Efficacy, durability, and safety of faricimab up to every 16 weeks in patients with neovascular age-related macular degeneration: 2-year results from the Japan subgroup of the phase III TENAYA trial.

PURPOSE: To evaluate 2-year efficacy, durability, and safety of faricimab in the TENAYA Japan subgroup and pooled global TENAYA/LUCERNE cohort of patients with neovascular age-related macular degeneration (nAMD). METHODS: Subgroup analysis of TENAYA/LUCERNE (NCT03823287/NCT03823300): phase III, multicentre, randomised, active comparator-controlled, double-masked, non-inferiority trials. Treatment-naïve patients aged ≥ 50 years with nAMD were randomised (1:1) to intravitreal faricimab (6.0 mg up to every 16 weeks [Q16W] after 4 initial Q4W doses) or aflibercept (2.0 mg Q8W after 3 initial Q4W doses). Outcomes were assessed through year 2 for the TENAYA Japan subgroup (N = 133) and global pooled TENAYA/LUCERNE cohort (N = 1329). RESULTS: Vision and anatomic improvements achieved with faricimab at year 1 were maintained over 2 years and were generally comparable between the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Adjusted mean best-corrected visual acuity (BCVA) change from baseline at year 2 for the TENAYA Japan subgroup and global pooled TENAYA/LUCERNE cohort was +7.1 (3.7-10.5) and +4.4 (3.2-5.5) letters in the faricimab arm, respectively, and +5.2 (1.9-8.6) and +4.3 (3.1-5.4) letters in the aflibercept arm, respectively. At week 112, the proportion of faricimab-treated patients on Q16W dosing was 61.0% and 63.1% in the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Faricimab was well tolerated through year 2. CONCLUSION: Year 2 TENAYA Japan subgroup findings for faricimab were generally consistent with the pooled global TENAYA/LUCERNE results in patients with nAMD. Vision and anatomical benefits with faricimab were similar to those with aflibercept but with fewer injections.

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.

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.

Novel Manifestation of Retinal Hemangioblastomas Detected by OCT Angiography in von Hippel-Lindau Disease.

PURPOSE: To elucidate the clinical characteristics of atypical retinal vascular proliferation in patients with von Hippel-Lindau (VHL) disease using OCT angiography (OCTA). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-seven consecutive patients with a diagnosis of VHL disease who visited Kyoto University Hospital between January 2019 and March 2022. METHODS: Retinal hemangioblastomas (RHs) were assessed using multimodal imaging including OCTA. Retinal hemangioblastomas were classified into 2 phenotypes: nodular and flat. Nodular RHs were defined as typical RHs that were globular, well-circumscribed tumors, often accompanied with dilated feeder arterioles and draining venules. Flat RHs lacked a protruded red or colored mass, had variable and indistinct borders, and were not accompanied with feeder and draining vessels. MAIN OUTCOME MEASURES: The prevalence, distribution, and description of atypical flat RHs. RESULTS: Among 57 consecutive patients with VHL disease, 37 patients (64.9%) showed RHs in at least 1 eye. Bilateral RHs were seen in 23 patients (62.2%). Among 58 eyes of 37 patients with RHs, typical nodular RHs were detected in 54 eyes. Nodular RHs were seen mainly in the peripheral retina and occasionally in the peripapillary region, and they showed exudative changes in some cases. Flat RHs were detected in 7 eyes (12.1%). Four eyes showed only flat RHs, and 3 eyes showed both types in the same eye. Most flat RHs appeared as retinal hemorrhages or faint flat abnormal retinal vessels in the inner retina on the fundus examination, often within the macula area or peripapillary. In all eyes with flat RHs, OCTA showed abundant blood flow in the lesions. OCT revealed that flat RHs were seen mainly between the retinal nerve fiber layer and the ganglion cell layer, and occasionally within the inner nuclear layer. During a mean follow-up period of 20.4 ± 15.0 months, no flat RHs accompanied exudative change, tractional retinal detachment, or progression in size. CONCLUSIONS: Patients with VHL disease can demonstrate 2 distinct types of RHs: the classic nodular type and an atypical flat type. OCT angiography can be useful in improving the detection of atypical flat RHs, which can be difficult to detect clinically. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Genome-Wide Association Study of Age-Related Macular Degeneration Reveals 2 New Loci Implying Shared Genetic Components with Central Serous Chorioretinopathy.

