Fuchs Corneal Dystrophy Research Articles

MCQs

Objectives: To describe the surgical technique of penetrating keratoplasty (PKP) combined with scleral fixation of posterior chamber intraocular lens (PC-IOL). To determine the visual outcome and complications of PKP combined with scleral fixation of PC-IOL. Study Design: Prospective study. Setting: Department of Ophthalmology and Ophthalmic out-patient clinic, Nahariya Medical Center, Israel. Patients: 10 patients, aged 47–81 (mean 66.4 years), underwent PKP combined with scleral fixation of PC-IOL and were followed for periods of 20–34 months (mean 27.4 months). Seven of the patients had aphakic bullous keratopathy, one had Fuch's corneal dystrophy with cataract and two had corneal opacities and cataract. Main Outcome Measures: Periodic visual acuity, complete eye examination and fluorescein angiography, when indicated. Results: Visual acuity improved in all patients from light perception to counting fingers preoperatively, to 20/40 to 20/300 postoperatively. Pre-existing ocular pathologic findings were the main reason for only partial improvement of visual acuity in some of the patients. No significant complications were encountered in any of the patients. Conclusions: Scleral fixation of PC-IOL may be considered as an alternative surgical procedure to anterior chamber IOL implantation when combined with PKP and when capsular or zonular support is absent or unsafe.

Fuchs Corneal Dystrophy: Aberrant Collagen Distribution in an L450W Mutant of theCOL8A2Gene

To characterize histologically Descemet's membrane in an early-onset Fuchs corneal dystrophy (FCD) COL8A2 mutant and compare these findings with corneas from late-onset FCD and normal corneas. A corneal explant from a patient with the L450W COL8A2 mutation and others with late-onset disease were studied with antibodies to collagens IV, VIIIA1, VIIIA2, fibronectin, and laminin. Transmission electron microscopy was performed on a portion of the explant. Control explants included eye bank corneas without known disease and surgical explants from unrelated conditions. In normal corneas, a regular array of colocalized COL8A1 and COL8A2 was observed in the anterior half of Descemet's membrane. In the L450W mutant, Descemet's membrane was several times thicker than normal and traversed by refractile strands and blebs that stained intensely for COL8A2, a feature also observed in late-onset FCD. Both the alpha1 and alpha2 subtypes of collagen VIII were observed at high levels along the anterior edge of Descemet's, another abnormal feature also found in late-onset FCD. Ultrastructure of the L450W cornea revealed a well-formed anterior banded layer more than three times thicker than normal. An unusual, thin internal layer was rich in patches of wide-spaced collagen. The layer is a distinctive pathologic structure that is associated with FCD and is characterized by approximately 120 nm periodicity and the presence of collagen VIII. Depositions of collagen IV, fibronectin, and laminin were also greatly increased in the of posterior Descemet's membrane, yet another general feature shared between early- and late-onset disease. Early-onset COL8A2 L450W disease involves massive accumulation and abnormal assembly of collagen VIII within Descemet's membrane, a process that is presumed to begin during fetal development. Both early- and late-onset subtypes of FCD appear to be the result of abnormal basement membrane assembly rather than a primary defect in endothelial metabolism.

Cryptococcus albidus Keratitis After Corneal Transplantation

To report suspected donor-to-host transmission of Cryptococcus albidus after penetrating keratoplasty. Review of the literature and a case report of a 69-year-old woman who underwent penetrating keratoplasty for Fuchs corneal dystrophy and developed persistent corneal infiltrates 7 months postoperatively are presented. Cryptococcus albidus was cultured from the original donor tissue at the time of the repeat keratoplasty. This case demonstrates an unusual case of cryptococcal keratitis after keratoplasty suspected to be a donor-to-host transmission.

