Genome-Wide Association Analysis Identifies LILRB2 Gene for Pathological Myopia.

Pathological myopia (PM) is one of the leading causes of blindness, especially in Asia. To identify the genetic risk factors of PM, a two-stage genome-wide association study (GWAS) and replication analysis in East Asian populations is conducted. The analysis identified LILRB2 in 19q13.42 as a new candidate locus for PM. The increased protein expression of LILRB2/Pirb (mouse orthologous protein) in PM patients and myopia mouse models is validated. It is further revealed that the increase in LILRB2/Pirb promoted fatty acid synthesis and lipid accumulation, leading to the destruction of choroidal function and the development of PM. This study revealed the association between LILRB2 and PM, uncovering the molecular mechanism of lipid metabolism disorders leading to the pathogenesis of PM due to LILRB2 upregulation.

Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals.

PURPOSE: To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. DESIGN: Cross-sectional analysis. PARTICIPANTS: Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). METHODS: We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. MAIN OUTCOME MEASURE: Proportion of patients with POAG after stratification according to the GRS. RESULTS: We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35-8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79-9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r = 0.08: P = 4.0 × 10-4) and vertical cup-to-disc ratio (r = 0.11; P = 4.0 × 10-6). CONCLUSIONS: The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical Characteristics and Progression of Pachychoroid and Conventional Geographic Atrophy.

Purpose: To elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA). Design: Retrospective, multicenter, observational study. Participants: A total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from 6 university hospitals in Japan were included. All patients were Japanese, aged ≥50 years and with fundus autofluorescence images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group. Methods: The studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semiautomatically measured on fundus autofluorescence images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype. Main Outcome Measures: Clinical characteristics and progression rates of pachychoroid and conventional GA. Results: The pachychoroid GA group was significantly younger (70.3 vs. 78.7 years; P < 0.001), more male-dominant (89.5 vs. 55.6%; P < 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution; P = 0.002), thicker choroid (312.4 vs. 161.6 µm; P < 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%; P < 0.001), and smaller GA area (0.59 vs. 3.76 mm2;P < 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs. 0.27 mm/year; P < 0.001). Conclusions: Demographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in White populations. Some characteristics of GA in Japanese population differ from those in Waucasian populations, which may be due to the inclusion of pachychoroid GA. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Differences between pathologic and non-pathologic high myopia in 4-year outcomes of anti-VEGF therapy for macular neovascularization.

This retrospective observational study aimed to investigate the difference in 4-year outcomes of ranibizumab or aflibercept therapy for macular neovascularization (MNV) with high myopia between pathologic myopia (PM) and non-PM. This study was conducted at Kyoto University Hospital and included consecutive treatment-naïve eyes with active myopic MNV, in which a single intravitreal ranibizumab or aflibercept injection was administered, followed by a pro re nata (PRN) regimen for 4 years. Based on the META-PM study classification, eyes were assigned to the non-PM and PM groups. This study analyzed 118 eyes of 118 patients (non-PM group, 19 eyes; PM group, 99 eyes). Baseline, 1-year, and 2-year best-corrected visual acuity (BCVA) were significantly better in the non-PM group (P = 0.02, 0.01, and 0.02, respectively); however, the 3-year and 4-year BCVA were not. The 4-year BCVA course was similar in both groups. However, the total number of injections over 4 years was significantly higher in the non-PM than in the PM group (4.6 ± 2.6 vs. 2.9 ± 2.6, P = 0.001). Four-year BCVA significantly correlated only with baseline BCVA in both non-PM (P = 0.047, ß = 0.46) and PM groups (P < 0.001, ß = 0.59). In conclusion, over the 4-year observation period, the BCVA course after anti-VEGF therapy for myopic MNV was similar in the eyes with non-PM and those with PM; however, more additional injections in a PRN regimen were required in the eyes with non-PM compared to those with PM. Thus, more frequent and careful follow-up is required for the eyes with non-PM compared with those with PM to maintain long-term BCVA.

