamura and Jun Kishi : A case of IgG4-related disease manifesting a variety of ocular lesions over a prolonged course, Japanese Journal of Clinical Ophthalmology, Vol.69, No.8, 1253-1258, 2015.
Mahmoud Mohamed Farouk, Takeshi Naito, Kayo Shinomiya, Hiroshi Eguchi, Khulood Mohammed Sayed, Toshihiko Nagasawa, Takashi Katome and Yoshinori Mitamura : Optical Coherence Tomography Reveals New Insights into the Accommodation Mechanism., Journal of Ophthalmology, Vol.2015, 510459, 2015.
(Summary)
Purpose. To evaluate the movement of the anterior and posterior lens poles during naturally stimulated accommodation in children using anterior segment optical coherence tomography (OCT). Methods. This is a prospective, observational, noncomparative case series including 18 eyes of nine children. Analysis of the anterior segment in the accommodated and unaccommodated state (with cycloplegia) was done using anterior segment OCT. The main outcome measures were the position of the anterior and posterior lens poles (in relation to the cornea) and lens thickness (LT). Results. A Statistically significant forward movement of the anterior lens pole and backward movement of the posterior lens pole with an increase in LT were found during accommodation (P < 0.001). There was no significant difference between the degree of movement of the anterior lens pole and the posterior lens pole during accommodation (P = 0.944). Conclusions. Anterior segment OCT provides a rapid noncontact method for studying accommodation in children. The backward movement of the posterior lens pole during accommodation nearly equals the forward movement of its anterior pole. These data minimize the theoretical hydraulic effect of the vitreous during accommodation, adding more support to the capsular theory of Helmholtz.
Akiko Mino, Kayo Shinomiya, Takashi Kawanaka, Mika Sakaki, 吉本 聖, 坂本 佳也, 荒瀬 友子 and Yoshinori Mitamura : Palliative radiotherapy was effective in a case of sebaceous carcinoma of presumed lacrimal gland origin, Japanese Journal of Clinical Ophthalmology, Vol.69, No.3, 397-402, 2015.
Akiko Iwata, Yoshinori Mitamura, Masanori Niki, Kentaro Senba, Mariko Egawa, Takashi Katome, Shozo Sonoda and Taiji Sakamoto : Binarization of enhanced depth imaging optical coherence tomographic images of an eye with Wyburn-Mason syndrome: a case report., BMC Ophthalmology, Vol.15, 19, 2015.
(Summary)
To report a thicker choroid and larger choroidal luminal area in an eye with Wyburn-Mason syndrome. To the best of our knowledge, this is the first report demonstrating an increase in the choroidal thickness and the luminal area in a case of Wyburn-Mason syndrome. In addition, we report the changing appearance of retinal arteriovenous malformations over a 16-year period. A 27-year-old woman, who was diagnosed with Wyburn-Mason syndrome at age 11 years, visited our clinic. Her best-corrected visual acuity was 20/12.5 in the right eye and light perception in the left eye. Severely dilated, tortuous vascular loops were distributed from the optic disc over all four quadrants of the left fundus. The vascular loops in some areas were more dilated and tortuous than 16 years earlier. Optical coherence tomography (OCT) showed retinal edema with cystic changes and enlarged choroidal vessel lumens in the left eye. The subfoveal choroidal thickness was manually measured by the caliper function in the enhanced depth imaging OCT (EDI-OCT) images. Binarization of the EDI-OCT images was performed with publicly accessible ImageJ software. The examined area of the subfoveal choroid was 1,500 m wide, and the dark areas representing the luminal areas were traced by the Niblack method. After determining the distance of each pixel, the luminal area was automatically calculated. The subfoveal choroidal thickness was 250 m in the right eye and 462 m in the left eye. The luminal area of the 1,500-m-wide subfoveal choroid was computed to be 307,165.6 m(2) in the right eye and 545,780.7 m(2) in the left eye. The EDI-OCT images showed a thicker choroid, and binarization of the EDI-OCT images showed that the luminal areas were significantly larger in the affected eye, suggesting a dilatation of the choroidal vessels. The results demonstrated that conversion of EDI-OCT images to binary images was a useful method to quantify the choroidal structure.
Xiaoli Guo, Kazuhiko Namekata, Atsuko Kimura, Takahiko Noro, Yuriko Azuchi, Kentaro Semba, Chikako Harada, Hiroshi Yoshida, Yoshinori Mitamura and Takayuki Harada : Brimonidine suppresses loss of retinal neurons and visual function in a murine model of optic neuritis., Neuroscience Letters, Vol.592, 27-31, 2015.
(Summary)
Optic neuritis is inflammation of the optic nerve and is strongly associated with multiple sclerosis (MS), an inflammatory demyelinating syndrome of the central nervous system. It leads to retinal ganglion cell (RGC) death and can cause severe vision loss. Brimonidine (BMD) is a selective α2-adrenergic receptor agonist that is used clinically for the treatment of glaucoma. BMD lowers intraocular pressure, but recent evidence suggests that its therapeutic efficacy may also mediate through mechanisms independent of modulation of intraocular pressure. In this study, we examined the effects of topical administration of BMD on retinal degeneration during optic neuritis in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE was induced with MOG35-55 in C57BL/6J mice and BMD eyedrops were applied daily. In the EAE retina, the number of RGCs was significantly decreased and this effect was suppressed with BMD treatment. Consistent with histological analyses, the visual impairment observed in EAE mice was inhibited with BMD treatment, indicating the functional significance of the neuroprotective effect of BMD. Furthermore, BMD increased the expression level of basic fibroblast growth factor in the EAE retina, particularly in Müller glial cells and RGCs. Our findings suggest that topical administration of BMD may be available for RGC protection during optic neuritis, as well as for glaucoma.
Takamasa Kinoshita, Hiroko Imaizumi, Hirotomo Miyamoto, Utako Okushiba, Yuki Hayashi, Takashi Katome and Yoshinori Mitamura : Changes in metamorphopsia in daily life after successful epiretinal membrane surgery and correlation with M-CHARTS score., Clinical Ophthalmology, Vol.9, 225-233, 2015.
(Summary)
To determine the correlation between the changes in metamorphopsia in daily life environment and the M-CHARTS scores after epiretinal membrane (ERM) removal, and to determine the criterion for determining whether clinically significant changes in the metamorphopsia score have occurred in M-CHARTS. We studied 65 eyes undergoing vitrectomy for unilateral ERM. Self-administered questionnaires were used to examine the metamorphopsia in their daily life. The degree of metamorphopsia was determined by M-CHARTS. The receiver operating characteristic curve was used to determine the best predictor of the changes in metamorphopsia in daily life. To determine the reproducibility of the M-CHARTS score, another set of 56 eyes with ERM was tested twice on two different days. The postoperative changes in the logarithm of the M-CHARTS score was defined as M2-value. The area under the receiver operating characteristic curve for the M2-value as a predictor of the changes in metamorphopsia in daily life was larger than area under the receiver operating characteristic curve obtained for any other parameter. The optimal cutoff value was -0.4. The 95% limits of agreement between test and retest measurements had a reproducibility of ±0.3 logarithm of the M-CHARTS score. Taking into account not only the reproducibility but also the consistency with the subjective changes, we determined the criterion for clinically significant changes in the M-CHARTS scores as a change of the M2-value by ≥0.4. Evaluating the changes in the M-CHARTS scores in logarithmic form is favorable not only theoretically but also from the perspective of consistency with the subjective changes.
Hiroshi Eguchi, Toshi Toibana, Fumika Hotta, Tatsuro Miyamoto, Yoshinori Mitamura and Takashi Yaguchi : Severe fungal sclerokeratitis caused by Metarhizium anisopliae: a case report and literature review., Mycoses, Vol.58, No.2, 88-92, 2015.
(Summary)
To date, there has been only one published report on the infectious sclerokeratitis caused by Metarhizium anisopliae, which is an entomopathogenic fungus. Regarding corneal infection, three reports have been published to date. Although the prognoses of the corneal infections are favourable, prognosis when scleral infection is involved is very poor. A 76-year-old patient presented with foreign body sensation in the left eye. Microscopic examination with Fungi Flora Y staining of the corneal scraping revealed fungal infection. The conjunctiva was melted by the infection over a wide area. Although intensive medications were administered, an emergency surgery was necessary because scleral thinning, corneal perforation and lens prolapse occurred. The fungal isolate was identified as M. anisopliae by sequencing the internal transcribed spacer region. Herein, we report the second known case worldwide of M. anisopliae sclerokeratitis, and we review the literature related to the ocular infections.
Akiko Mino, Yoshinori Mitamura, Takashi Katome, Kentaro Senba, Mariko Egawa and Takeshi Naito : Case of adult-onset Coats' disease with epiretinal membrane treated with 25-gauge pars plana vitrectomy., The Journal of Medical Investigation : JMI, Vol.62, No.1-2, 85-88, 2015.
(Summary)
We describe a case of untreated adult-onset Coats' disease with a proliferative epiretinal membrane (ERM) treated successfully with 25-gauge pars plana vitrectomy (25GPPV). A 26-year-old man presented with a 3-week history of decreased vision in his left eye. At the initial examination, the decimal best-corrected visual acuity (BCVA) was 0.7 in the left eye. Ophthalmoscopy revealed the typical appearance of Stage 2A Coats' disease but with a proliferative ERM in the posterior pole. The patient received 2 monthly intravitreal injections of 2.5 mg bevacizumab, 5 laser photocoagulations to the area of telangiectasia, and 1 session of cryoretinopexy. Nine months after the initial visit, a traction by the ERM on the parafoveal area developed causing macular edema which reduced the BCVA to 0.3. He underwent 25GPPV with the removal of the ERM. In addition, the peripheral telangiectasia was treated intraoperatively with both laser photocoagulation and cryoretinopexy. Postoperatively, the traction to the parafoveal area was released and the BCVA improved to 0.6 which remained stable during the follow-up period of 13 months. We conclude that 25GPPV combined with ERM peeling, laser photocoagulation, and cryoretinopexy can be effective for adult-onset Coats' disease associated with an ERM.
Mariko Egawa, Kentaro Senba, Tatsuro Miyamoto, Takeshi Naito and Yoshinori Mitamura : A case of endogenous endophthalmitis due to Listeria monocytogenes, Japanese Journal of Clinical Ophthalmology, Vol.68, No.13, 1737-1740, 2014.
Yosuke Nakamura, Yoshinori Mitamura, Akira Hagiwara, Ken Kumagai, Gen Miura, Takeshi Sugawara, Mariko Egawa and Shuichi Yamamoto : Relationship between retinal microstructures and visual acuity after cataract surgery in patients with retinitis pigmentosa., The British journal of Ophthalmology, Vol.99, No.4, 508-511, 2014.
(Summary)
To study the relationship between the retinal microstructures and the best-corrected visual acuity (BCVA) after cataract surgery in patients with retinitis pigmentosa (RP). 58 eyes of 43 consecutive RP patients who underwent cataract surgery were studied. The BCVA was measured before and 3 months after the surgery. The appearance of the inner segment/outer segment (IS/OS) line of the photoreceptors in the optical coherence tomographic (OCT) images at the fovea was graded; Grade 1, IS/OS line not visible; Grade 2, IS/OS line abnormal or discontinuous; and Grade 3, IS/OS line normal. The central foveal thickness (CFT) and the length of the IS/OS line were measured in the spectral-domain OCT images. The postoperative BCVAs in logMAR units (Grade 1, 1.04±0.36; Grade 2, 0.33±0.16; Grade 3, 0.08±0.14) and the improvements in the BCVA in logMAR units (Grade 1, 0.22±0.28; Grade 2, 0.53±0.48; Grade 3, 0.54±0.35) were significantly different among Grade 1, 2 and 3 groups (p<0.0001, p=0.0378; respectively). A postoperative BCVA of <0.2 logMAR units was achieved in 0% in Grade 1, 20% in Grade 2 and 74% in Grade 3 (p<0.0001). There was a significant correlation between the postoperative BCVA and the length of the IS/OS line (r=-0.601 p<0.0001) or the CFT (r=-0.510, p<0.0001). The presence of normal IS/OS line in the OCT images is associated with good visual recovery after cataract surgery in RP patients. The integrity of the IS/OS line may be important for predicting good postoperative BCVA.
Yuki Hayashi, Hiroshi Eguchi, Toshi Toibana, Yoshinori Mitamura and Takashi Yaguchi : Polymicrobial Sclerokeratitis Caused by Scedosporium apiospermum and Aspergillus cibarius., Cornea, Vol.33, No.8, 875-877, 2014.
(Summary)
The aim of this study was to report the first case of polymicrobial fungal sclerokeratitis caused by infection with both Scedosporium apiospermum and Aspergillus cibarius, and notify the medical community of the possibility of infection caused by A. cibarius in humans. A 78-year-old woman presented to a medical practitioner with epiphora and a purulent discharge in her left eye. After concurrent administration of topical antibiotics and systemic steroids, her symptoms worsened, and she was referred to the Tokushima University Hospital. Because of suspected fungal infection, microscopic examination and cultivation of both corneal and scleral scrapings were performed. Fungi were observed on microscopic examination, and S. apiospermum was isolated only from the sclera in the early stage of the clinical course. Although administration of an adequate medication regimen comprising topical and systemic antifungal drugs resulted in an improvement in the sclera, keratitis persisted, and the infected sclera was melted. After scleral transplantation, administration of systemic caspofungin and high concentrations of voriconazole solution eye drops resulted in a gradual improvement in keratitis. A strain of filamentous fungus was isolated from the cornea 6 weeks after the cultivation on a Sabouraud agar plate, and it was identified as A. cibarius. A. cibarius may infect human tissue. Coinfection of the cornea and the sclera with 2 different species of fungi is likely to follow a complex clinical course.
K Semba, K Namekata, X Guo, C Harada, T Harada and Yoshinori Mitamura : Renin-angiotensin system regulates neurodegeneration in a mouse model of normal tension glaucoma., Cell Death & Disease, Vol.5, e1333, 2014.
(Summary)
Glaucoma, one of the leading causes of irreversible blindness, is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs, and the loss of EAAC1 leads to RGC degeneration without elevated intraocular pressure (IOP). In the present study, we found that expressions of angiotensin II type 1 receptor (AT1-R) and Toll-like receptor 4 (TLR4) are increased in RGCs and retinal Müller glia in EAAC1-deficient (KO) mice. The orally active AT1-R antagonist candesartan suppressed TLR4 and lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expressions in the EAAC1 KO mouse retina. Sequential in vivo retinal imaging and electrophysiological analysis revealed that treatment with candesartan was effective for RGC protection in EAAC1 KO mice without affecting IOP. In cultured Müller glia, candesartan suppressed LPS-induced iNOS production by inhibiting the TLR4-apoptosis signal-regulating kinase 1 pathway. These results suggest that the renin-angiotensin system is involved in the innate immune responses in both neural and glial cells, which accelerate neural cell death. Our findings raise intriguing possibilities for the management of glaucoma by utilizing widely prescribed drugs for the treatment of high blood pressure, in combination with conventional treatments to lower IOP.
K Semba, K Namekata, A Kimura, C Harada, Yoshinori Mitamura and T Harada : Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma., Cell Death & Disease, Vol.5, e1341, 2014.
(Summary)
Glaucoma is one of the leading causes of irreversible blindness that is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino-acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs, and the loss of EAAC1 leads to RGC degeneration without elevated intraocular pressure (IOP). Brimonidine (BMD) is an α2-adrenergic receptor agonist and it is commonly used in a form of eye drops to lower IOP in glaucoma patients. Recent studies have suggested that BMD has direct protective effects on RGCs involving IOP-independent mechanisms, but it is still controversial. In the present study, we examined the effects of BMD in EAAC1-deficient (KO) mice, an animal model of normal tension glaucoma. BMD caused a small decrease in IOP, but sequential in vivo retinal imaging and electrophysiological analysis revealed that treatment with BMD was highly effective for RGC protection in EAAC1 KO mice. BMD suppressed the phosphorylation of the N-methyl-D-aspartate receptor 2B (NR2B) subunit in RGCs in EAAC1 KO mice. Furthermore, in cultured Müller glia, BMD stimulated the production of several neurotrophic factors that enhance RGC survival. These results suggest that, in addition to lowering IOP, BMD prevents glaucomatous retinal degeneration by stimulating multiple pathways including glia-neuron interactions.
Masanori Niki, Hiroshi Eguchi, Yuki Hayashi, Tatsuro Miyamoto, Fumika Hotta and Yoshinori Mitamura : Ineffectiveness of intrastromal voriconazole for filamentous fungal keratitis., Clinical Ophthalmology, Vol.8, 1075-1079, 2014.
