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Descemet’s membrane detachment (DMD) is a rare but serious complication of phacoemulsification surgery. A small DMD may resolve spontaneously, but extensive DMD often requires intracameral injection of air, nonexpansile gases, or expansile gases. A 92-year-old man who underwent phacoemulsification and aspiration with intraocular lens placement in the right eye had significantly reduced visual acuity, with a hazy cornea after surgery. Anterior segment optical coherence tomography (AS-OCT) examination revealed extensive DMD throughout the cornea. He was treated with intracameral injection of 20% sulfur hexafluoride. As a result, the Descemet membrane was successfully reattached, and the corneal edema resolved. AS-OCT was helpful in confirming the presence and extent of DMD, provided useful information to determine the appropriate treatment, and was useful for monitoring DMD.

Purpose To evaluate the association between daily coffee consumption and intraocular pressure (IOP) in healthy persons without glaucoma and the association between daily coffee consumption and history of glaucoma. Design Cross-sectional study. Participants A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. Methods All participants underwent a standardized ophthalmic examination. Self-reporting questionnaires were completed by all participants. First, the association between habitual coffee consumption and IOP among nonglaucoma individuals was evaluated by a multivariate linear regression analysis, adjusting for possible confounders. Second, the association between habitual coffee consumption and history of glaucoma also was evaluated using a multivariate logistic regression analysis. Main Outcome Measures The association between habitual coffee consumption and IOP among nonglaucoma individuals. Results Of 9850 participants, 9418 did not have history of glaucoma. Among these participants, the mean ± standard deviation IOP of both eyes was 14.7 ± 2.9 mmHg. The multivariate regression analysis revealed that habitual coffee consumption was associated significantly with IOP (P Conclusions Frequent coffee consumption was associated with a slightly lower IOP in people without glaucoma but was not associated with a decreased risk of glaucoma developing. Additional experimental studies are needed to examine the effects of coffee on IOP and glaucoma risk.

Purpose: The pathology of branch retinal vein occlusion (BRVO), a retinal circulatory disease, is related to monocular metamorphopsia-related vision impairment of the affected eyes, but the association of binocular metamorphopsia in such patients is unclear. This study aimed to examine the frequency of binocular metamorphopsia and its association with the clinical characteristics of patients with BRVO. Methods: A total of 99 patients who were treated for BRVO-associated macular edema (ME) were included in this study. At baseline and 1 and 3 months after the initiation of anti-vascular endothelial growth factor (VEGF) treatment, we quantified metamorphopsia in the affected eyes and binocular metamorphopsia using the M-CHARTS® diagnostic tool. Results: At baseline, 59 and 10 patients had metamorphopsia in the affected eyes and binocular metamorphopsia, respectively. Although the visual acuity improved significantly after the initiation of anti-VEGF treatment, the mean M-CHARTS score in the affected eyes did not change from the baseline score. At 3 months, 13 patients showed binocular metamorphopsia; it was significantly associated with metamorphopsia in the affected eyes with a 95% confidence interval of 0.037–0.172 (β = 0.305, p = 0.003). Conclusion: Metamorphopsia in the affected eyes can cause binocular metamorphopsia in patients with BRVO-ME.

[Purpose] To investigate the distribution of clinically significant nonperfusion areas (NPAs) on widefield OCT angiography (OCTA) images in patients with diabetes. [Design] Prospective, cross-sectional, observational study. [Participants] One hundred and forty-four eyes of 114 patients with diabetes. [Methods] Nominal 20 × 23 mm OCTA images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of en face images 20-mm (1614 pixels) in diameter centering on the fovea. The nonperfusion squares (NPSs) were defined as the 10 × 10 pixel squares without retinal vessels, and the ratio of eyes with the NPSs to all eyes in each square was referred to as the NPS ratio. The areas with probabilistic differences (APD) for proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) (APD[PDR] and APD[NPDR]) were defined as sets of squares with higher NPS ratios in eyes with PDR and NPDR, respectively. The P ratio (NPSs within APD[PDR] but not APD[NPDR]/all NPSs) was also calculated. [Main Outcome Measures] The probabilistic distribution of the NPSs and the association with diabetic retinopathy (DR) severity. [Results] The NPSs developed randomly in eyes with mild and moderate NPDR and were more prevalent in the extramacular areas and the temporal quadrant in eyes with severe NPDR and PDR. The APD(PDR) was distributed mainly in the extramacular areas, sparing the areas around the vascular arcades and radially peripapillary capillaries. The APD(PDR) contained retinal neovascularization more frequently than the non-APD(PDR) (P = 0.023). The P ratio was higher in eyes with PDR than in those with NPDR (P < 0.001). The multivariate analysis designated the P ratio (odds ratio, 8.293 × 107; 95% confidence interval, 6.529 × 102–1.053 × 1013; P = 0.002) and the total NPSs (odds ratio, 1.002; 95% confidence interval, 1.001–1.003; P < 0.001) as independent risk factors of PDR. Most eyes with NPDR and 4-2-1 rule findings of DR severity had higher P ratios but not necessarily greater NPS numbers. [Conclusions] The APD(PDR) is uniquely distributed on widefield OCTA images, and the NPA location patterns are associated with DR severity, independent of the entire area of NPAs. [Financial Disclosure(s)] Proprietary or commercial disclosure may be found after the references.

To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population.Genome-wide association study (GWAS).Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses.We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants.Associations of genetic variants with AMD.A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P5.0 × 10Our findings imply shared genetic components conferring the risk of both AMD and CSC.Proprietary or commercial disclosure may be found after the references.

[Purpose] To elucidate the incidence and treatment pattern of active exudative age-related macular degeneration (AMD). [Design] A population-based cohort study conducted using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), a national claims database managed by the Japanese Ministry of Health, Labour, and Welfare (MHLW). [Participants] The entire Japanese population aged 40 years or older (76 million people). [Methods] With the permission of the MHLW, we accessed the complete NDB dataset and identified patients with newly diagnosed active exudative AMD between 2011 and 2018. The incidence of active exudative AMD was categorized by age and sex per year between 2011 and 2018; moreover, details regarding first-line therapy and number of anti-vascular endothelial growth factor (VEGF) injections per elapsed year since initial treatment were obtained and changes in treatment pattern were investigated. [Main Outcome Measures] Incidence rate of active exudative AMD. [Results] During the specified 8-year period, 246 064 incident cases of active exudative AMD were identified; 61.4% of these patients were men. The overall incidence rate was 40.66 per 100 000 person-years (95% confidence interval [CI], 40.49–40.82) in the general population aged 40 years or older, 53.22 (95% CI, 52.95–53.49) in men, and 29.78 (95% CI, 29.60–29.98) in women. Mean age of onset was lower in men than in women (72.51 ± 10.50 years vs. 73.90 ± 10.46 years). Among patients with newly diagnosed active exudative AMD, 92.9% received anti-VEGF injections for initial treatments, whereas 1.8% underwent combination therapy with photodynamic therapy. The number of anti-VEGF injections in the first year (0–12 months), second year (13–24 months), and third year (25–36 months) after the initial injection was 3.66 ± 2.30, 1.39 ± 2.20, and 1.23 ± 2.19, respectively. Patients who received fewer injections in the first year received fewer injections in subsequent years and vice versa. [Conclusions] This is a relatively large population-based study on the detailed epidemiology and actual treatment patterns of active exudative AMD in clinical practice. Our results can be a fundamental information source to ensure healthy eyes and promote well-being for all at all ages., 失明原因となる加齢黄斑変性の日本人の疫学と治療実態を明らかに --国の診療報酬請求データベースを用いた臨床研究--. 京都大学プレスリリース. 2022-03-04.

