CASE REPORT
Phenotypic Heterogeneity of Corneal Endothelium in Iridocorneal Endothelial Syndrome by In Vivo Confocal Microscopy Chintan Malhotra, MS, Surinder S. Pandav, MS, Amit Gupta, MS, and Arun K. Jain, MD
Purpose: To present a case of iridocorneal endothelial (ICE) syndrome showing phenotypic heterogeneity of endothelial morphology between the 2 eyes of a patient as visualized by in vivo confocal microscopy (IVCM).
Methods: Confocal microscopy using the Heidelberg Retina Tomograph (HRT)-3 with Rostock Cornea Module was performed bilaterally during routine follow-up on a 60-year-old lady being managed as a case of ICE syndrome with secondary glaucoma in the right eye. Results: IVCM revealed endothelial changes in both eyes, which however varied in morphology. Endothelium of the right eye showed a “total ICE” pattern with “ICE-type of cells,” that is, diffuse involvement with enlarged, pleomorphic “epithelioid” cells having hyper-reflective nuclei and no intervening areas of the normal endothelium. The left endothelium had broad areas of normal hexagonal endothelial mosaic interspersed with different types of ICE cells showing nipple-shaped evaginations, light dark reversal and central craters with hyper-reflective rims. Conclusions: This report with the help of IVCM demonstrates that though ICE syndrome is a clinical entity which classically has been considered predominantly unilateral, the endothelial changes can be bilateral and heterogeneous. The apparent heterogeneity in the present case may represent 2 different stages of the disease process at the level of the corneal endothelium-advanced disease OD and presymptomatic disease OS. Key Words: iridocorneal endothelial syndrome, in vivo confocal microscopy, corneal endothelium (Cornea 2014;33:634–637)
I
ridocorneal endothelial (ICE) syndrome includes a spectrum of disorders due to abnormalities of the structural and proliferative properties of the corneal endothelium.1 Ultrastructural analysis of the endothelium by transmission and scanning elecReceived for publication November 20, 2013; revision received March 1, 2014; accepted March 4, 2014. Published online ahead of print April 10, 2014. From the Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. The authors have no funding or conflicts of interest to disclose. Reprints: Chintan Malhotra, Advanced Eye Centre, PGIMER, Sector 12, Chandigarh-160012, India ([email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
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tron microscopy (SEM) has revealed the presence of welldifferentiated cells with epithelial features, such as desmosomes, tonofilaments, and microvilli.2 The patients may remain asymptomatic or develop visually significant corneal edema, progressive formation of peripheral anterior synechiae (PAS), secondary glaucoma, and iris defects. ICE syndrome is traditionally divided into Chandler syndrome, essential iris atrophy, and Cogan–Reese syndrome, although these may not always present with distinctive characteristics.3 Although ICE syndrome has classically been regarded as being unilateral, bilateral disease either manifesting clinically or having subtle changes in the endothelium of the contralateral eye has been reported previously.4–6 In Vivo Confocal Microscopy (IVCM) has become a well-established modality for imaging the endothelial changes in ICE syndrome because it has superior resolution and image contrast as compared with specular microscopy and also is less affected by corneal alterations like edema or mild scarring.7,8
MATERIALS AND METHODS A 60-year-old lady being treated since 2005 for glaucoma secondary to ICE syndrome in the right eye was referred recently to the cornea services for confocal microscopy. Previous records revealed that she had undergone a mitomycin C–augmented trabeculectomy in the right eye in 2008, followed a year later by implantation of an Ahmed glaucoma valve for uncontrolled intraocular pressure (IOP). The left eye was asymptomatic and at no point had an IOP of greater than 14 mm Hg by Goldmann applanation tonometry been documented. A detailed slit-lamp biomicroscopic examination was done for both eyes followed by bilateral IVCM using the Heidelberg Retina Tomograph (HRT)-3 with Rostock Cornea Module.
