CORNEAL HAZE DEVELOPMENT AFTER PRK IS REGULATED BY VOLUME OF STROMAL TISSUE REMOVAL

Purpose. To determine whether excimer laser transepithelial photoablat ion can reduce the initial keratocyte loss seen after manual epithelia l debridement. Second, to establish the relationship between initial d epth of keratocyte and stromal loss and the subsequent development of corneal haze. Methods. Five rabbits received a 5-mm diameter monocular epithelial debridement by manual scraping. An additional five rabbits received a 5-mm diameter excimer laser transepithelial photoablation to a preset (intended) depth of 60 mu m to ensure complete epithelial removal and to generate a superficial stromal keratectomy in all corne as. At various times during a 3-month period, animals were evaluated b y in vivo confocal microscopy through focusing (CMTF), which generates a quantitative image intensity depth profile of the cornea that provi des measurements of (i) depth of keratocyte loss, (ii) epithelial and stromal thickness, and (iii) backscattered light from the anterior cor nea as an objective estimate of corneal haze. Results. Manual epitheli al debridement was associated with an initial loss of anterior stromal keratocytes to a depth of 108 +/- 14 mu m that was followed by repopu lation with migratory keratocytes. These cells showed increased reflec tivity producing significant backscattering of light equivalent to cli nical haze grade 1-2 (1,442 +/- 630 U) at 3 weeks. Furthermore, repopu lation occurred without detectable inflammation and was associated wit h a rapid restoration of normal keratocyte morphology and reflectivity . Transepithelial photoablation induced complete epithelial debridemen t in all corneas in addition to a superficial stromal keratectomy of 1 4-44 mu m Photoablation induced 36% less initial keratocyte loss (69 /- 19 mu m) in the anterior stroma than manual debridement (p < 0.01) but was associated with intense concomitant inflammation. Photoablated corneas showed significantly more light backscattering (p < 0.01) com pared with manually debrided corneas with a threefold increase at 3 we eks (4,397 +/- 1,367 U) and a sixfold increase at 3 months (1,483 +/- 1,172 compared with 234 +/- 91 U). Backscattering of light or haze inc reased proportionally with increasing stromal keratectomy depth (r = 0 .95, p < 0.001) but was unrelated to depth of induced keratocyte death . The increased backscatter in photoablated corneas appeared related t o (i) a more pronounced keratocyte repopulation response with a higher density and reflectivity of migratory fibroblasts and (ii) myofibrobl ast transformation after repopulation. Conclusions, Excimer laser tran sepithelial photoablation induced significantly less keratocyte loss t han manual epithelial debridement; however, photoablation was followed by a more intense inflammatory response and a greater increase in bac kscattering of light (haze) that was associated with increased keratoc yte activation and myofibroblast transformation. Most important, the m agnitude of corneal wound repair and the development and duration of c orneal haze increased proportionally with increasing stromal photoabla tion depth (i.e., the volume of stromal tissue removal) but were unrel ated to depth of initial keratocyte loss.