To evaluate the association between central serous chorioretinopathy (CSC) susceptibility genes and choroidal parameters in a large Japanese cohort.Retrospective cohort study.Of the 9850 individuals in the Nagahama study whose second visit was between 2013 and 2016, those with optical coherence tomography (OCT) images with enhanced depth imaging (EDI), axial length, and genome-wide single nucleotide polymorphism (SNP) genotyping data were included. We calculated subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), normalized choroidal intensity (NCI), and vertical asymmetry of choroidal thickness. Genome-wide quantitative trait locus (QTL) analyses were performed for each parameter. We screened for four CSC susceptibility SNPs: CFH rs800292, TNFRSF10A rs13278062, GATA5 rs6061548, and VIPR2 rs3793217. Whenever an SNP was not included in the genotyping data after quality control, its proxy SNP was selected.In total, 4586 participants were evaluated. CFH rs800292 was significantly associated with SFCT (P0.001) and CVI (P0.001). VIPR2 rs3793217 was significantly associated with SFCT (P0.001) but not with CVI. Whereas, TNFRSF10A rs13254617 and GATA5 rs6061548 were not significantly associated with SFCT or CVI. None of these SNPs was associated with NCICFH, VIPR2, TNFRSF10A, and GATA5 showed different association patterns with choroidal parameters. Although the mechanism of CSC pathogenesis by choroidal changes is not fully understood, this finding suggests that each gene may be involved in different mechanisms of CSC development. Our genetic study provides a basis for understanding the role of CSC susceptibility genes.

Sufian Elfandi,1 Sotaro Ooto,1 Manabu Miyata,1 Naoko Ueda-Arakawa,1 Yousif Subhi,1,2 Kenji Yamashiro,1 Hiroshi Tamura,1 Akio Oishi,1 Masayuki Hata,1 Nagahisa Yoshimura,1 Akitaka Tsujikawa1 1Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan; 2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Sotaro OotoDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine Email ohoto@kuhp.kyoto-u.ac.jpPurpose: To compare the 12-month efficacy of intravitreous aflibercept (IVA) injection between eyes with pachychoroid neovasculopathy and neovascular age-related macular degeneration (AMD).Methods: Retrospective, comparative case series analysis. Twenty-seven eyes with pachychoroid neovasculopathy and sixty-three eyes with neovascular AMD. All patients received three initial monthly, followed by bimonthly, IVA injections.Results: Twelve months after initial treatment, the mean best-corrected visual acuity (BCVA) had improved both in pachychoroid neovasculopathy (from 0.28 to 0.14 logMAR; P = 0.001) and neovascular AMD (from 0.40 to 0.29 logMAR; P < 0.001). Twelve months after initial treatment, eyes with pachychoroid neovasculopathy exhibited decreased mean central retinal thickness (CRT) and subfoveal choroidal thickness (both, P < 0.001) and presence of polyps (P = 0.039) and improved integrity of external limiting membrane (ELM) (P = 0.008) and ellipsoid zone band (P = 0.001). At the 12-month follow-up, 77% and 68% of eyes with pachychoroid neovasculopathy and neovascular AMD, respectively, exhibited dry macula (P = 0.30). Baseline CRT was correlated with 12-month BCVA in eyes with pachychoroid neovasculopathy (P = 0.02). In eyes with neovascular AMD, CRT (P = 0.005) and presence of intact ELM (P = 0.007) were significant predictors of 12-month BCVA.Conclusion: Periodic IVA injection leads to anatomical and functional improvement in eyes with pachychoroid neovasculopathy and in eyes with neovascular AMD.Keywords: age-related macular degeneration, aflibercept, pachychoroid neovasculopathy, choroidal thickness

Purpose To describe the distribution of ocular biometry and refraction in Japanese adults. Design Cross-sectional analysis of a prospective cohort study. Participants A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. Participants were between 34 and 80 years of age. Methods All participants underwent axial length (AL; in millimeters), anterior chamber depth (ACD; in millimeters), corneal diameter (white to white; in millimeters), and central corneal thickness (CCT; in micrometers) measurement (IOL Master; Carl Zeiss Meditec, Dublin, CA) and refraction (spherical equivalent [SE]; in diopters [D]) and corneal curvature (CC; in millimeters) measurement (ARK-530A; Nidek, Aichi, Japan). Distribution of these ocular biometric parameters and prevalence of myopia, high myopia, and extreme myopia were summarized. Main Outcome Measures Distribution of ocular biometry and refraction. Results After standardization to the national population of 2015, estimates of mean AL and SE were 24.21 mm and –1.44 D, respectively. Estimates of mean CC, corneal diameter, CCT, and ACD were 7.69 mm, 12.01 mm, 543.96 μm, and 3.21 mm, respectively. After standardization of age and gender, the prevalence of myopia (SE, ≤–0.5 D) and high myopia (SE, ≤–6.0 D) were 49.97% and 7.89%, respectively. Approximately 70% of the younger participants (34–59 years of age) showed myopia, whereas high myopia was observed in approximately 10%. Although the number of individuals with myopia or high myopia was higher in the younger age groups, the prevalence of more extreme phenotypes remained stable across all ages, especially in women. Axial length of more than 30 mm was observed only in older women (n = 5 [0.05%]). Conclusions We showed detailed distributions of various ocular biometry and refraction parameters using a large general Japanese cohort. Prevalences of myopia and high myopia from 2013 through 2016 were higher than those in earlier studies, which reflects recent environmental change. However, constant prevalence of extreme myopia across all ages suggests high genetic predisposition of the extreme phenotype.

ImportanceThere is no widespread effective treatment to halt the progression of retinitis pigmentosa. Consequently, adequate assessment and estimation of residual visual function are important clinically.ObjectiveTo examine whether deep learning can accurately estimate the visual function of patients with retinitis pigmentosa by using ultra-widefield fundus images obtained on concurrent visits.Design, Setting, and ParticipantsData for this multicenter, retrospective, cross-sectional study were collected between January 1, 2012, and December 31, 2018. This study included 695 consecutive patients with retinitis pigmentosa who were examined at 5 institutions. Each of the 3 types of input images—ultra-widefield pseudocolor images, ultra-widefield fundus autofluorescence images, and both ultra-widefield pseudocolor and fundus autofluorescence images—was paired with 1 of the 31 types of ensemble models constructed from 5 deep learning models (Visual Geometry Group–16, Residual Network–50, InceptionV3, DenseNet121, and EfficientNetB0). We used 848, 212, and 214 images for the training, validation, and testing data, respectively. All data from 1 institution were used for the independent testing data. Data analysis was performed from June 7, 2021, to December 5, 2022.Main Outcomes and MeasuresThe mean deviation on the Humphrey field analyzer, central retinal sensitivity, and best-corrected visual acuity were estimated. The image type–ensemble model combination that yielded the smallest mean absolute error was defined as the model with the best estimation accuracy. After removal of the bias of including both eyes with the generalized linear mixed model, correlations between the actual values of the testing data and the estimated values by the best accuracy model were examined by calculating standardized regression coefficients and P values.ResultsThe study included 1274 eyes of 695 patients. A total of 385 patients were female (55.4%), and the mean (SD) age was 53.9 (17.2) years. Among the 3 types of images, the model using ultra-widefield fundus autofluorescence images alone provided the best estimation accuracy for mean deviation, central sensitivity, and visual acuity. Standardized regression coefficients were 0.684 (95% CI, 0.567-0.802) for the mean deviation estimation, 0.697 (95% CI, 0.590-0.804) for the central sensitivity estimation, and 0.309 (95% CI, 0.187-0.430) for the visual acuity estimation (all P Conclusions and RelevanceResults 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.

