Comprehensive dry eye management: Short-term therapy is a much needed addition
By Deepika N. Shah, MD, MPH
We used to think dry eye was sort of a passive disease, where it would stay at the same level of severity constantly. Although we might have had patients call in and say, “my dry eye is really bad, I’m having flare-ups,” the pathophysiology and the mechanism behind it was not well understood.
Now we know that dry eye is an inflammatory disease. As reported in TFOS DEWS 2, hyperosmolarity is considered to be the trigger for the release of inflammatory mediators and proteases that in turn cause goblet cell and epithelial cell loss and damage to the epithelial glycocalyx.1 Activated T cells release inflammatory mediators on the ocular surface, reinforcing the damage resulting in tear film instability which leads to early tear film breakup. This sets off a vicious circle of events and self-perpetuation of the disease, the executive committee reported.
As with other such inflammatory conditions, many patients with dry eye disease (DED) have periods of acute exacerbations of signs and symptoms— called dry eye flares, and periods of relative quiescence. Triggers for the increase in symptoms range from wind, low humidity, air conditioning, prolonged reading/visual tasks, and exposure to increased ozone concentrations.2-10 About 8 out of 10 dry eye patients experience inflammatory spikes of acute exacerbation, and about half of DED patients experience flares without continuous symptoms between 4 to 6 times per year.11-14
It is possible that by not treating acute dry eye flares, DED can get worse. Think of dry eye as a graph with spikes that represent an acute exacerbation of symptoms. If these patients go untreated when this happens, the overall possible trajectory of the ocular surface health might decline over time because those inflammatory mediators lingered on the surface.
Short-term Steroid Option
When we would treat these patients, we offered a corticosteroid drop off label— maybe a sample, and were sure to counsel them to use it as directed. Some eye care physicians (ECPs) may have even been hesitant to use the agent at all in dry eye due to concerns around potential side effects such as elevated IOP. Today, we have the option of using an FDA-approved corticosteroid, loteprednol etabonate ophthalmic suspension 0.25% (Eysuvis; Kala Pharmaceuticals), specifically indicated for the short-term (up to 2 weeks) treatment of the signs and symptoms of DED.
This treatment was studied in more than 2800 patients and exhibited a well-tolerated safety profile. In treatment and vehicle groups, respectively, 0.2% and 0% of subjects experienced a ≥10 mm Hg increase from baseline resulting in an IOP measurement of ≥21 mm Hg at any post-baseline visit up to 29 days.15,16 Researchers observed statistically significant improvement in the measures of conjunctival hyperemia and patient-reported ocular discomfort severity score in subjects in the loteprednol etabonate ophthalmic suspension 0.25% group. Patients experienced rapid relief with improvement in symptoms as early as day 4.17
With convincing data showing Eysuvis to be well-tolerated, we can be comfortable prescribing it to patients along with a refill to keep therapy on hand when their dry eye flares occur (to be used as directed by the ECP). We know it will help them effectively manage their exacerbations and possibly prevent or hasten long-term chronicity of the dry eye. Aggressively treating flares along with maintaining appropriate patients on daily immunomodulator therapy with cyclosporine 0.05% (Restasis; Allergan, An AbbVie Company), lifitegrast 5% (Xiidra; Novartis), or cyclosporine 0.09% (Cequa; Sun Pharmaceutical) has been a bit of a paradigm shift in the way we treat dry eye.
Dry Eye Consultation
I start my new patient consultations by carefully listening to patients describe their symptoms and finding out what they have tried in the past. I move to my clinical exam and the objective findings. I assess the tear film including the meniscus, tear breakup time (TBUT), and keratopathy patterns along with measuring osmolarity and the presence of inflammatory mediators such as MMP-9 on the ocular surface. In someone having an acute flare-up, I usually find at least 3 out of 5 of those objective signs confirmatory. These patients typically have a fair amount of fluorescein and Lissamine staining, a decreased and unstable tear film, and often are positive for inflammation. In these cases, I start with loteprednol etabonate for induction along with an immunomodulator for long-term management. The third point-of-care test I use is LipiScan (Johnson & Johnson Vision Care) to view the meibomian glands.
