(071) Ocular adverse events associated with platins: A disproportionality analysis of pharmacovigilance data and extensive systematic review of case reports

Background: Anti-cancer drugs, particularly platins, have been showing ocular adverse events in patients undergoing chemotherapy.

Objectives: To evaluate the potential association between platins (Cisplatin, Carboplatin, and Oxaliplatin) and the risk of ocular adverse events by analyzing the spontaneous reports through disproportionality analysis and reviewing case reports.

Methods: We carried out a retrospective case/non-case study using spontaneous reports in the FDA Adverse Event Reporting System (FAERS) database from the date of approval by the FDA till 31st December 2023. A disproportionality analysis was performed by calculating the Proportional Reporting Ratio (PRR), Lower Bound Reporting Odds Ratio (LB ROR), and the Information Component (IC) to identify ocular adverse event signals (if PRR ≥ 2, LB ROR > 1, and IC025 > 0) for platins. We also performed a signal refinement analysis by eliminating the confounding co-prescribed medications to identify the robustness of the findings. In parallel, a review of case reports for ocular adverse events from platins was conducted by a systematic literature search in PubMed and Google Scholar.

Results: A total of 4262 spontaneous reports of ocular adverse events caused by platins were identified from the FAERS Database, including 258 Ocular events. Using disproportionality analysis, 68 signals were identified for platins and ocular adverse events (Carboplatin: 42, Oxaliplatin: 16, Cisplatin: 10). Ocular adverse events such as Choroidal Infarction [PRR = 215.1; LB ROR = 140.7; IC025 = 5.1], Staphyloma [PRR = 60.0; LB ROR = 19.8; IC025 = 1.3], and Dacryostenosis Acquired [PRR = 13.1; LB ROR = 9.5; IC025 = 3.0] had the highest strength signals identified for carboplatin. Trichomegaly [PRR = 109.3; LB ROR = 59.5; IC025 = 3.6], Amaurosis Fugax [PRR = 16.8; LB ROR = 10.8; IC025 = 2.9] for oxaliplatin and cortical blindness [PRR = 23.7; LB ROR = 14.8; IC025 = 3.1], xerophthalmia [PRR = 6.9; LB ROR = 2.8; IC025 = 0.6] for cisplatin were the highest strength ocular adverse event signals identified. A total of 32 case reports of ocular events associated with platins (Carboplatin: 4, Oxaliplatin: 12, Cisplatin: 16) were identified through a systematic search in PubMed and Google Scholar and thus strengthened the association between platins and ocular adverse events.

Conclusions: The study revealed a potential risk of ocular adverse events when using platins as an anticancer medication. Since only the cisplatin leaflet has a safety alert for ocular events currently, it is crucial to extrapolate to the remaining platins through further safety analysis.