Corneal dystrophies. II. Endothelial dystrophies

doi:10.1016/0039-6257(78)90151-0

Survey of Ophthalmology

Volume 23, Issue 3, November–December 1978, Pages 147-168

https://doi.org/10.1016/0039-6257(78)90151-0 Get rights and content

Abstract

In general, endothelial dystrophies present three types of clinical manifestations: 1) production of collagenous tissue posterior to Descemet's membrane which appears as cornea guttata, polymorphic excrescences or gray sheets; 2) a disrupted endothelial mosaic in specular reflection; and 3) corneal edema as a reflection of decreased endothelial barrier and pump functions. In this review, the authors discuss three endothelial dystrophies — Fuchs', posterior polymorphous and congenital hereditary. They describe the clinical, histopathologic and biochemical features, and illustrate each dystrophy with a composite drawing. Dystrophies of the epithelium, Bowman's layer, and stroma were reviewed separately in the September–October 1978 issue of this journal.

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Cited by (152)

Corneal endothelial dystrophy
2023, Ophthalmic Pathology: The Evolution of Modern Concepts
Like many ocular disorders, the recognition of corneal endothelial dystrophy as a distinct nosologic entity can be traced to Ernst Fuchs, who in 1910 described 13 patients with bilateral vision loss caused by a non-inflammatory clouding of the cornea. It was not obvious at first that the nidus of disease was the endothelial cell since epithelial bullae were mostly responsible for visual degradation. A century later, genetic investigations have implicated at least 15 loci on 9 chromosomes, a far more complex picture of inheritance and molecular dysfunction than anticipated. This chapter recounts the events that led to a modern understanding of Fuchs' corneal dystrophy as well as congenital hereditary endothelial dystrophy. The photograph gallery includes the histopathology of normal cornea, Fuchs' dystrophy with stromal and epithelial edema, secondary basement membrane changes, classic guttata and diffuse thickening of Descemet's membrane, and posterior polymorphous dystrophy.
Fuchs Endothelial Corneal Dystrophy associated risk variant, rs3768617 in LAMC1 shows allele specific binding of GFI1B
2022, Gene
Citation Excerpt :
The accumulation of numerous vacuoles inside the cells with the fragmented plasma membrane and the loss of intercellular junctions causes endothelial cells to degenerate, reducing the endothelial pump's capacity to keep the cornea in its usual dehydrated state (Iwamoto and DeVoe, 1971). The effects are differences in endothelial cell shape, also known as polymagethism and pleomorphism, stromal and epithelial hydration, and corneal edema which causes corneal deformation and loss of vision (Adamis et al., 1993; Waring et al., 1978). Based on the population's ethnicity, the disease prevalence ranges from 1.9% to 11.0% .
To investigate the genetic and functional association of an intronic variant of LAMC1, rs3768617 with Fuchs endothelial corneal dystrophy (FECD) in the Indian population.
Blood samples were collected from age and sex matched 356 controls and 120 FECD patients after a detailed assessment via specular microscopy. Genomic DNA was extracted and genotyping was done by fluorescence based capillary electrophoresis. The genetic association of rs3768617 polymorphisms was computed by the chi-square (χ²) test. Bioinformatics studies were performed to find the allele specific binding of different transcription factors in the region of rs3768617 and functional evaluation assessed by luciferase assay followed by Electrophoretic Mobility Shift Assay (EMSA) and Chromatin Immunoprecipitation assay (ChIP). Immunofluorescence assay was carried out to check for any differential expression of GFI1B between control and FECD endothelium samples.
SNP rs3768617 {chr1:183123365 (GRCh38.p13)} was found to be genetically associated with FECD in Indian population (p = 2.646 × 10⁻⁸). Luciferase assay suggested that the rs3768617 locus has a regulatory role. In silico analysis showed that the transcription factor, GFI1B binds to the risk allele ‘G' of rs3768617, but not to the protective allele ‘A’ which was also experimentally validated by EMSA. High enrichment of DNA flanking the surrounding region of rs3768617 was also found in presence of GFI1B specific antibody in ChIP assay. There was a 0.63 fold decrease in GFI1B expression in FECD affected corneal endothelium compared to control endothelium.
The genetic association of rs3768617 in LAMC1 with FECD pathogenesis is mediated by GFI1B, thus finding the functional role of LAMC1 in FECD pathogenesis.
Fuchs endothelial corneal dystrophy: The vicious cycle of Fuchs pathogenesis
2021, Progress in Retinal and Eye Research
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.
Diurnal Variation in Corneal Edema in Fuchs Endothelial Corneal Dystrophy
2019, American Journal of Ophthalmology
Citation Excerpt :
In summary, given the characteristic posterior profile changes, the amount of diurnal edema variation of 31-58 μm, and the relative stability of the anterior cornea, posterior corneal changes are likely to be key in diurnal edema variation in Fuchs dystrophy.12–14,22,23 In contrast, for vision and subjective diurnal variation, structural anterior corneal changes and surface irregularities inducing scatter might play a role.3,11 The results of this study will allow overcoming measurement error of Scheimpflug imaging, particularly in Fuchs dystrophy corneas.
