COVID-19 Vaccine-Associated Uveitis in Patients With a History of Uveitis.

Importance: Understanding the potential risk of uveitis recurrence after COVID-19 vaccination in individuals with a history of uveitis is crucial for vaccination strategies and clinical monitoring. Objective: To investigate the risk of uveitis recurrence after COVID-19 vaccination in a cohort of individuals with a history of uveitis. Design, Setting, and Participants: This retrospective population-based cohort study included individuals diagnosed with uveitis between January 1, 2015, and February 25, 2021, in South Korea. After excluding individuals without COVID-19 vaccination or with SARS-CoV-2 infection, individuals with a history of uveitis who had received at least 1 dose of a messenger RNA (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) or adenovirus vector-based (ChAdOx1 [AstraZeneca] or Ad26.COV2.S [Janssen]) COVID-19 vaccine were included. Data were analyzed from February 26, 2021, to December 31, 2022. Exposure: Demographic and clinical data, along with vaccination details, were retrieved from the Korean National Health Insurance Service and Korea Disease Control and Prevention Agency databases. Main Outcomes and Measures: Outcomes of interest were incidence and risk of postvaccination uveitis in association with different COVID-19 vaccines and periods before and after COVID-19 vaccination. Uveitis was categorized by onset (early, within 30 days, or delayed) and type (anterior or nonanterior). Hazard ratios (HRs) with 95% CIs were calculated to evaluate the risk of uveitis following COVID-19 vaccination, stratified according to vaccine type and vaccination period. Results: Of 543 737 individuals with history of uveitis, 473 934 individuals (mean [SD] age, 58.9 [17.4] years; 243 127 [51.3] female) had documented COVID-19 vaccination and were included in analysis. The cumulative incidence of postvaccination uveitis was 8.6% at 3 months, 12.5% at 6 months, and 16.8% at 1 year, predominantly of the anterior type. Variations in the risk of postvaccination uveitis were observed across different vaccines and intervaccination periods. The risk of early postvaccination uveitis was increased for individuals receiving the BNT162b2 (HR, 1.68; 95% CI, 1.52-1.86), mRNA-1273 (HR, 1.51; 95% CI, 1.21-1.89), ChAdOx1 (HR, 1.60; 95% CI, 1.43-1.79), and Ad26.COV2.S (HR, 2.07; 95% CI, 1.40-3.07) vaccines. The risk of uveitis was higher particularly between the first and second vaccination doses (HR, 1.64; 95% CI, 1.55-1.73). Conclusions and Relevance: These findings suggest that there was an elevated risk of uveitis following COVID-19 vaccination, with the vaccine type and period mediating this risk. For individuals with a history of uveitis, clinicians should consider the potential risk of uveitis recurrence in vaccination strategies and clinical monitoring.

Nationwide Screening Practices for Tamoxifen Retinal Toxicity in South Korea: A Population-Based Cohort Study.

(1) Background/Objectives: To investigate the nationwide screening practices and trends in tamoxifen retinal toxicity (tamoxifen retinopathy) in South Korea using national health insurance claims data. (2) Methods: A total of 43,848 patients who started tamoxifen therapy between 2015 and 2020 and had no prior ophthalmic diseases or other conditions requiring screening for retinopathy were included. The annual numbers of tamoxifen users and new initiators of tamoxifen therapy were assessed. The screening examinations were separated into baseline (first ophthalmic examination after tamoxifen administration) and subsequent monitoring examinations. The timing and modalities for the baseline and subsequent monitoring examinations performed between 2015 and 2021 were assessed in tamoxifen users. (3) Results: The annual number of tamoxifen users increased over the study period from 54,056 in 2015 to 81,720 in 2021. The number of patients who underwent ophthalmic examination after tamoxifen administration was 8961 (20.4%). Baseline screening was performed in 6.5% of patients within 1 year of use, and subsequent monitoring was performed in 27.8% of patients who underwent baseline screening. Funduscopy or fundus photography was performed most commonly for baseline screening and subsequent monitoring (99.0% and 98.6%, respectively), while optical coherence tomography was performed only in 21.9% and 29.6% of baseline and monitoring examinations, respectively. The average number of monitoring examinations per year was 0.68 ± 0.45. Although the annual percentage of patients receiving a baseline examination within 1 year gradually increased over time, the percentage of those with subsequent monitoring performed within 1 year was similar over the study period. (4) Conclusions: Our finding, appropriate screening in a small proportion of patients receiving tamoxifen, suggests the need to promote awareness among healthcare professionals and develop a standardized approach for screening for tamoxifen retinopathy.

