Refractive outcome and tomographic changes after Descemet membrane endothelial keratoplasty in pseudophakic eyes with Fuchs' endothelial dystrophy.

PURPOSE: To analyze refractive and topographic changes secondary to Descemet membrane endothelial keratoplasty (DMEK) in pseudophakic eyes with Fuchs' endothelial dystrophy (FED). METHODS: Eighty-seven pseudophakic eyes of 74 patients who underwent subsequent DMEK surgery for corneal endothelial decompensation and associated visual impairment were included. Median post-operative follow-up time was 12 months (range: 3-26 months). Main outcome measures were pre- and post-operative manifest refraction, anterior and posterior corneal astigmatism, simulated keratometry (CASimK) and Q value obtained by Scheimpflug imaging. Secondary outcome measures included corrected distance visual acuity (CDVA), central corneal densitometry, central corneal thickness, corneal volume (CV), anterior chamber volume (ACV) and anterior chamber depth (ACD). RESULTS: After DMEK surgery, mean pre-operative spherical equivalent (± SD) changed from + 0.04 ± 1.73 D to + 0.37 ± 1.30 D post-operatively (p = 0.06). CDVA, proportion of emmetropic eyes, ACV and ACD increased significantly during follow-up. There was also a significant decrease in posterior corneal astigmatism, central corneal densitometry, central corneal thickness and corneal volume over time (p = 0.001). Only anterior corneal astigmatism and simulated keratometry (CASimK) remained fairly stable after DMEK. CONCLUSION: Despite tendencies toward a hyperopic shift, changes in SE were not significant and refraction remained overall stable in pseudophakic patients undergoing DMEK for FED. Analysis of corneal parameters by Scheimpflug imaging mainly revealed changes in posterior corneal astigmatism pointing out the relevance of posterior corneal profile changes during edema resolution after DMEK.

Ectatic diseases.

Ectatic corneal disease (ECD) comprises a group of disorders characterized by progressive thinning and subsequent bulging of the corneal structure. Different phenotypes have been recognized, including keratoglobus, pellucid marginal degeneration (PMD), and keratoconus (KC). Keratoconus has been widely investigated throughout the years, but the advent of laser refractive surgery boosted an immediate need for more knowledge and research about ectatic diseases. This article discusses nomenclature of ectatic disease, etiology and pathogenesis, along with treatment options, with special focus ok KC and forme fruste keratoconus.

Biomechanical diagnostics of the cornea.

Corneal biomechanics has been a hot topic for research in contemporary ophthalmology due to its prospective applications in diagnosis, management, and treatment of several clinical conditions, including glaucoma, elective keratorefractive surgery, and different corneal diseases. The clinical biomechanical investigation has become of great importance in the setting of refractive surgery to identify patients at higher risk of developing iatrogenic ectasia after laser vision correction. This review discusses the latest developments in the detection of corneal ectatic diseases. These developments should be considered in conjunction with multimodal corneal and refractive imaging, including Placido-disk based corneal topography, Scheimpflug corneal tomography, anterior segment tomography, spectral-domain optical coherence tomography (SD-OCT), very-high-frequency ultrasound (VHF-US), ocular biometry, and ocular wavefront measurements. The ocular response analyzer (ORA) and the Corvis ST are non-contact tonometry systems that provide a clinical corneal biomechanical assessment. More recently, Brillouin optical microscopy has been demonstrated to provide in vivo biomechanical measurements. The integration of tomographic and biomechanical data into artificial intelligence techniques has demonstrated the ability to increase the accuracy to detect ectatic disease and characterize the inherent susceptibility for biomechanical failure and ectasia progression, which is a severe complication after laser vision correction.

