Treatment of epithelial defects can be an involved process

Neurotrophic keratitis is well explored in the cover story of this issue of Healio | OSN.

The approval and commercialization of Oxervate (cenegermin-bkbj, Dompé) in the United States has improved our ability to treat corneal persistent epithelial defects (PEDs) or corneal epitheliopathy associated with reduced or absent corneal sensation. I would like to share a few personal thoughts for the practicing clinician after managing these difficult-to-treat patients for 5 decades.

The corneal epithelium usually heals well and rapidly, and a PED occurs in only 200,000 or so patients each year. Depending on the location of one’s practice, 30% to 50% of PEDs will demonstrate reduced corneal sensation. Corneal sensation evaluation is an important test to perform in every patient with a PED as well as in patients with nonresponding corneal epitheliopathy with stain. These are the patients whose corneas “stain without pain.”

First, a few basic thoughts on corneal epithelial wound healing. The healing of an epithelial defect requires epithelial cell migration, adhesion and mitosis. The epithelial cells must migrate over the epithelial defect. This step requires healthy limbal stem cells and residual peripheral epithelium. It also requires stored epithelial cell glycogen as an energy source. There is enough energy stored in a healthy human epithelial cell to support rapid migration for 72 to 96 hours. Then migration slows. Ideally, we want every epithelial defect to heal in 4 days or fewer, and most do. If an epithelial defect persists for 5 days or longer, I get nervous. If not healed in a week, I consider it a PED that deserves aggressive therapy, as epithelial defects that last longer than a week can result in permanent corneal opacity or, worse yet, corneal ulceration. For the clinician who does not desire to treat these often challenging and sight-threatening cases, referral to a corneal specialist whenever a patient’s surface does not epithelialize in a week is an option.

Following epithelial cell migration to cover an epithelial defect, the new basal epithelial cell layer must adhere to Bowman’s layer or the stroma. This requires healthy basement membrane and the creation of epithelial cell adhesion complexes to the underlying cornea and between adjacent epithelial cells. If these cellular adhesion complexes do not form normally, a recurrent erosion syndrome often occurs. In some cases, a therapeutic mechanical debridement of the cornea and the “stalled out” leading epithelial cells is required to encourage epithelial cell migration and adhesion. If this is performed, slides for Gram and Giemsa staining, cultures and/or PCR testing can be obtained to rule out infection. Herpes infection is a common cause of nonhealing PEDs with reduced sensation and is an often-missed diagnosis that will modify treatment. Protecting the ocular surface from the mechanical impact of the eyelids and exposure with a bandage contact lens or, in recalcitrant cases, an amniotic membrane graft or the more recently available BrightMEM Descemet’s membrane graft (Brightstar Therapeutics) is also helpful. Finally, temporary tarsorrhaphy is an underutilized treatment that protects migrating epithelial cells, enhances surface lubrication by reducing evaporation and supports the creation of healthy cellular adhesion complexes.

Once the epithelial defect is healed with a single monolayer of migrating cells with good cellular adhesion complexes, epithelial cell mitosis can allow epithelial hyperplasia to recreate the normal five to six layers of epithelium. This process also requires energy and protection from mechanical trauma, which a healthy eye provides through limbal vessels, limbal stem cells and a normal tear film containing glucose, growth factors and the hundreds of virtuous cytokines and proteins in natural tears. Aggressive dry eye therapy is helpful in all PEDs.

My practice pattern when referred a new patient with a PED starts with determining whether corneal sensation is normal, reduced or absent. This simple determination is critically important and often neglected. Next, ruling out an infectious etiology is important. Common in my practice were patients who did not heal following epithelial debridement by an ophthalmic surgeon for refractive surgery or corneal surface disease or after keratoplasty, pterygium or vitrectomy surgery, especially in those with diabetes. In most cases, when seeing me, the patient was being treated with multiple topical eye drops, many preserved with benzalkonium chloride, all capable of retarding epithelialization.

Step one for me in a noninfected case is to stop all current eye drops and replace them with frequent nonpreserved artificial tears. If medication is required for herpes, oral therapy is employed. If a touch of steroid is appropriate, I use nonpreserved Lotemax (loteprednol etabonate ophthalmic ointment 0.5%, Bausch + Lomb) at night. Topical antibiotics are routinely discontinued, and oral doxycycline 50 mg twice daily is prescribed. Punctal occlusion is performed, and Lacrifill (Nordic Pharma) is well suited for patients with PEDs. In noninfected patients, a bandage soft contact lens is placed, and I prefer the Acuvue Oasys therapeutic bandage contact lens (Johnson & Johnson).

For me, stopping all potentially toxic topical eye drops, replacing them with frequent nonpreserved artificial tears, employing lacrimal outflow occlusion, treating with oral doxycycline and, in recalcitrant cases, performing a temporary suture tarsorrhaphy are effective in healing nearly all cases of PED. I believe this represents quality, compassionate and cost-effective office-based care for a sight-threatening disease. In the rare case that does not respond to this treatment regimen, the addition of serum tears (Vital Tears) is a useful adjunct. In the face of significant corneal hypoesthesia, treatment with Oxervate is indicated and discussed in the accompanying cover story.

• For more information:
• Richard L. Lindstrom, MD, can be reached at rllindstrom@mneye.com.

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Sources/Disclosures

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Source:
Expert Submission

Disclosures:
Lindstrom reports having dis­closures for Bausch + Lomb, Combangio, Johnson & Johnson Vision/Vistakon, Nordic Pharma and Visant.

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