Published in Ocular Surface

The Missing Piece of the Therapeutic Equation: Excessive Tear Evaporation in Dry Eye Disease

This post is sponsored by Bausch + Lomb
6 min read

“To effectively combat the rising tide of dry eye disease, it is now more critical than ever to consider etiology and the mechanisms underlying a patient’s DED, emphasizing the need for development of prescription anti-evaporative drop therapies that address this root cause of the disease.” —Darrell E. White, MD

The Missing Piece of the Therapeutic Equation: Excessive Tear Evaporation in Dry Eye Disease
Dry eye disease (DED) is a multifactorial disease of the tears and ocular surface that results in tear film instability, symptoms of discomfort, and visual disturbance accompanied by potential damage to the ocular surface.1 Despite the multifactorial nature of DED, the current body of evidence has clearly elucidated excessive tear evaporation as a key driver,2 with up to 90% of cases having an evaporative etiology (Figure 1).3-5 Presently, there are no prescription drops available that target excessive tear evaporation,6-9 constituting a considerable shortfall in the current DED treatment armamentarium.
Figure 1. Classification of DED according to underlying cause(s)3
Figure 1. Classification of DED according to underlying cause(s)3
As one of the most prevalent medically treatable eye diseases seen by eye care professionals,2,10 DED has emerged as a growing public health concern. DED conveys a socioeconomic burden that interferes with quality of life, including visual disturbance, ocular discomfort, reduced vitality, eye pain, and limitations in performing daily activities.2
The COVID-19 pandemic has further intensified the urgency to address the growing burden of DED. While the impact of the pandemic on DED is still an active area of research, it has been postulated that new onset or worsening of symptoms may be associated with such factors as rising screen time in an increasingly digital world,11 chronic sequelae associated with contraction of SARS-CoV2,12 and increased tear evaporation following prolonged mask use.13 To effectively combat the rising tide of DED, it is now more critical than ever to consider etiology and the mechanisms underlying a patient’s DED, emphasizing the need for development of prescription anti-evaporative drop therapies that address this root cause of the disease.

Pathophysiology of evaporative DED

Meibomian gland dysfunction (MGD) is widely recognized as the primary driver of evaporative DED.3-5 Together, a growing body of population-based studies strongly suggest that among patients with DED, a large majority—roughly 70%-90%—display evidence of MGD.3-5
Meibum is a complex lipid secretion of the meibomian glands that forms the tear film lipid layer, which protects the ocular surface as an essential part of a healthy tear film.14 MGD is characterized by changes in meibum composition and reduced meibum secretion with resultant breakdown of the tear film lipid layer.15,16 MGD is progressive, with increasing gland atrophy and dropout as well as reduction of meibum quality and quantity as patients age.16 MGD causes unchecked evaporation and tear film instability, triggering a self-perpetuating cycle of ocular surface damage, downstream inflammation, and worsening of DED symptoms, as shown in Figure 2.2,17
Figure 2. The vicious, self-perpetuating cycle of evaporative DED.

Desiccation stress and downstream inflammation

Following breakdown of the tear film lipid layer and accelerated rates of evaporation, desiccation stress further complicates the course of DED. Desiccation stress occurs when tear evaporation exceeds tear production, leading to drying and damage of the corneal epithelium; cell apoptosis; upregulation of innate and adaptive inflammatory pathways; and loss of goblet cells and tight junctions.17 These events ultimately contribute to a loss of ocular surface homeostasis, as supported by recent literature, including research utilizing a murine model of desiccation stress.18

Current treatments: Benefits and challenges

Directly managing excessive evaporation downstream of MGD could potentially help address the cycle of ocular surface damage and inflammation that chronically persists in patients with evaporative dry eye. Current devices and procedures—including intense pulsed light,19,20 thermal pulsation,21 and hot compresses—that help address a key upstream driver of evaporation, MGD, have shown evidence of providing at least short-term relief from DED signs and symptoms.
Current prescription treatment options are effective at targeting two of three potential contributing factors to DED: tear insufficiency and inflammation. However, anti-inflammatories and tear stimulators may be insufficient to resolve symptoms of DED,22 and the side-effect profile associated with topical steroids limits their potential use to a 2-week course.7 These limitations are further compounded by high discontinuation and low adherence rates to available therapies. Real-world analysis of cyclosporine and lifitegrast usage found that over 60% of patients with DED discontinued these treatments within 12 months of initiation.23 This demonstrates a significant unmet need for additional DED treatments that address the underlying etiology of the disease.


Excessive tear evaporation continues to hinder DED treatment efforts. No prescription drops targeting evaporation are currently available.6-9 As long as excessive evaporation continues to occur, signs and symptoms of DED may chronically persist.
Dr. White is a paid consultant of Bausch & Lomb Incorporated or its affiliates.

