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PURPOSE To compare the visual/anatomical outcomes and feasibility of epiretinal membrane surgery between patients with multifocal or monofocal intraocular lenses (IOLs). METHODS We reviewed the medical records of 46 patients who underwent epiretinal membrane surgery under multifocal or monofocal IOL pseudophakia. The operation time, mean changes in best-corrected visual acuity, and central macular thickness, and complications were compared between the groups. RESULTS Macular surgery was performed in 22 and 24 eyes with multifocal and monofocal IOLs, respectively. The total operation time and the total membrane peeling time were similar in both groups (P = 0.125, P = 0.462, respectively). The mean time to create a membrane edge or flap with retinal microforceps was longer for multifocal than for monofocal IOLs (P = 0.013). The mean changes in best-corrected visual acuity and central macular thickness were similar in both groups (P = 0.682, P = 0.741, respectively). Complications were similar between groups. CONCLUSION With multifocal IOLs, vision outside the central surgical field was blurred, requiring more time to create the membrane flap. Retinal surgeons should anticipate the difficulty in precise focusing when creating a membrane flap in macular surgery in patients with multifocal IOLs and should pay more attention to the macular surgery.

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 investigate the efficacy of intravitreal bevacizumab injections (IVBs) for vitreous haemorrhage (VH) in proliferative diabetic retinopathy (PDR) with prior complete panretinal photocoagulation (PRP). METHODS: A multicentre cohort study of eyes with new VH in PDR after documented previous complete PRP was performed. Eyes were grouped according to IVB treatment at baseline, and cumulative rate of vitrectomy and spontaneous clear-up rate were compared as the main outcome. Eyes requiring vitrectomy within 1 month, or with tractional retinal detachment (TRD), or with spontaneous clear-up within 1 month, were excluded. RESULTS: In total, 44 eyes with IVB and 92 control eyes without IVB were followed up to 20.1 months. Cumulative probability of vitrectomy was lower in the IVB group at 12 months (0.16 vs 0.42, IVB vs controls), and throughout the follow-up period (p = 0.005). Cumulative probability of spontaneous clear-up was higher in the IVB group at 12 months (0.81 vs 0.68, IVB vs controls), and throughout the follow-up period (p = 0.013). Best-corrected visual acuity (BCVA) at 1 month after onset of VH was significantly better in the IVB group (0.513 vs 0.942 logarithm of the minimal angle of resolution, p = 0.002); however, the difference of BCVA lost significance with further follow-up. IVB treatment was the only factor significantly associated with vitrectomy risk on multivariate analysis (p = 0.047, hazard ratio 0.506). CONCLUSION: In VH after prior complete PRP, IVB was effective in decreasing vitrectomy requirement, although overall visual benefit was short-term. IVB can be considered to defer vitrectomy in PDR VH eyes with prior complete PRP and no TRD.

Objectives. We, herein, report two novel USH2A variants from two unrelated Korean families and their clinical phenotypes, with attention to severe or more than severe sensorineural hearing loss (SNHL).Methods. Two postlingually deafened subjects (SB237-461, M/46 and SB354-692, F/34) with more than severe SNHL and also with suspicion of Usher syndrome type II (USH2) were enrolled. A comprehensive audiological and ophthalmological assessments were evaluated. We conducted the whole exome sequencing and subsequent pathogenicity prediction analysis.Results. We identified the following variants of USH2A from the two probands manifesting more than severe SNHL and retinitis pigmentosa (RP): compound heterozygosity for a nonsense (c.8176C>T: p.R2723X) and a missense variant (c.1823G>A: p.C608Y) in SB237, and compound heterozygosity for two frameshift variants (c.14835delT: p.S4945fs & c.13112_13115delAAAT: p.G4371fs) in SB354. Based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, two novel variants, c.1823G>A: p.C608Y and c.14835delT: p.Ser4945fs, can be classified as “uncertain significance” and “pathogenic,” respectively. The audiogram exhibited more than severe SNHL and a down-sloping configuration, necessitating cochlear implantation. The ophthalmic examinations revealed typical features of RP. Interestingly, one proband (SB 354-692) carrying two truncating compound heterozygous variants exhibited more severe hearing loss than the other proband (SB 237-461), carrying one truncation with one missense variant.Conclusion. Our results provide insight on the expansion of audiological spectrum encompassing more than severe SNHL in Korean subjects harboring USH2A variants, suggesting that USH2A should also be included in the candidate gene of cochlear implantation. A specific combination of USH2A variants causing truncating proteins in both alleles could demonstrate more severe audiological phenotype than that of USH2A variants carrying one truncating mutation and one missense mutation, suggesting a possible genotype-phenotype correlation. The understanding of audiological complexity associated with USH2A will be helpful for genetic counseling and treatment starategy.

Congenital Stationary Night Blindness due to Novel TRPM1 Gene Mutations in a Korean Patient

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.

