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OCULAR ONCOLOGY CASES FROM COLE

Section Editor: Arun D. Singh, MD

Iridocorneal
Endothelial Syndrome
This disease is often misdiagnosed as an iris tumor.
BY ELISABETH P. APONTE, MD; ROBERT M. STERN, MD;
BRANDY C. HAYDEN, BS C , ROUB; AND ARUN D. SINGH, MD
CASE PRESENTATION
A 76-year-old white man was referred to our clinic for
evaluation of a pigmented lesion that recently increased in
size. He had first noticed the abnormal iris pigmentation
of his right eye 20 years ago and had been under observation for the previous 5 years. The patient denied any ocular or systemic symptoms; his past medical history was significant for cataracts in both eyes and hypertension.
On examination, the patients visual acuity was 20/70 in
the right eye and 20/60 in the left. The IOP was 20 mm Hg
in both eyes. The eyelids and conjunctiva were normal bilaterally. Anterior segment examination of his left eye revealed
map-dot-fingerprint dystrophy of the left corneal epithelium. The right eye was remarkable for corectopia and oval
elongation of the pupil (Figure 1). There was evidence of
pigmentary migration from the posterior margin of the iris,
across the anterior surface, and into the nasal limbal cornea.
The cornea appeared to be decompensated near the
3-oclock limbus, corresponding to an area of calcium
deposits. Peripheral anterior synechiae extended from the
2- to the 5-oclock position, with evidence of iridoschisis
inferior nasally. A gonioscopic evaluation confirmed the
presence of broad-based anterior synechiae (Figure 2).
Vascularization of the iris or angle was absent. There was no
evidence of an iris or ciliary body mass, either on clinical
examination or by ultrasound biomicroscopy (Figure 3). The
dilated fundus examination was normal in both eyes.
The clinical findings were diagnostic of iridocorneal
endothelial (ICE) syndrome.
DISCUSSION
The term ICE syndrome was first used by Yanoff in 1979
to describe a group of disorders with similar iris, corneal,
and angle abnormalities.1 It affects women predominantly
and is usually diagnosed between the ages of 30 and
50 years.2 The underlying mechanism is the migration of
corneal endothelial cells across the trabecular meshwork
into the iris, causing contraction and distortion of the

Figure 1. Anterior segment photography of the right eye


showing pupillary distortion and iridoschisis with an area of
calcium deposits in the cornea (low magnification [A]; high
magnification [B]).

Figure 2. Gonioscopic evaluation showed broad-based


anterior synechiae (arrow).

pupil and iris. The stimulus for this phenomenon is


unknown. Some have speculated that ICE syndrome is
secondary to a viral infection such as herpes simplex virus
or Epstein Barr virus.3 Others believe it to be a result of
neural crest cell abnormality or embryonic ectopia.4
Patients with ICE syndrome are asymptomatic in the
early stages and present with significant visual loss in later
stages secondary to corneal dysfunction or glaucoma.
The syndrome has three variants, namely iris nevus
(Cogan-Reese) syndrome, Chandler syndrome, and essential iris atrophy.5 Although the presentations of the three
SEPTEMBER 2010 ADVANCED OCULAR CARE 31

OCULAR ONCOLOGY CASES FROM COLE

Figure 3. Ultrasound biomicroscopy demonstrated anterior


synechiae with iridoschisis (arrow). Note the absence of an
iris mass.

variants overlap, Cogan-Reese is characterized by the


presence of pigmented nodules on the iris along with
variable changes of the iris and cornea, which are also
seen in the other two variants.6 Patients with Chandler
syndrome generally have fewer marked iris changes but
more corneal edema than essential iris atrophy. Essential
iris atrophy, first described in the early 1900s, is a progressive deformity of the iris and pupil associated with
corneal edema and glaucoma. The distinction between
the three variants of ICE syndrome is not crucial, but differentiating this syndrome from an iris melanoma is
essential.
The diagnosis of ICE syndrome is clinical and may be
confirmed by specular microscopy in which ICE cells can
be identified. These consist of unusually large and pleomorphic endothelial cells with prominent hyperreflective
nuclei. The endothelial cells body is normally light, and the
cell junction is dark; ICE cells, however, have dark-light
reversal in which the cell body is darker than the cell junction, a feature of epithelial cells.5 On histopathology, these
ICE cells have shown an epithelial phenotype because of
their coexpression of cytokeratin and vimentin and possession of microvilli and desmosomes.2,7,8 Our patients specular microscopy showed slightly pleomorphic endothelial
cells but did not have the hyperreflective nuclei or darklight reversal described in some reports (Figure 4).
CONCLUSION
ICE syndrome is a progressive and incurable disease.
However, many treatment regimens exist for the sequelae, namely unilateral glaucoma, which occurs in approximately 50% of patients with ICE syndrome and corneal
32 ADVANCED OCULAR CARE SEPTEMBER 2010

Figure 4. Specular microscopy showed slightly pleomorphic


endothelial cells but did not have the hyperreflective nuclei
or dark-light reversal described in some patients with ICE
syndrome.

edema.9 Glaucoma is often treated with topical drops to


lower the IOP by decreasing the production of aqueous
humor. Glaucoma filtering surgeries such as trabeculectomy or shunts are often needed. When corneal edema
becomes clinically significant, patients may be eligible for
a corneal transplant.
Section Editor Arun D. Singh, MD, is director
of the Department of Ophthalmic Oncology at
the Cole Eye Institute, Cleveland Clinic
Foundation. Dr. Singh may be reached at (216)
445-9479; singha@ccf.org.
Elisabeth P. Aponte, MD, is a resident at the
Cole Eye Institute, Cleveland Clinic Foundation.
Dr. Aponte may be reached at apontee@ccf.org.
Brandy C. Hayden, BSc, ROUB, is the manager of diagnostic imaging at the Cole Eye
Institute, Cleveland Clinic.
Robert M. Stern, MD, is the division chief of ophthalmology at St. John Medical Center, Cleveland. Dr. Stern may be
reached at (440) 835-6255; rms@sterneyes.com.
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