Mechanisms of disease: Fuchs' endothelial dystrophy

Borboli, Sheila; Colby, Kathryn

doi:10.1016/s0896-1549(01)00016-5

Cited by 87 publications

(63 citation statements)

References 58 publications

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“…These changes compromise the endothelial pumping function and corneal oedema forms. Oedema spreads anteriorly through the corneal layers as the disease progresses, and eventually, the entire corneal structure becomes swollen with the formation of bullae and painful erosions (Borboli & Colby 2002).…”

Section: Introductionmentioning

confidence: 99%

Visual acuity and contrast sensitivity after posterior lamellar keratoplasty

Nielsen

Hjortdal

2011

Acta Ophthalmologica

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. Purpose: It has previously been reported that patients who suffer from Fuchs’ endothelial dystrophy (Fuchs’ ED) have decreased contrast sensibility threshold. The removal of endothelial guttata by Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK) surgery has also been demonstrated to decrease intraocular light scatter and improve contrast thresholds. The purpose of this study was to compare different visual qualities in patients that had undergone DSAEK surgery in one eye while having untreated Fuchs’ dystrophy in the other eye. Methods: Thirty‐two eyes of 16 patients with bilateral Fuchs’ ED who had DSAEK surgery performed in one eye were enrolled. Visual acuity at 100% contrast and contrast sensitivity (CS) as evaluated by a modified simulation of the Freiburg Acuity and Contrast Test, was measured in both eyes of each patient. Results: Snellen visual acuity improved in treated eyes from 0.66 ± 0.35 (SD) before surgery to 0.38 ± 0.18 after surgery (log MAR units; p < 0.01). In eyes with untreated Fuchs’ dystrophy, visual acuity was 0.46 ± 0.14. In a pairwise comparison, there was no difference in Snellen visual acuity between treated and nontreated eyes (p = 0.12). Contrast sensitivity was significantly better in DSAEK‐treated eyes compared with untreated eyes. Mean log CS in DSAEK‐treated eyes was 1.06 ± 0.25 compared with a mean log CS of 0.84 ± 0.16 in untreated eyes (p < 0.01). Fourteen of 16 patients (88%) reported that vision in their DSAEK‐treated eye had the best visual quality. Conclusion: In this study, using a paired design, we demonstrate improved CS in DSAEK‐operated eyes when compared with the other eye that had untreated Fuchs’ ED despite the fact that no difference in visual quality was detected with standard Snellen visual acuity. Contrast sensitivity appears to be superior to normal visual acuity measurements in the evaluation of overall visual quality after DSAEK.

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Section: Introductionmentioning

confidence: 99%

Visual acuity and contrast sensitivity after posterior lamellar keratoplasty

Nielsen

Hjortdal

2011

Acta Ophthalmologica

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“…Yet, reports that show ultrastructural signs of "stress" with abundance of degenerated mitochondria, suggest that the mitochondria might be specific targets of oxidant-induced macromolecular damage in susceptible FECD CE cells. 12,13 In this study, we sought to determine whether FECD is associated with oxidant-antioxidant imbalance, and if so, whether oxidant-induced DNA damage (specifically mitochondrial DNA damage) is present in diseased endothelium. We performed antioxidant gene profiling, comparing FECD CE with normal, and detected a decreased antioxidant defense system in FECD.…”

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confidence: 99%

Evidence of Oxidative Stress in the Pathogenesis of Fuchs Endothelial Corneal Dystrophy

Jurkunas

Bitar

Funaki

et al. 2010

The American Journal of Pathology

264

267

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Fuchs endothelial corneal dystrophy (FECD) is a progressive, blinding disease characterized by corneal endothelial (CE) cell apoptosis. Corneal transplantation is the only measure currently available to restore vision in these patients. Despite the identification of some genetic factors, the pathophysiology of FECD remains unclear. In this study, we observed a decrease in the antioxidant response element-driven antioxidants in FECD corneal endothelium. We further demonstrated that nuclear factor erythroid 2-related factor 2, a transcription factor known to bind the antioxidant response element and activate antioxidant defense, is down-regulated in FECD endothelium. Importantly, we detected significantly higher levels of oxidative DNA damage and apoptosis in FECD endothelium compared with normal controls and pseudophakic bullous keratopathy (iatrogenic CE cell loss) specimens. A marker of oxidative DNA damage, 8-hydroxy-2-deoxyguanosine, colocalized to mitochondria, indicating that the mitochondrial genome is the specific target of oxidative stress in FECD. Oxidative DNA damage was not detected in pseudophakic bullous keratopathy corneas, whereas it colocalized with terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling-positive cells in FECD samples. Ex vivo, oxidative stress caused characteristic morphological changes and apoptosis of CE, suggestive of findings that characterize FECD in vivo. Together, these data suggest that suboptimal nuclear factor erythroid 2-related factor 2-regulated defenses may account for oxidant-antioxidant imbalance in FECD , which in turn leads to oxidative DNA damage and apoptosis. This study provides evidence that oxidative stress plays a key role in FECD pathogenesis. Corneal endothelium (CE) is a monolayer of cells situated in the anterior chamber surface of the cornea; its primary function is to maintain the cornea in a state of deturgescence through sodium-activated ATPase pumping of water, thus, transparency. Fuchs endothelial corneal dystrophy (FECD) is the most common cause of endogenous corneal endothelial degeneration and is characterized by alterations in corneal endothelial cell morphology, progressive loss of CE cells, and concomitant accumulation of extracellular deposits in the basement membrane that eventually lead to corneal edema and opacity. Because CE does not divide in vivo, loss of endothelial cells seen in FECD is permanent. Corneal transplantation is the only treatment modality that can restore lost vision-rendering FECD the second most common cause of corneal transplants performed on the elderly (Ͼ60 years old) in the United States.2 Lack of knowledge of the mechanism of CE degeneration in FECD precludes the development of pharmacotherapeutics for this common and blinding condition.FECD has been termed a disorder of aging; it is a bilateral and slowly progressive disorder, typically appearing after the age of 60 years. FECD is usually a sporadic condition, but it can be inherited as an autosomal dominant trait.3-5 FECD is characterized by endo...

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“…Review of several studies done in North America identified Fuchs' corneal dystrophy as the second most common www.jors.js.iknito.com indication for keratoplasty (15%) ranking second after pseudophakic bullous keratopathy (PBK) (38%) [17][18][19] . Significant proportion of patients with Fuchs dystrophy remain compensated for life and will benefit from cataract surgery to improve their vision, hence the need to minimize further damage on their corneas during cataract surgeries.…”

Section: A Fuchs Corneal Dystrophymentioning

confidence: 99%