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BACKGROUND: To evaluate the relationship between the number of trinucleotide repeats (TNR) in late-onset Fuchs corneal endothelial dystrophy (FCED) and to compare the endothelial properties of FCED, first-degree relatives, and controls. METHODS: Blood samples were collected from FCEDs to determine TNR number. The FCED patients, first-degree relatives, and controls were examined with specular microscopy for central corneal thickness (CCT), endothelial cell density (ECD), pleomorphism and polymegatism, and with corneal topography for specific indicators such as (i) displacement of thinnest point of cornea, (ii) loss of isopachs, (iii) focal posterior surface depression towards anterior chamber. RESULTS: This study included 92 patients with FCED, 92 first-degree relatives, and 96 controls. CCT was thickest in FCEDs (558.0 µm) (p < 0.05) while there was no difference between relatives (533.0 µm) and controls (530.4 µm) (p = 0.845). ECD was decreased in both FCED (2069.2 mm2) and relatives (2171.4 mm2) than controls (2822.9 mm2) (p < 0.05 in both). The presence of pleomorphism and polymegatism was significant in patients with FCED (93.4% and 93.4%, respectively), relatives (86.9% and 86.04%, respectively), and controls (8.33% and 1.04%, respectively) (p < 0.05). Specific topographic indicators differed among the groups (p < 0.05). The mean repeat number of the FCED patients was 17.48 ± 4.54 (12-25) times. The TNR number of FCED cases correlated with the relative CCT (p < 0.05, R = 0.615) and cell density (p = 0.009, R = -0.499). CONCLUSIONS: A strong association between the corneal endothelium in relatives and TNR number of FCEDs was defined. Relatives tended to have fewer corneal endothelial cells, even though they did not have clinical findings.

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The corneal endothelial monolayer and associated Descemet's membrane (DM) complex is a unique structure that plays an essential role in corneal function. Endothelial cells are neural crest derived cells that rest on a special extracellular matrix and play a major role in maintaining stromal hydration within a narrow physiologic range necessary for clear vision. A number of diseases affect the endothelial cells and DM complex and can impair corneal function and vision. This review addresses different human corneal endothelial diseases characterized by loss of endothelial function including: Fuchs endothelial corneal dystrophy (FECD), posterior polymorphous corneal dystrophy (PPCD), congenital hereditary endothelial dystrophy (CHED), bullous keratopathy, iridocorneal endothelial (ICE) syndrome, post-traumatic fibrous downgrowth, glaucoma and diabetes mellitus.

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BACKGROUND: The current case report describes successful phacoemulsification with the aid of perioperative topical ascorbic acid (AA) in two patients with corneal endothelial disorders to prevent postoperative corneal endothelial decompensation. CASE SUMMARY: Two eyes of two patients underwent phacoemulsification with pre-existing corneal endothelial disorders including Fuchs corneal endothelial dystrophy (Patient 1) and endotheliitis (Patient 2). Topical AA was applied to both patients at least one month before and after with a frequency of four times per day. After the surgery, both eyes improved best-corrected visual acuity (BCVA) and there was limited human corneal endothelial cell loss without signs of corneal endothelial decompensation, such as deteriorated BCVA or persistent corneal edema during the follow-up of at least two years. CONCLUSION: Perioperative administration of topical AA may be an alternative therapy to the triple procedure in patients expecting to undergo cataract surgery.

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PURPOSE: The purpose of this study is to identify predictors for the best-corrected visual acuity (BCVA), central corneal thickness (CCT), and the endothelial cell density (ECD) after primary Descemet's membrane endothelial keratoplasty (DMEK). METHODS: In a prospective observational study, 108 eyes with Fuchs' endothelial dystrophy underwent a primary DMEK. Preoperative data, histologic parameters from host's Descemet's membrane, and follow-up data of the first eye were analyzed in regard to BCVA, CCT, and ECD, 12 months after surgery. RESULTS: Overall, 12 months postoperative, the BCVA improved to 0.11 ± 0.11 logMAR, the CCT declined to 529 ± 42 µm, and the ECD measured 1675 ± 418 cells/mm2. A significant influence of the preoperative CCT on postoperative BCVAs and CCTs was observed (r = 0.299, p = 0.014 and r = 0.507, p < 0.001, respectively). Especially eyes with a CCT <625 µm demonstrated a better BCVA (0.05 ± 0.07 logMAR) than eyes with a CCT ≥625 µm (0.13 ± 0.11 logMAR, p = 0.002). Furthermore, the identification of eyes with an early visual restitution was possible by considering follow-up data of the first eye. A preoperative CCT ≥625 µm was also sensitive to identify eyes with a persistent corneal swelling. The anterior banded layer thickness, which was obtained histologically, correlated to the preoperative CCT and the frequency of graft detachments (r = 0.601, p = 0.023 and r = 0.652, p = 0.041, respectively). Furthermore, a graft's baseline ECD ≤2100 cells/mm2 was found to be a risk factor for an ECD deterioration under 1000 cells/mm2 (1.8% vs. 15.8%, p = 0.020). CONCLUSIONS: Simple clinical parameters, such as the preoperative CCT, the course of visual restitution of the first eye, and the graft's baseline ECD, are efficient predictors for relevant outcome parameters after DMEK and therefore may be used for stratification. Furthermore, our findings indicate that a DMEK should be performed in eyes with Fuchs' endothelial corneal dystrophy, if possible, before the CCT exceeds 625 µm to maintain good clinical results.