Screening Practices and Late Diagnosis of Hydroxychloroquine Retinopathy in Asian Patients.

PURPOSE: To investigate the associations between screening practices and late diagnosis in Asian patients with hydroxychloroquine retinopathy. METHODS: In total, 92 Korean patients with hydroxychloroquine retinopathy were included and separated into late diagnosis and earlier diagnosis groups according to the retinopathy stage at the time of diagnosis. Details of screening practices regarding timing and modalities for baseline and annual monitoring examinations were compared between the two groups. Adherence to the current American Academy of Ophthalmology (AAO) guidelines was compared between the two groups. RESULTS: Timing of baseline and initial monitoring examinations was appropriate as per the AAO guidelines in only 5.3% of patients with late diagnosis. There were significant differences in the proportions of patients receiving initial monitoring at 5 years of use and those receiving annual monitoring between the late and earlier diagnosis groups (P=0.003 and <0.001, respectively). The duration from the start date of hydroxychloroquine therapy to the first monitoring examination was significantly prolonged in the late diagnosis group (P<0.001). Multivariate logistic regression revealed significant association of the time duration to the first monitoring exam (P=0.042) and age (P=0.028) with late diagnosis. CONCLUSION: Our results suggest that poor adherence to the AAO guideline, particularly delayed initial monitoring, may be associated with late diagnosis of hydroxychloroquine retinopathy.

Comparison of Incidence or Recurrence of Anterior Uveitis in Patients with Ankylosing Spondylitis Treated with Tumor Necrosis Factor Inhibitors.

Background: Anterior uveitis (AU) is a significant concern in patients with ankylosing spondylitis (AS), and the choice of tumor necrosis factor inhibitors (TNFi) as a treatment modality raises questions regarding its effects on AU. We compared the effects of TNFi on AU in patients with AS. Methods: Patients diagnosed with AS and treated with at least one TNFi, including anti-TNFα antibodies (adalimumab and infliximab) or a soluble TNF receptor molecule (etanercept), between January 2010 and December 2022, were retrospectively reviewed. We compared the recurrence rate of AU in patients with a history of uveitis and the incidence of new-onset AU in those without a history of uveitis among the three TNFi groups. We also compared the effects of two different TNFi agents in patients who underwent TNFi switching. Results: Within two years of treatment initiation, there was no significant difference in AU recurrence among the three TNFi groups. However, the incidence of new-onset AU was significantly higher in the etanercept group than in the adalimumab group (26.4% vs. 6.3%; p = 0.024). After two years, the AU recurrence rate was significantly lower in the adalimumab group than in the other groups (p < 0.001). Among patients who underwent anti-TNFi switching, adalimumab treatment was associated with a significantly lower incidence of uveitis than etanercept (p = 0.023). Conclusion: In the short-term period following TNFi therapy, etanercept induced new-onset AU more frequently than adalimumab in patients with AS. Adalimumab recipients experienced fewer AU recurrences during the subsequent long-term period compared to other TNFi recipients.

Distinct Clinical Effects of Two RP1L1 Hotspots in East Asian Patients With Occult Macular Dystrophy (Miyake Disease): EAOMD Report 4.

Purpose: To characterize the clinical effects of two RP1L1 hotspots in patients with East Asian occult macular dystrophy (OMD). Methods: Fifty-one patients diagnosed with OMD harboring monoallelic pathogenic RP1L1 variants (Miyake disease) from Japan, South Korea, and China were enrolled. Patients were classified into two genotype groups: group A, p.R45W, and group B, missense variants located between amino acids (aa) 1196 and 1201. The clinical parameters of the two genotypes were compared, and deep learning based on spectral-domain optical coherence tomographic (SD-OCT) images was used to distinguish the morphologic differences. Results: Groups A and B included 29 and 22 patients, respectively. The median age of onset in groups A and B was 14.0 and 40.0 years, respectively. The median logMAR visual acuity of groups A and B was 0.70 and 0.51, respectively, and the survival curve analysis revealed a 15-year difference in vision loss (logMAR 0.22). A statistically significant difference was observed in the visual field classification, but no significant difference was found in the multifocal electroretinographic classification. High accuracy (75.4%) was achieved in classifying genotype groups based on SD-OCT images using machine learning. Conclusions: Distinct clinical severities and morphologic phenotypes supported by artificial intelligence-based classification were derived from the two investigated RP1L1 hotspots: a more severe phenotype (p.R45W) and a milder phenotype (1196-1201 aa). This newly identified genotype-phenotype association will be valuable for medical care and the design of therapeutic trials.

