Topical fl uorouracil after surgery for ocular surface squamous neoplasia in Kenya: a randomised, double-blind, placebo-controlled trial

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

Topical fl uorouracil after surgery for ocular surface squamous neoplasia in Kenya: a randomised, double-blind, placebo-controlled trial

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

Delay along the care-seeking journey of patients with ocular surface squamous neoplasia in Kenya

Abstract Background In Africa, accessing eye health services is a major challenge. Ocular surface squamous neoplasia (OSSN) is a substantial ocular health problem in Africa related to solar UV light exposure and HIV infection among other risk factors. The disease causes visual loss and even death in advanced cases. This study was conducted to assess referral pathway and treatment delay for patients with OSSN in Kenya. Methods Adults with conjunctival lesions presenting to four eye centres were asked about their occupations, when they noticed the growth, health facilities visited in seeking care, cost of consultation, surgery, medicines and histopathology and dates at each step. The time-to-presentation was divided into quartiles and correlates analysed using ordinal logistic regression. Results We evaluated 158 first-time presenters with OSSN. Most were women (102 [65%]), living with HIV (78/110 tested [71%]), with low to medium income (127 [80%]). Most of the HIV patients (49/78 [63%]) were in antiretroviral care programs. About half (88/158, [56%]) presented directly to the study centres while the rest were referred. Indirect presenters sought care earlier than direct presenters (median 2.0 months vs 5.5 months) and travelled a shorter distance to the first health facility (median 20 km vs 30 km) but had surgery later (median 12.5 months vs 5.5 months). Visits beyond the first health facility for indirect presenters markedly increased delay (median 7.3, 29.0, 37.9, and 32.0 months for 1–4 facilities, respectively). Delay was associated with number of health facilities visited (adjusted ordered OR = 9.12; 95%CI 2.83–29.4, p < 0.001) and being female (adjusted ordered OR = 2.42; 95%CI 1.32–4.44, p = 0.004). At the time of presentation at the study centres for surgery the median tumour diameter in both directly and indirectly presenting patients was 6 mm (p = 0.52) and the histological spectrum of OSSN was similar between the groups (p = 0.87). Conclusions Referral delays definitive treatment for OSSN. Women were more likely to experience delay. Despite regular contact with the health system for those with known HIV infection, delays occurred. Early detection and referral of OSSN in the HIV service might reduce delays, but reassuringly delay did not give rise to a larger proportion with more advanced grade of OSSN