PURPOSE: To compare the efficacy and side-effect profile of interferon alpha-2b (IFNα2B) and topical 5-fluorouracil (5-FU) as primary treatment modalities for ocular surface squamous neoplasia (OSSN). METHODS: Retrospective comparative study of 116 OSSN eyes treated with topical 1 MIU IFNα2B with/without 5 MIU/cc subconjunctival injection (group 1) or topical 1% 5-FU (group 2) in mutually exclusive time periods of treatment. RESULTS: Of the 116 eyes with OSSN, 64 eyes belonged to group 1 and 52 eyes to group 2. The mean tumor basal conjunctival diameter for groups 1 and 2 was 10 mm (median, 10 mm
range 0-28 mm) and 5 mm (median, 4 mm
range, 0-24 mm) respectively (p <
0.0001). Complete tumor regression with medical management alone was achieved in 51 (80%) eyes in group 1 and 43 (83%) eyes in group 2 (p = 0.6814). The mean number of sessions/cycles of treatment for complete tumor regression was 3 (median, 3
range, 1-6) for group 1 versus 2 (median, 2
range, 1-6) for group 2 (p <
0.0001). Tumor recurrence was noted in 3 (5%) eyes in group 1 over a mean follow-up period (months) of 11 (median, 7
range, 3-41) versus 1 (2%) in group 2 (p = 0.25) over a mean follow-up period (months) of 6 (median, 5
range, 1-25). Side-effects included transient conjunctival hyperemia (9%), and flu-like symptoms (3%) in group 1 versus transient conjunctival hyperemia (2%), punctal stenosis (2%), and partial limbal stem cell deficiency (2%) in group 2. CONCLUSION: Primary treatment of OSSN with IFNα2b or 5-FU offers comparable and good tumor control with minimal side-effects.