M. Bruce Shields,
Sarwat Salim
HISTORIC BACKGROUND AND TERMINOLOGY
During the latter part of the nineteenth century, a number of isolated case reports appeared in the literature describing a uniocular condition that was characterized by striking abnormalities of the iris, with corectopia, iris atrophy, and occasional hole formation. Some patients had additional findings that included glaucoma and corneal edema. However, it was not until a report by Harms[1] in 1903 that these disorders became recognized as a discrete entity. Because the iris abnormalities were the most striking feature and because the pathogenesis was unknown, the condition became known as essential iris atrophy.
Many reports of essential iris atrophy appeared in the literature during the first half of the twentieth century. During the second half of that century, additional reports appeared, suggesting that essential iris atrophy might be only one variation of a broader spectrum of disorders. In 1956, Chandler[2] described patients with a similar form of uniocular glaucoma, who differed from those with essential iris atrophy by having mild or absent iris changes but more frequent corneal edema. In 1969, Cogan and Reese[3] reported two patients with uniocular features resembling those described by Harms and Chandler but differing by the additional finding of pigmented nodules on the iris.
In 1978, Campbell and associates[4] postulated that these various clinical conditions were linked by a common abnormality of the corneal endothelium, which was responsible for the corneal edema as well as the iris changes and glaucoma. This theory was supported by clinical and histopathologic studies.[5,6] The term iridocorneal endothelial (ICE) syndrome was proposed to encompass this spectrum of disease.[6] Within this spectrum, three clinical variations have been distinguished, primarily on the basis of iris changes.
CLINICAL VARIATIONS
PROGRESSIVE IRIS ATROPHY
This clinical variation of the ICE syndrome was originally referred to as essential iris atrophy or progressive essential iris atrophy. However, since the iris atrophy is not the essential or primary feature of the disease, the term progressive iris atrophy is more commonly used. As with all forms of the ICE syndrome, corneal edema and associated glaucoma with characteristic peripheral anterior synechia may be present. The distinguishing feature of this clinical variation, however, is the extreme atrophy of the iris with hole formation.
CHANDLER'S SYNDROME
The variation described by Chandler[2] subsequently became known as Chandler's syndrome. The corneal edema occurs somewhat more frequently in this variation, but the changes in the iris are limited to slight corectopia and mild stromal atrophy, or they may be absent altogether. Intermediate variations between progressive iris atrophy and Chandler's syndrome may also be seen, in which changes in the iris are more extensive than the latter condition but lack the hole formation of the former variation.
COGAN-REESE SYNDROME
Since the report by Cogan and Reese,[3] it has been confirmed that pigmented nodules of the iris may occur throughout the complete spectrum of the ICE syndrome.[7,8] This clinical variation has become known as the Cogan-Reese syndrome. Similar cases have been described with diffuse nevi, rather than nodules, on the surface of the iris, which has been referred to as the iris nevus syndrome.[7] There has been a tendency to group the Cogan-Reese syndrome and iris nevus syndrome together as variations of the ICE syndrome. However, the iris lesions of the two conditions are clinically and histologically different, and there is insufficient evidence to include the iris nevus syndrome as a clinical variation of the ICE syndrome.
In one study of 37 consecutive cases of the ICE syndrome, Chandler's syndrome was the most common clinical variation, accounting for 21 cases (56%), with the remaining cases being equally divided between the other two major clinical variations (Table 208.1).[9] However, in a study of 60 consecutive Thai patients with the ICE syndrome, 38 had the Cogan-Reese variation, 14 had Chandler's syndrome and eight had progressive iris atrophy.[10]
TABLE 208.1 -- Major Clinical Variations
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Names |
Characteristic Features |
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Progressive iris atrophy |
Iris features predominate, with marked corectopia, atrophy, and hole formation |
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Chandler's syndrome |
Changes in the iris are mild to absent, whereas corneal edema, often at normal intraocular pressure, is typical |
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Cogan-Reese syndrome |
Nodular, pigmented lesions of the iris are the hallmark and may be seen with the entire spectrum of corneal and other iris defects |
GENERAL FEATURES OF PATIENTS
It is important to recognize that these clinical variations represent only minor differences within a common spectrum of disease. Although subtle differences with regard to the frequency and severity of corneal edema and associated glaucoma have been recognized among the clinical variations, all patients with the ICE syndrome share the following general features.
