Reticular Bullous Epithelial Corneal Edema after Netarsudil Use for Elevated Intraocular Pressure with Concurrent Fuchs Endothelial Corneal Dystrophy: A Case Report
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PROVIDER: S-EPMC11023690 | biostudies-literature | 2024 Jan
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Project description:Background: This phase 2 study evaluated the therapeutic potential of netarsudil to reduce corneal edema and to improve vision in patients with Fuchs corneal dystrophy (FCD). Methods: Patients (N = 40) with baseline central corneal thickness (CCT) of ≥600 μm and best-corrected visual acuity (BCVA) of 70-20 letters (20/40-20/400 Snellen equivalent) were randomized 1:1 to receive netarsudil once a day (QD) or twice a day (BID) for 8 weeks. Primary endpoint was mean CCT change from baseline at week 4. Results: Netarsudil QD and BID significantly reduced CCT at week 4 [mean change (standard error of mean), 28.4 (7.99) μm, P = 0.0021; and 20.1 (8.75) μm, P = 0.0335, respectively]. Five (12.5%) patients achieved complete resolution of corneal edema at week 4. BCVA improved by 3.2 (2.76) letters with QD and 1.5 (2.84) letters with BID, and 10 (25%) patients [5 with QD (P = 0.0078) and 5 with BID (P = 0.0096)] gained ≥10 letters at week 4. Improvements in CCT and vision were observed at week 2 and persisted at week 8, without significant differences between the 2 doses at any time point. Netarsudil QD significantly improved visual acuity and glare factor scores on the Visual Function and Corneal Health Status (V-FUCHS) questionnaire at weeks 4 and 8 (mean change, -0.4 to -0.3; P ≤ 0.0200). Netarsudil was well tolerated. Reticular edema developed in one (2.5%) patient with BID, which resolved with treatment discontinuation. Conclusions: Netarsudil QD led to significant reductions in corneal edema as well as improvements in vision and patient-reported symptoms of glare and visual impairment in patients with FCD. Clinical Trial Registration Number: NCT04498169.
| S-EPMC9784611 | biostudies-literature
Project description:IntroductionImplantation of toric intraocular lenses (IOLs) in patients with Fuchs endothelial corneal dystrophy (FECD) is still considered relatively contraindicated, without sufficient clinical evidence. Therefore, this study was designed to evaluate the results of toric IOL implantation in patients with FECD.MethodsA retrospective case-control study of 28 eyes of FECD patients and 84 eyes of healthy control patients who received toric IOLs during routine cataract surgery was performed. The outcome measures were uncorrected and corrected distance visual acuity, spherical equivalent, and refractive residual astigmatism.ResultsThe mean postoperative uncorrected and corrected distance visual acuity in the FECD eyes compared to the control eyes were 0.15 ± 0.14 vs. 0.13 ± 0.17, respectively (P = 0.32), and 0.05 ± 0.08 vs. 0.06 ± 0.10, respectively (P = 0.95). The spherical equivalent in the FECD eyes compared to the control eyes was - 0.29 ± 0.43 vs. - 0.21 ± 0.50, respectively (P = 0.19). The preoperative corneal centroid astigmatism in the FECD eyes compared to the control eyes was 0.85 D@93° ± 2.42° vs. 0.23 D@68° ± 2.50°, respectively (P = 0.43), and the mean preoperative corneal astigmatism magnitude was 2.26 ± 1.1 D vs. 2.28 ± 1.03 D, respectively (P = 0.82). A trend toward higher postoperative refractive centroid astigmatism was found in the FECD eyes compared with the control eyes: 0.24 D@28° ± 0.57° vs. 0.03 D@127° ± 0.53°, respectively (P = 0.09). However, the mean refractive astigmatism magnitude was similar in FECD eyes and the healthy control eyes: 0.52 ± 0.31 D vs. 0.42 ± 0.31 D, respectively (P = 0.44) (D diopters).ConclusionThe postoperative refractive astigmatism (both centroid astigmatism and mean magnitude astigmatism) was no higher than 0.52 D in both groups. Therefore, FECD patients without corneal edema can be considered for toric IOLs.