Interventions to increase time spent outdoors for preventing incidence and progression of myopia in children.

BACKGROUND: Myopia or nearsightedness is a type of refractive error. It causes people to see near objects clearly but distant objects as blurred. Good vision can be obtained if the refractive error is corrected properly but, where this is not possible, impaired vision will remain. The remaining myopia imposes a considerable personal and societal burden. In addition, the progression of myopia is more likely to be accompanied by other ocular diseases such as cataract, glaucoma and retinal detachment. Myopia has emerged as a significant global public health problem in recent years. The World Health Organization (WHO) reported uncorrected or undercorrected myopia to be a major cause of visual impairment worldwide. From both an individual and social perspective, it is important to prevent the onset of myopia and slow down its progression. Observational studies have shown that children who spend more time outdoors have a lower incidence of myopia. Several other non-Cochrane systematic reviews have focused on the association between increasing children's outdoor activity time and the prevention of myopia. However, none of these systematic reviews were limited to randomised controlled trials (RCTs), as they included all types of study designs, including observational studies and non-RCTs, in addition to RCTs. OBJECTIVES: To assess the effects of interventions to increase outdoor time on the incidence and progression of myopia in children. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, ISRCTN registry, ClinicalTrials.gov, and the WHO ICTRP with no language restrictions. The databases were last searched on 24 June 2022. SELECTION CRITERIA: We included RCTs and cluster-RCTs in which interventions were performed to increase the outdoor time for children with the aim of preventing the incidence and progression of myopia. DATA COLLECTION AND ANALYSIS: We employed the standard methods recommended by Cochrane and assessed the certainty of the evidence using GRADE. We considered the following outcome measures: mean change in refractive error from baseline, incidence of myopia, mean change in the axial length from baseline, mean change in unaided distance visual acuity from baseline, quality of life and adverse event. MAIN RESULTS: We included five RCTs in this review, four of which were cluster-RCTs. The total number of participants was 10,733. The included participants were primary school children, most of whom were in first or second grade (aged six to nine years). Four cluster-RCTs involved school-based interventions to encourage children to spend more time outdoors. The interventions included classroom time outdoors, routine for spending recess outdoors, motivational tools for spending time outdoors, and encouragement through electronic information tools. The intervention groups had less change in refractive errors in the direction of myopia; however, 95% confidence intervals (CIs) included no benefit or both benefit and harm at years one and three, and differences at year two included both clinically important and unimportant benefits (at 1 year: mean difference (MD) 0.08 dioptres (D), 95% CI -0.01 to 0.17; 4 studies, 1656 participants; low-certainty evidence; at 2 years: MD 0.13 D, 95% CI 0.06 to 0.19; 4 studies, 2454 participants; moderate-certainty evidence; at 3 years: MD 0.17 D, 95% CI -0.17 to 0.51; 1 study, 729 participants; low-certainty evidence). Our protocol defined a difference of 0.1 D in the change in refractive error as clinically important. At one year, the difference was less than 0.1 D, but at two and three years it was more than 0.1 D. The incidence of myopia was lower in the intervention groups compared to the control groups, but 95% CIs included no change or clinically unimportant benefits (at 1 year: 7.1% with intervention versus 9.5% with control; risk ratio (RR), 0.82, 95% CI 0.56 to 1.19; 3 studies, 1265 participants; low-certainty evidence; at 2 years: 22.5% with intervention versus 26.7% with control; RR 0.84, 95% CI 0.72 to 0.98; 3 studies, 2104 participants; moderate-certainty evidence; at 3 years: 30.5% with intervention versus 39.8% with control; RR 0.77, 95% CI 0.59 to 1.01; 1 study, 394 participants; moderate-certainty evidence). Our protocol defined a difference of 3% in the incidence of myopia as clinically important. At one year, the difference was 2.4%, but there were clinically important differences between the two groups at two (4.2%) and three years (9.3%). The intervention groups had smaller changes in axial lengths in the direction of myopia than the control groups; however, 95% CIs included no benefit or both benefit and harm at years one and three (at 1 year: MD -0.04 mm, 95% CI -0.09 to 0; 3 studies, 1666 participants; low-certainty evidence; at 2 years: MD -0.04 mm, 95% CI -0.07 to -0.01; 3 studies, 2479 participants; moderate-certainty evidence; at 3 years: MD -0.03 mm, 95% CI -0.13 to 0.07; 1 study, 763 participants; moderate-certainty evidence). No included studies reported changes in unaided distance visual acuity and quality of life. No adverse events were reported. AUTHORS' CONCLUSIONS: The intervention methods varied from adopting outdoor activities as part of school lessons to providing information and motivation for encouraging outdoor activities. The results of this review suggest that long-term interventions to increase the time spent outdoors may potentially reduce the development of myopia in children. However, although the interventions may also suppress the progression of myopia, the low certainty of evidence makes it difficult to draw conclusions. Further research needs to be accumulated and reviewed.

