Water, hyaluronan and surface shape in corneal wound healing after excimer surgery : experimental studies

Abstract: Excimer laser photorefractive keratectomy (PRK) has evolved to a widely performed procedure. The excimer laser corrects refractive ametropias by removing a calculated amount of anterior corneal stroma with great precision and with minimal damage to the adjacent tissues. The correction of myopia up to -5.00 diopters (D) with excimer laser ablation yields good results with 99 % of the final refractions within ± 1.00 D of that intended. In some patients, however, the clinical practice faces problems like insufficient predictability in refractive outcome, haze and myopic regression in the postoperative course. Hyaluronan (HA) has been detected in the wound area after excimer laser surgery in the rabbit cornea as well as in a few human corneal specimens. In paper I we apply histochemical methods to confirm its presence in human corneas after excimer laser ablation. Hyaluronan in wound scrapings of corneas that had to be reoperated because of unsatisfactory outcome has been associated with aggressive myopic regression and with severe haze. Hyaluronan is capable of binding considerable amounts of water. In paper II we apply quantitative microradiography and histochemical HA staining to demonstrate its subepithelial colocalization with water in rabbit corneas postoperatively. The final result of excimer laser surgery depends on the ablation quality and on the individual corneal healing response to the treatment quality. Ablation depth, -diameter and -slope are variables that might affect reepithelialization and stromal healing after surgery. In paper III we utilize a modified planimetry to evaluate the healing reaction by measuring the subepithelial water accumulation. Our results suggest that a shallow slope causes less activity during the subsequent healing, when compared to a steep curve refractive treatment. Any departure from a smooth surface might degrade the optical qualities of the ablated cornea and thereby impair the clinical results. Paper IV provides information about the time course of stromal irregularities and their impact on wound healing as compared to a rather smooth postablational surface. Corticosteroids are still the primary therapeutical agent proposed to modulate the corneal healing response. Corticosteroids may influence the refractive result after PRK at least by two ways, one by reducing the postoperative epithelial thickness, the other by suppressing the subepithelial remodeling. Paper V addresses these issues and concludes that corticosteroids reduce subepithelial HA accumulation and prevent epithelial hyperplasia. By these means corticosteroids are likely to affect the refractive status of the cornea. In conclusion, we show that subepithelial HA is formed in human corneas after excimer laser surgery. In rabbits HA is demonstrated to colocalize with water in the subepithelial area. The planimetric evaluation of subepithelial water accumulation shows that a steep curve refractive treatment causes more healing reaction when compared to an ablation with shallow slope, this independently to treatment depth. The inflammatory response is more pronounced after a laser treatment leaving postablational surface irregularities, when compared to a laser treatment leaving a smooth postablational surface. Corticosteroids are shown to reduce subepithelial HA accumulation and prevent epithelial hyperplasia.