This case report discusses using adaptive optics imaging in a patient with acute macular neuroretinopathy with retinal structural changes.

In glaucoma, retinal ganglion cells degenerate progressively, leading to visual field loss and blindness. Presently, the only treatment strategy for glaucoma is lowering the intraocular pressure. However, there are cases in which patients develop progressive visual field loss even though their intraocular pressures are within normal ranges. Therefore, the development of novel therapeutic strategies is an urgent endeavor. Besides high intraocular pressure, several other factors have been proposed to be associated with glaucoma progression, e.g., myopia, blood flow impairment, and amyloid β accumulation. We have previously reported that hop flower extracts possess γ-secretase inhibitory activities and reduce amyloid β deposition in the brains of Alzheimer’s disease model mice. In the current study, we showed that administration of hop flower extracts to glutamate-aspartate transporter (GLAST) knockout mice, the glaucoma model mice, attenuated glaucomatous retinal ganglion cell degeneration. Preservation of retinal ganglion cells in hop flower extract-administered mice was confirmed using optical coherence tomography, confocal scanning laser ophthalmoscopy, and retinal flatmount and histological evaluations. Hop flower extracts are, therefore, deemed a possible candidate as a novel therapeutic agent to treat glaucoma.

Purpose To identify novel susceptibility loci for high myopia. Design Genome-wide association study (GWAS) followed by replication and meta-analysis. Participants A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls). Methods We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses. Main Outcome Measures We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study. Results We identified 9 loci with genome-wide significance (P Conclusions The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.

We included 97 patients with unilateral rhegmatogenous retinal detachment (RRD) with posterior vitreous detachment who underwent vitrectomy, and examined pigmentary lesion (PL) characteristics around the sites of original tears using pre- and postoperative ultra-widefield scanning light ophthalmoscopy, green light fundus autofluorescence (FAF) imaging, and intraoperative digital video. If PL did not involve RRD, we used OCT to preoperatively assess any pathologic changes to the lesion. A total of 116 retinal tears (mean count, 1.2 ± 0.5; range, 1–4 per eye) were observed in the detached retina. Overall, 102 (88%), 63 (54%), 14 (12%), and 25 (22%) tears were accompanied by lattice degeneration (LD) or PL, both LD and PL, only LD, and only PL, respectively. In green FAF images, LD showed normal to mild-hyper fluorescence, whereas all PL showed hypofluorescence. On OCT, PL were located at the RPE level, while choroid abnormalities were unclear. In the retinal areas of 22 eyes, which were not affected by RRD, we observed PL without retinal tears; some were accompanied by vitreous traction and tractional retinal detachment. Pre-, intra-, and post-operative assessments of original flap tears suggested that PL might be a risk factor for RRD, developing alongside or separately from LD.

Purpose To investigate the choriocapillaris changes associated with pachychoroid pigment epitheliopathy (PPE) in comparison with healthy eyes. Methods Nine 3 × 3 mm macular optical coherence tomography angiography images were acquired in patients with PPE and age-matched healthy participants. Multiple en face image averaging of the choriocapillaris was binarized for quantitative image analysis of the flow voids. In PPE eyes, we evaluated the presence of pachyvessels and the association between the location of the choriocapillaris flow deficit and pachyvessels. Results Thirty-two eyes with PPE and 30 eyes of healthy participants were included. In PPE eyes, the mean total area (1.16 ± 0.18 vs. 0.91 ± 0.16, p < 0.001) and average size of the flow voids (790 ± 144 vs. 520 ± 138; p < 0.001) were significantly larger than those in control eyes. Composite images of the choriocapillaris and choroid showed choriocapillaris flow deficits just above and outside the pachyvessels. The mean proportion of the flow void area overlying the pachyvessels against the whole flow void area of the choriocapillaris was 21.3% ± 10.2% (9.38%-44.42%) in PPE eyes. Conclusions In PPE eyes, the blood flow area of the choriocapillaris decreased diffusely within the macular area compared to control eyes, and the choriocapillaris flow deficit was not necessarily related to pachyvessel location.

Purpose Although there have been many population-based studies of age-related macular degeneration (AMD), only limited information is available in Asia on the epidemiology of geographic atrophy (GA). We aimed to determine the prevalence and patterns of GA through an analysis of multiple studies conducted within the Asian Eye Epidemiology Consortium (AEEC). Design Cross-sectional meta-analyses. Participants A total of 97 213 individuals aged 40 years and older. Methods Data from 22 population-based studies from countries belonging to the AEEC were included. In all studies, AMD was defined on the basis of standardized grading systems. Geographic atrophy was defined as an area of pallor in the fundus with visibility of the underlying choroidal blood vessels and sharply defined borders. Random-effects meta-analysis was performed to estimate overall and age-, gender-, and region-specific pooled prevalence of GA. Main Outcome Measures Prevalence of GA per 1000 persons. Results The mean age was 60.8 ± 10.0 years, and 42 673 (43.9%) were male. Overall, a total of 223 individuals (0.2%) had GA. The pooled overall prevalence of GA was 1.57 per 1000 persons (95% confidence interval [CI], 1.04–2.10), which was 3 times less than that of neovascular AMD of 5.20 per 1000 persons (95% CI, 3.97–6.43). Compared with those aged 50 to 59 years, the prevalence of GA increased from 0.34 per 1000 persons (95% CI, 0.07–0.62) to 2.90 per 1000 persons (95% CI, 1.55–4.25) in those aged ≥70 years. The GA prevalence per 1000 persons was similar between urban (2.22; 95% CI, 1.22–3.23) and rural residents (1.33; 95% CI, 0.70–1.96). Geographic atrophy was more prevalent in South Asia (based on studies from India and Nepal, 3.82 per 1000 persons; 95% CI, 1.72–5.93) compared with East Asia (based on studies from China, Korea, Hong Kong, Taiwan, and Japan, and the Singapore Chinese Eye Study, 0.76 per 1000 persons; 95% CI, 0.31–1.22, P = 0.005). Conclusions Geographic atrophy is uncommon in Asian populations compared with those of European ancestry. Even within Asia, geographic differences in GA prevalence were seen. The findings of this meta-analysis suggest that better dissection of risk factors in the Asian population for GA may provide insights into the biological pathways that drive these late-stage manifestations, thus suggesting better targets for prevention.

