Topic: To evaluate the efficacy and safety of anti-VEGF and panretinal photocoagulation (PRP) for the treatment of proliferative diabetic retinopathy (PDR). The outcomes examined are changes in best-corrected visual acuity (BCVA), neovascularization (NV), central macular thickness (CMT), and adverse outcomes. Clinical relevance: Diabetic retinopathy is the leading cause of blindness in working-aged adults globally. At present, no consensus has been reached on the optimal choice for the treatment of PDR. Methods: Cochrane, Embase, PubMed, Scopus, Web of Science, and CiNAHL were searched for articles from their inception to June 2023 according to the Preferred Reporting Items for Systematic Reviews and Meta- analysis. The review was registered prospectively with PROSPERO (CRD42023437778). Tool data analysis was performed using RevMan software version 5.4 (Review Manager [RevMan] [computer program], The Cochrane Collaboration, 2020). Randomized control trials (RCTs) of PDR patients treated with anti-VEGF, PRP, or a combination were included. Risk of bias was assessed using the Rob2 assessment tool (revised tool for risk of bias in randomized trials), and certainty of evidence was assessed with the Grading Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Nineteen studies were included, with 1361 patients (n = 1788 eyes) treated for PDR with either antiVEGF (n = 274), PRP (n = 482), or combination (n = 320). Our results show more favorable BCVA outcomes with anti-VEGF compared with PRP at 3 months (mean difference [MD] = 2.35 letters; 95% confidence interval [CI], 1.18-3.52; I2 = 0%) and 12 months follow-up (MD = 3.39 letters; 95% CI, 0.63-6.14; I2 = 26%). Combination treatment showed better BCVA outcomes compared with PRP at 12 months (MD = 4.06 letters; 95% CI, 0.26-7.86; I2 = 0%). Combination showed lower CMT at 3 months (MD =-33.10mm; 95% CI,-40.12 to-26.08; I2 = 25%) and 6 months (MD =-34.28 mm; 95% CI,-55.59 to-12.97; I2 = 85%) compared with PRP, but CMT results were similar at 12 months. Complete regression of total NV (NVT) was more likely with anti-VEGF compared with PRP (odds ratio = 6.15; 95% CI, 1.39-27.15; I2 = 80%). Posttreatment vitreous hemorrhage, vitrectomy, and increased intraocular pressure events were similar between the anti-VEGF and combination groups compared with PRP; however, macular edema results favored the anti-VEGF over the PRP group. Using the GRADE assessment, BCVA evidence was rated to be of moderate certainty, whereas CMT and NVT evidence certainty was rated as very low. Conclusion: Anti-VEGF and combination treatments could be regarded as alternative approaches to PRP alone in the management of PDR after engaging in a shared decision-making process based on patients' adherence, diabetic macular edema status, and preference. Limitations of this meta-analysis include the heterogeneity in participants' characteristics, treatment regimens, and outcome reporting between studies. Further RCTs should be conducted to compare the effectiveness of these treatments in the long term.