  1. Lemp MA. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf. 2007;5(2):75-92. doi:10.1016/S1542-0124(12)70081-2
  2. Craig JP, Nelson JD, Azar DT, et al. TFOS DEWS II report executive summary. Ocul Surf. 2017;15(4):802-812. doi:10.1016/j.jtos.2017.08.003
  3. Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 2012;31(5):472-478. doi:10.1097/ICO.0b013e318225415a
  4. Rabensteiner DF, Aminfar H, Boldin I, Schwantzer G, Horwath-Winter J. The prevalence of meibomian gland dysfunction, tear film and ocular surface parameters in an Austrian dry eye clinic population. Acta Ophthalmol. 2018;96(6):e707-e711. doi:10.1111/aos.13732
  5. Badian RA, Utheim TP, Chen X, et al. Meibomian gland dysfunction is highly prevalent among first-time visitors at a Norwegian dry eye specialist clinic. Sci Rep. 2021;11(1):23412. doi:10.1038/s41598-021-02738-6
  6. Cequa. Prescribing information. Sun Pharmaceutical Industries, Inc; 2019.
  7. Eysuvis. Prescribing information. Kala Pharmaceuticals; 2022.
  8. Restasis. Prescribing information. Allergan; 2017.
  9. Xiidra. Prescribing information. Novartis Pharmaceuticals Corporation; 2020.
  10. Uchino M, Schaumberg DA. Dry eye disease: impact on quality of life and vision. Curr Ophthalmol Rep. 2013;1(2):51-57. doi:10.1007/s40135-013-0009-1
  11. Saldanha IJ, Petris R, Makara M, Channa P, Akpek EK. Impact of the COVID-19 pandemic on eye strain and dry eye symptoms. Ocul Surf. 2021;22:38-46. doi:10.1016/j.jtos.2021.06.004
  12. Gambini G, Savastano MC, Savastano A, et al. Ocular surface impairment after coronavirus disease 2019: a cohort study. Cornea. 2021;40(4):477-483. doi:10.1097/ICO.0000000000002643
  13. White, DE. MADE: a new coronavirus-associated eye disease. Ocular Surgery News blog. June 22, 2020. Accessed August 24, 2022.
  14. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011;52(4):1922-1929. doi:10.1167/iovs.10-6997a
  15. Bron AJ, de Paiva CS, Chauhan SK, et al. TFOS DEWS II pathophysiology report. Ocul Surf. 2017;15(3):438-510. doi:10.1016/j.jtos.2017.05.011
  16. Yeotikar NS, Zhu H, Markoulli M, Nichols KK, Naduvilath T, Papas EB. Functional and morphologic changes of meibomian glands in an asymptomatic adult population. Invest Ophthalmol Vis Sci. 2016;57(10):3996-4007. doi:10.1167/iovs.15-18467
  17. Pflugfelder SC, de Paiva CS. The pathophysiology of dry eye disease: what we know and future directions for research. Ophthalmology. 2017;124(11S):S4-S13. doi:10.1016/j.ophtha.2017.07.010
  18. Zhang R, Pandzic E, Park M, Wakefield D, Di Girolamo N. Inducing dry eye disease using a custom engineered desiccation system: impact on the ocular surface including keratin-14-positive limbal epithelial stem cells. Ocul Surf. 2021;21:145-159. doi:10.1016/j.jtos.2021.04.006
  19. Tashbayev B, Yazdani M, Arita R, Fineide F, Utheim TP. Intense pulsed light treatment in meibomian gland dysfunction: a concise review. Ocul Surf. 2020;18(4):583-594. doi:10.1016/j.jtos.2020.06.002
  20. Suwal A, Hao JL, Zhou DD, Liu XF, Suwal R, Lu CW. Use of intense pulsed light to mitigate meibomian gland dysfunction for dry eye disease. Int J Med Sci. 2020;17(10):1385-1392. Published online June 1, 2020. doi:10.7150/ijms.44288
  21. Qiao J, Yan X. Emerging treatment options for meibomian gland dysfunction. Clin Ophthalmol. 2013;7:1797-1803. doi:10.2147/OPTH.S33182
  22. White DE, Zhao Y, Jayapalan H, Machiraju P, Periyasamy R, Ogundele A. Treatment satisfaction among patients using anti-inflammatory topical medications for dry eye disease. Clin Ophthalmol. 2020;14:875-883. Published 2020 Mar 19. doi:10.2147/OPTH.S233194
  23. 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
Darrell E. White, MD
About Darrell E. White, MD

Darrell White, MD, is the president and CEO of SkyVision Centers in Westlake, Ohio. He successfully planned, launched, and built his patient-centered eyecare business, in addition to creating a unique business and marketing model for the integration of multiple types of practitioners. Dr. White is a consultant for Bausch & Lomb as well as a member of the editorial board for Ocular Surgery News.

Darrell E. White, MD
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