| S-EPMC10164209 | biostudies-literature
Project description:Fuchs endothelial corneal dystrophy (FECD) is considered a contraindication for the implantation of presbyopia-correcting IOLs, without sufficient corroborating evidence. A Retrospective, case-control study. Nineteen eyes of ten patients with grade 2-5 FECD (study group) and 57 healthy eyes of 57 patients (control group) who underwent cataract surgery with implantation of presbyopia-correcting IOLs, at the Ein-Tal Eye Center, Tel Aviv, Israel, were included. The target refraction was emmetropia for both groups. Two subgroups of IOLs were analyzed separately: extended depth of focus (EDOF), (9 eyes of FECD patients and 27 eyes of control patients) and multifocal IOLs (10 eyes of FECD patients and 30 eyes of control patients). Main outcome measures were visual acuity and refraction 6 weeks after the surgery. Secondary outcomes were patient perceptions of visual acuity, spectacle independence, photic phenomena and satisfaction scores, reported in a self-assessment questionnaire. FECD patients in the EDOF IOL subgroup had inferior uncorrected distance visual acuity (P = 0.007) and better uncorrected near visual acuity (P = 0.001) compared to the controls. They had less spectacle independence for the intermediate range (P = 0.01) and overall (P = 0.006). However, they did not have more photic phenomena. In the multifocal IOL subgroup, no significant differences were found between the FECD and the control group in visual acuity for all ranges and in spectacle independence. FECD patients had more photic phenomena than the controls (P = 0.006), but it did not interfere with daily life activities. There was no difference in post-operative mean spherical equivalent, patient reported visual perception, and general satisfaction between FECD and control patients in both groups. Our results suggest that presbyopia-correcting IOLs can be carefully considered in patients with grade 2-5 FECD, with slightly inferior results compared with healthy eyes.
| S-EPMC9842705 | biostudies-literature
Project description:Fuchs' corneal dystrophy (FCD) is a common late-onset genetic disorder of the corneal endothelium. It causes loss of endothelial cell density and excrescences in the Descemet membrane, eventually progressing to corneal edema, necessitating corneal transplantation. The genetic basis of FCD is complex and heterogeneous, demonstrating variable expressivity and incomplete penetrance. To date, three causal genes, ZEB1, SLC4A11 and LOXHD1, have been identified, representing a small proportion of the total genetic load of FCD. An additional four loci have been localized, including a region on chromosome 18 that is potentially responsible for a large proportion of all FCD cases. The elucidation of the causal genes underlying these loci will begin to clarify the pathogenesis of FCD and pave the way for the emergence of nonsurgical treatments.
| S-EPMC3622272 | biostudies-literature
Project description:Fuchs endothelial corneal dystrophy (FECD) is the most common primary corneal endothelial dystrophy and the leading indication for corneal transplantation worldwide. FECD is characterized by the progressive decline of corneal endothelial cells (CECs) and the formation of extracellular matrix (ECM) excrescences in Descemet's membrane (DM), called guttae, that lead to corneal edema and loss of vision. FECD typically manifests in the fifth decades of life and has a greater incidence in women. FECD is a complex and heterogeneous genetic disease where interaction between genetic and environmental factors results in cellular apoptosis and aberrant ECM deposition. In this review, we will discuss a complex interplay of genetic, epigenetic, and exogenous factors in inciting oxidative stress, auto(mito)phagy, unfolded protein response, and mitochondrial dysfunction during CEC degeneration. Specifically, we explore the factors that influence cellular fate to undergo apoptosis, senescence, and endothelial-to-mesenchymal transition. These findings will highlight the importance of abnormal CEC-DM interactions in triggering the vicious cycle of FECD pathogenesis. We will also review clinical characteristics, diagnostic tools, and current medical and surgical management options for FECD patients. These new paradigms in FECD pathogenesis present an opportunity to develop novel therapeutics for the treatment of FECD.
| S-EPMC7648733 | biostudies-literature
Project description:The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial-mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases.
| S-EPMC10968125 | biostudies-literature
Project description:PurposeTo report the observation of a triple corneal dystrophy association consisting of keratoconus (KC), epithelial basement membrane corneal dystrophy (EBMCD) and Fuchs' endothelial corneal dystrophy (FECD).MethodsA 55-year-old male patient was referred to our cornea service for blurred vision and recurrent foreign body sensation. He reported bilateral recurrent corneal erosions with diurnal visual fluctuations. He underwent corneal biomicroscopy, Scheimpflug tomography, in vivo HRT confocal laser scanning microscopy and genetic testing for TGFBI and ZEB1 mutations using direct DNA sequencing.ResultsBiomicroscopic examination revealed the presence of subepithelial central and paracentral corneal opacities. The endothelium showed a bilateral flecked appearance, and the posterior corneal curvature suggested a possible concomitant ectatic disorder. Corneal tomography confirmed the presence of a stage II KC in both eyes. In vivo confocal laser scanning microscopy revealed a concomitant bilateral EBMCD with hyperreflective deposits in basal epithelial cells, subbasal Bowman's layer microfolds and ridges with truncated subbasal nerves as pseudodendritic elements. Stromal analysis revealed honeycomb edematous areas, and the endothelium showed a strawberry surface configuration typical of FECD. The genetic analysis resulted negative for TGFBI mutations and positive for a heterozygous mutation in exon 7 of the gene ZEB1.ConclusionThis is the first case reported in the literature in which KC, EBMCD and FECD are present in the same patient and associated with ZEB1 gene mutation. The triple association was previously established by means of morphological analysis of the cornea using corneal Scheimpflug tomography and in vivo HRT II confocal laser scanning microscopy.