Epithelial Innervation of Human Cornea

Evaluation of a new method to visualize distribution and morphology of human corneal nerves (Adelta- and C-fibers) by means of fluorescence staining, confocal laser scanning microscopy, and 3-dimensional (3D) reconstruction. Trephinates of corneas with a diagnosis of Fuchs corneal dystrophy were sliced into layers of 200 microm thickness using a Draeger microkeratome (Storz, Germany). The anterior lamella was stained with the Life/Dead-Kit (Molecular Probes Inc.), examined by the confocal laser scanning microscope "Odyssey XL," step size between 0.5 and 1 microm, and optical sections were digitally 3D-reconstructed. Immediate staining of explanted corneas by the Life/Dead-Kit gave a complete picture of the nerves in the central human cornea. Thin nerves running parallel to the Bowman layer in the subepithelial plexus perforate the Bowman layer orthogonally through tube-like structures. Passing the Bowman layer, Adelta- and C-fibers can be clearly distinguished by fiber diameter, and, while running in the basal epithelial plexus, by their spatial arrangement. Adelta-fibers run straight and parallel to the Bowman layer underneath the basal cell layer. C-fibers, after a short run parallel to the Bowman layer, send off multiple branches penetrating epithelial cell layers orthogonally, ending blindly in invaginations of the superficial cells. In contrast to C-fibers, Adelta-fibers show characteristic bulbous formations when kinking into the basal epithelial plexus. Ex-vivo fluorescence staining of the cornea and 3D reconstructions of confocal scans provide a fast and easily reproducible tool to visualize nerves of the anterior living cornea at high resolution. This may help to clarify gross variations of nerve fiber patterns under various clinical and experimental conditions.

Inheritance of a NovelCOL8A2Mutation Defines a Distinct Early-Onset Subtype of Fuchs Corneal Dystrophy

To characterize the genetic basis and phenotype of inherited Fuchs corneal dystrophy (FCD). DNA from blood was used for genome-wide linkage scans with tandem repeat polymorphisms. Mutation detection involved sequencing PCR-amplified exons. Families with FCD were clinically evaluated and graded on the Krachmer severity scale. Confocal specular microscopy visualized the morphology of endothelial guttae, small protrusions of Descemet's membrane that are characteristic of FCD. Linkage was obtained to 1p34.3-p32 for the autosomal dominant kindred originally reported by Magovern in 1979. All 21 cases with FCD and one with posterior polymorphous dystrophy were heterozygous for L450W, a novel point mutation in the COL8A2 gene. Of 62 independent cases of familial FCD, none had the previously reported mutations in COL8A2. Corneal guttae in COL8A2 patients were small, rounded, and associated with the endothelial cell center. This contrasts with common FCD, in which guttae were larger, sharply peaked, and initially positioned at edges of endothelial cells. The profile of age and disease severity for the L450W FCD kindred suggested that disease onset occurred in infancy, compared with an average age of onset of 50 years estimated for 201 familial FCD patients in 62 other families. A novel pathogenic L450W COL8A2 mutation was identified and its highly distinctive pathology characterized. This indicates that COL8A2 mutations give rise to a rare subtype of FCD. This study also provides the first direct evidence that COL8A2-FCD progresses from early to late stages in 25 years, a rate similar to that estimated for late-onset FCD.

A Morphologic Study of Fuchs Dystrophy and Bullous Keratopathy

To describe the morphologic features of Fuchs corneal dystrophy and compare them with those of bullous keratopathy. This was an observational case series. The study group consisted of 32 corneal buttons with a diagnosis of Fuchs dystrophy and the comparison group consisted of 22 corneal buttons with bullous keratopathy. Morphologic analysis was performed of corneal buttons from patients with the clinical diagnosis of Fuchs dystrophy or bullous keratopathy by light and electron microscopy. The main outcome measure was identification of degenerated keratocytes, granular material in and around keratocytes, and lipid keratopathy. The overall morphologic features of Fuchs dystrophy and bullous keratopathy are similar to those described in previous literature. A high proportion of keratocytes exhibited degenerative changes (78.9% in Fuchs dystrophy versus 50.5% in bullous keratopathy). Granular material was identified in and around variably degenerated keratocytes in all cases of Fuchs dystrophy and in 14 of 22 (64%) of the corneas with bullous keratopathy. The percentage of keratocytes with granular deposits was higher in Fuchs dystrophy corneas as compared with corneas with bullous keratopathy (51.7% versus 14.1%, P < 0.0005). Lipid keratopathy was a common occurrence in both Fuchs dystrophy and bullous keratopathy (23/32 [72%] versus 12/22 [55%]). Histopathologic changes in the corneal stroma and keratocytes occur in Fuchs dystrophy. Secondary lipid keratopathy ensues and may contribute to corneal haze. A higher proportion of keratocytes in Fuchs dystrophy have granular deposit than in bullous keratopathy. That a high proportion of keratocytes had degenerative changes in both Fuchs dystrophy and bullous keratopathy suggests that keratocytes may degenerate secondary to altered stromal microenvironment because of endothelial cell loss.

