Automated Image Segmentation of the Corneal Endothelium in Patients With Fuchs Dystrophy.

Purpose: To perform segmentation of specular microscopy (SM) images of the corneal endothelium for comparing average perimeter length (APL) between Fuchs endothelial corneal dystrophy (FECD) patients and healthy subjects. Methods: A retrospective review of clinical records of FECD patients and those with healthy endothelium was carried out to collect images of the endothelium. The images were segmented by modified U-Net, a deep learning architecture, followed by the Watershed algorithm to resolve merged cell borders (<5%). The segmented images were analyzed for endothelial cell density (ECDUW) and APL. Results: The combination of the U-Net and Watershed algorithm, referred to as the UW approach, enabled a complete segmentation of the endothelium. In healthy, ECDUW was close to estimates by SM and manual segmentation (31 subjects; P > 0.1). However, in FECD, ECDUW was closer to estimates by manual segmentation but not by SM (27 patients; P < 0.001). ECDUW in FECD (2547 ± 499 cells/mm2; 60 patients) was smaller compared to that in the healthy (2713 ± 401 cells/mm2; 70 subjects) (P < 0.001). APL in the healthy was 66.87 ± 7.68 µm/cell (70 subjects), but it increased with %Guttae in FECD (56.60-195.30 µm/cell; 60 patients) (P < 0.0001). Conclusions: The UW approach is precise for the segmentation of SM images from the healthy and FECD. Our analysis has revealed that APL increases with %Guttae. Translational Relevance: The average perimeter length of the corneal endothelium, which represents the length of the paracellular pathway for fluid flux into the stroma, is increased in Fuchs dystrophy.

Dual corneal involvement by endothelial and epithelial corneal dystrophies in Steinert's disease: A case of triple dystrophy.

INTRODUCTION: A case of dual corneal involvement due to Fuchs endothelial corneal dystrophy and epithelial basement membrane corneal dystrophy in a patient with Steinert's myotonic dystrophy type 1 is described, and a literature review on the triple association is made. CASE DESCRIPTION: A 52-year-old male diagnosed with myotonic dystrophy type 1 presented due to progressive bilateral vision loss during the past year. A full ophthalmological evaluation was made, with biomicroscopy, funduscopy, anterior segment optical coherence tomography, and endothelial cell count using specular microscopy. Exploration revealed bilateral superior palpebral ptosis, visual acuity 0.5 in the right eye and 0.3 in the left eye, and with an intraocular pressure of 11 and 10 mmHg, respectively. Biomicroscopy revealed map-dot-fingerprint lesions characteristic of epithelial basement membrane corneal dystrophy in both eyes, as well as abundant endothelial guttae due to Fuchs endothelial corneal dystrophy (stage II) and bilateral nuclear and posterior subcapsular cataracts. Specular microscopy in turn showed cell loss and a destructured endothelial map. Finally, anterior segment optical coherence tomography revealed the accumulation of epithelial basement membrane and hyperreflective endothelial excrescences corresponding to guttae. CONCLUSION: The association of Fuchs endothelial corneal dystrophy with myotonic dystrophy has been described and explained by a common genetic basis in the expansion of a CTG trinucleotide repeat, though this is the first reported case of the triple association of Fuchs endothelial corneal dystrophy, epithelial basement membrane corneal dystrophy, and myotonic dystrophy type 1. New mutations or still unknown genetic alterations could possibly explain the triple association reported in our case.

[Change of corneal radii after Descemet membrane endothelial keratoplasty measured by optical coherence tomography and Scheimpflug tomography]. / Veränderung der Hornhautradien nach "Descemet membrane endothelial keratoplasty" gemessen mittels optischer Kohärenztomographie und Scheimpflug-Tomographie.

