QuizWise 12

Iridocorneal Endothelial Syndrome

1. Iridocorneal Endothelial Syndrome includes following ocular pathologies, except –
   a. Chandler syndrome
   b. Progressive iris atrophy
   c. Cogan-Reese syndrome
   d. Axenfeld-Rieger syndrome
   
2. The cobblestone or hammered- silver appearance of the abnormal endothelium results from –
   a. The reflection of light from the posterior surface of the abnormal endothelial cells
   b. Abnormal Descemet membrane
   c. Guttae
   d. Polymorphism and polymegathism of cells
   
3. Specular microscopy findings in cases of Iridocorneal Endothelial Syndrome –
   a. Pleomorphism
   b. Dark-light reversal pattern
   c. Vesicles
   d. All of the above
   
4. All are features of endothelial cells in ICE syndrome on confocal microscopy, except-
   a. Hypo-reflective nuclei
   b. Hyper-reflective nuclei 
   c. Normal size with loss of hexagonality
   d. Pseudo-thickening of stromal nerves
   
5. Iris changes in Progressive iris atrophy includes all except –
   a. Corectopia and areas of stromal thinning
   b. Stretch hole
   c. Heterochromia
   d. Ectropion uveae
   
6. All may help in differentiating between Iridocorneal endothelial syndrome (ICE)  and Axenfeld-Rieger syndrome (ARS), except –
   a. Presence of a layer of endothelial-like cells, that extends from the cornea, across the anterior chamber angle, and over the anterior surface of the iris
   b. Corneal endothelial changes
   c. Presence of posterior embryotoxon with iris strands
   d. Peripheral anterior synechiae

Answers :

1. Answer – d : Axenfeld-Rieger syndrome

The iridocorneal endothelial syndrome (ICE) is characterized by the proliferation of corneal endothelial cells that migrate toward the iridocorneal angle and iris surface causing corneal edema and decompensation, and secondary glaucoma. The condition comprises three clinical variants: Chandler syndrome, progressive iris atrophy, and Cogan-Reese syndrome.

Axenfeld-Rieger syndrome is a bilateral, congenital, autosomal dominant disorder in most cases, but also may occur sporadically, that includes iris abnormalities such as corectopia, polycoria, and iridocorneal attachments to a posterior embryotoxon. It does not have corneal endothelial changes, in contrast with ICE syndrome

Reference – Silva L, Najafi A, Suwan Y, Teekhasaenee C, Ritch R. The iridocorneal endothelial syndrome. survey of ophthalmology. 2018 Sep 1;63(5):665-76. DOI – 10.1016/j.survophthal.2018.01.001

2. Answer – a : The reflection of light from the posterior surface of the abnormal endothelial cells

The cobblestone or hammered- silver appearance of the abnormal endothelium, which results from the reflection of light from the posterior surface of the endothelial cells rather than from an abnormal Descemet membrane, may be seen in any of the ICE syndrome variants.

Reference – Silva L, Najafi A, Suwan Y, Teekhasaenee C, Ritch R. The iridocorneal endothelial syndrome. survey of ophthalmology. 2018 Sep 1;63(5):665-76. DOI – 10.1016/j.survophthal.2018.01.001

3. Answer – b : Dark-light reversal pattern

Under the specular microscope, the ICE cells are characterized by a cell surface that is dark instead of light, often with a central, hyper-reflective nucleus, and the intercellular junctions which are light instead of dark. Isolated ICE tissue “ICE-bergs” and PPCD vesicles may appear to be analogous. An ICE-berg consists of a nest of ICE cells surrounded by a thin dark edge, lying within the endothelium and distorting cells adjacent to it, while a PPCD vesicle is a pit delineated by a thick, dark border and lying anterior to endothelial cells without distorting them.

Reference – Liu YK, Wang IJ, Hu FR, Hung T, Chang HW. Clinical and specular microscopic manifestations of iridocorneal endothelial syndrome. Japanese journal of ophthalmology. 2001 May 1;45(3):281-7. https://doi.org/10.1016/S0021-5155(00)00383-X

4. Answer – a : Hyporeflective nuclie

Confocal microscopy reveal epithelioid endothelial cells with hyper-reflective nuclei, with preservation of the tissue  organization of the corneal endothelium and absence of inflammatory cells. It shows two distinct patterns of changes of endothelial cells in ICE syndrome :

• relatively regular size and shape and conserving a pattern similar to normal endothelial cells, with loss of normal hexagonality and prominent uniform ‘‘cobblestone-like’’ nuclei occupying the central area of the cells.
• endothelial cells more irregular in size and shape, with hyperreflective diversely shaped nuclei adjacent to the boundaries of the cells. The stromal nerves appear to be thicker (pseudo-thickening) compared to the non-involved side

It helps to differentiate between Fuchs endothelial dystrophy and ICE syndrome. It will identify the presence of the “ICE cells” on the corneal endothelium in ICE syndrome, and the hyporeflective nuclei in Fuchs endothelial dystrophy.

Reference – Chiou AG, Kaufman SC, Beuerman RW, Ohta T, Yaylali V, Kaufman HE. Confocal microscopy in the iridocorneal endothelial syndrome. British journal of ophthalmology. 1999 Jun 1;83(6):697-702. http://dx.doi.org/10.1136/bjo.83.6.697

5. Answer – c : Heterochromia

Iris changes in progressive iris atrophy are usually seen late in the course of disease by developing corectopia and areas of stromal thinning. The pupil is typically dragged toward a prominent PAS with corresponding ectropion uveae . The iris is stretched on the side opposite to the direction of pupillary distortion, and develops stromal atrophy and hole formation, called a “stretch hole’’. Progressive synachae formation and pupillary displacement related to membrane shrinkage put tension on the iris. Ultimately, with increasing synechial closure, tension on the stroma increases, stromal collagen and vessels give way, and iris atrophy and full-thickness hole formation result. In contrast, there is a less common type of iris atrophy called a “melting hole” in which surrounding iris  is not stretched. This type of hole has been demonstrated as the result of an ischemic process by fluorescein angiography  The iris pattern remains normal except in the sites of atrophy. Heterochromia usually does not occur, and ectropion uveae is rare.

Reference – Silva L, Najafi A, Suwan Y, Teekhasaenee C, Ritch R. The iridocorneal endothelial syndrome. survey of ophthalmology. 2018 Sep 1;63(5):665-76. DOI – 10.1016/j.survophthal.2018.01.001

6. Answer – a : Presence of a layer of endothelial-like cells, that extends from the cornea, across the anterior chamber angle, and over the anterior surface of the iris

Histopathologically, both ICE syndromes and ARS include a monolayer of endothelial-like cells, with a Descemet-like membrane that extends from the cornea, across the anterior chamber angle, and over the anterior surface of the iris. While in ICE syndrome the membrane is acquired after birth, in ARS it is thought that the membrane is derived, not from abnormal corneal endothelium, but from retention of the primordial endothelial layer lining the anterior chamber during gestation. A presence of a posterior embryotoxon with iris strands is seen in ARS. In ICE syndrome, instead of iris strands there may be  Peripheral anterior synechiae (PAS) to the Schwalbe line or beyond, and a posterior embryotoxon is rarely seen.

Reference – Silva L, Najafi A, Suwan Y, Teekhasaenee C, Ritch R. The iridocorneal endothelial syndrome. survey of ophthalmology. 2018 Sep 1;63(5):665-76. DOI – 10.1016/j.survophthal.2018.01.001