Genome-wide association study of subfoveal choroidal thickness in a longitudinal cohort of older adults.

To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values < 1.0 × 10-4 in both the right and left eyes, followed by validation using the Bundang AMD cohort dataset. This association was further confirmed by a functional in vitro study using human umbilical vein endothelial cells (HUVECs). The ages of the cohort participants in the discovery and validation datasets were 73.5 ± 3.3 and 71.3 ± 7.9 years, respectively. In the discovery dataset, three SNPs (rs1916762, rs7587019, and rs13320098) were significantly associated with choroidal thickness in both eyes. This association was confirmed for rs1916762 (genotypes GG, GA, and AA) and rs7587019 (genotypes GG, GA, and AA), but not for rs13320098. The mean choroidal thickness decreased by 56.7 µm (AA, 73.8%) and 31.1 µm (GA, 85.6%) compared with that of the GG genotype of rs1916762, and by 55.4 µm (AA, 74.2%) and 28.2 µm (GA, 86.7%) compared with that of the GG genotype of rs7587019. The SNPs rs1916762 and rs7587019 were located close to the FAM124B gene near its cis-regulatory region. Moreover, FAM124B was highly expressed in vascular endothelial cells. In vitro HUVEC experiments showed that the inhibition of FAM124B was associated with decreased vascular endothelial proliferation, suggesting a potential mechanism of choroidal thinning. FAM124B was identified as a susceptibility gene affecting subfoveal choroidal thickness in older adults. This gene may be involved in mechanisms underlying retinal diseases associated with altered choroidal thickness, such as age-related macular degeneration.

Moyamoya Disease increased the risk of Retinal Vascular Occlusion: A Nationwide Cohort Study in Korea.

PURPOSE: To investigate the risk of retinal vascular occlusion in patients with Moyamoya disease (MMD). DESIGN: Retrospective, longitudinal cohort study using the Korean National Health Insurance Service database. PARTICIPANTS: Newly diagnosed MMD patients (n=34,627), who were diagnosed between 2004 and 2022, and their propensity score matched controls (n=136,945) were included. METHODS: We identified retinal vascular occlusion events using diagnostic codes for central retinal artery occlusion, other retinal artery occlusion, and retinal vein occlusion. After a washout-period from 2002 to 2003, information on the diagnosis of retinal vascular occlusion was extracted in both MMD and control group during the follow up period. The association between MMD and the risk of subsequent retinal vascular occlusion was investigated using a time-dependent Cox proportional hazard model and Kaplan-Meier survival analysis with log-rank test adjusted for age, sex, and comorbidities. MAIN OUTCOME MEASURES: Hazard ratios (HRs) and 95% confidence intervals (CIs) for retinal vascular occlusion development according to the MMD. RESULTS: MMD was associated with an increased risk of subsequent retinal vascular occlusion even after adjusting for confounding variables (HR, 1.22; 95% CI, 1.09-1.36). Among the subtypes of retinal vascular occlusion, central retinal artery occlusion showed a highest HR (2.23; 95% CI, 1.35-3.7). Incidence probability of retinal vascular occlusion was significantly higher among MMD patients than controls (P < 0.001, log-rank test). CONCLUSION: In this nationwide population-based cohort study, patients with MMD in Korea had an elevated risk of retinal vascular occlusion, suggesting that the MMD is one of the risk factors for retinal vascular occlusion.

Practice Patterns and Challenges in Managing Inherited Retinal Diseases Across Asia-Pacific: A Survey from the APIED Network.

PURPOSE: The objective of this paper is to shed light on the current landscape of genotyping practices, phenotyping practices and availability of essential vision rehabilitation management for inherited retinal diseases (IRD) in the Asia-Pacific (APAC) Region. METHODS: The 62-item questionnaire was distributed electronically via email. The questions covered five domains: (1) structure of the IRD service and registry/database; (2) genotyping practices; (3) genetic counselling; (4) deep phenotyping practices; (5) low-vision rehabilitation services. RESULTS: The survey was completed by 36 of 45 centres in twelve countries and regions in APAC. Among these centres, 42 % reported managing more than 1000 patients. Notably, 39 % of centres lack an IRD database or registry, and 44 % of centres have tested less than one-quarter of their IRD patients. The majority of centres (67 %) do not have genetic counsellors. While there was consistency in the imaging-based investigations, there was marked heterogeneity for functional testing using electrophysiology and formal perimetry. Only 34 % of centres confirmed the availability of access to low-vision assistive devices. CONCLUSIONS: This study reveals several critical gaps in managing IRDs in the APAC region. These include the lack of IRD database/registry in one-third of centres, a substantial proportion of patients remaining genetically undiagnosed, and limited availability of genetic counsellors. The findings also underscore a need to harmonise investigations for evaluating retinal function and identify areas for improvement in the provision of low-vision rehabilitation services.