BACKGROUND: The aim of the study was to compare the measurement of corneal radii using Scheimpflug tomography (Pentacam®, Oculus, Wetzlar, Germany) and optical coherence tomography (OCT, Optovue® XR-Avanti, Fremont, CA, USA) in eyes of patients with Fuchs' endothelial dystrophy (FED) before and after Descemet membrane endothelial keratoplasty (DMEK). MATERIAL AND METHODS: In a retrospective analysis 35 eyes with (FED) that underwent DMEK were included. Pentacam® and Optovue® corneal measurements were performed preoperatively and at least 3 months postoperatively. The four primary objectives were the radii of the anterior and posterior corneal surfaces, the corneal thickness and the posterior to anterior corneal curvature radii ratio. The change in the primary targets after DMEK was analyzed and the measurement results of both methods were compared. A Bland-Altman plot was created to graphically illustrate the correlation between the two measuring methods. RESULTS: A significant decrease in corneal thickness was observed after DMEK with both methods. The radii of the anterior corneal surface, measured with Scheimpflug as well as with OCT showed no significant changes after surgery, while the radii of the posterior corneal surface significantly decreased (Pentacam®: preoperative = 7.24 mm ± 0.99 mm; postoperative = 6.38 mm ± 0.40 mm, P < 0.001; Optovue®: preoperative = 7.63 mm ± 1.43 mm; postoperative = 6.57 mm ± 0.43 mm, P < 0.001). The Bland-Altman plots of all primary objectives showed a better agreement postoperatively compared to the preoperative measurements. CONCLUSION: Both Scheimpflug and OCT showed a significant decrease in the radius of the posterior corneal surface after DMEK. The postoperative measurements showed a higher agreement between the devices than those performed preoperatively.

[Imaging features of Fuchs endothelial corneal dystrophy].

Objective: To investigate the imaging features of Fuchs endothelial corneal dystrophy (FECD) and to provide imaging evidence for the diagnosis of this disease. Methods: Retrospective case series study. A total of 128 eyes (64 patients, including 19 males and 45 females) diagnosed with FECD at the Beijing Tongren Eye Center of Capital Medical University from January 2014 to December 2016 were enrolled. The average age was 57.8±12.9 years. There were 25 eyes of stage Ⅰ (19.5%), 81 eyes of stage Ⅱ (63.3%), 16 eyes of stage Ⅲ (12.5%) and 6 eyes of stage Ⅳ (4.7%).All patients underwent specular microscopy, and 41 patients (82 eyes) had in vivo confocal microscopy (IVCM). The patients' general data, clinical stage, and image features of specular microscopy and IVCM were analyzed. The enumeration data was compared by chi-square test. Differences of measurement data were compared by ANOVA. Data which cannot be accurately measured was compared by rank sum test. Results: As the disease progressed, the number, incidence rate, and fusing rate of dark"holes"on specular microscopy increased. The number of guttata on IVCM increased, and the fusing pattern of guttata developed from pair-like, chain-like to group-like. On specular microscopy, the mean rank of stage Ⅰ (78.2), stage Ⅱ (228.4), stage Ⅲ (284.5) and stage Ⅳ (288.5) was statistically different (χ²=84.183, P=0.000). All positions of all eyes of stage I had no fusion of the dark "holes". The incidence of fusion on the peripheral cornea gradually increased significantly (χ²=27.167, P=0.000) from stage Ⅱ (45.1%, 146/324), stage Ⅲ (76.3%, 45/59) to stage Ⅳ (83.3%, 15/18). Conclusions: The imaging features of specular microscopy and IVCM can be applied as an important basis for early diagnosis of FECD. Specular microscopy is a practical method for rapid screening of FECD. IVCM is an important imaging basis for clarifying the appearance of guttata and analyzing fusion features, so as to guide the differentiation of stages. (Chin J Ophthalmol, 2020, 56:938-943).

Predicting the Prognosis of Fuchs Endothelial Corneal Dystrophy by Using Scheimpflug Tomography.

