Purpose: Acute submacular hemorrhage (SMH) is a vision-threatening complication common in patients affected by age-related macular degeneration (AMD). This study evaluates safety, long-term clinical outcomes and associated treatment factors following intravitreal triple injection of recombinant tissue plasminogen activator (rtPA), SF₆ gas, and Bevacizumab due to acute SMH secondary to AMD. Methods: A retrospective analysis on patients who received treatment between January 2014 and December 2020 (n = 37) was conducted. Visual acuity (VA), central retinal thickness (CRT), central retinal volume (CRV), and axial pigment epithelial detachment height were analyzed at baseline (B), 4 weeks after triple injection (FU1), after the following anti-VEGF injection series (FU2), after 1 year (FU3), after 2 years (FU4), and at the final follow-up examination after 4.4 ± 1.6 years (FU5). Further, treatment courses and clinical outcomes were compared to a patient cohort treated for exudative AMD without prior SMH. Furthermore, an explorative data analysis on final VA was conducted, and adverse events following triple therapy were investigated. Results: Triple injection was performed on average 5.6 ± 5.7 days after onset of symptoms. Patients received 16 ± 3 additional intravitreal anti-VEGF injections due to persistent macular edema over the subsequent 2 years. Significant improvements were observed at FU1 in VA (p < 0.001), CRT (p = 0.005), and CRV (p = 0.007), as well as at FU2 in axial PED height (p < 0.001), with all improvements being stable until final follow-up examination. In the group comparison, patients with SMH demonstrated significantly worse functional and anatomical outcomes at 24 months except for the 24-month CRT, and patients on average received more intravitreal injections. Five of 37 patients (13.5%) experienced a retinal pigment epithelial tear following triple injection. Final VA correlated positively and significantly with FU1 VA, while no correlation was observed with baseline VA, the size or height of SMH, or the number of additional anti-VEGF injections. Conclusions: Triple injection constitutes a simple and effective therapy with long-term functional and anatomical improvements following treatment due to SMH, although patients have an increased risk for RPE tears. The 4-week postoperative VA following triple injection was predictive for long-term visual function.

The choroid is critical for maintaining vision and implicated in several ocular diseases, being the sole source of nutrients and waste removal for the outer retina. Genetic discovery can help elucidate the pathways through which choroidal features influence disease risk. Our meta-analysis of genome-wide association studies (n= 78,682 participants) identified 30 genomic regions, including 20 novel loci, associated with choroidal thickness. Findings suggest inflammatory and vascular processes drive choroidal thickness, with overlapping mechanisms shared with refractive error. Genome-wide independently significant SNPs accounted for 18.7% of the genetic variance in choroidal thickness. Mendelian randomisation analyses showed a causal effect of age-related macular degeneration on choroidal thickness, and suggest a bidirectional causal effect between choroidal thickness and primary angle-closure glaucoma. These findings provide insight into the shared genetic architecture and biological pathways linking choroidal thickness and related diseases.

Objectives: Children with large optic discs are frequently referred to as glaucoma suspects. The aim of this study was to longitudinally analyze and compare the peripapillary retinal nerve fiber layer (pRNFL) thickness and minimum rim width (BMO-MRW) of large optic discs in children (LOD-C), normal sized optic discs in children (NOD-C) and large optic discs in adults (LOD-A) in order to evaluate longitudinal structural stability and intergroup differences in optic nerve head morphology. Methods: Briefly, 85 LOD-C, 72 NOD-C and 78 LOD-A were included. Large optic discs were identified based on a Bruch’s membrane opening (BMO) area threshold of ≥2.5 mm². pRNFL thickness and minimal rim width (BMO-MRW) of optical coherence tomography (OCT) were compared between baseline and follow-up examination at a median of 1.4 [1.0; 2.5] years. Results: Mean global pRNFL thickness and BMO-MRW did not significantly change during the follow-up period. LOD-C showed a significant increase in pRNFL thickness in the superonasal segments, NOD-C in the nasal segments. pRNFL and BMO-MRW of LOD-A decreased during the follow-up period. However, there was a higher variance of pRNFL thickness change in LOD-C as compared with NOD-C in the superotemporal and inferonasal segments. Four optic discs in the LOD-A group showed a glaucomatous conversion, whereas none of the discs of LOD-C or NOD-C progressed to glaucoma. Conclusions: Children with large optic discs presented with stable pRNFL and BMO-MRW and without clinical progression to glaucoma at follow-up. A careful interpretation of the OCT measurement results is necessary when assessing pediatric large optic discs, as growth and remodelling may impair the accuracy of segmentation and automated classification algorithms.

