research in practice

A Concomitant Course

There's evidence for steroid use in chronic dry eye.

Mile Brujic, O.D., Crystal Brimer, O.D.

Anti-inflammatory and immunomodulatory agents have helped us better manage dry eye disease signs, such as conjunctival injection, and symptoms, such as burning and itching. Two recent studies reconfirm that short-term steroid use can enable chronic dry eye disease patients to improve their quality of life by enhancing their ocular comfort.

Supporting research

One recent study reveals chronic dry eye disease patients who take a short-term topical steroid in addition to topical cyclosporine 0.05% (Restasis, Allergan, Inc.) may experience quicker dry eye disease symptom relief vs. those who take Restasis alone.¹ In addition, the researchers noted ocular sign improvement with this regimen and no serious complications.

Specifically, the study shows that a group of patients (21) who took Restasis for three months along with 1% methylprednisolone acetate for the initial three weeks of treatment had “greater improvements” in Schirmer strip readings, corneal staining and symptomatic relief at one month vs. a group (23) who took just Restasis. However, both conjunctival staining and tear breakup time (TBUT) showed no statistical differences between the groups. Also, at the end of the study, no difference existed between the two groups in the interleukin-6 (IL-6) and interleukin 8 (IL-8) tear concentrations. All of the findings were improved after the three-month study compared to baseline in each arm of the study.

A chronic dry eye patient before (left) and after concomitant treatment with a topical steroid and Restasis. Notice how the patient's staining significantly improved in the second photo. Also, the patient's tear film pattern improved, as it is more of a solid green.”

The researchers utilized patient symptoms, Schirmer strip readings, TBUT, corneal and conjunctival staining at baseline and at one, two and three months post-treatment, and tear concentration of IL-6 and IL-8 at baseline and at three months post-treatment to determine the level of treatment success.

Additional research has supported short-term topical steroid use to improve dry eye disease signs and symptoms. Studies have shown an increase in goblet cells, a reduction in nerve growth factor levels, a decrease in matrix metalloproteinase-9, a reduction in pro-inflammatory cytokines, a decrease of corneal staining and an improvement in symptoms, presumably through the agent's relatively effective anti-inflammatory activity.^2-7

A relatively recent retrospective study shows the concomitant use of loteprednol etabonate 0.5% (Lotemax; Bausch + Lomb) with Restasis may decrease the stinging associated with the immunomodulatory agent.⁸

Specifically, the study reveals that out of a group of 36 chronic dry eye patients pre-treated with Lotemax for between two-to-16 months before adding Restasis, only two noted significant stinging, with one discontinuing Restasis use as a result. (This group discontinued Lotemax after three-to-six months of concomitant use.) Meanwhile, out of a group of 36 patients treated with just Restasis, eight reported stinging, with three ceasing Restasis use as a result.

Implications for patient care

Dry eye disease is known to have an inflammatory component, which makes either a topical immunomodulator or an anti-inflammatory agent a logical treatment choice.

Concurrent treatment with topical steroids and Restasis has been shown to reduce dry eye disease symptoms. Since chronic dry eye can cause a great deal of discomfort, we should keep this regimen in mind for our moderate-to-severe dry eye disease patients.

Additionally, research shows that patients pre-treated with topical steroids notice less discomfort than when starting Restasis alone. Given that approximately 17% of patients who initiate Restasis experience ocular stinging,⁹ which may impact a patient's adherence to the therapy, it is important we remember this treatment course as well.

Of course, we must remember that topical steroids can have significant side effects, such as risk of cataract formation, decreased resistance to infection and increased intraocular pressure (IOP).⁷ (If you decide to start a patient on a topical steroid, be sure to assess their IOP seven-to-10 days after initiating therapy.) Although the incidence of these events is low, take care to minimize these risks by utilizing the steroids until symptoms are controlled and then discontinuing the steroid drops. For a number of patients, utilizing steroids for three weeks on a q.i.d. dosing schedule concomitantly with Restasis is usually enough to control symptoms. Tapering the drops through a three-to-five day period to prevent symptom recurrence is a good idea as well.

Keep the aforementioned treatment options in mind for your chronic dry eye disease patients. They will feel relief sooner and will likely have a more favorable experience with their treatment plan. OM

1. Byun YJ, Kim Ti, Kown SM, et al. Efficacy of combined 0.05% cyclosporine and 1% methylprednisolone treatment for chronic dry eye. Cornea. 2012 May; 31(5):509-13.
2. Avunduk AM, Avunduck MC, Varnell ED, Kaufman HE. The comparison of efficacies of topical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: a clinical and immunocytochemical study. Am J Ophthalmol. 2003 Oct;126(4): 593-602.
3. Lee HK, Ryu IH, Seo KY, et al. Topical 0.1% prednisolone lowers nerve growth factor expression in keratoconjunctivitis sicca patients. Ophthalmology. 2006 Feb;113(2):198-205. Epub 2005 Dec 19.
4. Nagelhout TJ, Gamache DA, Roberts L, et al. Preservation of tear film integrity and inhibition of corneal injury by dexamethasone in a rabbit model of lacrimal gland inflammation-induced dry eye. J Ocul Pharmacol Ther. 2005 Apr; 21(2):139-48.
5. Lekhanont K, Leyngold IM, Suwan-Apichon O, et al. Comparison of topical dry eye medications for the treatment of keratoconjunctivitis sicca in a botulinum toxin B-induced mouse model. Cornea. 2007 Jan;26(1):84-9.
6. Yang CQ, Sun W, Gu YS. A clinical study of the efficacy of topical corticosteroids on dry eye. J Zhejiang Univ Sci B. 2006 Aug;7(8):675-8.
7. Pavesio CE, Decory HH. Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol. 2008 Apr;92(4):455-9. Epub 2008 Feb 1.
8. Sheppard JD, Scoper SV, Samudre S. Topical loteprednol pretreatment reduces cyclosporine stinging in chronic dry eye disease. J Ocul Pharmacol Ther. 2011 Feb;27(1):23-7. Epub 2010 Dec 6.
9. Allergan. Restasis (Cyclosporine ophthalmic emulsion) 0.05%. www.allergan.com/assets/pdf/restasis_pi.pdf (Accessed 6/10/12')