PURPOSE: To determine if Scheimpflug tomography pachymetry map and posterior elevation map patterns, central corneal thickness (CCT), and corneal backscatter can predict the prognosis of Fuchs endothelial corneal dystrophy (FECD). DESIGN: Cross-sectional study with follow-up of outcomes. PARTICIPANTS: Ninety-six eyes (56 subjects) with a range of severity of FECD. METHODS: Corneas were graded by cornea specialists according to the area and confluence of guttae and the presence of clinically definite edema. Masked and randomized Scheimpflug imaging pachymetry map and posterior elevation map patterns were assessed by 1 observer for loss of regular isopachs, displacement of the thinnest point of the cornea, and the presence of posterior surface depression. The prognosis of eyes over a 5-year (median) follow-up period was determined based on FECD progression (new onset of clinically definite edema or ≥5% increase in CCT) or intervention by endothelial keratoplasty. Cumulative probabilities of progression and intervention were estimated from survival analyses, with risk factors determined by using Cox proportional hazards models. MAIN OUTCOME MEASURES: Pachymetry map and posterior elevation map patterns, corneal backscatter, and CCT (ultrasonic pachymetry). RESULTS: In univariate analyses, loss of regular isopachs (hazard ratio [HR], 18.00) displacement of the thinnest point (HR, 11.53), focal posterior surface depression (HR, 10.21), and anterior corneal backscatter (HR, 1.22, per 1-grayscale unit increment), were risk factors for progression or intervention (P < 0.001), whereas CCT (HR, 1.30, per 25-µm increment) was not (P = 0.15). In multivariate analyses, loss of regular isopachs (HR, 11.57; P < 0.001) and displacement of the thinnest point (HR, 5.61; P = 0.02) were independent and clinically important risk factors for progression and intervention. The 5-year cumulative risk of disease progression and intervention was 7%, 48%, and 89% when none, 1 or 2, and all 3 pachymetry map and posterior elevation map parameters were present, respectively (P <0.001). The 4-year cumulative risk of disease progression and intervention after uncomplicated cataract surgery was 0%, 50%, and 75% when none, 1 or 2, and all 3 pachymetry map and posterior elevation map parameters were present, respectively (P < 0.001). CONCLUSIONS: Three Scheimpflug tomography pachymetry map and posterior elevation map patterns can predict FECD prognosis independent of CCT. The risk of FECD progression and intervention, including after uncomplicated cataract surgery, increases according to the number of parameters present.

Imaging the Corneal Endothelium in Fuchs Corneal Endothelial Dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is characterized by the progressive degeneration of the corneal endothelium (CE). The purpose of this article is to review the diagnostic tools available to image and assess the CE in FECD. Slit-lamp biomicroscopy with specular reflection and retroillumination are important techniques to assess the CE. Objective diagnostic tests, such as retroillumination photographic analysis, specular microscopy, in vivo confocal microscopy (IVCM), and anterior segment optical coherence tomography, are valuable tools to evaluate the CE in FECD. Specular microscopy can be performed rapidly without touching the eye but requires a clear cornea with a smooth CE. In contrast, IVCM can image all layers of the cornea, even in advanced FECD. However, IVCM is contact-based and more technically challenging. It is important to select the appropriate objective diagnostic test to image and assess the CE in managing patients with FECD.

Capabilities of Gabor-domain optical coherence microscopy for the assessment of corneal disease.

To identify the microstructural modification of the corneal layers during the course of the disease, optical technologies have been pushing the boundary of innovation to achieve cellular resolution of deep layers of the cornea. Gabor-domain optical coherence microscopy (GD-OCM), an optical coherence tomography-based technique that can achieve an isotropic of ∼2-µm resolution over a volume of 1 mm × 1 mm × 1.2 mm, was developed to investigate the microstructural modifications of corneal layers in four common corneal diseases. Since individual layer visualization without cutting through several layers is challenging due to corneal curvature, a flattening algorithm was developed to remove the global curvature of the endothelial layer and display the full view of the endothelium and Descemet's membrane in single en face images. As a result, GD-OCM revealed the qualitative changes in size and reflectivity of keratocytes in Fuchs endothelial corneal dystrophy (FECD), which varied by the degree of disease. More importantly, elongated shape and hyperactivation characteristics of keratocytes, associated with the early development of guttae, appeared to start in the posterior stroma very early in the disease process and move toward the anterior stroma during disease progression. This work opens a venue into the pathogenesis of FECD.