Identifying patients with glaucoma who are at risk of rapid disease progression is crucial to preventing vision loss. We aimed to develop and externally validate G-PROG, a deep learning model that predicts 2-5-year glaucoma progression from baseline colour fundus photographs (CFPs). G-PROG was trained and validated on data from a single centre (UZ Leuven, Leuven, Belgium); the other datasets (Brussels, Belgium; Liège, Belgium; Tampere, Finland; Mainz, Germany; and Hangzhou, China) served as external test sets. Across six glaucoma departments, we analysed 161 827 fundus images from 127 962 visits (13 913 patients), totalling 128 021 eye-years of follow-up. Progression was defined by the G-RISK slope, calculated via within-eye linear regression on longitudinal G-RISK predictions over follow-up intervals of 2-5 years. G-RISK is a previously validated deep learning model that quantifies glaucomatous optic nerve damage from CFPs. We trained 20 G-PROG configurations with varying inclusion criteria applied to the number of visits, image quality, time between visits, and G-RISK at baseline. Performance was evaluated using the area under the receiver operating characteristic curve (AUC), the coefficient of determination (R²), and explained variance score (EVS). G-RISK slope as a progression biomarker was validated against the visual field mean deviation (MD) slope and average retinal nerve fibre layer thickness (RNFL) slope. Significant AUC values were obtained in 18 out of 20 model configurations, with internal validation reaching a maximum AUC of 0·98 (95% CI 0·97-1·00) across follow-up intervals (2-5 years). In glaucomatous eyes with a baseline G-RISK exceeding 0·6, the maximum AUC was 0·92 (0·85-0·98). For external validation, the predictions from the eight top-performing configurations (selected based on positive R² and minimal discrepancy between R² and EVS in internal validation) were averaged. Maximum AUC values ranged from 0·74 to 0·86 across the five test datasets. G-RISK slope showed significant agreement with established progression markers, with maximum AUCs of 0·82 for MD slope and 1·00 for average RNFL slope. Externally validated across five international cohorts, G-PROG predicts 2-5-year glaucoma progression from baseline CFPs. Prospective evaluation is warranted to assess whether G-PROG can improve risk stratification and resource allocation in glaucoma care. This work was funded and supported by grants from the National Medical Research Council, National Research Foundation Singapore, National Health Innovation Centre Singapore, SingHealth and Duke-NUS, Duke-NUS, the Singapore Eye Research Institute and Nanyang Technological University and the Singapore Eye Research Institute, the Competitive Research Funding of the Pirkanmaa Wellbeing Services County, the LUX-Foundation for Glaucoma Research, state funding for university-level health research at Tampere University Hospital, Wellbeing Services County of Pirkanmaa, the Tampere University Hospital Support Foundation, and the Belgian Ophthalmology Cooperation in Clinical Sciences initiative hosted by the Funds for Research in Ophthalmology.

A diagnosis of glaucoma often carries a substantial psychological burden. The chronic nature of the disease, the prospect of lifelong treatment, the possibility of surgery, and concerns about progressive vision loss can contribute to significant psychological distress. Despite growing recognition of these emotional challenges, there has been no systematic synthesis of the burden of psychological distress among adults with glaucoma in Africa or of the psychological support services available within glaucoma care. This protocol, registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD420261338962), outlines a systematic review designed to address this gap. The review will comprehensively assess the prevalence and determinants of psychological distress among adults with glaucoma and identify interventions or support services integrated into glaucoma care across African settings. Searches will be conducted in PubMed, Scopus, CINAHL, Google Scholar, and African Journals Online without language or date restrictions. Retrieved records will be managed in EndNote and screened in Covidence by two independent reviewers, with disagreements resolved through consensus or consultation with a senior reviewer. Risk of bias and methodological quality will be evaluated using established critical appraisal tools. Where sufficient data are available, findings will be synthesized through meta-analysis; otherwise, a structured narrative synthesis following synthesis-without-meta-analysis principles will be undertaken. By consolidating the available evidence, this review aims to inform the integration of psychological care into glaucoma management and support more holistic approaches to preserving both visual and mental well-being.