PURPOSE: To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population. DESIGN: Genome-wide association study (GWAS). PARTICIPANTS: Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses. METHODS: 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. MAIN OUTCOME MEASURES: Associations of genetic variants with AMD. RESULTS: A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P < 5.0 × 10-8). Of these loci, 4 were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2), and 2 were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all datasets, we observed strong associations in these loci (P = 1.88 × 10-12 and P = 1.35 × 10-9 for meta-analysis for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were associated significantly with CSC (P = 4.86 × 10-3 and P = 4.28 × 10-3 for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (rg [the measure of genetic correlation] = -0.33; P = 0.01; false discovery rate, 0.099). CONCLUSIONS: Our findings imply shared genetic components conferring the risk of both AMD and CSC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Seven-year outcome after 1-year fixed regimen of intravitreal aflibercept injections followed by pro re nata treatment for neovascular age-related macular degeneration.

PURPOSE: The study aims to investigate the 7-year best-corrected visual acuity (BCVA) course after 1-year fixed regimen of intravitreal aflibercept injection (IVA) for neovascular age-related macular degeneration (nAMD) and to identify factors affecting this BCVA. METHODS: This longitudinal, observational study included 63 treatment-naïve eyes (61 patients) with nAMD, treated with 1-year fixed regimen of IVA-3 monthly injections and 4 subsequent bimonthly injections-essentially followed by PRN regimen of IVA but sometimes followed by agent switching, photodynamic therapy (PDT), or vitrectomy, as needed. We assessed BCVA changes over a 7-year period. Morphologically, we assessed central retinal thickness (CRT), central choroidal thickness (CCT), subfoveal pigment epithelial detachment (PED) height, vitreomacular traction/adhesion (VMT/VMA), epiretinal membrane (ERM), and macular atrophy involving the fovea. RESULTS: Logarithm of the minimum angle of resolution (logMAR) BCVA changed from 0.20 ± 0.24 to 0.29 ± 0.45 over 7 years. BCVA improved significantly after years 1 and 2 (P = 0.002 and 0.001, respectively) and then slowly decreased. BCVA after years 3-7 did not significantly differ from baseline. CRT and CCT decreased significantly during follow-up, while PED height did not. VMT/VMA decreased significantly, whereas ERM and macular atrophy increased significantly. Seven-year and baseline BCVA positively correlated (P = 0.007, ß = 0.35). CONCLUSIONS: BCVA was maintained for 7 years in nAMD eyes after 1-year fixed regimen of IVA, essentially followed by PRN regimen, but sometimes followed by agent switching, PDT, or vitrectomy, without severe drug-induced complications. Thus, early diagnosis and treatment of nAMD are essential for maintaining good long-term BCVA, even in eyes with relatively poor baseline vision.

CHORIOCAPILLARIS STRUCTURE IN THE FELLOW EYES OF PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: An OCT Angiography Image Averaging Study.

