Topical Eyedrop Therapy for Keratoconus

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Project Summary Keratoconus (KCN) is a progressive disorder associated with structural changes in corneal collagen organization that leads to corneal thinning and ruptures in Bowman’s layer and/or Descemet’s membrane. As the disease progresses, it leads to irregular astigmatism, progressive myopia, and subsequently poor visual acuity. Treatment options are surprisingly limited with no oral or topical pharmaceutical therapy. Most mild KCN can be corrected with glasses or soft contact lenses but very often patients will need toric or hard contacts as the disease progresses. Ultimately, 1 in 5 patients will require surgery. Our technology is based on a co-factor for lysyl oxidase (LOX activity) and that low LOX activity in the cornea has been linked to the development of keratoconus both genetically and biochemically. We provide the evidence in preliminary results of a new topical eye drop effect on human keratoconus corneas in increasing both LOX activity and cornea stiffening. We also show the first morphological evidence of induced central corneal flattening in rabbits with optical coherence tomography (OCT). Based on the current evidence base, we outline new proactive pathways for keratoconus management and enabling a non-invasive and relatively cost effective treatment for keratoconus. We propose a research plan under three specific aims that will a) study the safety and tolerability of the eye drops in rabbits in vivo, b) study the effect of dosing frequency on rabbit corneal shape and biochemical crosslinking in vivo and c) to determine whether the eye drops induce biochemical crosslinking on human keratoconic corneas ex vivo.