PATHOGENESIS

When the limbal stem cells are congenitally absent, injured, or destroyed, conjunctival cells migrate onto the ocular surface, often accompanied by surface irregularity and superficial neovascularization. The absence of limbal stem cells reduces the effectiveness of epithelial wound healing, as evidenced by compromised ocular surface integrity with an irregular ocular surface and recurrent epithelial breakdown.

Stem cell deficiency states result from both primary and secondary causes. Primary causes include PAX6 gene mutations (aniridia), ectodactyly–ectodermal dysplasia–clefting syndrome, sclerocornea, keratitis-ichthyosis-deafness (KID) syndrome, and congenital erythrokeratodermia. Secondary causes include chemical burns, thermal burns, radiation, contact lens wear, ocular surgery, immune-based mucous membrane conjunctivitis (eg, mucous membrane pemphigoid, Stevens-Johnson syndrome), mucous membrane conjunctivitis related to infection (eg, trachoma), pterygia, long-term use of topical medications (pilocarpine, β-blockers, antibiotics, antimetabolites), and dysplastic or neoplastic lesions of the limbus.

See Table 4-3 for an etiologic classification of limbal stem cell deficiency.

CLINICAL PRESENTATION

Clinically, stem cell deficiency of the cornea can be found in several ocular surface disorders. Affected patients usually have recurrent ulceration and decreased vision as a result of the irregular corneal surface. Corneal neovascularization is invariably present in the involved cornea. A whorl-like irregularity of the ocular surface emanating from the limbus can be more easily observed following the instillation of topical fluorescein (Fig 4-7).

Table 4-3 Etiologic Classification of Limbal Stem Cell Deficiency

Figure 4-7 Mild stem cell deficiency secondary to contact lens wear. A whorl-like irregularity of the ocular surface is seen following instillation of topical fluorescein.

(Courtesy of James J. Reidy, MD.)

MANAGEMENT

In mild or focal cases associated with local factors such as contact lens use or topical medications, any possible inciting cause should be discontinued. In these cases, treatment with topical corticosteroids is advocated by some clinicians. If the stem cell deficiency is sectoral and mild, the abnormal epithelium can be debrided, allowing for resurfacing of the denuded area with cells derived from the remaining intact limbal epithelium.

In more extensive or severe cases of limbal stem cell deficiency, initial therapy with a scleral contact lens may be helpful. If this is not effective, replacement of stem cells by limbal transplantation is an alternative. When the limbus is focally affected in 1 eye (eg, pterygium), a limbal or conjunctival autograft can be harvested from the same eye. For unilateral, moderate or severe chemical injuries, a limbal autograft can be obtained from the healthy fellow eye. For bilateral limbal deficiency, as with Stevens-Johnson syndrome or bilateral chemical burns, a limbal allograft from a human leukocyte antigen–matched living related donor (or, if unavailable, an eye bank donor eye) can be considered; however, systemic immunosuppression is required following limbal allograft transplantation (see the discussion of ocular surface surgery in Chapter 13). Another alternative in cases of severe limbal cell deficiency is a keratoprosthesis (see Chapter 15).

Zhao Y, Ma L. Systematic review and meta-analysis of transplantation of ex vivo cultivated limbal epithelial stem cell on amniotic membrane in limbal stem cell deficiency. Cornea. 2015;34(5):592–600.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.