Iridocorneal endothelial syndrome

1. IRIDOCORNEAL
ENDOTHELIAL SYNDROME

2. • INTRODUCTION
• HISTORY
• EPIDEMIOLOGY
• ETIOPATHOGENESIS
• CLINICAL FEATURES
• D/D
• INVESTIGATIONS
• MANAGEMENT

3. INTRODUCTION
• Iridocorneal endothelial (ICE) syndrome is a rare
disorder characterized by proliferative and
structural abnormalities of the corneal
endothelium, progressive obstruction of the
iridocorneal angle, and iris anomalies such as
atrophy and hole formation
• The consequences of these changes are
corneal decompensation and glaucoma,
which represent the most frequent causes of
visual function loss in patients with ICE
syndrome

4. • ICE syndrome is a group of disorders with three
clinical variants:
• 1. Iris Nevus / Cogan-Reese Syndrome
• 2. Chandler Syndrome
• 3. Essential / Progressive Iris Atrophy
• Among the three clinical variants of ICE
syndrome, Chandler syndrome appears to be
the most common

5. HISTORY
• In 1903 Harms extensively described a rare ocular
condition characterized by iris atrophy and glaucoma,
known as “progressive essential iris atrophy”
• Five decades later, Chandler described a rare, unilateral
ocular condition characterized by iris atrophy associated
with corneal endothelial alterations, corneal edema, and
glaucoma
• Subsequently, it was suggested that this “Chandler
syndrome” and the “progressive essential iris atrophy”
are two different forms of the same disease

6. • When Cogan and Reese described a similar condition
associated with iris nodules, a third clinical entity was
identified and subsequently named “iris nevus” or
“Cogan-Reese syndrome”
• Subsequent studies confirmed that these clinical entities
show similar history and clinical findings and share the
same pathogenic mechanisms characterized by an
abnormal proliferation of corneal endothelium and the
unifying term of “iridocorneal endothelial syndrome”
was suggested by Yanoff

7. EPIDEMIOLOGY
• Sporadic in presentation
• No consistent association to other ocular or systemic
disease, and familial cases have been very rare
• Unilateral disease, more common in women, between
the ages of 20 and 50
• Prevalence of less than one per two lakh population
• Glaucoma is present in approximately half of all cases.

8. ETIOLOGY
• 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.
• The term ‘proliferative endotheliopathy’ has therefore
been suggested to describe this disorder
• 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

9. • In line with this hypothesis, ICE syndrome diseases are
usually monolateral acquired disorders, suggesting that
affected patients had one eye primarily affected with a
virus during the postnatal age and the other eye
protected by immune surveillance established a few
weeks after the first infection.

10. PATHOGENESIS
• On a pathological level, it is felt that the normal
endothelial cells have been replaced with a more
epithelial-like cell with migratory characteristics
• The altered endothelium migrates posteriorly, moving
beyond Schwalbe 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.

11. • 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
• The corneal edema found in ICE syndrome patients is
felt 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

13. CLINICAL FEATURES
• Patients may present with differing degrees of pain,
decreased vision, and abnormal iris appearance
• The vision may be decreased from corneal edema,
which may be worse in the morning and becomes
improved later in the day.
• Patients also may present with a chief complaint of an
irregular shape or position of the pupil (corectopia), or
they may describe a dark spot in the eye, which may
represent hole formation

14. • Various degrees of iris atrophy characterize each of
the specific clinical entities

15. Progressive (Essential) Iris Atrophy
• This variation is characterized by severe iris atrophy that
results in heterochromia, marked corectopia, ectropion
uveae, and pseudopolycoria (hole formation) that usually
occur in the direction toward the quadrant with the most
prominent area of peripheral anterior synechia
• There appear to be two forms of atrophic iris holes. With
stretch holes, the iris is markedly thinned in the
quadrant away from the direction of pupillary distortion,
and the holes develop within the area that is being
stretched. In other eyes, melting holes develop without
associated corectopia or thinning of the iris, which is
thought to occur due to ischemia of the iris based on iris
angiography

16. • Iridal hole formation is the hallmark finding of
progressive iris atrophy

17. Chandler’s Syndrome
• This variation shows minimal or no iris stromal atrophy,
but mild corectopia may be present. The corneal edema
and angle findings are the predominant and typical
features
Beaten bronze appearance/
Hammered silver appearance

18. Iris-Nevus Syndrome (Cogan-Reese Syndrome)
• The extent of iris atrophy tends to be variable and less
severe. Tan, pedunculated nodules may appear on the
anterior iris surface , the nodules seen are composed of
underlying iris stroma pinched off by abnormal cellular
membrane..

19. • Gonioscopic Findings
• Peripheral anterior synechia, usually extending to or
beyond the Schwalbe line, is another clinical feature
common to the ICE syndrome

20. • In rare cases, the retrocorneal membrane of the ICE
syndrome may grow over the anterior lens surface,
simulating the anterior lens capsule, which can create
confusion when performing a capsulorrhexis during
cataract surgery .
• This retrocorneal membrane can also appear on the
anterior surface of an intraocular lens implant

21. INVESTIGATIONS
• Gonioscopy: to see irido trabecular synechiae. It must
be kept in mind that the membrane obstructing the
trabecular meshwork may be initially difficult to visualize
by gonioscopy, and the patients’ condition may be
confused with a more common open-angle glaucoma.
• Ultrasound biomicroscopy (UBM) :useful tool for the
detection of changes of the anterior chamber angle
structures in ICE syndrome, especially in the presence of
corneal edema that does not allow gonioscopic
visualization

22. • 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 areas with central
highlights and light peripheral borders.
• 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.