PURPOSE: Histological choriocapillaris abnormalities have been reported in age-related macular degeneration (AMD). Averaging multiple en face optical coherence tomography angiography improves the quality of imaging of the choriocapillaris. This study used multiple en face swept source optical coherence tomography angiography image averaging to examine the structural changes in the choriocapillaris in the fellow eyes of patients with neovascular AMD. METHODS: All patients underwent macular optical coherence tomography angiography imaging. One eye per subject was repeatedly imaged, and nine raster scan sets were obtained. Registered en face images were averaged, and area of flow voids and number of flow voids were measured using ImageJ software. RESULTS: Forty-eight patients with neovascular AMD were recruited for analysis. Twenty-seven patients had polypoidal choroidal vasculopathy, and 22 eyes had soft drusen. Twenty-six eyes of 26 healthy individuals were included as age-matched normal controls. The choriocapillaris had a meshwork appearance in all eyes. The mean flow void area of the choriocapillaris was larger in patients with AMD than normal controls (1.14 ± 0.16 mm2 vs. 1.01 ± 0.12 mm2, P = 0.002). The mean size of each flow void was greater in patients with AMD than normal controls (729 ± 210 µm2 vs. 583 ± 120 µm2, P = 0.003). The mean flow void area of the choriocapillaris was larger in eyes with soft drusen than without soft drusen (1.2 ± 0.2 mm2 vs. 1.1 ± 0.1 mm2, P = 0.024). CONCLUSION: Multiple en face image averaging revealed precise choriocapillaris structures in the fellow eyes of patients with neovascular AMD.

PREDICTORS OF 3-MONTH AND 1-YEAR VISUAL OUTCOMES AFTER VITRECTOMY WITH SUBRETINAL TISSUE PLASMINOGEN ACTIVATOR INJECTION FOR SUBMACULAR HEMORRHAGE.

PURPOSE: To investigate factors associated with 3-month or 1-year best-corrected visual acuity (BCVA) after vitrectomy with subretinal tissue plasminogen activator injection for submacular hemorrhage (SMH) and to identify the predictors of early displacement. METHODS: This prospective cohort study included consecutive eyes with SMH complicating neovascular age-related macular degeneration or retinal macroaneurysm that underwent vitrectomy with subretinal tissue plasminogen activator injection and were followed up for at least 3 months. Parameters that correlated with 3-month BCVA, 1-year BCVA, and 2-week displacement grade (0-3) were identified. RESULTS: Twenty-nine eyes of 29 patients (73.1 ± 8.4 years; neovascular age-related macular degeneration, 25 eyes) were included. Logarithm of the minimum angle of resolution BCVA improved 3 months after the surgery (baseline, 0.76 [20/115] ± 0.35; 3-month, 0.51 [20/65] ± 0.32; P = 0.006). In multivariable analyses, 1-year logarithm of the minimum angle of resolution BCVA correlated with age ( P = 0.007, ß = 0.39) and SMH recurrence within 1 year after surgery ( P < 0.001, ß = 0.65). Two-week displacement grade correlated with the contrast-to-noise ratio of SMH ( P = 0.001, ß = -0.54). Macular hole occurred in three eyes (10%) with small SMH size and was closed in all eyes via additional vitrectomy with an inverted internal limiting membrane flap technique. CONCLUSION: The recurrence of SMH negatively affected the 1-year visual outcome after vitrectomy with subretinal tissue plasminogen activator injection for SMH. The contrast-to-noise ratio was a useful predictor of early SMH displacement, but not of 1-year BCVA. Further research is necessary to determine the optimal treatment to prevent SMH recurrence.

TEN-YEAR VISUAL OUTCOME AND CHANGE IN CHORIORETINAL ATROPHY AFTER INTRAVITREAL RANIBIZUMAB FOR MACULAR NEOVASCULARIZATION IN PATHOLOGIC MYOPIA.

