IridoCorneal Endothelial (ICE) Syndrome

By Stuart Macfarlane

Abstract

Iridocorneal Endothelial (ICE) Syndrome is actually a grouping of three closely linked conditions: iris naevus (or Cogan-Reese) syndrome; Chandler's syndrome; and essential (progressive) iris atrophy. The link between the three variants is an abnormal endothelial cell layer which has the capacity to migrate across the angle onto the surface of the iris.

Introduction

• ICE tends to manifest in 30-50 year old females.
• Bilateral cases have been reported, though this is rare.
• It is characterised by a beaten silver-bronze appearance to the corneal endothelium, corneal oedema, iris atrophy and hole formation, corectopia and prominent iris naevus.
• Often peripheral anterior synechiae (PAS) with progressive angle closure and secondary closed-angle glaucoma are present. Vision may be affected by oedema caused by the corneal decompensation from endotheliopathy, or secondary glaucoma. The patient may occasionally complain of monocular diplopia secondary to an exposed area of full thickness iris causing polycoria. Polymerase Chain Reaction evidence shows that HSV DNA is present in a substantial percentage of ICE syndrome corneal specimens.
• These results provide direct evidence to support a hypothesis that the ICE syndrome has a viral origin.

Case Report

SD (patient 28315), a 74 year old male presented 12 May 2005 after referral by his General Practitioner for a routine initial examination with SM. He had noticed that his right pupil had "moved" 5 years ago. He had an otherwise normal ocular history. He was wearing ready-made spectacles and had first noticed blurred vision in the RE 10 years ago. This was his first eyetest for many years.

Slitlamp showed marked right corectopia and a patchy beaten bronze appearance to the corneal endothelium. His right pupil was within a few mm of his angle. Slight posterior corneal oedema was present. Temporal posterior synachae was evident which with gonioscopy was noted to extend 180 degrees. IOP was RE 18 and LE 18mmHg. Best corrected VA was RE 6/24 and LE 6/6. He had nuclear sclerotic changes in the RE and early changes in the LE. Dilated pupil examination was unremarkable with normal discs and cup-disc ratios of 0.35 OU. IOP post-dilatory was normal.

A diagnosis of ICE Syndrome (subclassified as Chandlers) was made. He mentioned that his vision blurs several times a week for an hour with a foreign body sensation. He was advised to return during one of these episodes to exclude exacerbations of corneal oedema or IOP spikes. At the time of writing he had not returned for review.

Discussion

The ICE syndromes represent a range of diseases involving three distinct entities, essential iris atrophy, Chandler syndrome and Cogan-Reese syndrome.

Essential iris atrophy is characterised by severe iris changes with progressive iris atrophy and hole formation, corectopia towards the areas of PAS, and conspicuous PAS. In between areas of atrophy the stroma appears normal.

Chandler syndrome is the more common of the three and is characterised by severe corneal changes and oedema with subsequent blurred vision and haloes. Patients with Chandler's syndrome typically have worse corneal oedema than the rest of the group, while secondary glaucoma is more severe in the other syndromes. Stromal atrophy is absent in 50% of cases. When present it is usually mild to moderate. Corectopia may be severe.

Cogan-Reese syndrome presents with either a diffuse naevus which covers the anterior iris, or by pigmented pedunculated iris nodules. The pattern of the iris surface is smudged and matted. Iris atrophy is absent in 50% of cases and in the remainder is usually mild to moderate. Corectopia may be severe.

All the ICE syndromes share a common underlying pathophysiology and can all be considered to be primary proliferative endothelial degenerations.5 The corneal endothelium has a fine beaten-silver appearance. This, along with ensuing corneal oedema, is a cause of vision reduction in these patients. The endothelium is most affected in essential iris atrophy.

It appears that the endothelial cells undergo a metaplastic transformation into "epithelial-like" cells that migrate in a membrane form over the anterior chamber angle to the iris. Subsequent contraction of the membrane pulls the iris toward the cornea with a chronic progressive synechial closure of the angle. This can result in secondary angle closure without pupil block. The cellular membrane may also cause aqueous outflow blockage in the absence of peripheral anterior synechiae.

Treatment

Management of ICE syndromes is case specific and should be dictated by the degree of corneal oedema and severity of the secondary glaucoma.

Topical aqueous suppressants are the medical mainstay for management of glaucoma secondary to ICE syndromes. Medications that stimulate aqueous outflow are typically less effective and should not be used. Also, laser trabeculoplasty is not seen as effective. In severe cases, trabeculectomy may be necessary, though there is a risk of closure of the sclerotomy site by the abnormal membranes, with subsequent surgeries required. Trabeculectomy with antifibrotic agents had a survival of 73% at 1 year, 44% at 3 years, and 29% at 5 years.6 Glaucoma surgical implant devices may be necessary for this reason. Glaucoma drainage implants had a survival of 71% at 1 year, 71% at 3 years, and 53% at 5 years.6

Corneal oedema can be treated by hypertonic gels and by lowering IOP. Lubricants may improve comfort if bullous keratopathy develops. However, despite adequate IOP control, corneal oedema may persist due to the endotheliopathy. In these cases, penetrating keratoplasty may be necessary to restore vision, though this procedure will not affect abnormalities in the iris or anterior chamber angle.

References

1. Shields MB. Progressive essential iris atrophy, Chandler's syndrome, and the iris nevus (Cogan-Reese) syndrome: a spectrum of disease. Surv Ophthalmol 1979; 24: 3-20.

2. Huna R, Barak A, Melamed S. Bilateral iridocorneal endothelial syndrome presented as Cogan-Reese and Chandler's syndrome. J Glaucoma 1996; 5: 60-2.

3. Eagle RC Jr, Font RL, Yanoff M, Fine BS. Proliferative endotheliopathy with iris abnormalities. The iridocorneal endothelial syndrome. Arch Ophthalmol 1979; 97: 2104-11.

4. Alvarado JA, Underwood JL, Green WR, Wu S, Murphy CG, Hwang DG, Moore TE, O'Day D. Detection of herpes simplex viral DNA in the iridocorneal endothelial syndrome. Arch Ophthalmol 1994; 112: 1601-9.

5. Langova A, Praznovska Z, Farkasova B. Progressive essential atrophy of the iris as a form of the iridocorneal endothelial (ICE) syndrome. Cesk Slov Oftalmol 1997; 53: 371-80.

6. Doe EA, Budenz DL, Gedde SJ, Imami NR. Long-term surgical outcomes of patients with glaucoma secondary to the iridocorneal endothelial syndrome. Ophthalmology 2001; 108: 1789-95.