Iridocorneal endothelial (ICE) syndrome is a group of disorders characterized by abnormal corneal endothelium that causes variable degrees of iris atrophy, secondary angle-closure glaucoma, and corneal edema. BCSC Section 8, External Disease and Cornea, discusses the corneal aspects of ICE syndrome. Three clinical variants have been described:
essential/progressive iris atrophy
iris nevus/Cogan-Reese syndrome
The condition is clinically unilateral, presents between 20 and 50 years of age, and occurs more often in women. No consistent association has been found with another ocular or systemic disease, and familial cases are very rare. Patients present with decreased vision, pain secondary to corneal edema or secondary angle-closure glaucoma, or an abnormal iris appearance. In each of the 3 clinical variants, the corneal endothelium appears abnormal and takes on a beaten bronze appearance, similar to corneal guttae seen in Fuchs corneal endothelial dystrophy. Microcystic corneal edema may be present without elevated IOP, especially in Chandler syndrome. The unaffected eye may have subclinical irregularities of the corneal endothelium without other manifestations of the disease.
High PAS are characteristic of ICE syndrome (Fig 5-17), and these often extend anterior to the Schwalbe line. The PAS are caused by the contraction of the single or multiple layers of endothelial cells and surrounding collagenous-fibrillar tissue that extend from the peripheral cornea over the trabecular meshwork and iris. These PAS result in synechial closure of the anterior chamber angle and lead to an angle-closure glaucoma. Similar to neovascular glaucoma, the degree of angle closure does not always correlate to the elevation in IOP, because some angles may be functionally closed by the endothelial membrane without overt synechial formation.
Various degrees of iris atrophy and corneal changes distinguish the specific clinical entities. The “progressive iris atrophy” variant of ICE syndrome is characterized by severe progressive iris atrophy resulting in heterochromia, corectopia, ectropion uveae, iris stromal and pigment epithelial atrophy, and hole formation (Fig 5-18). In Chandler syndrome, minimal iris atrophy and corectopia occur, and the corneal and angle findings predominate (Fig 5-19). Chandler syndrome is the most common of the clinical variants and makes up approximately 50% of the cases of ICE syndrome. The iris atrophy tends to be less severe in Cogan-Reese syndrome. This condition is distinguished by tan pedunculated nodules or diffuse pigmented lesions on the anterior iris surface.
Glaucoma occurs in approximately 50% of patients with ICE syndrome, and the glaucoma tends to be more severe in progressive iris atrophy and Cogan-Reese syndrome. In the 3 clinical variations, corneal endothelial abnormalities are seen with a fine, hammered metal appearance to the posterior cornea. In this condition, the corneal endothelium migrates posterior to the Schwalbe line onto the trabecular meshwork. Electron microscopy has shown this endothelial layer to vary in thickness, with areas of single and multiple endothelial layers, and to contain surrounding collagenous and fibrillar tissue. Unlike normal corneal endothelium, filopodial processes and cytoplasmic actin filaments are present, supporting the migratory nature of these cells. PAS are formed when this migratory endothelium and its surrounding collagenous, fibrillar tissue contract. A viral cause has been postulated for the mechanism of ICE syndrome after lymphocytes were seen on the corneal endothelium of affected patients.
The diagnosis of ICE syndrome must always be considered in young to middle-aged patients who present with unilateral, secondary angle-closure glaucoma. It is particularly important to maintain a high index of suspicion as this condition may mimic primary open-angle glaucoma when the iris and corneal features are subtle. Specular microscopy can confirm the diagnosis by demonstrating an asymmetric loss of endothelial cells and atypical endothelial cell morphology in the involved eye. Therapy is directed toward the corneal edema and secondary glaucoma. Hypertonic saline solutions and medications to reduce the IOP, when elevated, can be effective in controlling the corneal edema. The angle-closure glaucoma can be treated medically with aqueous suppressants. Miotics are ineffective, and the role of prostaglandin analogs remains uncertain. When medical therapy fails, filtering surgery (trabeculectomy or an aqueous shunt) can be effective. Late failures have been reported with trabeculectomy secondary to endothelialization of the fistula. These can be reopened in some cases with the Nd:YAG laser. Laser trabeculoplasty has no useful role in treating glaucoma related to ICE syndrome.