Topical chemotherapy may be used as an alternative to surgical excision for primary treatment of ocular surface tumors or as adjunctive therapy preceding or following surgical excision. Some authors advocate using topical treatment prior to surgical removal, the purpose being to reduce the size of large ocular surface tumors. Topical chemotherapy has the advantage of treating beyond areas of clinically visible involvement, but unlike surgical excision, it does not lead to histologic diagnosis or enable determination of clear margins. Further, since the appearance of some tumors is similar (eg, amelanotic conjunctival melanoma may resemble squamous cell carcinoma), there is concern that if chemotherapy is elected and the tumor does not respond, valuable time in the management of a potentially deadly lesion may have been lost.
Options for first-line therapy for squamous lesions are topical interferon-α2b or topical mitomycin C (MMC), or wide-margin surgical excision with cryotherapy (Figs 12-1, 12-2). Interferon-α2b is used most often as it has fewer adverse effects than MMC (ocular surface toxicity and potential stem cell deficiency); however, MMC can be used for a shorter duration—typically weeks rather than months—and may be more effective for melanocytic tumors. The antineoplastic 5-fluorouracil (5-FU) is less commonly used but may be considered for squamous lesions if other agents are unaffordable, ineffective, or poorly tolerated.
Figure 12-1 Treatment options for ocular surface squamous neoplasia. 5-FU = 5-fluorouracil; IFN-α2b = interferon-α2b; MMC = mitomycin C.
A, Ocular surface squamous neoplasia. B, The same eye 7 weeks after topical treatment with interferon-α2b 1 million IU/mL 4 times daily.
(Courtesy of David D. Verdier, MD.)
The optimal topical chemotherapy regimen has not been determined in controlled studies. Topical interferon-α2b 1 million IU/mL is typically given 4 times daily until clinical resolution, usually within 2 to 4 months. It is not unusual for tumors to appear unresponsive during the first 3 months of treatment and then show abrupt regression. In fact, several additional months of treatment may be beneficial, given recent evidence, obtained with ultrahigh-resolution optical coherence tomography (OCT), that residual tumor may be present for up to 3 months following clinical resolution. Subconjunctival/perilesional injection of interferon-α2b (3 million IU in 0.5 mL) can be given weekly in addition to, or as an alternative to, topical drops, especially if patient adherence is an issue. Subconjunctival interferon-α2b is associated with flulike symptoms in 10% of patients. Topical MMC 0.02% or 0.04%, because of its potential toxicity, is typically administered 4 times daily for 1 week, followed by a 1-week structured treatment interruption (drug holiday), for a maximum of 3 or 4 treatment cycles. If residual tumor persists, alternative treatment should be considered to avoid potential MMC toxicity. 5-Fluorouracil 1% may be given 4 times daily for 1 month, with a structured treatment interruption of at least several months if treatment is repeated; alternatively, it may be given 4 times daily for 1 week, followed by a 3-week structured treatment interruption, until resolution (maximum of 3 treatment cycles). Application of topical corticosteroids may help with the surface toxicity. Placement of punctal plugs reduces the likelihood of systemic absorption and helps prevent punctal stenosis.
Once a tumor has been managed, long-term, regular follow-up is essential because malignant conjunctival tumors can recur. Complete examination of the ocular surface and palpation of regional lymph nodes should be performed at each visit. Patients with malignant ocular surface tumors should be referred to a dermatologist for a complete skin evaluation.
Fraunfelder FT, Wingfield D. Management of intraepithelial conjunctival tumors and squamous cell carcinomas. Am J Ophthalmol. 1983;95(3):359–363.
Nanji AA, Moon CS, Galor A, Sein J, Oellers P, Karp CL. Surgical versus medical treatment of ocular surface squamous neoplasia: a comparison of recurrences and complications. Ophthalmology. 2014;121(5):994–1000.
Parrozzani R, Lazzarini D, Alemany-Rubio E, Urban F, Midena E. Topical 1% 5-fluorouracil in ocular surface squamous neoplasia: a long-term safety study. Br J Ophthalmol. 2011;95: 355–359.
Thomas BJ, Galor A, Nanji AA, et al. Ultra high-resolution anterior segment optical coherence tomography in the diagnosis and management of ocular surface squamous neoplasia. Ocul Surf. 2014;12(1):46–58.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.