Rethinking dry eye disease with acute steroid treatment

Ophthalmology Times EuropeOphthalmology Times Europe January / February 2022
Volume 18
Issue 01

Loteprednol etabonate suspension 0.25% demonstrates anti-inflammatory action and produces significant improvement in conjunctival hyperaemia and ocular discomfort.

Rethinking dry eye disease with acute steroid treatment

Ophthalmologists can now prescribe a corticosteroid for the treatment of dry eye disease (DED) with the confidence that they are doing so on-label, following the recent United States Food and Drug Administration (FDA) approval of a topical corticosteroid for short-term (up to 2 weeks’) use. Loteprednol etabonate ophthalmic suspension 0.25% (Eysuvis, Kala Pharmaceuticals) has a favourable adverse effect profile and a unique mechanism of action that is worth a closer look.

The drug product was studied in the largest clinical programme in DED to date, including more than 2,800 patients.1 In results from the STRIDE 1 and STRIDE 2 trials conducted by Kala Pharmaceuticals, it illustrated a beneficial safety profile, demonstrating similar intraocular pressure (IOP) levels to the vehicle arm. In treatment and vehicle groups, respectively, 0.2% and 0% of participants experienced a 10 mm Hg or greater increase from baseline, resulting in an IOP measurement of 21 mm Hg or greater at any post-baseline visit up to 29 days.2

In the STRIDE trials, investigators observed statistically significant improvement in the measures of conjunctival hyperaemia and patient-reported ocular discomfort severity scores. Participants assigned to treatment with the loteprednol etabonate suspension product experienced rapid relief, with improvement in symptoms as early as Day 4.3

The ophthalmic suspension has a novel formulation which utlises Kala Pharmaceuticals’ proprietary mucus-penetrating particle technology. These nanoparticles of approximately 300 nm in diameter are coated to facilitate their penetration through the mucus barrier.

This controlled delivery system enables the drug to spread more uniformly on the ocular surface to achieve longer retention and allow enhanced penetration to the target tissues, specifically the cornea and the conjunctiva.The formulation has demonstrated broad-spectrum anti-inflammatory action, leading to a more efficient and effective nanoparticle drug that rapidly reduces the symptoms and signs of DED, including in those patients with periodic acute exacerbations of worsening symptoms referred to as dry eye flares.

Relieving chronic disease and flares

DED is an inflammatory disease in which an unstable and hyperosmolar tear film sets off a cascading sequence of inflammatory activity on the ocular surface.As with other chronic inflammatory conditions, such as asthma and rheumatoid arthritis, most patients with DED have chronic disease with dry eye flares.5,6

The Tear Film & Ocular Surface Society Dry Eye Workshop II notes that patients can initially present with episodic dry eye in the absence of chronicity.7 Myriad triggers with varied intensity such as wind; low humidity; air conditioning; prolonged reading/visual tasks; and exposure to increased ozone concentrations have been shown to increase the incidence of flares.8-16 These inflammatory spikes occur in approximately eight out of 10 patients with dry eyes, and approximately half of patients with DED experience flares without continuous symptoms four-to-six times per year.17-18

Particularly in relation to the COVID-19 pandemic, I have seen more patients presenting with acute dry eye symptoms who have never before been symptomatic. Many are spending 10–12 hours a day staring at computer screens. Additionally, the data show that there is an under-diagnosis and under-recognition of DED overall.

In general, I prescribe loteprednol etabonate ophthalmic suspension 0.25% for patients who have periodic exacerbations of dry eye, including those who are self-medicating with artificial tears, those with ocular allergies, or those with contact lens-associated issues; patients with chronic DED who need induction therapy to quell surface inflammation quickly in order to initiate chronic therapy; and patients with breakthrough dry eye flares who are on chronic therapy.

Recent cases

Two recent examples from my practice are discussed as follows.

Case 1

A 42-year-old female contact lens wearer was referred to me for consultation for dry eye due to irritation from dust created by construction work on a nearby office. She had swelling in the left eye, with severe discomfort and complaints of dryness in both eyes for 5 weeks, and it was getting progressively worse.