To assess the characteristics of glaucoma patients who received systemic or topical steroid treatment. Patients who received steroid treatment were selected from a total of 4256 patients at our tertiary referral center of glaucoma management between August 2011 and October 2017. Clinical characteristics of the subjects were extracted from clinical records. To evaluate the factors influencing highest intraocular pressure during observation (max-IOP) or mean deviations (MDs) of visual field at the first and last visits, univariate and multivariate regression analyses were performed using a generalized estimating equation. Three hundred and eighty-two eyes of 196 patients were included in this study. The most frequent disease as the reason for steroid treatment was atopic dermatitis (58 eyes) followed by autoimmune diseases. The patients with atopic dermatitis were significantly younger (38.0 ± 11.2 years old, p < 0.001) and had lower MD (− 9.3 ± 9.1 dB at first visit, p = 0.01; − 10.6 ± 9.2 dB at last visit, p = 0.004) than those with other diseases. In multivariate regression analysis, age and MD at first visit, max-IOP, and atopic dermatitis were correlated with MD at last visit. The results of the present study suggest that patients with atopic dermatitis carry the risk of irreversible visual field loss even in youth. For earlier detection of high intraocular pressure, reinforcement of ophthalmological screening in management of atopic dermatitis should be recommended.

Inherited retinal dystrophy (IRD) patients often experience photophobia. However, its mechanism has not been elucidated. This study aimed to investigate the main wavelength of light causing photophobia in IRD and difference among patients with different phenotypes. Forty-seven retinitis pigmentosa (RP) and 22 cone-rod dystrophy (CRD) patients were prospectively recruited. We designed two tinted glasses: short wavelength filtering (SWF) glasses and middle wavelength filtering (MWF) glasses. We classified photophobia into three types: (A) white out, (B) bright glare, and (C) ocular pain. Patients were asked to assign scores between one (not at all) and five (totally applicable) for each symptom with and without glasses. In patients with RP, photophobia was better relieved with SWF glasses {“white out” (p

Variants in the PROM1 gene are associated with cone (-rod) dystrophy, macular dystrophy, and other phenotypes. We describe the clinical and genetic characteristics of 10 patients from eight Japanese families with PROM1-associated retinal disorder (PROM1-RD) in a nationwide cohort. A literature review of PROM1-RD in the Japanese population was also performed. The median age at onset/examination of 10 patients was 31.0 (range, 10-45)/44.5 (22-73) years. All 10 patients showed atrophic macular changes. Seven patients (70.0%) had spared fovea to various degrees, approximately half of whom had maintained visual acuity. Generalized cone (-rod) dysfunction was demonstrated in all nine subjects with available electrophysiological data. Three PROM1 variants were identified in this study: one recurrent disease-causing variant (p.Arg373Cys), one novel putative disease-causing variant (p.Cys112Arg), and one novel variant of uncertain significance (VUS; p.Gly53Asp). Characteristic features of macular atrophy with generalized cone-dominated retinal dysfunction were shared among all 10 subjects with PROM1-RD, and the presence of foveal sparing was crucial in maintaining visual acuity. Together with the three previously reported variants [p.R373C, c.1551+1G>A (pathogenic), p.Asn580His (likely benign)] in the literature of Japanese patients, one prevalent missense variant (p.Arg373Cys, 6/9 families, 66.7%) detected in multiple studies was determined in the Japanese population, which was also frequently detected in the European population.

Keratoconus is a common ocular disorder that causes progressive corneal thinning and is the leading indication for corneal transplantation. Central corneal thickness (CCT) is a highly heritable characteristic that is associated with keratoconus. In this two-stage genome-wide association study (GWAS) of CCT, we identified a locus for CCT, namely STON2 rs2371597 (P = 2.32 × 10−13), and confirmed a significant association between STON2 rs2371597 and keratoconus development (P = 0.041). Additionally, strong STON2 expression was observed in mouse corneal epithelial basal cells. We also identified SMAD3 rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM’s Watson question answering computer system (P = 0.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development., Yoshikatsu Hosoda et al. study the genetic basis for central corneal thickness (CCT) that is associated with keratoconus. They identify two susceptibility loci, STON2 rs2371597 and SMAD3 rs12913547, using two-step genome-wide association study (GWAS) and predictive analysis with IBM’s Watson question answering computer system, respectively.

Although strabismus is a well-known complication of glaucoma implant surgery, its surgical treatment is still challenging. We present a case with refractory strabismus after Baerveldt glaucoma implant (BGI) surgery, which was not sufficiently improved by strabismus surgery, but by removal of the BGI and fibrous adhesion. The patient was a 35-year-old woman who had multiple surgeries for secondary glaucoma. She had severe limitations of the movement of her right eye and binocular diplopia in all gaze positions after BGI surgery. Although she underwent two strabismus surgeries, the strabismus was not resolved. The surgery was performed by two specialists in glaucoma and strabismus. The BGI plate and the fibrous capsule were carefully removed. The fibrous tissue involved the muscle bellies of the inferior and particularly lateral rectus (LR) muscles and induced tight and wide adhesion between the muscle bellies and sclera. The adhesion was released after tenotomy at the insertion of the LR muscle, and the LR muscle was additionally resected by 6.0 mm. The ocular position and movement dramatically improved; however, intraocular pressure (IOP) increased immediately after the surgery. Then, Ahmed glaucoma valve implantation was performed 5 days after BGI removal. The IOP decreased and has been controlled. The improvement of ocular position and movement remained 9 months postoperatively and she obtained cosmetic satisfaction without diplopia or worsening of visual acuity. Removal of BGI and fibrous adhesion is a potential option for refractory mechanical strabismus following BGI surgery; however, it is important to prepare additional procedures for the subsequent IOP increase in advance.

The study aims to investigate the longitudinal changes in the circumpapillary retinal nerve fibre layer thickness (cpRNFLT) in progressive and non-progressive non-arteritic anterior ischaemic optic neuropathy (NAION). This retrospective observational case series study analysed 17 eyes with NAION. Patients sustaining any additional visual loss (additional decrease in visual acuity (VA) ≥0.2 logMAR) within two months after initial onset of symptoms were classified as having progressive NAION. Of the 17 eyes with NAION, 13 (76.5%) were diagnosed as non-progressive and 4 (23.5%) were diagnosed as progressive. Compared with control eyes, eyes with non-progressive NAION showed greater cpRNFLT in all four optic disc quadrants at the initial visit (temporal and superior: P

To investigate the effect of image averaging on qualitative and quantitative assessments of optical coherence tomography angiography (OCTA) images from eyes of patients with branch retinal vein occlusion (BRVO). Macular OCTA images of 33 eyes of 33 patients with BRVO were obtained using the HS100 HR-SD-OCT system (Canon, Inc.). For each eye, five OCTA cube scans were obtained with a 3 × 3 mm scan protocol, and the data were averaged and compounded into a single high image quality cube data using built-in software. Pre- and post-averaging images were compared qualitatively and quantitatively in superficial capillary plexus (SCP) and deep capillary plexus (DCP) OCTA image slabs. After averaging, all OCTA images showed marked improvement in image quality with less background noise and better vessel continuity. The number of microaneurysms in both the SCP and DCP was larger in single images than in averaged images. A significant increase in the detection rate of capillary telangiectasia in the DCP was noted after image averaging. The number of eyes with disrupted foveal avascular zone (FAZ) decreased significantly after averaging (P = .0253). Five eyes (15.2%) with a disrupted FAZ on the single image showed an intact FAZ after averaging. Vessel length density (VLD) and fractal dimension (FD) significantly decreased and vessel diameter index (VDI) increased after averaging, while significant changes were not observed in vessel density (VD) in both the SCP and DCP. In the SCP, lower VD, VLD, and fractal dimension were significantly correlated with worse visual acuity. OCTA averaging has a significant effect on qualitative and quantitative assessments in eyes with BRVO.