RESULTS A clinical examination disclosed a best-corrected visual acuity of counting fingers OD and 6/6 OS. Slit-lamp biomicroscopy of the right eye (Fig. 1A) revealed a thickened cornea with the corneal endothelium not being visualized because of corneal edema. The tube of the Ahmed glaucoma valve was visualized in the superotemporal quadrant of the anterior chamber. The patient was pseudophakic with an opacified anterior capsular rim OD. The iris displayed diffuse atrophy, an iridectomy at 12-o’clock and an atrophic hole at 9-o’clock position. Gonioscopy disclosed PAS covering Cornea Volume 33, Number 6, June 2014
Cornea Volume 33, Number 6, June 2014
Heterogeneity of Corneal Endothelium in ICE Syndrome
FIGURE 1. A, Slit-lamp photograph of the right eye showing corneal edema, opacified anterior capsular rim, tube of Ahmed glaucoma valve in superotemporal quadrant and iris hole (white arrow) at the 9-o’clock meridian. B, Hammered silver appearance (white arrow) of the corneal endothelium of the left eye.
nearly 6 clock hours of the iridocorneal angle with the rest of the areas showing heavy pigmentation of the trabecular meshwork. IOP measured on Goldmann applanation tonometry was 18 mm Hg (on topical travoprost, dorzolamide, and timolol). Slit-lamp biomicroscopy of the left eye (Fig. 1B) revealed the presence of a “hammered silver” appearance of the corneal endothelium. The iris did not show any structural changes. The angles were open on gonioscopy with no evidence of PAS. IOP in the left eye was 14 mm Hg without any antiglaucoma medications. The corneal thickness by ultrasonic pachymetry was 570 mm OD and 500 mm OS. Dilated fundus examination revealed a cup disc ratio of 0.9 OD and 0.3 OS.
Confocal Microscopy This revealed marked asymmetry between the endothelial layers of the right and left eyes. In the right eye, there was diffuse involvement with “epithelioid changes” of the endothelium in the form of enlarged cells with prominent hyperreflective nuclei and increased granularity of the cellular cytoplasm (Fig. 2A). Some cells demonstrated doubling of the nuclei (Fig. 2B). Cellular pleomorphism in the form of kite-shaped and triangular cells was also visualized (Fig. 2C). Some cells were abutted by variably shaped extracellular hyper-reflective bodies (Fig. 2C). No areas of normal hexagonal appearing endothelium were seen. Confocal microscopy of the left eye revealed endothelial changes that were more focal and remarkably different from those in the right eye. Some cells showed a nipple-like bulge in various stages of evagination with a few enlarged cells showing the classic “light dark reversal pattern,” that is, a dark cell body with light borders (Fig. 3A). Cells with a central crater-like concavity and hyperreflective rim were also visualized (Fig. 3B), and certain broader areas where the individual cell boundaries could not be well delineated (Fig. 3C). In contrast to the right eye, the regular hexagonal mosaic was maintained throughout most of the posterior corneal surface. Mean endothelial cell count was 1129 6 33 cells per square millimeter OD and 2434 6 65 cells per square millimeter OS. Ó 2014 Lippincott Williams & Wilkins
DISCUSSION A wide spectrum of endothelial changes in ICE syndrome has been reported in the affected eye using specular and confocal microscopy, and SEM.7,9–11 These include (1) epithelial endothelial cells with hyper-reflective nuclei and light dark reversal phenomenon,7 (2) small cells with indistinct borders and very bright and prominent uniform nuclei or larger epithelioid cells with irregular borders, and nonhomogenous diversely shaped nuclei9 that corresponded respectively to the ICE+ and ICE2 cells reported by Sherrard et al,10 and (3) “cobble-stone”–like central elevation, sac-like blisters, and partially collapsed “ruptured” blisters demonstrated by Sherrard et al10 using SEM and Garibaldi et al11 using IVCM. All these different cell types have been referred to as “ICE cells” or “ICE tissue” by various authors. In our patient, using Sherrard’s grading10 of classifying ICE tissue, the endothelium of the clinically affected right eye could be classified as having “total ICE” with ICE2type of cells, that is, the entire corneal endothelium is replaced with enlarged ICE