May 2010

 

COVER FEATURE

 

Ocular Surface & Dry Eye

New options abound for allergy and dry eye


By Matt Young EyeWorld Contributing Editor

 

At a glance

• Some doctors have become more aggressive at treating dry eye • Although conventional therapies for dry eye are still used, unconventional ones are at play too, such as one doctor’s use of testosterone cream • New treatment options for ocular surface disease are allowing for sustained release and some measures to overcome resistance

 

Ophthalmologists have more options than ever when it comes to treating dry eye and ocular surface disease, and they are using them aggressively and sometimes even experimentally. For moderate to severe dry eyes, Richard L. Lindstrom, M.D., Adjunct Professor Emeritus, department of ophthalmology, University of Minnesota, Minneapolis, and founder, Minnesota Eye Consultants, Minneapolis, is willing to leave patients on Restasis (ophthalmic cyclosporine emulsion, Allergan, Irvine, Calif.) forever. “For me, the shift in how I treat dry eye has been to be more aggressive from the onset than I used to be, at least with moderate to severe dry eye,” Dr. Lindstrom said. John D. Sheppard, M.D., professor of ophthalmology, microbiology, and immunology, Eastern Virginia Medical School, Norfolk, Va., is a big fan of Valtrex (valacyclovir, GlaxoSmithKline, Middlesex, England) for treating herpetic keratitis and sees that drug quickly replacing acyclovir. He has used both aggressively. “They both have a very safe profile and limited toxicity, even with chronic use,” Dr. Sheppard said. “I have prescribed both to women who are pregnant and have the disease.”

Brian S. Boxer Wachler, M.D., director, Boxer Wachler Vision Institute, Los Angeles, does whatever it takes to improve his dry-eye patients. “For dry eye, I use conventional and unconventional therapies,” he said. Under the unconventional umbrella, he uses testosterone 3%-5% cream applied to the eyelids for concomitant blepharitis, which can also cause dry eyes, he said. “My theory is that blepharitis is the result of testosterone deficiency locally to the eyelids,” Dr. Boxer Wachler said. The ophthalmologists use a host of other treatments as well, which they discussed to provide suggestions on how best to treat dry eye and ocular surface disease.

Attacking with force

As dry eye becomes more significant, Dr. Lindstrom quickly moves to using some of the most powerful agents in dry-eye relief, such as Lotemax (loteprednol, Bausch & Lomb, Rochester, N.Y.) four times a day for two weeks, for starters. “I’ll then institute Restasis,” he said, during which time he tapers off the steroid usage. “But if there are flares, such as from environmental exposure, I’m willing to use steroids again,” Dr. Lindstrom said.

That’s what he does personally, as well. “I have a little bit of dry eye, blepharitis, and ocular allergy,” Dr. Lindstrom said. “A short course of a safe steroid works for me. A topical lubricant makes me feel better, but loteprednol can also be effective and safe. If I put it in 3 to 4 times per day, and taper over a 4-day period, the flares from environmental exposure resolve very rapidly.”

It’s probably no accident Dr. Lindstrom has dry eye and blepharitis. “We’re learning that most dry eye likely is not going to be evaporative dry eye, but rather it will surface secondary to blepharitis,” Dr. Lindstrom said. “AzaSite [azithromycin, Inspire Pharmaceuticals, Durham, N.C.] is quite an effective and safe therapy for managing blepharitis.” Low-dose doxycycline is also helpful in treating blepharitis, he said. “Consider 20 to 40 milligrams per day rather than 100 milligrams,” Dr. Lindstrom said. “There’s much better tolerance and efficacy.”

Dr. Lindstrom also recommended omega-3 fatty acids, such as fish oil and flaxseed oil, to combat blepharitis, as well as hot packs. Aggressive treatment begins with a firm diagnosis of dry eye, and Dr. Lindstrom highly recommended the TearLab Osmolarity System (TearLab Corp., San Diego), which measures the osmolarity of human tears. “Good research shows that of all the diagnostic tests we have, tear film osmolarity is the most reliable in making the diagnosis of significant dry eye,” Dr. Lindstrom said. “That will be an advance.” The TearLab Osmolarity System will be useful for screening patients before LASIK and contact lens wear, and will not only allow for an accurate diagnosis, but also continued monitoring of dry eye, he said. Of course, if dry eye is diagnosed, a variety of artificial tears are useful as well, Dr. Lindstrom said. He named Blink Tears (Abbott Medical Optics, Santa Ana, Calif.), Oasis Tears (Oasis Medical, Glendora, Calif.), Systane (Alcon, Fort Worth, Texas), Refresh Optive (Allergan), and Soothe XP (Bausch & Lomb) as some of his favorites.

