Aconitase 2 (ACO2) gene variants are one of the most frequent causes of dominant optic atrophy (DOA). However, the associated phenotypes and genotypes still lack proper characterization. To characterize the clinical and genetic spectrum of ACO2-related DOA and evaluate genotype-phenotype correlations. This was a retrospective case series to describe the ophthalmological examination of novel DOA cases with a heterozygous ACO2 variant. Data were collected from 13 reference centers in ophthalmology from France and Great Britain between January 2021 and September 2025. Included participants were those patients with OA and confirmed heterozygous or compound heterozygous ACO2 variants. DOA cases with a heterozygous ACO2 variant. Positive molecular diagnosis for ACO2 variants by next-generation sequencing, clinical examination including age at diagnosis, sex, best-corrected visual acuity (BCVA), retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness, visual field mean deviation (MD), and fundus examination. Data for 55 patients (median [IQR] age at diagnosis for 45 patients, 24 [8-51] years; 33 male [67%]) from 37 families with ACO2 variants were compiled. Analyses were conducted on 49 patients who were strictly heterozygous or compound heterozygous with the c.220C>G benign variant. Clinical data disclosed a high variability of severity, from pauci-symptomatic up to legal blindness. Median BCVA was 0.46 logMAR (Snellen equivalent, 20/63; IQR 0.00-0.89; n = 45). Four patients exhibited retinal abnormalities: 3 displayed a foveopathy, and 1 had retinitis pigmentosa. There were 12 previously unreported variants (to the authors' knowledge), including the deletion of ACO2 exon 9. No correlation between BCVA and sex, age at diagnosis (Spearman ρ = -0.19; 95% CI, -0.45 to 0.07), or variant type (Kruskal-Wallis test P =.33) was found, but there was a correlation between BCVA and RNFL (Spearman ρ = -0.74; 95% CI, -0.85 to -0.54), GCL (Spearman ρ = -0.60; 95% CI, -0.79 to -0.30), and MD (Spearman ρ = -0.65; 95% CI, -0.89 to -0.31). RNFL correlated with GCL (Spearman ρ = 0.69; 95% CI, 0.42-0.87) and MD (Spearman ρ = 0.57; 95% CI, 0.14-0.85); age at diagnosis correlated with GCL (Spearman ρ = -0.37; 95% CI, -0.63 to -0.03). Results of this case series reveal the high clinical heterogeneity among patients with ACO2-related DOA and demonstrated that some of these patients can also exhibit retinal abnormalities. In addition, there was a deletion of an entire ACO2 exon, emphasizing the potential importance of searching for large genomic rearrangements in patients without a molecular diagnosis. These findings support further studies to explain clinical variability, as no genotype-phenotype correlation was encountered.

Among patients receiving ongoing intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy who experience stroke or myocardial infarction (MI), evidence is limited on the systemic safety of continuing injections and whether treatment should be paused or modified. To evaluate whether, among patients receiving intravitreal anti-VEGF therapy who experience cardiovascular events (CVE), there exist associations between anti-VEGF treatments administered shortly before or after CVE (peri-CVE) and mortality or major functional outcomes, and to evaluate whether systemic outcomes differ by anti-VEGF agents. This was a retrospective cohort study of TriNetX network deidentified electronic health records (EHR) from 2005 to 2025. This study setting was a multicenter, EHR-based network analysis including individuals with stroke or MI with established anti-VEGF history (≥3 months pre-CVE), matched between those receiving 1 or more anti-VEGF injections within 14 days before or up to 6 weeks after CVE and those with no anti-VEGF from 3 months before to 3 months after. Propensity score matching (PSM) balanced demographics, comorbidities, procedures, systemic medications, laboratory values, and anti-VEGF agent history. Exposures included intravitreal anti-VEGF during the peri-CVE window vs no peri-CVE anti-VEGF. Sensitivity analyses restricted exposure to 14 days or fewer pre-CVE and compared aflibercept, bevacizumab, or ranibizumab with other agents. The primary outcomes were 3-month and 1-year all-cause mortality, poststroke neurologic deficits, and post-MI heart failure. Data were expressed in relative risks (RRs) with 95% CIs. A total of 6073 and 5381 individuals with stroke or MI, respectively, were included before PSM. After PSM (1526 pairs with stroke; exposure [received peristroke anti-VEGF], mean [SD] age, 72.1 [12.9] years; 822 female [53.9%]; control [did not receive peristroke anti-VEGF], 72.7 [13.3] years; 840 female [55.0%]; and 1523 pairs with MI, exposure [received peri-MI anti-VEGF], 71.4 [13.5] years; 809 male [53.1%]; control [did not receive peri-MI anti-VEGF], 71.5 [13.3] years; 798 male [52.4%]), peristroke anti-VEGF was associated with lower mortality at 3 months (RR, 0.39; 95% CI, 0.29-0.53) and 1 year (RR, 0.52; 95% CI, 0.43-0.63) and fewer neurologic deficits at 3 months (RR, 0.64; 95% CI, 0.46-0.89) but not 1 year (RR, 0.79; 95% CI, 0.62-1.01). Peri-MI exposure was associated with lower mortality at 3 months (RR, 0.34; 95% CI, 0.26-0.43) and 1 year (RR, 0.58; 95% CI, 0.49-0.68) and lower heart failure at 3 months (RR, 0.65; 95% CI, 0.46-0.93) but not 1 year (RR, 0.87; 95% CI, 0.68-1.11). Timing-restricted analyses showed similar mortality findings without differences in neurologic deficits or heart failure. In agent-specific comparisons, there were no differences across aflibercept, bevacizumab, or ranibizumab for any outcome. Results of this cohort study reveal that peri-CVE anti-VEGF was not associated with increased mortality or morbidity. Outcomes did not differ among commonly used agents, supporting the safety of continuing intravitreal anti-VEGF therapy without modification during the peri-CVE period.

