Esen Akpek, M.D., the Bendann Family Professor of Ophthalmology and chief of the Ocular Surface Disease Clinic at Wilmer Eye Institute, is a world-renowned expert in the evaluation and treatment of dry eye disease.

Dry eye is a complex disease that has gained increased attention in recent years as an understudied and potentially debilitating condition. It affects more women than men, especially those in post-childbearing years, when hormonal fluctuations can influence the quality of tears. Increased screen time — already on a meteoric rise before the pandemic — can lead to or exacerbate dry eye symptoms because it reduces the blinking rate and increases evaporation of tears and thus the moisture level of the eyes.

There are two major types of dry eye. One, aqueous deficient dry eye, occurs when there is insufficient tear production. The other, evaporative dry eye, happens when Meibomian glands located along the margin of the eyelids malfunction. These glands are responsible for secreting meibum, an oily substance that coats the aqueous tears to form a protective film that keeps the eye lubricated. Without sufficient oil, the tears quickly evaporate.

Because of insufficient tears, insufficient meibum, or both, the eyes become dry. They may feel itchy, irritated or gritty, as though something is in the eye; vison may be blurry at times, and if the deficiencies are significant enough, the eyes can become inflamed and outright painful.

As dry eye has become an increasing problem, there has been a corresponding search for relief. Over-the-counter rewetting drops can be helpful for some people, but many others are left with significant discomfort and even dysfunction, in terms of their ability to read, for example. In recent years, prescription eye drops have been developed to target tear production, yet as Akpek has witnessed, many patients remain symptomatic even with prescription eye drops. That may be changing.

In May of this year, the FDA approved, for the first time, two water-free prescription eye drops for the treatment of dry eye: one that targets tear production and the other, for the first time, tear evaporation. The water-free solution helps the medication stay on the eye’s surface. But according to Akpek, who led the study of the drop that targets tear production, there’s more to the story.

Historically, the FDA has used a variety of criteria and measurements to evaluate eye drops that target dry eye. However, it has overwhelmingly relied on the Schirmer test, which measures tear production — and increased tear production at the level required for FDA approval hasn’t been shown to correlate with relief for patients. “Patients don’t care about tear production,” says Akpek. “They care about the discomfort or blurred vision.”

The other problem with the FDA’s approach of relying on increased tear production as a measure of effectiveness, she says, is that patient-reported outcomes are not considered. In other words, there’s no feedback from the people studied as to whether they saw relief from their symptoms.

In her clinic, Akpek relies not on the Schirmer test to assess improvement. Instead, she employs corneal staining, a test that uses colorful dyes to highlight areas of irregularity and damage on the ocular surface. “The corneal staining score is the only thing that correlates with the pain or blurred vision,” says Akpek, who would like to see the FDA adopt corneal staining and patient-reported outcomes as the primary criteria when evaluating any new drugs for the treatment of dry eye.

In fact, as lead investigator for one of the newly approved eye drops, she included corneal staining and responder analyses, both of which showed that the medication actually made a difference for the patients it’s intended to help.

She recently submitted a paper arguing for the need for standardized methodology when evaluating drugs for the treatment of dry eye, to include corneal staining, given its clinical correlation with ocular inflammation and the direct impact on visual function. “Dry eye is mostly about quality of life,” Akpek says. “Patients don’t care about tear production. They just want to feel better and see better.”