In a healthy eye, the primary function of the corneal endothelium is to pump fluid out of the corneal stroma to maintain clarity of the cornea. In eyes with degenerative disorders such as iridocorneal endothelial (ICE) syndrome and posterior polymorphous dystrophy (PPMD), the corneal endothelial cells may migrate over the trabecular meshwork onto the iris, bringing along a membrane that impairs aqueous humor outflow. Resultant elevations in IOP may become difficult to control, making the management of glaucoma associated with these disorders challenging.

ICE SYNDROME

Background

In a group of disorders collectively known as ICE syndrome, corneal endothelial degeneration leads to corneal edema, alterations to the anterior chamber angle, and structural changes of the iris. The three variations of ICE syndrome—Chandler syndrome, essential iris atrophy, and Cogan-Reese iris nevus syndrome—reflect its variable primary clinical appearance. These variations represent the spectrum of the disorder, and their clinical features and treatment overlap considerably. Each variation can also be associated with secondary glaucoma, and overall, glaucoma occurs in about 50% of ICE syndrome cases.1

Etiology

ICE syndrome is a primary abnormality of the corneal endothelium.2 The endothelial layer typically has a hammered silver appearance with fine guttata-like lesions on slit-lamp biomicroscopy. Specular microscopy often reveals cells of varying shape (pleomorphism) and size (polymegathism) and the characteristic dark cells with light borders (dark/light reversal).3 The abnormal endothelial cells may proliferate and migrate over the chamber angle onto the surface of the iris. Subsequent contraction of the migrating endothelial cell sheet causes the formation of peripheral anterior synechiae (PAS), iridocorneal adhesions, iris defects, and pedunculations.

Clinical Features

ICE syndrome is usually unilateral and typically affects women in their third or fourth decade. PAS are common, but typically, the glaucoma is worse than would be expected from the PAS, because the endothelium covering the angle has blocked aqueous outflow (Figure). In Chandler syndrome, the primary clinical finding is corneal changes with minimal abnormalities of the iris. Glaucoma in this setting is less common and generally milder than with the other ICE syndrome variants.

Iris pedunculations are the primary characteristic of iris nevus syndrome (Cogan-Reese). The iris assumes a velvety whorl-like surface with loss of crypts and ectropion uveae. A nevus of the anterior iris surface may be diffuse or nodular.

Atrophic iris defects are the defining feature of essential iris atrophy. The defects result from a progressive distortion of the pupil on the side opposite the PAS. As the PAS extend circumferentially, recalcitrant glaucoma develops.

Treatment

Corneal edema may be treated with hypertonic saline, although more severe cases may benefit from corneal surgery such as Descemet stripping endothelial keratoplasty.4 In most cases of Chandler syndrome, the increase in IOP is minimal or mild and can be controlled with aqueous suppressants. Prostaglandin analogues may be useful in certain cases if the iris' surface is relatively uninvolved. Laser trabeculoplasty is unlikely to be beneficial in the setting of extensive PAS.

Glaucoma incisional surgery is often required to control elevated IOP. Trabeculectomy with mitomycin C may be effective initially, but eyes with ICE syndrome are prone to bleb failure, as the endothelial membrane migrates over the sclerostomy.5 Nd:YAG laser goniopuncture of the membrane can often restore flow through the sclerostomy, but the effect is usually shortlived as the membrane recovers.6,7 The tube should be kept long and inserted away from the cornea and the iris' surface to lessen the risk of blockage by the proliferating membrane. Sulcus or pars plana placement of the tube may decrease the likelihood of its occlusion and lessen the potential damage to the already compromised cornea or graft. Occasionally, a second implant is required to achieve adequate IOP control.6

POSTERIOR POLYMORPHOUS DYSTROPHY

Background

PPMD is a rare congenital disorder characterized by epithelial-like behavior of the corneal endothelial cells, resulting in small opacifications of the posterior cornea and the thickening of Descemet membrane. The abnormal endothelial cells may migrate as a membrane over the chamber angle onto the iris' surface.8 Glaucoma occurs in 13% of PPMD cases.8