Corneal Densitometry After Secondary Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To evaluate Scheimpflug corneal densitometry (CD) in patients undergoing secondary Descemet membrane endothelial keratoplasty (DMEK) after previous Descemet stripping automated endothelial keratoplasty or DMEK surgery. METHODS: This was a retrospective institutional case series of 37 eyes of 37 patients. Two secondary DMEK groups, group 1A (n = 12 DMEK after Descemet stripping automated endothelial keratoplasty), group 1B (n = 11 repeat DMEK), and group 2 (n = 14 primary DMEK for Fuchs endothelial dystrophy) were formed. CD was obtained preoperatively, 1, 6, and 12 months postoperatively. In addition, corrected distance visual acuity, central corneal thickness, and endothelial cell density were assessed. RESULTS: A significant decrease in grayscale units was observed in the 0- to 2-mm and 2- to 6-mm zones in all groups. For the 0- to 2-mm zone, values decreased from 49.11 ± 17.96 preoperatively to 22.87 ± 5.24 at 12 months (group 1A), from 45.16 ± 9.22 to 24.53 ± 14.21 (group 1B), and from 27.90 ± 8.30 to 16.64 ± 1.51 (group 2) (P < 0.01). Group 2 showed significantly lower grayscale units than groups 1A and 1B preoperatively and 12 months postoperatively in the 0- to 2-mm and 2- to 6-mm zones. Significant correlations of CD and corrected distance visual acuity were found in groups 1A and 1B in the 0- to 2-mm zone at 12 months. There were no significant correlations between CD and central corneal thickness postoperatively. CONCLUSIONS: A decrease in CD could be demonstrated in secondary DMEK. Nevertheless, CD values remained significantly higher than in controls. This might point out the relevance of secondary corneal structural changes.

Corneal Biomechanics in Ectatic Diseases: Refractive Surgery Implications.

BACKGROUND: Ectasia development occurs due to a chronic corneal biomechanical decompensation or weakness, resulting in stromal thinning and corneal protrusion. This leads to corneal steepening, increase in astigmatism, and irregularity. In corneal refractive surgery, the detection of mild forms of ectasia pre-operatively is essential to avoid post-operative progressive ectasia, which also depends on the impact of the procedure on the cornea. METHOD: The advent of 3D tomography is proven as a significant advancement to further characterize corneal shape beyond front surface topography, which is still relevant. While screening tests for ectasia had been limited to corneal shape (geometry) assessment, clinical biomechanical assessment has been possible since the introduction of the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, USA) in 2005 and the Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) in 2010. Direct clinical biomechanical evaluation is recognized as paramount, especially in detection of mild ectatic cases and characterization of the susceptibility for ectasia progression for any cornea. CONCLUSIONS: The purpose of this review is to describe the current state of clinical evaluation of corneal biomechanics, focusing on the most recent advances of commercially available instruments and also on future developments, such as Brillouin microscopy.

Role of the corneal epithelium measurements in keratorefractive surgery.

PURPOSE OF REVIEW: Refractive surgery has stimulated considerable progress in corneal and anterior segment imaging, and optical characterization of the eye. From front surface corneal topography, we evolved to three-dimensional corneal tomography with limbus to limbus characterization of the front and back corneal surfaces and pachymetric mapping. Corneal anatomical evaluation has further evolved to layered or segmental tomography with the ability to characterize corneal epithelial thickness profile and the elevation of stromal front surface. Further characterization of even more specific structures, such as Bowman's layer and Descement's membrane, has been also demonstrated. The applications of such understanding in keratorefractive surgery are reviewed. RECENT FINDINGS: Understanding the corneal epithelial profile is of interest in many areas of ophthalmology, especially in refractive surgery. The most relevant applications include screening candidates at higher risk for complications (i.e. progressive ectasia and tear dysfunction syndrome), planning primary procedures, enhancements, and therapeutic surgery, and also postoperatively understanding the wound healing and clinical outcomes. SUMMARY: Corneal epithelial thickness was first available using digital very-high-frequency ultrasound. Advances in anterior segment optical coherence tomography enabled such fundamental evaluation, which accelerated progress. Such knowledge significantly impacts safety and efficacy of refractive surgery, and also allows for significant improvement for therapeutic procedures. VIDEO ABSTRACT.

Detection of ectatic corneal diseases based on pentacam.

Pentacam is a rotating Scheimpflug-based corneal and anterior segment tomographer that gives as comprehensive analysis of corneal 3D geometry. With this device the detection of mild keratoconus or ectasia susceptibility is possible. This is fundamental for screening ectasia risk prior to laser vision correction. The identification of susceptible cases at risk for developing progressive iatrogenic ectasia should go beyond (but not over) corneal front surface topography.

