Addressing the root cause of dry eye disease

Dry eye disease (DED) is more prevalent than many might expect, affecting about 37.1 million individuals worldwide and 16.4 million in the US. However, only about 28.1 million globally and 9.1 million domestically treat their symptoms with some form of medication.¹

Although patients sometimes come in specifically requesting a DED evaluation, others frequently report blurry vision, fluctuating clarity, and general eye discomfort when prompted with a survey such as the Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire. Many individuals do not recognize their symptoms as DED—they just know their eyes do not feel right.

Understanding the signs, symptoms, and root cause

The increased incidence of DED is fueled by a modern lifestyle that includes excessive screen time, environmental stressors, and prolonged contact lens wear. Beyond the classic symptoms of irritation, dryness, and redness, DED affects patients in ways that often go unnoticed (Sidebar). DED can impact work productivity, reading speed, photophobia, and even sleep quality, which underscores the importance of early detection and treatment.^2-8

Regardless of whether a patient has evaporative DED (ie, meibomian gland dysfunction) or aqueous-deficient DED (ie, insufficient tear production), the underlying culprit is the same—inflammation. Inflammation is both a cause and a consequence of DED, creating a vicious cycle that leads to worsening symptoms and progressive ocular surface damage.

As the disease advances, inflammatory mediators disrupt tear film stability, damage corneal and conjunctival cells, and impair meibomian gland function.⁹ This ongoing inflammation makes intervention with pharmaceuticals and other measures crucial for symptom relief and preventing long-term ocular surface damage.

Diagnosing DED in clinical practice

Patients do not always self-report dry eye symptoms. I rely on several tools to uncover DED, including a validated survey that helps quantify symptoms (eg, the SPEED questionnaire). In my practice, patients who score 8 or above warrant further investigation. This includes tear breakup time, ocular surface staining, meibomian gland function, and matrix metalloproteinase 9 testing.

The correlation of clinical signs with patient symptoms is key to diagnosing DED in clinical practice. Some clinicians may see DED but hesitate to treat it due to a lack of strong symptoms. This methodology, however, overlooks the progressive nature of the disease. Timely and consistent treatment is key to controlling inflammation, especially when symptoms fluctuate.

Sometimes, patient resistance to treatment or lack of adherence to existing treatments becomes a barrier to symptom relief. Educating patients that DED is a chronic inflammatory condition requiring long-term management—just like high blood pressure or diabetes—is key. I make a point to highlight to patients how untreated DED can impact their vision, quality of life, and even surgical outcomes if they ever need cataract or refractive surgery.

Treatment approaches

Setting realistic expectations can be challenging, as patients often expect instantaneous relief. Traditionally, DED treatments take time to work and frequently require a multimodal approach. Historically, we relied on prescription eye drops like cyclosporine 0.05% (Restasis; AbbVie), lifitegrast 5% (Xiidra; Bausch + Lomb), and cyclosporine 0.09% (Cequa; Sun Ophthalmics). Although effective at managing inflammation across multiple pathways, such treatments may be associated with drawbacks including prolonged time to efficacy; burning and irritation upon instillation; and dysgeusia (ie, altered taste), all of which may lead to a high dropout rate.¹⁰

Studies show that up to 90% of patients discontinued these treatments within a year, largely due to tolerability concerns and perceived lack of efficacy.¹¹ A retrospective cohort study of 73,356 patients from the American Academy of Ophthalmology’s IRIS Registry showed that more than half did not obtain a refill for their prescribed medication (cyclosporine 0.05%, lifitegrast 5%, and cyclosporine 0.09%) and 90% discontinued therapy. Very few (4%) switched to a different DED therapy. The main reasons for switching or discontinuing therapy included lack of efficacy and adverse events.

