Ocular Surface Squamous Neoplasia

Ocular surface squamous neoplasia (OSSN) is a spectrum of squamous epithelial dysplasia of the conjunctiva and cornea: from conjunctival intraepithelial neoplasia (CIN) of mild to severe grade, to carcinoma in situ, to invasive squamous cell carcinoma.

• Most common non-pigmented ocular surface tumour.
• Risk factors: ultraviolet light exposure (equatorial regions), HIV infection (young adults in sub-Saharan Africa, with aggressive disease), human papillomavirus (types 16 and 18), smoking, fair skin, xeroderma pigmentosum, immunosuppression, chronic inflammation, and petroleum exposure.
• Usually arises at the limbus in the interpalpebral fissure (nasal and temporal), where stem cells are concentrated.
• Invasive SCC can invade the globe or orbit, and metastasise to nodes (rare, about 1 to 2 percent).

• Gelatinous, leukoplakic (white keratinised plaque), papilliform or nodular mass at the limbus or on the conjunctiva, with feeder vessels, surface keratin, and sometimes corneal extension giving a grey, opaque, "sandy" cornea.
• Chronic redness, irritation or foreign body sensation, or an asymptomatic lesion, which can mimic pterygium or pinguecula.
• Pigmented variant in dark skinned individuals.
• Invasive: fixed lesion, scleral or intraocular invasion (raised pressure, glaucoma), orbital extension, lymphadenopathy.
• Young patients with OSSN should be tested for HIV.

• Slit lamp examination with fluorescein or rose bengal or lissamine green staining (stains the lesion), plus photography.
• High resolution anterior segment optical coherence tomography: thickened hyperreflective epithelium with abrupt transition to normal epithelium (differentiates OSSN from pterygium).
• Impression cytology for non-invasive diagnosis and follow up.
• Excisional biopsy with histology for definitive diagnosis, grading and margin assessment.
• HIV testing in all young patients; ultrasound biomicroscopy and MRI for suspected deep invasion; examine regional nodes.

• Topical chemotherapy (for non-invasive disease, including large lesions and positive margins), with about 80 to 90 percent success:
  • Interferon alpha-2b 1 million IU/mL four times daily for 4 to 12 weeks (until a month beyond resolution).
  • 5-fluorouracil 1 percent four times daily for 4 days on and 24 days off, for 3 to 4 cycles.
  • Mitomycin C 0.02 to 0.04 percent four times daily for 1 week on and 1 week off for 2 to 4 cycles. Punctal occlusion, toxicity monitoring (pain, punctal stenosis, limbal stem cell deficiency).
  • Check at 4 weeks; continue until resolved.
• Surgical excision (no touch technique) with 2 to 4 mm margins, cryotherapy to conjunctival margins, alcohol epitheliectomy for corneal extension, and amniotic membrane or conjunctival autograft; histology to confirm clear margins.
• Combined excision with adjuvant interferon, 5-fluorouracil or cryotherapy for recurrence reduction (recurrence after excision about 5 to 50 percent, higher with positive margins).
• Intraocular or orbital invasion: enucleation or exenteration; for orbital disease radiotherapy.
• Brachytherapy or radiotherapy for selected lesions.
• HIV-positive patients: start and optimise antiretroviral therapy; monitor closely for recurrence.
• Follow up every 3 months in year one, then every 6 months for 2 years, then annually, with sun protection and smoking cessation.