Electrophysiological Analysis of Retinal Organoid Development Using 3D Microelectrodes of Liquid Metals.

Despite of the substantial potential of human-derived retinal organoids, the degeneration of retinal ganglion cells (RGCs) during maturation limits their utility in assessing the functionality of later-born retinal cell subtypes. Additionally, conventional analyses primarily rely on fluorescent emissions, which limits the detection of actual cell functionality while risking damage to the 3D cytoarchitecture of organoids. Here, an electrophysiological analysis is presented to monitor RGC development in early to mid-stage retinal organoids, and compare distinct features with fully-mature mouse retina. This approach utilizes high-resolution 3D printing of liquid-metal microelectrodes, enabling precise targeting of specific inner retinal layers within organoids. The adaptable distribution and softness of these microelectrodes facilitate the spatiotemporal recording of inner retinal signals. This study not only demonstrates the functional properties of RGCs in retinal organoid development but also provides insights into their synaptic connectivity, reminiscent of fetal native retinas. Further comparison with fully-mature mouse retina in vivo verifies the organoid features, highlighting the potential of early-stage retinal organoids in biomedical research.

Extracellular fluid excess linked to reduced choroidal vascularity index in patients with chronic kidney disease.

Extracellular fluid (ECF) excess is common in patients with chronic kidney disease (CKD). This study (involving 284 patients with CKD) explored the association between choroidal vascularity index (CVI) and ECF excess. We categorised patients into three groups based on extracellular water/total body water: normal, mildly overhydrated, and severely overhydrated. The more severe ECF status was associated with a lower CVI after adjustment (B = - 0.902, p = 0.001). In non-diabetic patients, both vascular luminal (LA, p < 0.001) and stromal areas (SA, p = 0.003) were significantly reduced in patients with severe ECF excess compared to others, whereas diabetic patients showed no significant differences in LA (p = 0.96) and SA (p = 0.86) based on ECF excess status. These findings suggest that ECF status may influence CVI in patients with CKD, underscoring the need for further research to clarify its direct impact on choroidal changes.

Clinician-Driven Reanalysis of Exome Sequencing Data From Patients With Inherited Retinal Diseases.

Importance: Despite advances in next-generation sequencing (NGS), a significant proportion of patients with inherited retinal disease (IRD) remain undiagnosed after initial genetic testing. Exome sequencing (ES) reanalysis in the clinical setting has been suggested as one method for improving diagnosis of IRD. Objective: To investigate the association of clinician-led reanalysis of ES data, which incorporates updated clinical information and comprehensive bioinformatic analysis, with the diagnostic yield in a cohort of patients with IRDs in Korea. Design, Setting, and Participants: This was a multicenter prospective cohort study involving 264 unrelated patients with IRDs, conducted in Korea between March 2018 and February 2020. Comprehensive ophthalmologic examinations and ES analyses were performed, and ES data were reanalyzed by an IRD specialist for single nucleotide variants, copy number variants, mobile element insertions, and mitochondrial variants. Data were analyzed from March to July 2023. Main Outcomes and Measures: Diagnostic rate of conventional bioinformatic analysis and clinician-driven ES reanalysis. Results: A total of 264 participants (151 [57.2%] male; mean [SD] age at genetic testing, 33.6 [18.9] years) were enrolled, including 129 patients (48.9%) with retinitis pigmentosa and 26 patients (9.8%) with Stargardt disease or macular dystrophy. Initial bioinformatic analysis diagnosed 166 patients (62.9%). Clinician-driven reanalysis identified the molecular cause of diseases in an additional 22 patients, corresponding to an 8.3-percentage point increase in diagnostic rate. Key factors associated with new molecular diagnoses included clinical phenotype updates (4 patients) and detection of previously overlooked variation, such as structural variants (9 patients), mitochondrial variants (3 patients), filtered or not captured variants (4 patients), and noncanonical splicing variants (2 patients). Among the 22 patients, variants in 7 patients (31.8%) were observed in the initial analysis but not reported to patients, while those in the remaining 15 patients (68.2%) were newly detected by the ES reanalysis. Conclusions and Relevance: In this cohort study, clinician-centered reanalysis of ES data was associated with improved molecular diagnostic yields in patients with IRD. This approach is important for uncovering missed genetic causes of retinal disease.