This case report discusses a diagnosis of conjunctival Kaposi sarcoma in a male patient aged 26 years with a history of advanced HIV infection who presented with a painless red conjunctival nodule.

Metachronous bilateral conversion in initially unilateral retinoblastoma is uncommon but clinically consequential, potentially requiring intensified treatment and carrying worse prognosis. Clarifying how age at diagnosis refines genetic-risk stratification could enable safer, more efficient surveillance protocols. To estimate the incidence and timing of metachronous bilateral conversion in unilateral retinoblastoma and assess whether age at diagnosis and RB1 testing are associated with bilateral conversion risk. This was a retrospective cohort study at a tertiary center in Shanghai, China, including 1108 consecutive children with initially unilateral retinoblastoma diagnosed from July 2010 to October 2024 (after exclusions for short follow-up [n = 139], missing data [n = 53], or synchronous bilateral disease [n = 10]). The median (IQR) follow-up was 43.4 (24.2-67.6) months. Age at diagnosis and RB1 genetic status/subtypes assessed by next-generation sequencing and multiplex ligation-dependent probe amplification, including penetrance class (high vs low) and mosaic vs germline categorization. Time to metachronous bilateral conversion; cumulative incidence functions with death as a competing risk; spatial distribution of fellow-eye tumors. Among 1108 patients (median [IQR] age at diagnosis, 22.2 [12.0-31.4] months; 591 [53.3%] male), 24 (2.2%) developed metachronous bilateral disease. At 24 months, cumulative incidence was 2.2% (95% CI, 1.3-3.1) overall. By genetic status, the 24-month cumulative incidence was 24.8% (95% CI, 13.8-35.9) in RB1 variant-positive vs 1.6% (95% CI, 0.0-3.1) in RB1 variant-negative patients. Among RB1 variant-positive patients, risk clustered among those diagnosed before 9 months, whereas no conversions were observed among those diagnosed at older than 9 months. Four RB1 variant-negative patients who were initially diagnosed at notably late ages (20.9, 42.7, 79.6, and 118 months) subsequently converted; these cases likely represent undetected low-level mosaicism, somatic variants below detection thresholds, or rare genomic events not captured by standard sequencing panels. Fellow-eye tumors did not involve macula and showed a nasal-predominant distribution. The findings in this study suggest that age at diagnosis may refine genetic risk stratification for metachronous bilateral conversion. RB1 variant-positive patients diagnosed at 9 months or later represent a very low-risk subgroup that may warrant surveillance deescalation, while rare late conversions in RB1 variant-negative patients necessitate continued long-term monitoring.

Diagnosing fungal keratitis (FK) in patients with negative smear and culture results remains clinically challenging, highlighting the need for alternative diagnostic approaches. To determine the diagnostic accuracy of the clustered regularly interspaced short palindromic repeats (CRISPR)-based Rapid Identification of Mycoses using CRISPR (RID-MyC) assay for detecting FK in patients with negative smear and culture results using in vivo confocal microscopy (IVCM) as the reference standard. This prospective diagnostic accuracy study was conducted from December 2024 to March 2025 at Aravind Eye Hospital, a tertiary ophthalmology referral hospital in Coimbatore, India. Consecutive patients clinically suspected to have microbial keratitis with negative smear and culture results were eligible for inclusion. Data were analyzed from March 2025 to June 2025. All included participants underwent corneal scraping for RID-MyC assay and imaging by IVCM. The primary outcomes were sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic concordance of the RID-MyC assay compared with IVCM results. Of 245 consecutive patients clinically suspected to have microbial keratitis, 82 were smear negative. After exclusions due to contraindications or positive subsequent cultures, 41 patients with smear- and culture-negative results were ultimately included in the final analysis. Of these 41 patients (mean [SD] age, 51.0 [14.6] years; 21 [51.2%] women), RID-MyC demonstrated sensitivity of 82.1% (95% CI, 63%-94%) and specificity of 76.9% (95% CI, 46%-95%). Positive predictive value was 88.5% (95% CI, 74%-95%) and negative predictive value was 66.7% (95% CI, 46%-82%). Concordance between RID-MyC and IVCM was observed in 33 cases (80.5%). Notably, prior antifungal treatment was most frequent (4 of 5 [80%]) among patients with positive IVCM but negative RID-MyC results. Conversely, all patients (3 of 3 [100%]) with negative IVCM but positive RID-MyC findings had smaller, peripheral, or paracentral lesions. In this diagnostic study, in patients with smear- and culture-negative FK, the RID-MyC assay showed good diagnostic accuracy comparable with IVCM and was feasible in all cases, including those in whom imaging was not possible. With its rapid turnaround and minimal equipment needs, RID-MyC may serve as a practical adjunct to conventional diagnostics, particularly in high-burden, resource-limited settings where IVCM is unavailable or contraindicated.