Background: Spinocerebellar ataxia Type 7 (SCA7) is an autosomal dominant, progressive neurodegenerative disorder, primarily characterized by cerebellar ataxia. The disease is caused by the expansion of a CAG trinucleotide repeat within the ataxin-7 gene when its CAG repeat sequences are extended beyond 38. The degree of retinopathy can vary from pigment change in the fovea to foveal atrophy and is correlated with the number of CAG repeats. The present study describes a case of SCA7 with a retinal presentation similar to occult macular dystrophy (OMD) which is an inherited macular dystrophy characterized by presenting with a normal fundus and fluorescein angiography but with progressive central visual loss. Materials and Methods: Report of a case. Results: In this case, no specific abnormality was found on fundus examination, fluorescein angiography, full-field electroretinography and infrared autofluorescence. Spectral-domain optical coherence tomography showed foveal thinning, focal disruption of the ellipsoid zone, and central loss of the outer segment-retinal pigment epithelium interdigitation zone that were well matched with the multifocal electroretinography finding. Thirty-nine CAG repeats in ataxin-7 gene were identified through genetic testing. Conclusions: SCA7 can present with a very mild form of retinal degeneration similar to the classic phenotype of RP1L1-negative OMD in case of the lower number of CAG repeats.

Purpose To describe the functional phenotypic features of East Asian patients with RP1L1-associated occult macular dystrophy (i.e., Miyake disease). Design An international multi-center retrospective cohort study. Methods Twenty-eight participants (53 eyes) with Miyake disease were enrolled at three centres: in Japan, China, and Korea. Ophthalmological examinations including spectral-domain optic coherence tomography (SD-OCT) and multifocal electroretinogram (mfERG) were performed. Patients were classified into three functional groups based on mfERG: Group 1, paracentral dysfunction with relatively preserved central/peripheral function; Group 2, homogeneous central dysfunction with preserved peripheral function; and Group 3, widespread dysfunction over the recorded area. Three functional phenotypes were compared in clinical parameters and SD-OCT morphological classification (severe phenotype, blurred/flat ellipsoid zone and absence of the interdigitation zone; mild phenotype, preserved ellipsoid zone). Results There were eight eyes in Group 1, 40 eyes in Group 2, and five eyes in Group 3. The patients in Group 1 showed significantly later onset (P=.005) and shorter disease duration (P=.002), compared with those in Group 2. All eight eyes in Group 1 showed the mild morphological phenotype, while 43/45 eyes in Groups 2 and 3 presented the severe phenotype, which identified a significant association between the functional grouping and the morphological classification (P Conclusions A spectrum of functional phenotypes of Miyake disease was first documented with identifying three functional subtypes. Patients with paracentral dysfunction had the mildest phenotype, and those with homogeneous central or widespread dysfunction showed overlapping clinical findings with severe photoreceptor changes, suggesting various extents of visual impairment.

To report a case of melanoma-associated retinopathy (MAR) with autoantibodies against the transient receptor potential cation channel, subfamily M, member 1 (TRPM1) with asymmetric severe vision loss. We evaluated a patient with heel skin melanoma showing progressive vision loss in both eyes confirmed with a baseline ophthalmic examination, fluorescein angiography, spectral domain optical coherence tomography (OCT), visual field test, and full-field electroretinogram (ERG). Immunofluorescence assays and western blot analysis revealed autoantibodies in the patient’s serum. The patient’s best-corrected visual acuities were 20/50 in the right eye and hand motion in the left eye. Visual field test showed severely depressed visual fields especially in the left eye. Fluorescein angiography and OCT revealed extrafoveal choroidal neovascularization in the left eye. The patient had an electronegative ERG, suggesting MAR, and autoantibodies against TRPM1 and aldolase C were detected in the patient’s blood sample. The clinical features of MAR patients with positive anti-TRPM1 autoantibodies can be manifested as severe vision loss, and the identification of autoantibodies can be helpful for confirming the diagnosis.

This study aimed to characterize Korean patients with pseudoxanthoma elasticum (PXE) presenting with angioid streaks. Retinal phenotypes were longitudinally evaluated by multimodal ophthalmic imaging, and targeted gene panel sequencing for inherited retinal diseases was conducted. Seven subjects from unrelated families (median age, 51.2 years) were enrolled and followed for a median of 3.2 years. Four asymptomatic patients were significantly younger than three symptomatic patients with decreased visual acuity at presentation (mean age, 38.1 vs. 61.5 years, p = 0.020). The asymptomatic patients maintained good vision (20/32 or better) and had no choroidal neovascularization (CNV) over the observation period. The symptomatic patients showed additional reduction in visual acuity and bilateral CNV occurrence during the longitudinal follow-up. Pathogenic ABCC6 variants were identified in all patients, leading to a diagnosis of PXE. Heterozygous monoallelic variants were identified in four patients and compound heterozygous variants were detected in three patients. Nine ABCC6 variants were identified, including one novel variant, c.2035G&gt, T [p.Glu679Ter]. This is the first genetic study of Korean patients with PXE.