Comparison of a Novel Head-Mounted Objective Auto-perimetry (Gaze Analyzing Perimeter) and Humphrey Field Analyzer.

PURPOSE: To evaluate the agreement between 24-2 visual field (VF) test results obtained using the gaze analyzing perimeter (GAP; Findex) and the Humphrey field analyzer (HFA; Carl Zeiss Meditec). DESIGN: Cross-sectional study. PARTICIPANTS: Patients underwent HFA 24-2 for suspected or confirmed VF loss and were treated at the Kyoto University Hospital between December 2022 and July 2023. METHODS: Patients underwent consecutive VF tests on the same eye using HFA and GAP 24-2 tests. Bland-Altman analysis was used to compare GAP and HFA results. Examination points where the sensitivity measured using GAP was ≥ 10 dB higher than that measured using HFA were re-evaluated by referring back to the original gaze data; 2 ophthalmologists assessed whether the gaze moved linearly toward the new test target. MAIN OUTCOME MEASURES: Mean deviation (MD) and elapsed time on an individual basis and sensitivity on an examination point basis. RESULTS: Forty-seven eyes of 47 patients were analyzed. The correlation coefficient of the MD using HFA and GAP was 0.811 (95% confidence interval [CI]: 0.683-0.891). Bland-Altman analysis showed good agreement between HFA and GAP tests. The mean difference (95% limits of agreement) in MD between HFA and GAP results was -0.63 dB (-5.81 to 4.54 dB). Although no statistically significant differences were observed in the elapsed time (P = 0.99), measurements completed within 200 seconds were observed only in the GAP group (11 cases, 23.4%), who had significantly better HFA MD value than others (P = 0.001). On an examination point basis for sensitivity, the correlation coefficient between HFA and GAP was 0.691 (95% limits of agreement, 0.670-0.711). Original gaze data assessment revealed that the gaze moved linearly toward the new test target for 70.2% of the examination points with a sensitivity discrepancy. CONCLUSIONS: The results indicate that the GAP provides VF assessment outcomes comparable to those of the HFA. The GAP exhibited advantages in terms of testing time, particularly in patients with minimal VF impairment. Furthermore, the GAP records all eye movements, enabling the objective determination of VF abnormalities based on gaze patterns and facilitating easy posthoc verification. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Short-Term Outcomes of 3 Monthly intravitreal Faricimab On Different Subtypes of Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the efficacy and safety of faricimab injections for treatment-naïve neovascular age-related macular degeneration (nvAMD) patients, including subtypes and pachychoroid phenotypes, and identify predictive factors for visual outcomes. Methods: nvAMD patients were prospectively recruited, receiving three monthly faricimab (6 mg) injections. Best-corrected visual acuity (BCVA) two months after the last injection (month 4) was compared between subtypes, and between pachychoroid neovasculopathy (PNV) and non-PNV eyes. Regression analysis determined factors influencing month 4 BCVA. Results: The study involved 23 patients (12 typical AMD [tAMD], 10 polypoidal choroidal vasculopathy [PCV], 1 retinal angiomatous proliferation [RAP]). Eleven exhibited PNV phenotype. Significant BCVA (P = 4.9 × 10-4) and central retinal thickness (CRT) (P = 1.3 × 10-5) improvements were observed post-faricimab treatment. The therapy demonstrated favourable results for both tAMD and PCV eyes, and non-PNV and PNV eyes. Faricimab achieved dry macula in 77.3% of eyes, with subretinal fluid resolution in most cases, although intraretinal fluid (IRF) often persisted. Multivariable analysis identified external limiting membrane (ELM) presence and IRF as BCVA contributors at month 4. Conclusion: Faricimab demonstrated significant effectiveness and safety in treatment-naïve nvAMD patients, particularly for PCV and PNV eyes. ELM presence and IRF is predictive of visual outcomes.

