Morphological Features Among Gaussian, Sagittal, and Tangential Curvature Maps in Normal and Keratoconus Eyes Using Anterior Segment Optical Coherence Tomography.

PURPOSE: To investigate and compare the morphological features and differences among Gaussian, Sagittal, and Tangential anterior corneal curvature maps obtained with an anterior segment optical coherence tomographer combined with a Placido disc MS-39 device in keratoconus (KC) and normal eyes. METHODS: Prospective, cross-sectional study including 37 KC and 51 healthy eyes. The pattern of astigmatism and maximum keratometry (Kmax), keratometry at the thinnest point (Ktp) and 2 mm diameter (K2mm), and inferior-superior dioptric asymmetry values were obtained and calculated from Gaussian, Tangential, and Sagittal curvature maps using the MS-39 (CSO). RESULTS: In KC eyes, an asymmetric bowtie pattern was observed in 64.86% (24/37), 64.86% (24/37), and 0% in the Sagittal, Tangential, and Gaussian maps, respectively. In normal eyes, 51.0% (26/51), 51.0% (26/51), and 0% showed a symmetric bowtie pattern in the Sagittal, Tangential, and Gaussian maps, respectively. There was a significant difference for the variables Kmax, Ktp, and K2mm inferior among the Gaussian, Tangential, and Sagittal maps in both normal and KC groups. Sensitivity discriminating between normal and KC eyes was 100%, 97.3%, and 90.9% and specificity was 94.1%, 100%, and 100% for Kmax coming from the Tangential, Gaussian, and Sagittal maps, respectively. CONCLUSIONS: Gaussian maps displayed significantly different morphological features when compared with Sagittal and Tangential maps in normal and KC eyes. Anterior curvature maps from Gaussian maps do not show the morphological pattern of symmetric bowtie in normal eyes nor asymmetric bowtie in KC eyes. Kmax from Gaussian maps are more specific, however less sensitive than Tangential maps in discriminating KC from normal eyes.

The false positive rates for detecting keratoconus and potential ectatic corneal conditions when evaluating astigmatic eyes with Scheimpflug Technology.

PURPOSE: To quantify the false positive rates for keratoconus (KC) and potential ectatic corneal conditions in highly astigmatism eyes when using published parameters/indices obtained from the Pentacam and Galilei units. SETTING: Oftalmosalud Instituto de Ojos, Lima, Peru. DESIGN: Prospective cohort study. METHODS: 67 consecutive eyes with corneal astigmatism > 1.5 D, with a minimum follow ups of 36 months after an uneventful LASIK procedure were included. Indices for KC and other potential ectatic corneal conditions (subclinical KC, forme fruste KC, suspect KC) were obtained using the Pentacam and Galilei Scheimpflug cameras. MAIN OUTCOME MEASURES: The false positive rates for KC and potential ectatic corneal conditions were measured. Cut off values provided by previous studies and company-based parameters were used to assess the rate of false positivity. RESULTS: The range of false positive rates for a KC diagnosis depending on the lowest and highest cutoff values were: index of height decentration (61% - 1%), index of surface variance (76% - 0%), Posterior elevation (55% - 0%), maximum Ambrosio Relational thickness (100% - 13%), Belin Ambrosio enhanced ectasia display total deviation value (100% - 4%), Average pachymetric progression index (69% - 3%), Pachymetry at the thinnest point (58% - 1%), CSI Center Surround Index (100%), Differential sector index (51%). CONCLUSION: The false positive rates for KC and ectatic corneal conditions vary dramatically depending on the cut-off values used. Some indexes used for diagnosis of potential ectatic corneal conditions are inaccurate in normal, highly astigmatic eyes.

Repeatability of Corneal Deformation Response Parameters by Dynamic Ultra High-speed Scheimpflug Imaging in Normal and Keratoconus Eyes.