Long-term Outcomes of Surgeries for Retinal Detachment Secondary to Parasitic or Viral Infectious Retinitis.

PURPOSE: This study sought to compare the long-term outcomes of surgeries for retinal detachment (RD) secondary to viral or parasitic infectious retinitis. METHODS: A total of 47 eyes that received pars plana vitrectomy with or without scleral buckling due to RD secondary to polymerase chain reaction-proven viral (cytomegalovirus, varicella zoster virus, and herpes zoster virus) or parasitic (toxoplasma and toxocara) retinitis from October 1, 2006, to June 30, 2023, in a single medical center were retrospectively enrolled. RESULTS: Mean follow-up period was 59.03 ± 55.24 months in viral retinitis and 34.80 ± 33.78 months in parasitic retinitis after primary reattachment surgery. During follow-up, nine eyes (24.3%) with viral retinitis and five eyes (50.0%) with parasitic retinitis developed retinal redetachment. Visual acuity success at final follow-up was achieved in 19 eyes (51.4%) with viral retinitis and six eyes (60.0%) with parasitic retinitis (p = 0.64). The incidence of retinal redetachment during the 1st postoperative year was significantly higher in parasitic retinitis compared with viral retinitis (crude incidence, 0.21 vs. 0.85; p = 0.02). Hazard ratio analysis adjusted for age and sex showed 4.58-fold (95% confidence interval, 1.22-17.27; p = 0.03) increased risk of retinal redetachment in parasitic retinitis compared with viral retinitis during the 1st postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis. CONCLUSIONS: Compared with RD secondary to viral retinitis, RD secondary to parasitic retinitis showed higher incidence of retinal redetachment during the 1st postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis.

Factors predicting redislocation or suture-break in eyes after scleral-fixated intraocular lens.

PURPOSE: To investigate predictive factors for redislocation in patients with recurrent intraocular lens (IOL) dislocation following secondary scleral-fixated IOL (SFIOL) surgery. SETTING: Two tertiary referral hospitals. DESIGN: Retrospective case series. METHODS: Patients undergoing SFIOL surgery were grouped into redislocation and no-redislocation groups. Medical records of consecutive patients who underwent SFIOL surgery between June 2014 and December 2019 at two tertiary referral centers were reviewed. Data regarding patient demographics, treatment factors, anatomical and functional outcomes, and postoperative complications were recorded. RESULTS: We included 237 eyes of 225 patients (169 [75.1%] men). The redislocation group was more likely to have a younger mean age at the initial SFIOL surgery (redislocation vs no-redislocation, 55.4 vs 62.0 years, respectively; P=0.008), have a prior history of a previous suture-break (23 eyes, 52.3% vs 1 eye, 0.5%; P<0.001), and have undergone the initial SFIOL surgery using <1 mm-sized side-port incisions (17 eyes, 38.6% vs 32 eyes, 16.5%; P=0.002) than was the no-redislocation group. Additionally, the redislocation group had a higher occurrence of complications (P<0.001). Multivariable regression revealed that younger age, left eye involvement, aphakic status prior to the surgery, unremarkable primary IOL dislocation cause, need for ocular hypertension treatment and glaucoma surgery, and no large incision during the initial surgery were significantly (all P<0.05) associated with redislocation. CONCLUSION: Younger age, left eye involvement, postoperative complications like ocular hypertension and glaucoma, and techniques without large incisions increase the risk of redislocation. Conversely, lower risk factors include unremarkable surgery causes and a history of aphakic conditions.

Uveitis Risk After the First Dose of COVID-19 Vaccination Based on Uveitis History: Matched Cohort and Crossover Case Series Study.