Associations between Nocturnal Hypoxemia and Retinal Nerve Fiber Layer Thinning: The Nagahama Study.

Rationale: There have been meta-analyses that showed reduced retinal nerve fiber layer (RNFL) thickness, which is a surrogate marker of glaucoma, in patients with obstructive sleep apnea (OSA). However, the sample sizes in these reports were small (<300), and the mechanism of RNFL thinning in patients with OSA was not revealed.Objectives: To investigate the relationship of RNFL thickness with nocturnal hypoxemia or hypoxemic burden in a large-scale study.Methods: In this epidemiological study, 8,309 community residents were enrolled. The actigraphy-modified 3% oxygen desaturation index (acti-ODI3%) and cumulative percentage of sleep time with oxygen saturation <90% (acti-CT90) modified by objective sleep duration using actigraphy were measured. The hypoxemic burden is shown as acti-CT90. Circumpapillary RNFL thickness was determined using optical coherence tomography.Results: Multivariable logistic analysis models revealed that an increase in acti-CT90 was significantly associated with mean RNFL thinning after adjusting for several factors in participants without glaucoma diagnosed or treated previously (ß = -0.037; P = 0.009). There were significant differences in mean RNFL thickness among participants stratified according to acti-CT90 (>1.5 vs. ⩽1.5; P = 0.04). Although acti-ODI3% was significantly associated with acti-CT90 (ß = 0.72; P < 0.0001), acti-ODI3% was not significantly associated with mean RNFL thickness in the multivariable logistic analysis (ß = -0.011; P = 0.48). In addition, acti-CT90 was significantly associated with mean RNFL thickness both in the elderly (⩾60 yr; ß = -0.058; P = 0.002) and nonelderly (<60 yr; ß = -0.054; P = 0.007).Conclusions: Acti-CT90, but not acti-ODI3%, was associated with mean RNFL thinning in participants irrespective of age in the elderly or nonelderly. Further prospective studies are required to investigate whether the prevention of hypoxic burden, which was shown as acti-CT90 in this study, is favorable for RNFL thinning.

Risk Factors for Progression of Primary Open-Angle Glaucoma with Lower Normal Intraocular Pressure.

INTRODUCTION: This study aimed to investigate intraocular pressure (IOP)-independent factors associated with the progression of primary open-angle glaucoma (POAG) with IOP ≤15 mm Hg. METHODS: POAG patients with maximum IOP ≤15 mm Hg at the Kyoto University Hospital between January 2011 and August 2021 were retrospectively enrolled. We evaluated effects of various factors on the rate of mean deviation (MD) changes in the visual field (VF) examinations using a linear mixed model. These factors included hypertension, diabetes mellitus (DM), hyperlipidemia (HL), cardiovascular disease, arrhythmia, disc hemorrhage, sleep apnea syndrome, orthopedic diseases, and malignant tumors. RESULTS: In total, 98 eyes from 68 patients were included. The baseline MD was -9.74 ± 7.85 dB. The mean rate of MD change and IOP during the observation period were -0.28 ± 0.04 dB/year and 11.8 ± 1.0 mm Hg, respectively. Comorbidity of DM or HL showed a significant positive association with the rate of MD change (ß = 0.35, p = 0.0006 and ß = 0.18, p = 0.036, respectively) in the model adjusted for age, sex, axial length, mean IOP, and standard deviation of IOP during the observation period. However, no significant association of DM or HL was found after adjusting for central corneal thickness. CONCLUSION: This study suggests that DM or HL is associated with VF deterioration in glaucoma with lower IOP, but the association may be due to differences in IOP characteristics.

