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).