Clinically, the condition is almost always uniocular, although subclinical abnormalities of the corneal endothelium are seen in the fellow eye of some patients and rare, fully manifested bilateral cases have been reported.[11,12] The syndrome is usually recognized in early to middle adulthood, although the very rare occurrence in a child has been reported.[13] There is a predilection for women. Familial cases are rare, and there is no consistent association with any other ocular or systemic disorder.
The most common presenting manifestations are abnormalities of the iris, reduced visual acuity, and pain. Some patients may be prompted to seek medical attention because they notice a displacement of the pupil or a dark spot on the iris, which usually represents the atrophy or hole formation. Other patients may first notice reduced vision in the involved eye. This occurs typically in the morning, when the corneal edema is more severe, and subsides during the day, as exposure to air dehydrates the cornea. In more advanced cases, the patient may have chronic reduction in vision from corneal edema or glaucomatous optic atrophy. The pain is usually due to corneal edema and much less commonly to elevated intraocular pressure (IOP).
CLINICOPATHOLOGIC FEATURES
CORNEA
A common feature throughout the ICE syndrome is a corneal endothelial abnormality, which Chandler[2] described by slit-lamp examination as having a fine-hammered silver appearance of the posterior cornea, similar to that of Fuchs' dystrophy but less coarse (Fig. 208.1). Specular microscopy of the corneal endothelium reveals a characteristic, diffuse abnormality with variable degrees of pleomorphism in size and shape; dark areas within the cells, except for a light central spot and a light peripheral zone; and loss of the clear hexagonal margins (Fig. 208.2).[14,15] These cells have been called ICE cells and may be scattered among large endothelial cells with vague margins (disseminated ICE) or may occur in clusters of continuous cells, called ICE tissue, which may cover the entire posterior corneal surface (total ICE) or may be adjacent to endothelium composed of distinct small cells (subtotal ICE +) or larger than normal cells (subtotal ICE-).[15] The more normal areas may gradually disappear,[16,17] although, rarely, normal endothelium may replace the ICE tissue.[17] Specular microscopy is invaluable in estimating the diagnosis of ICE syndrome, although one study found that it is not a reliable predictor for the risk of corneal edema or elevated IOP.[18] In any case, these characteristic abnormalities of the corneal endothelium are present in all clinical variations of ICE syndrome and constitute the strongest evidence for a spectrum of disease.
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FIGURE 208.1 Slit-lamp view shows the fine-beaten silver appearance of the corneal endothelial abnormality (arrows) in the ICE syndrome. |
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FIGURE 208.2 Specular microscopic appearance of corneal endothelial cells in the ICE syndrome show pleomorphism in size and shape, dark areas within the cells, and loss of clear hexagonal margins. |
In many patients with ICE syndrome, the corneal endothelial abnormality may cause no symptoms. In other cases, it may cause corneal edema with variable degrees of reduced vision and pain, as described earlier. In some patients, the persistent corneal edema may lead to marked reduction in visual acuity, frequently requiring penetrating keratoplasty. The corneal edema may be aggravated by elevated IOP, although other patients may have edema with pressures that are normal or only slightly elevated. A slight reduction in endothelial cell count and mild cellular pleomorphism may be observed in the fellow eye of some patients,[19,20] although this is almost always asymptomatic and fully manifested bilateral cases of ICE syndrome are rare.[11,12]
Electron microscopic studies of the posterior cornea in the ICE syndrome have revealed varied and complex alterations of cells, lining multilayered collagenous tissue posterior to a normal Descemet membrane (Fig. 208.3).[21-23] Descriptions of the cellular layer differ among reports, which may relate to the varied response of the corneal endothelium in this syndrome, even within different areas of the same eye. Immunohistochemical studies of ICE cells have shown cytokeratins, suggesting epithelial-like cells,[24-26] although cross-reaction with vimentin supports the hypothesis that the cells are of endothelial lineage.[26,27] Some ICE cells have evidence of metabolic activity or have undergone division. Filopodial processes and cytoplasmic actin filaments suggest that these cells are capable of migration.[22,23] In some specimens, the endothelial cells are present in multiple layers, suggesting a loss of contact inhibition.[22] Other specimens reveal a monolayer of reduced cell density with disrupted and necrotic cells and occasional acellular zones. Chronic inflammatory cells have also been observed in some cases,[22,23,28] with one study describing mononuclear inflammatory cells between ICE cells in the monolayer.[28]