Demographic and clinical characteristics associated with screening practices for hydroxychloroquine retinopathy.

In this nationwide population-based cohort study, we investigated the demographic and clinical characteristics associated with hydroxychloroquine retinopathy screening using the National Health Insurance Review and Assessment database in South Korea. This study included a total of 32,732 at-risk patients, identified based on having been prescribed hydroxychloroquine for at least 6 months, and 15,477 long-term (> 5 years) users between January 2010 and December 2020. Participants were categorized based on the performance of baseline examinations (within 1 year of hydroxychloroquine use) and monitoring examinations (after 5 years of hydroxychloroquine use). Demographic and clinical factors, including hospitals and medical specialties prescribing hydroxychloroquine, indications for hydroxychloroquine use, and prescription details, were compared between groups. Significant differences were found in sex, residence, departments and hospitals (primary vs. referral centers) where hydroxychloroquine was prescribed, diagnosis for hydroxychloroquine therapy, and mean daily dose between patients who did and did not undergo baseline or monitoring examinations (all P < 0.01). Patients who received hydroxychloroquine prescriptions from referral hospitals were more likely to undergo baseline and monitoring examinations compared to those from primary clinics (both P < 0.001). Additionally, patients who received hydroxychloroquine prescriptions from the rheumatology department and had systemic lupus erythematosus were more likely to undergo baseline and monitoring examinations compared to other patients (all P < 0.001). There were notable differences in the number of modalities used for retinopathy screening between primary and referral centers (P < 0.001). Our findings suggest that several clinical factors related to hydroxychloroquine prescription and screening centers are associated with retinopathy screening practices.

Nationwide Usage of Pentosan Polysulfate and Practice Patterns of Pentosan Polysulfate Maculopathy Screening in South Korea.

OBJECTIVE: To investigate the nationwide use of pentosan polysulfate (PPS) and screening practices for PPS maculopathy (PPM), with a focus on the timing and modalities used. DESIGN: Population-based cohort study. PARTICIPANTS: For evaluation of nationwide usage, 133 762 individuals who received PPS prescriptions between 2012 and 2021 were included. To investigate practice patterns, 55 487 individuals (referred to as overall users) who initiated PPS therapy between 2018 and 2020 were identified using the Health Insurance Review and Assessment database. After excluding patients with ophthalmic diseases before PPS administration, 34 857 PPS users without prior ophthalmic diseases were identified. METHODS: Ophthalmic examinations performed after initiating PPS therapy were categorized as baseline and subsequent monitoring examinations. The timing and modalities employed for these examinations were analyzed. The annual trends in PPS utilization and maculopathy screening were evaluated by assessing the number of PPS users and determining the proportion of patients receiving retinal/macular examinations among these users. MAIN OUTCOME MEASURES: Performance of baseline and subsequent monitoring examinations and timing and modalities used for screening. RESULTS: The number of PPS users dramatically increased annually over the study period from 5494 in 2012 to 40 451 in 2021. However, the majority of PPS users did not undergo baseline or subsequent monitoring examinations for PPM. Only 27.2% and 12.4% of PPS users without prior ophthalmic disease underwent baseline and monitoring examinations, respectively. Funduscopy/fundus photography was the most commonly utilized, whereas OCT and fundus autofluorescence (FAF) were performed in only 45.2% and 5.3% of the PPS users without prior ophthalmic diseases for monitoring, respectively. The performance of the screening examinations differed significantly across the 3 different daily dose and duration groups (all P < 0.05). CONCLUSIONS: This study highlights the lack of performance of baseline and monitoring examinations for maculopathy in most patients taking PPS in South Korea. The limited use of OCT and FAF suggests potential insensitivity in detecting PPM. These findings emphasize the need for improvements in screening practices, including increased awareness and referrals to ophthalmologists, utilization of more sensitive modalities, and regular monitoring to enable early detection of PPM. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Occult Macular Dysfunction Syndrome: Identification of Multiple Pathologies in a Clinical Spectrum of Macular Dysfunction with Normal Fundus in East Asian Patients: EAOMD Report No. 5.

