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The aim was to assess the visual impact of ocular wavefront aberrations, corneal thickness, and corneal light scatter prospectively after performing a Descemet stripping automated endothelial keratoplasty (DSAEK) in humans.Data were obtained prospectively from 20 eyes preoperatively and at 1, 3, 6, and 12 months post-DSAEK. At each visit, the best spectacle-corrected visual acuity and visual acuity with glare (brightness acuity testing) were recorded, and ocular wavefront measurements and corneal optical coherence tomography (OCT) were performed. The magnitude and the sign of individual Zernike terms [higher-order aberrations (HOAs)] were determined. Epithelial, host stromal, donor stromal, and total corneal thicknesses were quantified. The brightness and intensity profiles of OCT images were generated to quantify light scatter in the whole cornea, subepithelial region, anterior and posterior host stroma, interface, and donor stroma.The mean best spectacle-corrected visual acuity and glare disability at low light levels improved from 1 to 12 months post-DSAEK. All corneal thicknesses and ocular lower-order aberrations and HOAs were found to be stable from 1 to 12 months, whereas total corneal, host stromal, and interface brightness intensities decreased significantly over the same period. A repeated measures analysis of variance performed across the follow-up period revealed that the change in scatter, but not the change in the HOAs, could account for the variability occurring in the acuity from 1 to 12 months post-DSAEK.Although ocular HOAs and scatter are both elevated over normal values post-DSAEK, our results demonstrate that the improvements in visual performance occurring over the first year post-DSAEK are associated with decreasing light scatter. In contrast, there were no significant changes in the ocular HOAs during this time. Because corneal light scatter decreased between 1 and 12 months despite there being stable corneal thicknesses over the same period, we conclude that factors that induced light scatter, other than tissue thickness or swelling (corneal edema), significantly impacted the visual improvements that occurred over time post-DSAEK. A better understanding of the cellular and extracellular matrix changes of the subepithelial region and interface, incurred by the surgical creation of a lamellar host–graft interface, and the subsequent healing of these tissues, is warranted.