Ocular Surface Squamous Neoplasia Treatment: Eye-Drop Chemotherapy or Surgery

Ocular surface squamous neoplasia — usually shortened to OSSN — is abnormal growth of the thin layer of cells that covers the white of the eye and the cornea, ranging from precancer to invasive squamous cell carcinoma. The encouraging news is that OSSN is usually curable, and modern ocular surface squamous neoplasia treatment with chemotherapy eye drops means that many patients never need an operation.

For other surface growths, see conjunctival tumors.

What is ocular surface squamous neoplasia?

The surface of the eye is covered by a thin sheet of squamous cells (the epithelium) resting on a basement membrane. OSSN is classified by how deep the abnormal cells go:

• Conjunctival intraepithelial neoplasia (CIN) — abnormal cells confined to the epithelium, graded from mild (CIN I) to near full-thickness (CIN III, or carcinoma in situ); on the cornea it is called corneal epithelial dysplasia.
• Invasive squamous cell carcinoma (SCC) — the cells have broken through the basement membrane and can invade the cornea, the sclera, the inside of the eye or the orbit, and occasionally the lymph nodes near the ear or in the neck.

OSSN is the most common non-pigmented malignant tumor of the ocular surface. In a Wills Eye series of 5,002 conjunctival tumors it accounted for 14%, and invasive SCC for 9%. The AJCC system stages these tumors from Tis (carcinoma in situ) to T4 (see eye cancer stages).

Who gets OSSN?

In Western countries OSSN typically affects fair-skinned men in their 60s and 70s with long sun exposure; in parts of Africa and Asia it appears at younger ages and is often more aggressive. It is more common within about 30° of the equator. The main risk factors are:

• Ultraviolet light. Spending 2–4 hours a day in direct daylight, or working outdoors, was linked with about 1.7 times the odds of OSSN.
• HIV. People with HIV had about 6 times the odds; in the United States about half of patients with OSSN under 50 were HIV-positive, so testing is commonly recommended for younger patients.
• Human papillomavirus (HPV). HPV was linked with about 2.6 times the odds (types 16 and 18 in particular), but OSSN is not passed on through everyday contact.
• Others: fair skin, older age, male sex, smoking, immune suppression (for example after an organ transplant) and xeroderma pigmentosum, an inherited extreme sensitivity to sunlight.

What does OSSN look like?

OSSN may cause redness, irritation or a foreign-body feeling, or no symptoms at all; vision blurs if it spreads over the cornea. Typical signs include:

• a gray-white, jelly-like or slightly raised growth at the limbus — the border between the cornea and the white of the eye — where about 95% of CIN begins;
• a white, crusty plaque of keratin (leukoplakia) or a bumpy, papilloma-like surface;
• looped "hairpin" or corkscrew-shaped blood vessels;
• a translucent gray, frosted sheet on the cornea with a finger-like edge.

A raised or nodular shape, large feeder vessels and fixation to the eye suggest invasion. In people with darker skin OSSN can be pigmented and mimic conjunctival melanoma, and it is often mistaken for a pterygium — see pterygium or tumor?

How is OSSN diagnosed?

• Slit-lamp examination and photography, sometimes with dyes such as lissamine green or rose bengal that stain the abnormal cells.
• High-resolution anterior segment OCT, a non-contact "optical biopsy", shows OSSN as a thickened, bright epithelium with an abrupt edge (a thickness above about 140 µm is suspicious), with a reported sensitivity of 94–100% and specificity of 100%. It also reveals disease that cannot yet be seen: in one study, 17% of lesions that looked resolved still had OSSN on the scan.
• Impression cytology collects surface cells on filter paper but cannot show invasion.
• Ultrasound biomicroscopy measures the depth of suspected invasion.
• Biopsy: small lesions are removed whole; large, diffuse or possibly invasive lesions are sampled first.

Many specialist centers now start drops for typical OSSN based on its appearance and OCT alone, using OCT to decide when to stop; a biopsy is still needed when invasion is suspected or the diagnosis is uncertain (see eye tumor diagnosis).

What are the options for ocular surface squamous neoplasia treatment?

