Many algorithms exist for the topographic/tomographic detection of corneas at risk for post-refractive surgery ectasia. It is proposed that the reason for the difficulty in finding a universal screening tool based on corneal morphologic features is that curvature, elevation, and pachymetric changes are all secondary signs of keratoconus and post-refractive surgery ectasia and that the primary abnormality is in the biomechanical properties. It is further proposed that the biomechanical modification is focal in nature, rather than a uniform generalized weakening, and that the focal reduction in elastic modulus precipitates a cycle of biomechanical decompensation that is driven by asymmetry in the biomechanical properties. This initiates a repeating cycle of increased strain, stress redistribution, and subsequent focal steepening and thinning. Various interventions are described in terms of how this cycle of biomechanical decompensation is interrupted, such as intrastromal corneal ring segments, which redistribute the corneal stress, and collagen crosslinking, which modifies the basic structural properties. Proprietary or commercial disclosures are listed after the references.

PURPOSE: To describe pachymetric progression indices (PPI) of the Pentacam HR (Oculus Optikgeräte GmbH) and the concept of relational thickness, and to test their accuracy for differentiating keratoconic and normal corneas compared with single-point thickness values. METHODS: One hundred thirteen individual eyes randomly selected from 113 normal patients and 44 eyes of 44 patients with keratoconus were studied using the Pentacam HR by acquiring central corneal thickness (CCT), thinnest point (TP), position of the TP and PPI at minimal (PPI Min) and maximal (PPI Max) meridians, and the average (PPI Ave) of all meridians. Relational thickness parameters were calculated as the ratios of TP and CCT and PPI values. Mann-Whitney U test assessed differences in groups for each variable. Receiver operating characteristic (ROC) curves were calculated for all variables and pairwise comparisons were performed. RESULTS: Statistically significant differences were noted between normal and keratoconic eyes for all parameters ( P <.001), except for horizontal position of TP ( P =.79). The best parameters, named Ambrósio’s Relational Thickness (ART), were ART-Ave (TP/PPI Ave) and ART-Max (TP/PPI Max) with areas under the ROC curves of 0.987 and 0.983, respectively. The best cutoffs were 424 μm and 339 μm for ART-Ave and ART-Max, respectively. Pachymetric progression indices and ART had a greater area under the curve than TP and CCT ( P <.001); TP (0.955) had a greater area under the curve than CCT (0.909; P =.002). CONCLUSIONS: Tomographic-derived pachymetric parameters were better able to differentiate normal and keratoconic corneas than single-point pachymetric measurements. Further studies are needed to evaluate the role of tomography in identifing early forms of ectasia as well as ectasia risk among LASIK candidates.

To evaluate visual acuity, refractive outcomes, and endothelial cell density 6 months after Descemet stripping and automated endothelial keratoplasty (DSAEK). We performed an institutional review board-approved prospective study of a surgical case series of 34 patients at 2 institutions undergoing DSAEK for Fuchs endothelial dystrophy, pseudophakic bullous keratopathy, or aphakic bullous keratopathy with or without simultaneous phacoemulsification and intraocular lens implantation. Clinical outcomes, including best spectacle-corrected visual acuity (BSCVA), spherical equivalent refraction, and refractive astigmatism and topographic or keratometric astigmatism, were assessed at the 6-month postoperative examination and compared with preoperative values with paired Student t tests. The change in endothelial cell density from the eye bank examination to 6 months after transplantation was similarly evaluated. BSCVA averaged 20/99 preoperatively and 20/42 postoperatively (P < 0.0001). After DSAEK, 30 (88.2%) of 34 patients showed improved BSCVA, and 21 (61.8%) of the 34 patients achieved a BSCVA of 20/40 or better. For patients not undergoing simultaneous phacoemulsification and intraocular lens implantation, a hyperopic shift in refraction of 1.19 +/- 1.32 D was noted. Refractive astigmatism, topographic astigmatism, and keratometry showed no statistically significant change. Endothelial cell density of donor corneas averaged 2826 +/- 370 cells/mm, whereas the mean postoperative density was 1396 +/- 440 cells/mm. This finding corresponded to an average loss of 1426 cells/mm (50% loss; P = 0.0001). The first half of cases experienced an average cell loss of 1674 cells/mm (59% loss) compared with 1181 (41% loss) in the second half of cases (P = 0.005). Three (9%) of 34 grafts experienced iatrogenic graft failure and required reoperation with new donor tissue. Also, 9 (27%) of 34 grafts experienced dislocation in the early postoperative period and required repositioning. In this prospective study of DSAEK for bullous keratopathy and Fuchs endothelial corneal dystrophy, improvement of visual acuity was achieved with only a mild tendency toward hyperopic shift and without significant induced astigmatism. Endothelial cell loss was significant, however, and may be related to surgical experience.

The aim of this study was to investigate the relationship between the level of stromal surface irregularity after photorefractive keratectomy (PRK) and myofibroblast generation along with the development of corneal haze. Variable levels of stromal surface irregularity were generated in rabbit corneas by positioning a fine mesh screen in the path of excimer laser during ablation for a variable percentage of the terminal pulses of the treatment for myopia that does not otherwise generate significant opacity. Ninety-six rabbits were divided into eight groups: [see table in text]. Slit lamp analysis and haze grading were performed in all groups. Rabbits were sacrificed at 4 hr or 4 weeks after surgery and histochemical analysis was performed on corneas for apoptosis (TUNEL assay), myofibroblast marker alpha-smooth muscle actin (SMA), and integrin alpha4 to delineate the epithelial basement membrane. Slit-lamp grading revealed severe haze formation in corneas in groups IV and VI, with significantly less haze in groups II, III, and VII and insignificant haze compared with the unwounded control in groups I and V. Analysis of SMA staining at 4 weeks after surgery, the approximate peak of haze formation in rabbits, revealed low myofibroblast formation in group I (1.2+/-0.2 cells/400x field) and group V (1.8+/-0.4), with significantly more in groups II (3.5+/-1.8), III (6.8+/-1.6), VII (7.9+/-3.8), IV (12.4+/-4.2) and VI (14.6+/-5.1). The screened groups were significantly different from each other (p < 0.05), with myofibroblast generation increasing with higher surface irregularity in the -4.5 diopter PRK groups. The -9.0 diopter PRK group VI had significantly more myofibroblast generation than the -9.0 diopter PRK with PTK-smoothing group VII (p < 0.01). Areas of basement membrane disruption were demonstrated by staining corneas for integrin alpha4 and were prominent in corneas with grade I or higher haze. SMA-positive myofibroblasts tended to be present sub-adjacent to basement membrane defects. Late apoptosis was detected at 1 month after surgery within clusters of myofibroblasts in the sub-epithelial stroma. In conclusion, these results demonstrated a relationship between the level of corneal haze formation after PRK and the level of stromal surface irregularity. PTK-smoothing with methylcellulose was an effective method to reduce stromal surface irregularity and decreased both haze and associated myofibroblast density. We hypothesize that stromal surface irregularity after PRK for high myopia results in defective basement membrane regeneration and increased epithelium-derived TGFbeta signalling to the stroma that increases myofibroblast generation. Late apoptosis appears to have a role in the disappearance of myofibroblasts and haze over time.