Dry Eye Dx and Tx
The Dry Eye Pipeline: What’s in it for Us?
BY WILLIAM TOWNSEND, OD, FAAO
During the last two decades, multiple studies and workshop reports have alerted us to the high frequency of dry eye (Smith et al, 2007; Nichols et al, 2011; Lemp et al, 1995). It is perhaps ironic that as our appreciation for the diverse disease states that cause dry eye has increased, the number of FDA-approved prescription therapies to treat them has not. There are currently two therapies specifically approved by the FDA for dry eye. Methylcellulose 0.5% (Lacrisert, Valeant Pharmaceuticals) was approved in 1981. Topical cyclosporine emulsion 0.05%, (Restasis, Allergan) received FDA approval in 2002.
New dry eye treatments may have tremendous economic impact; Gaylor et al (2012) linked the introduction of Restasis to much of the five-fold increase in the annual cost of dry eye treatment between 2001 and 2006.
At press time, the FDA listed 502 dry eye studies in some phase of the approval process (clinicaltrials.gov). One of them may bring us the next product to expand our treatment armamentarium. This article will highlight a few of these potential products.
Thymosin beta 4 is being evaluated as a dry eye therapy (clinicaltrials.gov, NCT01393132). Thymosins were first discovered in the thymus; the beta 4 form is recognized for its wound-healing attributes including down-regulation of inflammatory chemokines and cytokines, promotion of cell migration, vasculogenesis, and promoting cell survival.
Sosne at al (2012) reported that in an animal model, thymosin beta 4 improved wound healing as evidenced by reduced corneal staining. Another animal study demonstrated that it also decreases corneal inflammation and modulates the activity of matrix metalloproteinase (MMP) 2 and 9 (Sosne et al, 2005).
A trial sponsored by Korean pharmaceutical company Dong-A is evaluating the use of DA-6034 (7-carboxymethyloxy-3’,4’,5-trimethoxyflavone) to treat dry eye (clinicaltrials.gov, NCT01670357). Flavones are a class of flavonoids mainly found in cereals and herbs (Wikipedia).
In an animal model study, Seo et al (2010) demonstrated the anti-inflammatory attributes of DA-6034. They induced inflammation in rabbit lacrimal glands by injecting them with a proinflammatory agent and then instilled DA-6034. They reported significant reductions in MMP-9 and cytokines and restoration of the ocular surface.
The success of Restasis as a therapy for dry eye has prompted the investigation into similar molecules that may also prove beneficial. A group of Brazilian researchers has completed an FDA trial investigating tacrolimus as a potential dry eye therapy (clinicaltrials.gov, NCT01850979). Cyclosporine and tacrolimus antagonize calcineurin activity and hence, calcium-dependent T-cell activation. They exhibit many of the same therapeutic features.
Moscovici et al (2012) evaluated 0.03% tacrolimus eye drops (olive oil + tacrolimus 0.03%) for therapy of dry eye. They noted statistically significant improvement in corneal fluorescein staining and rose bengal staining after 14 days of treatment, with progressive improvement up to 90 days. Tear film breakup time showed improvement after 28 days and 90 days of therapy. CLS
For references, please visit www. clspectrum.com/references.asp and click on document #212.
Dr. Townsend practices in Canyon, Texas, and is an adjunct professor at the University of Houston College of Optometry. He is president of the Ocular Surface Society of Optometry and conducts research in ocular surface disease, lens care solutions, and medications. He is also an advisor to Alcon, B+L, CooperVision, Tearlab Corporation, and Vistakon. Contact him at firstname.lastname@example.org.