(Summary)
The purpose of this study is to describe the ineffectiveness of intrastromal voriconazole injection for filamentous fungal keratitis by contrasting the effectiveness for yeast keratitis. We examined seven fungal keratitis patients prospectively. All yeast was identified by molecular phylogenetic analyses of the chromosomal regions coding for the D1/D2 domain of the large-subunit 26S ribosomal RNA gene. All filamentous fungi were identified by the sequencing of internal transcribed spacers of the ribosomal DNA gene regions. Approximately 0.1 mL of voriconazole diluted with saline to 1.0% was injected with a 30-gauge needle inserted obliquely into the three to five clear cornea sites around the abscess. All subjects were administered natamycin ointment and oral itraconazole. When needed, intravenous micafungin, voriconazole, and/or intracameral voriconazole were added. Clinical courses were observed by the slit lamp microscope. Histopathology was examined when the corneas were removed. All cases that were caused by yeast healed quickly after injections. Two cases of keratitis caused by Fusarium, and one case caused by Aspergillus, did not heal completely. In the Fusarium cases, additional antifungal medications (3.0% topical voriconazole and intravenous injection of micafungin) were needed. After optical penetrating keratoplasty in one of the cases, fungi were found in the deep stroma of the removed cornea. In the case of Aspergillus keratitis, pathological findings also showed fungi deep in the stroma of the removed cornea and the keratitis recurred after therapeutic penetrating keratoplasty. Intrastromal voriconazole injection is successful in treating yeast keratitis. However this is not the case for filamentous fungal keratitis.
Kayo Shinomiya, 樋端 透史, 三田村 さやか, 岡本 里江, 木虎 亜希子, 伊藤 浩太郎, 宮下 領介 and Yoshinori Mitamura : A case of head tilt due to orbital floor fracture, Folia japonica de ophthalmologica clinica, Vol.7, No.4, 287-290, 2014.
Masayasu Kitahashi, Takayuki Baba, Madoka Sakurai, Hirotaka Yokouchi, Mariko Kubota-Taniai, Yoshinori Mitamura and Shuichi Yamamoto : Pneumatic displacement with intravitreal bevacizumab for massive submacular hemorrhage due to polypoidal choroidal vasculopathy., Clinical Ophthalmology, Vol.8, 485-492, 2014.
(Summary)
The purpose of this study was to compare the effectiveness of pneumatic displacement combined with intravitreal bevacizumab (IVB) with that of pneumatic displacement (PD) alone to treat massive submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV). Thirty-two eyes of 32 patients with massive SMH secondary to PCV were studied. Twenty-two eyes were treated with a combination of PD and 1.25 mg of intravitreal bevacizumab (PD + IVB group), and ten eyes with pneumatic displacement alone (PD group). Pretreatment, the differences in best-corrected visual acuity and size of the SMH between the two groups were not significant (P=0.59 and P=0.72, respectively). Complete displacement of the hemorrhage from under the fovea was achieved in 19 of 22 eyes (86.4%) in the PD + IVB group and in five of ten eyes (50%) in the PD group. The best-corrected visual acuity in the PD + IVB group was significantly better than that in the PD group at one, 3, and 6 months after treatment (P<0.001, P<0.001, and P<0.001, respectively). Improvement in best-corrected visual acuity by >0.3 logMAR units was obtained in 18 eyes (81.8%) in the PD + IVB group and two eyes (20%) in the PD group (P<0.001). The number of eyes that required additional treatments was significantly fewer in the PD + IVB group than in the PD group (P=0.0001). The combination of PD and IVB may be a better therapeutic procedure for eyes with massive SMH due to PCV in the short term because of the better visual outcome and less need for additional treatments.
Mariko Egawa, Yoshinori Mitamura, Yuki Hayashi, Kentaro Semba and Takeshi Naito : Changes of fundus autofluorescence and spectral-domain optical coherence tomographic findings after treatment of primary intraocular lymphoma., Journal of Ophthalmic Inflammation and Infection, Vol.4, No.1, 7, 2014.
(Summary)
We report the fundus autofluorescence (FAF), spectral-domain optical coherence tomographic (SD-OCT), microperimetric, and multifocal electroretinographic (mfERG) findings before, during, and after successful treatment of a primary intraocular lymphoma (PIOL). A 57-year-old man had biopsy-proven PIOL in his left eye, and he was treated with intravitreal methotrexate injections for 8 months. Before treatment, fundus examination disclosed many small, yellow lesions with distinct boundaries in the posterior fundus which became atrophic 9 months after the initial treatment. FAF showed a pattern of granular hypoautofluorescence and hyperautofluorescence before the treatments and patchy hypoautofluorescence corresponding to retinal pigment epithelial (RPE) atrophy after the treatments. SD-OCT showed increased nodularity at the level of and above the RPE, a separation of Bruch membrane from the RPE, partial damage of the RPE, disruption of the photoreceptor inner segment/outer segment (IS/OS) junction, multiple hyperreflective signals in the inner retina, foveal thinning, and parafoveal thickening. After treatment, the hyperreflective infiltrations in the inner retina were markedly decreased, and the RPE and IS/OS junction were restored. The foveal thinning and parafoveal thickening resolved, and the central choroidal thickness decreased. During the follow-up, the mfERGs remained decreased. In contrast, microperimetry showed a partial improvement of the retinal sensitivity. FAF and SD-OCT are useful noninvasive methods to evaluate the retinal and choroidal changes before and after treatment of PIOL. Our results suggest that visual recovery after successful treatment may be limited once macula is infiltrated.
Mariko Egawa, Yoshinori Mitamura, Yuki Hayashi and Takeshi Naito : Spectral-domain optical coherence tomographic and fundus autofluorescence findings in eyes with primary intraocular lymphoma., Clinical Ophthalmology, Vol.8, 335-341, 2014.
(Summary)
The purpose of this study was to evaluate the findings on spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) in three eyes with primary intraocular lymphoma (PIOL). The medical records of three eyes from three patients with biopsy-proven PIOL and retinal infiltrations were reviewed. The SD-OCT and fluorescein angiographic findings were evaluated in the three eyes and FAF images in two eyes. The PIOL in the three patients was monocular. Vitreous opacities and retinal infiltrations were observed in the three eyes, and iritis was present in two eyes. The cytologic diagnosis was class V in two eyes and class III in one eye. The interleukin-10/interleukin-6 ratio was >1.0 in the vitreous and aqueous humor of the three eyes. The FAF images for two eyes showed abnormal granular hyperautofluorescence and hypoautofluorescence which were the reverse of the pattern in the fluorescein angiographic images. In all three eyes, SD-OCT showed hyper-reflective infiltrations at the level of the retinal pigment epithelium (RPE), a separation of the Bruch membrane from the RPE, damage to the RPE, disruption of the photoreceptor inner segment/outer segment junction, and multiple hyper-reflective signals in the inner retina. Because of the characteristic FAF and SD-OCT findings in these eyes with PIOL, we suggest that these noninvasive methods may be used for a rapid diagnosis of PIOL and also for understanding the pathology of PIOL.
Tatsuro Miyamoto, Hiroshi Eguchi, Ehkhmaa Tserennadmid, Sayaka Mitamura-Aizawa, Fumika Hotta and Yoshinori Mitamura : Methicillin-Resistant Staphylococcus aureus Keratitis after Descemet's Stripping Automated Endothelial Keratoplasty., Case Reports in Ophthalmology, Vol.4, No.3, 269-273, 2013.
(Summary)
We report a case of methicillin-resistant Staphylococcus aureus (MRSA) keratitis after Descemet's stripping automated endothelial keratoplasty (DSAEK). An 87-year-old woman who had undergone a DSAEK 4 months previously was referred to Tokushima University Hospital with a diagnosis of infectious keratitis after DSAEK. A white abscess and infiltration in the inferior cornea of the right eye were observed. We started an empiric therapy using topical levofloxacin and chloramphenicol on the basis of the microscopic findings of the corneal scraping concurrently with cultivation of the cornea. A strain of MRSA was isolated from the corneal sample. Although the strain was susceptible to chloramphenicol, it was resistant to quinolone. The keratitis improved rapidly due to empiric therapy, and topical steroids could be resumed 6 days after initiation of the empiric therapy. To our knowledge, this is the first case of MRSA keratitis, and the second case of bacterial keratitis, after DSAEK. MRSA keratitis can occur following uneventful DSAEK. The empiric therapy on the basis of results from a light microscopic examination of a Gram-stained corneal scraping and restarting topical steroids in the early stages of medication contributed to the good clinical course of this case.
Hiroshi Eguchi, Tatsuro Miyamoto, Tomomi Kuwahara, Sayaka Mitamura and Yoshinori Mitamura : Infectious conjunctivitis caused by Pseudomonas aeruginosa isolated from a bathroom., BMC Research Notes, Vol.6, No.1, 245, 2013.
(Summary)
The elucidation of the routes of transmission of a pathogen is crucial for the prevention of infectious diseases caused by bacteria that are not a resident in human tissue. The purpose of this report is to describe a case of suture-related conjunctivitis caused by Pseudomonas aeruginosa for which we identified the transmission route using pulsed-field gel electrophoresis (PFGE). A 38-year-old man, who had undergone surgery for glaucoma 2 years ago previously, presented with redness, discomfort, and mucopurulent discharge in the right eye. A 9-0 silk suture had been left on the conjunctiva. A strain of P. aeruginosa was isolated from a culture obtained from the suture, and the patient was therefore diagnosed with suture-related conjunctivitis caused by P. aeruginosa. The conjunctivitis was cured by the application of an antimicrobial ophthalmic solution and removal of the suture. We used PFGE to survey of the indoor and outdoor environments around the patient's house and office in order to elucidate the route of transmission of the infection. Three strains of P. aeruginosa were isolated from the patient's indoor environment, and the isolate obtained from the patient's bathroom was identical to that from the suture. The case highlights the fact that an indoor environmental strain of P. aeruginosa can cause ocular infections.
Mariko Egawa, Yuki Hayashi and Yoshinori Mitamura : Outcome of Vogt-Koyanagi-Harada disease as related to clinical types, Japanese Journal of Clinical Ophthalmology, Vol.67, No.6, 981-984, 2013.
Yoshinori Mitamura, Sayaka Mitamura-Aizawa, Takashi Katome, Takeshi Naito, Akira Hagiwara, Ken Kumagai and Shuichi Yamamoto : Photoreceptor impairment and restoration on optical coherence tomographic image., Journal of Ophthalmology, Vol.2013, 518170, 2013.
(Summary)
With recent development of spectral-domain optical coherence tomography (SD-OCT), the pathological changes of retina can be observed in much greater detail. SD-OCT clearly delineates three highly reflective lines in the outer retina, which are external limiting membrane (ELM), photoreceptor inner and outer segment (IS/OS) junction, and cone outer segment tips (COST) in order from inside. These lines can serve as hallmarks for the evaluation of photoreceptor condition. In retinitis pigmentosa (RP) leading to photoreceptor degeneration, the ELM, IS/OS, and COST lines are shortened with the progression of the disease. In addition, shortening of the ELM, IS/OS and COST lines is significantly associated with each other. The line length is longest in the ELM, followed by the IS/OS, and COST, suggesting that retinal layer becomes disorganized first at the COST, followed by the IS/OS and finally the ELM. This finding is consistent with the previous report that the earliest histopathological change in RP is a shortening of the photoreceptor outer segments. On the other hand, retinal layer becomes restored first at the ELM, followed by the IS/OS and finally the COST after macular hole surgery. There may be a directionality of photoreceptor impairment or restoration on optical coherence tomographic image.
山中 千尋, Mariko Egawa and Yoshinori Mitamura : A case of early-onset sarcoidosis and Blau syndrome, Japanese Journal of Clinical Ophthalmology, Vol.67, No.4, 563-568, 2013.
Tomoaki Tatsumi, Shuichi Yamamoto, Juntaro Uehara, Takeshi Sugawara, Takayuki Baba, Masayuki Inoue, Hiroko Hata and Yoshinori Mitamura : Panretinal photocoagulation with simultaneous cryoretinopexy or intravitreal bevacizumab for neovascular glaucoma., Graefe's Archive for Clinical and Experimental Ophthalmology, Vol.251, No.5, 1355-1360, 2012.
(Summary)
To compare the therapeutic effects of panretinal photocoagulation (PRP) combined with intravitreal bevacizumab (IVB) and cryoretinopexy (CR-IVB) to that of PRP combined with IVB alone in eyes with neovascular glaucoma (NVG). Retrospective, consecutive, case-control study. The medical records of 102 eyes of 96 patients with NVG due to proliferative diabetic retinopathy, central retinal vein occlusion, and ocular ischemic syndrome were reviewed. The mean age of the patients was 59.6 ± 11.5 years, with a range of 34 to 84 years. Patients received either 1.25 mg/0.05 ml of IVB combined with 360° of cryotherapy of the peripheral retina (CR-IVB subgroup) or IVB alone (IVB alone subgroup) as adjunctive treatments to PRP. The patients were followed for at least 12 months. Fifty-four eyes of 49 patients had open-angle NVG; 30 of these eyes were treated by CR-IVB, and 24 eyes by IVB alone. Forty-eight eyes of 48 patients had angle-closure NVG; 22 of these eyes were treated by CR-IVB, and 26 eyes were by IVB alone. Failure was defined as a postoperative intraocular pressure (IOP) >21 mmHg for two consecutive follow-up visits, or the need of additional surgery such as trabeculectomy or diode laser cycloablation. The differences in the success rates between the CR-IVB and IVB alone subgroups for the eyes with open-angle and closed-angle NVG were compared. The success rate at 12 months in eyes with open-angle NVG was 80.0% in the CR-IVB subgroup and 41.7% in the IVB alone subgroup (P = 0.0096). In eyes with angle-closure NVG, the success rate at 12 months was 22.7% in the CR-IVB subgroup and 0% in the IVB-alone subgroup (P = 0.030). The significantly better IOP control after PRP combined with cryotherapy and IVB than after PRP with IVB alone indicates that cryotherapy enhances the effectiveness of PRP for neovascular glaucoma for at least 1 year.
Akira Hagiwara, Yoshinori Mitamura, Ken Kumagai, Takayuki Baba and Shuichi Yamamoto : Photoreceptor impairment on optical coherence tomographic images in patients with retinitis pigmentosa., The British journal of Ophthalmology, Vol.97, No.2, 237-238, 2012.
Takashi Katome, Kazuhiko Namekata, Takeshi Naito, Kentaro Semba, Xiaoli Guo, Chikako Harada, Takayuki Harada and Yoshinori Mitamura : Expression of promyelocytic leukemia protein and vascular endothelial growth factor in aqueous humor and vitreous fluid in patients with proliferative diabetic retinopathy., Diabetes Research and Clinical Practice, Vol.98, No.2, e9-e11, 2012.
(Summary)
To examine the expression of promyelocytic leukemia protein (PML) in the eye of proliferative diabetic retinopathy (PDR) patients. PML mRNA levels were measured in proliferative membranes from 12 PDR patients and idiopathic epiretinal membranes from 5 control patients by quantitative RT-PCR. Protein levels of PML and vascular endothelial growth factor (VEGF) in aqueous humor and vitreous fluid samples from 34 PDR patients and 38 control patients were determined using ELISA. The PML mRNA expression levels in membrane samples, and the PML protein concentrations in aqueous humor and vitreous fluid samples were significantly lower in PDR patients than control patients. We observed a statistically significant inverse correlation between the concentrations of PML and VEGF in the aqueous humor and vitreous fluid of PDR patients. PML may be a good candidate as a diagnostic marker and a therapeutic agent for PDR.
Takashi Katome, Yoshinori Mitamura, Toshihiko Nagasawa, Hiroshi Eguchi and Takeshi Naito : Quantitative analysis of cystoid macular edema using scanning laser ophthalmoscope in modified dark-field imaging., Retina, Vol.32, No.9, 1892-1899, 2012.
(Summary)
To quantitatively analyze cystoid macular edema (CME) using scanning laser ophthalmoscope in the modified dark-field imaging. We studied 37 eyes with CME associated with different diseases before and after treatment. The CME area was measured with the modified dark-field imaging and fluorescein angiography. The best-corrected visual acuity, mean deviation and macular sensitivity measured by Humphrey automated perimetry, and foveal thickness and macular volume determined by optical coherence tomography were investigated. The CME area could be clearly outlined in 50% with the fluorescein angiography and in 100% with the modified dark-field imaging (P < 0.0001). The CME area calculated using the modified dark-field imaging was significantly correlated with that using the fluorescein angiography (P = 0.0001). Before treatment, the CME area calculated using the modified dark-field imaging was significantly correlated with only the macular volume (P = 0.0230). Three months after treatment, decrease in the CME area was significantly correlated with improvement in the best-corrected visual acuity, mean deviation, macular sensitivity, foveal thickness, and macular volume (P < 0.05 for all). Our findings indicate that scanning laser ophthalmoscope in the modified dark-field imaging can measure the CME area and is useful in analyzing CME quantitatively. The findings can also be used to evaluate the effectiveness of treatment.
