Optimizing the diagnosis and treatment of evaporative dry eye through meibomian gland management

(Image credit: AdobeStock/Syda Productions)

Patients with evaporative dry eye (EDE) typically produce plenty of tears, but because the meibomian glands (MG) are not releasing enough oil, the lipid layer of the tear film is deficient. The tear film will spread unevenly and break up quickly, leaving many patients with ocular dryness, burning, irritation, intermittent blur, and, eventually, inflammation.

I screen most of my patients for EDE. This screening includes a good history, evaluation of the tear film and tear breakup time, corneal and conjunctival staining, and—perhaps most importantly—diagnostic gland expression. Meibography with a noninvasive imaging device (LipiView; Johnson and Johnson Vision) is also frequently performed, particularly in patients where EDE is suspected. With healthy MGs, you should see about one-third to one-half of the lower lid glands (and especially those on the nasal side) actively expressing meibum that is olive oil-like in consistency and appearance.¹ If the meibum is more of a toothpaste-like consistency, or the glands are not expressing at all, that is a clear sign of MG dysfunction and EDE.

The first step is to clear the blockage in the glands. No treatment for the ocular surface will truly work well unless you can address the obstruction and restore proper function to the MGs, allowing healthy lipids to be released into the tear film. Vectored thermal pulsation (LipiFlow; Johnson and Johnson Vision), which I combine with microblepharoexfoliation (BlephEx), is my preferred approach for addressing inspissated or blocked glands due to its proven safety and efficacy over the past 15 years.² Other in-office treatment options include iLux (Alcon) and TearCare (Sight Sciences).

Once the glands are treated, new semifluorinated alkane (SFA) therapies, which are water-free and preservative-free, can be introduced as supplementary treatments. Already in clinical use in ophthalmology for vitreoretinal surgery, SFAs have many other potential applications in medicine due to their unique properties, which include being physiologically inert, laser stable, and having the ability to self-aggregate into stable, well-organized supramolecular units.³ In rabbit studies, SFAs have been shown to improve the lipid layer after instillation and to rapidly spread on the ocular surface, with a near-zero contact angle.⁴ They also have the ability to dissolve lipophilic drugs, making them an effective vehicle for other agents.³

One of these SFA drops for topical use is a 100% perfluorohexyloctane drop for EDE (Miebo; Bausch and Lomb), for which I served as a clinical trial investigator. In a pooled analysis of two pivotal studies in which patients with clinical signs of MG dysfunction were enrolled and treated with one drop 4 times daily for eight weeks, there was a statistically significant improvement in total corneal fluorescein staining as early as Day 15. By Day 57, study subjects had a 32% improvement in staining vs a 16% improvement in the saline control group (P < .0001). Patients’ visual analog scores for eye dryness also improved significantly more than in the control group.⁵ Another study demonstrated that these improvements were maintained through one year.⁶ This agent is able to supplement and extend the benefits of thermal pulsation by directly addressing excessive tear evaporation.

For patients whose EDE also includes an inflammatory component, a novel immunomodulator in our toolbox (Vevye; Harrow) contains cyclosporine 0.1% dissolved in the SFA perfluorobutylpentane. Because of the SFA, it supports the tear film lipid layer even as it provides rapid onset of symptomatic relief. In this case, the SFA also increases the bioavailability and corneal penetration of cyclosporine, a drug with notoriously poor solubility.⁷ In my experience, compliance with this agent is better than with earlier-generation immunomodulators because patients do not complain of stinging, burning, or dysgeusia. I find it a nice alternative for those with known EDE or for patients who have already tried other immunomodulators but have stopped them because of intolerance or lack of efficacy.

I spend some time educating patients on the importance of addressing the root cause of EDE with vectored thermal pulsation. Then, a regimen of hot compresses, lid scrubs, perfluorohexyloctane drops, high-quality re-esterified omega-3 nutritional therapy, and when needed, cyclosporine in perfluorobutylpentane, can all help to maintain the newly cleared glands and promote healthy tears for patients with EDE.

Note: The thoughts and opinions expressed are those of the author and do not necessarily represent the opinions of this publication.

Alice T. Epitropoulos, MD, FACS

E: eyesmd33@gmail.com

Epitropoulos is in practice at Ophthalmic Surgeons and Consultants of Ohio and The Eye Center of Columbus and serves as a clinical assistant professor at The Ohio State University. She has received grants or research support from Bausch and Lomb and Sylentis, serves as chief medical officer of Physician Recommended Nutriceuticals (PRN), has patent royalty rights for the Hilco EpiGlare Tester, and is a consultant for many companies involved in ocular surface and lid disease treatment, including Alcon, Allergan (AbbVie), Bausch and Lomb, Biotissue, Bruder Healthcare, Dompe, Horizon (Amgen), ImprimisRx, Johnson and Johnson Vision, Ocular Therapeutix, Oyster Point (Viatris), PRN, Sight Sciences, Sun Ophthalmics, Tarsus Pharmaceuticals, and Trukera.

References

1. Tomlinson A, Bron AJ, Korb DR, et al. The international workshop on meibomian gland dysfunction: report of the diagnosis subcommittee. Invest Ophthalmol Vis Sci. 2011;52(4):2006-2049. Published March 30, 2011. doi:10.1167/iovs.10-6997f

2. Blackie CA, Murakami D, Donnenfeld E, Oliff HS. Vectored thermal pulsation as a treatment for meibomian gland dysfunction: a review spanning 15 years. Ophthalmol Ther. 2024;13(8):2083-2123. doi:10.1007/s40123-024-0976-1

3. Tsagogiorgas C, Otto M. Semifluorinated alkanes as new drug carriers — an overview of potential medical and clinical applications. Pharmaceutics. 2023;15(4):1211. Published April 11, 2023. doi:10.3390/pharmaceutics15041211

4. Agarwal P, Khun D, Krösser S, et al. Preclinical studies evaluating the effect of semifluorinated alkanes on ocular surface and tear fluid dynamics. Ocul Surf. 2019;17(2):241-249. doi:10.1016/j.jtos.2019.02.010

5. Miebo. Prescribing information. Bausch and Lomb; 2023. Accessed January 20, 2025. https://pi.bausch.com/globalassets/pdf/packageinserts/pharma/miebo-package-insert.pdf

6. Protzko EE, Segal BA, Korenfeld MS, Krösser S, Vittitow JL. Long-term safety and efficacy of perfluorohexyloctane ophthalmic solution for the treatment of patients with dry eye disease: the KALAHARI study. Cornea. 2024;43(9):1100-1107. doi:10.1097/ICO.0000000000003418

7. Agarwal P, Scherer D, Günther B, Rupenthal ID. Semifluorinated alkane based systems for enhanced corneal penetration of poorly soluble drugs. Int J Pharm. 2018;538(1-2):119-129. doi:10.1016/j.ijpharm.2018.01.019