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Primary corneal endothelial cell (CEC) cultures and 3D-engineered tissue models were used to study the aberrant deposition of extracellular matrix (ECM) in a vision impairing pathology known as Fuchs endothelial corneal dystrophy (FECD). CECs were isolated from excised Descemet membranes of patients with end-stage FECD. CECs isolated from healthy corneas served as controls. Microarray gene profiling was performed on postconfluent cultures of healthy and FECD cells. Protein expression analyses were conducted on tissue models that were engineered by seeding an endothelium on previously devitalized human stromal carriers. The engineered endothelia were kept in culture for 1-3 weeks to reform the endothelial monolayer. Protein expression of integrin subunits α4, α6, αv, and ß1, as well as laminin, type IV collagen, fibronectin, clusterin, and transforming growth factor ß-induced protein (TGFßIp) was then assessed by immunofluorescence. Microarray analysis showed nonstatistical twofold downregulation of collagen-coding genes (COL4A4, COL8A2, and COL21A1) and a twofold upregulation of the COL6A1, laminin α3 gene LAMA3, and integrin subunit α10 gene ITGA10 in FECD cells. Fibronectin type III domain containing 4 (FNDC4) and integrin ß5 (ITGB5) genes was significantly upregulated in FECD cells. Immunostainings demonstrated that the protein expression of the integrin subunits α4, α6, αv, and ß1, type IV collagen, as well as laminin remained similar between native and engineered endothelia. TGFßIp expression was found on the stromal side of both FECD and healthy Descemet's membrane, and only one out of three FECD specimens was positive for the clusterin protein. Interestingly, the ECM protein fibronectin was also found to have a stronger presence on engineered FECD tissues, a result consistent with the native FECD specimens. To conclude, this study allowed to identify fibronectin deposition as one of the first steps in the pathogenesis of FECD, as defined by our engineered tissue model. This opens the way to an entirely new perspective for in vitro pharmacological testing of new therapies for FECD, the leading indication for corneal transplantation in North America.

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The posterior face of the cornea consists of the corneal endothelium, a monolayer of cuboidal cells that secrete and attach to Descemet's membrane, an exaggerated basement membrane. Dysfunction of the endothelium compromises the barrier and pump functions of this layer that maintain corneal deturgesence. A large number of corneal endothelial dystrophies feature irregularities in Descemet's membrane, suggesting that cells create and respond to the biophysical signals offered by their underlying matrix. This review provides an overview of the bidirectional relationship between Descemet's membrane and the corneal endothelium. Several experimental methods have characterized a richly topographic and compliant biophysical microenvironment presented by the posterior surface of Descemet's membrane, as well as the ultrastructure and composition of the membrane as it builds during a lifetime. We highlight the signaling pathways involved in the mechanotransduction of biophysical cues that influence cell behavior. We present the specific example of Fuchs' corneal endothelial dystrophy as a condition in which a dysregulated Descemet's membrane may influence the progression of disease. Finally, we discuss some disease models and regenerative strategies that may facilitate improved treatments for corneal dystrophies.

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PURPOSE: To analyze the morphology and density of corneal tissue in patients with early stage Fuchs' corneal endothelial dystrophy (FCED) by in vivo confocal microscopy (IVCM). CASE SUMMARY: Each layer of the cornea in 2 patients with early-stage FCED was examined with IVCM (ConfoScan 4.0, NIDEK, Co. Ltd., albignasego, Italy). Cross-sectioned corneal images of the corneal epithelium, Bowman's layer, stromal layer, Descemet's membrane, and endothelium were evaluated. Corneal epithelium, Bowman's layer, and anterior stroma of both patients showed no abnormalities. Case 1 was diagnosed as Stage 1 FCED, demonstrating typical changes including pleomorphism, polymegathism, and the presence of guttae in the corneal endothelial layer. Case 2 was diagnosed as Stage 2 FCED, showing several hyper-reflective whitish dots in the posterior stroma, hypo-reflective vertical strands in the stroma adjacent to Descemet's membrane, and pleomorphism, polymegathism, and guttae in the corneal endothelial layer. CONCLUSIONS: IVCM is a non-invasive and effective tool to diagnose early-stage FCED.

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