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Progress in Retinal and Eye Research Jan 2021Fuchs endothelial corneal dystrophy (FECD) is the most common primary corneal endothelial dystrophy and the leading indication for corneal transplantation worldwide.... (Review)
Review
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.
Topics: Animals; Apoptosis; Disease Models, Animal; Fuchs' Endothelial Dystrophy; Humans; Mice; Mitochondrial Diseases; Oxidative Stress; Sex Distribution
PubMed: 32438095
DOI: 10.1016/j.preteyeres.2020.100863 -
Progress in Retinal and Eye Research Mar 2021Fuchs endothelial corneal dystrophy (FECD) is a common cause for heritable visual loss in the elderly. Since the first description of an association between FECD and... (Review)
Review
Fuchs endothelial corneal dystrophy (FECD) is a common cause for heritable visual loss in the elderly. Since the first description of an association between FECD and common polymorphisms situated within the transcription factor 4 (TCF4) gene, genetic and molecular studies have implicated an intronic CTG trinucleotide repeat (CTG18.1) expansion as a causal variant in the majority of FECD patients. To date, several non-mutually exclusive mechanisms have been proposed that drive and/or exacerbate the onset of disease. These mechanisms include (i) TCF4 dysregulation; (ii) toxic gain-of-function from TCF4 repeat-containing RNA; (iii) toxic gain-of-function from repeat-associated non-AUG dependent (RAN) translation; and (iv) somatic instability of CTG18.1. However, the relative contribution of these proposed mechanisms in disease pathogenesis is currently unknown. In this review, we summarise research implicating the repeat expansion in disease pathogenesis, define the phenotype-genotype correlations between FECD and CTG18.1 expansion, and provide an update on research tools that are available to study FECD as a trinucleotide repeat expansion disease. Furthermore, ongoing international research efforts to develop novel CTG18.1 expansion-mediated FECD therapeutics are highlighted and we provide a forward-thinking perspective on key unanswered questions that remain in the field.
Topics: Fuchs' Endothelial Dystrophy; Gene Expression Regulation; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Genetic; Transcription Factor 4; Trinucleotide Repeat Expansion
PubMed: 32735996
DOI: 10.1016/j.preteyeres.2020.100883 -
Ophthalmology and Therapy Apr 2023Corneal endothelium plays an important role in maintaining hydration homeostasis and clarity of the cornea. Fuchs endothelial corneal dystrophy (FECD) affects the... (Review)
Review
Corneal endothelium plays an important role in maintaining hydration homeostasis and clarity of the cornea. Fuchs endothelial corneal dystrophy (FECD) affects the corneal endothelium resulting in edema and characteristic excrescences on the Descemet's membrane known as corneal guttae. Descemet membrane endothelial keratoplasty (DMEK) has evolved to become the standard of care for patients with FECD with excellent visual acuity outcomes. Patients with FECD may have coexisting cataracts and therefore may require a cataract surgery, which increases the risk of corneal decompensation. The presence of FECD may not only influence the choice of intraocular lens but vision outcomes can also be affected by the corneal condition. The ability to combine the surgeries further raises important considerations regarding the timing and sequence of DMEK and cataract extraction for patients with FECD. This review provides a guide for corneal surgeons in choosing between endothelial keratoplasty and cataract surgery-alone, in combination or sequential-in their management of patients with FECD.
PubMed: 36637659
DOI: 10.1007/s40123-022-00637-1 -
Asia-Pacific Journal of Ophthalmology... 2017Endothelial keratoplasty (EK) has revolutionized corneal transplant surgery by providing rapid visual recovery and improved visual outcomes. In parts of the world with... (Review)
Review
Endothelial keratoplasty (EK) has revolutionized corneal transplant surgery by providing rapid visual recovery and improved visual outcomes. In parts of the world with Fuchs endothelial dystrophy, many patients may present with both cataracts and corneal degeneration requiring surgery. Other forms of endothelial decompensation may also present with cataracts. The staging or combination of transplant surgery and cataract surgery depend on both the abilities of the surgeon and the surgical techniques being considered. We currently use phacoemulsification to remove cataracts and routinely perform both cataract surgery and EK with topical anesthesia. The decision to perform either combined or staged cataract and transplant surgery depends upon the examination of the eye including assessment of the anterior chamber depth and the status of the anterior surface of the cornea, which affects the ability to reliably assess keratometry. Additional considerations include the type of lens implant to use, the desired refractive outcome, and the patient's preference about whether to undergo 1 or 2 surgical procedures per eye.
Topics: Cataract; Corneal Transplantation; Fuchs' Endothelial Dystrophy; Humans; Phacoemulsification; Visual Acuity
PubMed: 28726355
DOI: 10.22608/APO.2017127 -
Ugeskrift For Laeger Nov 2023Corneal grafting is performed approximately 650 times a year in Denmark. A summary of these procedures is given in this review. Fuchs' endothelial dystrophy and... (Review)
Review
Corneal grafting is performed approximately 650 times a year in Denmark. A summary of these procedures is given in this review. Fuchs' endothelial dystrophy and pseudophakic bullous keratopathy are frequent indications for transplantation. Previously, penetrating keratoplasty was the technique of choice but is nowadays mainly used for combined stromal and endothelial pathology. Instead, techniques specifically replacing diseased layers are more common. The Danish Cornea Bank is the only center in Denmark which undertakes preparation and distribution of tissue. The operative procedures are performed at Aarhus University Hospital or Rigshospitalet Glostrup.