Deep learning model for extensive smartphone-based diagnosis and triage of cataracts and multiple corneal diseases.

AIM: To develop an artificial intelligence (AI) algorithm that diagnoses cataracts/corneal diseases from multiple conditions using smartphone images. METHODS: This study included 6442 images that were captured using a slit-lamp microscope (6106 images) and smartphone (336 images). An AI algorithm was developed based on slit-lamp images to differentiate 36 major diseases (cataracts and corneal diseases) into 9 categories. To validate the AI model, smartphone images were used for the testing dataset. We evaluated AI performance that included sensitivity, specificity and receiver operating characteristic (ROC) curve for the diagnosis and triage of the diseases. RESULTS: The AI algorithm achieved an area under the ROC curve of 0.998 (95% CI, 0.992 to 0.999) for normal eyes, 0.986 (95% CI, 0.978 to 0.997) for infectious keratitis, 0.960 (95% CI, 0.925 to 0.994) for immunological keratitis, 0.987 (95% CI, 0.978 to 0.996) for cornea scars, 0.997 (95% CI, 0.992 to 1.000) for ocular surface tumours, 0.993 (95% CI, 0.984 to 1.000) for corneal deposits, 1.000 (95% CI, 1.000 to 1.000) for acute angle-closure glaucoma, 0.992 (95% CI, 0.985 to 0.999) for cataracts and 0.993 (95% CI, 0.985 to 1.000) for bullous keratopathy. The triage of referral suggestion using the smartphone images exhibited high performance, in which the sensitivity and specificity were 1.00 (95% CI, 0.478 to 1.00) and 1.00 (95% CI, 0.976 to 1.000) for 'urgent', 0.867 (95% CI, 0.683 to 0.962) and 1.00 (95% CI, 0.971 to 1.000) for 'semi-urgent', 0.853 (95% CI, 0.689 to 0.950) and 0.983 (95% CI, 0.942 to 0.998) for 'routine' and 1.00 (95% CI, 0.958 to 1.00) and 0.896 (95% CI, 0.797 to 0.957) for 'observation', respectively. CONCLUSIONS: The AI system achieved promising performance in the diagnosis of cataracts and corneal diseases.

Pigment Epithelial Detachment and Leak Point Locations in Central Serous Chorioretinopathy.

PURPOSE: To examine the associations between the vortex vein characteristics and locations of the pigment epithelial detachment (PED) and leak point in patients with central serous chorioretinopathy (CSC). DESIGN: Observational case series. METHODS: We evaluated 116 eyes of 104 patients with CSC. The PED and leak point locations were superimposed over the choroidal en face images using widefield swept-source optical coherence tomography and fluorescein angiography. We defined the draining areas of the superior and inferior vortex veins and analyzed their associations with the PED and leak point locations. RESULTS: One of the 116 eyes with a unique irrigation pattern dominated by the nasal vortex vein was excluded from the analysis. Sixty-nine (60%) of the remaining 115 eyes exhibited asymmetry between the superior and inferior vortex veins. PEDs and leak points were in the vortex vein draining area with greater dilation in 66 (96%) of 69 eyes with asymmetry, and none (0%) were in the opposite areas. Both the PEDs and leak points showed significant differences in their distributions (P < .001, respectively). Additionally, 74% of PEDs and 84% of leak points were located upstream of the vortex vein draining areas, whose frequency was significantly higher compared to other areas (P < .001, respectively). CONCLUSION: PED and leak point spatial distributions corresponded with the most terminal part of the dilated vortex veins, suggesting that blood flow disturbances, such as stasis within the affected vortex veins, may be essential in the pathogenesis of CSC.

