This document discusses iridocorneal endothelial syndrome (ICE), a rare disorder involving the corneal endothelium and iris. There are three clinical variants: Chandler syndrome, essential/progressive iris atrophy, and iris nevus/Cogan-Reese syndrome. The pathophysiology involves transformation of endothelial cells into migratory epithelial-like cells, resulting in corneal edema, iris changes, and secondary glaucoma. Diagnosis involves examining the cornea for edema and irregularity, the iris for atrophy or nodules, and gonioscopy for peripheral anterior synechiae. Specular microscopy can also reveal characteristic endothelial cell changes.

1. IRIDOCORNEAL
ENDOTHELIAL SYNDROME
PRESENTER: DR. IDDI NDYABAWE
Mmed Ophthalmology Year 1, Makerere University
MODULATOR: DR OTITI JULIET
DATE: 02/11/2020

2. INTRODUCTION
• Iridocorneal Endothelial Syndrome (ICE) syndrome is a unique
ophthalmic disorder that involves an irregular corneal endothelium
that can lead to varying degrees of corneal edema, iris atrophy, and
secondary angle-closure glaucoma.
• ICE syndrome is a group of disorders with three clinical variants:
• Chandler Syndrome
• Essential / Progressive Iris Atrophy
• Iris Nevus / Cogan-Reese Syndrome

3. PATHOPHYSIOLOGY
• corneal endothelium has a "hammered silver" or "beaten bronze"
appearance in ICE syndrome patients, similar to corneal guttae seen
in Fuchs Corneal Endothelial Dystrophy
• On a pathological level, it is felt that the normal endothelial cells have
been replaced with a more epithelial-like cell with migratory
characteristics.
• Transmission and Scanning Electron Microscopic examination of these
cells has demonstrated a population of well-differentiated cells with
epithelial features such as desmosomes, tonofilaments, and microvilli

4. PATHOPHYSIOLOGY
• The altered endothelium migrates posteriorly, moving beyond
Schwalbe's line, onto the trabecular meshwork, and at times, onto
peripheral iris.
• Contraction of this tissue within the angle and on the iris results in
the high peripheral anterior synechiae (PAS) and iris changes
characteristic of ICE syndrome.
• Secondary angle-closure glaucoma is a consequence of high PAS, but
can at times occur without overt synechiae because the advancing
corneal endothelium can functionally close the angle without
contraction.

6. .
• As a result, patients may initially present with what appears to be
open-angle glaucoma because the fibrovascular membrane
obstructing aqueous flow can be difficult to visualize with gonioscopy.
• The corneal edema found in ICE syndrome patients is thought to be
secondary to both elevated intraocular pressure (IOP) from secondary
angle-closure glaucoma, and from subnormal pump function from the
altered corneal endothelial cells. This can be found in any of the three
clinical variants, but is more common in patients with Chandler
syndrome.

7. ETIOLOGY
• The true etiology of ICE syndrome is not well understood.
• It has been theorized that an underlying viral infection with Herpes
simplex virus (HSV) or Epstein-Barr virus (EBV) leads to a low grade
inflammation at the level of the corneal endothelium, resulting in its
unusual epithelial-like activity
• Polymerase Chain Reaction (PCR) testing of corneal endothelial cells
from ICE syndrome patients has been found to have high percentages
of HSV DNA in comparison to normal controls.[6]

8. EPIDEMIOLOGY
• ICE syndrome is considered sporadic in presentation,
• no consistent association to other ocular or systemic disease, and
familial cases have been very rare.
• It presents as a unilateral disease,
• more common in women, between the ages of 20 and 50
• ICE syndrome must be considered within the differential diagnosis for
any young to middle-aged patient presenting with unilateral
glaucoma, corneal decompensation, and / or iris atrophy.

9. Clinical diagnosis and evaluation
The initial presentation of ICE syndrome patients may be:
• monocular pain (from corneal edema or elevated intraocular pressure from angle-
closure),
• blurry vision,
• or iris changes.
• Patients require a full ophthalmic work-up, with assessment of visual acuity and
refractive error, intraocular pressure, and slit-lamp examination, dilated fundus
examination, and gonioscopic examination.
• Close evaluation of the cornea should be done to assess for corneal edema and corneal
endothelial irregularity (a 'beaten bronze' or 'hammered silver' appearance when viewed
in specularly reflected light with the slit lamp).
• Iris changes (such as heterochromia, ectropion uveae, corectopia, hole formation, and
iris atrophy) may be evident on slit-lamp examination. Exam with gonioscopy may show
high PAS extending above Schwalbe line, which is pathognomonic for ICE syndrome.

14. CHANDLER’S SYNDROME
This is the most common of the three sub-types, representing
approximately 50% of all cases if ICE syndrome.
Of the three, Chandler Syndrome typically presents with a greater
degree of corneal pathology with associated corneal edema.
The edema can be microcystic, even with a normal intraocular pressure
(this is common of all three variants).
The iris findings are less common, and a majority of patients have no
iris changes at all, making the diagnosis a challenge

15. .

16. Essential / Progressive Iris Atrophy
• The iris findings of this variant can be quite robust and progressive
over time.
• Polycoria, corectopia, iris hole formation, ectropion uveae, and iris
atrophy are all common findings at the time of examination.

18. Iris Nevus / Cogan-Reese Syndrome
• This variant of ICE syndrome is distinguished by its unique iris
findings. The anterior surface of iris has tan pedunculated nodules or
diffuse pigmented lesions.[1] However, iris atrophy is uncommon with
these particular patients.

20. Diagnostic testing
• Specular microscopy is an important diagnostic tool, as the corneal
endothelium has a characteristic appearance in ICE syndrome
patients.
• Asymmetric endothelial cell loss and atypical endothelial cell
morphology is typically evident, which appears on a specular
photomicrograph as dark, larger than normal endothelial cells, with a
bright central spot.
• The endothelial cells have also been described to appear as dark
areas with central highlights and light peripheral borders

22. .
• These corneal endothelial cells are felt to be pathognomonic for ICE
syndrome, and have hence been referred to as "ICE cells" when seen
on specular photomicrographs
• Resulting corneal edema can be quantified with a pachymeter at each
visit

23. .
• Routine evaluation for glaucoma in these patients should be done by
measuring intraocular pressure and evaluating the angle for PAS with
gonioscopy.
• Greater diagnostic evaluation for glaucoma can be accomplished with
common testing devices utilized for any glaucoma patient.
• Stereo disc photographs and visual field analysis (Humphrey or
Goldmann), along with optic nerve and nerve fiber layer assessment
(heidelberg retinal tomogram (HRT) or optical coherence tomography
(OCT)), can all be implemented in the initial work-up and ongoing
evaluation for glaucoma progression in these patients

24. GONIOSCOPY FINDINGS

25. .