Topics: Humans; Corneal Diseases; Corneal Transplantation; Cornea; Fuchs' Endothelial Dystrophy; Keratoplasty, Penetrating
PubMed: 38018729
DOI: No ID Found -
Experimental Eye Research Apr 2021The corneal endothelial monolayer and associated Descemet's membrane (DM) complex is a unique structure that plays an essential role in corneal function. Endothelial... (Review)
Review
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.
Topics: Blister; Corneal Dystrophies, Hereditary; Corneal Edema; Corneal Stroma; Endothelium, Corneal; Fuchs' Endothelial Dystrophy; Humans; Iridocorneal Endothelial Syndrome; Vision Disorders
PubMed: 33596440
DOI: 10.1016/j.exer.2021.108495 -
Current Opinion in Ophthalmology Sep 2022Artificial intelligence has advanced rapidly in recent years and has provided powerful tools to aid with the diagnosis, management, and treatment of ophthalmic diseases.... (Review)
Review
PURPOSE OF REVIEW
Artificial intelligence has advanced rapidly in recent years and has provided powerful tools to aid with the diagnosis, management, and treatment of ophthalmic diseases. This article aims to review the most current clinical artificial intelligence applications in anterior segment diseases, with an emphasis on microbial keratitis, keratoconus, dry eye syndrome, and Fuchs endothelial dystrophy.
RECENT FINDINGS
Most current artificial intelligence approaches have focused on developing deep learning algorithms based on various imaging modalities. Algorithms have been developed to detect and differentiate microbial keratitis classes and quantify microbial keratitis features. Artificial intelligence may aid with early detection and staging of keratoconus. Many advances have been made to detect, segment, and quantify features of dry eye syndrome and Fuchs. There is significant variability in the reporting of methodology, patient population, and outcome metrics.
SUMMARY
Artificial intelligence shows great promise in detecting, diagnosing, grading, and measuring diseases. There is a need for standardization of reporting to improve the transparency, validity, and comparability of algorithms.
Topics: Algorithms; Artificial Intelligence; Dry Eye Syndromes; Fuchs' Endothelial Dystrophy; Humans; Keratitis; Keratoconus
PubMed: 35819899
DOI: 10.1097/ICU.0000000000000885 -
Eye and Vision (London, England) Jun 2021Fuchs endothelial corneal dystrophy is a hereditary disease and the most frequent cause of corneal transplantation in the worldwide. Its main clinical signs are an... (Review)
Review
BACKGROUND
Fuchs endothelial corneal dystrophy is a hereditary disease and the most frequent cause of corneal transplantation in the worldwide. Its main clinical signs are an accelerated decrease in the number of endothelial cells, thickening of Descemet's membrane and formation of guttae in the extracellular matrix. The cornea's ability to maintain stromal dehydration is impaired, causing painful epithelial bullae and loss of vision at the point when the amount of corneal endothelial cells cannot be compensated. At present, apart from corneal transplantation, there is no other effective treatment that prevents blindness.
MAIN TEXT
In this review, we first summarized the mutations of COL8A2, TCF4, TCF8, SLC4A11 and AGBL1 genes in Fuchs endothelial corneal dystrophy. The molecular mechanisms associated with Fuchs endothelial corneal dystrophy, such as endoplasmic reticulum stress and unfolded protein response pathway, oxidative stress, mitochondrial dysregulation pathway, apoptosis pathway, mitophagy, epithelial-mesenchymal transition pathway, RNA toxicity and repeat-associated non-ATG translation, and other pathogenesis, were then explored. Finally, we discussed several potential treatments related to the pathogenesis of Fuchs endothelial corneal dystrophy, which may be the focus of future research.
CONCLUSIONS
The pathogenesis of Fuchs endothelial corneal dystrophy is very complicated. Currently, corneal transplantation is an important method in the treatment of Fuchs endothelial corneal dystrophy. It is necessary to continuously explore the pathogenesis of Fuchs endothelial corneal dystrophy and establish the scientific foundations for the development of next-generation corneal therapeutics.
PubMed: 34130750
DOI: 10.1186/s40662-021-00246-2 -
Cells Jul 2021Fuchs endothelial corneal dystrophy (FECD) is a genetically complex, heterogenous, age-related degenerative disease of corneal endothelial cells (CEnCs), occurring in... (Review)
Review
Fuchs endothelial corneal dystrophy (FECD) is a genetically complex, heterogenous, age-related degenerative disease of corneal endothelial cells (CEnCs), occurring in the fifth decade of life with a higher incidence in females. It is characterized by extracellular matrix (ECM) protein deposition called corneal guttae, causing light glare and visual complaints in patients. Corneal transplantation is the only treatment option for FECD patients, which imposes a substantial socioeconomic burden. In FECD, CEnCs exhibit stress-induced senescence, oxidative stress, DNA damage, heightened reactive oxygen species (ROS) production, mitochondrial damage, and dysfunction as well as sustained endoplasmic reticulum (ER) stress. Among all of these, mitochondrial dysfunction involving altered mitochondrial bioenergetics and dynamics plays a critical role in FECD pathogenesis. Extreme stress initiates mitochondrial damage, leading to activation of autophagy, which involves clearance of damaged mitochondria called auto(mito)phagy. In this review, we discuss the role of mitochondrial dysfunction and mitophagy in FECD. This will provide insights into a novel mechanism of mitophagy in post-mitotic ocular cell loss and help us explore the potential treatment options for FECD.
Topics: Animals; DNA Damage; DNA, Mitochondrial; Endothelial Cells; Endothelium, Corneal; Energy Metabolism; Fuchs' Endothelial Dystrophy; Humans; Mitochondria; Mitochondrial Dynamics; Mitophagy; Signal Transduction
PubMed: 34440658
DOI: 10.3390/cells10081888