PURPOSE: To assess the repeatability of corneal dynamic response (CDR) parameters in normal and keratoconus (KC) eyes using ultra high-speed Scheimpflug imaging. METHODS: Prospective, comparative, observational study, including eyes of 112 patients that underwent high-speed Scheimpflug imaging analysis (Corvis ST, OCULUS). Twenty-one CDR parameters were evaluated to asses repeatability using: coefficient of repeatability (CR), coefficient of variation, intraclass correlation coefficient (ICC) and within-subject SD. Three consecutive measurements by the same operator were performed for each eye. RESULTS: There were no significant differences between the three consecutive measurements for all parameters in both normal and KC eyes. 71.42% (15 of the 21 parameters evaluated) and 85.71% (18 of the 21 parameters) were highly repeatable in the normal and KC group, respectively. The tomographic biomechanical index (TBI), corneal biomechanical index (CBI), and stiffness parameter (SPA1) showed an ICC of 0.978, 0.954, and 0.958 in normal and 0.982, 0.892, and 0.978 in KC eyes, respectively. The CR in normal eyes for TBI, CBI, and SPA1 were 0.169, 0.242, and 14.12, respectively, and for KC eyes 0.06, 0.23, and 13.64, respectively. CONCLUSIONS: Most of the corneal dynamic response parameters were highly repeatable in normal and KC eyes.

Acute Hydrops After Bowman Layer Transplantation for Keratoconus May Indicate that Descemet Membrane Rupture Is Secondary to Hydrops.

PURPOSE: The aim of this study was to review the postoperative course and imaging features of 7 eyes that presented with corneal hydrops after Bowman layer (BL) transplantation was performed for advanced keratoconus to determine the potential mechanisms of hydrops formation. METHODS: A retrospective analysis was performed of 7 eyes of 5 patients with advanced keratoconus that underwent midstromal BL transplantation at 2 tertiary referral centers and developed acute corneal hydrops on average 64 (±30) months (range 14-104 months) postoperatively. Corneal tomography and anterior segment optical coherence tomography (AS-OCT) images were reviewed to document the postoperative and posthydrops course. RESULTS: For all eyes, the post-BL transplantation course was uneventful until hydrops development. Despite stable postoperative topographies in 5 of 7 eyes, eyes developed hydrops with typical hypodense areas on AS-OCT that were limited to the stromal layers posterior to the BL graft. With AS-OCT (6/7 eyes), 2 eyes showed a break in Descemet membrane, whereas Descemet membrane was intact across the cornea in 2 eyes; in 2 eyes, the images were inconclusive. All patients admitted to continued eye rubbing, and all but 1 had a clinically significant allergy and/or atopic constitution. Most eyes (5/7) showed a relatively quick (visual) recovery within 1 to 4 months after hydrops. CONCLUSIONS: Hydrops formation in keratoconic corneas after midstromal BL transplantation may indicate that a break in Descemet membrane is secondary to hydrops development (and not vice versa). With a midstromal BL graft in situ limiting hydrops dimensions, resolution of the hydrops seemed relatively quick with recovery to prehydrops visual acuity in most eyes.

Correlation between lens thickness and lens density in patients with mild to moderate cataracts.

PURPOSE: To determine the relationships between lens thickness (LT), lens density and anterior segment parameters in patients with mild to moderate cataracts. SETTING: Oftalmosalud Instituto de Ojos, Lima, Perú. DESIGN: Prospective, single-centre, cross-sectional study. METHODS: 169 eyes with age-related mild to moderate cataracts had lens density assessed using the Lens Opacification Classification System III, the built-in Pentacam HR Nucleus Staging software and ImageJ software. LT and axial length (AL) were measured with the IOLMaster 700, and angle parameters were measured using anterior segment optical coherence tomography. Pearson correlation coefficients and Kruskal-Wallis tests were used for statistical analyses. RESULTS: Nuclear colour score was the only clinical parameter with a weak significant correlation with LT (r=0.24, p=0.003) after accounting for age, AL, gender and anterior chamber depth (ACD). The maximum value of average lens density and the mean nuclear density were significantly correlated with LT (r=0.24, p=0.003 and -0.17, p=0.03, respectively) after controlling for the same factors. Central LT greater than 4.48 mm was present in 54.5% of the eyes with a nuclear opalescence grade 1. CONCLUSIONS: LT is independent of lens density in mild to moderate cataracts after accounting for age, AL, ACD and gender contrary to previous studies.

