One of the main challenges in managing dry eye disease is that signs and symptoms rarely correlate. Some patients have mild signs and major symptoms, while the reverse is true for others. For me, the latter is much easier to wrap my head around, because if you have a damaged corneal epithelium for an extended period of time, the sensory nerves can become a bit numb. Fortunately, we have ways to demonstrate that the damage truly exists (i.e., photography) since asymptomatic patients can sometimes be hard to convince that they need treatment.

The opposite situation is also understandable. For instance, when a normal cornea becomes poorly protected by the tear film, it makes sense that patients could very well experience significant discomfort—it’s the normal process of the eye alerting us that there is a problem. But what about patients who complain of significant dry eye symptoms but have ultra-clear corneas, stable tear films, and excellent meibomian gland function? Can a person have “dry eye disease” in the absence of clinical signs?

Sure, there is the possibility that we simply got lucky and caught the disease process extremely early. Or, if they are self-prescribing over-the-counter eyedrops, the damage may have cleared before their visit. While either of these could be true, we also need to consider the possibility that such patients are suffering from neuropathic pain.

With neuropathic pain, the discomfort originates from the nerves themselves—either peripherally or centrally—rather than from damaged ocular tissue. For example, one specific type of corneal nerve is especially adept at detecting a drop in surface temperature, warning against a thinning tear film. In normal eyes, these nerves only fire when the temperature decreases 4° to 5°. In someone who has peripheral neuropathy, however, the nerves are in a hypersensitive state and might fire with only a 2° drop (Hirata and Rosenblatt, 2014; Neumann et al, 1996).

As those nerves chronically fire, central mechanisms may become involved, which means the persistent signal emerging from the peripheral nerves is no longer dampened by the central nervous system (Ploghaus et al, 2001). The patient then experiences heightened, prolonged pain, often in the absence of peripheral stimuli, even once the ocular surface is fully healed (Vehof et al, 2013).

How Is It Diagnosed?

There isn’t a test that will tell us definitively whether our patients are suffering from neuropathic pain versus dry eye disease. In fact, all current diagnostic strategies focus on tear film characteristics and ocular health. Several confocal microscopy studies have shown that repeated damage to a corneal nerve can cause it to form ultrasensitive sprouts at its terminal end. But, confocal microscopy isn’t widely available to most practitioners (Zhang et al, 2005; Benitez del Castillo et al, 2004).

Fully assessing a patient’s symptoms might give us our biggest clue. Neuropathic sufferers often complain of a burning, shooting, or electric pain that is often spontaneous as well as a pain response to seemingly normal environmental factors (i.e., air conditioning or cold weather). While the symptoms of our dry eye patients might very well worsen in these environments, those suffering from neuropathic pain will report significantly amplified levels.

What Can We Do?

If we suspect neuropathic pain, both in the presence or absence of ocular surface damage, we can always work to improve tear film stability and reduce external stimuli. Traditional dry eye therapy and scleral lenses can assist in this endeavor. Additionally, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, and anticonvulsants have shown promise in treating other chronic neuropathic pain disorders such as fibromyalgia and may be helpful if central sensitization has occurred. But, as with any disease process, prevention is the best “treatment” of all. CLS

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Dr. Gaume Giannoni is a clinical professor at the University of Houston College of Optometry and is the director of the Dry Eye Center at the University Eye Institute. She also sees patients in a private practice setting. She is a consultant or advisor to Alcon and Allergan.