Norihiro Nagai, Hisashi Matsubara, Hiroto Terasaki, Takao Hirano, Aki Kato, Akiko Miki, Hiromasa Hirai, Fumiko Murao, Hiroko Imaizumi, Fumi Gomi, Yoshinori Mitamura, Nahoko Ogata, Sentaro Kusuhara, Tsutomu Yasukawa, Toshinori Murata, Taiji Sakamoto, Mineo Kondo, Hajime Shinoda and Yoko Ozawa : Extent of Complete Retinal Pigment Epithelial and Outer Retinal Atrophy with Foveal Center Involvement is Associated with Visual Acuity., Ophthalmology Science, 5, 1, 2024.
(Summary)
To evaluate the OCT images of eyes with fovea-involved complete retinal pigment epithelial and outer retinal atrophy (cRORA) as well as best-corrected visual acuity (BCVA) to explore the pathogenesis of visual impairment and atrophy.Retrospective observational study.Data of eyes with cRORA associated with age-related macular degeneration with foveal center involvement were collected from 10 hospitals in Japan.Ophthalmic examination data, BCVA, and extents of retinal pigment epithelial and outer retinal atrophy (RORA), represented by choroidal hyper-transmission, and outer plexiform layer (OPL) deterioration, central retinal thickness (CRT), and central choroidal thickness (CCT) measured using built-in software on the sectional OCT images were evaluated.Relationship between BCVA and extents of RORA and OPL deterioration.Of the 64 eyes of 64 patients (mean age: 76.8 ± 9.5 years old), 38 eyes (59.4%) belonged to men. Mean BCVA was 0.602 ± 0.475 (median: 0.523; range, -0.079 to 1.523) in logarithm of the minimum angle of resolution (logMAR). Mean extent of RORA was 2921 ± 1291 (median: 3172; range: 479-5985) μm. BCVA in logMAR positively correlated with extents of RORA (P = 0.004) and OPL deterioration (P = 0.004) and negatively correlated with CRT (P = 0.022). Best-corrected visual acuity ≥0.5 was associated with extents of RORA ≥3000 μm (odds ratio [OR], 4.227; 95% confidence interval [CI], 1.440-12.408; P = 0.009) and OPL deterioration ≥1700 μm (OR, 2.984; 95% CI, 1.034-8.609; P = 0.043), and presence of complete central outer plexiform layer defect (cCOD) (OR, 12.700; 95% CI, 2.439-66.132; P = 0.003), after adjusting for age and sex. The extent of RORA ≥3000 μm was associated with BCVA ≥0.5 (OR, 4.213; 95% CI, 1.437-12.356; P = 0.009), extent of OPL deterioration ≥1700 μm (OR, 58.682; 95% CI, 6.865-501.592; P < 0.001), and presence of cCOD (OR, 4.107; 95% CI, 1.339-12.604; P = 0.014), after adjusting for age and sex. The extent of RORA positively correlated with that of OPL deterioration (P < 0.001), CRT (P = 0.001), and CCT (P = 0.041).A longer extent of cRORA in the OCT images with foveal center involvement was associated with a longer extent of OPL deterioration and the presence of cCOD and worse BCVA. Further studies focusing on OPL changes are warranted for understanding the pathogenesis of RORA and vision loss.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Hiroki Tsujinaka, Sho Imoto, Tetsuo Ueda, Makiko Wakuta, Yutaka Yamada, Takaaki Sugisawa, Fumiko Murao, Takao Hirano, Shigeo Yoshida, Kumiko Kato, Mariko Sasaki, Riko Matsumoto, Gaku Ishigooka and Nahoko Ogata : Incidence and prognosis of taxane-induced macular edema: a retrospective study from the Japan Clinical REtina Study Group (J-CREST), Scientific Reports, 14, 1, 19530, 2024.
(Summary)
Macular edema is a known side effect of taxane-based anticancer drugs. We retrospectively investigated data from 11 centers between January 2016 and December 2021. Among 14,260 patients, 30 (0.21%) developed macular edema; from these, the number of cases associated with nab-paclitaxel was 16 (0.43%), significantly higher than the number of cases associated with paclitaxel or docetaxel (P < 0.01). Visual acuity (VA) and retinal choroidal change were examined in 27 patients, with a follow-up of at least 3 months. The patients' mean age was 67.2 years; 14 (51.3%) were male and four (14.8%) had unilateral onset. The mean interval between anticancer drug initiation and the first ophthalmology visit was 290.1 days. Among the 20 patients who discontinued anticancer drugs, VA and edema significantly improved 2 months after discontinuation (LogMAR VA: 0.50 vs. 0.28, central retinal thickness: 472.7 µm vs. 282.5 µm, both P < 0.01). No significant changes were observed in the central choroidal thickness. A correlation was found between duration of taxane treatment and VA immediately before discontinuation of anticancer drugs (β = 0.00050; 95% confidence interval: 0.00036-0.00097; P < 0.05). Although taxane-induced macular edema is reversible, slower anticancer drug discontinuation worsened VA, highlighting the need for regular ophthalmologic evaluation during treatments.
