Contributor: Gordon K. Klintworth
Anterior segment dysgenesis involves the cornea, iris, and anterior chamber angle, either individually or collectively and phenotypic variation in a family is common. A spectrum of disorders ranges in phenotypical expression from posterior embryotoxon (Axenfeld anomaly) through a major disorganization of the anterior segment including leukomas and poorly formed anterior chamber angles. Phentypical variation in the expression of these anomalies can vary considerably in the two eyes of an affected person as well between individuals within affected families.
The corneal epithelium is not involved primarily in these anomalies but is affected secondarily. Most of the malformations relate to inappropriate growth and distribution of neural crest cells, as amount, migration failure, histogenetic maturity, and misdirected or inappropriate tissue arrangements. The lens, a surface ectodermal structure, may be involved in the condition called Peters anomaly. Infantile glaucoma is common.
Anomalies of the posterior segment and strabismus occur occasionally, but are not consistent features of this syndrome. Systemic features include developmental defects of the teeth and facial bones. Flattening of the mid-face, receding upper lip, maxillary hypoplasia, protrusion of the lower lip, hypertelorism, telocanthus, and a broad flat nose are characteristic of the anterior chamber dysgenesis syndrome . Cardiac, otologic, neurologic, and dermatologic changes occur with but are not specific features of the disorder.
A number of malformations, occurring singly or in combination, are recognized in the anterior chamber. Undue prominence of the connective tissue bundles, which are located in Schwalbe's ring between the termination of Descemet's membrane and the beginning of trabecular meshwork may be seen. Known as posterior embryotoxon, this anomaly can occur in isolation, but not uncommonly strands of connective tissue extend from the ring across the anterior chamber to the iris (Axenfeld anomaly). Congenital ectropion of the iris pigment epithelium, recently added as part of the spectrum of Axenfeld Rieger, consists of segments of iridic pigment epithelium over the iris in contact with retained primordial endothelial cells on the iris surface]. The combination of Axenfeld anomaly and arteriohepatic dyplasia are found in Alagille syndrome.
A severe anterior chamber deformity, in which prominent strands are associated with marked hypoplasia of the iris stroma, constitutes Rieger anomaly. Dysgenetic endothelial cells and Descemet's membrane with changes similar to those found in the corneas of congenital hereditary endothelial dystrophy have been reported in a patient with Rieger anomaly adding to the spectrum of this condition. Various abnormalities of the above-mentioned changes with dental and osseous deformities is Rieger syndrome.
Persistence of mesenchymal tissue in the angle probably forms the prominent Schwalbe's ring and attached iris strands. High insertion of the iris and dysgenesis of the aqueous drainage channel is causally related to the developmental glaucoma, which may have a delayed onset. Juvenile glaucoma develops in 50-70% of such eyes due to faulty development of the filtration angle.
Associated corneal anomalies are usually central abnormalities termed clinically corneal leukomas. A focal absence of the corneal endothelium and Descemet's membrane results in a gray to white corneal opacity. Ultrastructural examination of some cases show irregular basal epithelial cells, absence of Bowman's layer, stromal edema and scarring with derangement of the lamellar architecture, collagen fibrils with a larger than normal diameter in the posterior stroma, absence of Descemet's membrane, and endothelium in the central cornea. Fibrous tissue fills the defect. The main central corneal abnormalities are posterior keratoconus, Peters anomaly and von Hippel internal corneal ulcer (a corneal leukoma with strands from the iris adherent to the edge of the corneal opacity. Abnormal neural crest migration of the cells destined to become posterior corneal stroma, Descemet's membrane and endothelium can result in this rare anomaly. Inflammation is not a feature).