PURPOSE: To investigate the risk of noninfectious uveitis following the first dose of coronavirus disease 2019 (COVID-19) vaccination based on the uveitis history. DESIGN: Retrospective matched cohort and crossover case series study. METHODS: A random sample of 7 917 457 individuals who received COVID-19 vaccine between January 2021 and March 2022 in Korea, and had no recorded history of COVID-19 were categorized into the control and uveitis groups based on their uveitis history. After performing 3:1 propensity score matching, we assessed the cumulative incidence and risk of noninfectious uveitis in the 180 days after COVID-19 vaccination. Additionally, we performed a crossover case series analysis to compare the pre- and postvaccination incidence rate ratios (IRRs) of uveitis in individuals with and without a history of uveitis. RESULTS: In the matched cohort analysis, uveitis group had a significantly higher cumulative incidence of uveitis (15.4%) than control group (0.10%). The uveitis group exhibited increased risks of all uveitis types, anterior, and nonanterior uveitis in the first 60 days (hazard ratio [HR]: 169, 158, and 253, respectively) and in days 61 to 180 (HR: 166, 164, and 143, respectively) after vaccination. In the crossover case series analysis, uveitis occurred with relatively equal frequency in 20-day intervals during the 180 days before and after vaccination, regardless of uveitis history. For uveitis group, the adjusted IRRs for early and late postvaccination events were 0.92 (95% CI, 0.88-0.96) and 0.83 (95% CI, 0.80-0.85), respectively. CONCLUSIONS: COVID-19 vaccination did not increase the risk of uveitis, regardless of uveitis history.

Multitask Deep Learning for Joint Detection of Necrotizing Viral and Noninfectious Retinitis From Common Blood and Serology Test Data.

Purpose: Necrotizing viral retinitis is a serious eye infection that requires immediate treatment to prevent permanent vision loss. Uncertain clinical suspicion can result in delayed diagnosis, inappropriate administration of corticosteroids, or repeated intraocular sampling. To quickly and accurately distinguish between viral and noninfectious retinitis, we aimed to develop deep learning (DL) models solely using noninvasive blood test data. Methods: This cross-sectional study trained DL models using common blood and serology test data from 3080 patients (noninfectious uveitis of the posterior segment [NIU-PS] = 2858, acute retinal necrosis [ARN] = 66, cytomegalovirus [CMV], retinitis = 156). Following the development of separate base DL models for ARN and CMV retinitis, multitask learning (MTL) was employed to enable simultaneous discrimination. Advanced MTL models incorporating adversarial training were used to enhance DL feature extraction from the small, imbalanced data. We evaluated model performance, disease-specific important features, and the causal relationship between DL features and detection results. Results: The presented models all achieved excellent detection performances, with the adversarial MTL model achieving the highest receiver operating characteristic curves (0.932 for ARN and 0.982 for CMV retinitis). Significant features for ARN detection included varicella-zoster virus (VZV) immunoglobulin M (IgM), herpes simplex virus immunoglobulin G, and neutrophil count, while for CMV retinitis, they encompassed VZV IgM, CMV IgM, and lymphocyte count. The adversarial MTL model exhibited substantial changes in detection outcomes when the key features were contaminated, indicating stronger causality between DL features and detection results. Conclusions: The adversarial MTL model, using blood test data, may serve as a reliable adjunct for the expedited diagnosis of ARN, CMV retinitis, and NIU-PS simultaneously in real clinical settings.

Real-time in vivo monitoring of intraocular pressure distribution in the anterior chamber and vitreous chamber for diagnosis of glaucoma.

Glaucoma causes irreversible vision loss due to optic nerve damage and retinal cell degeneration. Since high intraocular pressure (IOP) is a major risk factor for glaucoma development, accurate IOP measurement is crucial, especially intravitreal IOP affecting the optical nerve and cells. However, conventional methods have limits in selectively and directly detecting local retina pressure. Here, we present continuous measurements of local IOP values in the anterior chamber and vitreous chamber of living animals using minimally invasive probes with pressure-sensitive transistors. After inducing glaucoma in animal models, we compared the local IOP distribution between normal and glaucomatous eyes. We also compared IOP values detected in the cornea using tonometry measurements. Our findings revealed that glaucoma induced higher IOP in the vitreous chamber than in the anterior chamber, indicating that measuring IOP in the vitreous chamber is key to the glaucoma model. This progress offers future directions for diagnosis and treatment of glaucoma.

Liquid-metal-based three-dimensional microelectrode arrays integrated with implantable ultrathin retinal prosthesis for vision restoration.