23. • Specular microscopy of corneal endothelium in ICE syndrome. Cell borders are
obscured, resulting in loss of the normal endothelial mosaic. Note dark areas within
endothelial cells. Brighter reflections are believed to be from cell borders. B: Cornea,
ICE syndrome. Scanning electron microscopy demonstrates sharp demarcation
between abnormal (ICE) cells with microvilli and relatively unaffected endothelial
cells.

24. • Resulting corneal edema can be quantified with a
pachymeter at each visit.
• Routine evaluation for glaucoma in these patients
should be done by measuring intraocular pressure
,evaluating the angle for PAS with gonioscopy, Stereo
disc photographs,visual field along with optic nerve and
nerve fiber layer assessment and can be implemented in
the initial work-up and ongoing evaluation for glaucoma
progression in these patients.

25. D/D
• Other disorders of the cornea and iris, many with
associated glaucoma, can be confused with ICE
syndromes.
• 1. Corneal endothelial disorders:
• Posterior polymorphous dystrophy (PPD)
• Rare, bilateral, hereditary endothelial dystrophy
• May have associated glaucoma, as well as changes of
the angle and iris that resemble ICE syndrome
• Differentiating features: bilateralism, hereditary and
different posterior corneal abnormalities which can be
identified by specular microscopy.

26. • Fuch's endothelial dystrophy
• Have clinically similar corneal changes to ICE syndrome,
but none of the angle or iris features
• Iris abnormalities
• Axenfeld-Rieger syndrome
• Has strikingly similar clinical and histopathological
findings
• Differentiating features: congenital nature, bilaterality
and associated systemic features

27. • Peter's anomaly:
• Congenital central corneal leukoma with synechiae
extending from the central iris to the periphery of the
corneal opacity.
• Some patients have keratolenticular adherence, while
others have anterior polar cataracts.
• Iridoschisis
• Characterized by separation of the superficial layers of
the iris stroma, usually in the elderly
• Associated angle closure type glaucoma is common.
• Aniridia
• Congenital Iris Hypoplasia
• Lacks the angle defects

28. • Nodular lesions of the iris
• Nodular lesions of neurofibroma and
• Melanosis of the iris, inflamatory nodules,. e.g. sarcoid
• Differential Diagnosis of darker colored iris with
glaucoma (heterochromia)
• 􀂾 Cogan-Reese syndrome
• 􀂾 Diffuse iris nevus
• 􀂾 Latanoprost use
• 􀂾 Malignant melanoma of the iris
• 􀂾 Neurofibromatosis
• 􀂾 Pigmentary glaucoma

29. • Differential Diagnosis of lighter colored iris with
glaucoma (heterochromia)
• Chronic iridocyclitis
• Fuchs heterochromic iridocyclitis
• Glaucomatocyclitic crisis.

30. MANAGEMENT
• Topical medication is the first line therapy for patients
with elevated intraocular pressure from secondary angle-
closure glaucoma in the setting of ICE syndrome
• More specifically, aqueous suppressants (such as
topical beta blockers, alpha agonists, and carbonic
anhydrase inhibitors) are typically used, rather than
medications that would target the aqueous drainage
sites of the eye (e.g. miotics).
• The role of prostaglandin analogs, which reduce
intraocular pressure by enhancing uveoscleral outflow,
remains unclear.

31. • Corneal edema in ICE syndrome patients may
be exacerbated by elevated IOP, and these corneal
changes may benefit from the reduction of IOP by topical
aqueous suppressants as well. Additionally, topical
hypertonic saline solutions and gels can be utilized to
improve corneal edema by dehydrating the cornea.
• Given the membrane theory of this disease laser
trabeculoplasty is not effective for this disease and is not
recommended as treatment.

32. • When medical therapy is unsuccessful at controling IOP,
surgical therapy with a filtering procedure may be
necessary
• A trabeculectomy with antifibrotic agents (mitomycin-
C or 5-fluorouracil) or a glaucoma drainage device
(aqueous shunt) have been found to be effective in
controling IOP in ICE syndrome patients.
• However, maintaining long-term success can be
challenging, as the fistula can be obstructed with
advancing abnormal corneal endothelial cells.

33. • If surgical success is not obtained with a trabeculectomy
or glaucoma drainage device, it may be necessary to
treat patients with a ciliary body destruction
procedure. Typically this is done with diode laser
cyclophotocoagulation (diode CPC), and is reserved
for intractable cases of glaucoma.
• Corneal decompensation can similarly be treated with
surgery when medical management fails. Penetrating
keratoplasy (PKP) or endothelial keratoplasty
(commonly DSEK or DSAEK) can be implemented to
replace the abnormal corneal endothelial cells and
improve corneal function. At times, both a filtering and
corneal transplant procedure are necessary. .

34. PROGNOSIS
• This is dependent on the timing of diagnosis within the
disease course, and the success or failure of treatment
• The glaucoma tends to be more severe in progressive
iris atrophy and Cogan-Reese syndrome.
• If surgical intervention is required for intraocular
pressure control, the prognosis tends to be more
guarded