A lot of chronic DED patients are also taking other medications that exacerbate the condition like SSRIs or daily antihistamines. I take a step back with them and look at the big picture to see what else might be going on. I find that dry eye patients I see are largely peri or post-menopausal women due to the influence of hormonal changes on the tear film and tear production. Plus, we cannot overlook the role of digital devices. I even see children in middle school with induced moderate to severe DED due to excessive screen time.
I counsel patients on the importance of keeping themselves hydrated, adding a humidifier to their office or bedroom, and taking an omega flax seed supplement to improve tear film stability. Additionally, I discuss the need to pay closer attention to the lids and meibomian glands as there is an increased prevalence of blepharitis or rosacea causing inflammation on or within the eyelid. Numerous device-based advances using thermal pulse energy are available in that realm, whether that’s TearCare (Sight Sciences), LipiFlow (Johnson & Johnson Vision), iLux Gen 2 (Alcon), or even home warm compresses.
I tell patients that having DED is like having hypertension or diabetes: It is a chronic disease, and it has to be proactively managed. We use the tools and medications that we have along with lifestyle and environmental modifications to control and hopefully stabilize the condition. When I prescribe new medications, patients always ask, will I have to be on this for life? While I tell them they will always have to manage their DED and dry eye flares in some shape or form, we now have an expanded armamentarium with both short-term and long-term treatment solutions to enhance the patient’s quality of life.
Deepika N. Shah, MD, MPH, is a Cornea, Cataract and Refractive ophthalmologist in practice at the Eye Doctors of Washington in Washington, DC. Dr Shah has served on the Kala Pharmaceuticals Ophthalmology Advisory Board. For inquiries, please contact her office at 301-215-7100.
- Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017;15: 276–283.
- Rolando M, Zierhut M, Barabino S. Should we reconsider the classification of patients with dry eye disease? Ocul Immunol Inflamm. 2019; DOI: 2.1080/09273948.2019.1682618.
- Amparo F, Dana R. Web-based longitudinal remote assessment of dry eye symptoms. Ocul Surf. 2018; 16: 249–253.
- Iyer JV, Lee SY, Tong L. The dry eye disease activity log study. ScientificWorldJournal. 2012;589875.
- Karakus S, Agrawal D, Hindman HB, et al. Effects of prolonged reading on dry eye. Ophthalmology. 2018;125: 1500–1505.
- 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.
- Ousler GW, Rimmer D, Smith LM, et al. Use of the controlled adverse environment (CAE) in clinical research: a review. Ophthalmol Thes. 2017;6:263–276.
- 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.
- Tesón M, Gonzalez-Garcia MJ, Lopez-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.
- Fernandez I, Lopez-Miguel A, Enriquez-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.
- Brazzell RK, Zickl L, Farrelly J, et al. Prevalence and characteristics of dry eye flares: a patient questionnaire survey. Presented at: AAO 2019: Oct 12-15, 2019. San Francisco, Calif.
- Brazzell RK, Zickl L, Farrelly J, et al. Prevalence and characteristics of symptomatic dry eye flares: results from patient questionnaire surveys. Poster presented at: AAOPT 2019: October 23-27, 2019; Orlando, FL.
- 2018 Study of Dry Eye Sufferers. Conducted by Multi-sponsor Surveys, Inc.
- 2020 Study of Dry Eye Sufferers. Conducted by Multi-sponsor Surveys, Inc.
- 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. doi: 10.1177/25158414211012797. eCollection.
- Korenfeld M, NIchols KK, Goldber D, et al. Safety of KPI-121 ophthalmic suspension 0.25% in patients with dry eye disease. Cornea. 2021;40(5):564-570. doi: 10.1097/ICO.0000000000002452.
- Holland E. Nichols KK, Foulks GN, et al. Safety and efficacy of KPI-121 ophthalmic suspension 0.25% for DED in rour RCTs. Paper presented at: AAO 2020; Nov 13-15, 2020; virtual meeting.