Observation is generally the management of choice for most benign, asymptomatic tumors of the conjunctiva. Selected examples of lesions that can be observed without interventional treatment include pingueculum, dermolipoma, and nevus. External or slit lamp photographs are advisable to document all lesions and are critical to follow-up of the more suspicious lesions. Most patients are examined every 6 to 12 months looking for evidence of growth, malignant change, or secondary effects on normal surrounding tissues.

Incisional biopsy is reserved for extensive suspicious tumors that are symptomatic or suspected to be malignant. Examples include large squamous cell carcinoma, primary acquired melanosis, melanoma, and conjunctival invasion by sebaceous gland carcinoma. It should be understood that if such tumors occupy four to six clock hours or less on the bulbar conjunctiva, excisional biopsy is generally preferable to incisional biopsy. However, larger lesions can be approached by incisional wedge biopsy or punch biopsy. Further definitive therapy would then be planned based on the results of biopsy. Incisional biopsy is also appropriate for conditions that are ideally treated with topical or systemic chemotherapy, interferon, or monoclonal antibody (rituximab), or those treatable with radiotherapy. Such lesions include squamous cell carcinoma, conjunctival intraepithelial neoplasia, primary acquired melanosis, papillomatosis, lymphoid tumors, and metastatic tumors.

Primary excisional biopsy is appropriate for intermediate and small tumors that are symptomatic or suspected to be malignant. In such situations, excisional biopsy is preferred over incisional biopsy to avoid inadvertent tumor seeding. Examples of benign and malignant lesions that are ideally managed by excisional biopsy include symptomatic limbal dermoid, epibulbar osseous choristoma, steroid-resistant pyogenic granuloma, squamous cell carcinoma, and melanoma. When such lesions are located in the conjunctival fornix they can be completely excised and the conjunctiva reconstructed primarily with absorbable sutures, sometimes with fornix deepening sutures or symblepharon ring to prevent adhesions. If the defect cannot be closed primarily, then a transpositional flap or graft with mucous membrane or amnion can be inserted.

Most primary malignant tumors of the conjunctiva, such as squamous cell carcinoma and melanoma, arise in the interpalpebral area near the limbus, and the surgical technique for limbal tumors is different than that for forniceal tumors.^1,8 Limbal neoplasms have a propensity to invade through the corneal epithelium and sclera into the anterior chamber and also through the soft tissues into the orbit. Thus, it is often necessary to remove a thin lamella of underlying sclera to achieve tumor-free margins and to decrease the chance for tumor recurrence. In this regard, we use a partial lamellar sclerokeratoconjunctivectomy with primary closure for such tumors (Fig. 10-1). Because cells from these friable tumors can seed into adjacent tissues, a precise technique without touching the tumor (no-touch technique) is mandatory. Additionally, the surgery should be performed using microscopic technique and the operative field should be left dry so that cells adhere to the resected tissue. It is best to avoid wetting the field with balanced salt solution until after the tumor is completely removed to minimize seeding of cells.

The technique for resection of limbal tumors is shown in Figure 10-1. Using retrobulbar anesthesia and the operating microscope, the corneal epithelial component is approached first and the conjunctival component is dissected second, with the goal of excising the entire specimen completely in one piece. Absolute alcohol soaked on a Weck-cel sponge is gently applied to the corneal component. This causes epithelial cellular devitalization, drying of the tissue, and allows easier release of the tumor cells from the Bowman layer. A Beaver blade is used to microscopically scroll off the involved epithelium starting at the centralmost portion and working toward the limbus. An epitheliorhexis technique about 2 mm outside the corneal component is the preferred technique. Next, a pentagonal incision based at the limbus is made 3 to 4 mm outside the tumor margin. Radial incisions on either side of the limbal mass in an anteroposterior direction followed by posterior connector incision complete the perilesional cuts. The incision is carried through the underlying Tenon fascia until the sclera is exposed so that full-thickness conjunctiva and Tenon fascia are incorporated into the excisional biopsy. Cautery is applied to control bleeding. Using a 57 Beaver blade, the limbal portion is removed with the blade flat and dissecting the tumor plus 1 mm of underlying thin scleral bed. This is necessary only at the limbus directly underneath the tumor to ensure that the entire tumor with tumor-free margins is removed in one piece. The tumor itself is never handled as only normal surrounding tissue is manipulated (no-touch technique). The removed specimen is then placed flatly on a piece of thin cardboard from the surgical tray and then placed in fixative and submitted for histopathologic studies. This step prevents the specimen from folding and allows better assessment of the tumor margins histopathologically. The used instruments are then replaced with fresh instruments for subsequent steps, to avoid contamination of healthy tissue with possible tumor cells.