New kids on the block

Beyond dry eye, Dr. Sheppard is excited about many new agents for ocular surface disease.

Zirgan (ganciclovir, Sirion Therapeutics, Tampa, Fla.) is one of them, and is approved for acute herpetic keratitis. Dr. Sheppard believes Zirgan will become either “a leader or the leader in treating herpes keratitis, in part because of relatively infrequent need to apply the drop and decreased toxicity in clinical trials.” Another emerging leader is Besivance (besifloxacin, Bausch & Lomb), which Dr. Sheppard suggested is a superior fluoroquinolone. “It uses the DuraSite (InSite Vision, Alameda, Calif.) vehicle, which provides sustained drug release,” Dr. Sheppard said. “It supplies high concentrations over a long period of time to treat bacterial conjunctivitis and prevent bacterial infection on the ocular surface. Knowing that patients are non-compliant even when it is recommended only twice a day, it maintains concentrations well above MIC [minimum inhibitory concentration] thresholds for all important organisms.” Besivance can also kill multi-resistant organisms—not only methicillin-resistant organisms, but also ciprofloxacin-resistant ones, Dr. Sheppard said. “Even so, one needs to be cautious about emerging methicillin resistance,” he said. “In another 5 to 10 years all Staphylococci will be resistant to methicillin. That’s not an encouraging prospect but one we need to be aware of.”

Unique usage

Like Dr. Lindstrom, Dr. Boxer Wachler uses artificial tears, Restasis, and oral flaxseed capsules for dry eye. But his use of testosterone cream to treat blepharitis is certainly unconventional, though buttressed by the literature to some extent. “Excess blood vessels are caused by relatively too much estrogen locally in the eyelids; hence, recalcitrant blepharitis results,” Dr. Boxer Wachler said. “Acne rosacea is associated with excess blood vessels on the nose and cheeks and can be associated with excess estrogen.” Dr. Boxer Wachler also pointed to a study published in the June 2002 issue of the Annals of the New York Academy of Sciences finding that women with primary and secondary Sjogren’s syndrome are androgen-deficient. “Our results demonstrate that: (1) androgens regulate the meibomian gland … and (2) androgen deficiency may lead to meibomian gland dysfunction, altered lipid profiles in meibomian gland secretions, tear film instability, and evaporative dry eye,” according to the researchers. “Thus, we have found that anti-androgen therapy in men is associated with meibomian gland disease, a decreased tear film breakup time, and functional dry eye. Furthermore, we have discovered that androgen receptor dysfunction in women with CAIS [complete androgen-insensitivity syndrome] is associated with meibomian gland changes and a significant increase in the signs and symptoms of dry eye.”

Of course, blepharitis is also associated with dysfunction and inflammation of the meibomian glands, which this study suggested is regulated by androgens like testosterone. Considering how aggressive and varied treatment for dry eye and ocular surface disease has become, perhaps Dr. Boxer Wachler’s regimen fits right into the mix after all.

Editors’ note: Dr. Lindstrom has financial interests with Abbott Medical Optics (Santa Ana, Calif.), Alcon (Fort Worth, Texas), Allergan (Irvine, Calif.), Bausch & Lomb (Rochester, N.Y.), and Inspire Pharmaceuticals (Durham, N.C.), among others. Dr. Sheppard has financial interests with many of the ocular allergy companies mentioned in this article. Dr. Boxer Wachler has no financial interests related to his comments.

Contact information

Boxer Wachler: 310-860-1900, bbw@boxerwachler.com
Lindstrom: 612-813-3633, rllindstrom@mneye.com
Sheppard: 757-622-2200, docshep@hotmail.com

New options for allergy and dry eye New options for allergy and dry eye
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