Light After the Storm: A Hopeful Look Ahead for Dry Eye Disease

By Laura M. Periman, MD

To treat a multifactorial condition like dry eye disease (DED), we need a multidisciplinary approach. Every new medication or therapeutic procedure is a new ray of light that improves our ability to provide targeted, directed, and comprehensive treatments for all facets of DED. New and emerging therapies address the underlying inflammatory mechanisms of DED and the consequences on the cornea, nerves, goblet cells, and meibomian glands that in turn contribute to an unstable tear film. The clouds of frustration are clearing for patients with DED and the future looks bright.

Light Shining Through the Clouds: New Help for Inflammation
A number of in-office procedures for DED have become available over the last 10 years, offering us a way to physically improve the meibomian gland dysfunction (MGD) that accompanies and contributes to DED. Thermal treatments such as LipiFlow from Johnson & Johnson Vision, TearCare from Sight Sciences, and iLux from Alcon all help us improve meibomian gland function.

An exciting new light-based, in-office procedure, OptiLight from Lumenis, has been shown to significantly improve tear breakup time, meibum quality, and meibomian gland expressibility,¹ decrease pro-inflammatory mediators,^2,3 and reduce the population of Demodex mites.⁴ OptiLight uses Lumenis’ patented Optimal Pulse Technology (OPT), the first and only intense pulsed light (IPL) therapy to be FDA approved for dry eye disease associated with MGD. Because most people with dry eye disease have MGD, OptiLight is an effective choice for many patients.

OptiLight features consistent energy delivery, which enhances safety, and is elegant to use. Each treatment takes about 15 minutes, which has made it easy to efficiently integrate into the practice. I now perform about 20 OptiLight procedures each week. My patients are very happy with the results, and they appreciate the convenience of having an in-office procedure.

After the Rain Drops: Topical Drops Go Beyond Hydration
Our go-to immunomodulators such as cyclosporin (Restasis, Allergan; Cequa, Sun Ophthalmics) and lifitegrast (Xiidra, Novartis) continue to be staples of the dry eye toolkit for addressing inflammation, which is at the epicenter of DED. Many of us have seen the positive results of immunomodulators as part of a comprehensive, long-term approach to controlling inflammation associated with DED. Once approved, the robust pipeline will expand our offerings to patients.

• Addressing combined ocular allergies and DED – Patients with DED can also have ocular allergies. In fact, the allergic cascade has an immunologic bridge to MGD as discussed in a recent review paper on the immunopathophysiology of DED.⁵ Far upstream of the adaptive immunity of DED is the activation of the innate immunity via liberation of reactive aldehyde species (RASP). To address this, Aldeyra Therapeutics has a new topical medication in phase 3 FDA trials called Reproxalap that works by inhibiting RASP. By neutralizing the aldehyde load far upstream, the drug may reduce downstream inflammation from DED and allergies.⁶
• Stimulating nerve recovery – With more awareness of early-stage neurotrophic changes in dry eye (stage 1 NK), we see where two new pipeline drugs may aid in the treatment of associated DED by promoting nerve regeneration of the corneal sub-basal plexus. Tavilermide from Mimetogen Pharmaceuticals is a nerve growth factor (NGF) mimetic in phase 3 FDA trials for DED and in phase 1 clinical trials for glaucoma.⁷ Neuroptika’s NRO-1 releases glial cell-derived neurotrophic factor, which may regenerate corneal nerves and promote wound healing.⁸
• Delivering a new kind of eye drop – With the goal of improving drug performance and reducing corneal toxicity, several companies are now developing topical drops for DED based on a patented water-free preservative-free vehicle by Novaliq called EyeSol.⁹ Novaliq’s CyclaSol is a water-free cyclosporin formulation, while NOV03 from Bausch + Lomb delivers perfluorohexyloctane, which has demonstrated highly statically significant improvement in corneal fluorescein staining and eye dryness scores.¹⁰
• Targeting DED with steroids – In recent years, I’ve been using steroid formulations indicated for ocular surface inflammation, such as Flarex (Eyevance, now Santen) and Lotemax SM (Bausch + Lomb) to treat patients with DED. Kala Pharmaceuticals’ Eysuvis, a low-dose loteprednol formulation with mucin barrier-penetrating technology, recently became the first steroid FDA approved specifically for the short-term treatment of DED including dry eye flares. DED patients can expect to have occasional flares, even if they’re controlled on chronic therapy.¹¹ Now Ocular Therapeutix, which makes the Dextenza intracanalicular insert of dexamethasone, is conducting clinical trials on a preservative-free insert, OTX-DED, to deliver the steroid short-term for patients with DED.¹²

The Rainbow: A Colorful Array of Options for DED
New DED therapeutics and devices are exciting to me as an ocular surface disease expert. The pipeline is promising. The multidisciplinary approaches that my practice offers to our patients with moderate or severe DED commonly include OptILight, iLux, chronic immunomodulators, and occasional steroids in addition to omega fatty acid supplements and lifestyle changes. The comprehensive approach helps patients achieve excellent relief and synergistic results. For patients who have suffered the storms DED, symptomatic relief is truly a ray of sunshine.