| S-EPMC4209271 | biostudies-literature
Project description:BackgroundIn patients with Fuchs endothelial corneal dystrophy (FECD), the most beneficial stage to perform Descemet membrane endothelial keratoplasty (DMEK) remains uncertain. The goal of this study was to compare the surgical outcomes after DMEK in FECD patients with subclinical corneal edema and clinical corneal edema to test the hypothesis of whether performing surgery in subclinical corneal edema stages achieves better surgical outcomes.MethodsIn this prospective, observational, single-institution cohort study, 106 pseudophakic eyes of 85 patients with FECD were divided into two groups depending on the presence of preoperative subclinical and clinical corneal edema. Subclinical corneal edema was diagnosed if more than one of the following criteria was present in Scheimpflug tomography: loss of regular isopachs, displacement of the thinnest point of the cornea, and focal posterior corneal surface depression. Clinical corneal edema was diagnosed with slit-lamp biomicroscopy. The primary outcome was the corrected distance visual acuity (CDVA) 4 months after DMEK. Secondary outcomes were central corneal thickness (CCT), thinnest corneal thickness (TCT), and total corneal density (TCD) in Scheimpflug tomography, as well as endothelial cell loss (ECL) and the re-bubbling rate. The differences between both groups were analyzed using clustered Wilcoxon rank-sum tests or a Chi-squared test.ResultsPostoperative CDVA was significantly better in the group with subclinical edema (0.18 ± 0.12 logMAR) compared to the group with clinical edema (0.24 ± 0.19 logMAR; P = 0.026). Four months after DMEK, TCD was higher in the group with preoperative clinical edema [31.7 ± 8.3 gray scale units (GSU)] compared to the group with subclinical edema (27.8 ± 6.1 GSU; P = 0.005). The postoperative CCT, TCT, ECL, and re-bubbling rates did not differ significantly between both groups (all P > 0.05).ConclusionsDMEK for FECD yielded better visual acuity after 4 months when performed in the early stage of FECD compared to a later stage with clinical edema. This may be attributable to persistent corneal fibrosis after DMEK in eyes with preoperative clinically evident corneal edema, as suggested by higher postoperative corneal density in eyes with clinical edema. Consequently, the findings advocate for the consideration of earlier DMEK in FECD patients to achieve better surgical recovery.
| S-EPMC11871603 | biostudies-literature
Project description:Fuchs endothelial corneal dystrophy (FECD) is amongst one of the most common indications for endothelial keratoplasty worldwide. Despite being originally described among Caucasians, it is now known to be prevalent among a large number of populations, including Asians. While the FECD phenotype is classically described as that of central guttate and pigment deposits associated with corneal endothelial dysfunction, there are subtle yet important differences in how FECD and its phenocopies may present in Caucasians vs Asians. Such differences are paralled by genotypic variations and disease management preferences which appear to be geographically and ethnically delineated. This article provides a succinct review of such differences, with a focus on diagnostic and management issues which may be encountered by ophthalmologists practicing in the different geographic regions, when evaluating a patient with FECD.
| S-EPMC7042366 | biostudies-literature
Project description:PurposeRNA toxicity from CTG trinucleotide repeat (TNR) expansion within noncoding DNA of the transcription factor 4 (TCF4) and DM1 protein kinase (DMPK) genes has been described in Fuchs' endothelial corneal dystrophy (FECD) and myotonic dystrophy, type 1 (DM1), respectively. We prospectively evaluated DM1 patients and their families for phenotypic FECD and report the analysis of CTG expansion in the TCF4 gene and DMPK expression in corneal endothelium.MethodsFECD grade was evaluated by slit lamp biomicroscopy in 26 participants from 14 families with DM1. CTG TNR length in TCF4 and DMPK was determined by a combination of Gene Scan and Southern blotting of peripheral blood leukocyte DNA.ResultsFECD grade was 2 or higher in 5 (36%) of 14 probands, significantly greater than the general population (5%) (P < 0.001). FECD segregated with DM1; six of eight members of the largest family had both FECD and DM1, while the other two family members had neither disease. All DNA samples from 24 subjects, including four FECD-affected probands, were bi-allelic for nonexpanded TNR length in TCF4 (<40 repeats). Considering a 75% prevalence of TCF4 TNR expansion in FECD, the probability of four FECD probands lacking TNR expansion was 0.4%. Neither severity of DM1 nor DMPK TNR length predicted the presence of FECD in DM1 patients.ConclusionsFECD was common in DM1 families, and the diseases cosegregated. TCF4 TNR expansion was lacking in DM1 families. These findings support a hypothesis that DMPK TNR expansion contributes to clinical FECD.
| S-EPMC6005624 | biostudies-literature