cells. Bilateral endothelial involvement in ICE syndrome has been documented in the literature.4–6,12 Lucas-Glass et al5 demonstrated that the clinically uninvolved contralateral eyes in patients with ICE syndrome had subclinical endothelial abnormalities as evidenced by a relatively low percentage of hexagonal cells and a relatively high coefficient of variation of cell area. They, however, did not find any specular microscopic features characteristic of ICE cells in these clinically uninvolved eyes. Hirst et al6 in their series of 17 patients with ICE syndrome clinically involving 1 eye only, also reported a subjective increase in pleomorphism in the contralateral clinically uninvolved eyes. Hemady et al4 reported the case of a 47-year-old lady with bilateral ICE syndrome, where specular microscopy of both eyes had a similar clinical picture showing areas of abnormal bizarre cells with highly reflective nuclei and rounded cell borders sharply demarcated from the areas of normal appearing cells. Liu et al12 in their study of 15 patients with ICE syndrome noted 1 patient to have bilateral disease (Chandler syndrome), with similar findings of subtotal ICE+10 cells on specular microscopy. Thus, previous studies have either documented nonspecific endothelial changes in the clinically uninvolved eye www.corneajrnl.com |
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Cornea Volume 33, Number 6, June 2014
FIGURE 2. IVCM images of the endothelium of the right eye: the “epithelioid” endothelial cells with hyper-reflective nuclei (A), the cells with doubling of nuclei (white arrows) (B), and the kite-shaped (white arrow) and triangular (white arrowhead) endothelial cells, with extracellular hyper-reflective bodies (black arrowhead) (C).
of patients with ICE syndrome,5,6 or in cases where pathognomonic “ICE tissue” was present bilaterally, the morphology of the ICE cells was similar.4,12 In the present case however, the apparently asymptomatic left eye showed the presence of a “hammered silver” appearance of the endothelium on slit-lamp biomicroscopy and the IVCM images of the endothelium revealed definitive evidence of “ICE cells” which were remarkably different in morphology from those seen in the right eye. The nipple-like evaginations of endothelial cells and cells having central craters with hyperreflective rims, seen interspersed amongst a regular hexagonal endothelial mosaic by IVCM in our case, are similar to findings demonstrated on SEM by Sherrard et al10 and provide further support to their proposal that blister formation and rupture are seen in the endothelial cells in ICE syndrome, and the convex and concave surfaces produced respectively are responsible for the specular or confocal microscopic images of ICE tissue. Sherrard et al10 have also postulated
that a variety of cell types found in histopathologic specimens of ICE syndrome may reflect the timing of acquisition of the specimens relative to the disease process. If the level of endothelial histopathologic change reflects the progression of the disease, the findings by Hirst et al6 of “pathognomonic endothelial changes and no areas of normal endothelial mosaic” in the affected eye and “frequent endothelial cell pleomorphism incommensurate with the patient’s age” in the clinically uninvolved contralateral eye may represent heterogeneity, although pathognomonic “ICE” tissue was not reported by them in the contralateral eye. To the best of our knowledge, this is the first case reported in the literature where IVCM was used to demonstrate such morphologic diversity between the endothelium of the 2 eyes in clinically unilateral ICE syndrome. This case might represent advanced disease OD and presymptomatic disease OS—a “gray zone” between nonspecific and pathognomonic signs. Longitudinal follow-up of the patient is necessary to determine if these subtle but definitive
FIGURE 3. IVCM images of the endothelium of the left eye: the nipple-like evaginations (white arrows) of the endothelial cells with the “light dark reversal pattern” (black arrow) of a few cells (A), the cells with a central crater-like concavity and hyperreflective rim (white arrows) (B), and the areas where the individual cell boundaries could not be well delineated (white arrowhead) (C).
