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Dry Eye/OSD
Exclusives

Inflammation and Dry Eye Flares: There’s a Drop for That

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Effective communication around the acute exacerbation of dry eye symptoms can help patients get relief.

 

By Francis Mah, MD

 

The role of inflammation in ocular surface disease (OSD) has become firmly established over the past 2 decades. Previously, the extent to which inflammation was involved in dry eye disease (DED) was perhaps considered somewhat controversial. More recently, however, we have begun to better understand DED and the concept of dry eye flares—periodic acute exacerbations of symptoms caused by any number of various triggers.

 

Inflammatory Response

Within the human immune system, exposure to an inflammation-causing event sets off an adaptive and innate response. With repeated exposures, the cycle could potentially continue to persist and the progression of the body’s response could accelerate priming the pump for a future dry eye flare. In DED specifically, inflammation is associated with an upregulation of intercellular adhesion molecule-1 along with matrix metalloproteinases, chemokines, tumor necrosis factor alpha, interleukins (ie, IL-1,6, and 8) in the epithelial cells of conjunctival and lacrimal tissues.1,2 These enzymes and inflammatory cells act like a moth to a flame by activating the inflammatory cascades inclusive of T-cell proliferation which mediates a neurosensory response leading to symptoms such as discomfort and irritation.

 

Similar to other chronic inflammatory conditions, we know a majority of DED patients have periodic flares rather than continuous symptoms.3 These episodic and acute symptomatic exacerbations are much more common than we may have realized in the past, affecting 80% or more of patients, and can be set off by a variety of activities and environmental situations.4 These dry eye flares may occur sporadically or cyclically depending on the trigger.

 

For example, dry eye flares may be more cyclical in a person who has seasonal allergies as a comorbidity triggering an inflammatory response that in turn causes an increase in dry eye symptoms. Other inciting factors such as travel that is often associated with low ambient humidity occur more sporadically. Contact lens use, blepharitis, and even stress that results in poor eating, sleeping, and hydration can trigger an exacerbation of symptoms.5-13

 

What to Say to Patients

Many times, patients present during a flare without necessarily having chronic disease. They may think of what they are experiencing as a random event or even mistakenly describe it as “an infection.” By asking directed questions, we can determine what has changed in their environment or lifestyle to initiate appropriate treatment as well as counsel them about other potential modifications for consideration. With proper education, patients are empowered to seek earlier treatment rather than letting their symptoms linger and intensify for several days or weeks.

 

In the past, off-label corticosteroids were our primary option for these patients. That has changed with the availability of FDA-approved Eysuvis (loteprednol etabonate ophthalmic suspension 0.25%; Kala Pharmaceuticals), indicated for the short-term (up to 2 weeks) treatment of the signs and symptoms of DED. Its formulation and dosing regimen have been well investigated, showing the agent to be effective with most patients feeling some relief within a week. Most importantly and from my clinical experience, it has been found generally safe in terms of the things that we are concerned about with topical steroids, such as IOP spikes and cataract development.

 

Loteprednol etabonate ophthalmic suspension 0.25% was studied in more than 2800 patients with DED, and the drop was well-tolerated with a low incidence of IOP increase similar to vehicle. In treatment and vehicle groups respectively, 0.2% and 0% of subjects experienced a ≥10 mm Hg increase from baseline resulting in an IOP measurement of ≥21 mm Hg at any post-baseline visit up to 29 days.14-16 Researchers observed statistically significant improvement in the measures of conjunctival hyperemia and patient-reported ocular discomfort severity score among subjects who were dosed 4 times a day for 2 weeks. Those treated with Eysuvis experienced rapid relief as measured by an improvement in symptoms as early as day 4.16 The drop has a novel formulation utilizing Ampplify, a proprietary mucus-penetrating particle technology. Nanoparticles of ~300 nm in diameter are coated to facilitate their penetration through the mucus barrier. This controlled delivery system enables the drop to spread more uniformly across the ocular surface.