Patient-Centered Economic Burden of Diabetic Macular Edema: Retrospective Cohort Study.

BACKGROUND: Diabetic macular edema (DME), a leading cause of blindness, requires treatment with costly drugs, such as anti-vascular endothelial growth factor (VEGF) agents. The prolonged use of these effective but expensive drugs results in an incremental economic burden for patients with DME compared with those with diabetes mellitus (DM) without DME. However, there are no studies on the long-term patient-centered economic burden of DME after reimbursement for anti-VEGFs. OBJECTIVE: This retrospective cohort study aims to estimate the 3-year patient-centered economic burden of DME compared with DM without DME, using the Common Data Model. METHODS: We used medical data from 1,903,603 patients (2003-2020), transformed and validated using the Observational Medical Outcomes Partnership Common Data Model from Seoul National University Bundang Hospital. We defined the group with DME as patients aged >18 years with nonproliferative diabetic retinopathy and intravitreal anti-VEGF or steroid prescriptions. As control, we defined the group with DM without DME as patients aged >18 years with DM or diabetic retinopathy without intravitreal anti-VEGF or steroid prescriptions. Propensity score matching, performed using a regularized logistic regression with a Laplace prior, addressed selection bias. We estimated direct medical costs over 3 years categorized into total costs, reimbursement costs, nonreimbursement costs, out-of-pocket costs, and costs covered by insurance, as well as healthcare resource utilization. An exponential conditional model and a count model estimated unbiased incremental patient-centered economic burden using generalized linear models and a zero-inflation model. RESULTS: In a cohort of 454 patients with DME matched with 1640 patients with DM, the economic burden of DME was significantly higher than that of DM, with total costs over 3 years being 2.09 (95% CI 1.78-2.47) times higher. Reimbursement costs were 1.89 (95% CI 1.57-2.28) times higher in the group with DME than with the group with DM, while nonreimbursement costs were 2.54 (95% CI 2.12-3.06) times higher. Out-of-pocket costs and costs covered by insurance were also higher by a factor of 2.11 (95% CI 1.58-2.59) and a factor of 2.01 (95% CI 1.85-2.42), respectively. Patients with DME had a significantly higher number of outpatient (1.87-fold) and inpatient (1.99-fold) visits compared with those with DM (P<.001 in all cases). CONCLUSIONS: Patients with DME experience a heightened economic burden compared with diabetic patients without DME. The substantial and enduring economic impact observed in real-world settings underscores the need to alleviate patients' burden through preventive measures, effective management, appropriate reimbursement policies, and the development of innovative treatments. Strategies to mitigate the economic impact of DME should include proactive approaches such as expanding anti-VEGF reimbursement criteria, approving and reimbursing cost-effective drugs such as bevacizumab, advocating for proactive eye examinations, and embracing early diagnosis by ophthalmologists facilitated by cutting-edge methodologies such as artificial intelligence for patients with DM.

Predictors of Disease Activity After Anti-VEGF Treatment for Neovascular Age-Related Macular Degeneration Using Real-World Data from the PROOF Study.

INTRODUCTION: The aim of this study was to investigate the predictive factors for persistent disease activity following anti-vascular endothelial growth factors (anti-VEGF) and their long-term effects in patients to be treated for neovascular age-related macular degeneration (nAMD) under real-world conditions. METHODS: Retrospective data analysis of the PROOF study, a multi-center real-world retrospective chart review conducted across Korea in patients with nAMD included treatment-naive patients with nAMD who received first anti-VEGF (ranibizumab, bevacizumab, or aflibercept) between January 2017 and March 2019 was performed. All 600 patients (cohort 1) had a minimum follow-up of 12 months of which 453 patients (cohort 2) were followed-up for 24 months from baseline. RESULTS: At month 12 after anti-VEGF therapy, 58.10% (95% confidence interval [CI]: 54.09, 62.12) of patients and at month 24, 66.02% of patients continued to have persistent retinal fluid. At both months 12 and 24, predictive factors for persistent disease activity were fibrovascular pigment epithelial detachments (PED) (P = 0.0494) and retinal fluid at month 3 after loading phase (P = 0.0082). The mean changes in visual acuity were + 6.2, + 10.1, and + 13.3 letters and in the central subfield thickness were - 79.1 µm, - 96.3 µm, and - 134.4 µm at 12 months from baseline, in the bevacizumab, aflibercept, and ranibizumab groups, respectively. CONCLUSIONS: The presence of retinal fluid after loading phase and fibrovascular PED were predictors of persistent disease activity after at least 1 year of anti-VEGF treatment.