Evaluation of the Suitability of Biocompatible Carriers as Artificial Transplants Using Cultured Porcine Corneal Endothelial Cells.

Purpose/Aim: Evaluating the suitability of bioengineered collagen sheets and human anterior lens capsules (HALCs) as carriers for cultivated porcine corneal endothelial cells (pCECs) and in vitro assessment of the cell-carrier sheets as tissue-engineered grafts for Descemet membrane endothelial keratoplasty (DMEK). MATERIALS AND METHODS: pCECs were isolated, cultured up to P2 and seeded onto LinkCell™ bioengineered matrices of 20 µm (LK20) or 100 µm (LK100) thickness, and on HALC. During expansion, pCEC viability and morphology were assessed by light microscopy. ZO-1 and Na+/K+-ATPase expression was investigated by immunohistochemistry. Biomechanical properties of pCEC-carrier constructs were evaluated by simulating DMEK surgery in vitro using an artificial anterior chamber (AC) and a human donor cornea without Descemet membrane (DM). RESULTS: During in vitro expansion, cultured pCECs retained their proliferative capacity, as shown by the positive staining for proliferative marker Ki67, and a high cell viability rate (96 ± 5%). pCECs seeded on all carriers formed a monolayer of hexagonal, tightly packed cells that expressed ZO-1 and Na+/K+-ATPase. During in vitro surgery, pCEC-LK20 and pCEC-LK100 constructs were handled like Descemet stripping endothelial keratoplasty (DSEK) grafts, i.e. folded like a "taco" for insertion because of challenges related to rolling and sticking of the grafts in the injector. pCEC-HALC constructs behaved similar to the DMEK reference model during implantation and unfolding in the artificial AC, showing good adhesion to the bare stroma. CONCLUSIONS: In vitro DMEK surgery showed HALC as the most suitable carrier for cultivated pCECs with good intraoperative graft handling. LK20 carrier showed good biocompatibility, but required a DSEK-adapted surgical protocol. Both carriers might be notional candidates for potential future clinical applications.

Comparison of the effect of LASIK parameters on the percent tissue altered (1-dimensional metric) versus percent volume altered (3-dimensional metric).

PURPOSE: To determine the theoretical volumes of flap and tissue ablation altered during laser in situ keratomileusis (LASIK) correction of myopic refractive errors. SETTING: Rothschild Foundation, Paris, France. DESIGN: Experimental study. METHODS: The theoretical volumes of the flap and ablated corneal lenticules for spherical myopic corrections were calculated by mathematical approximations based on a simplified geometric model. These results were then compared for various zone diameters, dioptric corrections, and the percentage of the volumes altered (PVA) with the percentage of tissue altered (PTA). RESULTS: The volume of the flap varied linearly with flap thickness and with the square of the flap diameter. The volume of ablated corneal tissue was estimated to be proportional to the magnitude of myopia treatment and to the 4th power of the treatment diameter. For the same depth of ablation, the volume of tissue ablated can vary significantly, depending on the magnitude of the correction and the optical zone diameter. As a result, the PTA calculation is not predictive of the actual PVA. CONCLUSIONS: The flap diameters and the laser correction were the most important determinants of the PVA altered during LASIK surgery. New models estimating the volume of the flap and corneal tissue might be necessary to determine their influence on corneal biomechanical stability and each procedure's outcome.

Histopathology of Failed Descemet Membrane Endothelial Transfer.

OBJECTIVES: To describe the postmortem histologic features after an unsuccessful Descemet membrane endothelial transfer (DMET) and assess any potential clinical implications. METHODS: Postmortem, an eye from a patient who previously underwent unsuccessful DMET for pseudophakic bullous keratopathy (PPBK) was harvested and processed for morphologic evaluation. RESULTS: Clinically and histologically, the host cornea showed evidence of diffuse stromal edema. Although the edges of the surgical descemetorhexis were well visualized, there was no evidence of endothelial migration or repopulation of the posterior stroma from any direction. A multilayered, retrocorneal membrane was present that appeared to originate from the trabecular meshwork. CONCLUSIONS: Descemet membrane endothelial transfer and "descemetorhexis alone" may be insufficient treatment for eyes operated on for PPBK, that is, eyes with a significantly depleted or dysfunctional endothelium.