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FIGURE 208.3 Transmission electron microscopic view of inner corneal surface in ICE syndrome shows part of an abnormal cell (arrow) on a four-layered membrane composed of the anterior nonbanded (1) and posterior-banded (2) portions of Descemet's membrane with abnormal compact collagenous (3) and loose collagenous (4) layers. ×6875. |
ANTERIOR CHAMBER ANGLE
The typical gonioscopic appearance of patients with ICE syndrome is that of broad peripheral anterior synechia, often extending to or beyond Schwalbe's line (Fig. 208.4). This finding does not differ significantly among the clinical variations of ICE syndrome by either gonioscopic or histologic examination. Histologic studies reveal a cellular membrane, consisting of a single layer of endothelial cells and a Descemet-like membrane, which is continuous with the cellular and collagenous layers of the posterior cornea. This membrane is usually seen in association with the peripheral anterior synechiae, although it may also be seen covering an otherwise open anterior chamber angle.
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FIGURE 208.4 Gonioscopic appearance in the ICE syndrome with broad peripheral anterior synechia extending beyond the trabecular meshwork. |
These changes in the anterior chamber angle are presumed to be the mechanism of the associated glaucoma in the ICE syndrome. Most patients with the ICE syndrome and glaucoma have extensive peripheral anterior synechia, although this does not correlate precisely with the glaucoma, and some patients may have an anterior chamber angle that appears to be entirely open. In the latter cases, the obstruction to aqueous outflow is presumably due to the membrane covering the trabecular meshwork. Although the anterior chamber angle alterations are seen in all variations of ICE syndrome, the associated glaucoma appears to be more severe with progressive iris atrophy and the Cogan-Reese syndrome.
IRIS
Although the abnormalities of the iris are the least significant with regard to visual impairment, they do constitute the primary basis for distinguishing the clinical variations within the ICE syndrome.
Progressive iris atrophy is characterized by marked atrophy of the iris, associated with variable degrees of corectopia and ectropion uvea (Fig. 208.5). The pupil is typically displaced toward the quadrant with the most prominent area of peripheral anterior synechia. The hallmark of progressive iris atrophy is hole formation of the iris, which occurs in two forms.[5] The most common form is a 'stretch hole', in which the iris is markedly thinned in the quadrant away from the direction of the pupillary distortion, with hole formation in the area that is being stretched. Less commonly, 'melting holes' develop without associated corectopia or iris thinning, and fluorescein angiographic studies suggest that this may be associated with ischemia of the iris.[8]
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FIGURE 208.5 Progressive iris atrophy, a variation of the ICE syndrome, with marked inferior corectopia and iris atrophy with multiple iris holes. |
The histopathologic characteristics of the iris in all variations of the ICE syndrome include a monolayer of cells, often with a Descemet-like membrane, on portions of the anterior iris surface, continuous with the similar layer that was described in the anterior chamber angle. These structures are most often found in the quadrant toward which the pupil is distorted.[4]
In some cases of Chandler's syndrome, the iris may appear entirely normal. The diagnosis may be difficult in these cases, and it should be emphasized that the corneal endothelium must always be examined carefully in cases of uniocular glaucoma. In most cases, however, patients with Chandler's syndrome have slight corectopia and mild atrophy of the iris stroma (Fig. 208.6). As previously noted, there are intermediate variations between Chandler's syndrome and progressive iris atrophy.
