Iridocorneal endothelial syndrome

IRIDOCORNEAL ENDOTHELIAL SYNDROME

bull INTRODUCTIONbull HISTORYbull EPIDEMIOLOGYbull ETIOPATHOGENESISbull CLINICAL FEATURESbull DDbull INVESTIGATIONSbull MANAGEMENT

INTRODUCTION

bull 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

bull 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

bull ICE syndrome is a group of disorders with three clinical variants

bull 1 Iris Nevus Cogan-Reese Syndromebull 2 Chandler Syndrome bull 3 Essential Progressive Iris Atrophy

bull Among the three clinical variants of ICE syndrome Chandler syndrome appears to be the most common

HISTORY

bull In 1903 Harms extensively described a rare ocular condition characterized by iris atrophy and glaucoma known as ldquoprogressive essential iris atrophyrdquo

bull Five decades later Chandler described a rare unilateral ocular condition characterized by iris atrophy associated with corneal endothelial alterations corneal edema and glaucoma

bull Subsequently it was suggested that this ldquoChandler syndromerdquo and the ldquoprogressive essential iris atrophyrdquo are two different forms of the same disease

bull When Cogan and Reese described a similar condition associated with iris nodules a third clinical entity was identified and subsequently named ldquoiris nevusrdquo or ldquoCogan-Reese syndromerdquo

bull 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 ldquoiridocorneal endothelial syndromerdquo was suggested by Yanoff

EPIDEMIOLOGY

bull Sporadic in presentationbull No consistent association to other ocular or systemic

disease and familial cases have been very rarebull Unilateral disease more common in women between

the ages of 20 and 50bull Prevalence of less than one per two lakh populationbull Glaucoma is present in approximately half of all cases

ETIOLOGY

bull 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

bull The term lsquoproliferative endotheliopathyrsquo has therefore been suggested to describe this disorder

bull 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

bull 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

PATHOGENESIS

bull On a pathological level it is felt that the normal endothelial cells have been replaced with a more epithelial-like cell with migratory characteristics

bull The altered endothelium migrates posteriorly moving beyond Schwalbe line onto the trabecular meshwork and at times onto peripheral iris

bull 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

bull 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

bull 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

CLINICAL FEATURES

bull Patients may present with differing degrees of pain decreased vision and abnormal iris appearance

bull The vision may be decreased from corneal edema which may be worse in the morning and becomes improved later in the day

bull 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

bull Various degrees of iris atrophy characterize each of the specific clinical entities

Progressive (Essential) Iris Atrophy

bull 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

bull 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

bull Iridal hole formation is the hallmark finding of progressive iris atrophy

Chandlerrsquos Syndrome

bull 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 appearanceHammered silver appearance

Iris-Nevus Syndrome (Cogan-Reese Syndrome)

bull 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

bull Gonioscopic Findingsbull Peripheral anterior synechia usually extending to or

beyond the Schwalbe line is another clinical feature common to the ICE syndrome

bull 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

bull This retrocorneal membrane can also appear on the anterior surface of an intraocular lens implant

INVESTIGATIONS

bull 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 patientsrsquo condition may be confused with a more common open-angle glaucoma

bull 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

bull Specular microscopy is an important diagnostic tool as the corneal endothelium has a characteristic appearance in ICE syndrome patients

bull 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

bull 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

bull 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

bull Resulting corneal edema can be quantified with a pachymeter at each visit

bull Routine evaluation for glaucoma in these patients should be done by measuring intraocular pressure evaluating the angle for PAS with gonioscopy Stereo disc photographsvisual 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

DD

bull Other disorders of the cornea and iris many with associated glaucoma can be confused with ICE syndromes

bull 1 Corneal endothelial disordersbull Posterior polymorphous dystrophy (PPD)bull Rare bilateral hereditary endothelial dystrophybull May have associated glaucoma as well as changes of

the angle and iris that resemble ICE syndromebull Differentiating features bilateralism hereditary and

different posterior corneal abnormalities which can be identified by specular microscopy

bull Fuchs endothelial dystrophybull Have clinically similar corneal changes to ICE syndrome

but none of the angle or iris features

bull Iris abnormalitiesbull Axenfeld-Rieger syndromebull Has strikingly similar clinical and histopathological

findingsbull Differentiating features congenital nature bilaterality and

associated systemic features

bull Peters anomalybull Congenital central corneal leukoma with synechiae

extending from the central iris to the periphery of the corneal opacity

bull Some patients have keratolenticular adherence while others have anterior polar cataracts

bull Iridoschisisbull Characterized by separation of the superficial layers of

the iris stroma usually in the elderlybull Associated angle closure type glaucoma is commonbull Aniridiabull Congenital Iris Hypoplasiabull Lacks the angle defects

bull Nodular lesions of the irisbull Nodular lesions of neurofibroma andbull Melanosis of the iris inflamatory nodules eg sarcoidbull Differential Diagnosis of darker colored iris with

glaucoma (heterochromia)bull 1048766 Cogan-Reese syndromebull 1048766 Diffuse iris nevusbull 1048766 Latanoprost usebull 1048766 Malignant melanoma of the irisbull 1048766 Neurofibromatosisbull 1048766 Pigmentary glaucoma

bull Differential Diagnosis of lighter colored iris with glaucoma (heterochromia)

bull Chronic iridocyclitisbull Fuchs heterochromic iridocyclitisbull Glaucomatocyclitic crisis

MANAGEMENT

bull Topical medication is the first line therapy for patients with elevated intraocular pressure from secondary angle-closure glaucoma in the setting of ICE syndrome

bull 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 (eg miotics)

bull The role of prostaglandin analogs which reduce intraocular pressure by enhancing uveoscleral outflow remains unclear

bull 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

bull Given the membrane theory of this disease laser trabeculoplasty is not effective for this disease and is not recommended as treatment

bull When medical therapy is unsuccessful at controling IOP surgical therapy with a filtering procedure may be necessary

bull 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

bull However maintaining long-term success can be challenging as the fistula can be obstructed with advancing abnormal corneal endothelial cells

bull 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

bull 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

PROGNOSIS

bull This is dependent on the timing of diagnosis within the disease course and the success or failure of treatment

bull The glaucoma tends to be more severe in progressive iris atrophy and Cogan-Reese syndrome

bull If surgical intervention is required for intraocular pressure control the prognosis tends to be more guarded