Although much remains to be learned about the ways in which diabetes mellitus causes damage to the corneal nerves, one mechanism likely involves direct nerve damage due to a buildup of intracellular sorbitol. In diabetes, glucose metabolism may be shifted toward the polyol pathway, the first step of which is the conversion of glucose to sorbitol in a reaction catalyzed by aldose reductase. This takes place in the cornea, lens, corneal nerves, and other tissues.
In addition to this “acute” change, there are also long-term changes in the microvasculature that supports the corneal nerves. Over time this may affect the nerves’ nutrient supply and cause damage indirectly.
In diabetes, corneal sensation is decreased, with the loss of sensation typically declining in parallel with overall disease progression. Patients with other diabetic complications—eg, retinopathy, nephropathy—are very likely to have reduced corneal sensation as well.
In addition to loss of sensation, the corneal stroma and epithelium lose the trophic support of the corneal nerves. Because the corneal epithelium is continually generating and losing cells, the loss of trophic supports disproportionately affects the epithelium; and epithelial breakdown is common in diabetic corneas.
Although the nerve fibers in the cornea are different from other peripheral nerves, particularly in their receptor endings, they seem to be affected by diabetes much like other nerves. In fact, some have suggested that in vivo confocal microscopy of the corneal nerves might be used in place of biopsy as a noninvasive way of assessing and monitoring diabetic peripheral neuropathy. Changes in corneal nerve fiber length, density, and branching appear to be associated with diabetes.1
Measuring the functional change in diabetes is a bit more of a challenge, because the devices used to measure corneal sensation in the clinic are not very precise. The most accurate tool we have for clinical use, the Cochet-Bonnet esthesiometer, uses a nylon filament that is applied to the center of the cornea to measure touch response. Although imperfect, it is far better than the taking a cotton-tipped applicator and twisting out a few fibers to touch to the cornea, as was done for many years.
The Diabetic Patient
The diabetic cornea does not tolerate insults as well as a normal cornea, and diabetic eyes need to be manipulated as gently as possible. Contact lens wear, which represents a mild insult to the cornea, is more difficult for diabetic patients, who may be both less tolerant of the lenses and at higher risk for surface breakdown and secondary infection.
Diabetic patients often require laser treatment for diabetic retinopathy. Typically this is performed using a therapeutic lens to aid in focusing the laser (and often the cornea is given a drop of anesthetic); but diabetic corneas do not tolerate those manipulations as well as normal corneas and should be treated as atraumatically as possible.
Diabetic patients, like dry eye patients, are often extremely sensitive to the preservatives in topical medications, so it may be wise to recommend they use nonpreserved lubricants. In fact, diabetic patients have a higher rate of dry eye than the general population, perhaps due to reduced corneal sensation, which may affect tear production.
Diabetic patients and patients with a history of shingles are the only ones in whom I routinely test corneal sensation. In these patients, corneal sensation may be a good indicator of corneal health.
Treating the Diabetic Cornea
Topical aldose reductase inhibitors have been tried (as a means to improve both cornea and lens) but so far without great success. Perhaps the single best thing ophthalmologists can do to help their diabetic patients maintain corneal health is to encourage them to keep up scrupulous glucose control.
Although good glucose control may slow the course of the disease, once damage is done to corneal nerves it tends to be permanent. Some of the acute damage caused by accumulation of sorbitol may be reversible. For example, edema of the crystalline lens that is sometimes seen in diabetic eyes can reverse when glucose levels normalize, and similar improvements may occur in other tissues.
Ophthalmologists should be aware that the diabetic cornea is easily damaged and should be treated accordingly. For physicians this means careful manipulation; and patients should know to limit environmental stress to the extent possible.
Sometimes the ophthalmologist is the first person to bring up diabetes to an affected patient. Changes in vision and refraction (due to lens edema) may trigger suspicion that the patient has diabetes. If there is also reduced corneal sensation in the absence of a history of shingles, a diabetic etiology is certainly possible.
Gary N. Foulks, MD, FACS, is the Arthur and Virginia Keeney professor of ophthalmology, University of Louisville, Louisville, KY, and is editor-in-chief of The Ocular Surface.
1. Messmer EM, Schmid-Tannwald C, Zapp D, Kampik A. In vivo confocal microscopy of corneal small fiber damage in diabetes mellitus. Graefes Arch Clin Exp Ophthalmol. 2010 Sep;248(9):1307-12.