In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.
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, 15, 1, 92-99, 2024.
(Summary)
This is a rare case of maxillary osteomyelitis associated with osteopetrosis, causing orbital inflammation.
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, 13, 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, 12, 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.
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, 105, 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.
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, 62, 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.
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, 10, 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, 11, 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, 10, 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.
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, 9, 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.
Fumiko Murao, Michiyo Kinosita, Misa Takeda, Momoyo Matsuoka and Kenta Sato : Early treatment was effective in a case of orbital apex syndrome suspected of fungal infection, Japanese Journal of Clinical Ophthalmology, 71, 3, 433-438, 2017.
Masaru Takebayashi, Takeshi Naito, Shingo Matushita, Takashi Katome, Hiroyuki Sato, Fumiko Murao and Hiroshi Shiota : Long-term outcome of vitrectomy for an idiopathic macular hole performed with the use of indocyanine green, The Journal of Medical Investigation : JMI, 55, 3-4, 283-286, 2008.
(Summary)
To evaluate the long-term outcome and safety of vitrectomy for the treatment of an idiopathic macular hole using indocyanine green (ICG) to peel the internal limiting membrane(ILM). By means of a retrospective study, we evaluated the outcomes of 56 eyes in 56 patients with an idiopathic macular hole who all underwent a primary vitrectomy with successful closure of macular hole. We compared the outcomes of 35 eyes in 35 patients who underwent a vitrectomy with ICG-assisted ILM peeling to those of 21 eyes in 21 patients who underwent the same procedure without ILM peeling. The main outcomes were compared between preoperative and postoperative visual acuities. The periods to achieve the postoperative best visual acuity were 11.1 months in the ILM peeling group and 8.9 months in the non-ILM peeling group. However, there were no significant differences between the two groups regarding the postoperative best visual acuity and the final visual acuity. Complications related to ILM peeling with ICG were not found. These results support the safety of ILM peeling with ICG.
(Keyword)
Idiopathic macular hole / Indocyanine green / Surgical removal of internal limiting membrane
Boonruang Khamsri, Fumiko Murao, Akiko Yoshida, Akiko Sakurai, Tsuneo Uchiyama, Hiroki Shirai, Yo Matsuo, Mikako Fujita and Akio Adachi : Comparative study on the structure and cytopathogenic activity of HIV Vpr/Vpx proteins, Microbes and Infection, 8, 1, 10-15, 2006.
(Summary)
The three-dimensional (3-D) structure of human immunodeficiency virus type 2 (HIV-2) Vpr/Vpx was predicted by homology modeling based on the NMR structure of human immunodeficiency virus type 1 (HIV-1) Vpr. The three proteins similarly have three major amphipathic alpha-helices. In contrast to HIV-1 Vpr, Vpr/Vpx of HIV-2 have a long N-terminal loop and clustered prolines in the second half of the C-terminal loop. HIV-2 Vpx uniquely contains a long region between the second and third major helices, and bears several glycines in the first half of the C-terminal loop. Instead of the glycines, there is a group of hydrophilic amino acids and arginines in the corresponding regions of the two Vprs. To compare the cytopathogenic potentials of HIV-1 Vpr and HIV-2 Vpr/Vpx, we examined the production of luciferase as a marker of cell damage. We further analyzed the characteristics of cells transduced with vpr/vpx genes driven by an inducible promoter. The results obtained clearly show that structurally similar, but distinct, HIV Vpr/Vpx proteins are detrimental to target cells.
(Keyword)
Amino Acid Sequence / Cytopathogenic Effect, Viral / Gene Expression Regulation / Gene Products, vpr / HIV-1 / HIV-2 / HeLa Cells / Humans / Molecular Sequence Data / Protein Conformation / Sequence Alignment / Viral Regulatory and Accessory Proteins / vpr Gene Products, Human Immunodeficiency Virus
Fumiko Murao, 西野 真紀, Makoto Kajima, Takeshi Naito and Hiroshi Shiota : Outcome of primary vitrectomy for proliferative diabetic retinopathy with rubeosis in the iris and chamber angle, Japanese Journal of Clinical Ophthalmology, 59, 9, 1535-1538, 2005.
Aya Mima, Hiroko Hata, Fumiko Murao and Hiroshi Shiota : Effect of latanoprost for normal-tension glaucoma by measuring the intraocular pressure at fixed time of day, Japanese Journal of Clinical Ophthalmology, 60, 9, 1613-1616, Oct. 2006.
Mikako Fujita, Boonruang Khamsri, Fumiko Murao, Akiko Yoshida, Akiko Sakurai, Tsuneo Uchiyama, K Kamada, Hiroki Shirai, Yo Matsuo and Akio Adachi : Comparative study on the structure and cytopathogenic activity of HIV Vpr/Vpx proteins, 5th Awaji International Forum on Infection and Immunity, Sumoto, Japan, Sep. 2005.