Iridocorneal endothelial syndrome

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. I ris Nevus / Cogan-Reese Syndrome 2. C handler Syndrome 3. E ssential / 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 N o consistent association to other ocular or systemic disease, and familial cases have been very rare U nilateral disease , more common in women , between the ages of 20 and 50 P revalence 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

12. 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

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

14. 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

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

16. 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

17. 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. .

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

19. 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

20. 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

21. 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.

22. 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.

23. 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.

24. 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.

25. 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

26. Peter's anomaly: C ongenital 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

27. Nodular lesions of the iris N odular lesions of neurofibroma and M elanosis 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

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

29. 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.

30. 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.

31. 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 .  

32.   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. .

33. 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