Hiroshi Eguchi, Tatsuro Miyamoto, Fumika Hotta, Machiko Tomida, Masayuki Inoue and Yoshinori Mitamura : Descemet-stripping automated endothelial keratoplasty for vitrectomized cases with traumatic aniridia and aphakic bullous keratopathy., Clinical Ophthalmology, Vol.6, 1513-1518, 2012.
(Summary)
The surgical indication for Descemet-stripping automated endothelial keratoplasty (DSAEK) is largely limited to phakic or pseudophakic cases of endothelial dysfunction with normal pupils, because the endothelial lenticule is generally attached to the recipient cornea by use of gas tamponade into the anterior chamber. Although it may be desirable for vitrectomized cases with aniridia and aphakic bullous keratopathy without capsule support to undergo DSAEK, one of the major problems is lenticule detachment during surgery or in the postoperative period. To perform DSAEK in such cases, special surgical techniques are needed in order to facilitate adhesion of the lenticule. Herein, we describe a suture technique for attaching the endothelial lenticule in DSAEK for aniridic and aphakic cases that have undergone vitrectomy for traumatic vitreoretinal disease.
Takashi Katome, K Namekata, X Guo, K Semba, D Kittaka, K Kawamura, A Kimura, C Harada, H Ichijo, Yoshinori Mitamura and T Harada : Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury., Cell Death and Differentiation, Vol.20, No.2, 270-280, 2012.
(Summary)
Optic nerve injury (ONI) induces retinal ganglion cell (RGC) death and optic nerve atrophy that lead to visual loss. Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase and has an important role in stress-induced RGC apoptosis. In this study, we found that ONI-induced p38 activation and RGC loss were suppressed in ASK1-deficient mice. Sequential in vivo retinal imaging revealed that post-ONI treatment with a p38 inhibitor into the eyeball was effective for RGC protection. ONI-induced monocyte chemotactic protein-1 production in RGCs and microglial accumulation around RGCs were suppressed in ASK1-deficient mice. In addition, the productions of tumor necrosis factor and inducible nitric oxide synthase in microglia were decreased when the ASK1-p38 pathway was blocked. These results suggest that ASK1 activation in both neural and glial cells is involved in neural cell death, and that pharmacological interruption of ASK1-p38 pathways could be beneficial in the treatment of ONI.
Yuki Hayashi, Hiroshi Eguchi, Tatsuro Miyamoto, Masayuki Inoue and Yoshinori Mitamura : A Case of Delayed-Onset Propionibacterium acnes Endophthalmitis after Cataract Surgery with Implantation of a Preloaded Intraocular Lens., Case Reports in Ophthalmology, Vol.3, No.3, 291-297, 2012.
(Summary)
To report a case of delayed-onset endophthalmitis after implantation of a preloaded intraocular lens (IOL) and examine the surgically removed IOL by scanning electron microscopy (SEM). A 77-year-old female underwent uneventful phacoemulsification and aspiration with preloaded silicone IOL implantation. Since intraocular inflammation unexpectedly worsened 1 month after the surgery, she was referred to our hospital. Her visual acuity was hand motion in the left eye. Hypopyon and fibrin formation were observed in the anterior chamber. A diagnosis of postoperative delayed-onset endophthalmitis was made, and vitrectomy with anterior chamber wash-out was performed. As intraocular inflammation remained unchanged postoperatively, an additional surgery with IOL removal was performed. We cultivated the surgically removed samples of aqueous humor and vitreous fluid under both aerobic and anaerobic conditions, performed 16S rDNA clone library analysis of these clinical samples, and examined the removed IOL by SEM. Inflammation subsided after the re-operation. Although cultures of aqueous and vitreous samples were negative, DNA of Propionibacterium acnes was detected in the aqueous humor. The SEM images showed that the rod bacteria and biofilm-like material formed on the tip of the IOL haptic. Delayed-onset endophthalmitis may occur after uneventful implantation of a preloaded IOL. The SEM findings suggested that the tip of the preloaded IOL haptic might scratch bacteria which adhered to the tip of the injector nozzle when the IOL was inserted into the anterior chamber. In some cases with delayed-onset endophthalmitis, IOL removal is needed to eliminate the bacteria which adhere to the tip of the IOL haptic.
Yuki Hayashi, Mariko Egawa and Yoshinori Mitamura : Choroidal folds in a case of acute posterior multifocal placoid pigment epitheliopathy, Japanese Journal of Clinical Ophthalmology, Vol.66, No.8, 1225-1228, 2012.
Takamasa Kinoshita, Hiroko Imaizumi, Utako Okushiba, Hirotomo Miyamoto, Tetsuo Ogino and Yoshinori Mitamura : Time course of changes in metamorphopsia, visual acuity, and OCT parameters after successful epiretinal membrane surgery., Investigative Ophthalmology & Visual Science, Vol.53, No.7, 3592-3597, 2012.
(Summary)
To follow the changes in the metamorphopsia, visual acuity, and OCT parameters after epiretinal membrane (ERM) removal. The study included 49 eyes of 49 patients with an ERM who underwent vitrectomy and membrane peeling. The changes in the best-corrected visual acuity (BCVA), metamorphopsia, and central foveal thickness (CFT) were evaluated at baseline and 1, 3, 6, 9, and 12 months postoperatively. M-CHARTS were used to quantify metamorphopsia. The mean BCVA, metamorphopsia scores for horizontal lines (MH) and vertical lines (MV), and CFT improved significantly at 12 months after surgery (P < 0.001). The baseline BCVA, MH score, and MV score were significantly correlated with the corresponding BCVA, MH score, and MV score at 12 months after surgery (P < 0.01). The MH and MV scores at 12 months was significantly correlated with the BCVA at 12 months (P < 0.01), and the baseline MV score was significantly correlated with the BCVA at 12 months (P < 0.05). The MH score but not the MV score was significantly correlated with the CFT at baseline and 12 months (P < 0.05). The preoperative BCVA, MH score, and MV score were prognostic factors for the corresponding postoperative BCVA, MH score, and MV score. These results suggest that surgery for ERM should be considered before severe reduction in the BCVA or the degree of metamorphopsia. In addition, the preoperative MV score was a prognostic factor for postoperative BCVA. The MH score but not the MV score was correlated with the CFT preoperatively and postoperatively.
(Keyword)
Aged / Aged, 80 and over / Epiretinal Membrane / Female / Follow-Up Studies / Humans / Male / Middle Aged / Postoperative Period / Prospective Studies / retina / Time Factors / Tomography, Optical Coherence / Treatment Outcome / Vision Disorders / Visual Acuity / vitrectomy
We report the case of a patient with an aggressive retinal astrocytoma accompanied with macular edema and neovascular vessels, who was initially treated with intravitreal bevacizumab injections. A 24-year-old male presented to our clinic complaining of visual disturbance in his right eye. At 8 years of age, he had been diagnosed as having tuberous sclerosis complex. Fundus examination demonstrated a retinal tumor accompanied with marked neovascular vessels on the surface, retinal hemorrhage, and macular edema. After six monthly intravitreal bevacizumab injections, fundus examination demonstrated marked regression of the macular edema and neovascular vessels. Two months later, a vitreous hemorrhage developed which necessitated pars plana vitrectomy. After additional intravitreal bevacizumab injection for preventing intraoperative bleeding, vitrectomy with endophotocoagulation for the tumor was performed. The vitreous sample was obtained during vitrectomy, and we measured the vascular endothelial growth factor concentration by enzyme-linked immunosorbent assay. The surgically removed epiretinal neovascular membrane and biopsied retinal tumor expressed vascular endothelial growth factor, although several intravitreal bevacizumab injections led to a vitreous vascular endothelial growth factor concentration of undetectable levels. The clinical course and immunohistochemical analyses indicate that intravitreal bevacizumab monotherapy may have been insufficient to treat the aggressive retinal astrocytoma with macular edema and that laser photocoagulation or photodynamic therapy for the tumor should be considered following intravitreal bevacizumab injection in such cases.
Takashi Katome, Yoshinori Mitamura, Fumika Hotta, Masanori Niki and Takeshi Naito : Two cases of focal choroidal excavation detected by spectral-domain optical coherence tomography., Case Reports in Ophthalmology, Vol.3, No.1, 96-103, 2012.
(Summary)
To report the clinical findings of 2 patients with focal choroidal excavation in the macula detected by spectral-domain optical coherence tomography (SD-OCT). Three eyes of 2 patients with a focal macular choroidal excavation detected by SD-OCT were studied. The eyes were examined by fundus autofluorescence (FAF), fluorescein angiography, fundus-related microperimetry, and multifocal electroretinography (mfERG). In spite of a complaint of metamorphopsia, the visual acuity was normal in 2 eyes. SD-OCT demonstrated a choroidal excavation in the macula but the foveal contour was normal in 3 eyes. The excavation involved the outer retinal layers up to the external limiting membrane in all eyes, and a type 2 secondary choroidal neovascularization (CNV) developed in 1 of the 3 eyes. There were areas of hypoautofluorescence in the FAF images, and areas of decreased retinal sensitivity determined by microperimetry. These areas corresponded to the choroidal excavation in all eyes. The P1 amplitudes of the mfERGs were decreased in the fovea of 1 eye without a CNV. The choroidal excavation remained stable for 3 years in 2 eyes, a secondary CNV developed in 1 eye during the course of the disease. More cases and longer follow-up periods will be necessary to determine the etiology, clinical course, and visual prognosis of eyes with a choroidal excavation.
Yosuke NAKAMURA, Norio TAKEDA, Tomoaki TATSUMI, Toshiyuki OSHITARI, Miyuki ARAI, Yoko TAKATSUNA, Yoshinori Mitamura and Shuichi YAMAMOTO : Macular Ischemia Following Intravitreal Bevacizumab Therapy for Diabetic Macular Edema, Acta Societatis Ophthalmologicae Japonicae, Vol.116, No.2, 108-113, 2012.
(Summary)
To examine the effects of macular ischemia after intravitreal bevacizumab (IVB) in patients with diabetic macular edema(DME). Thirty-three eyes of 33 patients with DME were treated with IVB. Fluorescein angiography (FA) was conducted before and 3 months after IVB, the pretreatment sizes of the foveal avascular zone (FAZ) calculated by FA were compared to the values at 3 months after IVB. This study was approved by the Chiba University Hospital Clinical Research Ethics Committee. After IVB, the size of the FAZ enlarged significantly (p = 0.03). Among the 33 patients treated with IVB, 2 patients (6%) had advanced macular ischemia with an FAZ enlarged by 50% or more. In both patients, the visual acuity did not worsen and the foveal thickness decreased. It is possible that IVB led to macular ischemia.
Khulood Mohammed Sayed, Takeshi Naito, Mahmoud Mohamed Farouk, Toshihiko Nagasawa, Takashi Katome, Ismail Mousa Abd El-Latif, Ahmad Mostafa Abdallah, Usama Ali Mohamed and Yoshinori Mitamura : Twenty five-gauge sutureless vitrectomy versus 20-gauge vitrectomy in epiretinal membrane surgery., The Journal of Medical Investigation : JMI, Vol.59, No.1-2, 69-78, 2012.
(Summary)
To compare visual outcomes, intraoperative and postoperative complications of 25-gauge transconjunctival sutureless vitrectomy (25-G TSV) versus conventional 20-gauge vitrectomy in epiretinal membrane (ERM) surgery. A retrospective comparative study was conducted on 200 eyes with idiopathic ERM who underwent either primary 20-gauge vitrectomy (n=95) or 25-G TSV (n=105) with 6 months follow up. The following parameters were collected and compared: age, gender, best corrected visual acuity (BCVA), intraocular pressure (IOP), postoperative anterior chamber inflammation, intraoperative and postoperative complications. Twenty-five gauge group achieved a significantly better vision at the 1(st) postoperative month (p=0.008) and a significantly higher incidence of visual improvement 6 months postoperatively (p=0.04) than 20-gauge group. Intraocular pressure was significantly higher at the 1(st), 3(rd) and 6(th) postoperative months compared with baseline in the 20-G group. However, in the 25-gauge group IOP remained near to the baseline at the same period. Twenty five-gauge group achieved a significantly lower anterior chamber inflammation and a lower incidence of postoperative cystoid macular edema (CME) (p=0.01), hyphema (p=0.000) and after cataract (p=0.000) than 20-gauge group. The 25-gauge sutureless vitrectomy achieves rapid and higher visual improvement, less postoperative inflammation and complications than the 20-gauge vitrectomy in ERM surgery.
Tatsuro Miyamoto, Hiroshi Eguchi and Yoshinori Mitamura : Ocular findings following discontinuation of oral pilocarpine in patients with dry eye, Japanese Journal of Clinical Ophthalmology, Vol.66, No.1, 67-71, 2012.
Tatsuro Miyamoto, Hiroshi Eguchi, Takashi Katome, Toshihiko Nagasawa, Yoshinori Mitamura and Geoffrey Crawford : Efficacy of the Quickert procedure for involutional entropion: the first case series in Asia., The Journal of Medical Investigation : JMI, Vol.59, No.1-2, 136-142, 2012.
(Summary)
To report the efficacy of the Quickert procedure in the first case series of involutional entropion in an elderly Asian population, and to introduce the technique to Asian ophthalmologists including general ophthalmologisits and ophthalmic trainees. We conducted a retrospective review of 13 consecutive patients underwent the Quickert procedure for involutional entropion by occasional eyelid surgeons at Tokushima University Hospital or Mino Tanaka Hospital from September 2003 to April 2010. Demographic data, including gender, age, history of previous eyelid surgery, systemic disease, recurrence of entropion, postoperative complications, and symptoms were analyzed. There were 5 male (38.5%) and 8 female (61.5%) subjects with a mean age of 77.8 years. Three patients underwent previous surgery for entropion were included. Entropion was rectified in all patients by a single Quickert procedure, and no recurrence was observed for a maximum of 89 months after the surgery. Although notching of the eyelid margin and mild symblepharon were observed in one patient, no symptoms associated with these complications were reported. The Quickert procedure can be one of the surgical procedures of choice for involutional entropion and should be common surgical approach for occasional eyelid surgeons in Asia as well as in western countries.
(Keyword)
Aged / Aged, 80 and over / aging / Asian Continental Ancestry Group / Entropion / Eyelids / Female / Humans / Male / Ophthalmologic Surgical Procedures / Retrospective Studies
Yoshinori Mitamura, Sayaka Mitamura-Aizawa, Toshihiko Nagasawa, Takashi Katome, Hiroshi Eguchi and Takeshi Naito : Diagnostic imaging in patients with retinitis pigmentosa., The Journal of Medical Investigation : JMI, Vol.59, No.1-2, 1-11, 2012.
(Summary)
Retinitis pigmentosa (RP) is a progressive inherited retinal disease, and patients with RP have reduced visual function caused by a degeneration of the photoreceptors and retinal pigment epithelium (RPE). At the end stage of RP, the degeneration of the photoreceptors in the fovea reduces central vision, and RP is one of the main causes of acquired blindness in developed countries. Therefore, morphological and functional assessments of the photoreceptors in the macula area can be useful in estimating the residual retinal function in RP patients. Optical coherence tomography (OCT) is a well-established method of examining the retinal architecture in situ. The photoreceptor inner/outer segment (IS/OS) junction is observed as a distinct, highly reflective line by OCT. The presence of the IS/OS junction in the OCT images is essential for normal visual function. Fundus autofluorescence (FAF) results from the accumulation of lipofuscin in the RPE cells and has been used to investigate RPE and retinal function. More than one-half of RP patients have an abnormally high density parafoveal FAF ring (AF ring). The AF ring represents the border between functional and dysfunctional retina. In this review, we shall summarize recent progress on diagnostic imaging in eyes with RP.
Yuki Hayashi, Mariko Egawa, Takeshi Naito and Yoshinori Mitamura : Vitreous biopsy for the diagnosis of intraocular lymphoma in twenty-three eyes, Japanese Journal of Clinical Ophthalmology, Vol.65, No.7, 1069-1073, 2011.
Emi Ooka, Yoshinori Mitamura, Takayuki Baba, Masayasu Kitahashi, Toshiyuki Oshitari and Shuichi Yamamoto : Foveal microstructure on spectral-domain optical coherence tomographic images and visual function after macular hole surgery., American Journal of Ophthalmology, Vol.152, No.2, 283-290.e1, 2011.