Pharmacokinetics-based safety evaluation in half-dose verteporfin photodynamic therapy.

INTRODUCTION: This study was conducted to assess the systemic pharmacokinetic profiles of half-dose verteporfin photodynamic therapy (PDT) using concentration data from a previous clinical trial, and to subsequently suggest the safety precaution guidelines. METHODS: Coefficients for the bi-exponential model were obtained from published data on post-infusion plasma verteporfin concentrations within a period of 0.17-4 h. Using the extrapolative forecasting method, we plotted the 48 h post-verteporfin plasma concentration model. The time required to achieve a comparable level of verteporfin 48 h after a conventional -dose (6 mg/m2 body surface area, BSA) infusion was calculated for a half-dose infusion (3 mg/m2 BSA). RESULTS: At 24 and 48 hours post-verteporfin infusion, the plasma concentration following the conventional dose was 1.28 × 10⁻4 µg/mL and 5.06 × 10⁻8 µg/mL, compared to 3.57 × 10⁻5 µg/mL and 7.54 × 10⁻9 µg/mL for the half-dose PDT, representing concentrations that were 3.6 times and 6.7 times higher, respectively. The estimated time required to attain the same level of verteporfin 48 h after a conventional -dose was calculated as 42 h post- half-dose PDT. CONCLUSIONS: The study results of this study indicate that it is advisable to take necessary precautionary measures should be taken to avoid sunlight following both half and conventional doses of PDT. Nevertheless, given the substantially higher plasma concentration levels associated with conventional-dose PDT as compared withto the half-dose, systemic safety should be given duecarefully consideredation whenwhile administering conventional-dose PDT.

Intraocular Concentration of Stem Cell Factor/c-KIT and Galectin-1 in Retinal Diseases.

Purpose: To investigate the intraocular concentration profiles of stem cell factor (SCF)/c-KIT, galectin-1 (GAL-1), and vascular endothelial growth factor (VEGF)-A with regard to retinal disease and treatment response. Methods: The study group included 13 patients with dry age-related macular degeneration (AMD), 196 with neovascular AMD (nAMD), 21 with diabetic macular edema (DME), 10 with retinal vein occlusion (RVO), and 34 normal subjects with cataracts. Aqueous humor levels of SCF, c-KIT, GAL-1, and VEGF-A were analyzed by immunoassay according to disease group and treatment response. Results: Increased aqueous levels of SCF, c-KIT, and GAL-1 were observed in eyes with nAMD (2.67 ± 3.66, 296.84 ± 359.56, and 3945.61 ± 5976.2 pg/mL, respectively), DME (1.64 ± 0.89, 238.80 ± 265.54, and 3701.23 ± 4340.54 pg/mL, respectively), and RVO (4.62 ± 8.76, 509.63 ± 647.58, and 9079.60 ± 11909.20 pg/mL, respectively) compared with controls (1.13 ± 0.24, 60.00 ± 0.00, and 613.27 ± 1595.12 pg/mL, respectively). In the eyes of nAMD, the levels of all three cytokines correlated positively with VEGF-A levels. After intravitreal injections of anti-VEGF agents, the levels of GAL-1 and VEGF-A decreased significantly, whereas those of SCF and c-Kit showed no significant change. Eyes of nAMD patients with improved vision after treatment had significantly lower levels of c-KIT, GAL-1, and VEGF-A at baseline. Conclusions: The intraocular levels of cytokines were significantly elevated in eyes with nAMD, DME, and RVO compared to the controls and they showed different response to anti-VEGF treatment. With this result and their known association with angiogenesis, these cytokines may be potential therapeutic targets for future research.

Ultra-Widefield Fluorescein Angiographic Features Influencing Visual Prognosis in Coats Disease.