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Ó 2014 Lippincott Williams & Wilkins
Cornea Volume 33, Number 6, June 2014
endothelial changes in the left eye reflect incomplete or arrested ICE syndrome or whether these progress to manifest clinically definitive disease. Ophthalmologists treating patients with apparently unilateral ICE syndrome should keep in mind the possibility that the disease may be bilateral, although asymmetrical. REFERENCES 1. Campbell DG, Shields MB, Smith TR. The corneal endothelium and the spectrum of essential iris atrophy. Am J Ophthalmol. 1978;86:317–324. 2. Levy SG, Kirkness CM, Moss J, et al. The histopathology of the iridocorneal-endothelial syndrome. Cornea. 1996;15:46–54. 3. Shields MB. Progressive essential iris atrophy, Chandler’s syndrome, and the iris nevus (Cogan-Reese) syndrome: a spectrum of disease. Surv Ophthalmol. 1979;24:3–20. 4. Hemady RK, Patel A, Blum S, et al. Bilateral iridocorneal endothelial syndrome: case report and review of the literature. Cornea. 1994;13: 368–372.
Ó 2014 Lippincott Williams & Wilkins
Heterogeneity of Corneal Endothelium in ICE Syndrome
5. Lucas-Glass TC, Baratz KH, Nelson LR, et al. The contralateral corneal endothelium in the iridocorneal endothelial syndrome. Arch Ophthalmol. 1997;115:40–44. 6. Hirst LW, Quigley HA, Stark WJ. Specular microscopy of iridocorneal endothelialsyndrome. Am J Ophthalmol. 1980;89:11–21. 7. Chiou AG, Kaufman SC, Beuerman RW, et al. Confocal microscopy in the iridocorneal endothelial syndrome. Br J Ophthalmol. 1999;83:697–702. 8. Cavanagh HD, Petroll WM, Alizadeh H, et al. Clinical and diagnostic use of in vivo confocal microscopy in patients with corneal disease. Ophthalmology. 1993;100:1444–1454. 9. Grupcheva CN, McGhee CN, Dean S, et al. In vivo confocal microscopic characteristics of iridocorneal endothelial syndrome. Clin Experiment Ophthalmol. 2004;32:275–283. 10. Sherrard ES, Frangoulis MA, Muir MG. On the morphology of cells of posterior cornea in the iridocorneal endothelial syndrome. Cornea. 1991; 10:233–243. 11. Garibaldi DC, Schein OD, Jun A. Features of the iridocorneal endothelial syndrome on confocal microscopy. Cornea. 2005;24:349–351. 12. Liu YK, Wang IJ, Hu FR, et al. Clinical and specular microscopic manifestations of iridocorneal endothelial syndrome. Jpn J Ophthalmol. 2001;45:281–287.
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Phenotypic Heterogeneity of Corneal Endothelium in Iridocorneal Endothelial Syndrome by In Vivo Confocal Microscopy Chintan Malhotra, MS, Surinder S. Pandav, MS, Amit Gupta, MS, and Arun K. Jain, MD
Purpose: To present a case of iridocorneal endothelial (ICE) syndrome showing phenotypic heterogeneity of endothelial morphology between the 2 eyes of a patient as visualized by in vivo confocal microscopy (IVCM).
Methods: Confocal microscopy using the Heidelberg Retina Tomograph (HRT)-3 with Rostock Cornea Module was performed bilaterally during routine follow-up on a 60-year-old lady being managed as a case of ICE syndrome with secondary glaucoma in the right eye. Results: IVCM revealed endothelial changes in both eyes, which however varied in morphology. Endothelium of the right eye showed a “total ICE” pattern with “ICE-type of cells,” that is, diffuse involvement with enlarged, pleomorphic “epithelioid” cells having hyper-reflective nuclei and no intervening areas of the normal endothelium. The left endothelium had broad areas of normal hexagonal endothelial mosaic interspersed with different types of ICE cells showing nipple-shaped evaginations, light dark reversal and central craters with hyper-reflective rims. Conclusions: This report with the help of IVCM demonstrates that though ICE syndrome is a clinical entity which classically has been considered predominantly unilateral, the endothelial changes can be bilateral and heterogeneous. The apparent heterogeneity in the present case may represent 2 different stages of the disease process at the level of the corneal endothelium-advanced disease OD and presymptomatic disease OS. Key Words: iridocorneal endothelial syndrome, in vivo confocal microscopy, corneal endothelium (Cornea 2014;33:634–637)
I