Corneal endothelium features in Fuchs' Endothelial Corneal Dystrophy: A preliminary 3D anterior segment optical coherence tomography study.

PURPOSE: To evaluate the feasibility of 3D anterior segment optical coherence tomography (AS-OCT) for the detection of corneal endothelial features in patients with Fuchs' Endothelial Corneal Dystrophy (FECD). METHODS: Twenty patients with clinical diagnosis of FECD (group A), and 20 control subjects (group B) were enrolled. In all patients a complete ophthalmological examination was performed, including best corrected visual acuity (BCVA), slit lamp examination for subjective grading of FECD and corneal endothelial specular microscopy. A 512x128 AS-OCT cube centered on the corneal apex was performed, and then the inner surface of the cornea was visualized and analyzed individually. RESULTS: Overall, the study participants were adults (mean age was 57.35 ± 8.45 years [mean ± SD] 80% female) with a BCVA ranged from 1.3 to 0 LogMAR. The OCT analysis disclosed three different patterns of the corneal endothelium (1, 2, 3) according to the signal distribution and the level of reflectivity: a homogenous, hypo-reflective surface (pattern 1); the presence of hyper-reflective orange-yellowish points (pattern 2); and a mottled appearance with a variable number of hyper-reflective areas (pattern 3). The distributions of these morphological models in the two populations were as follows: patterns 1, 2 and 3 were observed respectively in 0%, 80%, and 20% of patients in group A, and in 80%, 20% and 0% of subjects in group B. Correlation analysis unveiled a positive relationship between OCT corneal endothelium reflectivity and the clinical severity score (assessed with biomicroscopy), as well as an inverse relationship between the OCT pattern and the integrity of corneal endothelium. CONCLUSION: 3D AS-OCT is a useful tool in investigation of endothelial features and therefore may represent a valuable support in the setting of FECD diagnosis and staging.

Scanning Acoustic Microscopy Comparison of Descemet's Membrane Normal Tissue and Tissue With Fuchs' Endothelial Dystrophy.

Purpose: To describe the application of scanning acoustic microscopy in the GHz-range (GHz-SAM) for qualitative imaging and quantitative characterization of the micromechanical properties of the Descemet's membrane and endothelial cells of cornea tissue. Methods: Investigated were samples of a normal tissue and a tissue with Fuchs' endothelial dystrophy (FECD, cornea Guttata). Descemet's membranes were fixed on glass substrates and imaged utilizing a focused acoustic lens operating at a center frequency of 1 GHz. Results: GHz-SAM data, based on the well-established V(z) technique, revealed discrepancies in the velocity of the propagation of Rayleigh surface acoustic waves (RSAW). RSAW were found to be slower in glass substrates with FECD samples than in the same glass substrates (soda-lime) with normal Descemet membrane, which indicates lower shear and bulk moduli of elasticity in tissues affected by FECD. Conclusions: Noninvasive/nondestructive GHz-SAM, is utilized in this study for the imaging and characterization of Descemet membranes, fixated on glass substrates. V(z) signatures containing sufficient oscillations were obtained for the system of Descemet membranes on glass substrates. The observed variation in the microelastic properties indicates potential for further investigations with GHz-SAM based on the V(z) technique.

In Vivo Confocal Microscopy Shows Alterations in Nerve Density and Dendritiform Cell Density in Fuchs' Endothelial Corneal Dystrophy.