Cyclosporine is typically a first-line treatment for DED. One of the most exciting advancements in cyclosporine formulations is cyclosporine 0.1% dissolved in a semifluorinated alkane, perfluorobutylpentane (Vevye; Harrow), the first and only cyclosporine approved for the treatment of the signs and symptoms of DED. This next-generation treatment offers significant advantages over older formulations of cyclosporine, including its role in reducing inflammation, increasing tear production, and repairing corneal surface damage.¹²

Unlike traditional cyclosporine drops, my patients have reported minimal stinging and burning upon the instillation of Vevye. Additionally, I have seen a high refill rate, indicating high patient satisfaction.

My experience corresponds with clinical studies indicating that 99.8% of patients experienced no or mild instillation site pain.^12-15 Further, studies have shown clinically meaningful and statistically significant improvement over perfluorobutylpentane in total corneal fluorescein staining by day 15.^16,17

In my practice, a comprehensive approach to DED management is key. We can ensure long-term success by integrating patient education, multimodal treatment, and follow-up strategies. The key is understanding that inflammation is at the core of DED and treating it should be mandatory.

Conclusion

With improved diagnostic tools and the emergence of better-tolerated, more effective treatments, we can enhance our patients’ visual outcomes and quality of life.

References

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2. Dry eye syndrome slows reading rate, study suggests. News release. Johns Hopkins Medicine. November 15, 2018. Accessed February 6, 2025. https://www.hopkinsmedicine.org/news/newsroom/news-releases/2018/11/dry-eye-syndrome-slows-reading-rate-study-suggests
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8. Gu Y, Cao K, Li A, et al. Association between sleep quality and dry eye disease: a literature review and meta-analysis. BMC Ophthalmol. 2024;24(1):152. doi:10.1186/s12886-024-03416-7
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10. White DE, Zhao Y, Ogundele A, et al. Real-world treatment patterns of cyclosporine ophthalmic emulsion and lifitegrast ophthalmic solution among patients with dry eye. Clin Ophthalmol. 2019;13:2285-2292. doi:10.2147/OPTH.S226168
11. Mbagwu M. Characterization of discontinuation and switching patterns of dry eye disease medications using linked EHR registry and claims data. Paper presented at: ASCRS Annual Meeting 2024; April 5-9, 2024; Boston, MA.
12. Sheppard JD, Wirta DL, McLaurin E, et al. A water-free 0.1% cyclosporine A solution for treatment of dry eye disease: results of the randomized phase 2B/3 ESSENCE study. Cornea. 2021;40(10):1290-1297. doi:10.1097/ICO.0000000000002633
13. Vevye. Prescribing information. Harrow; 2023. Accessed March 12, 2025. https://vevyepatient.stagingcontent.site/_files/ugd/984798_fa67b9451a1f4a72bcc5422433d876c0.pdf
14. Akpek EK, Wirta DL, Downing JE, et al. Efficacy and safety of a water-free topical cyclosporine, 0.1%, solution for the treatment of moderate to severe dry eye disease: the ESSENCE-2 randomized clinical trial. JAMA Ophthalmol. 2023;141(5):459-466. doi:10.1001/jamaophthalmol.2023.0709
15. Akpek EK, Sheppard JD, Hamm A, Angstmann-Mehr S, Krösser S. Efficacy of a new water-free topical cyclosporine 0.1% solution for optimizing the ocular surface in patients with dry eye and cataract. J Cataract Refract Surg. 2024;50(6):644-650. doi:10.1097/j.jcrs.0000000000001423
16. Sheppard JD, Wirta DL, McLaurin E, et al. Water-free 0.1% cyclosporine A solution for treatment of dry eye disease: results of the randomized phase 2B/3 ESSENCE study. Cornea. 2021;40(10):1-8. doi:10.1097/ICO.0000000000002633
17. Akpek EK, Wirta DL, Downing JE, et al. Efficacy and safety of a water-free topical cyclosporine, 0.1%, solution for the treatment of moderate to severe dry eye disease: the ESSENCE-2 randomized clinical trial. JAMA Ophthalmol. 2023;141(5):459-466. doi:10.1001/jamaophthalmol.2023.0709.