(Summary)
To determine the correlation between the recovery of foveal microstructure and the visual acuity or the foveal sensitivity after idiopathic macular hole (MH) closure. Prospective, consecutive, observational case series. We studied 43 eyes of 43 patients before and 1, 3, and 6 months after MH surgery. The best-corrected visual acuity (BCVA), the foveal sensitivity measured by MP1 microperimetry, and the photoreceptor inner and outer segment (IS/OS) junction and the external limiting membrane (ELM) determined by spectral-domain optical coherence tomography were investigated. Preoperatively, the lengths of the IS/OS junction defect and the ELM defect were significantly correlated with only the foveal sensitivity (P<.0001). At all postoperative times, the lengths of both the IS/OS and ELM defects were significantly correlated with both the BCVA and the foveal sensitivity (P<.05 for all). The preoperative lengths of both the IS/OS and ELM defects were significantly correlated with the foveal sensitivity at 6 months after surgery (P=.0022, P=.0031, respectively). The IS/OS junction defect was significantly correlated with the ELM defect at all times (P<.0001 for all). No restoration of the IS/OS junction was observed in eyes without the ELM restoration. The restoration of the ELM is closely associated with that of the IS/OS junction. The preoperative IS/OS or ELM defect was associated with the postoperative foveal sensitivity. The restoration of not only the IS/OS junction but also the ELM may reflect the morphologic and functional recovery of the foveal photoreceptors in surgically closed MHs.
Akira Hagiwara, Shuichi Yamamoto, Kazuha Ogata, Takeshi Sugawara, Ayako Hiramatsu, Mamiko Shibata and Yoshinori Mitamura : Macular abnormalities in patients with retinitis pigmentosa: prevalence on OCT examination and outcomes of vitreoretinal surgery., Acta Ophthalmologica, Vol.89, No.2, e122-5, 2011.
(Summary)
Abstract. Purpose: To determine the prevalence of macular abnormalities detected by optical coherence tomography (OCT) in patients with retinitis pigmentosa (RP), and to report the results of pars plana vitrectomy (PPV) in five patients with RP. Methods: OCT images of the macula of 622 eyes of 323 patients with RP were evaluated. All patients had a complete clinical examination, and PPV was performed on two RP patients with a macular hole (MH), two patients with vitreomacular traction (VMT) syndrome, and one patient with cystoid macular oedema (CME). Results: A macular lesion was detected by OCT in 46 eyes (7.4%) of 37 patients (11.5%). CME was detected in 34 eyes (5.5%) of 26 patients, an epiretinal membrane in four eyes of four patients, VMT in five eyes of four patients, and full-thickness MH in three eyes of three patients. PPV was performed on five of these eyes. The MH was closed with vision improvement after a single surgery in one eye, and was closed after repeated PPVs with a decrease of vision in another eye. In both patients with VMT, the visual acuity decreased after the surgery. The macular morphology and visual acuity did not improve postoperatively on the one patient with CME who underwent PPV. Conclusion: When OCT is used, macular abnormalities are present in 7.4% of patients with RP, which is lower than the prevalence reported earlier. Although vitrectomy can improve the macular morphology in some patients with RP, improvement of visual function may be limited most likely because of the long-standing retinal dysfunction.
Purpose. To assess the effects of spermidine on the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), with a focus on optic neuritis often associated with MS and EAE. Methods. Myelin oligodendrocyte glycoprotein-induced EAE mice were administered with or without spermidine at 30 mM in drinking water for 25 days. Clinical signs of EAE were scored daily and visual functions were measured by multifocal electroretinograms. Histopathology analysis of the spinal cord and optic nerve were performed after mice were sacrificed on day 25. Hydrogen peroxide (H(2)O(2)) was detected using the probe 2'-7' dichlorofluorescein diacetate (DCFDA) in the optic nerve. The effect of spermidine on H(2)O(2)-induced retinal ganglion cell apoptosis was investigated by lactate dehydrogenase assay. Results. Everyday clinical scoring revealed that the severity of EAE was significantly attenuated in spermidine-treated group, which was confirmed by milder demyelination and improved axon survival in the spinal cord of spermidine-treated mice. Visual functions were significantly improved in spermidine-treated mice compared with vehicle-treated mice. Spermidine treatment ameliorated the extent of demyelination in the optic nerve and prevented cell loss in the retinal ganglion cell layer. Furthermore, fewer DCFDA-labeled cells were found in the optic nerve in the spermidine-treated EAE mice, and in vitro analysis revealed that spermidine reduced H(2)O(2)-induced retinal ganglion cell apoptosis, suggesting that spermidine alleviated the severities of EAE, particularly of optic neuritis, by acting as an antioxidant. Conclusions. The results from this study suggest that oral spermidine administration could be a useful treatment for MS.
平野 香織, Yoshinori Mitamura and 小片 一葉 : Three cases of retinal arterial macroaneurysm on the optic disc, Acta Societatis Ophthalmologicae Japonicae, Vol.114, No.9, 801-804, 2010.
(Summary)
Retinal arterial macroaneurysm typically involves the second order arterioles and is relatively uncommon on the optic disc. Here, we present three cases of retinal arterial macroaneurysm. Case 1 was a 56-year-old woman, Case 2 was a 78-year-old man, and Case 3 was an 86-year-old man. In Cases 1 and 3, the fundus could not be observed visually at the time of initial examination because of vitreous bleeding. Retinal arterial macroaneurysm was revealed during vitrectomy. In Case 2, retinal arterial macroaneurysm was found on the optical disc along with a retinal hemorrhage which disappeared without any treatment. In all three cases, visual acuity was normal after treatment. Since retinal arterial macroaneurysm on the optical disc may be overlooked when treating vitreous bleeding in cases where the cause is not known, we believe that retinal arterial macroaneurysm should be taken into consideration as a possible underlying cause. While photocoagulation of retinal arterial macroaneurysm on the optic disc is infrequently used to, localized photocoagulation retinal arterial macroaneurysm on the optic disk is considered to be difficult. We are of the opinion that progression should be observed carefully till the macroaneurysm is absorbed.
Yoshinori Mitamura, Masayasu Kitahashi, Mariko Kubota-Taniai and Shuichi Yamamoto : Comparison of intravitreal bevacizumab to photodynamic therapy for polypoidal choroidal vasculopathy: short-term results., Indian Journal of Ophthalmology, Vol.58, No.4, 291-296, 2010.
(Summary)
AIMS: To compare the short-term therapeutic effects of intravitreal bevacizumab (IVB) to those of photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV). MATERIALS AND METHODS: Retrospective interventional case study. Eighty-nine eyes of 89 patients with symptomatic PCV were treated by IVB or PDT. Eighteen eyes were treated with a single injection of IVB (s-IVB group), 22 eyes with three consecutive monthly IVB injections (m-IVB group), and 49 eyes with PDT alone (PDT group). The best-corrected visual acuity (BCVA) and OCT-determined central foveal thickness (CFT) were evaluated before, and one and three months after the treatment. For statistical analyses, one-factor ANOVA and Chi-square test were used. RESULTS: The differences in the BCVA and CFT among the three groups at the baseline were not significant (P=0.992, P=0.981, respectively). Three months after the treatment, the BCVA improved by> 0.2 logMAR units in two out of 18 eyes (11%) in the s-IVB group, three out of 22 eyes (14%) in the m-IVB group, and 15 out of 49 eyes (31%) in the PDT group (P=0.124). A decrease in the CFT by> 20% was achieved in six out of 18 eyes in the s-IVB group, ten eyes (46%) in the m-IVB group, and 35 eyes (71%) in the PDT group (P=0.009). The resolution of polyps was achieved in three out of 18 eyes in the s-IVB group, one eye (5%) in the m-IVB group and 35 eyes (71%) in the PDT group (P < 0.001). CONCLUSION: The better short-term therapeutic outcomes in the PDT group than in the s-IVB and m-IVB groups indicate that PDT may be more effective than IVB in short term after treatment for PCV.
C Harada, K Namekata, X Guo, H Yoshida, Yoshinori Mitamura, Y Matsumoto, K Tanaka, H Ichijo and T Harada : ASK1 deficiency attenuates neural cell death in GLAST-deficient mice, a model of normal tension glaucoma., Cell Death and Differentiation, 2010.
(Summary)
Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase and has an important role in stress-induced retinal ganglion cell (RGC) apoptosis. In the mammalian retina, glutamate/aspartate transporter (GLAST) is a major glutamate transporter, and the loss of GLAST leads to optic nerve degeneration similar to normal tension glaucoma (NTG). In GLAST(-/-) mice, the glutathione level in the retina is decreased, suggesting the involvement of oxidative stress in NTG pathogenesis. To test this hypothesis, we examined the histology and visual function of GLAST(+/-):ASK1(-/-) and GLAST(-/-):ASK1(-/-) mice by multifocal electroretinograms. ASK1 deficiency protected RGCs and decreased the number of degenerating axons in the optic nerve. Consistent with this finding, visual function was significantly improved in GLAST(+/-):ASK1(-/-) and GLAST(-/-):ASK1(-/-) mice compared with GLAST(+/-) and GLAST(-/-) mice, respectively. The loss of ASK1 had no effects on the production of glutathione or malondialdehyde in the retina or on the intraocular pressure. Tumor necrosis factor (TNF)-induced activation of p38 MAPK and the production of inducible nitric oxide synthase were suppressed in ASK1-deficient Müller glial cells. In addition, TNF-induced cell death was suppressed in ASK1-deficient RGCs. These results suggest that ASK1 activation is involved in NTG-like pathology in both neural and glial cells and that interrupting ASK1-dependent pathways could be beneficial in the treatment of glaucoma, including NTG.Cell Death and Differentiation advance online publication, 21 May 2010; doi:10.1038/cdd.2010.62.
Sayaka Aizawa, Yoshinori Mitamura, Akira Hagiwara, Takeshi Sugawara and Shuichi Yamamoto : Changes of fundus autofluorescence, photoreceptor inner and outer segment junction line, and visual function in patients with retinitis pigmentosa., Clinical & Experimental Ophthalmology, 2010.
(Summary)
Abstract Background: To determine whether a significant correlation exists among the changes in the size of the abnormal parafoveal autofluorescence ring, the length of the photoreceptor inner and outer segment (IS/OS) junction, and the visual function in patients with retinitis pigmentosa. Methods: Retrospective observational case series. A total of 50 eyes of 26 patients with typical retinitis pigmentosa and an autofluorescence ring were examined by optical coherence tomography and microperimetry. During the follow-up period of >2 years, the changes in the diameter and area of the autofluorescence ring, the length of the IS/OS line, the best-corrected visual acuity and mean retinal sensitivity in the central 10 degrees were determined. Results: The diameter and area of the autofluorescence ring, and the length of the IS/OS line decreased significantly during the follow-up period (all, P < 0.0001). The decrease in autofluorescence ring diameter was significantly correlated with the decrease in retinal sensitivity, visual acuity and IS/OS length (P = 0.0105, P = 0.0252 and P < 0.0001, respectively). The decrease in autofluorescence ring area was significantly correlated with the decrease in retinal sensitivity, visual acuity and IS/OS length (P < 0.0001, P = 0.0026 and P = 0.0011, respectively). Conclusion: During the progression of retinitis pigmentosa, the progressive constriction of the autofluorescence ring reflects the morphological changes of the photoreceptors, and is associated with a worsening of visual function.
Tetsu Yoshida, Xiaoli Guo, Kazuhiko Namekata, Yoshinori Mitamura, Shoen Kume and Takayuki Harada : Expression of Epiplakin1 in the developing and adult mouse retina., Japanese Journal of Ophthalmology, Vol.54, No.1, 85-88, 2010.
(Summary)
PURPOSE: To assess the expression of Epiplakin1 (Eppk1) in the developing and adult mouse retina. METHODS: Eppk1 expression was examined using reverse transcription-polymerase chain reaction (RTPCR) analysis and immunoblot analysis. The Eppk1 expression pattern was examined by immunohistochemical analysis in embryonic and adult C57BL/6J mice. RESULTS: Both Eppk1 mRNA and protein were detected in adult mouse retina. Eppk1 was expressed in nestin-positive neural progenitor cells in the embryonic retina. In adults, Eppk1 was expressed in retinal ganglion cells, bipolar cells, and Müller glial cells. CONCLUSIONS: These results suggest that Eppk1 is expressed both in embryonic and adult retina and may be involved in retinal development.
Natsuyo Yoshida-Hata, Yoshinori Mitamura, Toshiyuki Oshitari, Kazuhiko Namekata, Chikako Harada, Takayuki Harada and Shuichi Yamamoto : Transcription factor, SP1, in epiretinal membranes of patients with proliferative diabetic retinopathy., Diabetes Research and Clinical Practice, Vol.87, No.3, e26-8, 2010.
(Summary)
SP1 mRNA was highly expressed in the epiretinal membranes of proliferative diabetic retinopathy (PDR), and the SP1 protein was mainly co-localized with vascular endothelial growth factor. SP1 might play an important role in the angiogenesis of PDR by regulating the promoter activity and expression of genes encoding angiogenesis-related factors.
Takayuki Baba, Mariko Kubota-Taniai, Masayasu Kitahashi, Kyoko Okada, Yoshinori Mitamura and Shuichi Yamamoto : Two-year comparison of photodynamic therapy and intravitreal bevacizumab for treatment of myopic choroidal neovascularisation., The British journal of Ophthalmology, Vol.94, No.7, 864-870, 2009.
(Summary)
AIM: To compare the long-term outcome of photodynamic therapy (PDT) with that of intravitreal bevacizumab (IVB) for myopic choroidal neovascularizations (mCNVs). METHODS: 24 eyes were selected from 40 consecutive patients with mCNV, and the patients were divided into Group A, consisting of 12 eyes treated by PDT, and Group B, consisting of 12 eyes treated by 1.25 mg IVB. The age and best-corrected visual acuity (BCVA) were matched between the two groups. The BCVA, size of the chorioretinal atrophy surrounding the CNV (CRA), central foveal thickness (CFT) and CNV thickness were determined before and at 12 and 24 months after the treatment. RESULTS: The BCVA did not change after PDT but was significantly improved from 0.75+/-0.25 to 0.49+/-0.42 logMAR units at 12 months and to 0.50+/-0.38 logMAR units at 24 months after IVB. The CFT were significantly reduced in both groups at 12 and 24 months. The CRAs were larger in group A than in group B at 12 and 24 months, and their sizes were correlated with the BCVA. CONCLUSION: At 24 months, IVB is more effective than PDT in treating mCNV. The enlargement of the CRA might be related to the incomplete visual recovery after PDT.
Glaucoma, one of the leading causes of irreversible blindness, is characterized by progressive degeneration of retinal ganglion cells (RGCs) and optic nerves. Although glaucoma is often associated with elevated intraocular pressure, recent studies have shown a relatively high prevalence of normal tension glaucoma (NTG) in glaucoma patient populations. In the mammalian retina, glutamate/aspartate transporter (GLAST) is localized to Müller glial cells, whereas excitatory amino acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs. Since the loss of GLAST or EAAC1 leads to retinal degeneration similar to that seen in NTG, we examined the effects of interleukin-1 (IL-1) on RGC death in GLAST- and EAAC1-deficient mice. IL-1 promoted increased glutamate uptake in Müller cells by suppressing intracellular Na(+) accumulation, which is necessary to counteract Na(+)-glutamate cotransport. The observed trends for the glutamate uptake increase in the wild-type (WT), GLAST- and EAAC1-deficient mice were similar; however, the baseline glutamate uptake and intracellular Na(+) concentration in the GLAST-deficient mice were significantly lower than those in the wild-type mice. Consistently, pretreatment with IL-1 exhibited no beneficial effects on glutamate-induced RGC degeneration in the GLAST-deficient mice. In contrast, IL-1 significantly increased glutamate uptake by Müller cells and the number of surviving RGCs in the wild-type and EAAC1-deficient mice. Our findings suggest that the use of IL-1 for enhancing the function of glutamate transporters may be useful for neuroprotection in retinal degenerative disorders including NTG.
Kyoko Okada, Mariko Kubota-Taniai, Masayasu Kitahashi, Takayuki Baba, Yoshinori Mitamura and Shuichi Yamamoto : Changes in visual function and thickness of macula after photodynamic therapy for age-related macular degeneration., Clinical Ophthalmology, Vol.3, 483-488, 2009.