PURPOSE: To evaluate corneal nerve and immune cell alterations in Fuchs' endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) by laser in vivo confocal microscopy (IVCM) as correlated to corneal sensation and endothelial cell loss. DESIGN: Prospective, cross-sectional, controlled study. METHODS: Thirty-three eyes with FECD were compared to 13 eyes with PBK and 17 normal age-matched control eyes at a tertiary referral center. FECD was classified into early (without edema) and late stage (with edema). Corneal IVCM and esthesiometry were performed. Corneal nerve and immune dendritiform cell (DC) alterations were evaluated and correlated to clinical parameters. RESULTS: FECD and PBK eyes showed significantly (P = .001) diminished total nerve length (11.5 ± 1.3 and 2.9 ± 0.7 mm/mm2) and number (8.8 ± 1.1 and 2.2 ± 0.4 n/frame), compared to controls (23.3 ± 8.1 mm/mm2 and 25.9 ± 1.3 n/frame). Decreased nerves corresponded to diminished sensation in FECD (4.9 ± 0.2 cm; R = 0.32; P = .045), compared to controls (5.9 ± 0.04 cm). Early- and late-stage FECD showed significantly reduced total nerve length (13.1 ± 1.4 and 9.9 ± 1.2 mm/mm2, respectively) and number (8.2 ± 2.5 and 6.5 ± 2.1 n/frame), compared to controls (P < .001). DC density was significantly increased in FECD (57.8 ± 10.4 cells/mm2; P = .01), but not in PBK (47.7 ± 11.6 cells/mm2; P = .60) compared to controls (22.5 ± 4.5 cells/mm2). A subset of early FECD patients (7/22) demonstrated very high DC density (>100/mm2). CONCLUSION: IVCM demonstrates profound diminishment of subbasal corneal nerves in early- and late-stage FECD and in PBK, correlating to decreased sensation. Increased DC density in early FECD demonstrates potential subclinical inflammation. The data suggest that reduction in subbasal nerves and increased immune activation may play a role in the pathophysiology of FECD.

Phenotypic Characterization of Corneal Endothelial Dystrophy in German Shorthaired and Wirehaired Pointers Using In Vivo Advanced Corneal Imaging and Histopathology.

PURPOSE: To evaluate corneal morphology using ultrasonic pachymetry (USP), Fourier-domain optical coherence tomography (FD-OCT), and in vivo confocal microscopy (IVCM) in 2 related canine breeds-German shorthaired pointers (GSHPs) and German wirehaired pointers (GWHPs)-with and without corneal endothelial dystrophy (CED). This condition is characterized by premature endothelial cell degeneration leading to concomitant corneal edema and is similar to Fuchs endothelial corneal dystrophy. METHODS: Corneas of 10 CED-affected (4 GSHP and 6 GWHP) and 19 unaffected, age-matched (15 GSHP and 4 GWHP) dogs were examined using USP, FD-OCT, and IVCM. A 2-sample t test or Mann-Whitney rank-sum test was used to statistically compare parameters between both groups. Data are presented as mean ± SD or median (range). RESULTS: Central corneal thickness determined using USP was significantly greater in CED-affected than in unaffected dogs at 1179 (953-1959) and 646 (497-737) µm, respectively (P < 0.001). Central epithelial thickness was found to be significantly decreased in CED-affected versus unaffected dogs at 47 ± 7.1 and 55 ± 7.1 µm, respectively (P = 0.011), using FD-OCT. With IVCM, corneal endothelial density was significantly less (P < 0.001) in 5 dogs with CED versus 19 unaffected controls at 499 ± 315 versus 1805 ± 298 cells/mm, respectively. CED-affected dogs exhibited endothelial pleomorphism and polymegethism, whereas CED-unaffected dogs had regular hexagonal arrangement of cells. CONCLUSIONS: GSHPs and GWHPs with CED exhibit marked differences in corneal morphology when compared with age-matched control dogs. These 2 CED-affected breeds represent spontaneous, large animal models for human Fuchs endothelial corneal dystrophy.

