BLOG: Does denervation drive dry eye?
Click Here to Manage Email Alerts
How important is the nerve supply to the health of the cornea?
We are all aware of advanced stages of neurotrophic keratopathy, where, for example, a lack of corneal sensitivity prohibits surface healing, as patients with completely insensitive corneas and persistent epithelial defects and corneal stromal thinning. But increasing evidence suggests that lesser degrees of corneal denervation are responsible for more routine but challenging “dry eye” cases. Stage 1 neurotrophic keratopathy, after all, is defined by nothing more than epithelial punctate staining paired with reduced corneal sensitivity. What share of our dry eye cases have decreased sensitivity? Does screen time, with its accompanying decreased blink rate, actually train our corneas to be insensitive? Do we know? Shouldn’t we?
A 2021 report in Ophthalmology by Anat Galor and others in Miami showed a correlation between objective measures of corneal hypersensitivity among patients with dry eye symptoms that exceeded objective findings (“pain, no stain”) and conversely reduced corneal symptoms among patients with signs but fewer symptoms (“stain, no pain”). It also showed reduced corneal sensitivity among older study participants. This all fits with multiple other studies that have now shown that, among the cataract surgery population, about two-thirds of patients have signs of dry eye, and about two-thirds of those have few or no symptoms. Impaired corneal sensitivity may be to blame.
A number of new treatments suggest that stimulating the sensory inputs that drive tear production is effective in treating dry eye. Our cover story in this issue of Healio/Ocular Surgery News discusses three stimulants to the trigeminal nerve: TrueTear electrical stimulation (Allergan), varenicline (Tyrvaya, Oyster Point), and a TRPM8 agonist, AR-15512, from Aerie (now Alcon). Each of these three works by a different trigeminal receptor, and each seems to be effective.
Repairing underfunctioning trigeminal nerves is another pathway to healing. Oxervate (recombinant human nerve growth factor, Dompé) is the only drug approved in the U.S. to treat neurotrophic keratopathy, but its six-figure price causes access issues. Neuroptika has enrolled its phase 2 trial of its glial cell line-derived neurotrophic factor agonists, and Recordati is testing udonitrectag, its own nerve growth factor receptor agonist. Several other companies are at earlier stages of drug development.
A variety of other approaches to denervated corneas have also met with anecdotal success. Tears derived from autologous serum are routinely used with success in the U.S. In Europe, insulin is routinely compounded to a concentration of 1 unit per cc and applied topically to nonhealing ulcers. A Spanish study is examining the role of cord blood, and surgical re-innervation of the cornea — so-called neurotization — is occasionally used, although it appears to be a surgically challenging procedure.
Most of all, what we lack is a complete understanding of where impaired corneal sensitivity fits in with other contributors to ocular surface disease. If we hope to master the ever-growing puzzle of this disease, we’re going to need more data. It’s time we establish standards for sensitivity testing and put them to use.
References:
- Galor A, et al. Ophthalmology. 2021;doi:10.1016/j.ophtha.2020.07.061.
Collapse