Figure 3-25 Topical anesthetic overuse with persistent corneal epithelial defect and necrotic ring opacity. (Courtesy of Kirk R.

Wilhelmus, MD.)

Differential diagnosis includes bacterial, fungal, herpetic, and amebic keratitis. Suspicion should be maintained in the face of negative cultures in any patient who is not responding to appropriate therapy. Often, the diagnosis is made only when the patient is discovered concealing the anesthetic drops. Once the diagnosis is made and infectious keratitis is ruled out, corneal healing usually occurs if all exposure to anesthetics is removed. In advanced cases, permanent corneal scarring or perforation may occur. Psychiatric counseling is sometimes helpful.

Dellen

Desiccation of the epithelium and subepithelial tissues occurs at or near the limbus adjacent to surface elevations such as those produced by pterygia, large filtration blebs, or dermoids. Because the tear film is interrupted by these surface elevations, normal blinking does not wet the involved area properly. Clinically, dellen are saucerlike depressions in the corneal surface. The epithelium exhibits punctate irregularities overlying a thinned area of dehydrated corneal stroma. Treatment with frequent ocular lubrication or pressure patching accelerates the healing process and restores stromal hydration.

The orbital and conjunctival tissues surrounding the sclera also play a role in maintaining scleral hydration. This function becomes especially evident during surgical procedures in which the conjunctiva and extraocular muscles are removed from the scleral surface. The exposed sclera becomes thinner and partially translucent unless it is continually remoistened. Removal of the perilimbal conjunctiva and interference with the wetting effect of the tear film (as after excision of a pterygium using the bare sclera technique) can cause the underlying sclera to become markedly thinned and translucent, forming a scleral delle.

Limbal Stem Cell Deficiency

PATHOGENESIS The ocular surface is composed of permanently renewing populations of epithelial cells. These epithelial cells are replaced through proliferation of a distinct subpopulation of cells known as stem cells. Corneal stem cells are located in the basal cell layer of the limbus, whereas conjunctival stem cells may be uniformly distributed throughout the bulbar surface or located in the fornices. Stem cells have an unlimited capacity for self-renewal and are slow cycling (ie, they have low mitotic activity). Once stem cell differentiation begins, it is irreversible. The process of differentiation occurs by means of transit amplification. Transit-amplifying cells, which have a limited capacity for self-renewal, can be found at the limbus as well as at the basal layer of the corneal epithelium. Each of these cells is able to undergo a finite number of cell divisions. Corneal and conjunctival stem cells can be identified only by indirect means, such as clonal expansion and identification of slow cycling.

Approximately 25%–33% of the limbus must be intact to ensure normal ocular resurfacing. The normal limbus acts as a barrier against corneal vascularization from the conjunctiva and invasion of conjunctival cells from the bulbar surface. When the limbal stem cells are congenitally absent, injured, or destroyed, conjunctival cells migrate onto the ocular surface, often accompanied by 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.

See Table 3-11 for an etiologic classification of limbal stem cell deficiency.

Table 3-11

CLINICAL PRESENTATION Clinically, stem cell deficiency of the cornea can be observed in several ocular surface disorders. 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 wavelike irregularity of the ocular surface emanating from the limbus can be more easily observed following the instillation of topical fluorescein (Fig 3-26). In some cases, increased epithelial permeability can be observed clinically by diffuse permeation of topical fluorescein into the anterior stroma.

Figure 3-26 Mild stem cell deficiency secondary to contact lens usage. A wavelike irregularity of the ocular surface is seen following instillation of topical fluorescein. (Courtesy of James J. Reidy, MD.)

Stem cell deficiency states result from both primary and secondary causes. Primary causes include PAX6 gene mutations (aniridia), ectrodactyly–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, mucous membrane conjunctivitis (eg, mucous membrane pemphigoid, trachoma, Stevens-Johnson syndrome), pterygia, use of topical medications (pilocarpine, β-blockers, antibiotics, antimetabolites), and dysplastic or neoplastic lesions of the limbus.

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 steroids may be helpful. 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, as with a pterygium, a limbal or conjunctival autograft can be harvested from the ipsilateral 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)