Variability of subjective classifications of corneal topography maps from LASIK candidates.

PURPOSE: To evaluate the variability of subjective corneal topography map classification between different experienced examiners and the impact of changing from an absolute to a normative scale on the classifications. METHODS: Preoperative axial curvature maps using Scheimpflug imaging obtained with the Pentacam HR (Oculus Optikgeräte, Wetzlar, Germany) and clinical parameters were sent to 11 corneal topography specialists for subjective classification according to the Ectasia Risk Scoring System. The study population included two groups: 11 eyes that developed ectasia after LASIK and 14 eyes that had successful and stable LASIK outcomes. Each case was first reviewed using the absolute scale masked to the patient group. After 3 months, the same cases were represented using a normative scale and reviewed again by the same examiners for new classifications masked to the patient group. RESULTS: Using the absolute scale, 17 of 25 (68%) cases had variations on the classifications from 0 to 4 for the same eye across examiners, and the overall agreement with the mode was 60%. Using the normative scale, the classifications from 11 of 25 (44%) cases varied from 0 to 4 for the same eye across examiners, and the overall agreement with the mode was 61%. Eight examiners (73%) reported statistically higher scores (P < .05) when using the normative scale. Considering all 550 topographic analyses (25 cases, 11 examiners, and two scales), the same classification from the two scales was reported for 121 case pairs (44%). CONCLUSION: There was significant inter-observer variability in the subjective classifications using the same scale, and significant intra-observer variability between scales. Changing from an absolute to a normative scale increased the scores on the classifications by the same examiner, but significant inter-observer variability in the subjective interpretation of the maps still persisted.

A microscopy study of the structural features of post-LASIK human corneas.

PURPOSE: To study the structural features of human post-LASIK corneas. METHODS: A pair of post-mortem donor corneas, from a 55-year old patient who underwent uncomplicated LASIK surgery five years previously, were bisected and fixed in 4% paraformaldehyde. The right cornea and one half of the left cornea were processed for light microscopy and scanning electron microscopy. One half of the right cornea was also examined by transmission electron microscopy. RESULTS: The flap-bed interface could be easily detected several years after LASIK and, although the flap appeared to be in close association with the stromal bed, there was a noticeable absence of reconnection between adjacent severed lamellae. Tissue gaps were evident at the flap margin, which once free of cellular components revealed the presence of a few bridging fibres. CONCLUSION: Examination of corneas five years after LASIK revealed evidence of primitive reparative scar development at the wound interface, but no reconnection of severed collagen lamellae. Such findings may explain the occurrence of flap dislocation following trauma in some patients months or years after surgery.

Corneal ectasia after LASIK despite low preoperative risk: tomographic and biomechanical findings in the unoperated, stable, fellow eye.

PURPOSE: To report a case of progressive corneal ectasia after LASIK with no detectable preoperative risk factors and to present three-dimensional corneal tomographic and biomechanical findings on the contralateral unoperated eye that would be considered low risk for ectasia and thereby a good LASIK candidate based on the Randleman Ectasia Risk Score System (ERSS). METHODS: A case report, literature review, and description of novel screening criteria based on Pentacam (Oculus Optikgeräte GmbH) corneal tomography are presented as well as Ocular Response Analyzer (ORA, Reichert Instruments) corneal biomechanical analysis. RESULTS: Progressive corneal ectasia after LASIK of the operated left eye was confirmed by corneal topography. Scheimpflug imaging identified a meniscus-shaped LASIK flap with a central thickness of 165 µm and residual stromal bed thickness of 280 µm. Randleman ERSS score was 2 for the ectatic eye before LASIK and 1 for the current status of the unoperated eye, which remained stable with normal topography and no change in refraction for >5 years. Low corneal hysteresis (8.6 mmHg) and corneal resistance factor (7.5 mmHg) were found in the unoperated, nonectatic eye, along with a suspicious waveform sign of a second rebounded peak after second applanation. Pentacam average pachymetric progression was 1.09 (normal is <1.15); the Belin-Ambrósio overall deviation index was 1.99 (normal is <1.9). CONCLUSIONS: Three-dimensional corneal tomographic and ORA biomechanical measurements provide additional information that may help identify individuals at high risk for naturally occurring or iatrogenic corneal ectasia.