The extent of diurnal variation in corneal edema in Fuchs dystrophy is unknown. We measured corneal thickness and posterior profile over the course of the day using Scheimpflug imaging.
Prospective cohort study.
Participants with clinically advanced Fuchs dystrophy eyes undergoing endothelial keratoplasty and participants with healthy corneas were assessed around noon the day before surgery and late afternoon, in presumed steady state. After controlled overnight patching to standardize eyelid closure, participants were assessed immediately upon eye opening in hospital the morning of surgery.
Directly upon awakening, patients had mean corneal thickness of 663 μm (interquartile range [IQR], 625-707) in Fuchs dystrophy (n = 44) and controls (n = 11) had thickness of 557 μm (IQR, 527-601). In control corneas, there were no systematic changes with time. In Fuchs dystrophy eyes, corneal thickness decreased after awakening. Ninety-five percent of patients can be expected to have a decrease in corneal thickness over the first 4 hours after awakening between 31 μm and 58 μm (95% prediction interval). Posterior Q decreased on average by 0.15 (95% confidence interval [CI], 0.07-0.23) and posterior radius of curvature decreased by 0.20 mm (95% CI, 0.14-0.27) over the first 4 hours, indicating that edema resolution steepened the central posterior cornea. Beyond 4 hours after awakening, corneas no longer changed considerably in Fuchs dystrophy.
Impaired hydration control in clinically advanced Fuchs dystrophy makes measurements of key corneal parameters unreliable directly after eye opening. Beyond the first hours after eye opening, corneal thickness measurements are unlikely to vary more in Fuchs dystrophy eyes than in normal eyes.
Comparing Outcomes of Phacoemulsification With Femtosecond Laser–Assisted Cataract Surgery in Patients With Fuchs Endothelial Dystrophy
2018, American Journal of Ophthalmology
To compare the outcome in patients with Fuchs endothelial dystrophy (FED) who underwent standard phacoemulsification vs femtosecond laser–assisted cataract surgery (FLACS) in the treatment of visually significant cataracts.
Retrospective, comparative, interventional case series.
Patient or Study Population: Between April 2013 and December 2016, 140 FED eyes with cataracts of all densities were included. Seventy-two eyes underwent phacoemulsification and 68 eyes underwent FLACS. Intervention or Observation Procedures: Automated noncontact specular microscopy was performed at baseline and postoperatively over a mean of 17.91 ± 10.47 months. Parameters collected include visual acuity, slit-lamp examination findings, and intraoperative findings. Main Outcome Measures: Pachymetry, endothelial cell density (ECD), and coefficient of variance (COV) were compared.
Phacoemulsification had significantly greater postoperative median loss of ECD of 229.0 cells/mm² (14.2%) compared to FLACS ECD of 133.0 cells/mm² (6.5%) (U = 1343.0, Z = -2.241, P = .025). Mean loss of ECD was 346.524 ± 420.472 cells/mm² and 119.964 ± 434.882 cells/mm² for phacoemulsification and FLACS, respectively (P = .005). Mean percentage loss of ECD was 15.3% ± 17.5% for phacoemulsification and 4.4% ± 25.0% for FLACS (P = .006). Eyes that underwent phacoemulsification had 10.7% ± 15.4% mean ECD loss in the mild cataract group, and in the moderate/hard cataract group 19.5% ± 18.0%, P = .045. Eyes that underwent FLACS had 0.9% ± 22.5% mean ECD loss in the mild cataract group, and 8.2% ± 26.3% in the moderate/hard cataract group, P = .291. Comparison between procedures of mean ECD loss for moderate/hard cataracts was significant (P = .043).
FLACS is shown to be superior to phacoemulsification in reducing postoperative endothelial cell loss in FED patients, which translates to a lower risk of corneal decompensation, especially in patients with moderate/hard cataract densities.
Small-incision lenticule extraction in posterior polymorphic corneal dystrophy
2016, Journal of Cataract and Refractive Surgery
We present the case of a 37-year-old man with posterior polymorphic corneal dystrophy who had small-incision lenticule extraction surgery to correct myopic refractive errors. The subjective refraction was −2.62 in the right eye and −2.50 −0.25 × 80 in the left eye. Slitlamp biomicroscopy revealed a band-like lesion in the corneal endothelium of the right eye. The endothelial cell count was 1745 cells/mm² in the right eye and 2945 cells/mm² in the left eye. Small-incision lenticule extraction was performed to correct the myopic refractive errors in both eyes. Twelve months after surgery, the uncorrected distance visual acuity in both eyes was 20/20 and the posterior polymorphic corneal dystrophy lesion had not progressed. The case suggests that small-incision lenticule extraction surgery can be performed successfully and safely in patients with posterior polymorphic corneal dystrophy.
None of the authors has a financial or proprietary interest in any material or method mentioned.

