Limbal stem cell deficiency (LSCD) may be partial or total. In congenital aniridia or in diseases with ongoing chronic inflammation, partial LSCD can progress over time to total LSCD. As seen in Figure 38.1, a patient with a severe alkaline chemical injury progresses over time from active conjunctival inflammation to partial LSCD and then total LSCD. If the visual axis remains unaffected in partial LSCD, the patient may not require transplantation and may be treated medically and monitored for progression. In quiet eyes, with small areas of conjunctival invasion, patients may benefit from sequential conjunctival epitheliectomy in the hope that the residual normal stem cells may repopulate the ocular surface. If several clock hours or more of LSCD exists, then a sectoral OSST may be used to treat that area of LSCD. In total LSCD, the only treatment options are complete OSST for restoration of the ocular surface with or without optical keratoplasty, or a KPro for visual rehabilitation.

Figure 38.1 Severe alkaline injury. (A) Acute conjunctival inflammation 1 week after the injury. (B) Same eye showing progression to partial limbal stem cell deficiency at 1 month. (C) Same eye showing progression to total conjunctivalization and symblepharon formation.

Extent of Conjunctival Involvement

The ocular surface diseases most difficult to treat are those that have both limbal stem cell and conjunctival involvement, such as in SJS and OCP. The conjunctiva itself is necessary for a healthy ocular surface, since it provides the mucin for a stable tear film and contains the lymphoid tissue to fight infection. Moreover, its structure of redundant folds allows for free movement of the eye within the orbit. Conjunctival disease may cause mucin–tear deficiency, subepithelial fibrosis, foreshortening of conjunctival fornices, symblepharon, ankyloblepharon, and in the most severe cases, keratinization of the ocular surface.

Activity of Inflammation

In patients with conjunctival involvement, a distinction must be made between previously inflamed conjunctiva and current active inflammation. The conjunctival inflammation from chemical/thermal injuries tends to subside slowly over a period of several months from the initial insult. In comparison, in autoimmune diseases, such as SJS or OCP, there tends to be a chronic background level of inflammation and associated exacerbations of conjunctival inflammation when the disease in active. When the conjunctiva is actively inflamed, there is an increase in immune mediators at the ocular surface. If surgery is performed during active inflammation, there is an increased risk of delayed epithelial healing, corneal melt, and immune rejection postoperatively.

It is important to manage the inflammation preoperatively and wait until the eye is quiet before performing the OSST or KPro. For chemical/thermal injuries, the authors recommend waiting at least 1 year after the initial insult. For autoimmune diseases, the underlying systemic disease should be optimally controlled and the ocular inflammation minimized with topical and often systemic anti-inflammatory agents before proceeding with surgery.

Schwartz et al.¹ proposed a classification system of ocular surface disease based on the extent of stem cell deficiency (stage I or II) and the presence or absence of conjunctival inflammation (stage a, b, or c) (Table 38.1). CLIK and aniridia are examples of stage Ia or IIa disease with partial/total stem cell deficiency but normal conjunctiva, as shown in Figures 38.2 and 38.3. A quiet eye with previous chemical or thermal injury would be an example of either stage Ib or IIb, depending on the extent of limbal stem cell loss, as shown in Figure 38.4. A chronically inflamed eye from OCP or SJS would be an example of either stage Ic or IIc disease, as shown in Figures 38.5 and 38.6.

Table 38.1

Classification of Ocular Surface Disease

Classification system of ocular surface disease based on the extent of stem cell deficiency and the presence or absence of conjunctival inflammation.

(Adapted from Schwartz GS et al. Ocular surface disease: medical and surgical management. New York: Springer-Verlag; 2002.)

Figure 38.2 Stage Ia ocular surface failure in a patient with contact-lens induced keratitis. Note the late fluorescein staining superiorly demonstrating the partial LSCD.

Figure 38.3 Stage IIa ocular surface failure in a patient with congenital aniridia. Note the total LSCD and anterior stromal scarring, with normal conjunctiva.

Figure 38.4 Stage IIb ocular surface failure in a patient with past chemical injury. Note the total LSCD, corneal stromal scarring, and resolved conjunctival inflammation.

Figure 38.5 Stage Ic ocular surface failure in an SJS patient, showing chronic conjunctival inflammation and partial LSCD.

Figure 38.6 Stage IIc ocular surface failure in a patient with a history of severe alkali injury, showing total LSCD and chronic conjunctival inflammation.