Correlation between epithelial ingrowth and basement membrane remodeling in human corneas after laser-assisted in situ keratomileusis.

OBJECTIVE: To further investigate the hypothesis that epithelial ingrowth in human corneas after laser-assisted in situ keratomileusis (LASIK) correlates with basement membrane remodeling, as suggested by the presence of matrix metalloproteinase 9 around epithelial cells in the lamellar scar. METHODS: Immunohistochemical analysis and transmission electron microscopy were applied to human postmortem corneas with post-LASIK epithelial ingrowth. RESULTS: Epithelial ingrowth into the flap margin was observed in 8 of 18 corneas (44%). Matrix metalloproteinase 9 immunolocalized around ingrown epithelium in 6 of these 8 corneas (75%). There was a positive correlation between the presence of matrix metalloproteinase 9 at the wound margin and discontinuities in the basement membrane, as determined by laminin and beta(4) integrin immunofluorescence. Transforming growth factor beta2 was present into the stroma of some corneas with epithelial ingrowth and interrupted basement membrane, suggesting some degree of epithelial-stromal interaction. Transmission electron microscopy confirmed large areas of remodeled basement membrane along ingrown epithelial cells. CONCLUSIONS: The neo-basement membrane components underlying the ingrown cells in human corneas with epithelial ingrowth after LASIK appear to be partially disassembled. Epithelial-stromal interaction over time may be related to prolonged wound healing remodeling, which calls into question the stability of the flap.

Histopathologic examination of failed grafts in descemet's stripping with automated endothelial keratoplasty.

PURPOSE: To study the histopathologic features of 19 corneal posterior lamellar grafts in eyes for which Descemet's stripping with automated endothelial keratoplasty (DSAEK) has failed. DESIGN: Retrospective case series with clinicopathologic correlation. PARTICIPANTS: Nineteen cases of DSAEK failures undergoing repeat DSAEK or penetrating keratoplasty. METHODS: The histopathologic results of posterior lamellar grafts (also termed DSAEK grafts), recipient corneas, or both from 19 cases of failed DSAEK were examined. MAIN OUTCOME MEASURES: Abnormalities in the DSAEK graft and in the interface between the recipient cornea and the DSAEK graft were assessed. RESULTS: Histopathologic features in 19 failed DSAEK grafts revealed attenuation of endothelial cells (16 cases) and presence in the graft-host interface of fibrocellular tissue (11 cases), retained Descemet's membrane (5 cases), epithelial ingrowth (4 cases), or a combination thereof. Four DSAEK grafts had full-thickness corneal layers at 1 edge. CONCLUSIONS: Presence of interface material, such as fibrocellular tissue, retained Descemet's membrane, and epithelial ingrowth, are potential causes of dislocation. Endothelial attenuation was the most common finding in failed grafts. Decentered DSAEK grafts with full-thickness corneal layers at 1 edge are a potential cause for epithelial ingrowth.

Corneal ectasia after excimer laser keratorefractive surgery: histopathology, ultrastructure, and pathophysiology.

