Neurotrophic keratopathy (NK) is caused by damage to the trigeminal nerve in which the loss of sensory supply to the cornea compromises the ocular surface and vision. While the most common cause of NK is cornea infection, many other causes – congenital conditions, surgery, trauma, systemic disease or central nervous system disorders – can result in abnormal cornea sensation. NK is a rare degenerative condition, with an estimated prevalence of persons.
Historically, treatment options for NK have been limited and few preserve vision. Christine Shieh, M.D. and Rachel Sobel, M.D., are part of a multidisciplinary team at Vanderbilt University Medical Center that has begun performing corneal neurotization, a new procedure with revolutionary potential to improve cornea nerve function and reestablish corneal sensation.
“Normal corneal sensation is required for maintaining epithelial integrity,” said Shieh, an assistant professor of ophthalmology and visual sciences and corneal specialist at the Vanderbilt Eye Institute (VEI). “When the epithelium becomes compromised, it can lead to ulceration, perforation, and in extreme cases the eye can even melt.”
“When the epithelium becomes compromised, it can lead to ulceration, perforation… the eye can even melt.”
“Corneal sensation is crucial to send signals to the structures around the eye, including the lacrimal gland and the eyelids, to help the cornea heal itself when there’s an injury,” said Sobel, an orbital and oculoplastic surgeon and assistant professor of ophthalmology and visual sciences at VEI. “When neurotrophic cornea occurs, the patient is more vulnerable to infection and scarring.”
Beyond Eye Closure
Based on disease severity in the classification, NK has historically been managed with ointment, drops, amniotic membrane transplantation, or tarsorrhaphy, which leaves the cornea less exposed. “Tarsorrhaphies are highly unpopular with patients because of how it affects appearance and peripheral vision,” Shieh said. “I’ve had patients come back and want the tarsorrhaphy opened up, even though they’re at risk for cornea ulcer recurrence and further damage.”
In corneal neurotization surgery, a healthy donor nerve segment from the patient is coapted to the damaged nerve to re-establish sensory innervation. “The transfer of a healthy nerve segment to the cornea-limbal area allows for release of nerve growth factors and causes the cornea nerves to regrow or become healthier; we are literally using the patient’s own body to help heal their eye.” In addition to the sural nerve in the leg, the Vanderbilt team has used a nearby nerve, the supraorbital nerve that innervates the forehead, to reestablish sensation in the cornea.
Collaborative Approach to Surgery
Patients sometimes present with corneal injury in which both the fifth (sensation) and seventh (eyelid closure) nerves are affected. “With these more challenging cases, I used to have to sew the lid nearly shut,” Sobel said. “Now, we hope to close the eye temporarily. If we can shorten the amount of time the eye is closed, it gives us a better option for treatment.”
Shieh and Sobel work closely on such surgeries with Scott Stephan, M.D., an assistant professor of otolaryngology and facial and plastic reconstructive surgery and director of the at Vanderbilt. Stephan specializes in nerve regeneration and facial reanimation in skull-base surgeries. Together, the team offers a multidisciplinary approach to ocular surgery. Said Stephan, “It was important for us to establish a clinical care pathway in which we can clearly measure outcomes, so that going forward we can better stratify patients.”
“If we can shorten the amount of time the eye is closed, it gives us a better option for treating challenging cases.”
Novel Agent Shows Promise
Last year, recombinant human nerve growth factor (rhNGF) Oxervate™ eye drops received FDA approval for neurotrophic keratopathy. “The early outcomes are encouraging, but we don’t yet have long-term data,” Shieh said, “And the price is prohibitive. Without insurance or financial assistance, it costs $95,000 for eight weeks of treatment.”
Shieh is interested in studying the long-term outcomes of Oxervate as compared to neurotization surgery. “Patients with neurotrophic corneas are a heterogeneous population. In the future, we hope to better understand whether one modality offers superior outcomes to the other. It is possible the answer may vary depending on the patient’s demographics and etiology,” she said. “But for now, it’s nice that we have these new options and are able to bring them to the Vanderbilt patient population.”