Purpose: The purpose of this study was to report the management of chemoimmunotherapy-resistant ocular surface squamous neoplasia (OSSN) with iodine-125 (I-125) brachytherapy.

Methods: A 36-year-old man presented to the clinic with biopsy-proven OSSN that covered ∼70% of the corneal surface and extended to the 6 o'clock position of the inferior limbus of the OS. The visual acuity was 20/20 in the OD and 20/40 in the affected OS. He was treated with topical interferon alpha-2b 1 MIU/mL (4 times daily [QID] for 6 weeks) and then 4 cycles of topical 5-fluorouracil 1% (QID, 1 week on, 3 weeks off) with an incomplete response. He switched to topical mitomycin C 0.04% (QID, 1 week on, 2 weeks off) for 2 cycles and received a subconjunctival injection 25 mg (0.5 mL of a 50-mg/mL solution) of 5-fluorouracil. The tumor persisted. The patient was ultimately cured with placement of an 18-mm I-125 brachytherapy plaque for 97 hours (50 Gy).

Results: Because of extensive corneal involvement and risks associated with surgery, an 18-mm I-125 brachytherapy plaque was placed over the cornea and limbus. The treatment led to full resolution of the tumor within 1 month of treatment and recovery of 20/20 vision in the affected eye. Thirty-two months after treatment, the patient developed a visually significant posterior subcapsular cataract OS and underwent successful phacoemulsification surgery, returning to 20/20 vision. He has remained tumor-free for over 55 months.

Conclusions: This case highlights the efficacy and safety of I-125 brachytherapy as an alternative for intraepithelial OSSN unresponsive to conventional chemoimmunotherapy, particularly when extensive surgical excision poses significant risks.