September 2015




Pharmaceutical focus

Plunging into dry eye medications

by Maxine Lipner EyeWorld Senior Contributing Writer

Punctate staining on eye


Punctate staining on the ocular surface using dyes shows the microerosions that occur from chronic dry eye disease.

Source: Marjan Farid, MD

Dry eye has become an epidemic, according to Marjan Farid, MD, associate professor of ophthalmology, University of California, Irvine. Prevalence has been increasing due to greater recognition of dry eye as a quality of life issue, improvements in diagnosis, and environmental factors such as increased screen time thanks to a wealth of electronic devices. This makes the hunt for new medications vital, Dr. Farid said. Dr. Farid said there is no one magic cure for dry eye disease right now. I tell my patients that we have to come up with a cocktail of treatments so that theyll have more good days than bad days because dry eye disease is hard to cure, she said, adding that the more treatments there are in the toolbox, the better practitioners can serve patients. Although the pathophysiology of dry eye disease is multifactorial, chronic dry eye disease, whether from aqueous deficiency or evaporative in nature, ends up in a cycle of inflammation. Whether it starts at the lid margin and then progresses to a secondary ocular surface disease or it starts as aqueous deficiency and inflammation carries into the lacrimal glands, the final piece is that there is a cycle of inflammation that leads to progression of symptoms and signs if left untreated, Dr. Farid said.

On the launch pad

Up to this point, there has been only one FDA-approved medication that has addressed this issueRestasis (cyclosporine, Allergan, Dublin, Ireland). However, now on the launch pad is the drug lifitegrast (Shire, Lexington, Mass.). It hits the cycle of inflammation at multiple steps. It is exciting to have such a potent treatment around the corner, Dr. Farid said, adding that where Restasis strictly prevents activation of new T-cells, lifitegrast prevents T-cell activation and shuts down already active T-cells that are in the patients tear unit. This rapid shutting down of the inflammatory cycle should give lifitegrast a more potent and quicker onset of action, Dr. Farid said. In addition to keeping T-cells from activating by interrupting those already in action on the ocular surface, it prevents them from producing inflammatory cytokines, Dr. Farid explained. Lifitegrast is an integrin inhibitor that stops the on switch in the inflammatory cycle as well as switching off 5 different steps of the inflammatory pathway. FDA studies indicate that the onset of action is as early as 2 weeks. Data have also indicated that symptom improvement is strong. Not only did the signs of dry eye improve, but the effect in terms of decreasing the pain and burning was rapid and potent, Dr. Farid said. The hope is that there will be a final answer in terms of FDA approval by the end of this year or early next.

Some off-label medications continue to play a role, according to Christopher E. Starr, MD, associate professor of ophthalmology, Weill Cornell Medical College, New York. He said that the antibiotic azithromycin is commonly used for meibomian gland disease. Also, topical steroids such as loteprednol are used to try to jumpstart the treatment of inflammation associated with dry eye, Dr. Starr said. Dr. Farid agreed that certain steroid formulations can be helpful for dry eye disease, especially when initiating treatment for Restasis. During the time that it takes for Restasis to work, she often puts patients on loteprednol to help kickstart their anti-inflammatory treatment. Its fast-acting, its gentle, and we dont see as many patients with IOP issues who are on Lotemax [loteprednol, Bausch + Lomb, Bridgewater, N.J.], she said. It also has almost zero cataractogenic effect, unlike some of the other steroids. However, Dr. Farid does tell her patients that this is not a long-term solution. But I think its underused in the short term for dry eye patients, and I think physicians should start to feel more comfortable using steroids like Lotemax that have a lower side effect profile, she said, adding that this can improve the quality of life for patients, particularly when they first come in for treatment. Just cooling down the eye can help them get onboard with a lot of treatments, she said.

Neda Shamie, MD, associate professor of ophthalmology, University of Southern California Eye Institute, Los Angeles, pointed to ProKera Slim (Bio-Tissue, Doral, Fla.) as another treatment option gaining momentum. Its a biological corneal bandage device that provides a protective barrier on the ocular surface with active anti-inflammatory and healing properties. The ProKera Slim is a bandage device made of a cryopreserved human amniotic membrane contained within a thin thermoplastic ring set that allows for close contact to the corneal surface and minimal discomfort, Dr. Shamie said. Its not a permanent treatment of dry eyes, but it is an excellent option for patients with dry eye-related epitheliopathy who have not yet fully responded to topical cyclosporine and/or steroids. For a patient who has severe dry eyes, this is a treatment that can be started concurrently with others to help kickstart the treatment response and lessen the patients symptoms.

Maximizing medications

When it comes to prescribing medications for dry eye patients, Dr. Shamie urged practitioners not to have a knee-jerk reaction to treatment. Its important to understand the multifactorial nature of the underlying cause, she said, adding that this means assessing evidence of anterior blepharitis, meibomian gland disease, ocular allergies, and conjunctivochalasis, to name a few common comorbidities. Its important to understand that inflammation is at the core of dry eyes and addressing the inflammatory component of the cycle is fundamental to reaching treatment success, she said. She also stressed the need to educate patients about dry eye and create the right expectations. Most patient do not consider dry eye disease as one thats progressive, and they may be expecting a rapid treatment response when in fact most treatment options require a course of at least 3 months, Dr. Shamie said. Spending the time to educate patients about the progressive nature of the disease, the potential visual detriment of delaying proper treatment, and the need for a commitment to a treatment course with the proper medication can help alleviate noncompliance and treatment failures. Likewise, Dr. Starr emphasized the need to caution patients that Restasis can take months to work. Thats something I always tell my patients about this drop, he said, because if patients dont know this they will think it is not working and will stop the medication prematurely.

He also reminds practitioners to alert patients that there can be burning and stinging with Restasis. We know that with Restasis, 17% of people in the FDA trial had significant burning, Dr. Starr said. You have to tell patients that it is going to burn a little and thats normal. Overall, Dr. Shamie stressed the need for medications to address inflammation. Inflammation is at the crux of all ocular surface disease, she said. Addressing the inflammation is the most critical point and everything else will follow.

Editors note: Dr. Farid has financial interests with Allergan, Shire, and TearScience (Morrisville, N.C.). Dr. Shamie has financial interests with Allergan, Nicox (Fort Worth, Texas), and Shire. Dr. Starr has financial interests with Alcon (Fort Worth, Texas), Allergan, Bausch + Lomb, Rapid Pathogen Screening (Sarasota, Fla.), Shire, and TearLab (San Diego).

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