PURPOSE: To investigate the 10-year visual outcome and chorioretinal atrophy after a single intravitreal ranibizumab injection followed by a pro re nata regimen for myopic macular neovascularization in pathologic myopia, and to identify the factors associated with 10-year best-corrected visual acuity (BCVA). METHODS: This retrospective observational study evaluated 26 consecutive treatment-naïve eyes (26 patients) with myopic macular neovascularization in pathologic myopia who underwent a single intravitreal ranibizumab followed by a pro re nata regimen of intravitreal ranibizumab and/or intravitreal aflibercept injection and observed over 10 years. We assessed changes in BCVA and morphological parameters, including the META-PM Study category as a chorioretinal atrophy index. RESULTS: The logarithm of the minimum angle of resolution BCVA changed from 0.36 (Snellen, 20/45) ± 0.39 to 0.39 (20/49) ± 0.36 over 10 years of observation. Compared to baseline, 1-year BCVA improved ( P = 0.002), whereas 2 to 10-year BCVA was not significantly different. Total injection frequency was 3.8 ± 2.6. In none of the eyes, 10-year BCVA was 20/200 or less. Ten-year BCVA correlated with baseline BCVA ( P = 0.01, r = 0.47). The META-PM Study category progressed in 60% of eyes. There were no drug-induced complications. CONCLUSION: Best-corrected visual acuity in eyes with myopic macular neovascularization in pathologic myopia was maintained for 10 years after a single intravitreal ranibizumab followed by a pro re nata regimen without drug-induced complications. The META-PM Study category progressed in 60% of eyes, especially those with older baseline age. Early diagnosis and treatment of myopic macular neovascularization are essential to maintain good long-term BCVA.

Influence of Tumor Characteristics on Visual Field Outcomes After Pituitary Adenoma Surgery.

BACKGROUND: There were few reports about the influence of tumor characteristics on the postoperative visual field outcomes after transsphenoidal surgery for pituitary adenoma. The purpose of this study was to explore the tumor characteristics that influenced perioperative visual field changes. METHODS: Patients who underwent transsphenoidal surgery under a diagnosis of pituitary adenoma at the Kyoto University Hospital between April 2012 and December 2018 were retrospectively enrolled. Correlations among circumpapillary retinal nerve fiber layer thickness, preoperative and postoperative mean deviation (MD) of visual field, MD change after the surgery, and maximum tumor diameter were evaluated by measuring Pearson correlation coefficient. We evaluated the influences on postoperative MD using a generalized estimating equation for univariate and multivariate regression analyses. We also compared the characteristics of cystic and solid tumors. RESULTS: Thirty-two eyes of 18 patients were included in this study (9 male and 9 female patients). Postoperative MD positively correlated with maximum tumor diameter only in multivariate regression {ß = 0.22 (95% confidence interval [CI], 0.004-0.43), P = 0.046}, although maximum tumor diameter negatively correlated with postoperative MD in univariate regression (ß = -0.16 [95% CI, -0.58 to 0.26], P = 0.46). In the investigation of perioperative MD changes, eyes with cystic tumors showed significantly better improvement those with solid tumors (8.93 ± 7.85 vs 0.18 ± 6.56 dB, P = 0.007). CONCLUSIONS: Cystic and solid tumors show different characteristics of visual loss and visual field defects. The MD in eyes with cystic tumors improved significantly more than that in eyes with solid tumors.

Pathological Neurovascular Unit Mapping onto Multimodal Imaging in Diabetic Macular Edema.

Diabetic retinopathy is a form of diabetic microangiopathy, and vascular hyperpermeability in the macula leads to retinal thickening and concomitant reduction of visual acuity in diabetic macular edema (DME). In this review, we discuss multimodal fundus imaging, comparing the pathogenesis and interventions. Clinicians diagnose DME using two major criteria, clinically significant macular edema by fundus examination and center-involving diabetic macular edema using optical coherence tomography (OCT), to determine the appropriate treatment. In addition to fundus photography, fluorescein angiography (FA) is a classical modality to evaluate morphological and functional changes in retinal capillaries, e.g., microaneurysms, capillary nonperfusion, and fluorescein leakage. Recently, optical coherence tomography angiography (OCTA) has allowed us to evaluate the three-dimensional structure of the retinal vasculature and newly demonstrated that lamellar capillary nonperfusion in the deep layer is associated with retinal edema. The clinical application of OCT has accelerated our understanding of various neuronal damages in DME. Retinal thickness measured by OCT enables us to quantitatively assess therapeutic effects. Sectional OCT images depict the deformation of neural tissues, e.g., cystoid macular edema, serous retinal detachment, and sponge-like retinal swelling. The disorganization of retinal inner layers (DRIL) and foveal photoreceptor damage, biomarkers of neurodegeneration, are associated with visual impairment. Fundus autofluorescence derives from the retinal pigment epithelium (RPE) and its qualitative and quantitative changes suggest that the RPE damage contributes to the neuronal changes in DME. These clinical findings on multimodal imaging help to elucidate the pathology in the neurovascular units and lead to the next generation of clinical and translational research in DME.