PURPOSE: To investigate the retinal vascular abnormalities in both affected and fellow eyes of presumed unilateral Coats disease patients using ultra-widefield fluorescein angiography (UWF-FA) and their association with visual prognosis. METHODS: A retrospective review of medical records was conducted on 30 patients diagnosed with presumed unilateral Coats disease, who were evaluated with UWF-FA from March 2003 to May 2024 at a tertiary referral hospital. Clinical features and multimodal imaging findings were evaluated, and factors related to final visual outcomes were analyzed. RESULTS: All 30 patients were diagnosed with presumed unilateral Coats disease at presentation, comprising 11 childhood-onset (36.7%) and 19 adult-onset patients (63.3%). Retinal vascular telangiectasia was observed in 51.7% of the fellow eyes. The extent of telangiectasia and exudate in the affected eyes did not significantly correlate with the extent of telangiectasia in the fellow eyes. In the more affected eyes, the childhood-onset group had a significantly greater extent of capillary dropout compared to the adult-onset group (5.0 clock hours vs. 2.8 clock hours, p = 0.023). In the fellow eyes, telangiectasia tended to be more frequent in the childhood-onset group, without statistical significance (63.6% vs. 44.4%, p = 0.160). In the multivariable regression analysis, the final best-corrected visual acuity (BCVA) in the more affected eyes was significantly associated with initial BCVA. The mean extent of telangiectasia in the temporal and nasal quadrants (odds ratio, 12.759; p = 0.043) and the initial BCVA of the more affected eyes (odds ratio, 11.841; p = 0.024) were identified as prognostic factors for final moderate to severe visual loss (Snellen BCVA <20 / 66). CONCLUSIONS: About half of the presumed unilateral Coats disease cases exhibited features of the bilateral disease. Visual prognosis is associated with the peripheral retinal telangiectasia in the temporal and nasal quadrants as well as initial BCVA in the affected eyes while it is not associated with retinal vascular abnormalities in the fellow eyes.

Early Developmental Characteristics and Features of a Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis.

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.

Late-Onset Slowly Progressing Cone/Macular Dystrophy in Patients With the Biallelic Hypomorphic Variant p.Arg1933Ter in RP1.

Purpose: Homozygous hypomorphic variants of the RP1 gene, including c.5797C>T, p.Arg1933Ter, have traditionally been considered non-pathogenic. This study aimed to elucidate the clinical manifestations of late-onset, slowly progressive cone/macular dystrophy in patients homozygous for p.Arg1933Ter in the RP1 gene. Methods: Five patients with biallelic p.Arg1933Ter in RP1 were retrospectively recruited, and their clinical profiles were analyzed. Copy number variation analysis and Alu insertion assessment of genes associated with inherited retinal diseases were conducted. The results of comprehensive ophthalmological examinations, multimodal imaging, and full-field electroretinogram tests were analyzed. Results: No specific sequencing errors or structural variations associated with the clinical phenotypes were identified. Alu element insertion in RP1 was not detected. The mean ± SD age at the first visit was 62.2 ± 9.8 years, with symptoms typically starting between 45 and 50 years of age. Two patients exhibited a mild form of cone/macular dystrophy, characterized by a relatively preserved fundus appearance and blurring of the ellipsoid zone on optical coherence tomography. Three patients had late-onset cone/macular dystrophy with significant atrophy. Conclusions: To our knowledge, this study is the first to report that a homozygous hypomorphic variant of RP1, previously considered non-pathogenic, leads to cone/macular dystrophy. Translational Relevance: The study introduces novel possibilities suggesting that the homozygous hypomorphic variant of RP1 may be linked to variant pathogenicity.

Association between Pentosan Polysulfate and Subsequent Maculopathy: Insights from a Nationwide Population-Based Study in Korea.