Multicenter Study of 6-Month Clinical Outcomes After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To report the 6-month clinical outcomes of a large cohort of Descemet membrane endothelial keratoplasty (DMEK) eyes operated by 55 starting or experienced surgeons. METHODS: This is a retrospective, multicenter, interventional, cohort study with a total of 2485 eyes. Best-corrected visual acuity (BCVA), endothelial cell density (ECD) decrease, and intra- and post-operative complications were evaluated. Three groups based on case order were compared: group I (cases 1-24), group II (cases 25-99), and group III (cases ≥100). Forty-nine percent of the surgeons were in their learning curve (<25 cases), representing 10.4% of the surgeries. RESULTS: Six months after DMEK, BCVA improved in 90.5% of eyes, remained unchanged in 4.6%, and deteriorated in 4.9% (n = 1936); 75.4% of eyes reached a BCVA of ≥20/40 (≥0.5), 45.4% ≥20/25 (≥0.8), and 25.8% ≥20/20 (≥1.0) (n = 1959) and ECD decreased by 40% (±19) (n = 1272, P < 0.05). BCVA and ECD outcomes did not differ between groups I and III (P > 0.05). Intraoperative complications were reported for 9.4% of eyes, whereas graft detachment was the main postoperative complication (27.4%), with lower intra- and post-operative complication rates in group III than group I (P < 0.05). Rebubbling was performed in 20.1% of eyes; 13.8% required secondary keratoplasty within 6 months. CONCLUSIONS: DMEK is applicable for surgeons in various settings with good clinical outcomes. After an arbitrary learning curve (<25 cases), virtually all transplant-related complications declined with experience. Notably, surgeons with a higher annual caseload may pass faster through their learning curve than surgeons performing their first surgeries over an extended period.

Evaluation of the percentage tissue altered as a risk factor for developing post-laser in situ keratomileusis ectasia.

PURPOSE: To assess the currently recommended percentage tissue altered (PTA) metric for its ability to screen for ectasia after laser in situ keratomileusis (LASIK). SETTING: Gavin Herbert Eye Institute, University of California, Irvine, California, USA, and Rothschild Foundation, Paris, France. DESIGN: Retrospective case series. METHODS: The study used a LASIK database created by 1 surgeon for LASIK cases with normal preoperative topography that had a minimum follow-up of 24 months with complete preoperative and intraoperative data to permit the calculation of PTA values to detect eyes at risk for developing ectasia. RESULTS: Of the eyes, 593 eyes had complete data and met the inclusion criteria. Based on measured flap thickness, 126 eyes (21%) had a PTA value of 40% or more (mean 44) and a percentage of that flap thickness accounted for the PTA (mean 66.7%; range 34% to 92%). The mean attempted laser ablation was 79.8 µm ± 29.2 (SD), and the mean residual bed thickness was 304.4 ± 29.2 µm (range 212 to 369 µm). No eye developed ectasia over a mean follow-up of 30 months. CONCLUSIONS: The current PTA calculation when applied to a LASIK population with normal preoperative topography and flap thickness measured with ultrasound did not predict the risk for ectasia. Differences between study populations and assumptions might have accounted for the different outcomes obtained in the initially published PTA study.

Intracorneal Inlays for the Correction of Presbyopia.

The current nonsurgical approaches for the correction of presbyopia are spectacles or contact lenses or the use of pharmaceuticals to create an artificial pupil and/or to stimulate residual accommodation. Refractive surgical procedures use a monovision approach and/or a multifocal corneal laser ablation with or without the induction of negative spherical aberration to improve near vision. More recently, new surgical approaches include intracorneal inlays. Inlay approaches include increasing corneal curvature alone, implanting a multifocal inlay, or by implanting a small aperture device that functions as a pinhole to restore unaided near and intermediate visual acuity. This review presents an analysis of the history and development of the various inlay approaches designed to improve presbyopia. Unlike other refractive surgical approaches, these newer techniques are removable. Each has its advantages and disadvantages.

