Best practices: cyclosporine use for dry eye

Specialists weigh in on treatment regimens

Although Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan, Irvine, Calif.) has been on the market for a few years now, exact guidelines on how often and how long dry-eye patients should use it are still debatable.
Add to that the duty of explaining to patients that cyclosporine is not a quick fix—unlike artificial tears, which provide more immediate relief for dry-eye symptoms—and it can be a treatment option that takes some getting used to.
That said, ophthalmologists welcome the chance to incorporate cyclosporine use into their practice because of the overall positive results seen in most patients and because it can even help reverse a worsening dry eye.
Here are the regimens that a number of specialists follow to prescribe and educate patients about cyclosporine usage for dry eye.

When to start it

The earlier you start cyclosporine, the more of a chance that you can eliminate worsening dry-eye inflammation, believes Esen K. Akpek, M.D., associate professor of ophthalmology, and director, Ocular Surface Diseases and Dry Eye Clinic, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore. If a patient is not responding to artificial tear use within a few weeks, she’ll write a prescription for cyclosporine.
“If someone needs artificial tears to get the day started, that’s someone with chronic dry eye,” said Marguerite B. McDonald, M.D., clinical professor of ophthalmology, Tulane University School of Medicine, New Orleans. That makes her more likely to recommend cyclosporine use.
John R. Wittpenn, Jr., M.D., associate clinical professor, Department of Ophthalmology, School of Medicine at Stony Brook Medical Center, Stony Brook, N.Y., backs this approach. “If patients say, ‘I have a dry eye, I use tears and they’re ineffective, I want something more,’ they get Restasis,” Dr. Wittpenn said.
The Ocular Surface Disease Index questionnaire and Schirmer test results without anesthesia can also be illuminating when determining the necessity for cyclosporine, said Henry D. Perry, M.D., clinical associate professor of ophthalmology, Weill School of Medicine, Cornell University, New York. “If their Schirmer is 5 mm or less off the bat, that signifies aqueous deficiency,” he said. “I like to treat early in the game rather than wait for irreversible changes.”
Although Dr. Wittpenn believes it is helpful to look at Schirmer score and staining benchmarks for dry eye, he said those aren’t always the best indicators of cyclosporine use. First, patients who have staining already have ocular damage—if they can start cyclosporine earlier, they may avoid that damage. Second, some patients may have little or no complaints about dry eye because their cornea is denervated, he said.
It’s also important to listen to patients during the initial consult to see if lagophthalmos, allergies, or lid disease are contributing to their symptoms, said Penny A. Asbell, M.D., professor of ophthalmology, Mount Sinai School of Medicine, New York. She prefers to try one treatment modality at a time to effectively gauge what does and does not work in patients.
These dry-eye specialists have recent research to support their approach of early use of cyclosporine. Research presented at the Association for Research in Vision and Ophthalmology (ARVO) meeting in April 2008 by Sanjay N. Rao, M.D., Chicago, found that while 31.8% of patients in a study group who used artificial tears experienced progressive dry-eye disease, the progression occurred in only 5.5% of patients who were using cyclosporine.

Explaining cyclosporine to patients

Patients need a little bit of explanation on how cyclosporine works because its beneficial effects don’t kick in immediately, ophthalmologists said. Patients may also feel discouraged because it can sting in some eyes, leading patients to stop using it.
“I tell them that this is a medicine designed to allow your eye to produce the maximum amount of tears that it is capable of producing. Three out of four patients who try it find that it’s a benefit … I tell them it’s not an artificial tear, it’s a medicine, and it’s not meant to feel good,” Dr. Wittpenn said. Telling patients this has encouraged some of them who stopped using it because of stinging to start using it again, Dr. Wittpenn said.
Dr. McDonald has a 2- to 3-minute “speech” that she prepared because she does not always have the same technicians available to adequately explain cyclosporine to her patients. As part of the speech, she highlights how cyclosporine looks (likening its container to a microwave dinner tray), tells patients how to use it, explains that it’s a powerful and safe but slow-moving drug, and informs them that it may take a month to notice a difference and 3 to 6 months to feel maximum medical benefits. She will also warn patients about possible stinging, which she offsets by simultaneously prescribing Lotemax (loteprednol etabonate ophthalmic suspension 0.5%, Bausch & Lomb, Rochester, N.Y.).
Dr. Akpek also treats some patients who have heard about cyclosporine being used as an immunomodulator in cancer patients, and they ask about its safety. “I tell them it’s very safe and won’t penetrate into the bloodstream to any significant levels,” she said. She’ll cite studies as necessary from Allergan that have shown this.
It’s also helpful to give written information about cyclosporine, Dr. Perry said. He will hand out articles he’s written about the drug to help answer patients’ questions.