(Summary)
PURPOSE: To determine the correlation between the changes in the central retinal sensitivity and the changes in the foveal thickness (FT) after photodynamic therapy (PDT) for age-related macular degeneration (AMD). METHODS: Nineteen eyes of 19 patients with choroidal neovasularizations (CNVs) secondary to AMD were studied. The pretreatment values of the central retinal sensitivity determined by Micro Perimeter 1 (MP1; Nidek Technologies), best-corrected visual acuity (BCVA), and optical coherence tomography (OCT)-determined FT were compared to the postoperative values at three and six months after PDT. RESULTS: At six months, the retinal sensitivity within the central 10 degrees was significantly improved (P = 0.02) and the FT was significantly thinner (P = 0.016). The BCVA, however, did not change significantly (P = 0.80). The changes in the retinal sensitivities were significantly correlated with the changes in the decrease in the FT (r = - 0.59, P = 0.012 within the central 10 degrees ) at six months after PDT. CONCLUSION: Significant improvements in retinal sensitivities within the central 10 degrees and a decrease in FT were observed even though the BCVA was not significantly improved. The measurement of retinal sensitivity by MP1 may be a better method to assess central visual function than the conventional visual acuity after PDT.
Yosuke NAKAMURA, Tomoaki TATSUMI, Miyuki ARAI, Yoko TAKATSUNA, Yoshinori Mitamura and Shuichi YAMAMOTO : Subthreshold Micropulse Diode Laser Photocoagulation for Diabetic Macular Edema with Hard Exudates, Acta Societatis Ophthalmologicae Japonicae, Vol.113, No.8, 787-791, 2009.
(Summary)
To examine the efficacy of subthreshold micropulse diode laser photocoagulation (SMDLP) in eyes with diabetic macular edema (DME) with hard exudates. Ten eyes of 10 patients with diffuse DME were treated with SMDLP (810 nm). Hard exudates had accumulated within the foveal avascular zone (FAZ) in all patients. The mean retinal sensitivity within the central 10 degrees was measured with a fundus-related microperimeter (MP 1); the best corrected visual acuity (BCVA) in logMAR units and optical coherence tomography (OCT)-determined foveal thickness (FT) were recorded before and at 3 months after SMDLP. The FT did not decrease significantly after SMDLP, but the BCVA improved significantly from 0.51 +/- 0.25 to 0.40 +/- 0.31 logMAR units (p= 0.02). There was no significant change in the mean retinal sensitivity within the central 10 degrees after SMDLP. SMDLP can improve the visual acuity even in eyes with DME and hard exudates. However, the therapeutic efficacy of SMDLP in these cases may be limited, because no significant improvement in either the foveal thickness or retinal sensitivity could be seen.
Xiaoli Guo, Chikako Harada, Kazuhiko Namekata, Kenji Kikushima, Yoshinori Mitamura, Hiroshi Yoshida, Yoh Matsumoto and Takayuki Harada : Effect of geranylgeranylacetone on optic neuritis in experimental autoimmune encephalomyelitis., Neuroscience Letters, Vol.462, No.3, 281-285, 2009.
(Summary)
Optic neuritis is an acute inflammatory demyelinating syndrome of the central nervous system (CNS) that often occurs in multiple sclerosis (MS). Since it can cause irreversible visual loss, especially in the optic-spinal form of MS or neuromyelitis optica (NMO), the present study was conducted to assess the effects of geranylgeranylacetone (GGA) on optic neuritis in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Myelin oligodendrocyte glycoprotein-induced EAE mice received oral administration of GGA at 500 mg/kg or vehicle once daily for 22 days. The effects of GGA on the severity of optic neuritis were examined by morphological analysis on day 22. Visual functions were measured by the multifocal electroretinograms (mfERG). In addition, the effects of GGA on severity of myelitis were monitored both on clinical signs and morphological aspects. The visual function, as assessed by the second-kernel of mfERG, was significantly improved in GGA-treated mice compared with vehicle-treated mice. GGA treatment decreased the number of degenerating axons in the optic nerve and prevented cell loss in the retinal ganglion cell layer. However, the severity of demyelination in the spinal cord remained unaffected with the treatment of GGA. These results suggest that oral GGA administration has beneficial effect on the treatment for optic neuritis in the EAE mouse model of MS.
Miyuki Arai, Shuichi Yamamoto, Yoshinori Mitamura, Eiju Sato, Takeshi Sugawara and Satoshi Mizunoya : Efficacy of vitrectomy and internal limiting membrane removal for macular edema associated with branch retinal vein occlusion., Ophthalmologica, Vol.223, No.3, 172-176, 2009.
(Summary)
AIM: To compare the results of vitrectomy with internal limiting membrane (ILM) peeling to that without ILM peeling for macular edema associated with branch retinal vein occlusion (BRVO). METHODS: The medical records of 47 eyes of 47 patients with BRVO-associated macular edema were examined. To treat the macular edema, a posterior vitreous detachment (PVD) was created, and the ILM was removed in 13 eyes (ILM-removed group), whereas a PVD was created and the ILM was not removed in 34 eyes (ILM-preserved group). The best-corrected visual acuity (BCVA) and the optical-coherence-tomography-determined foveal thickness were obtained preoperatively and at 6 months postoperatively. RESULTS: The mean postoperative BCVA was significantly better than the preoperative BCVA in both the ILM-removed and in the ILM-preserved groups (p = 0.0017 and p = 0.0002, respectively). The fovea was significantly thinner at 1 month after surgery in both groups (p = 0.0007 and p < 0.0001, respectively). The postoperative improvement of the mean BCVA and the foveal thickness were not significantly different for the two groups at any postoperative period. CONCLUSIONS: Because there was no significant difference in the improvement of BCVA between the two groups at 6 months postoperatively, there may be no additional benefit in removing the ILM for BRVO-associated macular edema.
Akihiro Uemura, Shuichi Yamamoto, Eiju Sato, Takeshi Sugawara, Yoshinori Mitamura and Satoshi Mizunoya : Vitrectomy alone versus vitrectomy with simultaneous intravitreal injection of triamcinolone for macular edema associated with branch retinal vein occlusion., Ophthalmic Surgery, Lasers & Imaging, Vol.40, No.1, 6-12, 2009.
(Summary)
BACKGROUND AND OBJECTIVE: To evaluate the efficacy of vitrectomy with simultaneous intravitreal injection of triamcinolone acetonide for macular edema associated with branch retinal vein occlusion. PATIENTS AND METHODS: A retrospective study of 45 eyes with macular edema associated with branch retinal vein occlusion. A posterior vitreous detachment was created and the vitreous cortex was completely removed, after which 23 eyes immediately had an intravitreal injection of triamcinolone acetonide (triamcinolone acetonide group) and 22 eyes did not (no triamcinolone acetonide group). Visual acuity, fluorescein angiograms, and foveal thickness determined by optical coherence tomography were examined preoperatively and postoperatively. RESULTS: Mean postoperative visual acuity at 12 months was significantly better than the preoperative visual acuity in both groups. The fovea was significantly thinner 1 month postoperatively in both groups. Foveal thickness gradually decreased until 12 months in the no triamcinolone acetonide group; however, foveal thickness increased for 12 months in the triamcinolone acetonide group. A recurrence of macular edema was more frequent in the triamcinolone acetonide group than in the no triamcinolone acetonide group (P = .006). CONCLUSIONS: Because there was no significant difference in the improvement of best-corrected visual acuity between the groups 12 months postoperatively, there may be no benefit in the use of intraoperative intravitreal triamcinolone acetonide.
Natsuyo Hata, Toshiyuki Oshitari, Akiko Yokoyama, Yoshinori Mitamura and Shuichi Yamamoto : Increased expression of IRE1α and stress-related signal transduction proteins in ischemia-reperfusion injured retina., Clinical Ophthalmology, Vol.2, No.4, 743-752, 2008.
(Summary)
The purpose of this study was to determine whether the expression of ER stress-related factors IRE1alpha, apoptosis signal-regulating kinase 1 (ASK1), SAPK/ERK kinase 1 (SEK1) and c-Jun N-terminal kinase (JNK) is associated with the damaged retinal neurons induced by ischemia-reperfusion injury. After 60 minutes of ischemia, the rat retinas were reperfused, and retinas were isolated and fixed after 6, 9, 12, 18, and 24 hours, and 2, 5, and 9 days of reperfusion. Cryosections were immunostained with Fluoro-Jade B, a degenerating neuron marker to label degenerating neurons. Semi-quantitative analysis of the expression of IRE1alpha, ASK1, SEK1, and JNK were performed in both control and ischemic retinas. In ischemic retinas, the intensities of IRE1alpha immunoreactivity in the ganglion cell layer (GCL) were significantly higher than in the control retinas. In ischemic retinas, the numbers of SEK1-, ASK1-, and JNK-positive cells were significantly increased in the GCL compared to those in the control retinas. In addition, the cells that were positive for SEK1-, ASK1-, and JNK were also positive for Fluoro-Jade B-positive cells. These results indicate that the increased expression of ER stress-related factors was, in part, associated with the retinal neuronal abnormalities after ischemia-reperfusion injury in rat retinas.
Yoshinori Mitamura, K Hirano, T Baba and S Yamamoto : Correlation of visual recovery with presence of photoreceptor inner/outer segment junction in optical coherence images after epiretinal membrane surgery., The British journal of Ophthalmology, Vol.93, No.2, 171-175, 2008.
(Summary)
AIMS: To investigate the relationship between the presence of the photoreceptor inner and outer segment (IS/OS) junction and visual acuity after epiretinal membrane (ERM) surgery. METHODS: Seventy eyes of 70 consecutive patients who had undergone vitrectomy for idiopathic ERM were examined by optical coherence tomography before and 3 and 6 months after surgery. The IS/OS junction was graded into three grades. The time course of recovery of the IS/OS junction, central foveal thickness (CFT) and best corrected visual acuity (BCVA) during the postoperative period was studied. RESULTS: A normal IS/OS junction was detected in 47.1% of the eyes before surgery and in 65.7% at 3 months and 75.7% at 6 months after. There was a significant correlation between the IS/OS grade and BCVA before and at 3 and 6 months after the operation (p = 0.0001, p<0.0001, p<0.0001, respectively). The preoperative IS/OS junction grade correlated significantly with BCVA at 6 months (p = 0.0239). CFT did not correlate significantly with BCVA at 3 and 6 months. CONCLUSIONS: The presence of a normal IS/OS junction was associated with good visual acuity after ERM surgery. A normal IS/OS junction probably indicates morphological and functional recovery of the photoreceptors.
大平 知美, 辰巳 智章 and Yoshinori Mitamura : A case of retinal hemangioma treated by vitrectomy for vitreous hemorrhage and epimacular membrane, Japanese Journal of Clinical Ophthalmology, Vol.62, No.8, 1361-1364, 2008.
Toshiyuki OSHITARI, Noriko ASAUMI, Masaru WATANABE, Ken KUMAGAI and Yoshinori Mitamura : A case of serous retinal detachment following vitrectomy for rhegmatogenous retinal detachment, Folia japonica de ophthalmologica clinica, Vol.1, No.3, 225-228, 2008.
Takayuki Baba, Shuichi Yamamoto, Miyuki Arai, Eika Arai, Takeshi Sugawara, Yoshinori Mitamura and Satoshi Mizunoya : Correlation of visual recovery and presence of photoreceptor inner/outer segment junction in optical coherence images after successful macular hole repair., Retina, Vol.28, No.3, 453-458, 2008.
(Summary)
PURPOSE: To determine the relationship between the postoperative visual acuity (VA) and the presence of a photoreceptor inner segment (IS) and outer segment (OS) junction (IS/OS) in optical coherence tomographic (OCT) images after macular hole (MH) surgery. METHODS: Twenty-three eyes of 23 cases of idiopathic MH treated by vitrectomy were studied. The postoperative VA and OCT3 images of the fovea at 1, 3, and 6 months were examined. The relationship between the presence of the IS/OS junction and the visual acuity was studied. RESULTS: All MHs were successfully closed. The IS/OS junction appeared as a distinct, highly reflective line just vitread to the retinal pigment epithelial layer in the postoperative OCT3 images. A normal IS/OS junction was detected postoperatively in one eye at 1 month, three eyes at 3 months, and seven eyes at 6 months. The VA was significantly better in eyes in which a normal IS/OS junction was detected than in those not detected at 3 and 6 months postoperatively (P = 0.046 and P = 0.040, respectively). CONCLUSION: The normal IS/OS junction observed in OCT3 images is associated with good visual recovery after MH closure. The presence of normal IS/OS junction may be important for visual recovery after MH repair.
(Keyword)
Aged / Aged, 80 and over / Female / Humans / Male / Middle Aged / Photoreceptor Cells, Vertebrate / Recovery of Function / Retinal Perforations / Tomography, Optical Coherence / Visual Acuity / Vitrectomy
Toshiyuki Oshitari, Noriko Asaumi, Masaru Watanabe, Ken Kumagai and Yoshinori Mitamura : Severe macular edema induced by pioglitazone in a patient with diabetic retinopathy: a case study., Vascular Health and Risk Management, Vol.4, No.5, 1137-1140, 2008.
(Summary)
We report a case of severe diabetic macular edema (DME) that developed after pioglitazone was used by a patient with proliferative diabetic retinopathy. A 30-year-old woman with poorly controlled type 2 diabetes mellitus visited our clinic in 2004. She had moderate pre-proliferative diabetic retinopathy OU. Because of the rapid progression of the diabetic retinopathy, she received pan-retinal photocoagulation in both eyes. Two weeks before using pioglitazone, her visual acuity was 0.9 OD and 0.7 OS. On October 2007, pioglitazone was prescribed by her internist because of poorly controlled blood glucose level. Two weeks later, her body weight increased, and her face became edematous. Her visual acuity decreased to 0.5 OU, and ophthlamoscopy showed severe DME in both eyes. Two weeks after stopping pioglitazone, her visual acuity improved to 0.8 OD and 0.5 OS, but the DME was still severe in the optical coherence tomographic images. Then, one half the usual dose (25 mg) of spironolactone, a diuretic, was given and her macular edema was resolved. Her final visual acuity improved to 0.9 OD and 0.7 OS. We recommend that when a patient taking pioglitazone complains of decreased vision, the physician should promptly consult an ophthalmologist.
Chikako Harada, Kazuaki Nakamura, Xiaoli Guo, Nobuyoshi Kitaichi, Yoshinori Mitamura, Kazuhiko Yoshida, Shigeaki Ohno, Hiroshi Yoshida and Takayuki Harada : Neuroprotective effect of geranylgeranylacetone against ischemia-induced retinal injury., Molecular Vision, Vol.13, 1601-1607, 2007.
(Summary)
PURPOSE: This study was conducted to assess the effects of geranylgeranylacetone (GGA) on ischemia-induced retinal injury. METHODS: Adult C57BL/6J mice were given oral treatments of GGA at 200 mg/kg daily for seven days. Ischemic retinal injury was carried out, and the extent of retinal cell death was quantitatively examined after 7 days. Immunohistochemistry for single-stranded DNA, phosphorylated form of p38 mitogen-activated protein kinase (p38 MAPK), and cleaved caspase-3 were performed one day after ischemic injury. RESULTS: In GGA-treated mice, we found the number of surviving retinal neurons was significantly increased compared with vehicle-treated mice. Ischemia-induced phosphorylation of p38 MAPK, which mediates apoptosis of retinal ganglion cells, was suppressed by GGA treatment. In such retinas, cleaved caspase-3- and single-stranded DNA-positive cells were also decreased compared with vehicle-treated mice. CONCLUSIONS: Oral GGA is a useful treatment for various retinal degenerative diseases that involve ischemic injury.
Nami Nishikiori, Makoto Osanai, Hideki Chiba, Takashi Kojima, Yoshinori Mitamura, Hiroshi Ohguro and Norimasa Sawada : Glial cell-derived cytokines attenuate the breakdown of vascular integrity in diabetic retinopathy., Diabetes, Vol.56, No.5, 1333-1340, 2007.
(Summary)
The blood-retinal barrier (BRB) is a biological unit comprised of specialized capillary endothelial cells firmly connected by intercellular tight junctions and endothelium-surrounding glial cells. The BRB is essential for maintaining the retinal microenvironment and low permeability and is compromised in an early phase during the progression of diabetic retinopathy. Here, we demonstrate that retinoic acid receptor (RAR)alpha stimulants preferentially act on glial cells rather than endothelial cells, resulting in the enhanced expression of glial cell line-derived neurotrophic factor (GDNF) through recruitment of the RARalpha-driven trans-acting coactivator to the 5'-flanking region of the gene promoter. Conversely, RARalpha decreases expression of vascular endothelial growth factor (VEGF)/vascular permeability factor. These gene expression alterations causally limit vascular permeability by modulating the tight junction function of capillary endothelium in a paracrine manner in vitro. The phenotypic transformation of glial cells mediated by RARalpha is sufficient for significant reductions of vascular leakage in the diabetic retina, suggesting that RARalpha antagonizes the loss of tight junction integrity induced by diabetes. These findings reveal that glial cell-derived cytokines such as GDNF and VEGF regulate BRB function, implying that the glial cell can be a possible therapeutic target in diabetic retinopathy.
