This article was originally published in a sponsored newsletter.

Neurotrophic keratitis (NK) can be a challenge for patients and providers, especially when patients don’t experience discomfort. The causes of NK are vast and include prior viral infections; prior corneal refractive surgery or retinal surgery; and even common conditions such as diabetes, chronic dry eye, and use of eye drops. The key for providers is to have NK on their differential diagnosis for any patient who presents with corneal staining or nonhealing epithelial defects.

Diagnosis

Checking for cornea sensation made easy: I use a sterile cotton swab, unwind the tip to make a point, and check the center and the 4 quadrants in both eyes. A corneal esthesiometer is even better, but may not be easy to find.

Staging: NK staging is important to document, especially for insurance purposes. I like the simplicity of the Mackie classification system. The main characteristic of stage 1 is corneal staining; stage 2 involves epithelial defects; and epithelial defects plus ulceration, thinning, or other cornea findings define stage 3.

Treatment

Treatment options have expanded over the past few years. Cenegermin-bkbj (Oxervate, Dompè) is the first FDA-approved topical medication for NK. It is a recombinant nerve growth factor used 6 times a day for 8 weeks. A multicentered FDA trial showed improvement of <0.5mm epithelial defect staining in 70% of patients treated with cenegermin compared to 29.2% in the placebo arm at Week 8. A secondary endpoint of cornea healing reached significance between the placebo and treatment arms by week 4 in the study.¹ Serum tears or plasma-rich growth factor offer another option for topical treatment²: The patient’s blood is compounded into eye drops that mimic the cytokines and nutrients in normal tear film. Newer off-label treatments such as topical insulin may also hold promise for these patients.³

Non-medication treatments have also expanded. Amniotic membrane can be utilized in the clinic or in the OR to cover nonhealing defects, and surgical treatments like tarsorrhaphy or cornea neurotization can be used to protect corneas that suffer from neurotrophic ulcers. In our practice, we often use scleral lenses that work with the scleral reservoir to protect the cornea. The scleral reservoir has tears that coat the cornea throughout the day, but can also be used to deliver drugs, including plasma-rich growth factor, a preservative-free antibiotic such as moxifloxacin 0.5%, and even preservative-free dexamethasone to the cornea.

While NK can present a challenge to physicians, we have a rich armamentarium of simple ways to diagnose and treat patients effectively.

References:

1. Pflugfelder SC, Massaro-Giordano M, Perez VL, et al. Topical recombinant human nerve growth factor (cenegermin) for neurotrophic keratopathy: a multicenter randomized vehicle-controlled pivotal trial. Ophthalmology. 2020 Jan;127(1):14-26. doi: 10.1016/j.ophtha.2019.08.020
2. Sanchez-Avila RM, Merayo-Lloves J, Riestra AC, et al. Treatment of patients with neurotrophic keratitis stages 2 and 3 with plasma rich in growth factors (PRGF-Endoret) eye-drops. Int Ophthalmol. 2018 Jun;38(3):1193-1204. doi: 10.1007/s10792-017-0582-7
3. Wang AL, Weinlander E, Metcalf BM, et al. Use of topical insulin to treat refractory neurotrophic corneal ulcers. Cornea. 2017 Nov;36(11):1426-1428. doi: 10.1097/ICO.0000000000001297