Importance: Recent studies have suggested an association between nonarteritic anterior ischemic optic neuropathy (NAION) with semaglutide usage. However, the limitations of those analyses warrant further investigation, given the frequency of use of these medications in people with and without diabetes.Objective: To investigate the association between semaglutide use and the risk of NAION among patients with diabetes.Design, Setting, and Participants: This cohort study used data from the TriNetX database between October 1, 2019, and December 31, 2023, to identify patients with diabetes with no history of NAION who were prescribed semaglutide. The semaglutide cohort was compared with a control group of randomly selected patients with diabetes who were prescribed non–glucagonlike peptide 1 (non–GLP-1) receptor agonist (RA) antidiabetic medications. The data analysis for this study was performed on September 1, 2024.Exposures: Semaglutide history, identified using diagnostic codes.Main Outcomes and Measures: Cumulative incidence and (HR) hazard ratio of NAION.Results: A total of 3 344 205 patients with diabetes were included in this study. Regarding the diabetes cohort, a total of 174 584 patients with diabetes who received semaglutide (mean [SD] age, 58.3 [12.5] years; 90 427 female [51.8%]; 71 739 male [41.1%]) and 174 584 patients with diabetes who received non–GLP-1 RA medications (mean [SD] age, 58.2 [14.3] years; 90 475 female [51.82%]; 71 989 male [41.24%]) were recruited. Patients with diabetes taking semaglutide exhibited an absence of NAION risk at the 1-month (HR, 2.99; 95% CI, 0.31-28.75), 3-month (HR, 1.33; 95% CI, 0.30-5.93), 6-month (HR, 1.79; 95% CI, 0.60-5.35), and 1-year (HR, 1.94; 95% CI: 0.93-4.02) time points after the index date. However, those taking semaglutide were found to have an increased risk for NAION at the 2-year (HR, 2.39; 95% CI, 1.37-4.18), 3-year (HR, 2.44; 95% CI, 1.44-4.12), and 4-year (HR, 2.05; 95% CI, 1.26-3.34) time points from the index date. Increased risk for NAION was also noted in patients with diabetes and concomitant hypertension who were taking semaglutide (HR, 2.42; 95% CI, 1.19-4.92). An increased NAION risk was also observed among patients with diabetes who had a history of Ozempic (Novo Nordisk) use or stand-alone Ozempic (Novo Nordisk) prescription history.Conclusions and Relevance: Results of this cohort study suggest that semaglutide use was associated with an increased risk of NAION in patients with diabetes. However, the study’s retrospective design presents limitations, as it can only infer associations rather than establish causality; further studies are needed.

Coronavirus disease 2019 (COVID-19) vaccines are associated with several ocular manifestations. Emerging evidence has been reported; however, the causality between the two is debatable. We aimed to investigate the risk of retinal vascular occlusion after COVID-19 vaccination. This retrospective cohort study used the TriNetX global network and included individuals vaccinated with COVID-19 vaccines between January 2020 and December 2022. We excluded individuals with a history of retinal vascular occlusion or those who used any systemic medication that could potentially affect blood coagulation prior to vaccination. To compare the risk of retinal vascular occlusion, we employed multivariable-adjusted Cox proportional hazards models after performing a 1:1 propensity score matching between the vaccinated and unvaccinated cohorts. Individuals with COVID-19 vaccination had a higher risk of all forms of retinal vascular occlusion in 2 years after vaccination, with an overall hazard ratio of 2.19 (95% confidence interval 2.00–2.39). The cumulative incidence of retinal vascular occlusion was significantly higher in the vaccinated cohort compared to the unvaccinated cohort, 2 years and 12 weeks after vaccination. The risk of retinal vascular occlusion significantly increased during the first 2 weeks after vaccination and persisted for 12 weeks. Additionally, individuals with first and second dose of BNT162b2 and mRNA-1273 had significantly increased risk of retinal vascular occlusion 2 years following vaccination, while no disparity was detected between brand and dose of vaccines. This large multicenter study strengthens the findings of previous cases. Retinal vascular occlusion may not be a coincidental finding after COVID-19 vaccination.

Purpose: To identify optical coherence tomography (OCT) biomarkers that may predict functional and anatomical outcomes in diabetic macular edema (DME) patients treated with intravitreal dexamethasone (DEX) implant.Materials and Methods: Sixty-four eyes from 50 patients with DME were enrolled. Best-corrected visual acuity (BCVA) and OCT biomarkers including central retinal thickness (CRT), subretinal fluid (SRF), intraretinal cysts (IRC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudate (HE), hyperreflective foci (HRF), epiretinal membrane (ERM), and vitreomacular interface (VMI) changes were evaluated at baseline and at 3, 6, and 12 months after treatment. Multiple logistic analysis was performed to evaluate each OCT biomarker as a predictive factor for functional and anatomical improvement at the end of treatment.Results: The presence of SRF at baseline was associated with a favorable outcome, with CRT improving by more than 100 μm after treatment from multivariate logistic regression analysis [odds ratio 6.16 (1.75–21.6)]. In addition, baseline SRF predicted a greater CRT improvement from multiple regression analysis (model R-square 0.11, p = 0.006). The reduction of DRIL, SRF, LONLC, IRC, and EZD were correlated with better CRT improvement (more than 100 μm) (P < 0.05). SRF and EZD recovery can also predict better visual prognosis (P < 0.05).Conclusion: OCT biomarkers can be used to predict who may benefit the most after DEX treatment. We suggest that the DEX implant should be considered as a first line treatment in DME patients with SRF.

