Inflammation is an important therapeutic target for managing dry eye disease (DED) and meibomian gland dysfunction because of its role in the pathophysiology of both diseases and in promoting ocular surface breakdown and symptoms of irritation. Multiple options—steroid and nonsteroidal topical medications—are available for controlling inflammation (Table).

Table. Topical Anti-Inflammatory Medications for Dry Eye Disease

Abbreviations: DED, dry eye disease; KCS, keratoconjuctivitis sicca; PF, preservative free.

Cyclosporine (CsA) emulsion, 0.05%, was the first topical anti-inflammatory medication approved with a specific indication for treating DED. It remains a useful option. Burning on instillation and delay in onset of benefit, however, can limit treatment adherence. A topical steroid used before starting CsA, 0.05%, or concomitantly can accelerate improvement and increase CsA tolerability.¹

Loteprednol etabonate and fluorometholone are less likely to increase intraocular pressure than other steroids.² Loteprednol etabonate is available in multiple formulations designed to improve bioavailability, including loteprednol etabonate, 0.25%, which is specifically approved for short-term use to treat dry eye flares.³

In addition, the lymphocyte function-associated antigen-1 antagonist lifitegrast and newer formulations of CsA have emerged that offer more rapid onset of action than does CsA, 0.05%, and a favorable safety profile (Table). In four 12-week trails including 2133 adults, lifitegrast, 5%, was shown to improve the signs and symptoms of DED as early as 2 weeks.⁴ Cyclosporine ophthalmic solution, 0.09%, is a clear, aqueous nanomicellar formulation that was investigated in 2 multicenter, randomized, vehicle-controlled trials enrolling 1046 patients.^5-7 In both studies, CsA, 0.09%, was associated with significantly greater improvement in total corneal fluorescein staining (tCFS) and central corneal fluorescein staining at day 28. At day 14, there were numerical differences favoring CsA vs vehicle in tCFS, conjunctival staining, and tear breakup time.⁸ Instillation site pain was reported by 21.8% of patients using CsA, 0.09%, but it was mostly mild, and 85% to 90% of patients reported no or mild discomfort at 3 minutes postinstillation.^6,7

Cyclosporine, 0.1%, is formulated in a preservative-, water-, and oil-free semifluorinated alkane vehicle that enables ocular surface spreading, prolongs residence time, minimizes blur, and increases penetration of the active ingredient.^9-11 The drop is also dispensed in a small volume (10 μL), which minimizes overflow and tear film destabilization.¹¹ In the vehicle-controlled ESSENCE-1 and ESSENCE-2 pivotal trials, CsA, 0.1%, was associated with significant improvements in tCFS and central corneal fluorescein staining at week 2 and significant improvements in DED symptoms.^12,13 Instillation site pain was the most common adverse event, occurring in approximately 8% of patients.¹⁴

References

1. Sheppard JD, Donnenfeld ED, Holland EJ, et al. Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%. Eye Contact Lens. 2014;40(5):289-296.
2. Chang DF, Tan JJ, Tripodis Y. Risk factors for steroid response among cataract patients. J Cataract Refract Surg. 2011;37(4):675-681.
3. Loteprednol etabonate suspension. Package insert. US National Library of Medicine. Updated March 26, 2024. Accessed July 29, 2024. https://dailymed.nlm.nih.gov/dailymed/
4. Holland EJ, Darvish M, Nichols KK, Jones L, Karpecki PM. Efficacy of topical ophthalmic drugs in the treatment of dry eye disease: a systematic literature review. Ocul Surf. 2019;17(3):412-423.
5. Malhotra R, Devries DK, Luchs J, et al. Effect of OTX-101, a novel nanomicellar formulation of cyclosporine A, on corneal staining in patients with keratoconjunctivitis sicca: a pooled analysis of phase 2b/3 and phase 3 studies. Cornea. 2019;38(10):1259-1265.
6. Toyos M, Gupta PK, Mitchell B, Karpecki P. The effect of OTX-101 on tear production in patients with severe tear-deficient dry eye disease: a pooled analysis of phase 2b/3 and phase 3 studies. Curr Eye Res. 2022;47(2):220-224.
7. Tauber J, Schechter BA, Bacharach J, et al. A phase II/III, randomized, double-masked, vehicle-controlled, dose-ranging study of the safety and efficacy of OTX-101 in the treatment of dry eye disease. Clin Ophthalmol. 2018;12:1921-1929.
8. Schechter BA, Urbieta M, Bacharach J, et al. Effect of OTX-101 in patients with dry eye disease at day 14 of treatment: ocular surface endpoint results from the phase 2b/3 clinical trial. Clin Ophthalmol. 2022;16:4145-4151.
9. 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.
10. Agarwal P, Korward J, Krösser S, Rupenthal ID. Preclinical characterization of water-free cyclosporine eye drops – factors impacting ocular penetration ex vivo and in vivo. Eur J Pharm Biopharm. 2023;188:100-107.
11. Wirta DL, Torkildsen GL, Moreira HR, et al. A clinical phase II study to assess efficacy, safety, and tolerability of waterfree cyclosporine formulation for treatment of dry eye disease. Ophthalmology. 2019;126(6):792-800.
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.
13. 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.
14. 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.

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