Electronic retinal prostheses for stimulating retinal neurons are promising for vision restoration. However, the rigid electrodes of conventional retinal implants can inflict damage on the soft retina tissue. They also have limited selectivity due to their poor proximity to target cells in the degenerative retina. Here we present a soft artificial retina (thickness, 10 µm) where flexible ultrathin photosensitive transistors are integrated with three-dimensional stimulation electrodes of eutectic gallium-indium alloy. Platinum nanoclusters locally coated only on the tip of these three-dimensional liquid-metal electrodes show advantages in reducing the impedance of the stimulation electrodes. These microelectrodes can enhance the proximity to the target retinal ganglion cells and provide effective charge injections (72.84 mC cm-2) to elicit neural responses in the retina. Their low Young's modulus (234 kPa), owing to their liquid form, can minimize damage to the retina. Furthermore, we used an unsupervised machine learning approach to effectively identify the evoked spikes to grade neural activities within the retinal ganglion cells. Results from in vivo experiments on a retinal degeneration mouse model reveal that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.

Noninfectious Uveitis Risk After COVID-19 Vaccination: A Nationwide Retrospective Cohort Study.

PURPOSE: To investigate the incidence and risk of noninfectious uveitis (NIU) following COVID-19 vaccination compared with an unvaccinated, uninfected control group. DESIGN: Retrospective population-based cohort study. METHODS: We included 5,185,153 individuals who received the first vaccine dose in the exposed group and 2,680,164 individuals in the unexposed, uninfected control group. The study observed for 180 days from their index date. Cumulative incidence and risk of NIU following COVID-19 vaccination, and attributable risk factors were assessed. RESULTS: Multivariable analysis showed elevated risk of nonanterior NIU within 60 days (hazard ratio [HR] 1.27 [95% confidence interval {CI} 1.03-1.55] and 61-180 days (HR 1.39 [95% CI 1.20-1.62]). Subgroup analysis highlighted an increased risk in females for early and delayed nonanterior uveitis (HR 1.44 [95% CI 1.08-1.92]; HR 1.78 [95% CI 1.43-2.20], respectively). Regardless of the location and onset timing of uveitis, a history of NIU was identified as the most significant risk factor, with a high hazard ratio ranging from 100 to 200. CONCLUSIONS: COVID-19 vaccination may modestly increase the risk of nonanterior uveitis especially in females. Despite adjustments, bias may persist in the exposed group, owing to significant differences between unexposed and exposed groups and low incidence of nonanterior uveitis in the unexposed group. Future research should aim to refine these findings by assessing uveitis risk in prior NIU patients and by enlarging the sample size or cohort matching.

Retinal Artery and Vein Occlusion Risks after Coronavirus Disease 2019 or Coronavirus Disease 2019 Vaccination.

PURPOSE: To evaluate the incidence of new retinal artery occlusion (RAO) and retinal vein occlusion (RVO) after the diagnosis of coronavirus disease 2019 (COVID-19) or vaccination against COVID-19 and compare the incidences with the population with neither. DESIGN: Nationwide population-based cohort study. PARTICIPANTS: From a nationwide population-based cohort, 8 418 590 patients were categorized into control (group 1), COVID-19 infection (group 2), and COVID-19 vaccination (group 3) groups. METHODS: The cumulative incidence of RAO and RVO was calculated in groups 1, 2, and 3 using the Kaplan-Meier method. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) based on the Poisson distribution for RAO and RVO according to each group and subgroup using Cox proportional hazards models, with group 1 as the reference. We conducted univariable and multivariable analyses for the risk factors of RAO and RVO according to each subgroup. MAIN OUTCOME MEASURES: Cumulative incidence and risks of incidence of RAO and RVO from the index date to day 60. RESULTS: In multivariable analysis, no significant increase in RAO and RVO risks after COVID-19 or COVID-19 vaccination were observed in either men or women. These results were observed consistently across various conditions in sensitivity analyses. In subgroup analysis, individuals who were vaccinated before infection showed no significant increase in RAO or RVO risks in both sexes compared with the control group. In the subgroup analysis of vaccinated patients, the HRs of RAO and RVO for different vaccine types did not show an increase compared with the control group; however, an exception was observed in women who received mRNA-1273 vaccines, who showed a higher RAO HR (4.65; 95% CI, 1.27-17.03; P = 0.021). CONCLUSIONS: Within 60 days of COVID-19 diagnosis or vaccination, RAO and RVO occurred rarely. We observed no increase in the HR of RVO and RAO relative to COVID-19 or COVID-19 vaccination except for a possible increase in the RAO HR in women who received mRNA-1273, for which the raw incidence was extremely low. Further investigation is required to validate this result. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Next-Generation Sequencing of Vitreoretinal Lymphoma by Vitreous Liquid Biopsy: Diagnostic Potential and Genotype/Phenotype Correlation.