After excision of the specimen, cryotherapy is applied to the margins of the remaining bulbar conjunctiva. This is performed by freezing the surrounding bulbar conjunctiva as it is lifted away from the sclera using the cryoprobe. A double freeze-thaw technique is used to treat all conjunctival margins, but not the corneal margin. The corneal margin and tumor bed are treated with absolute alcohol wash on Weck-cel sponge with removal of residual episcleral and corneal debris using a blunt sweeping technique of the cells onto dry sponge. Bipolar cautery allows for later hemostasis. Avoid direct cryotherapy to the sclera.

Using clean instruments, the conjunctiva is mobilized for closure of the defect by loosening the intermuscular septum with Steven scissor spreading and creation of sliding or transpositional conjunctival flaps. Larger defects are closed with mucosal grafts. Closure is completed with interrupted absorbable 6-0 or 7-0 sutures. In some cases, grafts and flaps are closed with tissue glue. If the surgeon prefers, an area of bare sclera can be left near the limbus, but we prefer complete closure as this promotes better healing and allows for facility of further surgery if the patient should develop recurrence. The patient is treated with topical antibiotics and corticosteroids for 2 weeks and then followed at 3- to 6-month intervals.

In the management of conjunctival tumors, cryotherapy can be used as a supplemental treatment to excisional biopsy as described previously. In such cases it can eliminate microscopic tumor cells and prevent recurrence of malignant tumors such as squamous cell carcinoma and melanoma. It can also be used as a principal treatment for papilloma, primary acquired melanosis, and pagetoid invasion of sebaceous gland carcinoma. If cryotherapy can devitalize the malignant or potentially malignant cells in such instances, radical surgery such as orbital exenteration can often be delayed or avoided.

Recent evidence has revealed that topical eyedrops composed of mitomycin C, 5-fluorouracil, or interferon are effective in treating epithelial malignancies such as squamous cell carcinoma, primary acquired melanosis, and pagetoid invasion of sebaceous gland carcinoma.^{10,12,13,14,15,16,17,18,19,20,21,22} These agents are used most successfully for squamous cell carcinoma, especially after tumor recurrence following previous surgery. Mitomycin C is prescribed topically for four times daily for a 1-week period followed by a 1-week hiatus to allow the ocular surface to recover (Table 10-1). This cycle is repeated once again so that most patients receive a total of 2 weeks of the chemotherapy topically over a 1-month period. Both mitomycin C and 5-fluorouracil are more effective for squamous cell carcinoma than for primary acquired melanosis and pagetoid invasion of sebaceous gland carcinoma. Toxicities include dry eye findings, superficial punctate epitheliopathy, and punctal stenosis. Corneal melt, scleral melt, and cataract can develop if these agents are used with open conjunctival wounds or used excessively. Topical interferon can be effective for squamous epithelial malignancies and is less toxic to the surface epithelium. Interferon can be delivered in a subconjunctival injection and is likewise well tolerated but perhaps with more systemic malaise. Topical interferon is delivered as 1 million units per cc four times daily for several months (Table 10-1).

Two forms of radiotherapy are used for conjunctival tumors, namely external beam radiotherapy and custom-designed plaque radiotherapy. External beam radiotherapy to a total dose of 3,000 to 4,000 cGy is used to treat conjunctival lymphoma and metastatic carcinoma when such lesions are too large or diffuse to excise locally. Side effects of dry eye, punctate epithelial abnormalities, and cataract should be anticipated.