Factors influencing visual outcome after penetrating keratoplasty combined with intraocular lens implantation.

To establish which factors influence visual outcome after penetrating keratoplasty combined with intraocular lens implantation. This retrospective noncomparative clinical interventional case series study included 135 consecutive patients (mean age 70.2 +/- 13.6 years) who underwent central penetrating allogenic keratoplasty combined with intraocular lens (IOL) implantation, all operated by the same surgeon. There were 79 triple procedures, 33 keratoplasties combined t with an exchange of OL, and 23 penetrating keratoplasties combined with a secondary implantation of posterior chamber lens. Mean follow-up was 28.3 +/- 18.7 months (range 3.3-112 months). Reasons for keratoplasty were herpetic or traumatic corneal scars or defects (46), Fuchs corneal endothelial dystrophy (22), pseudophakic or aphakic bullous keratopathy (49), corneal endothelial decompensation due to other reasons (15), and keratoconus (3). Main outcome measures were postoperative visual acuity and agin in visual acuitvy Mean postoperative visual acuity and mean gain in visual acuity were 0.33 +/- 0.21 (median 0.30) and 0.25 +/- 0.20 (median 0.20), respectively. Compared with the preoperative measurements, mean visual acuity increased in 129 patients (129 /135, 95.6%). Factors influencing postoperative visual outcome and gain in visual acuity were preoperative visual acuity (p < 0.005), reason for keratoplasty (p < 0.005), and diameter of the graft (p = 0.046). ostoperative visual outcome was independent of age, sex, right or left eye, presence of diabetes mellitus, preoperative refractive error, length of follow-up, duration of surgery, and preoperative intraocular pressure. The most important factors influencing visual outcome after central penetrating allogenic keratoplasty combined with IOL surgery are preoperative visual acuity, graft size, and reason for keratoplasty. Other factors such as age, sex, diabetes mellitus, and preoperative refractive error do not substantially influence postoperative visual outcome.

Fuch's corneal dystrophy in a patient with mitochondrial DNA mutations.

A patient with Fuch's corneal dystrophy, sensorineural hearing loss, diabetes, cardiac conduction defects, ataxia, and hyperreflexia is described. Analysis of lymphocyte mitochondrial DNA showed missense mutations usually associated with Leber's...

Visual Outcome and Complications Following Penetrating Keratoplasty Combined with Scleral Fixation of Posterior Chamber Intraocular Lens

Objectives: To describe the surgical technique of penetrating keratoplasty (PKP) combined with scleral fixation of posterior chamber intraocular lens (PC-IOL). To determine the visual outcome and complications of PKP combined with scleral fixation of PC-IOL. Study Design: Prospective study. Setting: Department of Ophthalmology and Ophthalmic out-patient clinic, Nahariya Medical Center, Israel. Patients: 10 patients, aged 47–81 (mean 66.4 years), underwent PKP combined with scleral fixation of PC-IOL and were followed for periods of 20–34 months (mean 27.4 months). Seven of the patients had aphakic bullous keratopathy, one had Fuch's corneal dystrophy with cataract and two had corneal opacities and cataract. Main Outcome Measures: Periodic visual acuity, complete eye examination and fluorescein angiography, when indicated. Results: Visual acuity improved in all patients from light perception to counting fingers preoperatively, to 20/40 to 20/300 postoperatively. Pre-existing ocular pathologic findings were the main reason for only partial improvement of visual acuity in some of the patients. No significant complications were encountered in any of the patients. Conclusions: Scleral fixation of PC-IOL may be considered as an alternative surgical procedure to anterior chamber IOL implantation when combined with PKP and when capsular or zonular support is absent or unsafe.