Purpose: To determine the diagnostic potential of next-generation sequencing (NGS) in vitreous samples, analyze genotype-phenotype characteristics, and compare NGS of matched vitreous and brain samples in patients with associated central nervous system lymphoma (CNSL). Methods: A total of 32 patients suspected of vitreoretinal lymphoma (VRL) who underwent diagnostic vitrectomy and NGS were included in this retrospective observational case-series. Fresh vitreous specimens from diagnostic vitrectomy of VRL-suspected patients underwent NGS using a custom panel targeting 747 candidate genes for lymphoma. They also underwent malignancy cytology, interleukin (IL)-10/IL-6, immunoglobulin heavy chain (IGH)/immunoglobulin kappa light chain (IGK) monoclonality testing. MYD88 L265P mutation was examined from anterior chamber tap samples. The diagnosis of VRL was made based on typical clinical characteristics for VRL, as well as malignant cytology, IGH/IGK clonality, or IL-10/IL-6 > 1. Sensitivity and specificity of NGS were compared with conventional diagnostic tests. Brain tissues suspected of lymphoma were collected by stereotactic biopsy and underwent NGS. Genetic variations detected in NGS of vitreous and brain tissue specimens were compared. Results: The sensitivity values for cytology, IL-10/IL-6 > 1, clonality assays for IGH and IGK, MYD88 L265P detection in anterior chamber tap samples, and vitreous NGS were 0.23, 0.83, 0.68, 0.79, 0.67, and 0.85, with specificity values of 1.00, 0.83, 0.50, 0.25, 0.83, and 0.83, respectively. The sensitivity (0.85) of vitreous NGS was the highest compared to other conventional diagnostic tests for VRL. The most common mutations were MYD88 (91%), CDKN2A (36%), PIM1 (32%), IGLL5 (27%), and ETV6 (23%). Although several gene alterations demonstrated heterogeneity between the brain and eyes, some common mutational profiles were observed in matched vitreous and brain samples. Conclusions: Overall, NGS of the vitreous demonstrated high sensitivity among conventional diagnostic tests. VRL and CNSL appeared to have both shared and distinct genetic variations, which may suggest site-specific variations from a common origin.

Retinal artery/arteriole occlusion risks after endovascular treatment for unruptured intracranial aneurysm.

BACKGROUND: To evaluate the association between retinal artery/arteriole occlusion (RAO) and unruptured intracranial aneurysm (UIA). METHODS: Incident UIA patients from a nationwide cohort (n=253 240) were categorised into three groups based on subsequent treatment: observation (n=208 993), microsurgical clipping (n=14 168) and endovascular treatment (EVT) groups (n=30 079). The incidence and the incident time of RAO were analysed. HRs of RAO and associated risk factors were evaluated. Additionally, a hospital cohort comprising 2569 consecutive UIA patients treated at a tertiary hospital was analysed with detailed clinical information of UIAs. RESULTS: In the nationwide cohort analysis, the incidence of RAO was significantly higher in EVT group than in observation and clipping groups, especially within 60 days (early RAO (within 60 days): HR=4.00, 95% CI: 2.44 to 6.56); delayed RAO (after 60 days): HR=1.74, 95% CI: 1.13 to 2.68). Multivariable analysis showed that the presence of chronic kidney disease (p=0.009) and use of a balloon microcatheter during the procedure (p=0.013) were associated with a higher risk of RAO. In hospital cohort analysis, 11 (0.8%) cases of RAO occurred after EVT, whereas none occurred after microsurgical clipping (p<0.001). Patients with RAO were younger and received balloon microcatheters more frequently than their counterparts. Ten cases of RAO (90.9%) occurred in paraclinoid aneurysms, where EVT was preferred over microsurgical clipping. CONCLUSIONS: Performing EVT for UIA may increase the risk of subsequent RAO. Care should be taken when treating paraclinoid aneurysms with balloon microcatheters.

Subset of retinoblastoma tumours is associated with BRCA1/2 mutations.

