Restasis and Adjunctive Tears
Cornea specialists discuss their recommendations.
BY ROCHELLE NATALONI, CONTRIBUTING EDITOR

Effective dry eye treatment often relies on a multitiered, multiproduct combination strategy that is customized to each patient's response. In many cases, treatment includes cyclosporine ophthalmic emulsion 0.05% (Restasis), which contains a topical immunomodulator with anti-inflammatory effects. Because this immunosuppressant can take from 3 to 9 months to become optimally effective -- recent studies indicate that 2 months is average -- adjunct artificial tears are typically recommended for palliative care.

Robert J. Noecker, M.D., director of the glaucoma service and associate professor/vice chair of the Department of Ophthalmology at the University of Pittsburgh, points out that most patients who end up on Restasis have already tried some type of eye drop for their symptoms. "When you're choosing which adjunct tears to recommend, the most important thing is to know what they have already used because almost invariably it is something suboptimal in terms of preservative or other ingredients in the drops besides lubricants," he says. "I typically tell these patients that the artificial tears are a 'Band-aid' to the problem because they can help in times of temporary irritation and blurred vision, but that if their symptoms are ongoing and persistent, the Restasis will get at the underlying problem, and help them to generate more of their own tears over time."

Dr. Noecker points out that the amount of artificial tears used in conjunction with Restasis is also highly variable. "Initially, the artificial tear use is stable and then is expected to decline over time," he says. "In the Restasis clinical study, patients had an unlimited supply of Refresh nonpreserved tears that they used less over time. In the 'real world' we use non-BAK-containing tears like Refresh, GenTeal or Systane. It is quite variable from patient to patient how much is used. Some people stop altogether [once the cyclosporine provides help] and others continue to use the tears frequently."

Dr. Noecker typically recommends Refresh tears to patients on Restasis, he says, because Refresh is packaged as a multidose and has a "benign" preservative, Purite. "If they need a more viscous tear I use Refresh Liquigel, or if they need to use a nonpreserved tear, I'll recommend Celluvisc or Refresh Plus," he said. For the most severe patients, he recommends a nighttime nonpreserved ointment or gel like Refresh PM or GenTeal Gel.

Stephen C. Pflugfelder, M.D., professor of ophthalmology at Baylor College of Medicine in Houston, says his only recommendation with respect to artificial tears used in conjunction with Restasis is to avoid drops containing a lipid such as Refresh Endura or Soothe because they may interfere with the delivery of the cyclosporine. "I usually recommend unit dose nonpreserved artificial tears to be used in conjunction with Restasis and I recommend they be instilled at least 30 minutes prior to or after the Restasis," he says. When Dr. Pflugfelder prescribes Restasis he explains that the cyclosporine "inhibits the inflammatory mediators that cripple tear production" and that over time the patient's ability to produce their own tears will improve. "I tell them that they may supplement this with artificial tears to lubricate their eyes until the Restasis kicks in and when they are performing activities where their tear evaporation increases, such as reading and working on a computer," he explains.

In the minority of his dry eye patients for whom cyclosporine is prescribed, James P. McCulley, M.D., professor and chairman of the University of Texas Southwestern Medical School, Department of Ophthalmology, Dallas, uses the immunosuppressant as adjunct therapy to shore up the effects of Systane, which is his front-line drug. "In patients who have underlying immune disease or in patients with severe dry eye with marked inflammation, my first goal is to try to get the ocular surface healthy because in the majority of those patients the inflammation is driven by ocular surface drying. To get the ocular surface healthy as quickly as I can, I start with Systane q.i.d. and a well-tolerated, more aqueous tear, such as Bion Tears, Tears Naturale II or TheraTears up to every hour," says Dr. McCulley. "I use Systane for its coating effect as well as its replacement of tears effect. However, if the eyes are severely dry and severely inflamed, q.i.d. is not adequate and patients don't tolerate Systane as well when it is used more than q.i.d., so in an instance like this, I would add Restasis."

In that scenario, Dr. McCulley said he would expect the principal benefit for the first 3 to 9 months to come from protecting the ocular surface with Systane and the more aqueous artificial tear. "If that is working well, I would continue with that, and then at some point decide if I need to add plugs, but I try to get patients under control before having to do that," he added.

According to Michael A. Lemp, M.D., Systane helps allow damaged cells on the surface of the eye to repair
by extending tear film break-up time (TFBUT). Dr. Lemp is a clinical professor of Ophthalmology at Georgetown University and George Washington University in Washington, D.C. "Systane's unique properties include the active demulcents polyethylene glycol and propylene glycol, along with the gelling agent HP guar. HP guar adjusts to the tear film pH to form a protective, gel-like coating that helps stabilize the tear film," he explains.

In a recent study involving 50 dry eye patients, Systane extended mean TFBUT up to 30 minutes post-instillation (an increase from baseline of 4.26 seconds at 5 minutes and 1.81 seconds at 30 minutes). This difference in TFBUT was significantly more than carboxymethylcellulose-based drops up to 20 minutes post-instillation and significantly more than glycerin/polysorbate 80-based drops up to 30 minutes post-instillation. (Christensen MT, et al. Evaluation of the Effect on Tear Film Break-up Time Extension by Artificial Tears in Dry Eye Patients. Presentation at the 23rd Biennial Cornea Research Conference, October 2003, Massachusetts Eye and Ear Infirmary, Boston, Mass.)

More recent data in a study reported by Alcon, Inc. shows that Systane is compatible with Restasis. "This study demonstrated that Systane, used concomitantly with Restasis, resulted in superior results versus Refresh Tears used with Restasis," according to Dr. Lemp.

Comfort Leads to Compliance

Whichever artificial tear you recommend for use with Restasis, according to dry eye experts, the results should be comfort for your patients so they are able to remain compliant with their treatment instructions and keep their symptoms under control for the long term.