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    2015 ARVO finds connections in innovative drug delivery, therapies

    Cutting-edge progress also continues in retina, cornea, dry eye, gene-based science


    Another therapeutic approach gaining favor for corneal disease is stem cell transplantation. One notable study used a mouse model of bacterial inflammation to demonstrate that the local delivery of mesenchymal stem cells is an effective and safe approach for immunomodulation and treatment of ocular inflammation (Zhang R. IOVS. 2015;56:ARVO E-Abstract 942).

    Two presentations used continuous monitoring technology to analyze blink behavior under natural conditions (Lane. IOVS. 2015;56:ARVO E-Abstract 4447; Harmeling. IOVS. 2015;56:ARVO E-Abstract 4486). These studies continue to advance clinicians’ understanding of compensatory mechanisms in ocular surface disease. (Photo courtesy of Keith Lane)Chronic keratitis—whether from infection, trauma, or surgical complication—remains a significant therapeutic challenge. As in past years, a wealth of studies from neurotrophic keratitis to dry eye were aimed at improving therapeutic outcomes for those with corneal disease.

    One study tested the efficacy of the rho-kinase inhibitor, AMA0076 (Amakem NV, Belgium), in a rabbit model of corneal debridement (Defert O. IOVS. 2015;56:ARVO E-Abstract 5610). Rho kinase inhibitors have been explored as potential therapies for open-angle glaucoma, and more recently, their role in cell inflammation and differentiation has been recognized.

    This study followed 4 days of healing for untreated animals (t.i.d., placebo), AMA0076-treated animals (also t.i.d.), and a positive comparator of recombinant growth hormone (q.i.d.). The kinase inhibitor and the GH treatments were comparable for both re-epithelialization and resolution of corneal haze, and both were superior to the control animals.

    Reports focusing on advancements in ocular allergy and inflammation included one study demonstrating the therapeutic potential for PI3K inhibitors (Whitlock A. IOVS. 2015;56:ARVO E-Abstract 4886). The study used reduction in ocular redness in a mouse model as a reporter for relief of allergic inflammation.

    Another presentation demonstrated how immune cell infiltration can be assessed using confocal microscopy, a new approach that is particularly useful in studies of chronic disease (Gomes P. IOVS. 2015;56:ARVO E-Abstract 4892).

    A novel treatment strategy for dry eye was examined with weekly dosing of cyclosporin delivered using mucoadhesive nanoparticles in a mouse model of dry eye (Lui S. IOVS. 2015;56:ARVO E-Abstract 5036). This delivery regime enhanced anti-inflammatory efficacy relative to placebo or to higher topical doses of drug.

    It has long been thought that dry eye was a condition most severe in winter months, but no studies have been done to test whether this belief is fact or fiction. Data were pooled from 10 clinical trials and identified 270 patients who had participated in at least one summer study (April to September) and one winter study (November to April), and were randomly assigned to placebo groups for both studies (Ousler et al. IOVS. 2015;56:ARVO E-Abstract 4462). Both ocular discomfort and dryness symptom scores were significantly higher during the winter months, consistent with the prevailing wisdom. It will be interesting to see if clinical signs of dry eye such as corneal staining show similar patterns.

    Many presentations this year examined the potential of repurposed compounds for dry eye. One of these tested the immunosuppressant, rapamycin (Rapamune, Pfizer), as a therapy for Sjögren’s syndrome, using a non-obese mouse model as a test platform. (Shah M. IOVS. 2015;56:ARVO E-Abstract 4810). After a 12-week treatment of bi.d. rapamycin, SS markers were all significantly reduced compared with placebo, including lacrimal lymphocytic infiltration (6.4-fold decrease) and tear cathepsin S activity (5.9-fold decrease).

    Another preclinical trial tested the integrin antagonist GW559090 in a mouse model of dry eye (Krauss AH. IOVS. 2015;56:ARVO E-Abstract 2472). Integrins are key players in lymphocyte activation and chemotaxis. Lifitegrast (Shire), a drug for treatment of dry currently under FDA review, inhibits another member of the integrin family, lymphocyte function antigen 1.

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