Dry Eye Dx and Tx
The Dry Eye Pipeline in 2011
By William Townsend, OD, FAAO
A visit to www.clinicaltrials.gov shows that there are 254 current and completed studies directed toward keratitis sicca. This article can address only a few of them.
Rebamipide is a mucosal-protective antiulcer drug. It stimulates prostaglandin biosynthesis and increases mucus glycoprotein synthesis in the superficial layers of the gastric mucosa. It also enhances expression of epidermal growth factor, scavenges free radicals, and suppresses neutrophil activation and inflammatory cytokine production.
Kohashi et al (2008) evaluated rebamipide in mice that had Sjögren's syndrome and found that it decreased apoptosis in the salivary and lacrimal glands compared to control mice and suppressed the activation of CD4+ T cells and Th1 cytokines. They concluded that rebamipide may be useful in managing keratitis sicca.
Pimecrolimus is a macrolactam derivative of ascomycin that impedes T-cell activation by inhibiting the synthesis and release of cytokines from T-cells. Ofri et al (2008) evaluated the efficacy of pimecrolimus oil-based eye drops in alleviating the clinical signs of keratoconjunctivitis sicca (KCS) in dogs. They also compared the efficacy of cyclosporine A ointment 1% to pimecrolimus emulsion and found that the latter is as safe as and is more effective than cyclosporine ointment in controlling KCS in dogs.
Meingassner et al (2003) investigated the efficacy of tacrolimus, cyclosporine, and pimecrolimus. All three molecules inhibit T-cell activation and the release of inflammatory cytokines, but pimecrolimus and tacrolimus were found to equally inhibit the elicitation (reactive) phase of atopic dermatitis. Pimecrolimus displays significantly less toxicity compared to the other products.
Cyclosporine, marketed as Restasis (Allergan) and successfully used for several years as an agent in treating inflammatory dry eye, is back in the pipeline. French pharmaceutical company Novagali completed a study evaluating Cyclokat (cyclosporine 1% in a proprietary gel preparation) for treating moderate-to-severe dry eye (2009). Cyclokat demonstrated significant treatment effect on multiple efficacy endpoints for signs and symptoms after treatment at month 1 and at month 3. These findings suggest potential clinical benefits of utilizing Cyclokat for keratitis sicca.
Dry eye has been successfully treated with both cyclosporine and punctal occlusion. Gupta and Chauhan (2011) reported a novel punctal plug that features a cylindrical HEMA core containing drug microparticles. The punctal plug releases cyclosporine over a three-month period and provides a sustained, dual mechanism treatment for dry eyes.
Dartt et al (2011) recently reported the potential for treating dry eye with resolvins, a new class of naturally occurring lipid mediators that can protect tissue that becomes inflamed in response to insult. Resolvins initially reduce inflammation, and once the insult subsides they promote healing. The researchers found cysteinyl leukotriene receptors in goblet cells and in cultured rat and human conjunctival tissue. Prior studies show that leukotrienes stimulate goblet cell secretion; this study established that selected resolvins reduce leukotriene-stimulated goblet cell excretion. Another clinical trial revealed that resolvins produced dose-dependent, statistically significant improvement in the primary endpoints for both the signs and symptoms of dry eye, including dryness, stinging, burning, grittiness, and ocular discomfort. CLS
For references, please visit www.clspectrum.com/references.asp and click on document #188.
Dr. Townsend practices in Canyon, Texas and is an adjunct faculty member at UHCO. He is an advisor to TearLab Corporation, has received research funds from Alcon and B+L and is an advisory panel member of Alcon, B+L, and Inspire Pharmaceuticals. You can reach him at email@example.com.