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FIGURE 208.6 Chandler's syndrome, a variation of the ICE syndrome, with irregular pupil and stromal iris atrophy. |
Patients with the Cogan-Reese syndrome may have any degree of iris abnormality from no corectopia or stromal atrophy to marked changes with hole formation. The distinguishing feature in these patients, however, is the presence of pigmented, pedunculated nodules on the surface of the iris (Fig. 208.7). In some cases, other features of the ICE syndrome may be present for many years before the nodules appear. Histologically, the nodules appear to consist of tissue similar to that in the underlying iris stroma, and they are always surrounded by the previously described cellular membrane.[4,6]
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FIGURE 208.7 Cogan-Reese syndrome, a variation of the ICE syndrome, with ectropion uvea and marked corectopia with iris atrophy, hole formation, and numerous dark nodules on the iris surface. |
The above-discussed clinicopathologic features are illustrated in Table 208.2.
TABLE 208.2 -- Clinicopathologic Features
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Structures |
Clinical Appearance |
Histopathologic Features |
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Cornea |
Fine-hammered silver appearance of posterior cornea in all cases |
Abnormal endothelial cells lining multilayered collagenous tissue posterior to Descemet's membrane |
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Corneal edema in some cases |
Stroma and epithelial edema associated with marked endothelial cell abnormality |
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Anterior chamber angle |
Associated glaucoma with open angle |
Single layer of endothelial cells and a Descemet-like membrane extending from the cornea across the open anterior chamber angle |
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Associated glaucoma with peripheral anterior synechia extending to or beyond Schwalbe's line |
Peripheral anterior synechia created by contracture of the cellular membrane |
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Iris |
Corectopia, ectropion uvea, and extensive iris atrophy with hole formation (progressive iris atrophy) |
Cellular membrane extends from the angle onto the iris, with subsequent contracture producing clinical findings |
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Normal iris or minimal corectopia and mild atrophy of the iris stroma (Chandler's syndrome) |
Normal iris or cellular membrane producing the milder clinical findings |
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Pigmented, pedunculated nodules on the iris surface with any degree of iris atrophy (Cogan-Reese syndrome) |
Nodules composed of tissue resembling the underlying iris stroma, surrounded by cellular membrane |
PATHOGENESIS
THEORIES OF ETIOLOGY
The precise cause of the ICE syndrome remains unknown. The absence of a positive family history suggests that the condition is acquired, rather than inherited. The onset in early to middle adulthood, as well as the histologic finding of a fully developed Descemet membrane, suggests that it is acquired at some point after birth. The finding of chronic inflammatory cells in corneal specimens has raised the possibility of a viral etiology,[22] although similar cells have been found in the endothelium of corneas with inherited diseases.[23] Using primer pairs and polymerase chain reaction methods, 16 of 25 corneas from ICE patients and four of six from patients with herpetic keratitis were positive for herpes simplex virus DNA but negative for herpes zoster and Epstein-Barr viruses.[29] All control corneas were negative for herpes simplex virus. These findings provide strong support for a viral etiology of the ICE syndrome.
THEORIES OF MECHANISM
The mechanism by which the corneal endothelial abnormality leads to the various changes in the ICE syndrome has been established with reasonable certainty. Campbell and associates[4] proposed a 'membrane theory' in which the endothelial defect not only causes the corneal edema in some patients but also leads to the proliferation of the previously described cellular membrane across the anterior chamber angle and onto the surface of the iris. The observation of filopodial processes, cytoplasmic actin filaments, and apparent loss of contact inhibition are all consistent with the concept of migrating cells. Subsequent contracture of the cellular membrane is believed to cause the formation of the peripheral anterior synechia as well as most, if not all, the iris changes. As the membrane in one quadrant contracts to create the peripheral anterior synechia and the corectopia and ectropion uvea toward the synechia, the iris in the opposite quadrant is put on stretch, especially when it is anchored by additional peripheral anterior synechiae in that quadrant. This stretching is considered to be the primary cause of the iris atrophy and hole formation, although other factors, such as ischemia, may also be involved.
The cellular membrane is also believed to be responsible for the development of the nodular lesions of the iris in the Cogan-Reese syndrome. It has been postulated that the membrane, as it grows across the iris, encircles and pinches off portions of the iris stroma to create the nodules.[4,30] As previously noted, the associated glaucoma in all variations of ICE syndrome is believed to be due to an obstruction of the trabecular meshwork by the peripheral anterior synechia or, less commonly, by the cellular membrane.