BACKGROUND AND OBJECTIVE: To report the clinical feature of dislocated retropupillary iris-claw aphakic intraocular lens (IOL) and outcomes of reenclavation. PATIENTS AND METHODS: In this multicenter, retrospective case series, 225 eyes of 225 patients underwent retropupillary fixation of iris-claw aphakic IOL and the cases with haptic dislocation were reviewed. RESULTS: Single haptic dislocation was observed in 22 of 225 eyes (9.8%) after 89 ± 77 days (range: 5 days to 277 days) postoperatively, and resolution was achieved through reenclavation without any intraoperative complications in all patients. Iris atrophy in 13 eyes (59%) and history of face washing at the time of dislocation in five patients (23%) were noted. Reenclavation did not cause statistically significant change in best-corrected visual acuity ( P = .315), spherical equivalent ( P = .660), or endothelial cell count ( P = .182) compared to those after the primary surgery. CONCLUSION: Single-haptic dislocation of retropupillary iris-claw aphakic IOL is not a rare complication and can be safely and effectively corrected by reenclavation. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:384–390.]

Background Because of genetically and phenotypically heterogenous features, identification of causative genes for inherited retinal diseases (IRD) is essential for diagnosis and treatment in coming gene therapy era. To date, there are no large-scale data of the genes responsible for IRD in Korea. The aim of this study was to identify the distribution of genetic defects in IRD patients in Korea. Methods Medical records and DNA samples from 86 clinically diagnosed IRD patients were consecutively collected between July 2011 and May 2015. We applied the next-generation sequencing strategy (gene panel) for screening 204 known pathogenic genes associated with IRD. Results Molecular diagnoses were made in 38/86 (44.2%) IRD patients: 18/44 (40.9%) retinitis pigmentosa (RP), 8/22 (36.4%) cone dystrophy, 6/7 (85.7%) Stargardt disease, 1/1 (100%) Best disease, 1/1 (100%) Bardet-Biedl syndrome, 1/1 (100%) congenital stationary night blindness, 1/1 (100%) choroideremia, and 2/8 (25%) other macular dystrophies. ABCA4 was the most common causative gene associated with IRD and was responsible for causing Stargardt disease (n = 6), RP (n = 1), and cone dystrophy (n = 1). In particular, mutations in EYS were found in 4 of 14 autosomal recessive RP (29%). All cases of Stargardt disease had a mutation in the ABCA4 gene with an autosomal recessive trait. Conclusion This study provided the distribution of genetic mutations responsible for causing IRD in the Korean patients. This data will serve as a reference for future genetic screening and treatment for Korean IRD patients., Graphical Abstract

Background: Angiogenin (ANG), a component of tears, is involved in the innate immune system and is related with inflammatory disease. We investigated whether ANG has an immune modulatory function in human corneal fibroblasts (HCFs). Methods: HCFs were cultured from excised corneal tissues. The gene or protein expression levels of interleukin (IL)-1beta (beta), IL-4, IL-6, IL-8, IL-10, complements, toll-like receptor (TLR) 4, myeloid differentiation primary response gene (MYD) 88, TANK-binding kinase (TBK) 1, IkappaB kinase-epsilon (IKK-epsilon) and nuclear factor-kappaB (NF-kappa B) were analyzed with or without ANG treatment in tumor necrosis factor-alpha (TNF-alpha)- or lipopolysaccharide (LPS)-induced inflammatory HCFs by real-time polymerase chain reaction (PCR), Western blotting and immunocytochemistry. Inflammatory cytokine profiles with or without ANG were evaluated through immunodot blot analysis in inflammatory HCFs. Corneal neovascularization and opacity in a rat model of corneal alkali burn were evaluated after application of ANG eye drops. Results: ANG decreased the mRNA levels of IL-1 beta, IL-6, IL-8, TNF-alpha receptor (TNFR) 1, 2, TLR4, MYD88, and complement components except for C1r and C1s and elevated the mRNA expression of IL-4 and IL-10. Increased signal intensity of IL-6, IL-8 and monocyte chemotactic protein (MCP)-1 and MCP-2 induced by TNF-alpha or LPS was weakened by ANG treatment. ANG reduced the protein levels of IKK-e by either TNF-alpha and LPS, and decreased TBK1 production induced by TNF alpha, but not induced by LPS. The expression of NF kappa B in the nuclei was decreased after ANG treatment. ANG application lowered corneal neovascularization and opacity in rats compared to controls. Conclusion: These results demonstrate that ANG reduces the inflammatory response induced by TNF-alpha or LPS in HCFs through common suppression of IKK-epsilon-mediated activation of NF-kappa B. This may support the targeting of immune-mediated corneal in