Iris Stromal Atrophy Research Articles

Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice.

Glaucomas are a major cause of blindness. Visual loss typically involves retinal ganglion cell death and optic nerve atrophy subsequent to a pathologic elevation of intraocular pressure (IOP). Some human glaucomas are associated with anterior segment abnormalities such as pigment dispersion syndrome (PDS) and iris atrophy with associated synechiae. The primary causes of these abnormalities are unknown, and their aetiology is poorly understood. We recently characterized a mouse strain (DBA/2J) that develops glaucoma subsequent to anterior segment changes including pigment dispersion and iris atrophy. Using crosses between mouse strains DBA/2J (D2) and C57BL/6J (B6), we now show there are two chromosomal regions that contribute to the anterior segment changes and glaucoma. Progeny homozygous for the D2 allele of one locus on chromosome 6 (called ipd) develop an iris pigment dispersion phenotype similar to human PDS. ipd resides on a region of mouse chromosome 6 with conserved synteny to a region of human chromosome 7q that is associated with human PDS. Progeny homozygous for the D2 allele of a different locus on chromosome 4 (called isa) develop an iris stromal atrophy phenotype (ISA). The Tyrpl gene is a candidate for isa and likely causes ISA via a mechanism involving pigment production. Progeny homozygous for the D2 alleles of both ipd and isa develop an earlier onset and more severe disease involving pigment dispersion and iris stromal atrophy.

The association of iridoschisis and primary angle-closure glaucoma.

Twelve patients with iridoschisis in one or both eyes were studied to determine the clinical features of the condition and to examine the relationship of iridoschisis to primary angle-closure glaucoma. A spectrum of iris pathology, from subtle intrastromal atrophy to extensive splitting of the anterior layer of iris with fibrillar disintegration, was found in the affected and fellow eyes. Gonioscopy revealed partial or complete angle closure, particularly involving the superior angle, in all patients. Seven had glaucomatous disc damage and five had normal discs. The mean axial length and anterior chamber depth measurements in patients with iridoschisis were similar to those found in matched patients with primary angle-closure glaucoma but were significantly less than the measurements found in matched normals (p < 0.001). This study suggests that iridoschisis is an unusual manifestation of iris stromal atrophy and results from intermittent or acute elevation of intraocular pressure. Primary angle-closure glaucoma should be excluded in patients who present with iridoschisis.

Clinical analysis of Fuchs' heterochromic cyclitis

Fuchs' heterochromic cyclitis (FHC) is an important diagnosis to make. Not only for the patient, because incorrect diagnosis may lead to unnecessary therapy and the failure to detect secondary glaucoma, but also for the comparison of studies on the etiology of FHC, which is still unknown. No clinical criteria for establishing the diagnosis of FHC have been internationally accepted yet. By means of clinical analyses of FHC patients in different parts of the world, predominant clinical features may be distinguished and combined to form (internationally accepted) diagnostic criteria. We report a clinical analysis of 51 FHC patients in the Netherlands. Acute symptoms (severe redness, pain or photophobia) were never (100%) encountered. Characteristic keratic precipitates (88%) and/or minimal aqueous cells and flare (60%) and/or vitreous opacities (84%) were major signs, indicating a chronic inflammatory activity, in which no synechiae (100%) were present. Heterochromia (82%) was not a constant sign, but iris stromal atrophy, which causes the heterochromia, was always present (100%). Cataract was present in 82% as a result of the chronic iridocyclitis. Secondary glaucoma was present in 22%. Based on the predominant clinical findings obtained from this analysis of FHC patients, and on data in the literature, we propose clinical diagnostic criteria for FHC. Future studies, also including other uveitis groups, are necessary to confirm these diagnostic criteria.

Clinical, Electron Microscopic, and Immunohistochemical Study of the Corneal Endothelium and Descemet's Membrane in the Iridocorneal Endothelial Syndrome

Two women with the iridocorneal endothelial syndrome had unilateral corneal edema, iris stromal atrophy, and glaucoma. Each underwent penetrating keratoplasty. Transmission electron microscopy of the corneal buttons disclosed a thin, normally structured Descemet's membrane bounded posteriorly by a posterior collagenous layer that contained banded and fibrillar tissue, indicating that the disorder was acquired after childhood. Scanning electron microscopy showed some degenerated corneal endothelial cells with filopodial cytoplasmic projections, suggesting endothelial migration. Transmission electron microscopy of the endothelium showed no signs of epithelial-like alteration, such as stratification, desmosomal junctions, or increased cytoplasmic fibrils. Immunohistochemical staining of fresh-frozen sections with monoclonal antibodies to keratin showed normal staining of the epithelium and no staining of the endothelium. Occasional lymphocytes were seen within the endothelium in one case but were also observed in one case of an inherited corneal disease, posterior polymorphous dystrophy, suggesting that they might be normal "passenger" cells migrating in the endothelial monolayer.

Pigmentary glaucoma: a clinical review of anterior segment pigment dispersal syndrome.

Sixty-eight cases (44 males, 24 females) of anterior segment pigment dispersal syndrome are reviewed. Five patients had no rise in intraocular pressure, 38 had ocular hypertension and 25 had glaucoma as shown by optic disc cupping and field loss. All cases had heavy deposition of pigment in the drainage angle together with Krukenberg spindles and/or light reflux through the iris. Other evidence of anterior segment pigment dispersal was common. The condition was commonest in young adult males, but could present at any age and in women. Medical treatment was often successful initially, but continued to control pressure in only 17 of 42 patients. Laser trabeculoplasty helped some patients. Drainage operations of various types were successful in 19 of 23 cases. Iris angiography showed evidence of vascular hypoperfusion of the iris which probably precedes pigment dispersal and suggests that the ultimate aetiology may be a congenital deficiency of the mesodermal support tissues of the iris. Some degree of iris stromal atrophy is also common and may become marked. Pigment dispersal from the pigment epithelium of the iris occurs in susceptible individuals and may be associated with the insertion of the dilator muscle. The term anterior segment pigment dispersal seems appropriate as the condition is limited to the anterior segment.

Iridoschisis Associated with Glaucoma and Bullous Keratopathy

Two of six patients (four women and two men ranging in age from 51 to 90 years) with bilateral senile iridoschisis also had secondary unilateral narrow angle or angle-closure glaucoma. All six patients had splitting of the iris stroma inferiorly. Histopathologic studies disclosed marked iris stromal atrophy without evidence of vascular or neural alterations. Vessels were present in the separated anterior stroma. Electron microscopy of iridectomy specimens from three patients and a corneal button from one disclosed scant or absent collagen fibrils in the area of separation. The cornea showed focal loss of endothelial cells, patchy posterior banding (110 nm) of Descemet's membrane, and stromal and epithelial edema. The posterior corneal surface showed degenerated endothelial cells and irregular connective tissue most marked inferiorly; the endothelial cells appeared to be normal.