Each clinical variation is believed to have this same basic mechanism. In some cases, the difference in clinical features may simply result from the time at which the patient is seen. For example, a patient with the initial findings of Chandler's syndrome may later develop iris hole formation or nodules, changing the diagnosis to progressive iris atrophy or to the Cogan-Reese syndrome, respectively.
DIFFERENTIAL DIAGNOSIS
There are several disorders of the cornea or iris, many of which have associated glaucoma, that could be confused with the various forms of ICE syndrome. It may be helpful to think of these conditions in the following three categories: corneal endothelial disorders, dissolution of the iris, and nodular lesions of the iris (Table 208.3).
TABLE 208.3 -- Differential Diagnosis
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Categories |
Entities |
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Corneal endothelial disorders |
Posterior polymorphous dystrophy |
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Fuchs' endothelial dystrophy |
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Dissolution of the iris |
Axenfeld-Rieger syndrome |
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Aniridia |
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Iridoschisis |
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Nodular iris lesions |
Iris melanoma |
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Iris nevus syndrome |
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Neurofibromatosis |
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Nodular inflammatory disorders |
CORNEAL ENDOTHELIAL DISORDERS
Two conditions with primary endothelial abnormalities that might be confused with the ICE syndrome are posterior polymorphous dystrophy and Fuchs' endothelial dystrophy. In the former, the differential diagnosis is further compounded by the fact that a small subset of these patients have anterior chamber angle and iris findings that resemble the ICE syndrome, as well as occasional associated glaucoma. However, the condition is bilateral and familial, and the clinical appearance of the corneal endothelial abnormality is more that of blisters or vesicles. The clinical appearance of the endothelial abnormality in Fuchs' dystrophy, in contrast, may be difficult to distinguish from that of ICE syndrome by slit-lamp biomicroscopy. However, this condition is typically bilateral and does not have the anterior chamber angle or iris features of the latter condition.
DISSOLUTION OF THE IRIS
Several conditions are characterized by changes in the iris that could be confused with that of the ICE syndrome. The condition with the most striking clinical and histopathologic similarities is the Axenfeld-Rieger syndrome. Patients with this syndrome typically have iridocorneal adhesions of the anterior chamber angle with associated glaucoma, as well as changes in the iris that are difficult to distinguish from those of the ICE syndrome. However, the bilateral and familial nature of the Axenfeld-Rieger syndrome allows a distinction to be made between these two conditions. Some advanced cases of progressive iris atrophy might resemble aniridia, in which a rudimentary stump of iris is present. Again, however, the latter condition is bilateral and congenital. Another condition associated with dissolution of the iris is iridoschisis, usually seen in elderly individuals. The iris changes in this condition, however, differ from those of the ICE syndrome by a separation of superficial layers of iris stroma.
NODULAR LESIONS OF THE IRIS
The nodular lesions of the Cogan-Reese syndrome may be confused with similar nodular iris lesions in a variety of additional conditions. Most important in this regard is to avoid mistaking the nodular lesions in the Cogan-Reese syndrome for melanoma of the iris. In most cases, the melanomas are larger and more diffuse than the small, pedunculated nodules of the Cogan-Reese syndrome. In other patients, iris nevi might be confused with iris nodules of the Cogan-Reese syndrome. As previously noted, a specific condition has been described as the iris nevus syndrome, in which additional features resembling the ICE syndrome might be present. Other patients may have iris melanosis, in which pedunculated nodules are difficult to distinguish from those of the Cogan-Reese syndrome, although this condition is typically bilateral and may be familial. Other conditions with nodules of the iris include neurofibromatosis and nodular inflammatory disorders, such as sarcoidosis.
MANAGEMENT
In the management of patients with the ICE syndrome, the primary concern has to do with the corneal edema and the associated glaucoma.
CORNEAL EDEMA
Mild corneal edema, especially with normal IOP, can often be controlled with hypertonic saline solutions. Some patients may also find it useful to allow the warm air of a hair dryer to blow toward their face in the morning to accelerate the dehydration of the cornea. Soft contact lenses may also be helpful in some cases of more persistent corneal edema. When IOP elevation is present, medical reduction of the pressure may also help to reduce the corneal edema. In severe cases, however, the corneal edema persists despite low pressures, and penetrating keratoplasty is often required.