Reference

1. Lumenis Receives FDA Approval for Its IPL Device to Manage Dry Eye Disease and Launches OptiLight™. https://www.prnewswire.com/news-releases/lumenis-receives-fda-approval-for-its-ipl-device-to-manage-dry-eye-disease-and-launches-optilight-301280500.html Accessed July 20, 2021.
2. Liu R, Rong B, Tu P, et al. Analysis of Cytokine Levels in Tears and Clinical Correlations After Intense Pulsed Light Treating Meibomian Gland Dysfunction. Am J Ophthalmol. 2017 Nov;183:81-90.
3. Yin Y, Liu N, Gong L, et al. Changes in the Meibomian Gland After Exposure to Intense Pulsed Light in Meibomian Gland Dysfunction (MGD) Patients. Curr Eye Res. 2018 Mar;43(3):308-313.
4. Prieto VG, Sadick NS, Lloreta J, et al. Effects of intense pulsed light on sun-damaged human skin, routine, and ultrastructural analysis. Lasers Surg Med. 2002;30(2):82-5.
5. Periman LM, Perez VL, Saban DR, et al. The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options. J Ocul Pharmacol Ther. 2020 Apr;36(3):137-146
6. Aldeyra Therapeutics Announces Positive Top-Line Symptom and Sign Results from Run-In Cohort of Phase 3 TRANQUILITY Trial in Dry Eye Disease. https://www.businesswire.com/news/home/20210107005235/en/Aldeyra-Therapeutics-Announces-Positive-Top-Line-Symptom-and-Sign-Results-from-Run-In-Cohort-of-Phase-3-TRANQUILITY-Trial-in-Dry-Eye-Disease Accessed July 18, 2021.
7. Mimetogen pharmaceuticals completes enrollment of mim-728 phase 3 trial for tavilermide for dry eye disease. http://www.mimetogen.com/news-publications/press-releases/3910-mimetogen-pharmaceuticals-completes-enrollment-of-mim-728-phase-3-trial-for-tavilermide-for-dry-eye-disease.html Accessed July 18, 2021.
8. Neuroptika Completes Enrollment In Phase 2 Clinical Trial For Dry Eye Disease. https://www.prnewswire.com/news-releases/neuroptika-completes-enrollment-in-phase-2-clinical-trial-for-dry-eye-disease-301112656.html#:~:text=17%2C%202020%20%2FPRNewswire%2F%20%2D%2D,patients%20with%20dry %20eye%20disease Accessed July 18, 2021.
9. Novaliq Announces First Patient Randomized in the Phase 3 trial ESSENCE-2 of CyclASol® Topical Ophthalmic Solution for the Treatment of Dry Eye Disease. https://www.prnewswire.com/news-releases/novaliq-announces-first-patient-randomized-in-the-phase-3-trial-essence-2-of-cyclasol-topical-ophthalmic-solution-for-the-treatment-of-dry-eye-disease-301187240.html Accessed July 18, 2021.
10. Bausch + Lomb Completes Enrollment Of Second Phase 3 Study For NOV03 (perfluorohexyloctane) https://ir.bauschhealth.com/news-releases/2021/07-07-2021-115911689 Accessed July 18, 2021.
11. Kala Pharmaceuticals Announces FDA Approval of EYSUVIS™ for the Short-Term Treatment of the Signs and Symptoms of Dry Eye Disease. https://www.biospace.com/article/releases/kala-pharmaceuticals-announces-fda-approval-of-eysuvis-for-the-short-term-treatment-of-the-signs-and-symptoms-of-dry-eye-disease/ Accessed July 19, 2021.
12. Ocular Therapeutix™ Announces First Patient Dosed in Phase 2 Clinical Trial of OTX-DED for the Short-Term Treatment of the Signs and Symptoms of Dry Eye Disease. https://www.businesswire.com/news/home/20210301005290/en/Ocular-Therapeutix™-Announces-First-Patient-Dosed-in-Phase-2-Clinical-Trial-of-OTX-DED-for-the-Short-Term-Treatment-of-the-Signs-and-Symptoms-of-Dry-Eye-Disease Accessed July 19, 2021.