Axenfeld-Rieger Syndrome

Signs and Symptoms

Patients displaying Axenfeld-Rieger (A-R) syndrome are generally asymptomatic. The condition is diagnosed based upon findings from routine biomicroscopic and gonioscopic evaluation. Historically, this condition was incorporated under the broader heading of anterior chamber cleavage syndromes, and included Axenfelds anomaly, Axenfelds syndrome, Riegers anomaly, and Riegers syndrome. Current theory now holds that these conditions are probably a continuum of a single developmental disorder, hence the name Axenfeld-Rieger syndrome. This anterior segment disorder always presents with posterior embryotoxon (a prominent, anteriorly displaced Schwalbes line) and one or more of the following findings: iris strands adherent to Schwalbes line, iris hypoplasia, focal iris atrophy with hole formation, corectopia, and ectropion uveae. Glaucoma may develop in approximately 50 percent of patients with A-R syndrome, but is more common in those with central iris changes and pronounced anterior iris insertion. Non-ocular manifestations of A-R syndrome may include developmental defects of the teeth and facial bones, pituitary anomalies, cardiac disease, oculocutaneous albinism, and redundant periumbilical skin. A-R syndrome is always bilateral but may be markedly asymmetric. The condition appears to be hereditary, displaying an autosomal dominant inheritance pattern with variable expression.

Pathogenesis
There has been much speculation as to the embryonic pathogenesis of A-R syndrome. The current and most widely held theory suggests a developmental arrest of specific anterior segment tissues derived from neural crest cells, which apparently occurs late in gestation. It is not understood why such a developmental arrest occurs, but the result is the retention of a primordial endothelial cell layer on portions of the iris and angle structures. Contraction of these endothelial "membranes" leads to the associated abnormalities in form and function of the anterior segment structures. Presumably, this same developmental arrest can affect other organ systems, resulting in orofacial and other anomalies sometimes encountered in A-R syndrome.

Management
A-R syndrome, a congenital disorder, generally requires little therapeutic intervention. In those instances where iris atrophy results in pseudopolycoria, patients may be fitted with opaque, cosmetic contact lenses to improve their appearance and decrease optical aberrations. The greatest concern in patients with A-R syndrome is the development of secondary glaucoma. In most cases, those who develop glaucoma do so in childhood or early adulthood. Still, patients must be monitored throughout life for elevations in intraocular pressure and optic nerve head changes. Glaucoma therapy for patients with A-R syndrome follows the same therapeutic algorithm as for primary open angle glaucoma, however miotics are reported to be less effective in this condition. Typical therapy begins with topical -blockers (e.g., Betoptic-S) or topical carbonic anhydrase inhibitors (e.g., Azopt). Unfortunately, many of these glaucoma cases become recalcitrant, and surgical intervention is often necessary.

Clinical Pearls
Axenfeld-Rieger syndrome is described as a rare, congenital ocular disorder. Still, these authors have encountered many patients with manifestations of A-R syndrome, some of which are exceedingly subtle. In general, A-R syndrome is more academically interesting than it is clinically challenging. Glaucoma must be a concern in every patient presenting with this disorder. In fact, when glaucoma does occur, it can be quite severe. In addition, patients with A-R syndrome should undergo both a comprehensive medical and dental evaluation to rule out non-ocular manifestations. Because of the known inheritance pattern and variable expression, recommend ocular evaluation for all family members when you detect A-R syndrome.