Occult macular dystrophy (OMD) is the most prevalent form of macular dystrophy in East Asia. Beyond RP1L1, causative genes and mechanisms remain largely uncharacterised. This study aimed to delineate the clinical and genetic characteristics of OMD syndrome (OMDS). Patients clinically diagnosed with OMDS in Japan, South Korea, and China were enrolled. The inclusion criteria were as follows: (1) macular dysfunction and (2) normal fundus appearance. Comprehensive clinical evaluation and genetic assessment were performed to identify the disease-causing variants. Clinical parameters were compared among the genotype groups. Seventy-two patients with OMDS from fifty families were included. The causative genes were RP1L1 in forty-seven patients from thirty families (30/50, 60.0%), CRX in two patients from one family (1/50, 2.0%), GUCY2D in two patients from two families (2/50, 4.0%), and no genes were identified in twenty-one patients from seventeen families (17/50, 34.0%). Different severities were observed in terms of disease onset and the prognosis of visual acuity reduction. This multicentre large cohort study furthers our understanding of the phenotypic and genotypic spectra of patients with macular dystrophy and normal fundus. Evidently, OMDS encompasses multiple Mendelian retinal disorders, each representing unique pathologies that dictate their respective severity and prognostic patterns.

Causes and trends of late diagnosis in Korean patients with hydroxychloroquine retinopathy.

Introduction: Late diagnosis of hydroxychloroquine retinopathy remains a major concern, with the potential for irreversible visual impairment. This study aimed to investigate the causes of late diagnosis in a hospital-based cohort of Korean patients with hydroxychloroquine retinopathy and assess the trend of late diagnosis from 2015 to 2022. Methods: Thirty-eight patients with a late diagnosis (severe stage at diagnosis) among 94 patients with hydroxychloroquine retinopathy were included in the analysis. The causes of late diagnosis were categorized as referral-related, patient-related, and screening-related factors. Results: The most prevalent cause was no or late referral to ophthalmologists, contributing to a significant gap in timely identification. Patient-related causes included delayed monitoring visits despite scheduled appointments and early-onset disease. Screening-related causes encompassed an insufficient number of sensitive tests, leading to inadequate evidence for diagnosis, and missed or wrong diagnoses by screening physicians. The proportion of late diagnoses decreased over time, indicating improvements in overall screening and detection. The decreasing proportions of screening-related causes suggest advancements in screening practices and the use of multiple sensitive tests for screening. Discussion: Efforts to further reduce late diagnoses and improve screening and diagnostic processes are necessary. Our data emphasize the importance of timely referral to ophthalmologists for early detection and management.

Unmet needs and future perspectives in hydroxychloroquine retinopathy.

Retinopathy is a well-recognized toxic effect of hydroxychloroquine treatment. As hydroxychloroquine retinopathy is potentially a vision-threatening condition, early detection is imperative to minimize vision loss due to drug toxicity. However, early detection of hydroxychloroquine retinopathy is still challenging even with modern retinal imaging techniques. No treatment has been established for this condition, except for drug cessation to minimize further damage. In this perspective article, we aimed to summarize the knowledge gaps and unmet needs in current clinical practice and research in hydroxychloroquine retinopathy. The information presented in this article may help guide the future directions of screening practices and research in hydroxychloroquine retinopathy.

Hydroxychloroquine-induced Retinal Toxicity.

Long-term use of hydroxychloroquine can cause retinopathy, which may result in severe and progressive visual loss. In the past decade, hydroxychloroquine use has markedly increased and modern retinal imaging techniques have enabled the detection of early, pre-symptomatic disease. As a consequence, the prevalence of retinal toxicity in long-term hydroxychloroquine users is known to be higher than was previously estimated. The pathophysiology of the retinopathy is incompletely characterised, although significant advances have been made in understanding the disease from clinical imaging studies. Hydroxychloroquine retinopathy elicits sufficient public health concern to justify the implementation of retinopathy screening programs for patients at risk. Here, we describe the historical background of hydroxychloroquine retinopathy and summarize its current understanding. We review the utility and limitations of each of the mainstream diagnostic tests used to detect hydroxychloroquine retinopathy. The key considerations towards a consensus on the definition of hydroxychloroquine retinopathy are outlined in the context of what is known of the natural history of the disease. We compare the current screening recommendations for hydroxychloroquine retinopathy, identifying where additional evidence is required, and the management of proven cases of toxicity. Finally, we highlight the areas for further investigation, which may further reduce the risk of visual loss in hydroxychloroquine users.

