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Examining Dry Eye Disease Flare Treatments

Dry eye is one of the most common eye conditions affecting nearly 16 million Americans, according to the National Eye Institute.1  

While the formal definition for dry eye disease (DED) varies as symptoms and prevalence differ across the globe, researchers published an article2 in which a clinical consensus was reached in a series of 4 meetings with global DED experts to propose a new definition and key criteria for diagnosis. 

“Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities,” stated the authors of the article published in the International Journal of Molecular Sciences. 

Data show that the prevalence of DED is increasing over the last several decades and with it, the need for guided research and improved treatments. 

With the newly proposed and easily applicable definition for DED, the authors believe the condition can be diagnosed with more consistency as well as inform future trials and research. 

Managing Episodic Flares

“Most patients with DED have episodic flares, which can be triggered by a variety of activities and environmental stresses,” explained Perez and colleagues.3 “These flares are typically associated with rapid exacerbation of discomfort symptoms, followed by prolonged elevation of

“Episodic symptoms can be triggered by a variety of activities and environmental stresses including dry or drafty environments, contact lens overwear, exacerbation of systemic autoimmune diseases, toxic medications and preservatives, and allergens, as well as more predictably triggered by cataract and refractive surgery or experimental controlled adverse environments,” said researchers in Perez and colleagues. 

Data show that approximately 80% of DED patients suffer flares4-6 and that inflammation can last for days or possibly even weeks.3 

Although episodic flares are extremely common in patients with DED or those who suffer from dry eye, the cause is not fully understood. Recent data focus3 on the innate and adaptive immune responses and how to suppress them. 

“…ocular surface inflammation in an acute flare begins with a rapid but nonspecific innate immune response, which can be followed by a slower but more specific adaptive immune response,” said Perez and colleagues. 

Acute flares have a number of underlying causes, but researchers note that they typically result from inflammatory cascades, in which corneal epithelial cells are responding to hyperosmolar stress and producing matrix metalloproteinases (MMPs) as well as other mediators. In healthy eyes, MMPs are proteolytic enzymes that can heal injuries but in the case of acute flare, cleave proinflammatory cytokines and other extracellular proteins which amplify an immune response.3

“Understanding of the inflammatory cascades activated during a flare may help to identify specific “flare targets” and guide management, and we are optimistic that additional research will further improve outcomes in the future,” concluded Perez and colleagues. 

Latest Treatment

Because flares and DED are so prevalent, symptoms can be debilitating and reduce quality of life, prompting the need for extended therapy to reduce symptoms. 

The first prescription therapy for the short-term treatment of DED was approved by the US Food & Drug Administration in October 2020 for Kala Pharmaceuticals. Loteprednol etabonate ophthalmic suspension (Eysuvis) 0.25% was approved for the short-term (up to 2 weeks) treatment of the signs and symptoms of DED.7

Eysuvis, an ocular corticosteroid, utilizes Kala Pharmaceuticals’ “mucus-penetrating particle drug delivery technology to enhance penetration of loteprednol etabonate (LE) into target tissue on the ocular surface. LE targets the immune responses that drive acute dry eye disease flares.”7

FDA approval was granted based on the results from 4 clinical trials, including 3 phase 4 trials and one phase 2 trial. Per a press release7 from Kala Pharmaceuticals, statistical significance was achieved after 2 weeks of dosing for the sign endpoint of conjunctival hyperemia in all three phase 3 trials.” Further, “Statistical significance was observed in two of the three phase 3 trials for the symptom endpoints of ocular discomfort severity in both the overall intent-to-treat (ITT) population and in a predefined subgroup of ITT patients with more severe ocular discomfort at baseline.”

“The approval of Eysuvis ushers in a new era in the treatment of dry eye disease and offers promise to the millions of dry eye patients who experience acute exacerbations, or flares, of their disease each year,” said Edward Holland, MD, director of cornea services at Cincinnati Eye Institute and professor of ophthalmology at the University of Cincinnati, OH, in a press release.7 “For the first time we will be able to offer dry eye patients a therapeutic option that provides rapid relief for both the signs and symptoms of the disease and that is safe and well-tolerated.”


  1. National Eye Institute. Dry eye. Updated December 22, 2020. Accessed May 10, 2021.
  2. Tsubota K, Pflugfelder SC, Liu Z, et al. Defining dry eye from a clinical perspective. Int J Mol Sci. 2020 Dec 4;21(23):9271.
  3. Perez VL, Stern ME, Pflugfelder. Inflammatory basis for dry eye disease flares. Exp Eye Res. 2020;201:108294. doi:10.1016/j.exer.2020.108294
  4. Brazzell RK, Zickl L, Farrelly J, et al. Prevalence and characteristics of dry eye flares: a patient questionnaire survey. Presented at: AAO 2019: October 12-15, 2019; San Francisco, CA.
  5. Brazzell RK, Zickl L, Farrelly J, et al. Prevalence and characteristics of symptomatic dry eye flares: results from patient questionnaire surveys. Poster presented at: AAOPT 2019: October 23-27, 2019; Orlando, FL.
  6. 2020 Study of Dry Eye Sufferers. Conducted by Multi-sponsor Surveys, Inc.
  7. BioSpace. Kala Pharmaceuticals Announces FDA Approval of EYSUVIS™ for the Short-Term Treatment of the Signs and Symptoms of Dry Eye Disease [news release]. October 27, 2020. Accessed May 10, 2021.

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