Diabetic macular edema (DME) refractory to anti-VEGF drugs is a socioeconomic burden. In this retrospective study, we investigated the relationship between DME remission and hyperreflective walls in foveal cystoid spaces, a novel finding on spectral domain optical coherence tomography (SD-OCT) images in DME. In a cross-sectional study, we assessed the relationship between hyperreflective walls in foveal cystoid spaces and other OCT findings in 110 eyes of 110 DME patients. Hyperreflective walls were delineated in 27 of 171 foveal cystoid spaces. Eyes with hyperreflective walls in foveal cystoid spaces had poorer visual acuity and more severe photoreceptor disruption than did those without such findings (P = 0.008 and P P = 0.025). We characterized hyperreflective walls in foveal cystoid spaces and designated them as a predictor of no DME remission under ranibizumab injections.

In glaucoma, retinal ganglion cells are damaged, leading to the progressive constriction of the visual field. We have previously shown that the valosin-containing protein (VCP) modulators, Kyoto University Substance (KUS)121 and KUS187, prevent the death of retinal ganglion cells in animal models of glaucoma, including the one generated by N-methyl-D-aspartate (NMDA)-induced neurotoxicity. KUSs appeared to avert endoplasmic reticulum (ER) stress by maintaining ATP levels, resulting in the protection of ganglion cells from cell death. To further elucidate the protective mechanisms of KUSs, we examined gene expression profiles in affected ganglion cells. We first injected KUS-treated mice with NMDA and then isolated the affected retinal ganglion cells using fluorescence-activated cell sorting. Gene expression in the cells was quantified using a next-generation sequencer. Resultantly, we found that KUS121 upregulated several genes involved in energy metabolism. In addition, we observed the upregulation of Zfp667, which has been reported to suppress apoptosis-related genes and prevent cell death. These results further support the suitability of KUS121 as a therapeutic drug in protecting retinal ganglion cells in ophthalmic disorders, such as glaucoma.

Anti-VEGF drugs are as the first-line therapies for diabetic macular edema (DME). In this study, we investigated the association between hyperreflective foci in the outer retinal layers and functional efficacy in DME patients who received intravitreal ranibizumab (IVR) injections. We retrospectively reviewed 77 eyes of 71 patients with DME treated with pro re nata IVR injections for at least 12 months. We evaluated how baseline hyperreflective foci in the outer retinal layers on spectral domain optical coherence tomography images were associated with an improvement in logarithm of the minimum angle of resolution visual acuity (logMAR VA) at 12 months. Forty-three eyes with hyperreflective foci in the outer retinal layers had greater VA improvement than 34 eyes without such foci at 12 months. Multivariate analyses demonstrated that both logMAR VA and hyperreflective foci in the outer retinal layers at baseline were associated with VA improvement. Structural analyses revealed that the central subfield thickness was decreased and that the ellipsoid zone of photoreceptors was improved more significantly in eyes with hyperreflective foci in the outer layers than eyes without such lesions. Baseline hyperreflective foci in the outer retinal layers predict the functional efficacy of IVR injections for DME.

Machine learning (ML) and deep learning (DL) are changing the world and reshaping the medical field. Thus, we conducted a systematic review to determine the status of regulatory-approved ML/DL-based medical devices in Japan, a leading stakeholder in international regulatory harmonization. Information about the medical devices were obtained from the Japan Association for the Advancement of Medical Equipment search service. The usage of ML/DL methodology in the medical devices was confirmed using public announcements or by contacting the marketing authorization holders via e-mail when the public announcements were insufficient for confirmation. Among the 114,150 medical devices found, 11 were regulatory-approved ML/DL-based Software as a Medical Device (SaMD), with 6 products (54.5%) related to radiology and 5 products (45.5%) related to gastroenterology. The domestic ML/DL-based SaMD were mostly related to health check-ups, which are common in Japan. Our review provides a global overview that can foster international competitiveness and further tailored advancements.

PURPOSE: Branch retinal vein occlusion (BRVO) causes macular edema (ME), which can be controlled with anti-VEGF treatments. However, these treatments are not curative, necessitating additional anti-VEGF treatments at recurrence. Long-term results, optimal anti-VEGF treatment regimens, and the comprehensive effects of ME recurrence are largely unknown. Thus, we aimed to examine the effects of foveal thickness (FT) fluctuation (FTF) on the visual and morphologic outcomes of anti-VEGF treatments for BRVO-ME administered via a pro re nata regimen. DESIGN: A retrospective, observational case series. SUBJECTS: This study analyzed 309 treatment-naïve patients (309 eyes) with BRVO-ME between 2012 and 2021 at a multicenter retinal practice. METHODS: The FT was assessed using OCT at each study visit. MAIN OUTCOME MEASURES: We evaluated the logarithm of the minimal angle of resolution (logMAR) best corrected visual acuity (BCVA) and the defect length of the foveal ellipsoid zone (EZ) band using OCT. RESULTS: At baseline, the mean logMAR BCVA was 0.30 ± 0.30 and the mean FT was 503 ± 162 μm. The number of anti-VEGF injections for BRVO-ME was 5.8 ± 4.6 during the mean follow-up period (50.6 ± 22.2 months). At the final examination, the mean logMAR BCVA and FT values were significantly improved compared with those at the baseline. Multiple regression analyses showed that age, baseline logMAR BCVA, and FTF were significantly associated with the final logMAR BCVA (β= 0.20, 0.35, and 0.30, respectively). Foveal thickness fluctuation (divided into groups 0-3 in ascending order of FTF) was significantly associated with logMAR BCVA and the defect length of the foveal EZ band at the final examination. The defect lengths of the foveal EZ band were longitudinally shortened in groups 0 and 1 and were slightly prolonged in groups 2 and 3. The logMAR BCVA showed improvements in groups 0 and 1 and worsened slightly in groups 2 and 3. CONCLUSIONS: 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.