Binocular metamorphopsia in patients with branch retinal vein occlusion: a multi-center study.

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 87 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, 53 and 7 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, 9 patients showed binocular metamorphopsia; it was significantly associated with metamorphopsia in the affected eyes with a 95% confidence interval of 0.021-0.122 (ß = 0.306, p = 0.006). CONCLUSION: Metamorphopsia in the affected eyes can cause binocular metamorphopsia in patients with BRVO-ME.

Genome-wide Survival Analysis for Macular Neovascularization Development in Central Serous Chorioretinopathy Revealed Shared Genetic Susceptibility with Polypoidal Choroidal Vasculopathy.

PURPOSE: To identify susceptibility genes for macular neovascularization (MNV) development in central serous chorioretinopathy (CSC). DESIGN: Genome-wide survival analysis using a longitudinal cohort study. PARTICIPANTS: 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. METHODS: 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 values < 1.0 × 10-5 were carried forward to the replication in the Kobe CSC dataset. Moreover, we evaluated the contribution of previously reported age-related macular degeneration (AMD) susceptibility loci. We used FUMA and ToppFun for the functional enrichment analysis. MAIN OUTCOME MEASURES: The association between SNPs and MNV development in patients with CSC. RESULTS: Rs370974631 near ARMS2 displayed a genome-wide significant association in the meta-analysis of discovery and replication result (hazard ratio [HR]meta, 3.63; Pmeta = 5.76 × 10-9). Among previously reported AMD susceptibility loci, we additionally identified CFH rs800292 (HR, 0.39, P = 2.55 × 10-4), COL4A3 rs4276018 (HR, 0.26, P = 1.56 × 10-3), and B3GALTL rs9564692 (HR, 0.56, P = 8.30 × 10-3) as susceptibility loci for MNV development in CSC. The functional enrichment analysis revealed significant enrichment of 8 pathways (GO:0051561, GO:0036444, GO:0008282, GO:1990246, GO:0015272, GO:0030955, GO:0031420, and GO:0005242) related to ion transport. CONCLUSIONS: 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.

Association between topical ß-blocker use and asthma attacks in glaucoma patients with asthma: a cohort study using a claims database.

PURPOSE: To investigate the association between the use of topical ß-blockers and subsequent asthma attacks in glaucoma patients with asthma. METHODS: This was a retrospective longitudinal cohort study using an administrative claims database. All patients aged 20 years or older who were registered in the health insurance claims database updated and managed by JMDC Inc. (Tokyo, Japan). Patients who were newly prescribed eye drops for glaucoma treatment were identified between 2011 and 2017. The patients with glaucoma were divided into two groups: ß-blocker users and non-ß-blocker users, based on the presence of a ß-blocker in the prescribed eye drops. We investigated whether the incidence of asthma attacks in patients with previously treated asthma differed between the two groups. RESULTS: We categorized 17,666 patients in the ß-blocker-user group and 12,609 patients in the non-ß-blocker-user group. A total of 580 patients in the ß-blocker group (3.28%) and 847 in the non-ß-blocker group (6.72%) underwent asthma treatment before the prescription of anti-glaucoma eye drops (P < 0.001). Furthermore, 94 patients in the ß-blocker-user group (0.53%) and 278 in the non-ß-blocker user group (2.20%) were undergoing current treatment for asthma (P < 0.001). The adjusted hazard ratios of asthma attacks were 0.73 (95% confidence interval, 0.46-1.16, P = 0.18) in patients with a history of asthma treatment and 1.22 (95% confidence interval, 0.56-2.70, P = 0.62) in patients with current asthma treatment, compared to the non-ß-blocker-user group. CONCLUSION: Our results clarified that several patients with asthma were prescribed topical ß-blockers for glaucoma treatment. However, asthma attacks may not be significantly attributed to topical ß-blockers, even in glaucoma patients under current asthma treatment. The administration of topical ß-blockers to asthma patients could be a treatment option in the absence of other treatment options, if adequate informed consent is obtained. Further studies are needed to draw a firm conclusion on this clinical question.