Clinical Features

The disorder is bilateral and may be asymmetric. It follows an autosomal dominant mode of inheritance but with variable expression. The onset of symptoms can occur at any age, including infancy. Blurred vision due to corneal edema is the most common symptom, although vision may be normal depending on the extent of corneal involvement. On slit-lamp biomicroscopy, small, irregular, polymorphic and/or vesicular opacifications may be seen on the posterior cornea. In severe cases, ridges, plaques, bands, or geographic structures may be seen. In about 25% of cases, iridocorneal adhesions develop, and the corneal changes often progress to edema.9 Endothelialization of the chamber angle is uncommon but can result in ectropion uvea and glaucoma. Gonioscopic evaluation of the angle may reveal anterior insertion of the iris or PAS.10

Management

Corneal edema can be treated with hypertonic saline; more severe cases may benefit from corneal surgery. Glaucoma treatment initially involves the use of aqueous suppressants such as beta-blockers, carbonic anhydrase inhibitors, and alpha-agonists. Prostaglandin analogues may also be effective. Glaucoma surgery may be necessary in some cases.

CONCLUSION

Although disorders of the corneal endothelium are uncommon, the secondary glaucoma associated with these disorders can be difficult to manage. Ophthalmologists must consider both the glaucoma and the primary corneal disorder, because the treatment of one can potentially exacerbate the other. Glaucoma drainage devices may worsen the corneal edema or increase the risk of the graft's failure, and corneal surgery may result in higher IOP. These conditions often require joint efforts by cornea and glaucoma specialists.

Darrell WuDunn, MD, PhD, is a professor of ophthalmology at the Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine in Indianapolis, Indiana. Dr. WuDunn may be reached at (317) 278-2661; dwudunn@iupui.edu.

  1. Laganowski HC, Kerr Muir MG, Hitchings RA. Glaucoma and the iridocorneal endothelial syndrome. Arch Ophthalmol. 1992;110(3):346-350.
  2. Levy G, McCartney ACE, Baghai MH, et al. Pathology of the iridocorneal-endothelial syndrome. The ICE-cell. Invest Ophthalmol Vis Sci. 1995;36(13):2592-2601.
  3. Chiou AG, Kaufman SC, Beuerman RW, et al. Confocal microscopy in the iridocorneal endothelial syndrome. Br J Ophthalmol. 1999;83(6):697-702.
  4. Price MO, Price FW Jr. Descemet stripping with endothelial keratoplasty for treatment of iridocorneal endothelial syndrome. Cornea. 2007;26(4):493-497.
  5. Lanzl IM, Wilson RP, Dudley D, et al. Outcome of trabeculectomy with mitomycin-C in the iridocorneal endothelial syndrome. Ophthalmology. 2000;107(2):295-297.
  6. Doe EA, Budenz DL, Gedde SJ, Imani NR. Long-term surgical outcomes of patients with glaucoma secondary to the iridocorneal endothelial syndrome. Ophthalmology. 2001;108(10):1789-1785.
  7. Kim DK, Aslanides IM, Schmidt CM, et al. Long-term outcome of aqueous shunt surgery in ten patients with iridocorneal endothelial syndrome. Ophthalmology. 1999;106(5):1030-1034.
  8. Cibis GW, Krachmer JA, Phelps CD, Weingeist TA. The clinical spectrum of posterior polymorphous dystrophy. Arch Ophthalmol. 1977;95(9):1529-1537.
  9. Cibis GW, Krachmer JH, Phelps CD, Weingeist TA. Iridocorneal adhesions in posterior polymorphous dystrophy. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol. 1976;81(5):770-777.
  10. Threlkeld AB, Green WR, Quigley HA, et al. A clinicopathologic study of posterior polymorphous dystrophy: implications for pathogenetic mechanism of the associated glaucoma. Trans Am Ophthalmol Soc. 1994;92:133-165.