Unilateral Conjunctival Disease

In a patient with unilateral ocular surface disease, preoperative planning should include careful evaluation of the status of the conjunctiva in both eyes. A patient with unilateral disease limited to the conjunctiva does not require limbal stem cell transplantation. Conditions in this category would include primary and recurrent pterygium and unilateral focal conjunctival tumors, such as squamous cell carcinoma or conjunctival intraepithelial neoplasia (CIN). These conditions may benefit from a conjunctival autograft from the same eye or from the contralateral eye. The autograft can be harvested from the superior or inferior bulbar conjunctiva, taking into consideration that symblepharon formation remains a slightly higher risk for inferior conjunctival grafts. Limbal tissue is not needed when harvesting an autologous conjunctival graft. Figure 54.1 provides a flow diagram for surgical treatment options.

If conjunctiva cannot be harvested from the same or contralateral eye, amniotic membrane can serve as an adjunct to close the conjunctival defect. Amniotic membrane by itself carries slightly higher risk for recurrence, compared to conjunctival grafts, but can be used when viable conjunctiva is not available.1,2 Conjunctival autograft or amniotic membrane fixation is performed with either suture or fibrin glue and requires local immunosuppression with corticosteroids. Systemic immunosuppression is not required with these techniques.

Unilateral Limbal Disease

When the ocular surface disease is unilateral and involves limbal tissue, as well as conjunctiva, assessment of the extent of limbal involvement in the affected eye is paramount to the clinical management decision. In this setting, the ophthalmologist should carefully assess the contralateral eye to determine if early limbal disease has occurred. An example of unilateral limbal insult would include a chemical injury or severe contact lens-induced stem cell damage to the ocular surface. If the disease involvement is localized to a small area (less than 50%), a sequential conjunctival epitheliectomy can be performed. If the area is more extensive, a conjunctival/limbal autograft (CLAU) can be taken from the contralateral eye. Options might include ex vivo stem cell expansion with either limbal autograft or allograft tissue. These techniques call for local immunosuppression with corticosteroids and/or cyclosporine, or in the case of the living-related or cadaveric donor tissue, systemic immunosuppression is required as well.

Unilateral Combined Conjunctival and Limbal Disease

When the ocular surface disease is unilateral, but involves both conjunctiva and limbal tissue, the extent of damage is an important preoperative consideration. Conjunctival inflammation must be controlled prior to consideration of any surgical techniques. The prognosis in this situation remains more guarded when compared to either unilateral conjunctival or limbal ocular surface disease alone. Clinical situations would include more extensive chemical ocular surface injury such as a severe alkaline burn. The same treatment strategies can be implemented as with limbal disease alone and include stem cell transplantation techniques such as CLAU or the modified Cincinnati procedure. In cases where the conjunctival and limbal stem cell damage is extensive, with severe ocular surface failure and broad symblepharon, it is felt that the ‘modified Cincinnati procedure’ is a more appropriate treatment option over CLAU alone. The ‘modified Cincinnati procedure’ utilizes lr-CLAL segments to the superior and inferior limbus in combination with cadaveric KLAL along the nasal and temporal limbus. Alternatively, a keratoprosthesis could be used in this setting, especially in the elderly patient with multiple systemic co-morbidities who are poor candidates for systemic immunosuppression.

Bilateral Limbal Disease with Normal Conjunctiva

When the ocular surface disease is bilateral and involves significant portions of the limbus but spares the conjunctiva, a limbal stem cell procedure will ultimately be needed for ocular surface restoration. Accurate assessment of the extent of limbal involvement is crucial to surgical planning. Congenital stem cell deficiencies, such as aniridia or bilateral severe contact lens-induced deficiency are examples of this disease situation. When limbal disease is partial (less than 50%), sequential conjunctival epitheliectomy can be an effective treatment strategy. When the limbal involvement is greater than 50%, the treatment options are limbal stem cell transplantation with a keratolimbal allograft (KLAL) or living-related conjunctival limbal allograft (lr-CLAL) The KLAL procedure provides an abundant source of stem cells and utilizes readily available cadaveric tissue. The lr-CLAL has the potential for an excellent tissue match between the donor and recipient and thus, a significant reduction in the risk of graft rejection. Patients undergoing KLAL or lr-CLAL will require topical and systemic immunosuppression for successful ocular surface rehabilitation. Keratoprosthesis surgery is another option for elderly patients or patients with significant systemic co-morbidities who cannot tolerate systemic immunosuppression.