Outcome and Histopathology of Secondary Penetrating Keratoplasty Graft Failure Managed by Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To describe the clinical outcome and histopathology of Descemet membrane endothelial keratoplasty (DMEK) performed for secondary graft failure after penetrating keratoplasty (PK). METHODS: A total of 11 eyes from 10 patients who underwent DMEK for secondary PK graft failure at a tertiary referral center were included in this retrospective study. Best-corrected visual acuity, endothelial cell density, and central pachymetry were evaluated before and at regular time intervals up to 36 months after DMEK and complications were recorded; 1 post mortem cornea was available for light microscopy. RESULTS: At their last follow-up visit (on average, 16 months after DMEK), 7 of 11 transplanted corneas were clear. In the 7 eyes with clear grafts, 5 had a best-corrected visual acuity of ≥20/25 (≥0.8), central pachymetry averaged 535 (±70) µm, and endothelial cell density averaged 1045 (±500) cells/mm. Of the 11 eyes, 4 required rebubbling in the early postoperative phase; 1 eye was left with a small (<1/3) detachment. Light microscopy of the pathology specimen showed complete attachment of the DMEK graft onto the preexisting PK posterior stroma, with interface scarring over DMEK graft folds and underneath the graft area that had initially been detached. CONCLUSIONS: DMEK may be a viable option to manage secondary PK graft failure with acceptable outcomes in many cases. Rebubbling for graft detachment may be anticipated, especially because of preexisting glaucoma conditions (severe decompensation, hypotony, and tubes from glaucoma-draining devices). Graft reattachment may occur through interface scarring.

Leak-Free Clear Corneal Incisions in Human Cadaver Tissue: Femtosecond Laser-Created Multiplanar Incisions.

OBJECTIVES: To evaluate femtosecond (FS) laser-assisted leak-free clear corneal incisions (CCI) and paracentesis (P) in human eyes of deceased donors. METHODS: Multiplanar CCI and P were created using an FS laser on human eyes of deceased donors (whole globe and corneal rims). Laser settings were programmed to multiplanar for CCI and single plane for P. Corneas were imaged by optical coherence tomography (OCT) and evaluated for leak by Seidel testing at various intraocular pressure (IOP) levels, and the wound was manipulated to mimic cataract surgery. Corneal endothelium cell damage and histological architecture were evaluated by microscopy. RESULTS: The corneal incision software of the FS laser was used to create homogeneous CCI and P incisions. Morphological changes assessed by OCT and light microscopy/scanning electron microscopy showed consistent true multiplanar incisions with predefined intersecting planes. All Seidel testing was negative, indicating that FS laser-assisted incisions did not leak. Trypan blue stain of the endothelial surface showed limited cell damage from the FS laser incisions. CONCLUSIONS: The FS laser-created incisions corresponded well with the treatment plans, as evidenced by true multiplanar architecture. Incisions were sharply demarcated and demonstrated limited cell damage. No postprocedure leaking at extreme IOP or postcataract surgery-simulated conditions was noted. The FS laser may potentially reduce postoperative complications, such as infections that may be associated with CCI.

Sex Chromosome Analysis of Postmortem Corneal Endothelium After Sex-Mismatch Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To identify the origin of corneal endothelial cells (host or donor) present on grafts at various time points after Descemet membrane endothelial keratoplasty (DMEK), using fluorescence in situ hybridization (FISH) of sex chromosomes on post mortem corneas with sex mismatch between the donor and host. METHODS: Corneoscleral buttons of 6 post mortem DMEK eyes of 4 patients, operated for Fuchs endothelial dystrophy, with an average postoperative time of 2.6 (±1.8) years (range, 7 months-4.5 years), of 2.5 (±1.7) years (range, 7 months-4 years), were processed for FISH detection of XX (female) or XY (male)-labeling signals in corneal endothelial cells in the central area of the DMEK graft. Two male patients underwent bilateral DMEK with grafts from female donors, and 2 female patients underwent unilateral DMEK and received a graft from a male donor. RESULTS: FISH consistently showed the presence of donor endothelial cells across the graft area, with signaling of sex chromosomes opposite to the sex of the host. CONCLUSIONS: Donor endothelial cells may survive up to 4.5 years after DMEK. If so, the lower incidence of allograft rejection in DMEK may not be explained by early host cell replacement. Potential host cell migration may be limited by donor/recipient cell-cell contact inhibition.