BACKGROUND: We investigated the potential association between pathogenic BRCA1/2 variants and retinoblastoma pathogenicity. METHODS: In this single-centre, retrospective case series, we performed hereditary cancer panel tests using blood samples for patients with retinoblastoma diagnosed between March 2017 and October 2021. Bioinformatics prediction tools were then used to conduct in silico pathogenicity assessments for patients with BRCA1/2 family variants, in addition to the American College of Medical Genetics and Genomics (ACMG) variant classification. One patient with a germline BRCA1 variant was analysed with whole-genome sequencing (WGS), mutational signature analysis and methylation analysis for RB1 and BRCA using the patient's tumour and blood samples. RESULTS: Of 30 retinoblastoma patients who underwent panel sequencing, six (20%) were found to carry germline variants in the BRCA1/2 or BRIP1 genes. Among these six patients, two had pathogenic or likely pathogenic variants as per the ACMG variant classification. Additionally, three patients showed potential pathogenic BRCA1/2 family variants through further analysis with alternative bioinformatics prediction tools. In the WGS analysis of a tumour from a patient with a germline likely pathogenic BRCA1 variant in one allele, we observed the loss of one RB1 allele due to a large deletion. No somatic non-synonymous mutations or frameshift indels were detected in the RB1 locus of the remaining allele. This sample also showed BRCA1 gene promoter hypermethylation in the tumour, indicating additional epigenetic silencing. CONCLUSION: This study demonstrated that some retinoblastoma patients harboured germline BRCA1/2 family variants, which may be associated with the development of retinoblastoma along with RB1 mutations.

Retinal vascular occlusion risks during the COVID-19 pandemic and after SARS-CoV-2 infection.

The coronavirus disease 2019 (COVID-19) has been reported to affect vascular networks including the eye. However, evidence on the causal relationship between COVID-19 infection and retinal vascular occlusions remains limited. This study aimed to determine the change in retinal vascular occlusion incidence during COVID-19 era and whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces retinal vascular occlusion. Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) incidences during 2018-2019 and 2020-July 2021 were compared, those in confirmed and suspected COVID-19 patients diagnosed from 2020 to January 2021 were calculated, and those in COVID-19 patients during 180 days prior and 180 days after diagnosis were assessed. Additionally, the standardized incidence ratio of RVOs in COVID-19 patients was analyzed. Incidence rates per 100,000 people/year of RVO during 2018-2019 and 2020-2021 was 102.0 and 98.8, respectively. RAO incidence rates during 2018-2019 and 2020-2021 were 11.7 and 12.0, respectively. In both confirmed and suspected COVID-19 patients, the incidence of RVO and RAO did not change significantly from 180 days before to after diagnosis in the adjusted model. RVO incidence slightly decreased while RAO incidence increased during the COVID-19 pandemic. SARS-CoV-2 infection did not significantly increase RVO or RAO incidence.

Clinical and genetic features of Koreans with retinitis pigmentosa associated with mutations in rhodopsin.

Purpose: To investigate the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa (RHO-associated RP). Design: We conducted a retrospective, multicenter, observational cohort study. Participants: We reviewed the medical records of 42 patients with RHO-associated RP of 36 families who visited 4 hospitals in Korea. Methods: Patients with molecular confirmation of pathogenic variants of the RHO gene were included. The patients were divided into two subgroups: the generalized and sector RP groups. A central visual field of the better-seeing eye of <10° or a best-corrected visual acuity of the better-seeing eye <20/40 indicated the progression to late-stage RP. Results: The mean age at which symptoms first appeared was 26.3 ± 17.9 years (range: 8-78 years), and the mean follow-up period was 80.9 ± 68.7 months (range: 6-268 months). At the last follow-up visit, the generalized RP group showed a significantly higher rate of visual field impairment progression to late-stage RP than that of the sector RP group (22 of 35 [62.9%] vs. 0 of 7 [0.0%], p = 0.003). No cases in the sector RP group progressed to generalized RP. Best-corrected visual acuity deterioration to late-stage RP was observed only in the generalized RP group (13 of 35 patients; 37.1%), whereas no deterioration was observed in the sector RP group. We identified 16 known and three novel RHO mutations, including two missense mutations (p.T108P and p.G121R) and one deletion mutation (p.P347_A348del). The pathogenic variants were most frequently detected in exon 1 (14 of 36 [38.9%]). The most common pathogenic variants were p.P347L and T17M (5 of 36 [13.9%] families). Among 42 patients of 36 families, 35 patients of 29 families (80.6%) presented with the generalized RP phenotype, and seven patients of seven families (19.4%) presented with the sector RP phenotype. Three variants (p.T17M, p.G101E, and p.E181K) presented with both the generalized and sector RP phenotypes. Conclusion: This multicenter cohort study provided information on the clinical and genetic features of RHO-associated RP in Koreans. It is clinically important to expand the genetic spectrum and understand genotype-phenotype correlations to ultimately facilitate the development of gene therapy.