How often to use it

Although most of the physicians interviewed believe in the twice-a-day regimen—once in the morning and once in the evening—Dr. Akpek actually starts patients out on cyclosporine four times a day for 2 to 3 months. “I believe it works better that way. It’s more efficient. If it’s used twice a day, it might take longer” to notice the effect, she said. After that initial period, she’ll taper down to twice a day.
Dr. McDonald helps give patients immediate relief by prescribing cyclosporine and other treatments at the same time. She’ll recommend cyclosporine, Lotemax four times a day for two weeks and twice a day for two weeks, artificial tears 4 to 16 times a day, omega-3 nutritional supplements, and a nighttime ointment.
“It seems like a lot, but patients get an immediate response, and they feel great and they look great,” she said. It’s also easy to change the regimen once patients come in for a 4- or 6-week follow-up, she added. At that time, patients may be able to eliminate some of the treatments. If they need additional relief, Dr. McDonald will insert Oasis punctal plugs (Glendora, Calif.).
If patients have trouble using cyclosporine twice a day because of stinging, Dr. Wittpenn will advise them to use an artificial tear before instilling the medication. In addition, they can chill cyclosporine in the refrigerator so it feels better, he said. He advises patients to try and stick to cyclosporine use for 6 to 8 weeks to see what the results are.
Some patients may gripe about the cost of cyclosporine, which can reach nearly $40 even with health insurance. To help combat this, Dr. Wittpenn tells patients they can get a rebate from Allergan of up to $20.
The specialists interviewed also said that even though each cyclosporine vial is slated for one-time use, they tell patients they can cut down costs by using each vial twice—one drop at night and one drop in the morning. “You can safely get two doses out of each vial, cutting the cost in half. But you must open the vial at night because the vials can become contaminated in eight to nine hours,” Dr. McDonald tells patients.

When to stop using it

The question of when to stop using cyclosporine is a trick question because dry eye is often a lifetime problem.
“I can’t say patients will use cyclosporine their whole lifetime because there may be another drug available for them [in the future]. This is the best medicine we have at the present time,” Dr. Perry said.
Still, “most patients have to use it chronically,” Dr. Akpek said.
Dr. Wittpenn was involved with a previously reported study of 44 patients, two of whom stopped using cyclosporine and felt they didn’t need it anymore, two of whom stopped it because they weren’t sure it was helping, and 40 of whom continued taking it even after the study treatment period. Dr. Perry is involved with a study of approximately 100 patients to see how they fare once they stop cyclosporine use.
If patients want to try to use it only once a day, Dr. Wittpenn said they can try that. “Eighty percent of people can go to once a day. The other 20% need twice a day,” he said. He’ll advise patients to try the once-a-day approach for 3 to 4 months before they determine if once- or twice-a-day use is necessary.
The possibility of once-a-day dosing or even pulsed dosing is under examination now, Dr. McDonald said. Until the results show a benefit of once-daily use, she continues to tell patients that twice a day is the best recommended dosage.
If patients switch to cyclosporine use only once a day, there’s another logistical problem they must face, Dr. Asbell said. “Once you open the vial, many patients can use it for two doses. You may not gain much in terms of cost savings,” considering patients should only keep their open vial for a few hours, she said.

Editors’ note: Dr. Akpek has no financial interests related to her comments. Dr. McDonald is has financial interests with Abbott Medical Optics (Santa Ana, Calif.), Allergan (Irvine, Calif.), and Santen (Napa, Calif.), among other ophthalmic companies. Drs. Wittpenn and Perry have financial interests with Allergan. Dr. Asbell has financial interests with Alcon (Fort Worth, Texas), Allergan, and Inspire Pharmaceuticals (Durham, N.C.), among other ophthalmic companies.

Contact information

Akpek: 410-955-5494, esakpek@jhmi.edu
Asbell: 212-241-7977, penny.asbell@mssm.edu
McDonald: 516-593-7709, margueritemcdmd@aol.com
Perry: 516-766-2519, hankcornea@aol.com
Wittpenn: 631-941-3363, jrwittpenn@aol.com