PURPOSE: To determine the association between pentosan polysulfate (PPS) use and the subsequent development of maculopathy in an Asian population. DESIGN: A nationwide, population-based retrospective cohort study using the Health Insurance Review and Assessment Service database. PARTICIPANTS: A total of 103 553 individuals in the PPS user group and 205 792 individuals in the PPS nonuser group, all newly diagnosed with cystitis between 2009 and 2020. METHODS: The association between PPS use and maculopathy was evaluated using a time-dependent Cox proportional hazard model. Additionally, 2 sensitivity analyses were conducted by defining PPS users as individuals with an observation period over 6 months from the initial prescription or those with a cumulative dose exceeding 9 g, using the same analysis. MAIN OUTCOME MEASURES: The outcome measures included the hazard ratios (HRs) representing the association between PPS use and maculopathy. RESULTS: Use of PPS was associated with an increased risk of subsequent maculopathy in univariate (HR, 1.7; 95% confidence interval [CI], 1.66-1.75) and multivariate analysis (HR, 1.34; 95% CI, 1.31-1.38). These results were also confirmed in 2 sensitivity analyses. The mean cumulative dose of PPS for the cohort was 37.2 ± 76.7 g. CONCLUSIONS: In this nationwide cohort study involving an Asian population, individuals with cystitis using PPS exhibit an increased risk of developing subsequent maculopathy. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION AND POOR VISUAL ACUITY.

PURPOSE: To investigate the significance of intravitreal anti-vascular endothelial growth factor treatment in patients with neovascular age-related macular degeneration and poor visual acuity. METHODS: Retrospective study of patients with neovascular age-related macular degeneration with baseline best-corrected visual acuity of ≤20/200. Patients were divided into regular treatment and scarce treatment groups according to whether they underwent consecutive intravitreal anti-vascular endothelial growth factor treatments at intervals of ≤4 months or not. RESULTS: A total of 131 eyes were included: 87 and 44 eyes in the regular treatment and scarce treatment groups, respectively. The regular treatment group showed significantly improved preservation of lesion size at both Years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage. Improvements in visual acuity, reduction in central subfield macular thickness, and maximal height of choroidal neovascularization were significantly favorable in the regular treatment group at Year 1, and central subfield macular thickness was significantly decreased at Year 2. Survival analysis revealed that the regular treatment group had significantly greater preservation of visual acuity and lesion size than that in the scarce treatment group. CONCLUSION: Maintaining intravitreal anti-vascular endothelial growth factor treatment for patients with neovascular age-related macular degeneration and poor vision showed significant advantages in visual acuity and lesion size stability and reduced the incidence of new subretinal hemorrhage, which suggests preservation of paracentral vision.

LONGITUDINAL CHANGE OF RETINAL LAYER THICKNESS IN COGNITIVELY NORMAL ELDERLY SUBJECTS: Population-Based Cohort Study.

PURPOSE: To identify longitudinal retinal layer thickness changes in normal eyes of cognitively healthy elderly people. METHODS: Post hoc analysis was performed on 57 cognitively healthy elderly participants from the population-based Korean Longitudinal Study on Health and Aging and Korean Longitudinal Study on Cognitive Aging and Dementia cohort studies who underwent baseline and final optical coherence tomography scans. The peripapillary retinal nerve fiber layer, subfoveal choroid, and average retinal layer thickness at four quadrant (nasal, temporal, superior, and inferior) points 1 mm, 2 mm, and 3 mm from the center of the fovea were measured. RESULTS: The mean age of subjects was 75.1 years and the mean follow-up period was 55.9 months. Among the analyzed retinal layers, both the ganglion cell-inner plexiform layer and the outer nuclear layer at all 1 mm, 2 mm, and 3 mm points showed a statistically significant decrease in thickness at the final visit compared with baseline. The annual decrease rates were -1.2 µm/year at 1 mm (total -6.6%), -1.3 µm/year at 2 mm (total -8.4%), and -1.1 µm/year at 3 mm (total -9.7%) for ganglion cell-inner plexiform layer and -0.6 µm/year at 1 mm (total -4.2%), -0.5 µm/year at 2 mm (total -3.9%), and -0.4 µm/year at 3 mm (total -4.1%) for outer nuclear layer. CONCLUSION: Aging plays a significant role in the reduction of ganglion cell-inner plexiform layer and outer nuclear layer thicknesses in cognitively healthy elderly individuals.

Magnetically Controlled Intraocular Delivery of Dexamethasone Using Silica-Coated Magnetic Nanoparticles.

