Anti-TGFβ treatment reduces corneal haze but not regression of ablative effict following excimer laser prk in the rabbit

Purpose. Previous studies have suggested that corneal fibrosis controlled by the TGFβ mediated cytocrine pathway underlies tie development of corneal haze and regression following excimer laser PRK. Using blocking antibodies, we evaluated the role of TGFβ in the development of post-PRK haze .ind regression as measured by a novel in vivo Confocal Microscopic Through Focusing technique (CMTF). Methods. Fifteen rabbits received a monocular, 6-mm diameter, 9.0 D PRK myopic correction. After surgery 5 animals received 50 u-g of anti-TGFβ blocking antibodies (1D11, Celtrix) applied topically 3x/day for three days, while 5 animals received vehicle alone and five were left untreated. Animals were evaluated at vai ious times by CMTF which uses an image pixel intensity depth profile to identify the li »cation and reflectivity of corneal structures to measure corneal haze, epithelial and stro nal thickness. Results. In normal rabbit cornea, the epithelial basal lamina, the onl; intra-corneal structure showing significant reflectivity, had a CMTF integrated pixel intensity haze estimate (Hest) of 148±66 U. In untreated eyes one week post-PRK theie was a significantly increase (p<0.001) in Hes, associated with increased reflection fron the photoablated stromal surface (1483±286 U) and from underlying activated keratoi:ytes (749.4:517 U). Haze peaked at 3 weeks (5478±1438 U) and showed a gradual decline in values to 889±700 U by 6 months. AntiTGFβ treated eyes showed a signifie mt reduction in corneal haze (p<0.02) and a significantly more rapid loss of haze to 1053±389 U (p<0.02) at 8 weeks post-PRK. Stromal thickness in treated eyes sho wt d maximal thinning, 126± 10 urn, at one to two weeks post-surgery with a gradual inert ase of 63±11 urn by 8-weeks similar to treated eyes (NS). Corneal epithelium showed no post-operative hyperplasia. Conclusions. A major cause of post-PRK comeal haze is associated with TGFβ mediated activation and migration of comeal keratocytes, Most interestingly, however, regression appeared related to stromal growth. Based on these findings we propose that comeal thickness may be tightly controlled by an unknown, non-TGFβ, mediated pathway.