Wide excision, cryotherapy, amniotic membrane transplant can be used to treat ocular surface squamous neoplasia

Thomas John

Ocular surface squamous neoplasia was first described by Lee and Hirst in 1995 as an umbrella term that encompasses both intraepithelial and invasive squamous cell carcinoma — namely, carcinoma in situ, intraepithelial neoplasia, and invasive squamous cell carcinoma of the conjunctiva and cornea. It is the most common nonpigmented ocular surface tumor.

Ocular surface squamous neoplasia (OSSN) incidence ranges from 0.02 to 3.5 cases per 100,000 people and varies geographically, with a higher frequency near the equator. It is usually a slow-growing tumor that rarely metastasizes, but it is capable of causing significant local tissue destruction. Bilateral OSSN occurrence is extremely rare. The disease appears to be associated with solar radiation (ultraviolet light) exposure, HIV and human papilloma virus. Symptoms include redness, itching, foreign body sensation, pain and an eye growth. Usually found at the limbus, growths may also be located on the palpebral or forniceal conjunctivae. The appearance may be velvety, papilliform, gelatinous, leukoplakic, nodular, diffuse or a combination of these characteristics.

Medical treatments for OSSN include mitomycin C, 5-fluorouracil and interferon alpha-2b, while surgical modalities include conjunctival tumor excision with wide margins, absolute alcohol epitheliectomy of involved cornea, and cryotherapy in a double-freeze/slow-thaw cycle to the limbus and conjunctival margins. Postoperative recurrences range from 5% to 33% in negative margins to about 56% in positive surgical margins.

In this column, Drs. Hodson and Karp discuss their surgical technique of tumor excision with cryotherapy and amniotic membrane transplantation for the treatment of OSSN.

Thomas John, MD
OSN Surgical Maneuvers Editor

A thorough slit-lamp examination must be performed preoperatively in both eyes to document the presence of disease. Rose bengal staining can be used to delineate the margins of the lesion, and an outline of the tumor should be sketched for use in the operating room.

Operative technique

Local anesthesia is adequate for this procedure and includes a peribulbar or retrobulbar injection of a 1:1 mixture of 2% lidocaine and 0.75% bupivacaine and monitored anesthesia care. Pupil dilation allows for better visualization of the corneal component of the tumor and is achieved with 2.5% phenylephrine ophthalmic solution. Using the preoperative sketch and rose bengal staining to identify tumor borders, the tumor is outlined with a marking pen using 4-mm to 6-mm margins (Figure 1).

The conjunctival portion of the tumor is excised using Westcott scissors. Care is taken to avoid touching the tumor with any surgical instruments, as this can lead to seeding of tumor cells. During excision, it is important to only spread under the marked margins and avoid spreading directly underneath the tumor (Figure 2). If the tumor is adherent, a partial-thickness sclerectomy should be performed using a 75 blade and forceps. When excising the limbal portion of the tumor, pressure is applied to the scissors so that they are flush with the sclera and cut underneath the tumor. The specimen is marked with sutures in the proper orientation and then transferred to a piece of paper marked with pencil, as pen will dissolve in formalin (Figure 3). The specimen is allowed to dry before being placed in 10% formalin and sent to pathology.

Figure 1. Tumor outlined with marking pen with 4-mm to 6-mm margins.

Figure 2. Conjunctival tumor being excised using Westcott scissors. Images: Hodson KL, Karp CL and John T

Figure 3. Tumor placed in proper orientation on marked cardboard.

Figure 4. Absolute dehydrated alcohol applied to corneal surface for 60 seconds.

Figure 5. Application of cryotherapy to conjunctival margins.

Figure 6. Amniotic membrane placed over defect with stromal side down.

If there is corneal involvement, a Weck-Cel spear (Medtronic Ophthalmics) soaked in dehydrated alcohol (American Regent) is applied to the affected corneal surface for 60 seconds to devitalize the epithelial cells (Figure 4). The alcohol is irrigated away with copious balanced salt solution (BSS, Alcon). A beaver blade is used to “scroll” the corneal epithelium to the limbus and onto a Weck-Cel to be sent for histopathologic analysis. It is important to avoid penetration of Bowman’s layer in this step.

After the conjunctival and corneal portions of the tumor are removed, the limbus and scleral bed are scraped with a 64 blade. Wet-field cautery is used for hemostasis. Cryotherapy is then applied to the limbus and conjunctival margins in a double-freeze/slow-thaw cycle (Figure 5).

Fresh instruments are used in the closure of the defect to avoid any possible seeding of tumor cells. Because wide excisions are preferred, we generally use amniotic membrane transplantation after excision of these tumors. The amniotic membrane is thawed, peeled from the nitrocellulose paper, and then placed on the ocular surface with the stromal side facing down (Figure 6). Tissue adhesive (Evicel, Omrix Biopharmaceuticals) is applied underneath the membrane. We prefer to apply the two components of the glue separately, but they can be applied together. We use a 30-gauge cannula to first apply the fibrinogen and then the fibrin component, using a muscle hook to smooth the membrane onto the underlying sclera. Excess membrane and glue are trimmed off the ocular surface, and one drop each of fibrinogen and thrombin is applied to the exposed cornea to provide a temporary covering, much like a bandage contact lens. Ophthalmic antibiotic ointment is placed on the eye, and the eye is patched and shielded for the first 24 hours after surgery.

Postoperative treatment

Postoperatively, patients use topical antibiotics four times per day for 1 week and topical steroids four times per day for 1 week, followed by a 3-week taper of the steroid. If margins are found to be positive for OSSN on histopathologic exam, either topical chemotherapy or further surgery may be necessary.

References:

• Lee GA, Hirst LW. Ocular surface squamous neoplasia. Surv Ophthalmol. 1995;39(6):429-450.
• Nelson KD, McSoley JJ. Clinical findings and management of conjunctival intraepithelial neoplasia. Optometry. 2011;82(1):15-21.
• Scott IU, Karp CL, Nuovo GJ. Human papillomavirus 16 and 18 expression in conjunctival intraepithelial neoplasia. Ophthalmology. 2002;109(3):542-547.
• Shields CL, Demirci H, Karatza E, Shields JA. Clinical survey of 1643 melanocytic and nonmelanocytic conjunctival tumors. Ophthalmology. 2004;111(9):1747-1754.
• Sturges A, Butt AL, Lai JE, Chodosh J. Topical interferon or surgical excision for the management of primary ocular surface squamous neoplasia. Ophthalmology. 2008;115(8):1297-1302.

• Thomas John, MD, is a clinical associate professor at Loyola University at Chicago and is in private practice in Oak Brook, Tinley Park and Oak Lawn, Ill. He can be reached at 708-429-2223; fax: 708-429-2226; e-mail: tjcornea@gmail.com.
• Kelly L. Hodson, MD, and Carol L. Karp, MD, can be reached at Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th St., Miami, FL 33136; e-mail:ckarp@med.miami.edu, kellylaraann@gmail.com.
• Disclosures: Dr. John has no financial interest in any aspect of this article. Drs. Hodson and Karp have no financial interest in any materials or methods described within this article. Financial Support: Supported in part by an unrestricted grant from Research to Prevent Blindness.