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Purpose To investigate the genotype and long-term clinical phenotype of patients with Bietti crystalline dystrophy (BCD) in Korea and Japan. Design Retrospective case series. Participants We analyzed 62 patients with clinical features of BCD who harbor pathogenic biallelic CYP4V2 variants in their homozygote or compound heterozygote. Methods Data were collected from patient charts, including age, best-corrected visual acuity (BCVA), Goldmann perimetry results, fundus photography, OCT findings, fundus autofluorescence results, and electroretinography findings. We compared the clinical course of the patients with homozygous c.802-8_810de117insGC [exon7del], the most common mutation in the East Asian population, with those of the patients with other genotypes. Main Outcome Measures Best-corrected visual acuity, visual field (VF), and their changes during follow-up. Results The mean age at the first visit was 55.2 years, with a mean follow-up of 7.1 years. The mean BCVAs at the first and last visits were 0.28 logarithm of the minimum angle of resolution (logMAR) and 0.89 logMAR, respectively. In genetic testing, c.802-8_810de117insGC was detected in 86 of 124 alleles of the patients, and 36 patients were homozygous for this mutation. The age, BCVA, VF area, central foveal thickness, and abnormal hypoautofluorescent area at either the first or last visit were not different between the exon7del homozygotes and the others. The mean BCVA changes per year were 0.089 logMAR in the exon7del homozygotes and 0.089 logMAR in the others. An age- and gender-adjusted linear regression analysis showed no association between the exon7del homozygote status and the rate of vision loss. Characteristic crystalline deposits in the posterior pole were generally observed in younger patients and disappeared over time along with progressive retinochoroidal atrophy. Conclusions Patients with BCD and a homozygote for c.802-8_810de117insGC accounted for more than 50% of this cohort of Korean and Japanese patients, and the clinical effect of this deleterious variant was not severe in the spectrum of CYP4V2 retinopathy.

Purpose This study investigated the 10-year incidence of progression from intermediate to exudative age-related macular degeneration (AMD) and identified genetic and environmental factors influencing that progression in the Korean population. Design Retrospective, observational cohort study. Methods In total, 632 eyes of 418 patients (age: ≥50 years) with intermediate AMD were enrolled. The incidence of exudative AMD was assessed from color fundus photographs and optical coherence tomography images obtained at baseline and during annual visits. Data regarding lifestyle variables and dietary habits were acquired through comprehensive questionnaires. Genotyping data concerning 3 single nucleotide polymorphisms (SNPs), rs800292 and rs1061170 in the CFH gene and rs10490924 in ARMS2 were also analyzed. The cumulative incidence of exudative changes was estimated using Kaplan-Meier analysis. Associated influential factors were evaluated using univariate and multivariate Cox regression models. Results The mean follow-up period was 3.99 ± 2.85 years. The cumulative incidence of progression to exudative AMD was 5.6%, 14.8%, and 28.4% at 2, 5, and 10 years, respectively. Multivariate Cox analysis showed that age (hazard ratio [HR]: 1.041; P = .0393), family history of AMD (HR: 3.175; P = .0184), and pre-existing exudative AMD in the fellow eye (HR: 3.186; P = 5.31 × 10−5) were positively associated with exudative changes. Regular intake of green tea (HR: 0.632; P = .0475) was associated with a decrease in exudative changes. The ARMS2 SNP rs10490924 (HR: 1.482; P = .0185) showed a significant association with AMD progression. Conclusions The annual progression rate from intermediate to exudative AMD in the Korean population is approximately 2.8%, which is comparable with that for whites. Intake of green tea may be a modifiable protective factor against exudative changes.

Purpose To describe the clinical and genetic characteristics of the cohort enrolled in the East Asian studies of occult macular dystrophy (OMD). Design International, multicenter, retrospective cohort studies. Participants A total of 36 participants from 21 families with a clinical diagnosis of OMD and harboring pathogenic RP1L1 variants (i.e., Miyake disease) were enrolled from 3 centers in Japan, China, and South Korea. Methods A detailed history was obtained, and comprehensive ophthalmological examinations including spectral-domain OCT were performed. All detected sequence variants in the RP1L1 gene were reviewed, and in silico analysis was performed, including allele frequency analyses and pathogenicity predictions. Main Outcome Measures Onset of disease, visual acuity (VA) converted to the logarithm of the minimum angle of resolution (logMAR), OCT findings, and effect of detected variants. Results Eleven families from Japan, 6 from South Korea, and 4 from China were recruited. There were 12 female and 24 male participants. The median age of onset was 25.5 years (range, 2–73), and the median age at the latest examination was 46.0 years (range, 11–86). The median VA (logMAR) was 0.65 (range, –0.08–1.22) in the right eye and 0.65 (–0.08–1.10) in the left eye. A significant correlation between onset of disease and VA was revealed. The Classical morphologic phenotype showing both blurred ellipsoid zone and absence of interdigitation zone of the photoreceptors was demonstrated in 30 patients (83.3%), and subtle photoreceptor architectural changes were demonstrated in 6 patients (16.6%). Eight pathogenic RP1L1 variants were identified, including 6 reported variants and 1 novel variant: p.R45W, p.T1194M/p.T1196I (complex), p.S1199C, p.G1200A, p.G1200D, p.V1201G, and p.S1198F, respectively. Two variants were recurrent: p.R45W (11 families, 52.4%) and p.S1199C (5 families, 23.8%). The pathogenic missense variants in 10 families (47.6%) were located within the previously reported unique motif, including 6 amino acids (1196–1201). Conclusions There is a large spectrum of clinical findings in Miyake disease, including various onset of disease and VA, whereas the characteristic photoreceptor microstructures were shared in most cases. Two hot spots including amino acid numbers 45 and 1196–1201 in the RP1L1 gene were confirmed in the East Asian population.

Glaucoma is a vision-threatening disorder characterized by progressive death of retinal ganglion cells (RGCs), although little is known about therapeutic milestones. Due to its complex and multifactorial pathogenesis, multipronged therapeutic approach is needed. Angiogenin (ANG), now called ribonuclease (RNase) 5, has been previously known as angiogenic factor and more recently its biologic activity is extended to promoting cell survival via its ribonucleolytic activity. Here, we revealed the defect of ANG in human glaucomatous trabecular meshwork (TM) cells and identified novel multiple functions of ANG as an anti-glaucomatous strategy. ANG was highly expressed in normal eyes and normal TM cells compared to glaucomatous TM cells. ANG induced intraocular pressure (IOP) lowering in rat models of both normal and elevated IOP, and as a possible mechanism, activated Akt-mediated signals for nitric oxide (NO) production, an important regulator of IOP in glaucomatous TM cell. Moreover, we demonstrated ANG-induced production of matrix metalloproteinase (MMP)-1 and -3 and rho-kinase inhibition for TM remodeling. For anti-glaucomatous defense optimization, ANG not only elicited immune-modulative pathways via indolamine 2,3-dioxygenase (IDO) activation in TM cells and suppression of Jurkat T cells, but also rescued neural stem cells (NSCs) from apoptosis induced by glaucomatous stress. These results demonstrate that novel multi-functional effects of ANG may have benefits against glaucoma in ocular tissues.