Off the Cuff: Dry Eye and Inflammation: A Clinically Correct Perspective

Having a practice limited to dry eye in one of the driest places on earth provides unique perspective. What I am about to say may confuse some and upset others; however, the majority of dry eye—or at least what we call dry eye—is not caused by inflammation. Not that inflammation doesn’t occur in dry eye patients, but for most, it occurs only after the ocular surface can’t compensate in other ways for the challenges it encounters. The body’s innate ability to right the ship is described as homeostasis, a concept brilliantly appended to the definition of dry eye by Dr. Kelly Nichols, then chair of the DEWS II Definition and Classification committee.

The ocular surface environment is a complex interwoven fusion of form and function, protecting one of the most critical systems essential for survival. We often miss its complexity and the fact that both ocular surface function and homeostatic mechanisms that compensate for dysfunction are active and centrally controlled. For example, tear viscosity and gel-forming mucin production increases in patients with MGD who have insufficient lipid production. The body naturally attempts to restore tear stability and ocular surface protection.

Only when homeostatic compensatory mechanisms fail, does the body resort to its most primal defense—inflammation. While many patients are able to regain normal function through homeostatic control, in my experience, about 20% are unable to and inflammation ensues.

There is another subset of dry eye patients, those with systemic inflammation and autoimmune disorders. Inflammation is nonselective, and a patient with rheumatoid arthritis may have little joint involvement, but severe ocular surface disease. This primary inflammatory surface disease subgroup represents less than 10% of my patient population.

You are probably wondering why then do so many experts believe that dry eye is primarily an inflammatory disease? There is no simple answer to this, other than to say if you are a hammer or own a lot of hammers, the world most likely looks like it’s filled with nails. Add the general confusion I referenced in a prior Off The Cuff, and it’s no surprise that patients who need anti-inflammatory treatment aren’t receiving it while patients who don’t are.

For treating patients with inflammatory dry eye and ocular surface disease, the FDA has approved two anti-inflammatory medications to treat the signs and symptoms of dry eye. First approved was Xiidra, which is a marvel of pharmacoengineering. It blocks binding of T-cells to ocular surface adhesion complexes by serving as an adhesion complex decoy. This effectively shuts down the inflammatory cascade. Clinically, I’ve found Xiidra to be effective and safe for long-term use.

More recently, the FDA approved Eysuvis, a novel loteprednol formulation leveraging an extremely advanced controlled drug-delivery system to maximize efficacy at a low-dose. Eysuvis, used up to four times daily for up to two weeks, has been extremely effective at shutting down dry eye inflammatory exacerbations and has proven so safe that I have even cautiously prescribed it for my dry eye patients who are steroid responders. What makes Eysuvis especially powerful is that it returns control to dry eye sufferers who have been tormented by the lack of control over often debilitating signs and symptoms. From a prescriber’s perspective its on-label indication also provides an extra margin of safety from a medicolegal perspective.

What we call dry eye is a complex mélange of dysfunction and misery. It is not a simple disorder, but we make it more complex than it needs to be. As a result, we make it overly confusing and more difficult to effectively manage. Yes, inflammation is a piece of the dry eye puzzle, but there is a lot more to dry eye than inflammation.

Arthur B. Epstein, OD, FAAO Chief Medical Editor artepstein@optometricphysician.com

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Write to Dr. Epstein at artepstein@optometricphysician.com. The views expressed in this editorial are solely those of the author and do not necessarily represent the opinions of Jobson Medical Information LLC (JMI), or any other entities or individuals.