Automated Retroillumination Photography Analysis for Objective Assessment of Fuchs Corneal Dystrophy.

PURPOSE: Retroillumination photography analysis is an objective tool for the assessment of the number and distribution of guttae in eyes affected with Fuchs corneal dystrophy (FCD). Current protocols include manual processing of images; here, we assess validity and interrater reliability of automated analysis across various levels of FCD severity. METHODS: Retroillumination photographs of 97 FCD-affected corneas were acquired, and total counts of guttae were previously summated manually. For each cornea, a single image was loaded into ImageJ software. We reduced color variability and subtracted background noise. Reflection of light from each gutta was identified as a local area of maximum intensity and counted automatically. Noise tolerance level was titrated for each cornea by examining a small region of each image with automated overlay to ensure appropriate coverage of individual guttae. We tested interrater reliability of automated counts of guttae across a spectrum of clinical and educational experience. RESULTS: A set of 97 retroillumination photographs was analyzed. Clinical severity as measured by a modified Krachmer scale ranged from a severity level of 1 to 5 in the set of analyzed corneas. Automated counts by an ophthalmologist correlated strongly with Krachmer grading (R = 0.79) and manual counts (R = 0.88). Intraclass correlation coefficients demonstrated strong correlation at 0.924 (95% CI, 0.870-0.958) among cases analyzed by 3 students, and 0.869 (95% CI, 0.797-0.918) among cases for which images were analyzed by an ophthalmologist and 2 students. CONCLUSIONS: Automated retroillumination photography analysis allows for grading of FCD severity with high resolution across a spectrum of disease severity.

Cellular and subbasal nerve alterations in early stage Fuchs' endothelial corneal dystrophy: an in vivo confocal microscopy study.

PURPOSE: To analyze the morphology and density of corneal epithelial cells, keratocytes, and subbasal nerves, in patients with early stage Fuchs' endothelial corneal dystrophy (FECD) by in vivo confocal microscopy (IVCM). METHODS: IVCM (Confoscan 4, Nidek, Inc.) of the central cornea was performed in 30 corneas of 30 patients with early stage FECD and 13 corneas of 13 normal controls. Images were analyzed for morphology and density of the superficial and basal epithelial cells, keratocyte density, endothelial cell density (ECD), as well as subbasal corneal nerve parameters. Central corneal thickness (CCT) was measured in all patients and normals by ultrasound pachymetry. RESULTS: The ECD was significantly lower (-45.5%, P<0.001) in FECD patients as compared with controls. Total number of nerves and main nerve trunks were significantly reduced (-46.3%, P<0.001; -39.7%, P<0.001) in patients with FECD. Posterior keratocyte density was significantly higher in FECD patients (P<0.001). Significant inverse correlations were found between CCT and total number of nerves (r=-0.69, P<0.001), CCT and main nerve trunks (-0.47, P=0.016), as well as CCT and total nerve length (r=-0.62, P=0.006). Significant correlation was found between ECD and total number of nerves (r=0.44, P=0.012) as well as between ECD and main nerve trunks (r=0.65, P<0.001). CONCLUSIONS: IVCM demonstrates alterations in corneal innervation in patients with early stage FECD, suggesting a potential role of corneal nerves in the pathogenesis of FECD. Additional studies are required to investigate whether subbasal nerve alterations are caused by nonspecific corneal edema, from FECD-induced decrease in ECD, or potentially leading to loss of endothelial cells.

In vivo confocal microscopy of combined pre-descemet membrane corneal dystrophy and fuchs endothelial dystrophy.

