WAIKOLOA, HAWAII – Topical cyclosporine 0.05% ophthalmic emulsion significantly outperformed artificial tears for the treatment of ocular rosacea in a double-blind, randomized, multicenter study.
"It’s a fairly small study, but I think it gives us some valuable information. This gives us a new option topically," Dr. Julie C. Harper said in highlighting the study at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).
She referred to a clinical trial conducted by Florida ophthalmologists who randomized 37 patients with ocular rosacea to twice-daily topical cyclosporine 0.05% (Restasis) or artificial tears for 3 months.
The outcome that most impressed Dr. Harper was the topical cyclosporine group’s mean 11.5-point improvement from a baseline of 14.1 on the Ocular Surface Disease Index, a validated patient questionnaire assessing the eye disease’s impact on quality of life. Patients who received artificial tears – a widely prescribed treatment for ocular rosacea – had a significantly lesser mean 2.9-point improvement.
"People definitely felt better with this product than with artificial tears," observed Dr. Harper, a dermatologist at the University of Alabama at Birmingham.
In addition, the topical cyclosporine group fared significantly better in the other study end points, which focused on eye dryness and tear production. For example, mean scores on Schirmer\'s test (a measure of eye-surface wetness) improved by 2.7 mm over the course of 3 months of treatment, from a baseline of 8.3, compared with a 1.4-mm deterioration in the artificial tears group.
Dr. Julie C. Harper
Also, tear break-up time (a measure of how quickly an eye becomes dry) increased by a mean of 3.56 seconds in the cyclosporine group, a significantly more favorable effect than the 0.04-second decrease in the artificial tears arm (Adv. Ther. 2009;26:651-9).
The investigators speculated that topical cyclosporine’s clinical benefits in ocular rosacea are due to the drug’s anti-inflammatory effects, including a cyclosporine-mediated reduction in the number of activated lymphocytes in the conjunctiva, in combination with stimulation of increased tear production
The ophthalmologists emphasized that ocular rosacea can be a serious and potentially even a blinding condition. They noted that in one classic study, 13 of 131 patients had corneal complications resulting in visual acuity loss at the time they presented to ophthalmology. Of those 13 patients, 7 were left with worse than 20/400 eyesight, and 6 of the 13 required penetrating keratoplasty during the course of their disease (Ophthalmology 1997;104:1863-7).
Dr. Harper said that since she learned of the randomized trial, she has tried using topical cyclosporine for ocular rosacea but doesn’t yet have enough experience to say how well it works in her own hands. Usually, she gives the topical agent in combination with an oral tetracycline in patients whose ocular disease isn’t responding adequately to oral therapy alone.
Her preferred oral agent is delayed-release doxycycline (Oracea) at the anti-inflammatory but subantimicrobial dose of 40 mg once daily, a dosage that is Food and Drug Administration approved for treatment of rosacea. She favors this regimen because it doesn’t contribute to the worsening, global, antibiotic-resistance public health problem, and the once-daily aspect is a real plus from the patient adherence standpoint.
For patients who don’t have insurance coverage for this relatively costly drug, her second-favorite option is generic doxycycline at 20 mg BID, which is also an anti-inflammatory yet subantimicrobial dosage. It’s important to recognize, however, that bumping up the dosage of generic doxycycline to 50 mg/day would cross the threshold into the antibacterial range that could contribute to the resistance problem, the dermatologist added.
Topical cyclosporine for ocular rosacea is off-label therapy. The drug’s approved indication is in treating chronic dry eyes. Conference codirector Dr. Joseph F. Fowler Jr. predicted that the product may never gain an indication for ocular rosacea. That’s because ophthalmologists have a difficult time in quantifying the severity of ocular rosacea for research purposes, and even in distinguishing it from dry eye.
"My own crude approach is that if you’ve got rosacea on the skin and you’ve got itchy, gritty eyes, then I generally assume you’ve got ocular rosacea," explained Dr. Fowler, a dermatologist at the University of Louisville (Ky.).
Like Dr. Harper, he typically prescribes topical cyclosporine for ocular rosacea in combination with oral doxycycline.
"I find it very useful," he added.
Dr. Fowler disclosed that he has received research grants from Allergan, which markets Restasis. He also serves as a consultant to Galderma, which markets Oracea, as well as to numerous other pharmaceutical companies. Dr. Harper is on the speakers bureaus for Allergan, Galderma, and a handful of other companies.