Dry Eye Resource Center
On the Horizon

Dry eye and inflammation: A discussion with Dr. Michael Lemp

John J. Murphy, MDLinx | May 04, 2017

Background:
Dry eye disease affects an estimated 7% to 34% of all Americans, and is involved in one out of every four visits to an eye doctor. The causes of dry eye are multifactorial, but “it is now well recognized that the pathophysiology of chronic dry eye disease can include a cycle of inflammation involving both innate and adaptive immune responses,” according to a recent review article written by the ODISSEY European Consensus Group and published in the journal Acta Ophthalmologica. In short, inflammation is a key contributor to the pathogenesis of dry eye disease.

Advertisement

It’s important to recognize that while we know inflammation is one of the mechanisms to cause damage to the ocular surface in dry eye disease, the role of inflammation is not completely understood.

In this interview, Dr. Michael Lemp—an expert in dry eye and one of the authors of the ODISSEY paper—discusses how the cycle of inflammation plays an active role in dry eye. Dr. Lemp also describes what treatments are available (and forthcoming) to intervene in the inflammatory process.
 
MDLinx: What was the impetus for this paper on the role of inflammation in dry eye?

Dr. Lemp: It’s important to recognize that while we know inflammation is one of the mechanisms to cause damage to the ocular surface in dry eye disease, the role of inflammation is not completely understood.

The whole inflammatory process is a very complicated process throughout the body. But from a treatment point of view, the inflammatory process is also one that has a lot of “entry points” that can be attacked. In other words, for drugs that interfere with the process of inflammation, there are a lot of different points along the process that can be vulnerable to different kinds of therapeutic agents that you could develop. So inflammation is a very attractive target for investigators and companies developing new drugs.

MDLinx: Inflammation is one of the mechanisms of dry eye, but it’s not necessarily the origin of dry eye, correct?

Dr. Lemp: That’s certainly an interesting question, but the answer is something that those of us in the field don’t all agree on. I’d say that it’s not completely understood—but we’ve learned a lot, particularly in the last 15 years, about the pivotal role that inflammation plays in the damage that occurs on the surface of the eye.

MDLinx: So, where does inflammation enter into the sequence of events in the development of dry eye?

Dr. Lemp: There are various ways in which you can develop dry eye disease, but they basically fall into two different subtypes. The most common form of dry eye disease is evaporative dry eye, where you have increased evaporative loss of water and you get a concentrated tear film. The other form is aqueous tear-deficient dry eye, which occurs when you’re not producing enough tears due to a dysfunction of the lacrimal glands.

But for most people with moderate to severe dry eye, they actually coexist. Why do they coexist? When one of them develops, whether it’s evaporative dry eye or aqueous deficient dry eye, the other mechanism comes in as a compensatory mechanism to try to stabilize it—which then exhausts that secondary facility. So anybody who has moderate-to-severe dry eye has elements of both evaporative dry eye and aqueous tear-deficient dry eye.

Now, to get back to the question of inflammation: in the evaporative form of dry eye, the surface of the eye becomes exposed to a concentrated, hyperosmolar solution. This destroys the cells on the ocular surface, which elicits an inflammatory response. However, inflammation itself may lead to dysfunction of tear secretion, which therefore increases osmolarity. Also, a small percentage of dry eye sufferers have the condition due to autoimmune diseases such as Sjögren's syndrome, rheumatoid arthritis, and other systemic diseases where inflammation plays a primary role in attacking the lacrimal glands. In such cases, you get inflammation in two different ways: one as an early event and the other as a later event.

The therapeutic products that we have on the market right now can break down the process and decrease the inflammatory response. These include Restasis® (0.05% cyclosporine, Allergan), Ikervis® (0.1% cyclosporine, Santen; not yet approved in the United States), and Xiidra® (5% lifitegrast, Shire), which attacks the inflammatory process by a different mechanism than cyclosporine.

MDLinx: Are there any other anti-inflammatories in the pipeline or potential therapies specifically for hyperosmolarity?

Dr. Lemp: Yes, there are new approaches besides anti-inflammatory therapies that are in the works, and many of them do decrease tear osmolarity. The research is finding that after the treatment lowers the tear osmolarity, the symptoms don’t clear up for about a month. The reason for that is that it’s easier to lower the osmolarity in the tears but then you still have a surface that’s been beaten up. So it takes little longer for the surface to heal.

All of this is part of a journey of discovery in various aspects of the disease that have happened in the last five to eight years. It’s a field that’s changing fairly rapidly, and that’s a good thing. We’re finding much better ways of recognizing the disease, grading its intensity, and we’ll be getting much better drugs on the market to help these patients with dry eye, particularly those with moderate to severe dry eye.

About Dr. Lemp: Michael A. Lemp, MD, is a clinical professor of ophthalmology at Georgetown University and George Washington University schools of medicine in Washington, DC, and is founding editor of The Ocular Surface journal.

The workshops leading to the ODISSEY article were funded by Santen.

Advertisement