Histopathologic Features of Descemet Membrane Endothelial Keratoplasty Graft Remnants, Folds, and Detachments.

PURPOSE: To describe the histologic features of postmortem eyes after Descemet membrane endothelial keratoplasty (DMEK) and their potential clinical implications. DESIGN: Histopathologic study. PARTICIPANTS: Eleven postmortem DMEK corneas of 8 patients who underwent surgery for Fuchs endothelial dystrophy, with an average postoperative time of 4±1.9 years (range, 7 months-6.5 years). METHODS: Eleven corneas transplanted with a DMEK graft were procured after death and processed for light microscopy evaluation. MAIN OUTCOME MEASURES: Histologic findings at the donor-host interface and at the host edge. RESULTS: Of the 11 corneas available for analysis, 9 showed normal anatomic features in the corneal center; that is, the donor-host interface resembled that of a virgin eye. One eye also had an anatomically normal periphery, but the remaining 10 eyes showed specific abnormalities in the periphery. Nine demonstrated overlapping of the DMEK graft onto the host edge of the descemetorhexis (and in 6 of these, the overlapping tissue showed a contracted inward fold at its peripheral edge with scar tissue); 1 eye showed a dense, acellular scar overlying a portion of the DMEK graft that clinically had shown a detachment followed by spontaneous adherence; 3 eyes showed subtle graft folds with scar tissue anteriorly; in 2 eyes (of the same patient), the anterior banded layer of the host Descemet membrane (DM) was still in situ across the cornea (both of these eyes had required rebubbling); and 2 eyes showed host DM remnants within the corneolimbal tunnel incision that may have interfered with incisional wound healing. CONCLUSION: Incomplete host DM removal may relate to postoperative DMEK graft detachment and wound instability. Graft detachments may reattach with interface scarring. Rebubbling procedures may be performed within 4 to 6 weeks, before portions of the detached graft scar. Subtle DMEK graft folds may explain subjective reports of monocular diplopia.

Penetrating and Intrastromal Corneal Arcuate Incisions in Rabbit and Human Cadaver Eyes: Manual Diamond Blade and Femtosecond Laser-Created Incisions.

OBJECTIVES: To compare morphologic differences between freehand diamond or femtosecond laser-assisted penetrating and intrastromal arcuate incisions. METHODS: Freehand diamond blade, corneal arcuate incisions (180° apart, 60° arc lengths) and 150 kHz femtosecond laser (80% scheimpflug pachymetry depth corneal thickness) arcuate incisions were performed in rabbits. Intrastromal arcuate incisions (100 µm above Descemet's membrane, 100 µm below epithelium) were performed in rabbit corneas (energy 1.2 µJ, spot line separation 3 × 3 µm, 90° side cut angle). Eyes were examined by slit lamp and light microscopy up to 47 days post-procedure. Freehand diamond blade penetrating incisions, and femtosecond laser penetrating and intrastromal arcuate incisions (energy 1.8 µJ, spot line separation 2 × 2 µm) were performed in cadaver eyes. Optical coherence tomography was performed immediately after surgery and the corneas were fixed for light scanning and transmission electron microscopy. RESULTS: The rabbit model showed anterior stromal inflammation with epithelial hyperplasia in penetrating blade and laser penetrating wounds. The laser intrastromal and penetrating incisions showed localized constriction of the stromal layers of the cornea near the wound. In cadaver eyes, penetrating wound morphology was similar between blade and laser whereas intrastromal wounds did not affect the cornea above or below incisions. CONCLUSION: Penetrating femtosecond laser arcuate incisions have more predictable and controlled outcomes shown by less post-operative scarring than incisions performed with a diamond blade. Intrastromal incisions do not affect uncut corneal layers as demonstrated by histopathology. The femtosecond laser has significant advantages in its ability to make intrastromal incisions which are not achievable by traditional freehand or mechanical diamond blades.