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^☆: Part I of this review, covering dystrophies of the Bowman's layer, epithelium and stroma, appeared in the September–October 1978 issue of this journal.

^☆☆: Supported in part by grants from the Commonwealth Fund and the American Academy of Ophthalmology.

^★: Reprints are not available of Part I or Part II of this review.

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ReviewCorneal dystrophies. II. Endothelial dystrophies☆,☆☆,★

Abstract

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Am J Ophthalmol

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Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Granular dystrophy of the cornea. Characteristic electron microscopic lesion

Arch Ophthalmol

Penetrating keratoplasty and cataract extraction. Combined vs. nonsimultaneous surgery

Arch Ophthalmol

Dystrophie congenitale de la cornée

Arch Ophtalmol (Paris)

Cornea guttata in donor material

Arch Ophthalmol

Relations entre les degenerescences hérédofamiliales et les opacités congenitales de la cornée (étude clinique et genealogique)

Ophthalmologica

Tonography in cornea guttata. A preliminary report

Arch Ophthalmol

Iridocorneal adhesions in posterior polymorphous dystrophy

Trans Am Acad Ophthalmol Otolaryngol

The clinical spectrum of posterior polymorphous dystrophy

Arch Ophthalmol

La dystrophie vésiculiform goupée en ilots et en bandes de l'endothélium cornéen (herpes posterior de Schnyder)

Bull Soc Ophtalmol Fr

Inheritance of Fuchs' endothelial dystrophy

Arch Ophthalmol

À propos d'un cas de dystrophie cornéenne parenchymateuse familiale à hérédité dominate

Bull Soc Ophtalmol Fr

The management of endothelial dystrophy of the cornea

Am J Ophthalmol

Familial congenital cornea guttata in association with anterior polar cataract

Acta Ophthalmol (Kbh)

Normal and abnormal development

Diseases of the outer eye

Dystrophia cornealis posterior polymorpha (Hornhautdystrophie von Schlichting)

Ophthalmologica

Classification and treatment of hereditary corneal dystrophies

Arch Ophthalmol

Essai de classification anatomique des dégénérescences familiales de la cornée

Ophthalmologica

Hérédo-dystrophie annulaire de' l'endothélium cornéen

J Genet Hum

Review
Corneal dystrophies. II. Endothelial dystrophies☆,☆☆,★