By Darrell E. White, MD
The contents of this article are informational only and are not intended to be a substitute for professional medical advice, diagnosis, or treatment recommendations. This editorial presents the views and experiences of the author and does not reflect the opinions or recommendations of the publisher of Ophthalmology 360.
Dry eye disease (DED) is a common condition worldwide, and its prevalence is expected to rise, driven by population aging and the growing impact of lifestyle and environmental risk factors.1,2 Detection and management of DED are important because the disease can affect vision, appearance, and comfort, impairing quality of life through reduced productivity, difficulty with vision-related daily tasks, and adverse effects on physical and mental well-being.2,3
Understanding DED pathophysiology and etiology establishes a rationale for effective targeted treatment that relieves existing signs and symptoms while also mitigating the risk of progression. Development and progression of DED can be explained by a vicious circle model in which tear film instability, desiccation caused by tear evaporation in excess of production, tear hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities are etiologic factors and propagate the cycle (see Figure). Ocular surface damage causes symptoms and generates inflammatory responses that maintain disease chronicity and lead to worsening of ocular surface damage.4
Figure. DED vicious circle
Inflammation can be the primary etiologic factor leading to DED. It can also develop secondarily as a downstream consequence of tear hyperosmolarity, tear film instability, evaporative stress, or neurosensory abnormalities. Regardless of its cause, inflammation represents an important therapeutic target because of its role in the DED pathophysiologic pathway. Treatment that controls inflammation is also important when viewed from the perspective of patients because ocular surface inflammation underlies various DED signs and symptoms, including ocular redness and discomfort, that impair quality of life and prompt patients to seek eye care.
Optimizing anti-inflammatory intervention
Available options for treating DED-related inflammation include topical corticosteroids and topical T-cell immunomodulatory drugs comprising various cyclosporine products: cyclosporine ophthalmic emulsion 0.05% (Restasis, AbbVie), cyclosporine ophthalmic solution 0.09% (Cequa, Sun Pharmaceuticals), cyclosporine 0.1% ophthalmic solution (Vevye, Harrow), and lifitegrast ophthalmic solution 5.0% (Xiidra, Bausch + Lomb).
Topical corticosteroids can provide rapid improvement in inflammation. Therefore, they are very helpful in the treatment of symptom flare-ups and have an important role in reducing symptoms while longer-term therapies are being instituted. Due to their safety concerns, however, topical corticosteroids have a limited therapeutic role as chronic, ongoing therapy.5
All topical T-cell immunomodulatory medications have demonstrated efficacy and acceptable safety in premarketing clinical trials. In real-world use, however, the effectiveness of any medication depends on treatment adherence. For patients with DED, time to onset of benefit for improving disease-related signs and symptoms and tolerability are key factors influencing treatment adherence.6
Cyclosporine ophthalmic emulsion 0.05%, which was the first topical immunomodulatory drug specifically approved for treating DED in 2002, suffers from both delayed onset of benefit and a history of poor tolerability; these issues have been cited to explain high rates of treatment discontinuation.6-8 Nevertheless, cyclosporine emulsion 0.05% may have a particular role in less severe cases of DED where it might be less likely to cause intolerable side effects.
Clinical trials investigating the efficacy, safety, and tolerability of lifitegrast ophthalmic solution 5.0%, cyclosporine ophthalmic solution 0.09%, and cyclosporine ophthalmic solution 0.1% provide evidence that these medications offer a faster onset of action than cyclosporine ophthalmic emulsion 0.05%. In the phase 3 OPUS 3 study, patients using lifitegrast twice daily achieved significant improvement in eye dryness score by day 14, and a postmarketing study of patients starting lifitegrast for DED diagnosed prior to cataract surgery found improvements in DED signs and symptoms after 14 days.9,10 However, there is also evidence of patient dissatisfaction with the onset of action of lifitegrast and its side effects, including instillation site burning and dysgeusia.5,6
To overcome the limitations of cyclosporine ophthalmic emulsion 0.05%, cyclosporine ophthalmic solution 0.09%, and cyclosporine ophthalmic solution 0.1%, use advanced vehicles to increase cyclosporine bioavailability and medication comfort. Pooled results from the 2 phase 3 clinical trials investigating cyclosporine ophthalmic solution 0.1% showed good tolerability. It was statistically superior to vehicle for reducing total corneal fluorescein staining at day 15 (the first visit for efficacy assessment).11 Patient symptoms, measured using Eye Dryness Score, improved from baseline in the cyclosporine group, but the change compared with vehicle was not statistically significant at days 15 or 29 (end of study).12
Cyclosporine ophthalmic solution 0.9% is an aqueous, clear solution that utilizes proprietary nanomicellar technology (NCELL®) to improve cyclosporine physicochemical stability and bioavailability while also minimizing ocular adverse effects.13,14 Clinical trials investigating cyclosporine ophthalmic solution 0.09% demonstrate that it acts quickly to improve signs and symptoms of DED, and it is well tolerated.
COAT (CEQUA’S ONSET of Action Trial) is a postmarketing study investigating cyclosporine 0.09% for treating DED in patients scheduled for cataract surgery.15 In COAT, statistically significant improvements in corneal higher order aberrations, SPEED score, conjunctival hyperemia, tear breakup time, and the percentage of patients with grade 0-1 corneal staining were achieved at the first follow-up visit conducted after 1 week (see Table).