Practice Patterns of Screening for Hydroxychloroquine Retinopathy in South Korea.

Importance: Practice patterns of hydroxychloroquine retinopathy screening have not yet been reported at a national level in South Korea. Objective: To investigate the practice patterns of timing and modality for hydroxychloroquine retinopathy screening in South Korea. Design, Setting, and Participants: This nationwide population-based cohort study of patients in South Korea used data from the national Health Insurance Review and Assessment database. Patients at risk were identified as those who had initiated hydroxychloroquine therapy between January 1, 2009, and December 31, 2020, and used it for 6 months or more. Patients were excluded if they underwent any of the 4 screening modalities recommended by the American Academy of Ophthalmology (AAO) for other ophthalmic diseases prior to hydroxychloroquine use. The timing and modalities of screening used in baseline and monitoring examinations were assessed between January 1, 2015, and December 31, 2021, among patients at risk and long-term (≥5 years) users. Exposure: Adherence of baseline screening practices to the 2016 AAO recommendations (fundus examination within 1 year of drug use) was evaluated; adherence of monitoring examinations in year 5 was classified as appropriate (≥2 tests recommended by the AAO), unscreened (no test performed), and underscreened (insufficient number of tests). Main Outcomes and Measures: Timing of screening and modalities used at baseline and monitoring examinations. Results: A total of 65 406 patients at risk (mean [SD] age, 53.0 [15.5] years; 50 622 women [77.4%]) were included; 29 776 patients were long-term users (mean [SD] age, 50.1 [14.7] years; 24 898 women [83.6%]). Baseline screening was performed for 20.8% of the patients within 1 year, with a gradual increase from 16.6% in 2015 to 25.6% in 2021. Monitoring examinations, mostly using optical coherence tomography and/or visual field tests, were performed for only 13.5% of the long-term users in year 5 and for 31.6% of the long-term users after 5 years. Appropriate monitoring was performed for less than 10% of long-term users each year from 2015 to 2021; however, the percentage gradually increased over time. The percentage of patients undergoing any monitoring examination in year 5 was 2.3 times greater for those who had received baseline screening than for those who did not (27.4% vs 11.9%; P < .001). Conclusions and Relevance: This study suggests there is an improving trend in retinopathy screening among hydroxychloroquine users in South Korea; however, most long-term users remained unscreened after 5 years of use. Baseline screening may be useful in reducing the number of unscreened long-term users.

Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer Thicknesses in Hydroxychloroquine Retinopathy.

OBJECTIVE: To investigate macular ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (RNFL) thicknesses in patients with hydroxychloroquine retinopathy of differing severity. DESIGN: Cross-sectional, case-control comparison study. PARTICIPANTS: From patients screened for hydroxychloroquine retinopathy between January 2016 and October 2021 using swept-source optical coherence tomography (SS-OCT), fundus autofluorescence (FAF), and standard automated perimetry, 66 patients with retinopathy and 66 without retinopathy were included by 1:1 propensity score matching based on age, sex, systemic diseases, history of tamoxifen and pentosan use, and kidney disease. METHODS: Eyes with hydroxychloroquine retinopathy were divided into early, moderate, and severe stages. Inner-retinal thickness parameters, including macular GCC (RNFL + ganglion cell layer + inner plexiform layer) and peripapillary RNFL thicknesses, were automatically obtained using SS-OCT (DRI-OCT Triton, Topcon Inc., Japan) and compared between patients with and without retinopathy and between severity subgroups. The structure-function relationships between GCC or peripapillary RNFL thicknesses and perimetric parameters including mean deviation (MD) and visual field index (VFI) of Humphrey 30-2 test were evaluated. MAIN OUTCOME MEASURES: Macular GCC and peripapillary RNFL thickness parameters. RESULTS: The average macular GCC and peripapillary RNFL thicknesses were significantly decreased in patients with hydroxychloroquine retinopathy relative to those without retinopathy. Macular GCC thicknesses in 4 of 6 macular sectors and peripapillary RNFL thicknesses in 9 of 12 clock-hour sectors were significantly different between the groups. The differences in the average and sectoral macular GCC parameters were statistically significant among the severity subgroups, particularly between severe and earlier stages. Average macular GCC and peripapillary RNFL thicknesses significantly correlated with MD and VFI in all patients (all P < .001). CONCLUSIONS: Macular GCC and peripapillary RNFL thinning was more prominent in eyes with severe hydroxychloroquine retinopathy, as indicative of inner-retinal thinning in eyes with advanced-stage disease. Further, as inner-retinal thinning showed a significant correlation with worse perimetric function, cautious evaluation of the inner retina may be required for eyes with advanced hydroxychloroquine retinopathy.