ridocorneal endothelial (ICE) syndrome includes a spectrum of disorders due to abnormalities of the structural and proliferative properties of the corneal endothelium.1 Ultrastructural analysis of the endothelium by transmission and scanning elecReceived for publication November 20, 2013; revision received March 1, 2014; accepted March 4, 2014. Published online ahead of print April 10, 2014. From the Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. The authors have no funding or conflicts of interest to disclose. Reprints: Chintan Malhotra, Advanced Eye Centre, PGIMER, Sector 12, Chandigarh-160012, India ([email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
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tron microscopy (SEM) has revealed the presence of welldifferentiated cells with epithelial features, such as desmosomes, tonofilaments, and microvilli.2 The patients may remain asymptomatic or develop visually significant corneal edema, progressive formation of peripheral anterior synechiae (PAS), secondary glaucoma, and iris defects. ICE syndrome is traditionally divided into Chandler syndrome, essential iris atrophy, and Cogan–Reese syndrome, although these may not always present with distinctive characteristics.3 Although ICE syndrome has classically been regarded as being unilateral, bilateral disease either manifesting clinically or having subtle changes in the endothelium of the contralateral eye has been reported previously.4–6 In Vivo Confocal Microscopy (IVCM) has become a well-established modality for imaging the endothelial changes in ICE syndrome because it has superior resolution and image contrast as compared with specular microscopy and also is less affected by corneal alterations like edema or mild scarring.7,8
MATERIALS AND METHODS A 60-year-old lady being treated since 2005 for glaucoma secondary to ICE syndrome in the right eye was referred recently to the cornea services for confocal microscopy. Previous records revealed that she had undergone a mitomycin C–augmented trabeculectomy in the right eye in 2008, followed a year later by implantation of an Ahmed glaucoma valve for uncontrolled intraocular pressure (IOP). The left eye was asymptomatic and at no point had an IOP of greater than 14 mm Hg by Goldmann applanation tonometry been documented. A detailed slit-lamp biomicroscopic examination was done for both eyes followed by bilateral IVCM using the Heidelberg Retina Tomograph (HRT)-3 with Rostock Cornea Module.
RESULTS A clinical examination disclosed a best-corrected visual acuity of counting fingers OD and 6/6 OS. Slit-lamp biomicroscopy of the right eye (Fig. 1A) revealed a thickened cornea with the corneal endothelium not being visualized because of corneal edema. The tube of the Ahmed glaucoma valve was visualized in the superotemporal quadrant of the anterior chamber. The patient was pseudophakic with an opacified anterior capsular rim OD. The iris displayed diffuse atrophy, an iridectomy at 12-o’clock and an atrophic hole at 9-o’clock position. Gonioscopy disclosed PAS covering Cornea Volume 33, Number 6, June 2014
Cornea Volume 33, Number 6, June 2014
Heterogeneity of Corneal Endothelium in ICE Syndrome
FIGURE 1. A, Slit-lamp photograph of the right eye showing corneal edema, opacified anterior capsular rim, tube of Ahmed glaucoma valve in superotemporal quadrant and iris hole (white arrow) at the 9-o’clock meridian. B, Hammered silver appearance (white arrow) of the corneal endothelium of the left eye.
nearly 6 clock hours of the iridocorneal angle with the rest of the areas showing heavy pigmentation of the trabecular meshwork. IOP measured on Goldmann applanation tonometry was 18 mm Hg (on topical travoprost, dorzolamide, and timolol). Slit-lamp biomicroscopy of the left eye (Fig. 1B) revealed the presence of a “hammered silver” appearance of the corneal endothelium. The iris did not show any structural changes. The angles were open on gonioscopy with no evidence of PAS. IOP in the left eye was 14 mm Hg without any antiglaucoma medications. The corneal thickness by ultrasonic pachymetry was 570 mm OD and 500 mm OS. Dilated fundus examination revealed a cup disc ratio of 0.9 OD and 0.3 OS.