Purpose To investigate conjunctival and intrascleral vasculature in glaucoma eyes using anterior segment (AS)-optical coherence tomography angiography (OCTA) and assess the factors contributing to the vessel density in AS-OCTA images. Design Prospective, cross-sectional study. Methods Thirty-four patients with primary open-angle glaucoma and 20 healthy subjects were included. A swept-source OCT system was used to obtain the AS-OCTA images of the corneoscleral limbus at the nasal and temporal quadrants. Vessel densities were measured in the superficial (from the conjunctival epithelium to a depth of 200 μm) and deep (from a depth of 200 to 1000 μm) layers. The vessel density was compared between healthy and glaucoma eyes, and the associations of the vessel density with possible confounding factors were analyzed using univariable and multivariable analyses. Results The vessel density was not significantly different between healthy eyes and eyes with glaucoma. There was a significant association of superficial vessel density with the use of a prostaglandin analog (P = .007) and with nasal location (P = .016) in eyes with glaucoma. Deep vessel density was significantly smaller with advancing age (P = .029) in healthy eyes and greater with higher intraocular pressure (P = .021) in eyes with treated glaucoma. Conclusions AS-OCTA images may be useful for the objective assessment of conjunctival hyperemia and helpful for understanding the pathophysiology of post-trabecular aqueous humor outflow.

To identify susceptibility genes for macular neovascularization (MNV) development in central serous chorioretinopathy (CSC).Genome-wide survival analysis using a longitudinal cohort study.We included 402 and 137 patients with CSC but without MNV at their first visit from the Kyoto CSC Cohort and Kobe CSC dataset, respectively. All patients underwent detailed ophthalmic examinations, including multimodal imaging, such as fundus autofluorescence, spectral-domain OCT, and fluorescein angiography/indocyanine green angiography or OCT angiography.We conducted a genome-wide survival analysis using the Kyoto CSC Cohort. We applied the Cox proportional hazard model to adjust for age, sex, and the first principal component. Single nucleotide polymorphisms (SNPs) with P values1.0 × 10The association between SNPs and MNV development in patients with CSC.Rs370974631 near ARMS2 displayed a genome-wide significant association in the meta-analysis of discovery and replication result (hazard ratio [HR]ARMS2, CFH, COL4A3, and B3GALTL were identified as susceptibility genes for MNV development in CSC. These 4 genes are known as susceptibility genes for AMD, whereas COL4A3 and B3GALTL were previously reported to be polypoidal choroidal vasculopathy (PCV)-specific susceptibility genes. Our findings revealed the shared genetic susceptibility between PCV and MNV secondary to CSC.

Optical coherence tomography angiography (OCTA) is a new technique for non-invasive imaging of blood vessels, allowing combined evaluation of both deep and surface vessels. The purpose of this study was to evaluate the post-trabeculectomy longitudinal changes in complete avascular area (CAA) of filtering blebs using anterior segment (AS-) OCTA and their association with surgical outcomes. This study included 57 eyes of 53 patients who had undergone trabeculectomy with mitomycin C. AS-OCTA images of filtering bleb were acquired at 3 and 6 months after trabeculectomy, and at 1 month in possible cases. CAAs, regions where complete blood flow was not depicted in AS-OCTA images, were evaluated for their presence, extent, and change over time. CAAs were detected in 37 eyes (65%) and 33 eyes (58%) at 3 and 6 months postoperatively, respectively. The extent of CAAs reduced over time after surgery in most cases. No parameters related to CAAs were significantly associated with surgical success (i.e., intraocular pressure (IOP) ≤ 12 mmHg and IOP reduction > 20% without medication). In conclusion, although it is difficult to predict surgical success by CAA itself, AS-OCTA may be useful for the objective evaluation of the vascularity of filtering blebs.

Purpose: To evaluate the clinical feasibility of peripheral chorioretinal imaging through a front prism on swept-source optical coherence tomography angiography (SS-OCTA). Methods: We prospectively obtained en face OCTA images using SS-OCTA in 10 eyes of 10 healthy volunteers. For the peripheral chorioretinal imaging, the scanning laser passed and refracted through a 45 −90 −45 right-angle prism. We evaluated the qualitative and quantitative characteristics of chorioretinal vessels in the periphery. Results: Using peripheral chorioretinal imaging through a prism, the retinal vasculature was delineated to the equator on the OCTA images, and varices of the vortex vein ampullae were observed on choroidal OCT images. The 3×3-mm images revealed three-dimensional morphologies unique to the peripheral vasculature, such as the gap between retinal arterioles and venules in the superficial capillary plexus (SCP) and elliptical and greater lobules in the choriocapillaris layer. Compared with OCTA images obtained without the prism, those obtained through the prism demonstrated an approximately 1.24-fold increase in the lengths in the base apex direction, whereas the lengths in the perpendicular direction showed concordance. The peripheral vessel density (VD) in the inferior quadrant was lower than those in the other quadrants on the SCP and deep capillary plexus, whereas on the SCP images of the macula the lowest VD was observed in the temporal subfield. Conclusions: Peripheral chorioretinal imaging allowed us to generate ultra-widefield panoramic OCTA images and demonstrated morphologic characteristics unique to peripheral chorioretinal vessels. Translational Relevance: OCTA imaging through a front prism can be a technique for acquiring chorioretinal vasculature images in the periphery.

Peripherin-2 (PRPH2) is one of the causative genes of inherited retinal dystrophy. While the gene is relatively common in Caucasians, reports from Asian ethnicities are limited. In the present study, we report 40 Japanese patients from 30 families with PRPH2-associated retinal dystrophy. We identified 17 distinct pathogenic or likely pathogenic variants using next-generation sequencing. Variants p.R142W and p.V200E were relatively common in the cohort. The age of onset was generally in the 40’s; however, some patients had earlier onset (age: 5 years). Visual acuity of the patients ranged from hand motion to 1.5 (Snellen equivalent 20/13). The patients showed variable phenotypes such as retinitis pigmentosa, cone-rod dystrophy, and macular dystrophy. Additionally, intrafamilial phenotypic variability was observed. Choroidal neovascularization was observed in three eyes of two patients with retinitis pigmentosa. The results demonstrate the genotypic and phenotypic variations of the disease in the Asian cohort., Genes, 12(11), art. no. 1817; 2021

To evaluate the 3-year outcome in eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal anti-vascular endothelial growth factor monotherapy or rescue therapy using standard verteporfin photodynamic therapy (PDT), and corroborate efficacy of rescue PDT.Patients were administered aflibercept injections once a month for 3 months followed by once every 2 months in the first year. After year 1, treatment with aflibercept monotherapy as indicated or in combination with PDT at the retinal specialist's discretion. Only cases completing the three-year follow-up were included. Regression analysis with visual acuity and macular atrophy at year 3 was performed for the dependent variable.Of the 292 eyes, 15 eyes underwent rescue PDT following year 1. The best-corrected visual acuity (logarithm of minimal angle of resolution, mean/Snellen equivalent ± SD) was 0.35 (20/45) ± 0.38, 0.23 (20/30) ± 0.36, 0.26 (20/35) ± 0.38, and 0.31 (20/40) ± 0.42 at baseline, year 1, year 2, and year 3, respectively. Multiple regression analysis revealed that the rescue PDT was significantly associated with macular atrophy and poor visual outcome at year 3 (odds ratio = 1.2, p 0.001; β = 0.23, p = 0.0029, respectively).The visual outcome in eyes with nAMD retained baseline levels at year 3; however, patients treated with rescue PDT developed macular atrophy more frequently and poor visual outcomes.