PURPOSE: To evaluate the histopathology and ultrastructure of corneas developing ectasia after LASIK or photorefractive keratectomy (PRK). DESIGN: Retrospective case series. PARTICIPANTS: Thirteen specimens from 12 patients undergoing corneal transplantation for progressive ectasia after LASIK (12 specimens) or PRK (1 specimen) were obtained for histopathologic and ultrastructural evaluation. METHODS: All 13 ectatic corneas were submitted in formalin for light microscopy. Nine specimens were bisected, and the second half was placed in 2.5% glutaraldehyde for transmission electron microscopy (TEM). MAIN OUTCOME MEASURES: Corneal histopathology, ultrastructure, and pathophysiology. RESULTS: Light microscopy of the post-LASIK specimens showed corneal epithelial hypoplasia and occasional foci of epithelial hyperplasia, Bowman's layer breaks, a normal stromal thickness of the LASIK flap, a normal thickness of the hypocellular primitive stromal scar, a thinned residual stromal bed (RSB), and larger than normal artifacteous interlamellar clefts in the RSB of the ectatic region. The post-PRK specimen showed similar findings with the addition of a thinned hypercellular fibrotic stromal scar. TEM showed thinning of the collagen lamellae and loss of lamellar number in the RSB of post-LASIK ectasia corneas or throughout the entire corneal stromal bed in the post-PRK ectasia cornea, with the posterior aspect of the corneal stroma being most affected. CONCLUSIONS: Histopathologic and ultrastructural studies suggest that interlamellar and interfibrillar biomechanical slippage occurs when the cornea becomes ectatic after LASIK or PRK in the postoperative stress-bearing regions of the corneal stroma. This 2-phase chronic biomechanical failure process is similar to that seen in keratoconus. Composite sciences classify this chronic biomechanical failure process as interfiber fracture. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Correlations of long-term matrix metalloproteinase localization in human corneas after successful laser-assisted in situ keratomileusis with minor complications at the flap margin.

OBJECTIVE: To determine whether matrix metalloproteinases (MMPs) are present long-term in human corneas after successful laser-assisted in situ keratomileusis (LASIK). METHODS: Eighteen postmortem corneas from 10 patients with postoperative intervals of 2 to 8 years after LASIK surgery and 4 normal control corneas from 2 patients were collected from US eye banks and processed for histologic analysis and immunolocalization with antibodies to MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, and MMP-14. RESULTS: Matrix metalloproteinase 7 was present in the epithelium of all corneas. Other MMPs were localized to the wound margin in some post-LASIK corneas. Matrix metalloproteinase 9 was detected around epithelial cells trapped in the lamellar scar in 5 of 6 corneas with epithelial ingrowth. Various MMPs were detected in fibrotic tissue at the wound margin in 2 of 2 corneas with flap retraction. CONCLUSIONS: The presence of MMPs in post-LASIK corneas correlates with an ongoing wound healing process associated with minor post-LASIK complications. Matrix metalloproteinases might contribute to instances of ongoing flap instability, and if so, judicious use of MMP inhibitors could provide benefit.

Depth-dependent cohesive tensile strength in human donor corneas: implications for refractive surgery.

PURPOSE: To determine the cohesive tensile strength throughout the stroma of normal human donor corneas and evaluate the relevance of these findings within the context of current excimer laser surgical techniques. METHODS: Twenty normal corneoscleral buttons from 11 donors were obtained from the Georgia Eye Bank. The corneas were cut into 3-mm strips, dissected at varying stromal depths, mechanically separated through the dissection plane using a motorized extensometer, and measured for cohesive tensile strength. Central corneal thickness and dissection depth were measured by routine light microscopy and correlated with cohesive tensile strength measurements. RESULTS: A strong negative correlation was noted between stromal depth and cohesive tensile strength (r = -0.93). The anterior corneal stroma directly adjacent to Bowman's layer followed by the underlying anterior 40% of the corneal stroma had the highest cohesive tensile strength. Cohesive tensile strength plateaued from 40% to 90% corneal stromal depth and then declined rapidly from the posterior 10% of the stroma to Descemet's membrane. The anterior 40% of the corneal stroma had significantly higher cohesive tensile strength than the posterior 60% (33.3 g/mm vs 19.6 g/mm, P < .00001). Within the central 40% to 60% depth, a positive correlation was found between increased age and increased tensile strength (r = 0.67), with corneal tensile strength increasing 38% from ages 20 to 78 years. CONCLUSIONS: The anterior 40% of the central corneal stroma is the strongest region of the cornea, whereas the posterior 60% of the stroma is at least 50% weaker. The risk for ectasia may therefore be greater with ablations into the posterior stroma. Increasing age is associated with increased corneal cohesive tensile strength.

Biomechanical and wound healing characteristics of corneas after excimer laser keratorefractive surgery: is there a difference between advanced surface ablation and sub-Bowman's keratomileusis?