Fumio HOSAKA, Yoshinori Mitamura, Shinichi NISHIMURA and Hiroshi OHGURO : A Case of Branch Retinal Artery Occlusion Associated with Rupture of Retinal Arterial Macroaneurysm, Journal of the Eye, Vol.24, No.2, 239-242, 2007.
Kazuha Ogata, Shuichi Yamamoto, Yoshinori Mitamura, Takeshi Sugawara and Satoshi Mizunoya : Changes in multifocal oscillatory potentials after internal limiting membrane removal for macular hole: multifocal OPs after ILM removal., Documenta Ophthalmologica, Vol.114, No.2, 75-81, 2007.
(Summary)
PURPOSE: To determine whether removal of the internal limiting membrane (ILM) during macular hole (MH) surgery alters the retinal function. METHODS: Multifocal electroretinograms (mfERGs) were recorded preoperatively and 3 months after surgery from 11 eyes of 10 patients with an idiopathic MH treated successfully by pars plana vitrectomy accompanied by ILM removal. A low frequency (9.4 Hz) pseudorandom binary m-sequence stimulus was used to elicit the mfERGs from different retinal loci. The bandpass of the amplifier was set at 10-300 Hz to record the mfERGs and at 100-300 Hz to record the oscillatory potentials (OPs). RESULTS: An anatomical closure of the MH was achieved in all patients, and the mean visual acuity was significantly improved postoperatively. No significant difference was observed in both the amplitudes and implicit times of the negative and positive waves of the mfERGs and the OPs recorded preoperatively to those recorded postoperatively. CONCLUSIONS: MH surgery with ILM removal does not alter the electrophysiological function of both the outer and inner retina of the posterior pole where the ILM was removed.
Kiyoe MIYANISHI, Yoshinori Mitamura, Asako TASHIMO, Tomoko SUZUKI and Hiroshi OHGURO : A Case of Central Retinal Artery Occlusion and Anterior Ischemic Optic Neuropathy Associated with Temporal Arteritis, Journal of the Eye, Vol.23, No.11, 1493-1496, 2006.
Nagako MIYANO and Yoshinori Mitamura : Young Female with Cilioretinal Artery Occlusion and Impending Central Retinal Vein Occlusion, Journal of the Eye, Vol.23, No.11, 1489-1492, 2006.
Yasushi NAKAMURA, Yoshinori Mitamura, Hiroki ITO and Kahoru KONDOU : Optical Coherence Tomographic Findings of Spontaneous Closure of Traumatic Macular Hole, Journal of the Eye, Vol.23, No.7, 966-968, 2006.
Chikako Harada, Akinori Okumura, Kazuhiko Namekata, Kazuaki Nakamura, Yoshinori Mitamura, Hiroshi Ohguro and Takayuki Harada : Role of monocyte chemotactic protein-1 and nuclear factor kappa B in the pathogenesis of proliferative diabetic retinopathy., Diabetes Research and Clinical Practice, Vol.74, No.3, 249-256, 2006.
(Summary)
Intraocular concentrations of monocyte chemotactic protein-1 (MCP-1) are increased in proliferative diabetic retinopathy (PDR). Nuclear factor kappa B (NF-kappaB) is a transcription factor, and NF-kappaB binding site is located in gene promoter of MCP-1. This study was conducted to investigate the potential role of MCP-1 and NF-kappaB in the pathogenesis of PDR. Epiretinal membrane (ERM) samples were obtained during vitrectomy from 19 eyes with PDR and 16 eyes with idiopathic ERM. They were processed for RT-PCR analysis. Four PDR ERMs were processed for immunohistochemical analysis. In addition, cultured Müller glial cells were stimulated with glycated albumin or high glucose. After the stimulation, we examined nuclear localization of NF-kappaB p50, MCP-1 promoter activity, and MCP-1 concentration in culture media. MCP-1 mRNA expression was significantly higher in PDR (74%) than in idiopathic ERMs (38%) (P < 0.05). Immunohistochemical analysis revealed that MCP-1 protein is colocalized with active form of NF-kappaB p50. In vitro studies demonstrated that glycated albumin or high glucose induces NF-kappaB activation followed by up-regulation of MCP-1 promoter activity and protein production in glial cells. These results suggest that MCP-1, under the regulation of NF-kappaB, is involved in the pathogenesis of PDR.
Asako TASHIMO, Nagako MIYANO, Yoshinori Mitamura and Kenji OHTSUKA : Surgical Outcome of Vitrectomy for Retinal Detachment Due to Macular Hole in Highly Myopic Eyes, Journal of the Eye, Vol.23, No.2, 269-272, 2006.
Chikako Harada, Kazuaki Nakamura, Kazuhiko Namekata, Akinori Okumura, Yoshinori Mitamura, Yoko Iizuka, Kenji Kashiwagi, Kazuhiko Yoshida, Shigeaki Ohno, Atsushi Matsuzawa, Kohichi Tanaka, Hidenori Ichijo and Takayuki Harada : Role of apoptosis signal-regulating kinase 1 in stress-induced neural cell apoptosis in vivo., The American Journal of Pathology, Vol.168, No.1, 261-269, 2006.
(Summary)
Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in oxidative stress-induced apoptosis. In the present study, we used ASK1 knockout (KO) mice to examine the possibility that ASK1 is involved in the neural cell apoptosis that occurs during retinal development and ischemic injury. ASK1 was expressed in retinal neurons, including retinal ganglion cells (RGCs), but retinal structure and extent of cell death during development were normal in ASK1 KO mice. On the other hand, the strain was less susceptible to ischemic injury, and the number of surviving retinal neurons was significantly increased compared with that in wild-type mice. Interestingly, ischemia-induced phosphorylation of p38 mitogen-activated protein kinase (p38), which mediates RGC apoptosis, was almost completely suppressed in ASK1 KO mice. In such retinas, the numbers of cleaved caspase-3- and TUNEL-positive neurons were apparently decreased compared with those in wild-type mice. Furthermore, cultured RGCs from ASK1 KO mice were resistant to H(2)O(2)-induced apoptosis. Our findings suggest that ASK1 is involved in the neural cell apoptosis after various kinds of oxidative stress. Thus, inhibition of the ASK1-p38 pathway could be useful for the treatment of neurodegenerative diseases including glaucoma.
Kazuaki Nakamura, Chikako Harada, Akinori Okumura, Kazuhiko Namekata, Yoshinori Mitamura, Kazuhiko Yoshida, Shigeaki Ohno, Hiroshi Yoshida and Takayuki Harada : Effect of p75NTR on the regulation of photoreceptor apoptosis in the rd mouse., Molecular Vision, Vol.11, 1229-1235, 2005.
(Summary)
PURPOSE: Apoptosis is the final common pathway for photoreceptors in several forms of retinitis pigmentosa. Recent study has shown that continuous light exposure upregulates low-affinity neurotrophin receptor p75 (p75NTR), which is involved in light-induced photoreceptor apoptosis in rat retina. However, the function of p75NTR in inherited forms of photoreceptor degeneration has not yet been examined. This study was conducted to elucidate the potential role of p75NTR in the rd mouse, one of the best characterized animal models of retinitis pigmentosa. METHODS: Double-mutant (rd/rd, p75NTR-/-) mice were crossbred from rd/rd and p75NTR-/- mice. Retinas from control (+/+, p75NTR+/+; rd/rd, p75NTR+/+; rd/rd, p75NTR+/-), and double-mutant (rd/rd, p75NTR-/-) mice were examined by light microscopy and TdT-mediated dUTP nick end labeling (TUNEL) from postnatal day (P)9 through P20. p75NTR mRNA expression in +/+, p75NTR+/+, and rd/rd, p75NTR+/+ mice were examined by real-time PCR analysis. p75NTR protein expression in +/+, p75NTR+/+; rd/rd, p75NTR+/+; and rd/rd, p75NTR-/- mice were examined by immunohistochemistry. RESULTS: p75NTR mRNA expression in rd/rd, p75NTR+/+ mice was significantly upregulated compared with +/+, p75NTR+/+ mice at P13 and P20. p75NTR protein expression was observed mainly in Müller glial cells, and its expression was upregulated in the outer nuclear layer during photoreceptor degeneration. However, histochemical analyses showed that the time course of retinal degeneration and the extent of photoreceptor apoptosis in rd/rd, p75NTR-/- double-mutant mice was indistinguishable from that in rd mice carrying functional p75NTR (rd/rd, p75NTR+/+, and rd/rd, p75NTR+/-). CONCLUSIONS: These results suggest that in contrast to its role in light-induced photoreceptor degeneration, p75NTR is not essential for apoptosis in the rd mouse.
Yoshinori Mitamura and Kenji Ohtsuka : Relationship of dissociated optic nerve fiber layer appearance to internal limiting membrane peeling., Ophthalmology, Vol.112, No.10, 1766-1770, 2005.
(Summary)
PURPOSE: The dissociated optic nerve fiber layer (DONFL) appearance features numerous arcuate striae after vitrectomy for idiopathic epiretinal membrane or macular hole. We studied the relation between the DONFL appearance and internal limiting membrane (ILM) peeling and performed static microperimetry to explore the possible mechanisms underlying the DONFL appearance. DESIGN: Prospective cohort study. PARTICIPANTS: Ninety-five eyes of 88 consecutive patients undergoing vitrectomy for idiopathic macular hole. METHODS: Vitrectomy and gas tamponade were performed with or without ILM peeling. All eyes were examined postoperatively using fundus photography with blue filters. Static microperimetry was performed in 31 eyes with a clearly visible DONFL appearance. MAIN OUTCOME MEASURE: The postoperative incidence of the DONFL appearance on blue-filtered fundus photographs. The secondary outcome measure included the microperimetry threshold value in the arcuate striae and the surrounding normal retina within the papillomacular bundle. RESULTS: On blue-filtered photographs, 46 (62.2%) of 74 eyes with ILM peeling exhibited the DONFL appearance, compared with 0 (0%) of 21 eyes without ILM peeling (P = 0.0002). The area of the DONFL appearance was limited to the area of ILM peeling. There was no difference in the microperimetry threshold value between the arcuate striae and the surrounding normal retina (P = 0.9312). CONCLUSION: The present study indicates that the DONFL appearance might be related to ILM peeling and is not associated with the loss of optic nerve fibers. These results are consistent with the suggestion that the DONFL appearance might be caused by cleavage of the optic nerve fiber bundles due to damage to the Müller cells, which are in close contact with the ILM and act to maintain the close proximity of the nerve fiber bundles.
Yasushi NAKAMURA, Yoshinori Mitamura, Hiroki ITO and Kahoru KONDOU : Retinal Arteriolar Macroaneurysm on the Optic Disc, Journal of the Eye, Vol.21, No.10, 1411-1412, 2004.
Asako TASHIMO, Yoshinori Mitamura and Kenji OHTSUKA : A Case of Retinitis Pigmentosa with Tractional Retinal Detachment, Journal of the Eye, Vol.21, No.9, 1265-1267, 2004.
Nagako MIYANO, Yoshinori Mitamura, Asako TASHIMO, Nobuko SEKINE, Hiroshi TAGAWA and Kenji OHTSUKA : A Case of Chronic Myeloid Leukemia and Hyperviscosity Syndrome with Peripheral Retinal Nonperfusion and Vitreous Hemorrhage, Journal of the Eye, Vol.21, No.8, 1141-1144, 2004.
Yoshinori Mitamura, Tomoko Suzuki, Takamasa Kinoshita, Nagako Miyano, Asako Tashimo and Kenji Ohtsuka : Optical coherence tomographic findings of dissociated optic nerve fiber layer appearance., American Journal of Ophthalmology, Vol.137, No.6, 1155-1156, 2004.
(Summary)
PURPOSE: To examine the features of optical coherence tomographic (OCT) findings of dissociated optic nerve fiber layer (DONFL) appearance. DESIGN: Case-control study. METHODS: Twenty-four eyes undergoing vitrectomy for idiopathic epiretinal membrane or macular hole were examined postoperatively using OCT. RESULTS: Thirteen of the 24 eyes exhibited the DONFL appearance. In these 13 eyes, the OCT images indicated dimples in the retinal nerve fiber layer (RNFL) corresponding to each stria. The RNFL thickness (mean +/- SD) at the dimple site was 38.1 +/- 9.3 microm. The depth of each dimple was 28.6 +/- 8.0 microm. The depths of all the dimples were limited to the RNFL thickness. In the other 11 eyes without the DONFL appearance, OCT images showed no distinct dimples. CONCLUSIONS: The DONFL appearance is caused by dimples the depths of which are limited to the RNFL thickness.
Nami NISHIKIORI, Osamutaro FUJIWARA, Yoshinori Mitamura, Asako TASHIMO, Tomoko SUZUKI, Nagako MIYANO, Takamasa KINOSHITA and Kenji OHTSUKA : Two Cases with Adenoma of Ciliary Body Nonpigmented Epithelium, Journal of the Eye, Vol.21, No.4, 539-542, 2004.
Takamasa KINOSHITA, Yoshinori Mitamura, Tomoko SUZUKI, Nagako MIYANO, Osamutaro FUJIWARA, Asako TASHIMO and Kenji OHTSUKA : Three Cases of High Myopia with Foveal Detachment, Retinoschisis and No Macular Hole, Journal of the Eye, Vol.21, No.4, 543-546, 2004.
Asako TASHIMO, Yoshinori Mitamura and Kenji OHTSUKA : A Case of Endophthalmitis 8 Years after Transscleral Fixation of Intraocular Lens, Journal of the Eye, Vol.21, No.2, 258-260, 2004.
Yoshinori Mitamura, Osamutarou Fujiwara, Kiyoe Miyanishi, Hiroko Sato, Kenji Saga and Kenji Ohtsuka : Nodular scleritis and panuveitis with erythema elevatum diutinum., American Journal of Ophthalmology, Vol.137, No.2, 368-370, 2004.
(Summary)
PURPOSE: To report a case of nodular scleritis and panuveitis associated with erythema elevatum diutinum, a rare immunocomplex-mediated skin disease. DESIGN: Observational case report. METHODS: A 22-year-old woman who was diagnosed with erythema elevatum diutinum developed nodular scleritis and panuveitis of the right eye. She had experienced peripheral ulcerative keratitis with corneal perforation. RESULTS: All other known causes of nodular scleritis and panuveitis were investigated and ruled out. CONCLUSIONS: Erythema elevatum diutinum should be considered as an underlying systemic disease associated with nodular scleritis and panuveitis as well as peripheral keratitis.
Chikako Harada, Takayuki Harada, Yoshinori Mitamura, A Hun-Meng Quah, Kenji Ohtsuka, Satoshi Kotake, Shigeaki Ohno, Keiji Wada, Shinobu Takeuchi and Kohichi Tanaka : Diverse NF-kappaB expression in epiretinal membranes after human diabetic retinopathy and proliferative vitreoretinopathy., Molecular Vision, Vol.10, 31-36, 2004.
(Summary)
PURPOSE: Formation of epiretinal membranes (ERMs) after proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR) results in progressive deterioration of vision, but its pathogenic mechanisms are still unknown. This study was conducted to examine the role of nuclear factor kappa B (NF-kappaB) in the formation of ERMs after PDR and PVR. METHODS: ERM samples were obtained by vitrectomy from 10 patients with PDR (aged 53+/-12 years with 14+/-5 years of diabetes), 20 patients with PVR, and 17 patients with idiopathic ERMs. Ten PVR and 17 idiopathic ERM samples were processed for reverse transcription-polymerase chain reaction (RT-PCR) analysis. In addition, 10 PDR and 10 PVR membranes were processed for immunohistochemical analysis. RESULTS: NF-kappaB mRNA expression levels were significantly higher (10 of 10 versus 9 of 17 subjects in idiopathic ERM, p=0.0119) in PVR subjects. Immunohistochemical analysis showed NF-kappaB protein expression in 8 of the 10 PDR samples as well as all 10 PVR samples, and NF-kappaB positive cells were partially double labeled with glial cell markers. Interestingly, NF-kappaB protein was also overlapped with angiogenic factor interleukin-8 (IL-8) in glial cells as well as vascular endothelial cells. CONCLUSIONS: These results suggest that NF-kappaB is involved in the formation of both glial and vascular endothelial cell components, and that these two cell types might have functional interactions that lead to the enlargement of intraocular proliferative membranes.