 

In My Clinic

In my experience, the vast majority of patients feel better within a week and experience no IOP spikes. After a follow-up visit at 4 to 6 weeks, I am comfortable having compliant patients keep the medication on hand to use 4 times a day for 2 weeks as needed several times a year. In educating patients, I say: “This drug is not meant to be used for 2 weeks every month. If you start having to use it 4 times a day for 2 weeks, every single month, we need to re-evaluate and ensure we have the correct diagnosis and optimal therapy.” At that point, I would want to add or alter therapy to ensure patients are not overusing the medication.

 

I also implement Eysuvis as induction therapy when starting chronic medications like cyclosporine or lifitegrast, especially in cases where patients are very inflamed, or prior to cataract or refractive surgery. I let them know that the drop will help quiet their eyes while we wait for the chronic therapy to take effect. Examples are patients with contact lens-associated keratopathy or those with underlying conditions such as Sjögren’s syndrome or rheumatoid arthritis. Loteprednol etabonate ophthalmic suspension 0.25% is a nice bridge therapy.

 

Conclusion 

Eysuvis, specifically developed to be the steroid of choice for the short-term treatment of the signs and symptoms of DED, has been well studied. It was purposefully formulated with a low concentration of the active ingredient loteprednol etabonate and created with nanotechnology that enhances ocular surface penetration. We now have an on-label drop to help patients with dry eye flares feel better quickly.

 

Francis S. Mah, MD is Director, Cornea Service, Scripps Clinic, La Jolla, California

Contact: [email protected]

Financial disclosure: Consultant to Allergan, and Abbvie Company, Kala Pharmaceuticals, Novartis, Oyster Point, and Sun Pharmaceuticals.

 

Reference
1. Pflugfelder SC, de Paiva CS. The pathophysiology of dry eye disease: what we know and future directions for research. Ophthalmology. 2017;124:S4–S13.
2. Gao J, Morgan G, Tieu D, et al. ICAM-1 expression predisposes ocular tissues to immune-based inflammation in dry eye patients and Sjögrens syndrome-like MRL/lpr mice. Exp Eye Res. 2004;78(4):823-835.
3. Perez VL, Stern ME, Pflugfelder SC. Inflammatory basis for dry eye disease flares. Exp Eye Res. 2020;201:108294. doi: 10.1016/j.exer.2020.108294
4. Lienert JP, Tarko L, Uchino M, et al. Long-term natural history of dry eye disease from the patient’s perspective. Ophthalmology. 2016;123(2):425-433. doi: 10.1016/j.ophtha.2015.10.011.
5. Rolando M, Zierhut M, Barabino S. Should we reconsider the classification of patients with dry eye disease? Ocul Immunol Inflamm. 2021;29(3):521-523. DOI: 9.1080/09273948.2019.1682618.
6. Amparo F, Dana R. Web-based longitudinal remote assessment of dry eye symptoms. Ocul Surf. 2018;16:249–253.
7. Iyer JV, Lee SY, Tong L. The dry eye disease activity log study. ScientificWorldJournal. 2012;2012: 589875.
8. Karakus S, Agrawal D, Hindman HB, et al. Effects of prolonged reading on dry eye. Ophthalmology. 2018;125:1500–1505.
9. Kim Y, Paik HJ, Kim MK, et al. Short-term effects of ground-level ozone in patients with dry eye disease: a prospective clinical study. Cornea. 2019;38:1483–1488.
10. Ousler GW, Rimmer D, Smith LM, et al. Use of the controlled adverse environment (CAE) in clinical research: a review. Ophthalmol Ther. 2017;6:263–276.
11. López-Miguel A, Tesón M, Martín-Montañez V, et al. Dry eye exacerbation in patients exposed to desiccating stress under controlled environmental conditions. Am J Ophthalmol. 2014;157:788–798.
12. Teson M, Gonzalez-Garcia MJ, Lopez-Miguel A, et al. Influence of a controlled environment simulating an in-flight airplane cabin on dry eye disease. Invest Ophthalmol Vis Sci. 2013;54:2093–2099.

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