Background Ocular surface squamous neoplasia (OSSN) is an aggressive eye tumour particularly aff ecting people
with HIV in Africa. Primary treatment is surgical excision; however, tumour recurrence is common. We assessed the
eff ect of fl uorouracil 1% eye drops after surgery on recurrence.
Methods We did this multicentre, randomised, placebo-controlled trial in four centres in Kenya. We enrolled patients
with histologically proven OSSN aged at least 18 years. After standard surgical excision, participants were randomly
allocated to receive either topical fl uorouracil 1% or placebo four times a day for 4 weeks. Randomisation was stratifi ed
by surgeon, and participants and trial personnel were masked to assignment. Patients were followed up at 1 month,
3 months, 6 months, and 12 months. The primary outcome was clinical recurrence (supported by histological
assessment where available) by 1 year, and analysed by intention to treat. The sample size was recalculated because
events were more common than anticipated, and trial enrolment was stopped early. The trial was registered with
Pan-African Clinical Trials Registry (PACTR201207000396219).
Findings Between August, 2012, and July, 2014, we assigned 49 participants to fl uorouracil and 49 to placebo.
Four participants were lost to follow-up. Recurrences occurred in fi ve (11%) of 47 patients in the fl uorouracil group
and 17 (36%) of 47 in the placebo group (odds ratio 0·21, 95% CI 0·07–0·63; p=0·01). Adjusting for passive smoking
and antiretroviral therapy had little eff ect (odds ratio 0·23; 95% CI 0·07–0·75; p=0·02). Adverse eff ects occurred
more commonly in the fl uorouracil group, although they were transient and mild. Ocular discomfort occurred in
43 of 49 patients in the fl uorouracil group versus 36 of 49 in the placebo group, epiphora occurred in 24 versus fi ve,
and eyelid skin infl ammation occurred in seven versus none.
Interpretation Topical fl uorouracil after surgery substantially reduced recurrence of OSSN, was well-tolerated, and its
use recommended