Efficacy and safety of topical 0.5% 5-Fluorouracil as primary treatment of ocular surface squamous neoplasia

Objective: To assess the efficacy and safety of topical 0.5% 5-Fluorouracil (5-FU) as a primary therapy of ocular surface squamous neoplasia (OSSN). Design: Retrospective study. Participants: Patients with clinically suspected OSSN referred to a Brazilian tertiary health center between October 2015 and December 2022. Methods: After diagnostic confirmation of OSSN with exfoliative cytology, 0.5% 5-FU was administered topically 4 times daily for 2 weeks followed by a pause of 2 weeks. Results: A total of 54 patients were included in this study, 32 males (59.3%), mean age of 62.9 years old. Complete resolution of OSSN was achieved in 70.4%. The median number of cycles was 2 (range 1-5). Side effects were reported in 35.2%, which included eyelid erythema, conjunctival hyperemia, and punctal stenosis. None of the patients stopped treatment due to adverse effects. Patients who had partial response to 0.5% 5-FU had complementary treatment with surgery, Mitomycin-C and/or Interferon a2b. Overall recurrence was 14.8%. Median follow-up was 14 months (range 2-92 months). In a multivariate Cox regression analysis, the risk of relapse was 84% lower in patients who had complete response to 0.5% 5-FU (p = 0.018). Conclusion: Topical 0.5% 5-FU may be considered a safe and effective primary therapy for OSSN, with a low rate of side effects.