Purpose: To evaluate the mutual effect of widening the field of view and multiple en face image averaging on the quality of optical coherence tomography angiography (OCTA) images. Methods: This prospective, observational, cross-sectional case series included 20 eyes of 20 healthy volunteers with no history of ocular or systemic disease. OCTA imaging of a 3 × 3-mm, 6 × 6-mm, and 12 × 12-mm area centered on the fovea was performed nine times using the PLEX Elite 9000. We acquired averaged OCTA images generated from nine en face OCTA images. The corresponding areas in the three scan sizes were evaluated for the original single-scanned OCTA images and averaged OCTA images both qualitatively and quantitatively. Quantitative measurements included vessel density (VD), vessel length density (VLD), fractal dimension (FD), and contrast-to-noise ratio (CNR). Results: Significant differences in VD, VLD, FD, and CNR (P < 0.001) were observed due to the mutual effect of averaging and differences in scan size. Both qualitative and quantitative evaluations indicated that the quality of 6 × 6-mm averaged images was equal to or better than that of 3 × 3-mm single-scanned images. However, the quality of 12 × 12-mm averaged images did not reach that of 3 × 3-mm single-scanned images. Conclusions: To some extent, multiple en face OCTA image averaging can compensate for the deterioration in image quality caused by widening the field of view. Translational Relevance: Multiple en face OCTA image averaging can be a technique for acquiring wider field OCTA images with good quality.

To investigate the clinical significance of intercapillary spaces on swept source optical coherence tomography angiography images in diabetic retinopathy.We retrospectively reviewed 110 eyes of 110 patients suffering from diabetic retinopathy without macular edema for whom 3 × 3 mm swept source optical coherence tomography angiography images centered on the fovea were obtained. Automatic image processing of the superficial slab images allowed us to define the areas encircled by retinal vessels as intercapillary spaces within the central 2-mm circle. We evaluated how the quantitative parameters of intercapillary spaces are associated with logMAR and feasible to diagnose diabetic macular ischemia.Total counts (ρ = -0.419; Plt; 0.001) rather than morphologic parameters of the intercapillary spaces showed a significant correlation with logMAR. There were individual levels of correlations between logMAR and counts of intercapillary spaces in individual sectors. In particular, the summed numbers of the spaces in three highly significant sectors were more significantly associated with logMAR (ρ = -0.515; Plt; 0.001). Multivariate analyses confirmed that the number of the intercapillary spaces (β = -0.266; P = 0.016) and foveal avascular zone area (β = 0.227; P = 0.042) were related to logMAR. The clustering using the foveal avascular zone area and the number of intercapillary spaces revealed two major clusters; one had fewer intercapillary spaces (Plt; 0.001) and poorer logMAR (Plt; 0.001) than the other, with a wide range of the foveal avascular zone area.Decreased intercapillary spaces contribute to visual impairment in diabetic retinopathy and suggest one possible criterion of objective diagnosis of diabetic macular ischemia.

Peripherin-2 (PRPH2) is one of the causative genes of inherited retinal dystrophy. While the gene is relatively common in Caucasians, reports from Asian ethnicities are limited. In the present study, we report 40 Japanese patients from 30 families with PRPH2-associated retinal dystrophy. We identified 17 distinct pathogenic or likely pathogenic variants using next-generation sequencing. Variants p.R142W and p.V200E were relatively common in the cohort. The age of onset was generally in the 40’s; however, some patients had earlier onset (age: 5 years). Visual acuity of the patients ranged from hand motion to 1.5 (Snellen equivalent 20/13). The patients showed variable phenotypes such as retinitis pigmentosa, cone-rod dystrophy, and macular dystrophy. Additionally, intrafamilial phenotypic variability was observed. Choroidal neovascularization was observed in three eyes of two patients with retinitis pigmentosa. The results demonstrate the genotypic and phenotypic variations of the disease in the Asian cohort.

To investigate the 2-year effectiveness of reduced-fluence photodynamic therapy (rf-PDT) for chronic central serous chorioretinopathy (cCSC).Retrospective cohort study.A total of 223 consecutive patients with newly diagnosed cCSC with active serous retinal detachment (SRD) were included from May 2007 to June 2017 and followed up for at least 2 years. Patients who underwent ocular treatment other than cataract surgery before the beginning of recruitment and those who had macular neovascularization at baseline were excluded.All patients underwent a comprehensive ophthalmic evaluation, including measurements of best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain OCT. An inverse probability of treatment weighting (IPTW) methodology was applied to balance 18 baseline characteristics between patients who received rf-PDT (rf-PDT group) and those who did not receive treatment (controls). Inverse probability of treatment weighting survival analysis and regression were performed.The proportion of patients whose BCVA at 24 months was the same or improved compared with the baseline visual acuity (VA) (VA maintenance rate).A total of 155 eyes (rf-PDT group: 74; controls: 81) were analyzed. The patients' backgrounds were well balanced after IPTW with standardized differences of0.10. An IPTW regression analysis revealed that the VA maintenance rate was significantly higher in the rf-PDT group than in the controls (93.6% vs. 70.9%,The study suggests the beneficial effect of rf-PDT for cCSC for both VA maintenance and higher proportion of complete SRD remission in the clinical setting.

The aim of this retrospective, observational study was to examine the intraretinal locations of ruptured retinal arterial macroaneurysms (RMAs) and investigate the associations with the visual prognosis. Fifty patients (50 eyes) with untreated RMA rupture who visited the Department of Ophthalmology at Kyoto University Hospital (April 2014–July 2019) were included. The intraretinal position of the ruptured RMAs relative to the affected retinal artery was examined using optical coherence tomography (OCT) and color fundus photography (CFP). The relative RMA positions were anterior to (anterior type, 44%), at the same level as (lateral type, 20%), or posterior to (posterior type, 34%) the affected artery. At the initial visit, the posterior type showed greater subretinal hemorrhage thickness than did the lateral and anterior types (P = 0.016 and 0.006, respectively), and poorer visual acuity (VA) than did the anterior type (P = 0.005). At the final visit, the length of the foveal ellipsoid zone band defect was longer (P = 0.005) and VA was poorer (P

PURPOSE To investigate whether the efficacy of anti-vascular endothelial growth factor (VEGF) monotherapy for polypoidal choroidal vasculopathy (PCV) differs between pachychoroid and non-pachychoroid phenotypes in the long term. METHODS This retrospective longitudinal study included 115 treatment-naive eyes in 115 consecutive patients with symptomatic PCV who were treated with anti-VEGF monotherapy and were followed up for 5 years. Eligible eyes were assigned to either a pachy-PCV group, with a pachychoroid phenotype, or a non-pachy-PCV group, without a pachychoroid phenotype. Best-corrected visual acuity (BCVA) and other parameters over a 5-year period were compared between the groups. RESULTS Forty-eight eyes and 67 eyes were classified into the pachy-PCV and non-pachy-PCV groups respectively. Baseline and 5-year BCVA (logarithm of the minimum angle of resolution) were 0.19 ± 0.20 and 0.16 ± 0.28 in the pachy-PCV group, respectively, and 0.25 ± 0.26 and 0.26 ± 0.36 in the non-pachy-PCV group respectively. BCVA did not change significantly in either group (p = 0.18 and 0.08 respectively). BCVA did not differ between the groups at any observation time-point. Subfoveal choroidal thickness (SFCT) at baseline and at 5 years was significantly higher in the pachy-PCV group than in the non-pachy-PCV group (both p

We have established a stepwise method to differentiate induced pluripotent stem cells (iPSCs) into retinal pigment epithelium (RPE) (iPSC-RPE), which enables efficient isolation and purification of patient-derived iPSC-RPE cells with high quality. Here, we describe in detail the process of differentiating iPSCs into iPSC-RPE.