DETECTION AND CHARACTERISTICS OF UNRUPTURED RETINAL ARTERIAL MACROANEURYSMS.

PURPOSE: To determine the presence of unruptured retinal arterial macroaneurysms (RAMs) and to examine the characteristics of the detected lesions. METHODS: This retrospective observational study included the affected and contralateral eyes of 50 patients (100 eyes) with symptomatic, unilateral, ruptured RAMs who visited the Department of Ophthalmology at the Kyoto University Hospital (April 2014-April 2020) and were followed up for at least 6 months after the onset. The presence and characteristics of unruptured RAMs were examined by reviewing the findings of color fundus photography and infrared scanning laser ophthalmoscopy performed before the onset or during the follow-up period. RESULTS: Unruptured RAMs were detected in six of the 50 patients. Some patients had bilateral or multiple unruptured RAMs, and a total of 12 unruptured RAMs were detected in eight eyes of the six patients. Among the detected lesions, eight exhibited a longitudinal increase in their diameter during the follow-up period, whereas six exhibited ruptures. CONCLUSION: Unruptured RAM is not an uncommon retinal vascular abnormality and can enlarge and progress to ruptured RAM.

MACULAR BLOOD FLOW CHANGES IN BRANCH RETINAL VEIN OCCLUSION EXAMINED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VARIABLE INTERSCAN TIME ANALYSIS.

PURPOSE: To examine the relationship between changes in retinal blood flow and the recurrence of macular edema in eyes with branch retinal vein occlusion. METHODS: This observational study included 32 eyes in 32 patients (18 men and 14 women) with branch retinal vein occlusion who visited the Department of Ophthalmology at Kyoto University Hospital (February 2021-November 2021). At the time of inclusion in the study, each patient underwent optical coherence tomography angiography on a macular area measuring 4 × 4 mm 2 . For variable interscan time analysis, different interscan times were set at 7.6 (IST 7.6 ) and 20.6 ms (IST 20.6 ) for the optical coherence tomography angiography. The parafoveal vessel densities were measured sectorally at IST 7.6 and IST 20.6 , and their relationship with the longitudinal changes evident in the retinal thicknesses during the variable interscan time analysis examination and 2 months later was evaluated. RESULTS: The parafoveal vessel densities in the affected sector was significantly greater at IST 20.6 than at IST 7.6 ( P = 0.011). At 2 months after the variable interscan time analysis examination, 6 patients (19%) showed recurrence of macular edema involving the fovea. The difference in the parafoveal vessel densities (IST 20.6 - IST 7.6 ) in the affected sector was significantly associated with longitudinal retinal thickening in the corresponding parafovea ( P = 0.020) and fovea ( P = 0.014). CONCLUSION: In eyes with branch retinal vein occlusion, optical coherence tomography angiography variable interscan time analysis facilitated the detection of retinal blood flow changes that might be predictive for the recurrence of macular edema.

