Topical 5-Fluorouracil Appropriate for Most Ocular Surface Squamous Neoplasias

Topical 5-fluorouracil eye drops are a safe and effective primary treatment for ocular surface squamous neoplasia.

Most patients with ocular surface squamous neoplasia (OSSN) respond to treatment with topical 5-fluorouracil (5FU) eye drops, with complete resolution achieved in 87% of eyes treated, according to results of a study published in The Ocular Surface. The study shows efficacy in 2 years worth of follow up with minimal side effects.

Patients (N=251; n=258 eyes) with OSSN who received 1% 5FU treatment between 2013 and 2021 at the University of Miami in the United States were included in this analysis. Most patients were prescribed a treatment protocol of 5FU drops 4 times daily for 1 week followed by a 3-week drug holiday in monthly cycles until tumor resolution. The primary outcomes were tumor resolution and recurrence.

The patients were aged mean 77.56 (range, 31-98) years, 73% were men, 84% were White, 11% had a previous OSSN, 76% had sun exposure, and 24% had a history of skin cancer. The tumors were left sided (56%), had corneal involvement (80%), limbal conjunctiva involvement (10%), American Joint Committee on Cancer stage T3 (74%), they had a leukoplakia appearance (32%), were located nasally (50%), temporally (45%), inferiorly (39%), superiorly (17%), and the average area was 28.05 (range, 0.96-242) mm2.

The average number of monthly treatment cycles until tumor resolution was 4.00 (range, 1.05-15.05), time to resolution was 167.81 (range, 30-889) days, and time to recurrence was 493.60 (range, 17-1760) days.

Resolution occurred in both small and large tumors.

Time to resolution associated with Black ethnicity compared with White ethnicity (hazard ratio [HR], 0.54; 95% CI, 0.30-0.96; P =.04), bulbar superior involvement (HR, 0.60; 95% CI, 0.41-0.88; P =.01), corneal involvement (HR, 0.69; 95% CI, 0.50-0.95; P =.02), limbal conjunctiva involvement (HR, 0.69; 95% CI, 0.48-0.99; P =.04), inferior location (HR, 0.72; 95% CI, 0.55-0.95; P =.02), and leukoplakia (HR, 0.72; 95% CI, 0.54-0.96; P =.03).

Among the 13% of patients who did not have tumor resolution, 40% switched to mitomycin C (MMC), 25% to interferon α-2b (IFN), 6% received both MMC and IFN, and 22% underwent surgical resection.

Most patients experienced no side effects at all, but among those who did the most common presentations were hyperemia, pain, and blurred vision. A total of 26% reported mild and 3% severe hyperemia. Patients also reported pain (23%), tearing (20%), and burning sensations (15%) associated with 5FU treatment. Long-term limbal stem cell deficiency occurred among 3%.

“To our knowledge, this is the largest long-term retrospective study of OSSN patients who underwent primary treatment with topical 5FU 1% eye drops,” the researchers report. “Resolution occurred in both small and large tumors. Recurrence rate was moderate and more likely to occur in individuals who had a large tumor area prior to treatment.”

The major limitation of this study was the retrospective design.

Disclosure: One study author has declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Wylegala A, Sripawadkul W, Zein M, et al. Topical 1% 5-fluorouracil eye drops as primary treatment for ocular surface squamous neoplasia: Long-term follow-up study. Ocul Surf. 2022;S1542-0124(22)00119-7. doi:10.1016/j.jtos.2022.12.002