Simultaneous penetrating keratoplasty, cataract extraction and artificial lens implantation ("triple procedure") 1981-1987

Between June 1981 and March 1987, the authors performed simultaneous penetrating keratoplasty, cataract extraction, and intraocular lens implantation in 90 eyes. The main indications were Fuchs's corneal endothelial dystrophy (38 cases), corneal cicatrization (33 cases) and corneal or scleral perforation (7 cases). Extracapsular cataract extraction with posterior chamber lens implantation was performed in 82 patients. The posterior capsule ruptured in nine eyes, necessitating an anterior vitrectomy in four of them. The corneal transplant was rejected in nine eyes (10%). The mean preoperative visual acuity of 9/100 in 89 patients improved to 39/100 six months after surgery in 59 patients who were followed up and to 50/100 in the 29 patients with Fuchs's corneal dystrophy. The authors believe that in cases presenting with both cataract and medically uncontrollable corneal disease, simultaneous penetrating keratoplasty with extracapsular cataract extraction and implantation of a posterior chamber lens represents the treatment of choice.

Keratoplasty and Intraocular Lenses

The art and science of intraocular lens implantation surgery is expanding. Highly successful results with elderly uncomplicated cataract patients have led to cautious implantation surgery in patients with co-existing eye disease. The results of implantation surgery achieved in sixteen patients with combined corneal disease and cataract formation are analyzed. In twelve patients penetrating keratoplasy was performed prior to cataract removal and implantation surgery, performed simultaneous with or in combination with secondary implantation in previously aphakic eyes. Vitrectomy was avoided in all primary lens insertion procedures but was necessary in two secondary implantations without ontoward effect. In this entire group of twelve patients all grafts have remained clear, there was minimal tissue reaction and visual return was excellent. In those with pre-existing corneal disease not requiring keratoplasty including one instance of Fuch's Corneal Dystrophy, there was no change in corneal status as a result of implantation surgery.

MARGINAL DEGENERATION OF THE CORNEA WITH PERFORATION.

Introduction Marginal degeneration of the cornea, also identified as peripheral furrow keratitis by Gifford, 1 senile marginal atrophy by Fuchs, 2 and ectatic corneal dystrophy by Terrien, 3 is infrequently encountered in practice. Its exact incidence is difficult to ascertain as there are many clinical variants, and some of the milder cases may be easily overlooked. One unusual complication of this relatively benign disease is spontaneous perforation of the cornea. Francois 4 found this to be present in 15% of the 130 cases with this diagnosis reported in the literature prior to 1936. Recently six patients were observed in varying stages of marginal degeneration. Surprisingly, in four of these patients there was a corneal perforation evidenced either by iris incarceration in the wound and resultant pupillary distortion, or prolapse of a nubbin of iris through the perforation. Report of Cases 1. Marginal Degeneration. —Early stage, 1; age 72; white male.

Interstitial Degeneration of the Cornea

The author describes a condition which he considers the commonest of all idiopathic corneal metaplasias in Southern India, a degeneration that takes place insidiously in the absence of any known etiological factor, develops slowly, without irritation, affecting males most commonly from 30 years old and up. A case is given in detail with histological examination of a deep shaving, and certain differences from the condition known as Fuchs's corneal dystrophy are pointed out. The author describes a condition which he considers the commonest of all idiopathic corneal metaplasias in Southern India, a degeneration that takes place insidiously in the absence of any known etiological factor, develops slowly, without irritation, affecting males most commonly from 30 years old and up. A case is given in detail with histological examination of a deep shaving, and certain differences from the condition known as Fuchs's corneal dystrophy are pointed out.