There are a number of causes of neurotrophic keratopathy, one being damage to cranial nerve V, which results in corneal hypoesthesia or anesthesia (Table 4-1). Probably the most common cause of neurotrophic keratopathy is herpetic keratitis, which can be associated with persistent or recurrent corneal epithelial defects in the absence of replicating virus or active inflammation. A neurotrophic cornea can also occur after penetrating keratoplasty or deep anterior lamellar keratoplasty, in the early postoperative period.
Some medications used to treat ocular surface disease and glaucoma may impair epithelial wound healing, resulting in the formation of persistent corneal epithelial defects. The drugs most frequently implicated include topical anesthetics, topical nonsteroidal anti-inflammatory drugs (NSAIDs), trifluridine, β-blockers, carbonic anhydrase inhibitors, and, in sensitive individuals, all eyedrops containing the preservative benzalkonium chloride (BAK). Some authors refer to the condition as toxic ulcerative keratopathy. This clinical problem usually presents as a diffuse punctate keratopathy, and the cause may be unrecognized by the ophthalmologist. In some instances, pericentral pseudodendritiform lesions and pseudogeographic defects may occur. These clinical findings are often misinterpreted as a worsening of the underlying disease and thus may lead to more frequent dosing of the offending medication.
Table 4-1 Causes of Neurotrophic Keratopathy and Persistent Corneal Epithelial Defects
In patients with diabetic retinopathy, persistent epithelial defects often occur following epithelial debridement in the course of vitreoretinal procedures. Diabetic neuropathy is thought to be a potential cause of neurotrophic keratopathy and nonhealing epithelial defects.
Persistent corneal epithelial defects typically occur in the central or paracentral cornea and tend to be located inferiorly or inferonasally because of the protective effect of the Bell phenomenon on the superior cornea. The round or oval lesions frequently have elevated gray-white edges of “heaped-up” epithelium, which are associated with underlying stromal inflammation (Fig 4-1). Left untreated, persistent corneal epithelial defects can progress to vascularization and corneal opacification or corneal thinning and possible perforation. Secondary bacterial keratitis may also occur in this setting.
Management of neurotrophic keratopathy with or without persistent epithelial defect starts with eliminating or limiting the use of potentially aggravating topical medications to the degree possible. Frequent lubrication with nonpreserved drops, gels, or ointments is suggested. Autologous serum drops (20%), which contain growth factors and fibronectin, can be useful. In cases involving significant dry eye, temporary or permanent punctal occlusion can be effective in improving the volume and stability of the tear film and restoring the ocular surface.
Patching, low-water-content bandage lenses (soft, thin, highly oxygen-permeable lenses), or scleral contact lenses with a fluid-filled reservoir may facilitate reepithelialization or improve the keratopathy.
In cases associated with stromal melting, medications with specific activity against matrix metalloproteinases (MMPs), such as a tetracycline administered orally, may help prevent or halt keratolysis. Corneal crosslinking performed early in the course of stromal ulceration has been reported to be useful in a small number of patients. Amniotic membrane transplantation has been reported to encourage healing of persistent epithelial erosions. Lateral and/or medial tarsorrhaphy may be required to prevent ocular surface desiccation. Tarsorrhaphy, which can be performed in a temporary or permanent manner, decreases the ocular surface area and tear film evaporation. Partial or total conjunctival flaps prevent corneal melting, but they should be used as a last resort. See Chapter 13 for further discussion of surgical management of ocular surface disorders.
Figure 4-1 Neurotrophic ulcer. Ovoid corneal ulceration with typical “heaped-up” gray-white epithelial edges.
(Courtesy of Stephen Orlin, MD.)
Goins KM. New insights into the diagnosis and treatment of neurotrophic keratopathy. Ocul Surf. 2005;3(2):96–110.
Jeng BH. Use of autologous serum in the treatment of ocular surface disorders. Arch Ophthalmol. 2011;129(12):1610–1612.
Jeng BH. Persistent epithelial defects. Focal Points: Clinical Practice Perspectives. San Francisco: American Academy of Ophthalmology; 2016, module 9.
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.