Table. Data from COAT (Cequa’s Onset of Action Trial)15*
| DED signs and symptoms‡ | Baseline | Day 7 |
| HOA ≤0.5µ | 7% | 17% |
| Corneal staining grade 0-1 | 0% | 74% |
| Corneal staining score (mean ± SD) | 1.97 ± –0.61 | 1.04 ± 0.87 |
| SPEED score ≤10 | 37% | 74% |
| TBUT ≥10 sec | 0% | 2% |
| Conjunctival redness†grade 10 | 35% | 63% |
*Participants (n=46) had central or inferior corneal fluorescein staining defined by the
Oxford Scale and tear breakup time (TBUT) ≤10 seconds. They used Cequa BID for 28 days.
‡Values for all endpoints except “corneal staining score” indicate % of patients meeting the criterion.
†Grading based on the Schulze scale.
Safety data collected in premarketing clinical trials show that most patients using cyclosporine 0.09% found it comfortable from the start, with instillation site pain reported as absent or mild by 95% of patients, with few patients withdrawing from study participation.16,17
Conclusion
The primary goal of treating DED is to restore tear film and ocular surface homeostasis that will lead to relief from bothersome signs and symptoms and minimize the risk for disease progression. Success in achieving this goal can involve multimodal strategies that consider disease- and patient-specific factors. However, treatment targeting inflammation is a core component in DED management because it addresses a key etiologic factor in DED development, interrupts the self-perpetuating pathophysiologic pathway that leads to disease progression, and provides improvement in DED signs and symptoms.
Eye care providers are fortunate to have several products to choose from when prescribing treatment to control inflammation in patients with DED. Among these options, cyclosporine ophthalmic solution 0.09% stands out for providing rapid onset of action and a comfortable treatment experience.
Darrell E. White, MD, is a cataract and refractive surgeon in private practice in Ohio. A primary part of his practice career has been devoted to research, development, and education around the topic of dry eye disease. Disclosures: Bausch + Lomb, Sun Pharmaceuticals, Allergan/AbbVie.
References
- Farrand KF, Fridman M, Stillman IÖ, Schaumberg DA. Prevalence of diagnosed dry eye disease in the United States among adults aged 18 years and older. Am J Ophthalmol. 2017;182:90-98. doi:10.1016/j.ajo.2017.06.033
- Dana R, Meunier J, Markowitz JT, Joseph C, Siffel C. Patient-reported burden of dry eye disease in the United States: results of an online cross-sectional survey. Am J Ophthalmol. 2020;216:7-17. doi:10.1016/j.ajo.2020.03.044
- Craig JP, Alves M, Wolffsohn JS, et al. TFOS Lifestyle Report Executive Summary: a lifestyle epidemic – ocular surface disease. Ocul Surf. 2023;30:240-253. doi:10.1016/j.jtos.2023.08.009
- 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
- Jones L, Craig JP, Markoulli M, et al; TFOS Collaborator Group. TFOS DEWS III: management and therapy. Am J Ophthalmol. 2025;279:289-386. doi:10.1016/j.ajo.2025.05.039
- White DE, Zhao Y, Jayapalan H, et al. Treatment satisfaction among patients using anti-inflammatory topical medications for dry eye disease. Clin Ophthalmol. 2020;14:875-883. doi:10.2147/OPTH.S233194
- 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
- Mah F, Milner M, Yiu S, et al. PERSIST: Physician’s Evaluation of Restasis(®) Satisfaction in Second Trial of topical cyclosporine ophthalmic emulsion 0.05% for dry eye: a retrospective review. Clin Ophthalmol. 2012;6:1971-1976. doi:10.2147/OPTH.S30261
- Holland EJ, Luchs J, Karpecki PM, et al. Lifitegrast for the treatment of dry eye disease: results of a phase III, randomized, double-masked, placebo-controlled trial (OPUS-3). Ophthalmology. 2017;124(1):53-60. doi:10.1016/j.ophtha. 2016.09.025
- Hovanesian J, Epitropoulos A, Donnenfeld ED, Holladay JT. The effect of lifitegrast on refractive accuracy and symptoms in dry eye patients undergoing cataract surgery. Clin Ophthalmol. 2020;14:2709-2716. doi:10.2147/OPTH.S264520
- Kaercher T, Sheppard JD, Hamm A, Akpek EK, Krösser S. Pooled results from two pivotal randomized controlled clinical trials: ESSENCE-1 and ESSENCE-2 to assess efficacy and safety of a water-free ciclosporin 0.1% formulation for the treatment of dry eye disease. Graefes Arch Clin Exp Ophthalmol. 2025;263(4):1051-1060. doi:10.1007/s00417-024-06688-3
- Flts A, Medina R, Akpek EK. The evolution of cyclosporine treatments for treatment of ocular surface diseases. Curr Opin Allergy Clin Immunol. 2024;24(5):360-367. doi:10.1097/ACI.0000000000001017
- Data on file. Cranbury, NJ: Sun Pharmaceutical Industries, Inc; 2022.
- US Patent 9937225B2.
- Hovanesian J, Berdy G, Sorensen R. CEQUA’s Onset of Action Trial: an investigation of cyclosporine 0.09% speed of onset in improving ocular surface health in dry eye patients. Presented at the 2025 American Society of Cataract and Refractive Surgery Annual Meeting; April 25-28, 2025; Los Angeles.
- Goldberg DF, Malhotra RP, Schechter BA, et al. A phase 3, randomized, double-masked study of OTX-101 ophthalmic solution 0.09% in the treatment of dry eye disease. Ophthalmology. 2019;126(9):1230-1237. doi:10.1016/j.ophtha.2019.03.050
- Cequa (cyclosporine ophthalmic solution 0.09%). Sun Pharmaceutical Industries, Inc. Accessed July 7, 2026. https://cequapro.com
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