Yoshinori Mitamura, Shinobu Takeuchi, Kenji Ohtsuka, Akira Matsuda, Teiko Yamamoto, Shuichi Yamamoto, Noriko Hiraiwa and Moriaki Kusakabe : Tenascin-C levels in the vitreous of patients with proliferative vitreoretinopathy., Ophthalmologica, Vol.217, No.6, 422-425, 2003.
(Summary)
PURPOSE: To determine whether tenascin-C levels are elevated in the vitreous of patients with proliferative vitreoretinopathy (PVR). METHODS: We assayed tenascin-C levels in vitreous samples of 110 consecutive patients with PVR (30 eyes), rhegmatogenous retinal detachment (RRD; 32 eyes), and macular hole or idiopathic epiretinal membrane (controls, 48 eyes) using an enzyme-linked immunosorbent assay. RESULTS: Vitreous levels of tenascin-C (median [range]) were significantly greater in PVR (845.0 ng/ml [411.0-1,050.0]) than in RRD (21.9 ng/ml [13.2-127.0]) and in the controls (18.0 ng/ml [9.9-199.0]) (p < 0.0001). CONCLUSION: The results indicate the possibility that tenascin-C is involved in the pathogenesis of PVR.
(Keyword)
Adult / Aged / Aged, 80 and over / Enzyme-Linked Immunosorbent Assay / Female / Humans / Male / Middle Aged / Retinal Detachment / Retinal Perforations / Tenascin / Vitreoretinopathy, Proliferative / Vitreous Body
Asako Tashimo, Yoshinori Mitamura, Nobuko Sekine, Muneyasu Takeda and Kenji Ohtsuka : Rhegmatogenous retinal detachment after rupture of retinal arterial macroaneurysm., American Journal of Ophthalmology, Vol.136, No.3, 549-551, 2003.
(Summary)
PURPOSE: To report two cases of rhegmatogenous retinal detachment following rupture of retinal arterial macroaneurysm. DESIGN: Observational case report. METHODS: Review of clinical records of 75 consecutive eyes (73 patients) with macroaneurysm. RESULTS: Ruptured macroaneurysm was present in 68 of the 75 eyes, and rhegmatogenous retinal detachment developed spontaneously in 2 (2.9%) of the 68 eyes. In the 2 eyes with retinal detachment, there were no predisposing lesions to retinal detachment and the detachment occurred either 2 weeks or 1 month after the rupture of a macroaneurysm. Retinal detachment and posterior vitreous detachment developed simultaneously after bleeding from the macroaneurysm spread into the vitreous in 1 eye. CONCLUSIONS: We report the occurrence of retinal detachment after macroaneurysmal rupture. Detailed fun-dus examination is required to detect retinal detachment in the follow-up of patients with ruptured macroaneurysm.
To evaluate the clinical features of nosocomial epidemic keratoconjunctivitis(EKC) occurring in the ophthalmology ward of Sapporo Medical University Hospital and to devise preventive measures for it. We studied the symptoms and clinical course of 2 patients who had EKC and 16 patients who had EKC caused by nosocomial infections in our hospital. We attempted to detect adenovirus antigen and viral DNA from conjunctival swabs and also to isolate the virus. The clinical symptoms of EKC were conjunctival hyperemia in 18 patients(100%), conjunctival follicles in 11 patients (61.1%), discharge in 8 patients(44.4%), superficial punctate keratopathy in 7 patients(38.9%), swelling of the eyelids in 3 patients(16.7%), and fever in 3 patients(16.7%). 72% were positive for Adeno-check. Adenovirus type 4 was isolated from the conjunctival swabs. We considered that the route of hospital infection was infection from the doctor's hands, from eye drops, and from contact lenses. We disclosed that nosocomical EKC had occurred in our hospital. The hospital infection was eliminated by closing the ophthalmology ward and sterilizing instruments and washing hands. The delay of proper measures increased the risk of nosocomical infection. We recognized the importance of careful observation of patients and immediate preventive efforts in nosocomical infection.
(Keyword)
Adenovirus Infections, Human / Cross Infection / Female / Humans / Keratoconjunctivitis / Male
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● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12894746
Yoshinori Mitamura, T Harada, C Harada, K Ohtsuka, S Kotake, S Ohno, K Tanaka, S Takeuchi and K Wada : NF-kappaB in epiretinal membranes after human diabetic retinopathy., Diabetologia, Vol.46, No.5, 699-703, 2003.
(Summary)
AIMS/HYPOTHESIS: Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to examine whether or not nuclear factor kappa B (NF-kappaB), a transcription factor that can be activated by various pathological conditions, is involved in the formation of ERMs after PDR. METHODS: ERM samples were obtained by vitrectomy from 22 cases with PDR aged 56+/-11 years with 18+/-10 years of diabetes and 15 cases with idiopathic ERM. They were processed for reverse transcription-polymerase chain reaction (RT-PCR) analysis. In addition, 5 ERM samples from PDR patients aged 51+/-16 years with 15+/-6 years of diabetes were processed for immunohistochemical analysis. RESULTS: NF-kappaB mRNA expression levels were higher (20 out of 22 cases vs. 9 out of 15 subjects in idiopathic ERM, p<0.05) in PDR subjects. Immunohistochemical analysis showed NF-kappaB protein expression in all the 5 ERMs derived from PDR patients, and that region was partially double-labelled with interleukin-8 (IL-8) and von Willebrand factor (vWF). CONCLUSIONS/INTERPRETATION: These results suggest a possibility that NF-kappaB is involved in the formation of ERMs after PDR, especially for the development of vascular endothelial cell component.
Asako Tashimo, Yoshinori Mitamura, Kenji Ohtsuka, Utako Okushiba, Hiroko Imaizumi and Muneyasu Takeda : Macular hole formation following ruptured retinal arterial macroaneurysm., American Journal of Ophthalmology, Vol.135, No.4, 487-492, 2003.
(Summary)
PURPOSE: To report four cases of macular hole formation following ruptured retinal arterial macroaneurysm. DESIGN: Case-control study. METHODS: Review of clinical records of 75 consecutive eyes (73 patients) with macroaneurysm. Macroaneurysms were confirmed using either fluorescein angiography or indocyanine green angiography or both that indicated a telangiectatic retinal vascular change. Clinical data of patients with macroaneurysm with and without macular hole (MH) formation were compared retrospectively. RESULTS: Of 75 eyes, four (5.3%; four patients) with macroaneurysm had a macular hole. In one of the four eyes, a macular hole was detected 2 days after the rupture. The distance from the macroaneurysm to the center of the fovea was significantly closer in the four eyes with a macular hole (MH group, 1.1 +/- 0.4 (mean +/- standard deviation [SD]) disk diameter) than in the 71 eyes without a macular hole (non-MH group, 1.9 +/- 0.9 disk diameter) (P =.0196). The incidence of subretinal hemorrhage in the macula was significantly greater in the MH group (100%) than in the non-MH group (35.2%) (P =.0195). CONCLUSIONS: Macular hole formation associated with ruptured macroaneurysm is not as uncommon as previously thought. We suggest that there might be early onset of macular hole formation following ruptured macroaneurysm. Macroaneurysms with early-onset macular hole are present near the center of the macula and are accompanied by subretinal hemorrhage in the macula.
Takayuki Harada, Chikako Harada, Yoshinori Mitamura, Chihiro Akazawa, Kenji Ohtsuka, Shigeaki Ohno, Shinobu Takeuchi and Keiji Wada : Neurotrophic factor receptors in epiretinal membranes after human diabetic retinopathy., Diabetes Care, Vol.25, No.6, 1060-1065, 2002.
(Summary)
OBJECTIVE: Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions, including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to determine whether neurotrophic factor receptors (tyrosine kinase receptors trkA, trkB, and trkC; low-affinity neurotrophin [NT] receptor p75 [p75(NTR)]; glial cell line-derived neurotrophic factor receptor-alpha1 [GFR alpha 1] and GFR alpha 2; and Ret) are involved in the formation of ERMs after PDR. RESEARCH DESIGN AND METHODS: ERM samples were obtained by vitrectomy from 19 subjects with PDR aged 57 +/- 8 years with 17 +/- 8 years of diabetes and 15 subjects with idiopathic ERM. They were processed for RT-PCR analysis. In addition, 11 ERM samples from PDR patients aged 47 +/- 18 years with 13 +/- 4 years of diabetes were processed for immunohistochemical analysis. RESULTS: Expressions of trkA, trkB, trkC, p75(NTR), and Ret mRNAs were similar in both groups. In contrast, GFR alpha 2 expression levels were significantly higher (17 of 19 vs. 2 of 15 subjects in idiopathic ERM, P < 0.0001) in PDR subjects. Accordingly, immunohistochemical analysis revealed expression of GFR alpha 2 protein in all of the 11 ERMs derived from PDR patients, and that region was double-labeled with glial cell-specific markers. On the other hand, GFR alpha 1 expression was lower (8 of 19 vs. 12 of 15 subjects with idiopathic ERM, P = 0.0258) in PDR subjects. CONCLUSIONS: These results suggest a possibility that glial cell line-derived neurotrophic factor receptor (GDNF) subtypes are differently involved in the formation of ERMs.
Wataru SAITO, Shuichi YAMAMOTO, Yoshinori Mitamura and Shinobu TAKEUCHI : Birdshot Chorioretinopathy : A Case Report and a Case Study in Japanese Patients, Acta Societatis Ophthalmologicae Japonicae, Vol.106, No.4, 229-235, 2002.
(Summary)
There have been numerous case reports of birdshot chorioretinopathy(BC) from Europe and USA. However, only 10 cases of BC have been reported in Japan. We report the case of a Japanese patient with BC and review the clinical characteristics of BC among Japanese patients previously reported. We report the case of a 64-year-old Japanese man, who was seen at our clinic and then diagnosed as hasing BC. 20 eyes of 11 patients with BC reported in the Japanese literature previously, including our patient, were studied. Age at the initial onset, sex, ocular findings, prognosis of visual acuity and the human leucocyte antigen (HLA) were evaluated. In our case bilateral cream-colored subretinal exudates presented symmetrically and in time developed depigmented atrophic 'birdshot like' scar lesions. Ocular inflammation responded to oral prednisolone without exacerbation and good visual acuity was maintained. The age at the onset ranged from 19 to 78 years(mean 54.5), and 8 patients were women. Cystoid macular edema(CME) was found in 30% of 11 Japanese patients, and optic disc edema was seen in 50%. Final visual acuity was more than 20/40 in 75% and less than 20/200 in 12.5% of the cases. HLA-A 29, which is frequently associated with Caucasian patients, was not positive in any of the Japanese patients, and no specific locus was determined. We observed a rare case of BC. Age at initial onset, sex, and ocular findings of Japanese patients with BC were consistent with those of Europe and the US and good visual acuity was maintained in almost all cases. We suggest that the disease mechanism of BC in Japanese patients is different from that of Caucasian patients, because HLA-A 29 was negative in all Japanease patients.
Yoshinori Mitamura, Shinobu Takeuchi, Shuichi Yamamoto, Teiko Yamamoto, Itsuro Tsukahara, Akira Matsuda, Yoshitsugu Tagawa, Yuka Mizue and Jun Nishihira : Monocyte chemotactic protein-1 levels in the vitreous of patients with proliferative vitreoretinopathy., Japanese Journal of Ophthalmology, Vol.46, No.2, 218-221, 2002.
(Summary)
PURPOSE: To assess the potential role of monocyte chemotactic protein-1 (MCP-1) in the pathogenesis of proliferative vitreoretinopathy (PVR) and to investigate its possible interaction with the macrophage migration inhibitory factor (MIF). METHODS: We assayed MCP-1 and MIF levels in the vitreous samples of 85 consecutive patients with PVR (29 eyes), rhegmatogenous retinal detachment (RRD; 22 eyes), and macular hole or idiopathic epimacular membrane (controls; 34 eyes), by enzyme-linked immunosorbent assay. RESULTS: Vitreous levels of MCP-1 were 1760.7 +/- 471.3 pg/mL (mean +/- SD) in PVR patients, 1200.4 +/- 579.8 pg/mL in RRD patients, and 436.3 +/- 286.1 pg/mL in the controls. Vitreous MCP-1 levels in PVR patients were significantly higher than those in RRD patients and in the controls (P <.0001, respectively). MCP-1 levels in grade C of PVR (1883.7 +/- 479.5 pg/mL) were significantly greater than those in grade D (1437.8 +/- 258.8 pg/mL) (P =.0112). Vitreous concentrations of MCP-1 had no correlation with those of MIF. CONCLUSIONS: The results indicate the possibility that MCP-1 may have a role mainly in the early stage of PVR and that the role of MCP-1 in PVR may differ from that of MIF.
Yoshinori Mitamura, Itsuro TSUKAHARA, Shuichi YAMAMOTO and Shinobu TAKEUCHI : Surgical Outcome of Vitrectomy with Indocyanine Green Staining and Internal Limiting Membrane Peeling for Retinal Detachment with Macular Hole, Journal of the Eye, Vol.18, No.11, 1451-1453, 2001.
Yoshinori Mitamura, S Takeuchi, A Matsuda, Y Tagawa, Y Mizue and J Nishihira : Monocyte chemotactic protein-1 in the vitreous of patients with proliferative diabetic retinopathy., Ophthalmologica, Vol.215, No.6, 415-418, 2001.
(Summary)
PURPOSE: To investigate the correlation between monocyte chemotactic protein-1 (MCP-1) levels in the vitreous and clinical findings in eyes with proliferative diabetic retinopathy (PDR). METHODS: We assayed MCP-1 levels by ELISA in vitreous samples of 88 consecutive patients with PDR (52 eyes) and macular holes or idiopathic epimacular membrane (controls, 36 eyes). RESULTS: The level of MCP-1 in the vitreous was 2,097.5 +/- 1,099.4 pg/ml (mean +/- SD) in PDR, and 504.3 +/- 405.6 pg/ml in the controls. In PDR eyes, multivariate regression analysis revealed a significant association between MCP-1 levels in the vitreous and the degree of proliferative membrane, and a significant negative association between MCP-1 levels and the extent of preoperative retinal photocoagulation. CONCLUSION: The results suggest that MCP-1 may play a role in the development of the proliferative phase of PDR.
N Akabane, S Yamamoto, I Tsukahara, M Ishida, Yoshinori Mitamura, T Yamamoto and S Takeuchi : Surgical outcomes in juvenile retinal detachment., Japanese Journal of Ophthalmology, Vol.45, No.4, 409-411, 2001.
(Summary)
PURPOSE: To evaluate retrospectively clinical features and surgical outcomes of rhegmatogenous retinal detachment in juvenile patients. METHODS: Between 1991 and 1996, 28 patients younger than 15 years of age with rhegmatogenous retinal detachment (32 eyes) underwent the first surgical procedure, scleral buckling and/or pars plana vitrectomy, at our hospital. RESULTS: The major types of juvenile detachment, in order of frequency, were idiopathic, familial exudative vitreoretinopathy, trauma, and high myopia. Proliferative vitreoretinopathy (PVR) of grade C or D was involved in 12 cases (37.5%). Among the 12 eyes with PVR, 7 attained retinal reattachment after the first surgery with scleral buckling. The overall reattachment rate was 28/32 (87.5%) after the first operation and 30/32 (93.8%) after the second operation. CONCLUSION: These findings indicate that the reattachment rate and visual prognosis can be as good in juvenile retinal detachment as in adult cases, when appropriate surgical procedures are used.
Yoshinori Mitamura, Yoshinori MITAMURA, Masanori HAYASHI, Shuichi YAMAMOTO and Shinobu TAKEUCHI : Vitrectomy for Proliferative Diabetic Retinopathy in Young Adults, Journal of the Eye, Vol.18, No.3, 401-403, 2001.
Yoshinori Mitamura, W Saito, M Ishida, S Yamamoto and S Takeuchi : Spontaneous closure of traumatic macular hole., Retina, Vol.21, No.4, 385-389, 2001.
Yoshinori Mitamura, S Takeuchi, A Matsuda, Y Tagawa, Y Mizue and J Nishihira : Macrophage migration inhibitory factor levels in the vitreous of patients with proliferative diabetic retinopathy., The British journal of Ophthalmology, Vol.84, No.6, 636-639, 2000.