PREDICTORS OF RETINAL PIGMENT EPITHELIUM TEAR DEVELOPMENT AFTER TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: The purpose of this study was to investigate the predictors of retinal pigment epithelium (RPE) tear development after treatment for neovascular age-related macular degeneration using swept source optical coherence tomography angiography. METHODS: This prospective study included 152 treatment-naïve eyes with neovascular age-related macular degeneration without high myopia that were followed up for 1 year after treatment. Eligible eyes were classified into eyes with or without RPE tear development. They were matched in a 1:2 ratio. The areas of choroidal neovascularization (CNV) and RPE detachment (pigment epithelial detachment [PED]) were measured from optical coherence tomography angiography and OCT en face images, respectively. The optical coherence tomography angiography-specific parameters representing CNV status were analyzed. RESULTS: Eight (5.3%) of the 152 eyes developed RPE tears (RPE tear group). After matching, 16 eyes without RPE tears were analyzed (non-RPE tear group). The ratio of the CNV/PED area was lower in the RPE tear group than that in the non-RPE tear group (P = 0.007). The PED area was broader (P = 0.008), and PED height was greater in the RPE tear group (P = 0.04). Optical coherence tomography angiography-specific parameters did not differ between the two groups. CONCLUSION: Neovascular age-related macular degeneration with pretreatment broad PED, high PED, and small CNV area relative to the PED area has a high risk of RPE tear development after therapy. However, CNV status may not have an association.

CONTRAST-TO-NOISE RATIO IS A USEFUL PREDICTOR OF EARLY DISPLACEMENT OF LARGE SUBMACULAR HEMORRHAGE BY INTRAVITREAL SF6 GAS INJECTION.

PURPOSE: To investigate predictors of early displacement of submacular hemorrhage (SMH) by simple intravitreal SF6 gas injection. METHODS: This retrospective study included 16 eyes of 16 consecutive patients (age: 74.5 ± 7.7 years; 15 men) with large SMH treated with simple intravitreal SF6 gas before inception of subretinal tissue plasminogen activator injection at our institution. The SMH displacement was graded at 1-week posttreatment as 0, 1, or 2. Central retinal thickness, central choroidal thickness, SMH height, SMH area, disease duration, use of anticoagulant or antiplatelet drugs, and contrast-to-noise ratio (CNR) of SMH on optical coherence tomography images were recorded. Correlations between displacement grading and baseline parameter were analyzed. RESULTS: Univariable correlation analysis revealed association of the 1-week displacement grading with the CNR (P = 0.004; r = -0.68) and SMH height (P = 0.03; r = -0.55). The CNR was most strongly associated with 1-week displacement on multivariable correlation analysis (P = 0.01; ß = -0.60). CONCLUSION: Findings of the present study showed that the CNR of SMH was a useful predictor of early displacement of large SMH after simple intravitreal SF6 gas injection. When vitrectomy with subretinal injection of tissue plasminogen activator is difficult in patients with large SMH, with low CNR on optical coherence tomography, simple intravitreal SF6 gas injection may be a treatment option.

Myopia Prevalence and Ocular Biometry Features in a General Japanese Population: The Nagahama Study.

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.

Deterioration of phagocytosis in induced pluripotent stem cell-derived retinal pigment epithelial cells established from patients with retinitis pigmentosa carrying Mer tyrosine kinase mutations.

Retinitis pigmentosa (RP) is an incurable retinal degenerative disease with an unknown mechanism of disease progression. Mer tyrosine kinase (MERTK), which encodes a receptor of the Tyro3/Axl/Mer family of tyrosine kinases, is one of the causal genes of RP. MERTK is reportedly expressed in the retinal pigment epithelium (RPE) and is essential for phagocytosis of the photoreceptor outer segment. Here, we established induced pluripotent stem cells (iPSC) from patients with RP having homozygous or compound heterozygous mutations in MERTK, and from healthy subjects; the RP patient- and healthy control-derived iPSCs were differentiated into RPE cells. Although cytoskeleton staining suggested that polarity may have been disturbed mildly, there were no apparent morphological differences between the diseased and normal RPE cells. The internalization of photoreceptor outer segments in diseased iPSC-RPE cells was significantly lower than that in normal iPSC-RPE cells. This in vitro disease model may be useful for elucidating the mechanisms of disease progression and screening treatments for the disease.