Novel imaging techniques for hydroxychloroquine retinopathy.

Hydroxychloroquine retinopathy is an increasingly recognized cause of iatrogenic, irreversible visual impairment due to the expanding use of hydroxychloroquine in combination with improvements in disease detection following advances in retinal imaging techniques. The prevalence of disease is estimated to be greater than 5% amongst individuals who have used the drug for 5 years or more. In addition to conventional imaging modalities, such as spectral-domain optical coherence tomography (OCT) and fundus autofluorescence (FAF), novel retinal imaging techniques such as en face OCT, OCT angiography, fluorescence lifetime imaging ophthalmoscopy, quantitative autofluorescence, and retromode imaging are capable of detecting structural changes in the retina. These novel retinal imaging techniques have shown promise in detecting earlier disease than is possible with current mainstream imaging modalities. Moreover, these techniques may identify disease progression as well as enabling functional correlation. In the future, these novel imaging techniques may further reduce the risk of visual loss from hydroxychloroquine retinopathy through the earlier detection of pre-clinical disease.

Visual field examinations using different strategies in Asian patients taking hydroxychloroquine.

In this study, we investigated the patterns of visual field (VF) defects and the diagnostic abilities of VF tests using different strategies in Asian patients with hydroxychloroquine retinopathy. Patients screened for hydroxychloroquine retinopathy using optical coherence tomography, fundus autofluorescence, VF, and/or multifocal electroretinography were included. The VF was performed using the Humphrey 30-2 and/or 10-2 strategy, and 2,107 eyes of 1,078 patients with reliable results, including 136 eyes of 68 patients with hydroxychloroquine retinopathy, were analyzed. The characteristics of VF findings were evaluated and the sensitivity and specificity were compared between the 30-2 and 10-2 tests in subgroups of retinopathy severity and pattern. The most common VF defect pattern was partial- or full-ring scotoma in both the 10-2 and 30-2 tests. Among the eyes with hydroxychloroquine retinopathy that underwent both tests, 14.2% showed a disparity between the two tests, almost all at the early stage. In overall and early pericentral retinopathy, the sensitivity of the 30-2 test was significantly higher than that of the 10-2 test (95.7% vs. 77.1% and 90.6% vs. 53.1%, respectively; P < 0.05). However, the specificity of the 10-2 test was significantly higher than that of the 30-2 test (89.6% vs. 84.8%, P < 0.001). Therefore, the pattern of retinopathy should be carefully considered when choosing a VF strategy for better detection of hydroxychloroquine retinopathy.

Clock-hour topography and extent of outer retinal damage in hydroxychloroquine retinopathy.

In this study, we investigated the clock-hour topographic characteristics and extent of photoreceptor and retinal pigment epithelium (RPE) damage and correlated the extent with functional defects in eyes with hydroxychloroquine retinopathy. A total of 146 eyes of 75 patients diagnosed with hydroxychloroquine retinopathy were included. The clock-hour topographic characteristics (relative to the fovea) and extent of the photoreceptor and RPE defects in the parafoveal and pericentral areas were evaluated by reviewing the radial-scan optical coherence tomography (OCT) and wide-field fundus autofluorescence (FAF) images. The extent of outer retinal damage in the parafoveal and pericentral areas were correlated with the perimetric parameters of the Humphrey 10-2 and 30-2 tests, respectively. Although the photoreceptor damage was most commonly noted at the temporal to inferior locations in both parafoveal and pericentral areas, the RPE damage in the pericentral eyes was most commonly noted in the nasal area and showed topographic discrepancies with photoreceptor damage. The extent of RPE damage was almost identical between OCT and FAF images, whereas photoreceptor defect extent was significantly greater on OCT images. The extent of parafoveal and pericentral photoreceptor damage on OCT images was significantly correlated with perimetric parameters of the 10-2 and 30-2 tests, respectively (all P < 0.05). Our findings on the detailed topographic characteristics using a clock-hour-based system and significant correlation between the structural extent and perimetric parameters suggest that this evaluation may facilitate more comprehensive descriptions of structural damage extent and predictions of visual function.