CLINICAL FEATURES AND PROGNOSTIC VALUE OF BACILLARY LAYER DETACHMENT IN ACUTE VOGT-KOYANAGI-HARADA DISEASE.

PURPOSE: To evaluate the characteristics of bacillary layer detachment (BALAD) in acute Vogt-Koyanagi-Harada (VKH) disease and determine its prognostic value. METHODS: Seventy patients with acute VKH disease with a minimum follow-up of 6 months were studied. The primary outcomes were clinical characteristics associated with BALAD, including features on multimodal imaging at baseline and follow-up. The secondary outcomes included best-corrected visual acuity and VKH with recurrence features. RESULTS: Of 70 eyes (36 patients), 41 (58.6%) showed BALAD. The mean baseline best-corrected visual acuity and mean best-corrected visual acuity after resolution of serous retinal detachment were significantly lower in the BALAD group than in the no-BALAD group (0.90 ± 0.49 vs. 0.35 ± 0.35 log minimum angle of resolution, P < 0.001 and 0.39 ± 0.27 vs. 0.20 ± 0.20 log minimum angle of resolution, P = 0.020). The loss of ellipsoid zone integrity at baseline, proportion of serous retinal detachment, duration of serous retinal detachment, loss of ellipsoid zone integrity at 1 month, and subfoveal choroidal thickness at baseline were significantly higher in the BALAD group ( P = 0.017, P = 0.006, P = 0.023, P = 0.002, and P = 0.046, respectively). The mean best-corrected visual acuity and subfoveal choroidal thickness did not differ between the two groups at 6 months ( P = 0.380 and P = 0.180, respectively). Bacillary layer detachment at baseline was found to be a significant prognostic factor for VKH with recurrence features ( P = 0.007). CONCLUSION: Vogt-Koyanagi-Harada with BALAD featured more severe clinical characteristics than VKH without BALAD during the acute phase. Patients with baseline BALAD require more vigilant monitoring as they are more likely to show recurrence features within the first 6 months.

Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans.

This study aimed to investigate the clinical characteristics of Korean patients with retinal dystrophy associated with pathogenic variants of cone rod homeobox-containing gene (CRX). We retrospectively enrolled Korean patients with CRX-associated retinal dystrophy (CRX-RD) who visited two tertiary referral hospitals. Pathogenic variants were identified using targeted panel sequencing or whole-exome sequencing. We analyzed clinical features and phenotypic spectra according to genotype. Eleven patients with CRX-RD were included in this study. Six patients with cone-rod dystrophy (CORD), two with macular dystrophy (MD), two with Leber congenital amaurosis (LCA), and one with retinitis pigmentosa (RP) were included. One patient (9.1%) had autosomal recessive inheritance, and the other ten patients (90.9%) had autosomal dominant inheritance. Six patients (54.5%) were male, and the mean age of symptom onset was 27.0 ± 17.9 years. At the first presentation, the mean age was 39.4 ± 20.6 years, and best-corrected visual acuity (BCVA) (logMAR) was 0.76 ± 0.90 in the better eye. Negative electroretinography (ERG) was observed in seven (63.6%) patients. Nine pathogenic variants were identified, including two novel variants, c.101-1G>A and c.898T>C:p.(*300Glnext*118). Taken together with the variants reported in prior studies, all variants within the homeodomain are missense variants, whereas most variants downstream of the homeodomain are truncating variants (88%). The clinical features of pathogenic variants within the homeodomain are either CORD or MD with bull's eye maculopathy, whereas variants downstream of the homeodomain cause more diverse phenotypes, with CORD and MD in 36%, LCA in 40%, and RP in 24%. This is the first case series in Korea to investigate the CRX-RD genotype-phenotype correlation. Pathogenic variants downstream of the homeodomain of the CRX gene are present as RP, LCA, and CORD, whereas pathogenic variants within the homeodomain are mainly present as CORD or MD with bull's eye maculopathy. This trend was similar to previous genotype-phenotype analyses of CRX-RD. Further molecular biologic research on this correlation is required.