MACULAR CHORIORETINAL ATROPHY AND VISUAL OUTCOMES IN RANIBIZUMAB- OR AFLIBERCEPT-TREATED MYOPIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To investigate the predictors of macular chorioretinal atrophy, consisting of patchy atrophy (PA) at the macula and choroidal neovascularization (CNV)-related macular atrophy (CNV-MA), during treatment with ranibizumab or aflibercept for myopic CNV (mCNV) and its impact on visual outcomes. METHODS: This retrospective study included 82 eyes with treatment-naïve mCNV who were treated with pro re nata injections of ranibizumab or aflibercept. RESULTS: Nine eyes (11.0%) presented with macular PA at baseline (PA group), and 73 eyes (89.0%) did not (non-PA group). VA improved during the first year in the non-PA group; a similar trend was noted in the PA group until 3 months after initial treatment. This improvement was maintained until 24 months ( P < 0.001) in the non-PA group, but not in the PA group. In the PA group, macular chorioretinal atrophy progressed faster ( P < 0.0001), and CNV-MA was more frequent during the 2 years of treatments ( P = 0.04). Even non-PA group eyes sometimes developed CNV-MA (42% at Month 24) if they had a larger CNV and thinner subfoveal choroidal thickness at baseline, resulting in poorer visual prognosis ( P < 0.01). CONCLUSION: Macular PA at baseline was a risk factor for CNV-MA development and was associated with poor visual outcomes.

Prevalence and Incidence of Strabismus by Age Group in Japan: A Nationwide Population-Based Cohort Study.

PURPOSE: To investigate the prevalence and incidence of strabismus in the Japanese population by age group and to estimate the subtype proportions. DESIGN: A nationwide population-based cohort study. METHODS: This study investigated the number of cases with previous and new diagnoses of strabismus by age group between 2009 and 2020 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan, which includes almost all (≥95%) medical claims data. We calculated the strabismus prevalence and 1-year incidence in 2019 and analyzed the proportion of each strabismus subtype. RESULTS: The strabismus prevalence was 2.154% (2 709 207/125 708 000; 95% CI, 2.152%-2.157%). It showed a bimodal distribution, with a high proportion in school and old ages (especially ≥75 years). Exotropia, esotropia, and cyclovertical strabismus proportions were 67.3%, 26.0%, and 6.7%, respectively. Cyclovertical strabismus was uncommon in patients aged ≤18 years (1.4%) and more common (10.2%) in those aged >18 years. The strabismus incidence in 2019 was 321 per 100 000 person-years (403 093/125 708 000; 95% CI, 320-322). The annual incidence proportion of cyclovertical strabismus as opposed to whole strabismus subtypes in patients aged >18 years (13.1%) was higher than that in those aged ≤18 years (1.4%). CONCLUSIONS: This is the first nationwide population-based cohort study to demonstrate strabismus's overall prevalence and incidence. The high prevalence of cyclovertical strabismus in adults compared with children may suggest that cyclovertical strabismus is a primarily age-related strabismus. The high prevalence of exotropia may indicate a genetic difference between Japanese and other ethnicities.

Annual trends of ophthalmic surgeries in Japan's super-aged society, 2014-2020: a national claims database study.

This study aimed to analyze the trends and factors influencing the number of ophthalmic surgeries in Japan using the open data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan published by the Ministry of Health, Labour and Welfare. We calculated the number of cataract, glaucoma, and vitreoretinal surgeries, categorized by sex, age, and surgical type, for the fiscal years (FY) 2014 to 2020. The number of cataract surgeries remained stable at approximately 1.45 million cases from FY 2014 to 2018, increased to nearly 1.6 million cases in FY 2019, and decreased to 1.45 million cases in FY 2020. Among glaucoma surgeries, surgical treatments were increased 1.8 times over 7 years, from 33,000 to 60,000 cases. Laser treatment remained steady at around 55,000 cases from FY 2014 to 2017 and then increased to approximately 60,000 cases. The number of vitreoretinal surgeries was increased 1.2 times from FY 2014 to 2019, from 120,000 to 140,000, and decreased to 130,000 by FY 2020. Trends in ophthalmic surgeries over the past 7 years may be influenced by population aging, minimally invasive surgery, and the coronavirus disease pandemic. These findings have implications on surgical decision-making and resource allocation.