Keratolimbal allograft (KLAL) replaces limbal stem cells only, whereas a living-related conjunctival limbal allograft (lr-CLAL) replaces both limbal stem cells and conjunctival goblet cells. Therefore, patients with conjunctival, as well as limbal involvement may benefit more from an lr-CLAL or combined KLAL/lr-CLAL (the Cincinnati procedure)² as opposed to a KLAL alone to help increase mucin production for a healthier ocular surface.

Tear Film Abnormalities

A healthy tear film is essential for epithelial healing after OSST and for prevention of corneal melts after KPro surgery. Tears contain growth factors, immunoglobulins, and electrolytes, and prevent desiccation of the ocular surface.³ The mucin component of tears is produced by the goblet cells of the conjunctiva, which may be deficient in conjunctival disease. The aqueous component is produced by the glands of Wolfring and Krause, which may be damaged by conjunctival disease causing subepithelial fibrosis and forniceal foreshortening. Similarly, conjunctival fibrosis may scar the lacrimal ductules that secrete aqueous from the lacrimal gland, further compounding aqueous deficiency. The lipid component may be deficient from damage caused from scarring of the tarsus.

The health of the tear film must be assessed preoperatively to help determine which OSST procedure or which KPro procedure is most likely to succeed. For example, patients with keratinization and dryness of the ocular surface would likely fail KLAL alone, or the cornea may melt with a Boston Type 1 KPro. Either a combined KLAL/lr-CLAL (which replaces conjunctival goblet cells) or a Boston Type 2 or osteo-odonto-keratoprosthesis (OOKP) would be a more appropriate choice.

Extent of Stromal Scarring

More than half the patients undergoing stem cell transplantation will require a future keratoplasty for visual rehabilitation.⁴ A keratoplasty may not be necessary if the corneal scarring is superficial and removed with the superficial keratectomy when performing stem cell transplantation. In diseases characterized by progressive LSCD, such as aniridia, the authors recommend that OSST be performed prior to the onset of stromal scarring in patients with significant epithelial disease.⁵ If corneal transplantation is necessary and the endothelium is normal, then a deep anterior lamellar keratoplasty (DALK) is preferred over a penetrating keratoplasty (PK). The epithelium should be allowed to heal completely, and ocular surface inflammation allowed to subside before keratoplasty is performed. Patients should be informed of the longer time-frame required to achieve visual improvement with OSST and keratoplasty, compared to the more immediate visual improvement with KPro.

Mechanical Eyelid Problems

Conjunctival inflammation and scarring may cause foreshortening of the fornices, symblepharon, ankyloblepharon, distichiasis, trichiasis, entropion or ectropion. Disorders of the lid–lash complex may cause microtrauma and perpetuate chronic inflammation through the mechanical rubbing of lashes against the ocular surface.⁶ Ectropion or lagophthalmos can cause exposure keratopathy and delay healing post-OSST, or predispose to corneal melting post-KPro surgery. Symblepharon and loss of fornices make it difficult to retain a bandage contact lens that is necessary to prevent corneal melting after KPro implantation. Figure 38.7 shows symblepharon formation after chemical injury.

Figure 38.7 Total surface failure and symblepharon formation after chemical injury.

Eyelid abnormalities should be assessed and surgically corrected prior to or at the time of ocular surface reconstruction surgery. In patients with chronic inflammation who are at high risk of corneal melt, a lateral tarsorrhaphy should be performed at the time of OSST or KPro surgery.

Other Ocular Disease: Glaucoma and Retinal disease

Glaucoma

Ocular stem cell transplantation (OSST) and KPro surgery may cause glaucoma or contribute to the progression of pre-existing glaucoma. The UC Davis study ⁷ showed that glaucoma is the major cause of long-term vision loss after KPro implantation. Many patients have pre-existing glaucoma from diseases, such as congenital aniridia or chemical/thermal injuries and may already have had surgical treatment, usually in the form of a glaucoma drainage device. Patients should be assessed by a glaucoma specialist preoperatively, and their IOP should be well controlled prior to OSST or KPro surgery. Given the difficult in measuring IOP after KPro surgery and the high risk of developing glaucoma, some surgeons have a lower threshold for placement of a glaucoma drainage device prior to KPro implantation. End-stage glaucoma is a contraindication for OSST and KPro surgery, since it is possible that postoperative spikes in IOP may snuff out a borderline optic nerve.