PURPOSE: To report the in vivo confocal microscopy (CM) findings of a patient with combined pre-Descemet membrane corneal dystrophy and Fuchs endothelial dystrophy. METHODS: A 38-year-old woman with pre-Descemet membrane corneal dystrophy and Fuchs endothelial dystrophy was studied. Routine ophthalmic examination, standard slit-lamp biomicroscopy, pachymetry, and in vivo CM analysis of the morphology of the corneal epithelium, subbasal nerves, stroma, and endothelium were performed. RESULTS: Biomicroscopy revealed bilateral corneal guttae with central corneal edema, beaten metal appearance, and pigment dusting of the endothelium. Numerous tiny pleomorphic opacities located in the deep stroma immediately anterior to Descemet membrane were evidenced in both eyes. In vivo CM showed numerous pleomorphic and highly reflective small particles in the cytoplasm of keratocytes in the deep stroma adjacent to the corneal endothelial layer. No abnormalities could be detected in the epithelial layer and in the midstromal layer. In the endothelial layer, there were multifocal hyporeflective areas with occasional central highlight among hyperreflective endothelial cells. The ultrasonic pachymetry showed corneal thicknesses of 652 and 628 µm in the right eye and in the left eye, respectively. CONCLUSIONS: In vivo CM is a powerful tool in the study of rare corneal dystrophies and degenerations and nonprogressive or slowly progressive corneal disorders where there is a limited availability of corneal tissue for examination and when the final diagnosis is difficult to obtain with conventional methods.

A novel PITX2 mutation and a polymorphism in a 5-generation family with Axenfeld-Rieger anomaly and coexisting Fuchs' endothelial dystrophy.

PURPOSE: To investigate the clinical and genetic appearance of Axenfeld-Rieger anomaly or syndrome (ARAS) and Fuchs' endothelial dystrophy (FED) in a 5-generation pedigree coexpressing both pathologic features in a large number of family members. DESIGN: Observational case-control and DNA linkage and screening study. PARTICIPANTS: Of 114 family members, 50 underwent clinical investigation and DNA analysis between July 2001 and March 2004. METHODS: Linkage at the PITX2 locus was demonstrated using a number of microsatellites mapping to the critical region 4q25 to 4q26. The PITX2 gene was subsequently screened for mutations in all investigated family members. MAIN OUTCOME MEASURE: Linkage of the ARAS and FED phenotype and mutation detection in the PITX2 gene. RESULTS: Twenty-seven patients were identified as being affected by ARAS. Fuchs' endothelial dystrophy was found in 19 patients. Fifteen patients presented both kinds of anomaly. Deoxyribonucleic acid sequencing revealed 2 heteroallelic DNA variants that segregated together (on the same allele) and were present in all severely affected ARAS individuals. The first variant, g.20913G>T, assumed to be the causative mutation for ARAS, causes amino acid substitution at codon 137 (G137V). A statistically significant 2-point logarithm of the odds score of 4.06 was obtained with marker D4S406. The second variant is likely a polymorphism in the intron between exons 2 and 3 (IVS2+8delCinsGTT) and was detected in heterozygous form in 20% of control individuals. CONCLUSION: This gene analysis revealed a novel PITX2 mutation and a polymorphism in a family with ARAS. Whether FED, also manifested in the severely affected individuals, is due to a different but cosegregating gene is to be determined.

Corneal decompensation after laser in situ keratomileusis in fuchs' endothelial dystrophy.

PURPOSE: To report corneal decompensation after laser in situ keratomileusis (LASIK) in a patient with Fuchs' endothelial dystrophy. METHODS: Observational case report. RESULTS: A 47-year-old woman with cornea guttata without symptoms or findings of corneal edema had uneventful LASIK for -5.50 -0.50 x 150 in the right eye and -4.00 -1.25 x 170 in the left eye. Postoperatively, she developed corneal edema, with significant loss of best-corrected visual acuity in both eyes. Preoperative corneal thickness was 587 microm in the right eye and 549 microm in the left eye, measured by ultrasound pachymetry. These readings were 550 and 560 microm on day 67 postoperatively. Endothelial cell counts showed means of 1209 and 1661 cells/mm2 in the right and left eyes, respectively. CONCLUSION: Caution is suggested when considering LASIK in eyes with severe cornea guttata.