Characteristics of Eyes Requiring Trabeculotomy for Glaucoma With Steroid Treatment: Atopic Dermatitis and Factors Affecting Surgical Outcomes.

PURPOSE: The aim is to analyze the surgical outcomes of glaucomatous patients with steroid treatment and investigate the factors, including atopic dermatitis, associated with the surgical success rate. MATERIALS AND METHODS: We retrospectively enrolled participants who required first trabeculotomy for glaucoma with steroid treatment between May 2005 and February 2018 and then compared the postoperative outcomes according to the history of atopic dermatitis or surgical procedures. Surgical success was defined as postoperative IOP ≤ 21 mmHg, ≥20% reduction from baseline, and absence of reoperation. The factors influencing the surgical success rates were investigated using mixed-effects Cox regression. RESULTS: The study included 70 eyes of 46 patients (18 eyes of 12 patients with atopic dermatitis). Postoperative intraocular pressure was not significantly different between eyes with and without atopic dermatitis (12 months after the surgery: patients without atopic dermatitis, 15.4 ± 3.6 mmHg; patients with atopic dermatitis, 16.1 ± 3.9 mmHg; P = 0.65). Twelve months after the surgery, the number of postoperative medications was higher in patients with atopic dermatitis than in those without (2.8 ± 1.3 vs. 2.0 ± 1.7; P = 0.060). However, no significant differences were noted in surgical success rates between patients with atopic dermatitis and those without (P = 0.54). Mixed-effects Cox regression of surgical success rate indicated that only the number of preoperative medications significantly influenced surgical success (P = 0.03). CONCLUSIONS: Regardless of the presence of atopic dermatitis, patients taking many preoperative glaucomatous medications might require reoperation.

Therapeutic effects of faricimab on aflibercept-refractory age-related macular degeneration.

Though vascular endothelial growth factors (VEGF) and other proangiogenic factors, such as angiopoietins (Ang), may be involved in the development of neovascular age-related macular degeneration (nvAMD), only drugs that inhibit the VEGF family are available for the treatment. The newly approved anti-VEGF drug faricimab, which also inhibits Ang-2, is expected to be effective in patients with AMD refractory to conventional anti-VEGF drugs. Therefore, we prospectively investigated the efficacy of faricimab in the treatment of aflibercept-refractory nvAMD. Patients with nvAMD who had been treated with aflibercept in the last year and required bimonthly injections were recruited. 25 eyes showed persistent exudative changes immediately before the faricimab injection (baseline). In these 25 eyes, switching to faricimab did not change visual acuity or central retinal thickness 2 months after the injection; however, 56% of eyes showed reduction or complete absorption of fluid. Notably, 25% of the eyes that showed dry macula at month 2 had no fluid recurrence for up to 4 months. These results indicate that faricimab could benefit some patients with aflibercept-refractory nvAMD.

Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes.

Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel ([Formula: see text]). Substantial genetic sharing between PCV and typical nAMD is noted (rg = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; [Formula: see text]) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.

Widefield choroidal vasculature associated with future condition of subretinal fluid in central serous chorioretinopathy.

