Discern best surgical, medical therapy for ocular surface squamous neoplasia

Reviewed by Carol L. Karp, MD

Miami-Though surgical or medical therapies are available to surgeons faced with treating ocular surface squamous neoplasia (OSSN), determining the appropriate therapy may not be so cut and dried.

Excision with cryotherapy is successful but can result in limbal stem cell deficiency when tumors are large, and lesion recurrences can occur even with negative margins.

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Chemotherapy options work well but depend heavily on patient compliance with drop instillation.

“Sometimes these cases are easy to resolve and sometimes not,” said Carol L. Karp, MD, professor of ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine. “Be ready to combine treatment options to cure the cancer.”

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Dr. Karp described a typical case of a 67-year-old woman who presented with a conjunctival and corneal lesion, which developed in the exposure zone. It had classic features that included leukoplakia, a mobile gelatinous limbal component, and an opalescent corneal lesion.

“This is a typical OSSN,” she explained, adding that OSSN is the umbrella terminology for conjunctival and corneal dysplasia up to but not including squamous cell carcinoma.

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OSSN risk factors include ultraviolet light exposure in most cases, human papilloma virus, and immune deficiency, such as HIV.

OCT in ocular surface oncology

OCT in ocular surface oncology

A new and exciting development in the management of OSSN is the use of high-resolution optical coherence tomography (OCT) to image tumors before, during, and after treatment both to confirm diagnoses and ensure tumor eradication, according to Dr. Karp.

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She demonstrated in a patient with OSSN that OCT was able to clearly differentiate the normal tissue from tumor. In normal areas, the epithelium is thin and dark.

In contrast, for OSSN, the epithelium is thickened and hyper-reflective with a non-abrupt transition between normal and tumor. Imaging may also show shadowing due to leukoplakia. All of these are the classic OSSN findings.

In addition to helping with the diagnosis of OSSN, OCT can help to monitor the tumor as it is treated with medication, to ensure the tumor is gone before terminating treatment.

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Treatment options for OSSN

The traditional approach is surgery, which is covered by insurance, and provides rapid resolution of OSSN.

However, there are a couple of limitations, in that obtaining clear surgical margins is not a given and extensive excisions can result in limbal stem cell deficiency, scarring, and dry eye.

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When performing surgery, Dr. Karp performs a wide excision with 4-mm margins, cryotherapy to the margins, and amniotic membrane transplantation.

A second option is medical therapy, the advantage of which is that the entire ocular surface and all subclinical and microscopic disease are treated. Interferon-alpha-2b, 5-fluorouracil (5-FU), and mitomycin C (MMC) are the chemotherapeutic agents from which surgeons can choose. Disadvantages are the amount of time involved in chemotherapy and patient compliance.

In addition, 5-FU and MMC cause ocular surface toxicity, Dr. Karp pointed out. All the eye drops are off label use of approved medications and often require out-of-pocket coverage.

Related factors

When considering the treatment approach to OSSN, she looks at the factors involved in each case.

“If the primary lesion is smaller than three or four clock hours, surgery or medical treatment works well. If the lesion is large and annular, I strongly prefer medical treatment. In most recurrent cases, I also prefer medical treatment. However, sometimes we often have to combine therapies when tumors become stubborn,” she stated.

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Dr. Karp prefers to use topical interferon when treating OSSN medically.

“I use 1 million international units (IU) per milliliter four times daily generally for 4 months,” she said. “I also use interferon injections, which is generally dosed at 3 million IU weekly until the tumor resolves.”

Advantages are that interferon drops are gentle and well tolerated on the ocular surface in addition to the drug’s very high success rate.

Downsides include the cost, $240 monthly. Success also requires patient adherence to therapy and refrigeration, she pointed out.

The drops must be compounded. Injections are commercially available, often therefore covered by insurance, and ensure compliance. They do give a flulike syndrome with each injection, which can be treated with acetaminophen.

In patients for whom cost, compliance, and refrigeration might be problematic because of jobs or lifestyle, Dr. Karp’s second favorite medical therapy is 5-FU 1% because of the minimal dosing requirement, i.e., one drop four times daily for 1 week followed by a 3-week drug holiday usually for four cycles.

Although also compounded, no refrigeration is required and the cost is minimal at $35 monthly. Generally four cycles are needed.

“The success rate is quite good-82% to 100%,” she said. “However, the treatment can be painful and does require compliance.”

Ocular surface toxicity

Topical MMC 0.04% or 0.02% is her least favorite medicine because of the resultant ocular surface toxicity. The dose is one drop four times daily for 1 week followed by a 2- to 3-week drug holiday. Generally, three to four cycles are needed to achieve the desired effect. The overall success rates range from 85% to 100%. Disadvantages are the high cost, toxicity, and the need for insertion of punctal plugs, patient compliance, compounding, and refrigeration.

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When attempting a make a definitive decision about the treatment course for OSSN, Dr. Karp noted that no head-to-head studies have been done to compare the efficacy of 5-FU, MMC, and interferon.

“We have looked at interferon versus surgery and found no significant difference between topical interferon and surgical excision in terms of recurrences of OSSN and complications,” she said. “In patients with a large multifocal lesion, surgery will cause significant limbal stem cell deficiency and medication is better.

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In patients with multiple recurrences, medication may be preferred. If patient compliance is an issue and they will not instill drops, surgery is better. If the diagnosis is in doubt, surgery will be both therapeutic and diagnostic, Dr. Karp noted.

“If medical therapy is selected, and patients can afford the medication, interferon is better,” she said. “If they cannot, 5-FU or surgery (if covered by insurance) should be considered.”

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Carol L. Karp, MD

E: [email protected]

Dr. Karp has no financial interest in the subject matter.