(Summary)
AIMS: To assess the potential role of macrophage migration inhibitory factor (MIF) in the pathogenesis of proliferative diabetic retinopathy (PDR). METHODS: MIF levels were assayed in the vitreous and paired serum samples of 73 consecutive patients with PDR (32 eyes) and macular hole or idiopathic epiretinal membrane (controls, 41 eyes). An enzyme linked immunosorbent assay technique was used to determine the concentrations of MIF. RESULTS: The median vitreous level of MIF was 11.93 ng/ml (range 4.16-103.85) in the patients with PDR, and 1.79 ng/ml (undetectable-8.93) in the controls. Vitreous levels in eyes with PDR were significantly greater than those in the controls (p<0.0001). Vitreous levels were significantly higher than serum levels in eyes with PDR (p=0.0026). MIF levels were significantly higher in the vitreous of PDR patients with severe fibrous proliferation than in those with slight proliferation (p<0.05). CONCLUSION: The results indicate increased levels of MIF in the vitreous of patients with PDR and a significant association between MIF levels and grades of fibrous proliferation, suggesting the possibility that MIF may play a part in the development of the proliferative phase of PDR.
(Keyword)
Adult / Aged / Cell Division / Diabetic Retinopathy / Epiretinal Membrane / Female / Humans / Macrophage Migration-Inhibitory Factors / Male / Middle Aged / Retinal Perforations / Severity of Illness Index / Vitreous Body
Yoshinori Mitamura, S Takeuchi, A Matsuda, Y Tagawa, Y Mizue and J Nishihira : Hepatocyte growth factor levels in the vitreous of patients with proliferative vitreoretinopathy., American Journal of Ophthalmology, Vol.129, No.5, 678-680, 2000.
(Summary)
PURPOSE: To determine whether the hepatocyte growth factor is increased in the vitreous of patients with proliferative vitreoretinopathy. METHODS: We assayed hepatocyte growth factor levels by enzyme-linked immunosorbent assay (ELISA) in vitreous samples from 65 consecutive eyes (65 patients) with proliferative vitreoretinopathy (23 eyes), rhegmatogenous retinal detachment (22 eyes), and macular hole or idiopathic epiretinal membrane (control subjects, 20 eyes) having undergone pars plana vitrectomy. RESULTS: Vitreous levels of hepatocyte growth factor were 3.94 +/- 2.29 (mean +/- SD) ng/ml in proliferative vitreoretinopathy, 2.02 +/- 0.84 ng/ml in rhegmatogenous retinal detachment, and 2.16 +/- 1.39 ng/ml in the control subjects. The vitreous levels in proliferative vitreoretinopathy were much greater than levels in rhegmatogenous retinal detachment (P =.0002) and in the control subjects (P =.0007). In proliferative vitreoretinopathy, there was a tendency toward higher levels in eyes with grade D by the Retina Society terminology. CONCLUSION: The results suggest the possibility that hepatocyte growth factor may play a role in the pathogenesis of proliferative vitreoretinopathy.
Yoshinori Mitamura, S Yamamoto and S Yamazaki : Corneal endothelial cell loss in eyes undergoing lensectomy with and without anterior lens capsule removal combined with pars plana vitrectomy and gas tamponade., Retina, Vol.20, No.1, 59-62, 2000.
(Summary)
PURPOSE: To assess prospectively the comeal endothelial damage associated with pars plana vitrectomy combined with lensectomy and gas tamponade. METHODS: The corneal endothelium was examined with a specular microscope preoperatively and 6 months postoperatively in 42 eyes that underwent pars plana vitrectomy combined with total lensectomy and gas tamponade with SF6 (19 eyes) or C3F8 (23 eyes), and in 12 control eyes that underwent vitrectomy combined with anterior capsule-preserved lensectomy and gas tamponade. RESULTS: The mean +/- SD endothelial cell loss was 17.19+/-7.88% in the SF6 tamponade group, 27.54+/-10.57% in the C3F8 tamponade group, and 3.49+/-2.68% in the control group. Significant differences were found in the mean cell loss among these three groups. The degree of cell loss was significantly related to gas tamponade duration in the eyes with total lensectomy. CONCLUSION: These results suggest that ophthalmic surgeons must try to preserve the lens capsule as much as possible in vitrectomy combined with lensectomy and long-acting gas tamponade in order to prevent corneal endothelial damage.
Yoshinori Mitamura, S Takeuchi and M Tsuruoka : Macular buckling combined with pars plana vitrectomy for complicated retinal detachment due to macular hole., Retina, Vol.20, No.6, 669-672, 2000.
Yoshinori Mitamura, S Takeuchi, A Matsuda, Y Tagawa, Y Mizue and J Nishihira : Macrophage migration inhibitory factor levels in the vitreous of patients with proliferative vitreoretinopathy., American Journal of Ophthalmology, Vol.128, No.6, 763-765, 1999.
(Summary)
PURPOSE: To assess the potential role of macrophage migration inhibitory factor (MIF) in the pathogenesis of proliferative vitreoretinopathy. METHODS: We assayed MIF levels in vitreous and paired serum samples of 74 consecutive patients with proliferative vitreoretinopathy (26 eyes), rhegmatogenous retinal detachment (22 eyes), and macular hole or idiopathic epiretinal membrane (control, 26 eyes) by enzyme-linked immunosorbent assay. RESULTS: Vitreous levels of MIF were 51.33 +/- 49.21 ng/ml (mean +/- SD) in proliferative vitreoretinopathy, 19.11 +/- 16.13 ng/ml in rhegmatogenous retinal detachment, and 2.98 +/- 2.55 ng/ml in the controls. The vitreous levels in eyes with proliferative vitreoretinopathy were significantly higher than levels in eyes with rhegmatogenous retinal detachment (P = .0005) and in the control subjects (P < .0001). The vitreous levels were significantly higher than the serum levels in proliferative vitreoretinopathy (P < .0001) and rhegmatogenous retinal detachment (P = .0019), respectively. CONCLUSIONS: The results suggest that MIF may be involved in the pathogenesis of proliferative vitreoretinopathy.
Fumihiko YAGI, Itsuro TSUKAHARA, Satoshi MATSUMURA, Yoshinori Mitamura, Haruhiko KUDO, Shuichi YAMAMOTO and Shinobu TAKEUCHI : Evaluation of DK-line^【○!R】 Efficacy in Surgery for Retinal Reattachment, Journal of the Eye, Vol.15, No.1, 129-132, 1998.
Atsushi Hayashi, Osman Cekic, Masanori Hangai, Yoshinori Mitamura and Andreas W. A. Weinberger : Multimodal imaging of the fundus., Journal of Ophthalmology, Vol.2013, 956761, 2013.
Ken Kumagai, Yoshinori Mitamura, Satoshi Mizunoya, Naoya Fujimoto and Shuichi Yamamoto : A case of anterior ischemic optic neuropathy associated with Fabry's disease., Japanese Journal of Ophthalmology, Vol.52, No.5, 421-423, 2008.
Yoshinori Mitamura and Shuichi Yamamoto : Sustained closure of surgically repaired macular hole after proliferative vitreoretinopathy., Indian Journal of Ophthalmology, Vol.56, No.6, 526-527, 2008.
Yoshinori Mitamura, Kazuha Ogata, Toshiyuki Oshitari, Noriko Asaumi and Shuichi Yamamoto : Retinal detachment with macular hole following intravitreal bevacizumab in patient with severe proliferative diabetic retinopathy., The British journal of Ophthalmology, Vol.92, No.5, 717-718, 2008.
Osamutaro Fujiwara, Yoshinori Mitamura and Kenji Ohtsuka : Herpes zoster panuveitis progression despite acyclovir treatment in a patient following bone marrow transplantation., Japanese Journal of Ophthalmology, Vol.49, No.6, 536-538, 2005.
Yoshinori Mitamura, Nagako Miyano and Kenji Ohtsuka : Bacterial endophthalmitis after triamcinolone acetonide-assisted pars plana vitrectomy., Japanese Journal of Ophthalmology, Vol.49, No.6, 538-539, 2005.
Acute annular outer retinopathy is an uncommon disorder of uncertain aetiology characterized by a unilateral visual field defect with an irregular annular band of grey-white, deep retinal opacification in a peripapillary location. Acute annular outer retinopathy is considered to be a variant of acute zonal occult outer retinopathy. The case is reported of acute annular outer retinopathy with spontaneous good visual recovery and no ophthalmoscopic sequelae.
Yoshinori Mitamura, Nagako Miyano, Yasuo Suzuki and Kenji Ohtsuka : Branch retinal artery occlusion associated with rupture of retinal arteriolar macroaneurysm on the optic disc., Japanese Journal of Ophthalmology, Vol.49, No.5, 428-429, 2005.
Yoshinori Mitamura, Kiyoe Miyanishi, Noriko Shizukawa, Asako Tashimo, Yasushi Nakamura, Hiroshi Tagawa and Kenji Ohtsuka : A case of X-linked retinoschisis diagnosed in an infant., Retina, Vol.23, No.5, 731-732, 2003.
W Saito, S Yamamoto, S Takeuchi and Yoshinori Mitamura : Ophthalmic artery occlusion following pars plana vitrectomy in a patient with Terson's syndrome., The British journal of Ophthalmology, Vol.86, No.9, 1063-1064, 2002.
Toshiyuki Oshitari and Yoshinori Mitamura : Optical coherence tomography for complete management of patients with diabetic retinopathy., Current Diabetes Reviews, Vol.6, No.4, 207-214, Jul. 2010.
(Summary)
Diabetic retinopathy is a major complication of patients with diabetes mellitus and can lead to a decrease in vision. The precise mechanisms leading to the development of diabetic retinopathy and the progressive decrease of vision are still undetermined. Recent studies have shown that not only vascular but also neuronal abnormalities are associated with the pathogenesis of diabetic retinopathy. Because neuronal cell death leads to an irreversible decrease in visual function, early changes in the morphology and physiology of the neural retinas of diabetic patients are important. The alterations of the morphology of the retina can be obtained by high-resolution B-scan optical coherence tomography (OCT). The thickness of the macular area and retinal nerve fiber layer can be measured reliably and accurately by the installed software of OCT instruments. The high-resolution images can be used to evaluate diabetic macular edema and optic nerve damage quantitatively in patients with diabetic retinopathy. This review describes how the OCT measurements can be used to manage patients with diabetic retinopathy. We also present the early retinal changes involved in the pathogenesis of diabetic retinopathy.
(Link to Search Site for Scientific Articles)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20522019
Yoshinori Mitamura and Shuichi YAMAMOTO : Minimal Surgery for Retinal Detachment With Scleral Buckling, Japanese Journal of Ophthalmic Surgery, Vol.20, No.1, 33-36, Jan. 2007.
Chikako Harada, Yoshinori Mitamura and Takayuki Harada : The role of cytokines and trophic factors in epiretinal membranes: involvement of signal transduction in glial cells., Progress in Retinal and Eye Research, Vol.25, No.2, 149-164, Dec. 2005.
(Summary)
Idiopathic epiretinal membranes (ERMs) in the macular region can cause a reduction in vision and sometimes recurs after surgical removal, but its pathogenic mechanisms are still unknown. On the other hand, the presence of secondary ERMs has been associated with various clinical conditions including proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). Recent studies have shown a significant association between clinical grades of PDR or PVR, and the expression levels of specific cytokines and/or growth factors in the vitreous fluid. Expression of these factors and their receptors are also observed in secondary ERMs. ERMs are composed of many cell types such as retinal pigment epithelial cells and vascular endothelial cells, however the role of glial cells is yet unclear. Interestingly, glial cells in ERMs express some trophic factor receptors and transcription factors, such as NF-kappaB, suggesting an involvement of glial signal transduction in the pathogenesis of ERMs. In this review, we summarize recent progress regarding the clinical and laboratory findings of ERMs.
Yoshinori Mitamura, Chikako Harada and Takayuki Harada : Role of cytokines and trophic factors in the pathogenesis of diabetic retinopathy., Current Diabetes Reviews, Vol.1, No.1, 73-81, Feb. 2005.
(Summary)
Diabetic retinopathy (DR) is one of the most frequent complications of diabetes and the leading cause of acquired blindness in developed countries. A note worthy problem in DR is the formation of fibrovascular epiretinal membranes (ERMs) which can cause tractional retinal detachment in the progressed stage of DR. Ocular vitreous fluid and ERMs, which can be obtained during vitrectomy, allow laboratory studies investigating the pathogenesis of DR. Recent studies have shown a significant association between clinical grades of DR and the expression levels of specific cytokines, such as vascular endothelial growth factor (VEGF), in the intraocular fluid. In addition, expression of various trophic factors and their receptors are reported in ERMs. ERM is composed of many cell types including endothelial cells, which is the primary target of glucose-induced dysfunction in the retina. However, some trophic factor receptors are observed in other cell types such as the glial cells, and their role in ERMs is unclarified. These findings may uncover the detailed pathogenesis of DR, which may lead to new therapeutic strategies. This review briefly summarizes recent research regarding the clinical and laboratory findings of DR.
Kentaro Senba, Takamasa Kinoshita, Kayo Shinomiya and Yoshinori Mitamura : Choroidal structure in healthy pediatric individuals determined by binarization of optical cohernce tomographic images, 2016米国眼科学会, Oct. 2016.
2.
Kayo Shinomiya, Sonoda Nao, Okamoto Satoe, Kitora AKiko, Iwata Akiko, Yoshinori Mitamura and Fujikado Takashi : Measuring Depth Perception during the Use of Microscope, XII MEETING of the international Strabismological Association, Kyoto International Conference Center(December 1-4,2014), Dec. 2014.
3.
Kayo Shinomiya, Sonoda Nao, Okamoto Satoe, Kitora AKiko, Iwata Akiko, Yoshinori Mitamura and Fujikado Takashi : (Poster)Measuring Depth Perception during the Use of Microscope, XII MEETING of the international Strabismological Association, Kyoto International Conference Center(December 1-4,2014), Dec. 2014.
4.
Kayo Shinomiya, Yoshinori Mitamura and Tomida Machiko : Mesopic contrast sensitivity in amblyopic children, European strabismological association,34th annual meeting, Sep. 2011.
(Keyword)
contrast sensitivity amblyopia
Proceeding of Domestic Conference:
1.
梶田 敬介 and Yoshinori Mitamura : Transplantationof huaman iPS-RPE strip in primate eyes with or without RPE damage, FUJIRETINA, Mar. 2024.
Rieko Arakaki, Hiroshi Eguchi, Akiko Yamada, Yasusei Kudo, Yoshinori Mitamura, Yoshio Hayashi and Naozumi Ishimaru : Eye drop administration of rebamipide is effective to a dry eye symptom in a model mice of Sjogren's syndorome., Proceedings of the Japanese Society for Immunology, Dec. 2013.
Rieko Arakaki, Hiroshi Eguchi, Akiko Yamada, Yasusei Kudo, Yoshinori Mitamura, Yoshio Hayashi and Naozumi Ishimaru : An Effective Therapy of Ocular Lesions in a Murine Model for Sjogren's Syndorome by Eye Drop Administration of Rebamipide., Proceedings of the Japanese Society for Immunology, Dec. 2012.
Y Yokota, M Kadota, Takayuki Ise, Takashi Iwase, T Hara, R Ota, Y Kawabata, K Ogasawara, Mika Bando, S Bando, T Matsuura, Toshiyuki Niki, J Hotchi, N Tomita, Yuka Ueda, Koji Yamaguchi, Yoshio Taketani, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata, Masashi Akaike, Mariko Egawa and Yoshinori Mitamura : 眼病変の経過中に心室中隔の肥厚および完全房室ブロックで発症した心サルコイドーシスの一例, 第245回徳島医学会学術集会(平成24年度夏期), Jul. 2012.
PPAR gamma-mediated role of cyclin-dependent kinase 5 in the pathogenesis of proliferative diabetic retinopathy (Project/Area Number: 16K11288 )
Generation of a marmoset model of normal tension glaucoma and investigation into neuroprotection and neuroregeneration for glaucoma therapy (Project/Area Number: 15H04999 )
Promyelocytic leukemia tumor suppressor as therapeutic agent for diabetic retinopathy (Project/Area Number: 22591929 )
Regulation of the angiogenesis in proliferative diabetic retinopathy using promyelocytic leukemia tumor suppressor (PML) (Project/Area Number: 19592005 )
Identification of molecular pathology of retinal degeneration (Project/Area Number: 18390463 )
The role of transcriptional factor in neovascularization of proliferative diabetic retinopathy (Project/Area Number: 17591846 )
Histologic and Electrophysiologic Study of Normal Neural Retinal Cell Transplantation in Mice with Retinal Degeneration (Project/Area Number: 11671761 )
Morphologic and Electrophysiologic Study of Retinal Pigment Epithelial Cell Transplantation in Age-Related Macular Degeneration (Project/Area Number: 10470367 )