approaches such as pars plana vitrectomy with panretinal endolaser and filtration surgery,156 the outlook for greater surgical success in treating neovascular glaucoma in the short-to-medium term appears brighter.

Iridocorneal endothelial syndrome

The iridocorneal endothelial (ICE) syndrome takes many clinical forms but usually includes some combination of iris atrophy, corneal edema, and secondary angle-closure glaucoma without pupillary block. This syndrome is caused by an abnormal corneal endothelium that forms a membrane over the anterior surface of the iris and the angle structures.When this membrane contracts, it distorts the iris and closes the angle (Fig. 16–5).158

Histopathology

Histopathologic examination of eyes affected by the ICE syndrome

reveals a thin, abnormal corneal endothelium and Descemet’s membrane separated by a thick accumulation of collagen.159–161 These

tissues form a multilayered membrane that covers the angle and extends onto the anterior surface of the iris.162–165 The endothe-

lial cells develop the epithelial-like characteristics of desmosomes,

microvilli, tonofilaments (contractile elements), and proliferation – none of which occur in normal corneal endothelium.166,167 Most

authorities believe this to be a metaplasia of endothelium into cells with epithelial characteristics, from an unknown trigger.168 These histopathologic changes are manifest on clinical examination by a ‘beaten silver’ appearance to the endothelium on slit-lamp examination; a loss of the normal, regular endothelial mosaic on specular reflection; and alterations in the size and shape of endothelial cells on specular microscopy.169 The size and shape of endothelial cells show great variation – some may be necrotic, and the findings are often patchy in the early stages of the condition. Even with the variation in clinical presentation, the endothelial findings are usually there if looked for carefully enough.

Pathogenesis

The most commonly accepted theory on the pathogenesis of the ICE syndrome proposes that the fundamental defect is in the corneal endothelium, whose dysfunction results in corneal edema. Furthermore, the corneal endothelium in this condition elaborates a membrane which causes a secondary angle closure. When the membrane contracts, it forms PAS leading to glaucoma, as well as iris defects such as corectopia, ‘stretch holes’, and iris nodules. Ischemia may be a secondary phenomenon producing ‘melt holes.’

At present we do not understand what causes the corneal endothelium to behave in this unusual manner. A few investigators170,171

postulate that there is an abnormal proliferation of neural crest cells or a fetal crest of epithelial cells.172 Other authorities173 suggest the endothelium proliferates because of inflammation. Electron micrographic, immunohistochemical, and serologic studies have suggested herpes simplex virus174 and, in another laboratory, Epstein-Barr virus.175 The viral theory is attractive and might explain the unilaterality of this syndrome in the vast majority of patients. In the past

it was proposed that the ICE syndrome was a primary iris defect or that the disease occurred because of vascular insufficiency.176,177

These latter theories no longer seem tenable.

Clinical presentation

The PAS are more extensive in the quadrant toward which the pupil is displaced. The iris in the opposite quadrant has thinner stroma and full-thickness holes in some cases. In the Cogan-Reese

(A)

(B)

(C)

(D)

Fig. 16–5  Schematic view of iridocorneal endothelial syndrome.

(A) Membrane forms in one area of angle. (B) Additional areas of angle are involved, and contraction of membrane displaces pupil. (C) As membrane contracts, iris thins and peripheral anterior synechiae form. (D) Almost total closure of angle with thinning of iris, pupillary displacement, and hole formation.

(Modified from Shields MB: Surv Ophthalmol 24:3, 1979.157)

syndrome, pigmented lesions project anteriorly from the iris surface and are surrounded by the multilayered membrane.The nodules are actually small portions of iris stroma that have been pinched off by the membrane.

Within the spectrum of the ICE syndrome there are three wellcharacterized clinical entities – progressive iris atrophy, Chandler’s syndrome, and Cogan-Reese syndrome – as well as a variety of intermediate forms.157 All of the variants of this syndrome appear

(A)

(B)

Fig. 16–6  (A) Early essential iris atrophy. (B) Goniophotograph of characteristic peripheral anterior synechia associated with iridocorneal endothelial syndrome.

in early to mid adult life,178–180 occur in whites more often than blacks, and affect women more commonly than men.181 The patients usually are seen after noticing a change in the appearance of their iris or pupil, a disturbance in their vision, or mild ocular discomfort. Although there are a few reports of familial cases,182 in most individuals the medical and family histories are unrevealing. The ICE syndrome almost always involves one eye, although the

fellow eye may have subclinical abnormalities of the iris or corneal endothelium.183,184 Furthermore, there have been a few well-

documented reports of individuals with bilateral involvement.185–188 Some degree of corneal endothelial abnormality is usually seen on slit-lamp examination in most patients with abnormal specular microscopy in all.

Progressive (essential) iris atrophy

In progressive iris atrophy (known as essential iris atrophy in the past) the clinical picture is dominated by corectopia and progressive dissolution of the iris (Fig. 16–6).189 The iris dissolution begins as a patchy disappearance of the stroma and progresses to full-thickness holes (Fig. 16–7). Some of the holes occur in quadrants away from the direction of pupillary displacement and are thought to be caused by traction (‘stretch holes’). Other holes occur without corectopia and are ischemic in nature (‘melt holes’), as demonstrated on fluorescein angiography of the iris. Broad patchy PAS

Fig. 16–7  Advanced essential iris atrophy with polycoria.

form attachments anterior to Schwalbe’s line.The synechiae lift the iris off the surface of the lens, and also produce ectopion uveae and corectopia. Depending on the distribution of the synechiae, the pupil can be displaced to one side or pulled into a pear, oval, or slit shape. As the PAS become more extensive, IOP rises. The severity of the glaucoma is usually related to the extent of the synechiae. On occasion, elevated IOP is noted despite open angles; in this situation the membrane has covered the angle but not yet contracted to form permanent adhesions. The corneal endothelium may appear normal but more often has the appearance of tiny guttata.The cornea may become edematous when IOP is elevated.

Chandler’s syndrome

Chandler’s syndrome is the most common variant of the ICE syndrome. The most prominent features of Chandler’s syndrome are corneal endothelial dysfunction and corneal edema.190 The endothelium has a hammered silver appearance that is similar to, but less coarse than, the abnormalities seen in Fuchs’ dystrophy. On specular microscopy the endothelial cells appear pleomorphic

with dark cytoplasmic areas and loss of the normal hexagonal patterns.191,192 Early in the course of the disease specular microscopy

may demonstrate normal and abnormal endothelial areas. With time, the normal areas diminish in size.193,194 Specular microscopy

also helps to distinguish early Chandler’s syndrome from posterior polymorphous dystrophy, which has some clinical similarities.195 The corneal endothelium becomes so dysfunctional that epithelial edema develops at normal or only slightly elevated IOPs. In contrast to the marked corneal changes, the iris involvement is generally mild and limited to superficial stromal dissolution. Corectopia is minimal or absent. Peripheral anterior synechiae form, but they are not as diffuse and do not extend as far anteriorly as in progressive iris atrophy. For this reason glaucoma is often mild.

Cogan-Reese syndrome

The Cogan-Reese, or iris nevus, syndrome is differentiated from progressive iris atrophy and Chandler’s syndrome by the occur-

rence of pigmented lesions of the iris.196 Some eyes have pedunculated iris nodules,197,198 other eyes have diffuse pigmented lesions,

and still others have both. The pigmented iris lesions may appear years after the other features of the syndrome and then may disappear spontaneously.199 These are definitively not nevi: instead, they