Risk of Ophthalmotoxicity Associated with Antibody-Drug Conjugates: A Systematic Review and Meta-analysis.

Background: Antibody-drug conjugates provide significant advantages in cancer therapy, but their associated ophthalmotoxicity remains insufficiently explored.

Objective: Our objective was to determine the prevalence and risk of ophthalmotoxicity in patients receiving antibody-drug conjugates.

Methods: We conducted a systematic search in MEDLINE, Embase, Web of Science, Cochrane, and ClinicalTrials.gov for phase II or III randomized clinical trials reporting ocular adverse events linked to antibody-drug conjugates up to 5 March, 2025. The Cochrane Bias Risk Assessment Tool was used to assess the risk of bias. The primary outcome was the risk of all-grade ocular adverse events induced by antibody-drug conjugates, measured by the risk ratio (RR) with 95% confidence intervals (CIs).

Results: Thirty-one trials consisting of 18,490 patients were ultimately included. The pooled incidence of all-grade ocular adverse events following antibody-drug conjugate therapy was 10.45% (95% CI 4.51-18.42). Antibody-drug conjugates were linked to a potentially increased risk of ophthalmotoxicity (RR = 1.76, 95% CI 1.25-2.48), particularly with monomethyl auristatin E (RR = 2.73, 95% CI 1.42-5.28) and monomethyl auristatin F (RR = 3.01, 95% CI 2.58-3.52) payloads. Dry eye was the most common ocular manifestation (15.49%, 95% CI 7.66-25.38).

Conclusions: Antibody-drug conjugate therapy has been associated with an elevated risk of ophthalmotoxicity. Further research is needed to explore the influence of antibody-drug conjugate components, disease characteristics, and treatment regimens on ophthalmotoxicity risk.

Clinical trial registration: PROSPERO register name and registration number: Antibody-drug conjugates-related to ocular toxicity: a network meta-analysis and real-world pharmacovigilance study of the FAERS database (CRD42023458065).