Although the number of patients with eye diseases is increasing, efficient drug delivery to the posterior segment of the eyeball remains challenging. The reasons include the unique anatomy of the eyeball, the blood-aqueous barrier, the blood-retina barrier, and drug elimination via the anterior chamber and uveoscleral routes. Solutions to these obstacles for therapeutic delivery to the posterior segment will increase the efficacy, efficiency, and safety of ophthalmic treatment. Micro/nanorobots are promising tools to deliver therapeutics to the retina under the direction of an external magnetic field. Although many groups have evaluated potential uses of micro/nanorobots in retinal treatment, most experiments have been performed under idealized in vitro laboratory conditions and thus do not fully demonstrate the clinical feasibility of this approach. This study examined the use of magnetic nanoparticles (MNPs) to deliver dexamethasone, a drug widely used in retinal disease treatment. The MNPs allowed sustainable drug release and successful magnetic manipulation inside bovine vitreous humor and the vitreous humor of living rabbits. Therefore, controlled drug distribution via magnetic manipulation of MNPs is a promising strategy for targeted drug delivery to the retina.

White matter microstructural integrity as a key to effective propagation of gamma entrainment in humans.

Gamma entrainment through sensory stimulation has the potential to reduce the pathology of Alzheimer's disease in mouse models. However, clinical trials in Alzheimer's disease (AD) patients have yielded inconsistent results, necessitating further investigation. This single-center pre-post intervention study aims to explore the influence of white matter microstructural integrity on gamma rhythm propagation from the visual cortex to AD-affected regions in 31 cognitively normal volunteers aged ≥ 65. Gamma rhythm propagation induced by optimal FLS was measured. Diffusion tensor imaging was employed to assess the integrity of white matter tracts of interest. After excluding 5 participants with a deficit in steady-state visually evoked potentials, 26 participants were included in the final analysis. In the linear regression analyses, gamma entrainment was identified as a significant predictor of gamma propagation (p < 0.001). Furthermore, the study identified white matter microstructural integrity as a significant predictor of gamma propagation by flickering light stimulation (p < 0.05), which was specific to tracts that connect occipital and temporal or frontal regions. These findings indicate that, despite robust entrainment of gamma rhythms in the visual cortex, their propagation to other regions may be impaired if the microstructural integrity of the white matter tracts connecting the visual cortex to other areas is compromised. Consequently, our findings have expanded our understanding of the prerequisites for effective gamma entrainment and suggest that future clinical trials utilizing visual stimulation for gamma entrainment should consider white matter tract microstructural integrity for candidate selection and outcome analysis.

Trends and Barriers in Diabetic Retinopathy Screening: Korea National Health and Nutritional Examination Survey 2016-2021.

BACKGROUND: The prevalence of diabetes is increasing globally, highlighting the importance of preventive healthcare. This study aimed to identify the diabetic retinopathy (DR) screening rates and risk factors linked to DR screening nonadherence in the Korean population through a nationally representative sample survey. METHODS: Among the Korea National Health and Nutrition Examination Survey database from 2016 to 2021, participants aged ≥ 40 years with diabetes were included. The weighted estimate for nonadherence to DR screening within a year was calculated. Risk factor analyses were conducted using univariate and multivariate logistic regression. RESULTS: Among the 3,717 participants, 1,109 (29.5%) underwent DR screening within the past year, and this national estimate exhibited no statistically significant difference from 2016 to 2021 (P = 0.809). Nonadherence to annual DR screening was associated with residing in rural areas, age ≥ 80 years, low educational level, self-reported good health, absence of ocular disease, current smoking, lack of exercise and dietary diabetes treatment, and no activity limitation (all P < 0.05). CONCLUSION: The recent DR screening rate in Korea was relatively low. Factors associated with apathy and complacency towards personal health were associated with the nonadherence to DR screening. Educational interventions have the potential to enhance the annual screening rate for diabetic patients.

Organ-specific Toxocara canis larvae migration and host immune response in experimentally infected mice.