Many of the ocular surface disease states are complicated by corneal scarring and opacification and will ultimately require subsequent keratoplasty. In such situations, deep anterior lamellar keratoplasty (DALK) may be advantageous over penetrating keratoplasty (PK) with elimination of potential endothelial rejection and improved tectonic wound stability.³ Keratoprosthesis surgery may also be useful after failed keratoplasty in lieu of DALK or PK in conditions where repeat cadaveric tissue transplantation has little to no chance of survival. Patients with bilateral limbal disease should not undergo DALK or PK prior to an ocular surface transplantation procedure, because the graft will not survive functionally if a significant amount of the limbal stem cells have been damaged.

Bilateral Limbal Disease with Prior Conjunctival Disease

This category of ocular surface disease involves conditions which cause bilateral limbal disease with previous but now subsided or controlled conjunctival inflammation. Box 54.1 lists the treatments that might be used to treat such inflammation. This category includes eyes with past injuries to the conjunctiva or previous episodes of inflammation from conjunctival inflammatory conditions. In these patients, KLAL or lr-CLAL, or a combination of the two (Cincinnati Procedure) are potential options for surgical treatment. Keratoprosthesis surgery is an additional option. If minimal conjunctival damage is present and/or no living-related donors are present, KLAL is the best option unless the patient is elderly or has systemic disease that would contraindicate the systemic immunosuppression needed with KLAL. If conjunctival damage is significant and a living-related donor is available, lr-CLAL remains the best options in a young and otherwise healthy patient as conjunctiva and limbal cells are provided to the ocular surface and a tissue match may be possible. In severe cases with large amounts of symblepharon and ocular surface failure, the preferred treatment option would be the Cincinnati procedure. This procedure combines lr-CLAL segments to the superior and inferior limbus in combination with cadaveric KLAL along the nasal and temporal limbus. Keratoprosthesis surgery may be the best option if systemic immunosuppression is contraindicated.

Bilateral Limbal Disease with Active Conjunctival Inflammation

Bilateral limbal disease with concurrent active conjunctival inflammation represents the most challenging situation for surgery of the ocular surface. This category of diseases includes conditions such as Stevens–Johnson syndrome, ocular cicatricial pemphigoid, and autoimmune inflammatory conditions. These disease states carry the poorest prognosis of diseases of the ocular surface. Prior to any surgical intervention, every effort must be made to mitigate conjunctival inflammation. The authors typically utilize topical, as well as systemic immunosuppressive therapy, including a number of additional adjunct medical treatments listed in Box 54.1. Autologous serum drops can be a particularly useful adjunct to topical and systemic immunosuppression, due to its constituents of vitamins, anti-inflammatory factors and growth factors that promote stabilization of the ocular surface.⁴ Any surgery should be delayed if possible until there is either resolution or significant improvement in conjunctival inflammation.

Once conjunctival inflammation is controlled, the best surgical treatment options include lr-CLAL, KLAL or a combination of the two (Cincinnati Procedure). Amniotic membrane may be used as an adjunct to this technique in an attempt to limit conjunctival fibrosis and inflammation. These techniques require intensive topical and systemic immunosuppression. Ex vivo stem cell expansion with autologous or living-related stem cells is another potential surgical treatment option for limbal disease with conjunctival inflammation and also requires both topical and systemic immunosuppression.

Ocular surface transplantation performs poorly in conditions with keratinized bulbar and palpebral conjunctiva, keratinized corneal surface, and/or little to no aqueous tear production. In these situations, keratoprosthesis surgery could be considered, but is also at high risk for failure. An osteo-odonto-kertoprosthesis (OOKP) may be the best option in these patients. Regardless of the procedure utilized, this clinical situation has a guarded prognosis and remains the most challenging of all ocular surface diseases for surgical treatment and surface rehabilitation.

While ocular surface disease, particularly limbal stem cell deficiency, often requires surgical treatment, medical therapies are important and useful adjuncts in stabilizing the ocular surface before, during, and after ocular surface transplantation. Although every ocular surface disease should be treated on an individual basis, this chapter presents the thought process the authors use in developing a treatment paradigm. Preoperative assessment of the laterality and extent of disease, as well as the degree of inflammation significantly enhances the surgical decision-making process. Moreover, any consideration of surgical rehabilitation of patients with ocular surface disease must first take into account ocular co-morbidities (e.g. glaucoma) and the anatomy and function of the ocular surface, including the eyelids, conjunctiva, and tear film. Consideration of patient age and systemic co-morbidities should also be taken into account, since many ocular surface transplant techniques require systemic immunosuppression which has potential side effects. Topical and systemic immunosuppression adds another layer of complexity to the successful management of ocular surface transplantation. While these situations can provide substantial surgical challenges, ocular surface transplant techniques enable the surgeon to convert some of the most challenging and debilitating conditions into rewarding and gratifying outcomes for both patient and surgeon.