Custom-designed plaque radiotherapy^23,24,25 to a dose of 3,000 to 4,000 cGy can be used to treat conjunctival lymphoma or metastasis. A higher dose of 6,000 to 8,000 cGy can be used to treat the more radiation-resistant melanoma and squamous cell carcinoma. In general, plaque radiotherapy is reserved for those patients who have diffuse tumors that are incompletely resected and for those who display multiple recurrences. The two designs for conjunctival custom plaque radiotherapy include a conformer plaque technique placed on the eye for a 1-week period as an outpatient or a nonshielded plaque technique with the device sutured onto the episcleral tissue as an outpatient. Such treatment should be performed by experienced radiation oncologists and ocular oncologists.

Modified enucleation is a treatment option for primary malignant tumors of the conjunctiva that have invaded through the limbal tissues into the globe, producing secondary glaucoma. Such an occurrence is quite rare but can occasionally occur with squamous cell carcinoma and melanoma. The uncommon mucoepidermoid variant of squamous cell carcinoma of the conjunctiva has a greater tendency for such invasion. At the time of enucleation, it is necessary to remove the involved conjunctiva intact with the globe so as to avoid spreading tumor cells. Thus, the initial peritomy should begin at the limbus, but when the tumor is approached, the incision should proceed posteriorly from the limbus to surround the tumor-affected tissue by at least 3 to 4 mm. The tumor will remain adherent to the globe at the limbus. Occasionally, a suture is used through the surrounding conjunctiva into the episclera to secure the tumor to the globe so that it will not be displaced during subsequent manipulation. The remaining steps of enucleation are gently performed and the globe is removed with tumor adherent after cutting the optic nerve from the nasal side. The margins of the remaining, presumed unaffected conjunctiva are treated with double freeze-thaw cryotherapy. Often this surgical technique leaves the patient with a limited amount of residual unaffected conjunctiva for closure. In these instances, a mucous membrane graft, amniotic membrane graft, dermis fat graft, or dermis graft may be necessary for adequate closure and to provide fornices for a prosthesis. In some instances, a simple horizontal inferior forniceal conjunctival incision from canthus to canthus may suffice, as long as the conformer is constantly worn as a template so the new conjunctival fornix grows deep and around this structure.

Orbital exenteration is probably the treatment of choice for primary malignant conjunctival tumors that have invaded the orbit or that exhibit complete involvement of the conjunctiva.^1,9,25,26 Either an eyelid-removing or eyelid-sparing exenteration is used, depending on the extent of eyelid involvement. The eyelid-sparing technique is preferred in that the patients have better cosmetic appearance and heal within 2 or 3 weeks. Specifically, if the anterior lamella of the eyelid is uninvolved with tumor, an eyelid-sparing (eyelid-splitting) exenteration may be accomplished.

Mucous membrane grafts are occasionally necessary to replace vital conjunctival tissue after removal of extensive conjunctival tumors. The best donor sites include the forniceal conjunctiva of the ipsilateral or contralateral eye and buccal mucosa from the posterior aspect of the lower lip or lateral aspect of the mouth. Such grafts are usually removed by a freehand technique, fashioned to fit the defect, and secured into place with cardinal and running absorbable 6-0 or 7-0 sutures. Currently, in most instances, we use a donor amniotic membrane graft to replace lost conjunctiva.^10,11 The tissue is delivered frozen and must be defrosted for 20 minutes. The fine, transparent material is carefully peeled off its cardboard surface, laid basement membrane side up, and sutured into place with absorbable sutures or glued with tissue glue. Topical antibiotic and steroid ointments are applied following all conjunctival grafting procedures.

It is important that the surgeon use a minimal manipulation technique for tumor resection. For graft harvest and placement, the surgeon should always use clean, sterile instruments at both the donor and the recipient sites. Free tumor cells can rest on instrument tips and later implant and grow in previously uninvolved areas if such precautions are not taken.