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.
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.
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.
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.
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.
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
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.
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
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.
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.
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.