The patient had initially been placed on tobramycin-dexamethasone 0.3%/0.1% twice a day and had a 95% improvement within the first week; however, on re-examination, her IOP had gone up to 35 mm Hg. She was then prescribed brimonidine-timolol 0.2%/0.5% (Combigan, Allergan) to decrease the pressure.

However, her symptoms worsened when she had an allergic reaction to the brimonidine-timolol 0.2%/0.5%. Although the drops were discontinued, her symptoms continued to worsen, with significant discomfort and redness, and she needed artificial tears every hour.

By the time she saw me, it was her 11th visit to a doctor in 5 weeks and she was desperate for relief. I gave her a diagnosis of allergic conjunctivitis, contact lens over-wear and dry eyes. I discontinued all previous drops and put her on loteprednol etabonate ophthalmic suspension 0.25% every other day, four times a day, for 2 weeks; preservative-free tears four times a day; and extra-strength over-the-counter olopatadine 0.7% (Pataday, Alcon) twice a day.

Within 1 week, she had great improvement in all her symptoms and felt that her eyes were back to normal. She completed the treatment course with full resolution of her symptoms and, much to her relief (and that of her referring provider), no increase in IOP.

Case 2

A 78-year-old woman with a variety of medical problems including multiple myeloma and colon cancer was referred for evaluation of severe dryness in both eyes. In particular, she was experiencing copious tearing from her right eye for the past several weeks, stating that her eye watered so much it felt as though she was looking through a “puddle”.

The patient had been taking cyclosporine ophthalmic emulsion 0.05% (Restasis, Allergan) for years, which she felt helped her, and recently had been given lifitegrast ophthalmic solution 5% (Xiidra, Novartis) to use in addition to Restasis, but she was still experiencing tearing. She was also using artificial tears, warm compresses and over-the-counter olopatadine 0.1% for allergic conjunctivitis.

On examination, the patient had evidence of chronic inflammation including conjunctivochalasis and corneal staining. I kept her on cyclosporine ophthalmic emulsion 0.05% and added loteprednol etabonate ophthalmic suspension 0.25% in both eyes four times a day for 2 weeks.

Within days, her tearing resolved and her vision improved from 20/40 to 20/25. The patient was very happy that she was no longer tearing and was thrilled with the improvement in vision.


When it comes to prescribing corticosteroids for DED, I am much more proactive and confident prescribing loteprednol etabonate ophthalmic suspension 0.25% for my patients because of its rapid onset and strong safety profile. I have had great success with the drop in many straightforward to complex cases, including patients with glaucoma, and have had no pressure increases measured at follow-up examination in my clinical experience so far. My patients and I are impressed by how quickly it works to quieten symptoms.

Having an on-label enhanced loteprednol formulation for short-term use in treating the signs and symptoms of DED is a welcome addition to our armamentarium. Dry eye can have a significant impact on patient quality of life and daily activities. Patients are extremely grateful and relieved to feel rapid relief from their DED symptoms, especially when they experience dry eye flares.

