Optical Effects of Anti-TGFβ Treatment after Photorefractive Keratectomy in a Cat Model

PURPOSE. To assess the contribution of corneal myofibroblasts to optical changes induced by photorefractive keratectomy (PRK) in a cat model. METHODS. The transforming growth factor (TGF)-beta-dependence of feline corneal keratocyte differentiation into alpha-smooth muscle actin (alpha SMA)-positive myofibroblasts was first tested in vitro. Twenty-nine eyes of 16 cats were then treated with -10 D PRK in vivo and divided into two postoperative treatment groups that received either 100 mu g anti-TGF beta antibody for 7 days, followed by 50 mu g dexamethasone for another 7 days to inhibit myofibroblast differentiation, or vehicle solution for 14 days (control eyes). Corneal thickness and reflectivity were measured by optical coherence tomography. Wavefront sensing was performed in the awake-behaving state before surgery and 2, 4, 8, and 12 weeks after surgery. Wound healing was monitored using in vivo confocal imaging and postmortem alpha SMA immunohistochemistry. RESULTS. In culture, TGF beta caused cat corneal keratocytes to differentiate into alpha SMA-positive myofibroblasts, an effect that was blocked by coincubation with anti-TGF beta antibody. In vivo, anti-TGF beta treatment after PRK resulted in less alpha SMA immunoreactivity in the subablation stroma, lower corneal reflectivity, less stromal regrowth, and lower nonspherical higher order aberration induction than in control eyes. However, there were no intergroup differences in epithelial regeneration or lower order aberration changes. CONCLUSIONS. Anti-TGF beta treatment reduced feline corneal myofibroblast differentiation in vitro and after PRK. It also decreased corneal haze and fine-grained irregularities in ocular wavefront after PRK, suggesting that attenuation of the differentiation of keratocytes into myofibroblast can significantly enhance optical quality after refractive surface ablations. (Invest Ophthalmol Vis Sci. 2009;50:634-643) DOI:10.1167/iovs.08-2277