We investigated organ specific Toxocara canis larval migration in mice infected with T. canis larvae. We observed the worm burden and systemic immune responses. Three groups of BALB/c mice (n=5 each) were orally administered 1,000 T. canis 2nd stage larvae to induce larva migrans. Mice were sacrificed at 1, 3, and 5 weeks post-infection. Liver, lung, brain, and eye tissues were collected. Tissue from 2 mice per group was digested for larval count, while the remaining 3 mice underwent histological analysis. Blood hematology and serology were evaluated and compared to that in a control uninfected group (n=5) to assess the immune response. Cytokine levels in bronchoalveolar lavage (BAL) fluid were also analyzed. We found that, 1 week post-infection, the mean parasite load in the liver (72±7.1), brain (31±4.2), lungs (20±5.7), and eyes (2±0) peaked and stayed constant until the 3 weeks. By 5-week post-infection, the worm burden in the liver and lungs significantly decreased to 10±4.2 and 9±5.7, respectively, while they remained relatively stable in the brain and eyes (18±4.2 and 1±0, respectively). Interestingly, ocular larvae resided in all retinal layers, without notable inflammation in outer retina. Mice infected with T. canis exhibited elevated levels of neutrophils, monocytes, eosinophils, and immunoglobulin E. At 5 weeks post-infection, interleukin (IL)-5 and IL-13 levels were elevated in BAL fluid. Whereas IL-4, IL-10, IL-17, and interferon-γ levels in BAL fluid were similar to that in controls. Our findings demonstrate that a small portion of T. canis larvae migrate to the eyes and brain within the first week of infection. Minimal tissue inflammation was observed, probably due to increase of anti-inflammatory cytokines. This study contributes to our understanding of the histological and immunological responses to T. canis infection in mice, which may have implications to further understand human toxocariasis.

Clinical characteristics of recurrent non-arteritic retinal artery occlusion.

OBJECTIVES: To investigate the recurrent non-arteritic retinal artery occlusion (RAO) in the same or opposite eye. METHODS: We searched the RAO registry at Seoul National University Bundang Hospital and included patients with recurrent RAO in the present study. Ophthalmic and systemic features were analysed to identify risk factors and visual outcomes. RESULTS: Of the 850 patients in the non-arteritic RAO cohort, 11 (1.3%) experienced a second RAO recurrence, either in the same (5 patients; 0.6%) or opposite (6 patients; 0.7%) eye. The same eye group experienced an earlier recurrence (1-2 months, median 1 month) than the opposite eye group, where the time to recurrence was notably longer (8-66 months, median 22 months). Best corrected visual acuity (BCVA) in the same eye group decreased after the recurrence of RAO. In the same eye group, initial BCVA ranged from 20/200 to counting fingers (CF), while BCVA during RAO recurrence ranged from CF to hand motion. When RAO recurred in the opposite eye, the reduction in visual acuity was less severe than the reduction of the initial episode: initial episode ranged from 20/400 to light perception and recurrent episode ranged from 20/25 to 20/400. Patients exhibited varying degrees of carotid (81.8%) and cerebral (9.1%) artery occlusions. Additionally, one patient in each group (total 2 patients, 18.2%) experienced a stroke 6 months after RAO recurrence. CONCLUSIONS: Since the RAO recurrences could lead to devastating visual impairment, it is essential to emphasise the importance of risk factor screening to patients while collaborating with neurologists and cardiologists.

Association of baseline factors with 1-year outcomes in the SB11-ranibizumab equivalence trial: A post hoc analysis.

PURPOSE: To identify baseline factors associated with 1-year outcomes when treating neovascular age-related macular degeneration (nAMD) with ranibizumab biosimilar SB11 or reference ranibizumab (rRBZ), and to compare efficacy of the two products within subgroups judged to be clinically relevant. DESIGN: Post hoc analysis of a prospective, equivalence phase 3 randomized clinical trial (RCT) METHODS: 705 patients with nAMD were randomized 1:1 to receive SB11 or rRBZ for 48 weeks. Pooled and randomized groups were used to identify baseline factors associated with clinical outcomes at Week 52 using multiple linear regression models. Significant factors identified in regression analyses were confirmed in analyses of variance. Subgroup analyses comparing best-corrected visual acuity (BCVA) changes between SB11 and rRBZ were conducted. RESULTS: 634 (89.9%) participants completed the 52-week visit. Regression analyses showed that younger age, lower BCVA, and smaller total lesion area at baseline were associated with greater BCVA gain at Week 52, while older age, lower BCVA, and thicker central subfield thickness (CST) at baseline were predictors of greater CST reduction in the pooled group. Subgroup analyses demonstrated that BCVA outcomes appeared comparable for the SB11 and rRBZ groups. CONCLUSION: Post hoc analyses of the SB11-rRBZ equivalence study showed that baseline age, BCVA, CST, and total lesion area were prognostic factors for visual or anatomical outcomes of nAMD, while subgroup analyses demonstrated comparable results for SB11 and rRBZ. Collectively, the results appear comparable to similar RCTs of anti-vascular endothelial growth factor reference products for nAMD and strengthen confidence in the biosimilarity of SB11.