There are two main routes — chemotherapy eye drops and surgery — often combined. The choice depends on the lesion's size and position, whether invasion is suspected, your general health, and how practical drops and follow-up are for you.

Eye-drop chemotherapy

Topical chemotherapy treats the whole ocular surface, including abnormal cells not yet visible, without a surgical scar.

In a 2025 comparison of 116 eyes, complete regression was similar with 5-FU (83%) and interferon (80%), and 5-FU caused fewer side effects at a far lower cost.

Pressing on the inner corner of the eyelids after each drop reduces drainage into the nose, and punctal plugs are often advised with mitomycin C. Irritation is managed with lubricants, short steroid courses or a pause; the drops act locally and do not cause hair loss.

Surgery: no-touch excision with cryotherapy

Surgery removes the lesion in one session and provides tissue to confirm the diagnosis and check the margins. The standard "no-touch" technique was described by Shields and colleagues in 1997:

1. Under the operating microscope, the tumor is removed with a 3–4 mm margin of normal-looking conjunctiva, without being grasped.
2. Any corneal part is loosened with absolute alcohol for 30–60 seconds and scraped away, sparing the deeper Bowman layer.
3. If the tumor is stuck to the sclera, a thin superficial layer is removed with it.
4. The edges and base are frozen with a double freeze–slow thaw cycle (cryotherapy).
5. The wound is closed directly or with amniotic membrane or a conjunctival graft; the specimen is laid flat and oriented for the pathologist.

Surgery avoids months of drops but can leave scarring, dry eye or damage to the stem cells at the edge of the cornea (limbal stem cell deficiency).

Drops or surgery?

A 2022 meta-analysis (318 patients) found no significant difference between topical treatment and surgery in complete resolution or recurrence, with overall recurrence around 10%; dry eye was reported most often after surgery (59%). The authors rated the evidence as low certainty, because the studies were small and retrospective.

In practice, drops are often favored for large, diffuse or multifocal lesions, mainly corneal disease, recurrences and patients unfit for surgery; surgery for small, well-defined lesions, suspected invasion, lesions that do not respond to drops, and when drops or follow-up would be difficult. Many patients receive both: drops to shrink a large lesion before surgery, or after it when the margins are not clear.

How often does OSSN come back?

• After surgery: about 10% at 1 year and 17–21% at 5 years in large series. Older series reported up to 56% when tumor remained at the margins, versus 0–21% in recent series that add cryotherapy. Even with clear margins, up to one-third recurred within 10 years in an older series.
• After drops: 10–14% with 5-FU, 0–4% with interferon and 0–20% with mitomycin C.

Recurrent tumors may behave more aggressively, but most can be treated again with drops, a further excision or both; radiotherapy is rarely needed.

What happens in advanced disease?

Neglected or deeply invasive carcinoma can grow into the eye or the orbit and may then require removal of the eye, plaque radiotherapy in selected cases, or orbital exenteration, sometimes with radiotherapy. In a series of 38 patients with advanced (T3–T4) conjunctival SCC, recurrence was 52% after local excision and 20% after exenteration, and 13% died of the cancer — figures that apply to advanced disease only.

Spread to lymph nodes is uncommon (3% in a staging series of 136 eyes). When it occurs, treatment is planned with head and neck surgeons, radiation oncologists and medical oncologists; immunotherapy used for advanced skin squamous cell carcinoma has been reported in a few such patients.

What does follow-up involve?

Recurrences can appear more than 5 years after treatment, so follow-up is long-term: typically every 3–4 months in the first year, every 6 months until year 5, then yearly, although intervals vary. Visits include slit-lamp photographs and, where available, high-resolution OCT. Wear UV-blocking sunglasses and a brimmed hat outdoors, avoid smoking and, where recommended, complete HIV testing.

Getting a specialist opinion in Antalya

Prof. Türkoğlu assesses the lesion, interprets the imaging and explains whether drops, surgery or both suit your situation; she performs the excision when surgery is chosen, and treatment for advanced disease is coordinated with the relevant specialist teams. From abroad, start with a remote second opinion, sending photographs, OCT scans, pathology reports and details of any drops used. If travel is needed, see international patients.