Purpose: To examine choroidal angiographic features in the posterior pole associated with resolution or persistency of subretinal fluid (SRF) in eyes with central serous chorioretinopathy (CSC). Design: Observational case series. Methods: Twenty-nine patients with treatment-naïve CSC were divided into two groups based on the presence or absence of SRF 3 months after the initial visit (month 3) without any treatment. Using enhanced depth imaging of widefield swept-source optical coherence tomography, the choroidal thickness (CT), vessel density (VD), and vessel diameter index (VDI) in the superotemporal and inferotemporal subfields on the temporal side of the 18-mm circle from the disc were measured at the initial visit. We calculated the vertical difference in CT and other choroidal angiographic parameters and evaluated their association with the SRF condition at 3 months. Results: The SRF-resolved and SRF-persistent groups included 10 and 19 patients, respectively. At the initial visit, sex, age, axial length, symptom duration, the logarithm of the minimum angle of resolution visual acuity, and foveal thickness were not significantly different between the two groups. The SRF status at month 3 was not associated with the vertical difference in CT and choroidal VD (P = .614, .065, respectively). However, the vertical difference in choroidal VDI was positively associated with the future presence of SRF (P = .017). Conclusions: Vertically asymmetric dilation of choroidal vessels in the posterior pole may be a vasculature feature associated with SRF from CSC and may be a good predictor of future SRF status.

Influence of Trabeculectomy with Mitomycin C on Longitudinal Changes in the Visual Field in Glaucoma Patients with High Myopia.

Purpose: To evaluate the effect of trabeculectomy (Trab MMC) on visual field (VF) progression in eyes with glaucoma and high myopia. Patients and Methods: Patients diagnosed with primary open-angle glaucoma or exfoliation glaucoma who underwent Trab MMC as the first glaucoma surgery along with ≥3 VF tests preoperatively and postoperatively were enrolled. High myopia was defined as an axial length ≥26.5 mm. Postoperative reductions in intraocular pressure (IOP) were assessed by survival analysis using IOP measurements obtained preoperatively. The longitudinal trends of the outcome measures were evaluated using linear mixed models. Results: Thirty-five eyes of 32 patients were included in this study, including 22 eyes of 20 patients in non-highly myopic group and 13 eyes of 12 patients in highly myopic group. IOP decreased after Trab MMC, and the survival rate did not differ significantly in relation to axial length. Linear mixed-model analyses suggested that the inhibitory effects of Trab MMC on the rate of mean deviation (MD) changes were significant in the non-highly myopic group (-0.53 ± 0.15 dB/year preoperatively to -0.16 ± 0.13 dB/year postoperatively; P = 0.004), but not in the highly myopic group (-0.66 ± 0.19 dB/year preoperatively to -0.48 ± 0.18 dB/year postoperatively; P = 0.32). Conclusion: Trab MMC reduced IOP in both highly myopic and non-highly myopic eyes, and IOP reduction was very similar in both groups. The VF deterioration rate decreased in both groups, but the change was weaker and nonsignificant in the highly myopic group.

Extensive reduction in choroidal thickness after photodynamic therapy in eyes with central serous chorioretinopathy.

We examined the effect of reduced fluence (rf)-photodynamic therapy (PDT) of the macular area on the wide-field choroidal thickness in 20 eyes with central serous chorioretinopathy (CSC) and 20 age- and sex-matched control eyes. The choroidal thickness at the posterior pole was measured before and after rf-PDT, using a grid with inner and outer rings, each divided into superotemporal, inferotemporal, superonasal, and inferonasal quadrants, respectively, making up a total of nine subfields including the central 3 mm ring. Before treatment, all eyes showed wide-field choroidal thickening from the dilated vortex vein ampulla to the fovea, along the course of the vein. After rf-PDT of the macular area, the choroidal thickness significantly decreased, not only in the irradiated macular area but also outside the arcade vessels in all quadrants (p < 0.001 for all inner subfields; p = 0.035 and p = 0.024 for the outer superonasal and inferonasal subfields, respectively; p < 0.001 and p = 0.004 for the outer superotemporal and inferotemporal subfields, respectively). For control eyes, the choroidal thickness did not differ between the initial visit and follow-up 1.2 ± 0.7 months after the initial visit (p > 0.05 for all subfields). These findings provide new insights into the pathogenesis of CSC and explain the reasons for the effectiveness of rf-PDT for this condition.