Lisa Nijm, MD, JD
Dr Nijm is the founder and medical director of Warrenville EyeCare & LASIK, a clinical assistant professor of ophthalmology at the Eye and Ear Infirmary at UI Health in Chicago, Illinois, US, and creator of and She is a consultant for Alcon, Allergan, Kala Pharmaceuticals and Novartis.
1. Gupta PK, Venkateswaran N. The role of KPI-121 0.25% in the treatment of dry eye disease: penetrating the mucus barrier to treat periodic flares. Ther Adv Ophthalmol. 2021;13:25158414211012797.
2. Korenfeld M, Nichols KK, Goldberg D, et al. Safety of KPI-121 ophthalmic suspension 0.25% in patients with dry eye disease: a pooled analysis of 4 multicenter, randomized, vehicle-controlled studies. Cornea. 2021 1;40:564-570.
3. Holland E, Nichols KK, Foulks GN, et al. Safety and efficacy of KPI-121 ophthalmic suspension 0.25% for DED in four RCTs. Presented at: American Academy of Ophthalmology virtual annual meeting. 13-15 Nov 2020; PO098.
4. Pflugfelder SC, de Paiva CS. The pathophysiology of dry eye disease: what we know and future directions for research. Ophthalmology. 2017;124(suppl 11):S4-S13.
5. Lienert JP, Tarko L, Uchino M, et al. Long-term natural history of dry eye disease from the patient's perspective. Ophthalmology. 2016;123:425-433.
6. Perez VL, Stern ME, Pflugfelder SC. Inflammatory basis for dry eye disease flares. Exp Eye Res. 2020;201:108294.
7. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017;15:276-283.
8. Rolando M, Zierhut M, Barabino S. Should we reconsider the classification of patients with dry eye disease? Ocul Immunol Inflamm. 2021;29:521-523.
9. Amparo F, Dana R. Web-based longitudinal remote assessment of dry eye symptoms. Ocul Surf. 2018;16:249-253.
10. Iyer JV, Lee SY, Tong L. The dry eye disease activity log study. ScientificWorldJournal. 2012;2012:589875.
11. Karakus S, Agrawal D, Hindman HB, et al. Effects of prolonged reading on dry eye. Ophthalmology. 2018;125:1500-1505.
12. Kim Y, Paik HJ, Kim MK, et al. Short-term effects of ground-level ozone in patients with dry eye disease: a prospective clinical study. Cornea. 2019;38:1483-1488.
13. Ousler GW 3rd, Rimmer D, Smith LM, et al. Use of the controlled adverse environment (CAE) in clinical research: a review. Ophthalmol Ther. 2017;6:263-276.
14. López-Miguel A, Tesón M, Martín-Montañez V, et al. Dry eye exacerbation in patients exposed to desiccating stress under controlled environmental conditions. Am J Ophthalmol. 2014;157:788-798.
15. Tesón M, González-García MJ, López-Miguel A, et al. Influence of a controlled environment simulating an in-flight airplane cabin on dry eye disease. Invest Ophthalmol Vis Sci. 2013;54:2093-2099.
16. Fernández I, López-Miguel A, Enríquez-de-Salamanca A, et al. Response profiles to a controlled adverse desiccating environment based on clinical and tear molecule changes. Ocul Surf. 2019;17:502-515.
17. Brazzell RK, Zickl L, Farrelly J, et al. Prevalence and characteristics of dry eye flares: a patient questionnaire survey. Presented at: American Academy of Ophthalmology 2019. 12-15 October 2019; San Francisco, California, US.
18. Brazzell RK, Zickl L, Farrelly J, et al. Prevalence and characteristics of symptomatic dry eye flares: results from patient questionnaire surveys. Program no. 195265. Presented at: American Academy of Optometry 98th annual meeting. 23-27 October 2019; Orlando, Florida, US.
Related Videos
ARVO 2024: Andrew D. Pucker, OD, PhD on measuring meibomian gland morphology with increased accuracy
 Allen Ho, MD, presented a paper on the 12 month results of a mutation agnostic optogenetic programme for patients with severe vision loss from retinitis pigmentosa
Noel Brennan, MScOptom, PhD, a clinical research fellow at Johnson and Johnson
ARVO 2024: President-elect SriniVas Sadda, MD, speaks with David Hutton of Ophthalmology Times
Elias Kahan, MD, a clinical research fellow and incoming PGY1 resident at NYU
Neda Gioia, OD, sat down to discuss a poster from this year's ARVO meeting held in Seattle, Washington
Eric Donnenfeld, MD, a corneal, cataract and refractive surgeon at Ophthalmic Consultants of Connecticut, discusses his ARVO presentation with Ophthalmology Times
John D Sheppard, MD, MSc, FACs, speaks with David Hutton of Ophthalmology Times
Paul Kayne, PhD, on assessing melanocortin receptors in the ocular space
Osamah Saeedi, MD, MS, at ARVO 2024
© 2024 MJH Life Sciences

All rights reserved.