We performed a prospective, longitudinal study to investigate the association between the preoperative intrascleral vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) and surgical outcomes of trabecular meshwork-targeted micro- or minimally invasive glaucoma surgery (MIGS). We included 37 patients with primary open-angle glaucoma. Preoperative AS-OCTA images of the sclero-conjunctiva of the nasal corneal limbus were acquired in the superficial (conjunctival) and deep (intrascleral) layers. The vessel densities (VDs) of each layer were measured separately in the entire area, limbal side, and fornix area. Surgical success was determined by postoperative intraocular pressure (IOP) and IOP reduction. Twenty-three and 14 eyes were classified as having successful and unsuccessful outcomes, respectively. The deep VDs of the entire area and fornix area were significantly lower in the successful group (P = 0.031 and P = 0.009). The success rate was significantly higher for eyes with a lower deep VD than for eyes with a higher deep VD. A greater IOP reduction was significantly associated with lower deep VD in the fornix area (P = 0.022) and higher preoperative IOP (P, 前眼部OCTAを用いた線維柱帯切開術効果予測 --房水主流出路の可視化による緑内障手術予後予測の可能性--. 京都大学プレスリリース. 2021-09-09.

High resolution imaging with optical coherence tomography angiography and offset pinhole adaptive optics scanning light ophthalmoscope helped us visualize the hemodynamic and structural changes in a ruptured retinal arterial macroaneurysm in a 78-year-old woman. Intravitreal injection of anti-vascular endothelial growth factor was administered to ameliorate the condition.

Purpose: The purpose of this study was to image and investigate the foveal microstructure of human cone and Müller cells using adaptive optics-optical coherence tomography. Methods: Six healthy subjects underwent the prototype adaptive optics-optical coherence tomography imaging, which allowed an axial resolution of 3.4 µm and a transverse resolution of approximately 3 µm. The morphological features of the individual retinal cells observed in the foveola were qualitatively and quantitatively evaluated. Results: In the six healthy subjects, the image B-scans showed hyper-reflective dots that were densely packed in the outer nuclear layer. The mean number, diameter, and density of hyper-reflective dots in the foveola were 250.8 ± 59.6, 12.7 ± 59.6 µm, and 6966 ± 1833/mm², respectively. These qualitative and quantitative findings regarding the hyper-reflective dots were markedly consistent with the morphological features of the foveal cone cell nuclei. Additionally, the images showed the funnel-shaped hyporeflective bodies running vertically and obliquely between the inner and external limiting membranes, illustrating the cell morphology of the foveal Müller cells. Conclusions: Using adaptive optics, we succeeded in visualizing cross-sectional images of the individual cone and Müller cells of the human retina in vivo. Translational Relevance: Adaptive optics-optical coherence tomography would help to improve our understanding of the pathogenesis of macular diseases.

Previous clinical studies have suggested that pachychoroid can induce macular neovascularization (MNV) to develop pachychoroid neovasculopathy (PNV) and that PNV can progress to polypoidal choroidal vasculopathy (PCV). Recent studies based on the pachychoroid concept are now gradually revealing the true nature of, at least some part of, PCV. However, previous studies on PNV and/or PCV have used different frameworks for the classification of PNV, PCV, and neovascular age-related macular degeneration (nAMD). These have hampered the rapid overhaul of the understanding of PCV. Some investigators have assumed that all PCV is pachychoroid-driven whereas other investigators have classified PCV into “pachychoroid PCV” and “non-pachychoroid PCV”. Furthermore, since there is no consensus as to whether PNV includes PCV, some studies have included PCV with PNV, while other studies have excluded PCV from PNV. To address these gaps, we summarize previous studies on PCV and pachychoroid. Even before the proposal of the pachychoroid concept, previous studies had suggested that PCV could be divided into two subtypes, of which one was characterized by pachychoroid features. Previous studies had also provided keys to understand relationship between PCV and PNV. We here recommend a refined conceptual framework for future studies on PNV, PCV, and nAMD. Considering the current inconsistent understanding of PCV, we should be cautious about using the term PCV until we understand the true nature of PCV.

We have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production.Intracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs.BCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time.BCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration.

We developed a novel scotoma detection system using time required for fixation to the random targets, or the” eye-guided scotoma detection method “. In order to verify the” eye-guided scotoma detection method “, we measured 78 eyes of 40 subjects, and examined the measurement results in comparison with the results of measurement by Humphrey perimetry. The results were as follows: (1) Mariotte scotomas were detected in 100% of the eyes tested; (2) The false-negative rate (the percentage of cases where a scotoma was evaluated as a non-scotoma) was less than 10%; (3) The positive point distribution in the low-sensitivity eyes was well matched. These findings suggested that the novel scotoma detection method in the current study will pave the way for the realization of mass screening to detect pathological scotoma earlier.Author summaryConventional perimeters, such as the Goldmann perimeter and Humphrey perimeter, require experienced examiners and space occupying. With either perimeter, subjects’ eye movements need to be strictly fixed to the fixation target of the device. Other perimeters can monitor fixation and automatically measure the visual field. With the eye-guided scotoma detection method proposed in the current study, subjects feel less burdened since they do not have to fixate on the fixation target of the device and can move their eyes freely. Subjects simply respond to visual targets on the display; then, scotomas can be automatically detected. The novel method yields highly accurate scotoma detection through an algorithm that separates scotomas from non-scotomas.

BACKGROUND AND OBJECTIVE: Investigations of morphological changes in photoreceptors in Behçet's disease (BD) using adaptive optics scanning light ophthalmoscope (AOSLO) are lacking. The authors aimed to evaluate macular cone density and regularity in BD patients with or without a history of uveitis with good visual acuity (VA). PATIENTS AND METHODS: The authors included 16 patients (29 eyes) with BD and 12 healthy volunteers (12 eyes) as controls. All subjects had VA of 20/20 or higher. Subjects underwent AOSLO to evaluate the photoreceptor status including cone density (numbers/mm 2 ) and proportion of hexagonal Voronoi domains. RESULTS: Hyporeflective patches that were not detected in color fundus photograph or optical coherence tomography were observed by AOSLO in BD patients both with and without past uveitis history; these were not detected in the control group. Cone density was significantly reduced in BD patients with a history of uveitis compared to controls ( P = .002). The proportion of hexagonal Voronoi domains was significantly reduced in BD eyes both with and without history of uveitis relative to controls ( P < .001). CONCLUSION: Macular photoreceptor damage was observed in BD patients with and without a history of uveitis. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:218–225.]