ASSOCIATED GLAUCOMA
In the early stages of glaucoma associated with ICE syndrome, the IOP elevation can often be controlled medically, especially with drugs that reduce aqueous production, such as the ?-blockers, carbonic anhydrase inhibitors and a2 agonists. Miotics are rarely effective, owing to the mechanical obstruction of the trabecular meshwork, and the benefit of topical prostaglandins has yet to be established.
When the IOP can no longer be controlled medically, filtering surgery is usually indicated. Laser trabeculoplasty is not indicated in these cases. Patients with the ICE syndrome do reasonably well with glaucoma filtering surgery,[31] although multiple procedures are often needed.[32] Some patients have late failure owing to the endothelialization of the fistula.[33] In some cases, these can be reopened with application of a neodymium: yttrium-aluminum garnet laser. Adjunctive mitomycin-C may improve the success of trabeculectomy in patients with the ICE syndrome,[34] and aqueous shunts have been reported to be effective.[35] In the rare case of a child with the ICE syndrome, goniotomy may have a role.[13]
THE FUTURE
As our understanding of the cause and mechanism of the ICE syndrome expands, it may be possible to direct therapy more specifically at the underlying disease process. For example, if the viral theory is substantiated, early intervention with antiviral agents may retard the progressive endothelial cell damage.[29] It may also become possible to prevent the membrane proliferation with agents such as immunotoxins, which have been shown to inhibit the proliferation of corneal endothelium in tissue culture.[36]
REFERENCES
1. Harms C: Einseitige spontane Luckenbildung der Iris durch Atrophie ohne mechanische Zerrung. Klin Monatsbl Augenheilkd 1903; 41:522.
2. Chandler PA: Atrophy of the stroma of the iris: endothelial dystrophy, corneal edema, and glaucoma. Am J Ophthalmol 1956; 41:607.
3. Cogan DG, Reese AB: A syndrome of iris nodules, ectopic Descemet's membrane, and unilateral glaucoma. Doc Ophthalmol 1969; 26:424.
4. Campbell DG, Shields MB, Smith TR: The corneal endothelium and the spectrum of essential iris atrophy. Am J Ophthalmol 1978; 86:317.
5. Shields MB, Campbell DG, Simmons RJ: The essential iris atrophies. Am J Ophthalmol 1978; 85:749.
6. Eagle Jr RC, Font RL, Yanoff M, Fine BS: Proliferative endotheliopathy with iris abnormalities: the iridocorneal endothelial syndrome. Arch Ophthalmol 1979; 97:2104.
7. Scheie HG, Yanoff M: Iris nevus (Cogan-Reese) syndrome: a cause of unilateral glaucoma. Arch Ophthalmol 1975; 93:963.
8. Shields MB, Campbell DG, Simmons RJ, Hutchinson BT: Iris nodules in essential iris atrophy. Arch Ophthalmol 1976; 94:406.
9. Wilson MC, Shields MB: A comparison of the clinical variations of the iridocorneal endothelial syndrome. Arch Ophthalmol 1989; 107:1465.
10. Teekhasaenee C, Ritch R: Iridocorneal endothelial syndrome in Thai patients. Clinical variations. Arch Ophthalmol 2000; 118:187.
11. Huna R, Barak A, Melamed S: Bilateral iridocorneal endothelial syndrome presented as Cogan-Reese and Chandler's syndrome. J Glauc 1996; 5:60.
12. DesMarchais B, Simmons RB, Simmons RJ, Shields MB: Bilateral Chandler's syndrome. J Glauc 1999; 8:276.
13. Salim S, Walton DS: Iridocorneal Endothelial Syndrome in a Child. J Pediatr Ophthalmol Strabismus (in press).
14. Hirst LW, Quigley HA, Stark WJ, Shields MB: Specular microscopy of the iridocorneal endothelial syndrome. Am J Ophthalmol 1980; 89:11.
15. Sherrard ES, Frangoulis MA, Kerr Muir MG, Buckley RJ: The posterior surface of the cornea in the irido-corneal endothelial syndrome: a specular microscopic study. Trans Ophthalmol Soc UK 1985; 104:766.
