Initial Therapy of Panretinal Photocoagulation vs Anti-VEGF Injection for Proliferative Diabetic Retinopathy

Importance: While combined treatment of anti-vascular endothelial growth factor (VEGF) injections plus panretinal photocoagulation (PRP) is a common approach for treating proliferative diabetic retinopathy (PDR) in the clinical practice setting, large randomized clinical trials typically use monotherapy. Subsequently, information is limited as to whether the order of treatment when combining PRP and anti-VEGF injections for PDR affects outcomes. Objective: To compare outcomes of patients with PDR treated with PRP and subsequent anti-VEGF injections with outcomes of matched patients treated with anti-VEGF injections and subsequent PRP. Design, Setting, and Participants: This retrospective cohort study used data from January 2003 to January 2024 in the TriNetX aggregated electronic health records network, with data analysis performed in January 2024. Patients with PDR treated with PRP and anti-VEGF injections were eligible for inclusion. Exposures: Patients with new PDR diagnoses stratified by therapy with PRP and subsequent anti-VEGF injections or anti-VEGF injections and subsequent PRP. Main Outcomes and Measures: The primary outcome was the need for pars plana vitrectomy (PPV), defined by Current Procedural Terminology codes 67040 or 67113. The secondary outcome included incidence of PPV, vitreous hemorrhage (VH), or tractional retinal detachment (TRD). Relative risk ratios, relative risk differences, and 95% CIs were all calculated for univariate comparison of the cohorts and the development of primary outcomes after matching. Results: Before propensity score matching (PSM), which controlled for baseline demographic characteristics and medical comorbidities, 2167 patients with PDR treated with PRP first and subsequent anti-VEGF injections and 1549 patients with PDR treated with anti-VEGF injections and subsequent PRP were included. Post-PSM, mean (SD) participant age was 63.0 (13.1) years in cohort 1 (PRP and subsequent anti-VEGF injection) and 63.0 (12.4) years in cohort 2 (anti-VEGF injection and subsequent PRP). Of 1377 total participants in each cohort, 641 patients (46.6%) and 663 patients (48.1%) in cohorts 1 and 2 were female, respectively. Treatment with PRP first and subsequent anti-VEGF injection was associated with higher rates of PPV at 5 years compared with patients treated with anti-VEGF injection and subsequent PRP (relative risk [RR], 1.88; 95% CI, 1.55-2.27; risk difference [RD], 8.93%; 95% CI, 6.31%-11.55%; P < .001), with similar associations at 6 months, 1 year, and 3 years. Treatment with PRP and subsequent anti-VEGF injection was associated with higher rates of VH at 5 years (RR, 1.40; 95% CI, 1.09-1.80; RD, 6.47%; 95% CI, 1.66%-11.29%; P < .001) and TRD at 5 years (RR, 1.85; 95% CI, 1.35-2.53; RD, 4.31%; 95% CI, 2.10%-6.52%; P < .001), with similar findings at 6 months, 1 year, and 3 years compared with patients treated with anti-VEGF injection and subsequent PRP. Conclusions and Relevance: In this retrospective cohort study, findings suggest that patients with PDR treated with PRP first then subsequent anti-VEGF injection are more likely to undergo PPV for VH and TRD compared with matched patients treated with anti-VEGF agents first, then PRP. These findings support the need for further investigations to determine if the order of PRP and anti-VEGF injections should be considered when treating patients with PDR.