Topical Chemotherapy for Ocular Surface Squamous Neoplasia: A Review of Adverse Effects and Their Clinical Management

Abstract

Topical chemotherapy is increasingly used to treat ocular surface tumors as a primary therapy and an adjuvant treatment after surgical excision. The most employed topical agents include mitomycin C (MMC), 5-fluorouracil (5-FU), and interferon alpha-2b (IFNα2b), each with distinct mechanisms of action, efficacy profiles, and toxicity risks. Although these agents offer effective tumor control and allow for a non-invasive approach in many cases, ocular surface complications requiring medical or surgical management can occur. This summarizes the adverse effect and outilines practical strategies for their prevention and treatment. MMC is the most potent agent but also the most toxic, with reported complications such as limbal stem cell deficiency, punctal stenosis, and persistent epithelial defects. 5-FU demonstrates a more favorable safety profile, although rare cases of corneal ulceration have been described. IFNα2b is well tolerated and associated primarily with mild, reversible reactions. The choice of the proper agent should be tailored according to patient's clinical presentation, ocular surface status, and ability to adhere to therapy and follow-up. Timely recognition and management of complications are essential to minimize long-term sequelae. Reliance on compounded formulations highlights the need for stable, standardized, and commercially available topical agents specifically designed for ocular use to ensure safety, reproducibility, and global accessibility.

Keywords: 5-fluorouracil; Ocular surface squamous neoplasia; interferon alpha-2b; mitomycin C; topical chemotherapy.

Figure 1. Clinical spectrum of ocular surface squamous neoplasia (OSSN). The image illustrates the morphological variability of OSSN, ranging from mild conjunctival intraepithelial neoplasia to fully invasive squamous cell carcinoma. Lesions may appear as gelatinous, leukoplakic, papilliform, or nodular, and can affect both the conjunctiva and cornea, with or without limbal involvement. All images were acquired using the SLITLAMP MICROSCOPE 700GL (Takagi Seiko Co., Ltd., Japan) integrated with the EyeGest Push.Print TD-10 software (version 6.0.10; Frastema Ophthalmics S.r.l., Varese, Italy) during routine clinical practice. (a) Early conjunctival intraepithelial neoplasia with mild epithelial thickening and minimal vascular changes. (b) Nodular, opaque lesion with feeder vessels, consistent with invasive squamous cell carcinoma. (c) Papilliform lesion involving the bulbar conjunctiva, suggestive of moderate-grade OSSN. (d) Leukoplakic lesion with limbal and corneal involvement, indicative of high-grade dysplasia. (e) Gelatinous, vascularized lesion of the inferior conjunctiva, consistent with low-grade OSSN. (f) Mixed nodular and gelatinous lesion with diffuse conjunctival and limbal involvement, suspicious for invasive carcinoma

Figure 1. Clinical spectrum of ocular surface squamous neoplasia (OSSN). The image illustrates the morphological variability of OSSN, ranging from mild conjunctival intraepithelial neoplasia to fully invasive squamous cell carcinoma. Lesions may appear as gelatinous, leukoplakic, papilliform, or nodular, and can affect both the conjunctiva and cornea, with or without limbal involvement. All images were acquired using the SLITLAMP MICROSCOPE 700GL (Takagi Seiko Co., Ltd., Japan) integrated with the EyeGest Push.Print TD-10 software (version 6.0.10; Frastema Ophthalmics S.r.l., Varese, Italy) during routine clinical practice. (a) Early conjunctival intraepithelial neoplasia with mild epithelial thickening and minimal vascular changes. (b) Nodular, opaque lesion with feeder vessels, consistent with invasive squamous cell carcinoma. (c) Papilliform lesion involving the bulbar conjunctiva, suggestive of moderate-grade OSSN. (d) Leukoplakic lesion with limbal and corneal involvement, indicative of high-grade dysplasia. (e) Gelatinous, vascularized lesion of the inferior conjunctiva, consistent with low-grade OSSN. (f) Mixed nodular and gelatinous lesion with diffuse conjunctival and limbal involvement, suspicious for invasive carcinoma

Figure 2. Clinical appearance of primary acquired melanosis (PAM) with cytological atypia. The lesion presents as flat, irregular brown pigmentation involving the bulbar conjunctiva and limbus. PAM with atypia is considered a precursor to conjunctival melanoma and requires close clinical monitoring and, in selected cases, surgical excision or adjunctive therapy. All images were acquired using the SLITLAMP MICROSCOPE 700GL (Takagi Seiko Co., Ltd., Japan) integrated with the EyeGest Push.Print TD-10 software (version 6.0.10; Frastema Ophthalmics S.r.l., Varese, Italy) during routine clinical practice

Figure 3. Corneal complications related to topical 5-fluorouracil therapy. All images were acquired using the SLITLAMP MICROSCOPE 700GL (Takagi Seiko Co., Ltd., Japan) integrated with the EyeGest Push.Print TD-10 software (version 6.0.10; Frastema Ophthalmics S.r.l., Varese, Italy) during routine clinical practice. (a) Delayed epithelial defect after treatment suspension in a patient with paralytic ectropion. (b) Epithelial defect induced by treatment, necessitating temporary discontinuation for complete resolution. (c) Severe corneal ulceration with impending perforation in a patient with extreme tear deficiency following dacryoadenectomy