16. Bourne WM: Partial corneal involvement in the iridocorneal endothelial syndrome. Am J Ophthalmol 1982; 94:774.
17. Bourne WM, Brubaker RF: Progression and regression of partial corneal involvement in the iridocorneal endothelial syndrome. Am J Ophthalmol 1992; 114:171.
18. Liu Y-K, Wong I-J, Hu F-R, et al: Clinical and specular microscope manifestations of iridocorneal endothelial syndrome. Jpn J Ophthalmol 2001; 45:281.
19. Kupfer C, Kaiser-Kupfer MI, Datiles M, McCain L: The contralateral eye in the iridocorneal endothelial (ICE) syndrome. Ophthalmology 1983; 90:1343.
20. Lucas-Glass TC, Baratz KH, Nelson LR, et al: The contralateral corneal endothelium in the iridocorneal syndrome. Arch Ophthalmol 1997; 115:40.
21. Shields MB, McCracken JS, Klintworth GK, Campbell DG: Corneal edema in essential iris atrophy. Ophthalmology 1979; 86:1533.
22. Alvarado JA, Murphy CG, Maglio M, Hetherington J: Pathogenesis of Chandler's syndrome, essential iris atrophy, and the Cogan-Reese syndrome. I. Alterations of the corneal endothelium. Invest Ophthalmol Vis Sci 1986; 27:853.
23. Rodrigues MM, Stulting RD, Waring GO III: Clinical, electron microscopic, and immunohistochemical study of the corneal endothelium and Descemet's membrane in the iridocorneal endothelial syndrome. Am J Ophthalmol 1986; 101:16.
24. Kramer TR, Grossniklaus ME, Vigneswaran N, et al: Cytokeratin expression in corneal endothelium in the iridocorneal endothelial syndrome. Invest Ophthalmol Vis Sci 1992; 33:3581.
25. Levy SG, McCartney ACE, Baghai MH, et al: Pathology of the iridocorneal-endothelial syndrome - the ICE cell. Invest Ophthalmol Vis Sci 1995; 36:2592.
26. Hirst LW, Bancroft J, Yamauchi K, Green WR: Immunohistochemical pathology of the corneal endothelium in iridocorneal endothelial syndrome. Invest Ophthalmol Vis Sci 1995; 36:820.
27. Howell DN, Damms T, Burchette Jr JL, Green WR: Endothelial metaplasia in the iridocorneal endothelial syndrome. Invest Ophthalmol Vis Sci 1997; 38:1896.
28. Lee WR, Marshall GE, Kirkness CM: Corneal endothelial cell abnormalities in an early stage of the iridocorneal endothelial syndrome. Br J Ophthalmol 1994; 78:624.
29. Alvarado JA, Underwood JL, Green WR, et al: Detection of herpes simplex viral DNA in the iridocorneal endothelial syndrome. Arch Ophthalmol 1994; 112:160.
30. Eagle Jr RC, Font RL, Yanoff M, Fine BS: The iris naevus (Cogan-Reese) syndrome: light and electron microscopic observations. Br J Ophthalmol 1980; 64:446.
31. Kidd M, Hetherington J, Magee S: Surgical results in iridocorneal endothelial syndrome. Arch Ophthalmol 1988; 106:199.
32. Doe EA, Budenz DL, Gedde SJ, Imani NR: Long-term surgical outcomes of patients with glaucoma secondary to the iridocorneal endothelial syndrome. Ophthalmology 2001; 108:1789.
33. Laganowski MC, Kerr Muir MG, Hitchings RA: Glaucoma and the iridocorneal endothelial syndrome. Arch Ophthalmol 1992; 110:346.
34. Lanzal IM, Wilson RP, Dudley D, et al: Outcome of trabeculectomy with mitomycin-C in the iridocorneal endothelial syndrome. Ophthalmology 2000; 107:295.
35. Kim DK, Aslanides IM, Schmidt Jr CM, et al: Long-term outcome of aqueous shunt surgery in ten patients with iridocorneal endothelial syndrome. Ophthalmology 1999; 106:1030.
36. Fulcher S, Lui G, Houston LL, et al: Use of immunotoxin to inhibit proliferating human corneal endothelium. Invest Ophthalmol Vis Sci 1988; 29:755.