PURPOSE: To describe the biomechanical and wound healing characteristics of corneas after excimer laser keratorefractive surgery. METHODS: Histologic, ultrastructural, and cohesive tensile strength evaluations were performed on 25 normal human corneal specimens, 206 uncomplicated LASIK specimens, 17 uncomplicated sub-Bowman's keratomileusis (SBK) specimens, 4 uncomplicated photorefractive keratectomy (PRK) specimens, 2 uncomplicated advanced surface ablation (ASA) specimens, 5 keratoconus specimens, 12 postoperative LASIK ectasia specimens, and 1 postoperative PRK ectasia specimen and compared to previously published studies. RESULTS: Histologic and ultrastructural studies of normal corneas showed significant differences in the direction of collagen fibrils and/or the degree of lamellar interweaving in Bowman's layer, the anterior third of the corneal stroma, the posterior two-thirds of the corneal stroma, and Descemet's membrane. Cohesive tensile strength testing directly supported these morphologic findings as the stronger, more rigid regions of the cornea were located anteriorly and peripherally. This suggests that PRK and ASA, and secondarily SBK, should be biomechanically safer than conventional LASIK with regard to risk for causing keratectasia after surgery. Because adult human corneal stromal wounds heal slowly and incompletely, all excimer laser keratorefractive surgical techniques still have some distinct disadvantages due to inadequate reparative wound healing. Despite reducing some of the risk for corneal haze compared to conventional PRK, ASA cases still can develop corneal haze or breakthrough haze from the hypercellular fibrotic stromal scarring. In contrast, similar to conventional LASIK, SBK still has the short- and long-term potential for interface wound complications from the hypocellular primitive stromal scar. CONCLUSIONS: Ophthalmic pathology and basic science research show that SBK and ASA are improvements in excimer laser keratorefractive surgery compared to conventional LASIK or PRK, particularly with regard to maintaining corneal biomechanics and perhaps moderately reducing the risk of corneal haze. However, most of the disadvantages caused by wound healing issues remain.

Interface fluid syndrome in human eye bank corneas after LASIK: causes and pathogenesis.

PURPOSE: To evaluate the effects of corneal edema on human donor corneas that had previous LASIK using a laboratory model with histologic and ultrastructural correlations. DESIGN: Experimental study. PARTICIPANTS: Thirty human eye bank corneas from 15 donors (mean age +/- standard deviation, 49.9+/-8.9 years) who had had previous LASIK surgery (2-8 years before death). METHODS: The corneas were mounted in an artificial anterior chamber and the corneal endothelium was perfused for up to 5.0 hours with 0.9% saline solution (endothelial cell damage group) or BSS Plus at a pressure of 15 mmHg (control group), or BSS Plus at a pressure of 55 mmHg (high-pressure group). The corneas were evaluated by confocal and specular microscopy before, during, and at the end of the experimental period. Subsequently, the specimens were evaluated by light and electron microscopy. MAIN OUTCOME MEASURES: Corneal thickness, reflectivity, histology, and ultrastructure. RESULTS: Endothelial cell damage resulted in an increased (141.5+/-38.8 microm) total corneal thickness relative to controls (52.3+/-33.7 microm), whereas high pressure resulted in a decreased thickness (24.8+/-14.1 microm) relative to controls. This ultimately was due to swelling of the LASIK interface in both groups and swelling of the residual stromal bed (RSB) in the endothelial cell damage group or compression of the RSB and, possibly, the flap in the high-pressure group. A significant increase in corneal reflectivity at the LASIK interface occurred in both groups, primarily due to varying degrees of fluid accumulation and associated hydropic keratocyte degeneration, as well as increased corneal reflectivity in the RSB only in the endothelial cell damage group. CONCLUSIONS: After LASIK surgery, edematous corneas preferentially hydrate and swell in the paracentral and central interface wound, commonly resulting in a hazy corneal appearance primarily due to keratocyte hydropic degeneration. More severe corneal edema is characterized by the formation of an optically empty space corresponding to an interface fluid pocket. The spectrum of interface fluid syndrome can be described in 3 stages.