Neurodevelopmental outcomes in very low birthweight infants with retinopathy of prematurity in a nationwide cohort study.

In a nationwide prospective cohort of Korean infants with very low birthweights (VLBW, birth weight < 1500 g) from 70 neonatal intensive care units of the Korean Neonatal Network, we investigated neurodevelopmental outcomes in preterm infants with retinopathy of prematurity (ROP) from 2132 infants with VLBW who had undergone developmental assessments at 18-24 months of corrected age. Motor, cognitive, or language delay was determined using developmental scores that were less than 1 standard deviation from the average. Comparative analyses and multivariate regression analyses were performed to validate the association between ROP or its treatment and developmental delay. Motor (52.8% vs. 36.3%), cognitive (46.8% vs. 31.6%), and language delays (42.5% vs. 28.4%) were noted more frequently in infants with ROP than in those without ROP; this was statistically significant (all P < 0.001). Multivariate analyses showed that motor and cognitive delays were significantly associated with ROP. There were no remarkable differences between the neurodevelopmental outcomes and the treatment modalities (laser photocoagulation, anti-vascular endothelial growth factor injection, or both) for ROP, and both stratification and multivariate regression analyses confirmed no significant association between anti-vascular endothelial growth factor therapy and neurodevelopmental delay. As ROP is significantly associated with poor neurodevelopmental outcomes independent of extreme prematurity, neurodevelopmental functions should be given attention in infants with ROP.

Ophthalmic complications in retinopathy of prematurity in the first decade of life in Korea using the national health insurance database.

The aim of this study is to investigate the epidemiology of ophthalmic complications of retinopathy of prematurity (ROP) after preterm birth using population-based database in South Korea. Using the National Health Insurance database, ophthalmic complications among premature infants born in 2007-2008 during their 10-year follow-up period were identified. Annual cumulative incidence rate and period prevalence of complications at each age were analyzed among those with ROP and those who underwent treatment for ROP (tROP). The hazard ratios (HRs) according to the presence of ROP and treatment for ROP were also analyzed. We identified 18,256 premature infants, 6995 of whom had ROP. The prevalence at 10th year for overall ophthalmic complications was 11.1% and 35.9% among ROP and tROP, respectively. Strabismus, amblyopia, and glaucoma were the three most common complications. The presence of ROP was associated with higher risk of complications (HR 1.53, 95%CI 1.44-1.61) among premature infants, and the presence of treatment for ROP was associated with higher risk of complications (HR 4.31, 95%CI 3.74-4.98) among ROP cases. This study reports the nationwide epidemiologic data on ophthalmic complications of ROP during the first decade of life, which will help advance our understandings and establish national strategies in managing ROP.

Visual Field Characteristics in East Asian Patients With Occult Macular Dystrophy (Miyake Disease): EAOMD Report No. 3.

Purpose: The purpose of this study was to investigate the perimetric features and their associations with structural and functional features in patients with RP1L1-associated occult macular dystrophy (OMD; i.e. Miyake disease). Methods: In this international, multicenter, retrospective cohort study, 76 eyes of 38 patients from an East Asian cohort of patients with RP1L1-associated OMD were recruited. Visual field tests were performed using standard automated perimetry, and the patients were classified into three perimetric groups based on the visual field findings: central scotoma, other scotoma (e.g. paracentral scotoma), and no scotoma. The association of the structural and functional findings with the perimetric findings was evaluated. Results: Fifty-four eyes (71.1%) showed central scotoma, 14 (18.4%) had other scotomata, and 8 (10.5%) had no scotoma. Central scotoma was mostly noted in both eyes (96.3%) and within the central 10 degrees (90.7%). Among the three perimetric groups, there were significant differences in visual symptoms, best-corrected visual acuity (BCVA), and structural phenotypes (i.e. severity of photoreceptor changes). The central scotoma group showed worse BCVA often with severe structural abnormalities (96.3%) and a pathogenic variant of p.R45W (72.2%). The multifocal electroretinogram (mfERG) groups largely corresponded with the perimetric groups; however, 8 (10.5%) of 76 eyes showed mfERG abnormalities preceding typical central scotoma. Conclusions: The patterns of scotoma with different clinical severity were first identified in occult macular dystrophy, and central scotoma, a severe pattern, was most frequently observed. These perimetric patterns were associated with the severity of BCVA, structural phenotypes, genotype, and objective functional characteristics which may precede in some cases.