Risk of Ophthalmic Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis.

Background: Immune checkpoint inhibitors (ICIs) -induced adverse events (AEs) have been reported affecting almost all human organs. However, studies about ocular AEs are few. A meta-analysis was performed to evaluate the risks of ICI-related ophthalmic AEs compare to chemotherapy.Methods: Eligible studies were selected from phase II/III randomized controlled trials investigating ICIs. The data were analyzed by R software and Stata.Results: Odds ratio of treatment-related AE (trAEs) and nonspecific ophthalmic trAEs (NS-trAEs) were lower for PD-1/PD-L1 inhibitors than chemotherapy (OR 0.44, p < .05; OR 0.28, p < .001; OR 0.18, p < . 05; OR: 0.18, p < .001respectively). Compared with monotherapy, PD-1 plus CTLA-4 inhibitors increased the risks of immune-related AEs (irAEs) (OR 4.52, p < .01); ICIs plus chemotherapy increased the risks of trAEs and irAEs (OR 2.82, p < .001; OR 3.63, p < .05 respectively).Conclusions: PD-L1/PD-1 inhibitors had lower risks of trAEs and NS-trAEs than chemotherapy; Compared with monotherapy, combination therapy had higher risks of ophthalmic trAEs and irAEs.Abbreviation PD-1: programmed cell death protein 1; PD-L1: programmed cell death protein ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; ICI: immune checkpoint inhibitor; AE: adverse event; trAE: treatment-related adverse event;irAE: immune-related adverse events; NS-trAE: nonspecific ophthalmic treatment-related adverse event; RCT: randomized controlled trials; PFS: progression-free survival; OS: overall survival; ORR: objective response rate; MM: melanoma; NSCLC: non-small cell lung cancer; SCLC: small cell lung cancer; HNSCC: head-neck squamous cell carcinoma; PICOL: patient, intervention, comparison, and outcome; Versus: VS; Chem: chemotherapy; 95%CI: 95% confidence interval; FEM: fixed-effects model; REM: random-effects model; NA: not applicable; MeSH: medical subject heading.