Background and Objectives: The identification of possible biomarkers that can predict treatment response among DME eyes is important for the individualization of treatment plans. We investigated optical coherence tomography (OCT)-based biomarkers that may predict the one-year real-life outcomes among diabetic macular edema (DME) eyes following treatment by intravitreal ranibizumab (IVR) injections. Materials and Methods: A total of 65 eyes from 35 treatment-naïve patients with DME treated with ranibizumab injection were recruited. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), and OCT scans were retrospectively recorded at baseline before treatment and at 3 months, 6 months, and 12 months after treatment. The OCT scans were evaluated for biomarkers of interest, which included central retinal thickness (CRT), amount and locations of hyperreflective foci (HRF), subretinal fluid (SRF), intraretinal cysts (IRC), large outer nuclear layer cyst (LONLC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudates (HE), epiretinal membrane (ERM), and vitreomacular interface (VMI). Correlations between these OCT biomarkers and outcome measures (visual and structural) were statistically analyzed. Results: A total of 65 eyes from 35 patients with DME were enrolled. The mean age was 64.2 ± 10.9 years old. Significant improvement in terms of mean BCVA (p < 0.005) and mean CRT was seen at final follow-up compared to baseline. The biomarkers of DRIL, LONLC, and SRF were found to be predictive for at least 50 μm CRT reduction after treatment (with odds ratio of 8.69, 8.5, and 17.58, respectively). The biomarkers of IRC, LONLC, and SRF were predictive for significant improvement in terms of BCVA and CRT after treatment. Finally, the number of HRF was predictive for both BCVA improvement and a CRT reduction of less than 100 μm after treatment. No serious complications were reported during the study. Conclusion: Our study demonstrated the utility of OCT biomarkers as therapeutic predictors of ranibizumab treatment among DME eyes.

Objective: To explore the associations between the use of immune checkpoint inhibitors (ICIs) and the risk of developing uveitis among cancer patients.Methods: Cancer patients who received ICI therapy and a comparison group of cancer patients who did not receive ICI therapy were retrospectively recruited from the TriNetX electronic heath-record registry. The outcome of interest was the development of new-onset uveitis. Propensity score matching based on a 1:1 ratio was conducted in order to reduce bias. Multi-variate cox proportional hazard models and Kaplan Meier method were also utilized to assess for the risk of uveitis among cancer patients who received ICI therapy.Results: 71931 cancer patients (54.7% male; 76.5% white; mean age at index 63.6 ± 12.2 years) who received ICI treatment (ICI group) and 71931 cancer patients (54.7% male; 77% white; mean age at index 63.5 ± 12.4 years) who never received ICI (comparison group) were recruited. Associated Kaplan-Meier curves showed significantly increased uveitis risk among the ICI group for all follow-up years (p<0.001). The risk of uveitis was also higher among the ICI group during the 144-month follow-up period with a hazard ratio (HR) of 2.39 (95% CI: 2.07-2.75). Increased risk for specific uveitis diseases, such as iridocyclitis, chorioretinal inflammation, retinal vasculitis, unspecified purulent endophthalmitis, pan-uveitis and sympathetic uveitis were found. Subgroup analysis demonstrated an elevated hazard ratio for the development of uveitis among ICI recipients, spanning individuals below the age of 65 as well as those aged 65 and older. The elevated hazard ratio for uveitis development among ICI recipients was also observed across all genders, among those of white and Asian ethnicities, those with smoking history, and those with comorbid conditions such as hypertension and dyslipidemia, in comparison to their non-ICI counterparts. An additional subgroup analysis on monotherapy versus combinatory ICI regimens was also conducted. Individuals who received monotherapy from the class of anti-PD-1 (HR:1.98 [CI: 1.65-2.37]) and anti-CTLA-4 (HR:5.86 [CI:1.99-17.24]) exhibited elevated hazard ratios for uveitis development compared to their non-ICI comparators. Those exposed to combinatory ICI regimens, specifically a combination of anti-PD-1 and anti-CTLA4 (HR: 5.04 [CI:3.55-7.16]), showed increased hazard ratios for uveitis development compared to their non-ICI comparators. In contrast, individuals exposed to a combination of anti-PD-1 and anti-PD-L1 (HR: 2.47 [CI:0.81-7.50]) did not demonstrate an increased risk for uveitis compared to their non-ICI comparators.Conclusion: A significantly increased risk for uveitis diseases was found among the ICI group from the first year of follow-up. Increased awareness should be promoted on the occurrence of uveitis among cancer patients receiving ICI therapy.