Confocal Microscopy This revealed marked asymmetry between the endothelial layers of the right and left eyes. In the right eye, there was diffuse involvement with “epithelioid changes” of the endothelium in the form of enlarged cells with prominent hyperreflective nuclei and increased granularity of the cellular cytoplasm (Fig. 2A). Some cells demonstrated doubling of the nuclei (Fig. 2B). Cellular pleomorphism in the form of kite-shaped and triangular cells was also visualized (Fig. 2C). Some cells were abutted by variably shaped extracellular hyper-reflective bodies (Fig. 2C). No areas of normal hexagonal appearing endothelium were seen. Confocal microscopy of the left eye revealed endothelial changes that were more focal and remarkably different from those in the right eye. Some cells showed a nipple-like bulge in various stages of evagination with a few enlarged cells showing the classic “light dark reversal pattern,” that is, a dark cell body with light borders (Fig. 3A). Cells with a central crater-like concavity and hyperreflective rim were also visualized (Fig. 3B), and certain broader areas where the individual cell boundaries could not be well delineated (Fig. 3C). In contrast to the right eye, the regular hexagonal mosaic was maintained throughout most of the posterior corneal surface. Mean endothelial cell count was 1129 6 33 cells per square millimeter OD and 2434 6 65 cells per square millimeter OS. Ó 2014 Lippincott Williams & Wilkins
DISCUSSION A wide spectrum of endothelial changes in ICE syndrome has been reported in the affected eye using specular and confocal microscopy, and SEM.7,9–11 These include (1) epithelial endothelial cells with hyper-reflective nuclei and light dark reversal phenomenon,7 (2) small cells with indistinct borders and very bright and prominent uniform nuclei or larger epithelioid cells with irregular borders, and nonhomogenous diversely shaped nuclei9 that corresponded respectively to the ICE+ and ICE2 cells reported by Sherrard et al,10 and (3) “cobble-stone”–like central elevation, sac-like blisters, and partially collapsed “ruptured” blisters demonstrated by Sherrard et al10 using SEM and Garibaldi et al11 using IVCM. All these different cell types have been referred to as “ICE cells” or “ICE tissue” by various authors. In our patient, using Sherrard’s grading10 of classifying ICE tissue, the endothelium of the clinically affected right eye could be classified as having “total ICE” with ICE2type of cells, that is, the entire corneal endothelium is replaced with enlarged ICE cells. Bilateral endothelial involvement in ICE syndrome has been documented in the literature.4–6,12 Lucas-Glass et al5 demonstrated that the clinically uninvolved contralateral eyes in patients with ICE syndrome had subclinical endothelial abnormalities as evidenced by a relatively low percentage of hexagonal cells and a relatively high coefficient of variation of cell area. They, however, did not find any specular microscopic features characteristic of ICE cells in these clinically uninvolved eyes. Hirst et al6 in their series of 17 patients with ICE syndrome clinically involving 1 eye only, also reported a subjective increase in pleomorphism in the contralateral clinically uninvolved eyes. Hemady et al4 reported the case of a 47-year-old lady with bilateral ICE syndrome, where specular microscopy of both eyes had a similar clinical picture showing areas of abnormal bizarre cells with highly reflective nuclei and rounded cell borders sharply demarcated from the areas of normal appearing cells. Liu et al12 in their study of 15 patients with ICE syndrome noted 1 patient to have bilateral disease (Chandler syndrome), with similar findings of subtotal ICE+10 cells on specular microscopy. Thus, previous studies have either documented nonspecific endothelial changes in the clinically uninvolved eye www.corneajrnl.com |
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Malhotra et al
Cornea Volume 33, Number 6, June 2014
FIGURE 2. IVCM images of the endothelium of the right eye: the “epithelioid” endothelial cells with hyper-reflective nuclei (A), the cells with doubling of nuclei (white arrows) (B), and the kite-shaped (white arrow) and triangular (white arrowhead) endothelial cells, with extracellular hyper-reflective bodies (black arrowhead) (C).
of patients with ICE syndrome,5,6 or in cases where pathognomonic “ICE tissue” was present bilaterally, the morphology of the ICE cells was similar.4,12 In the present case however, the apparently asymptomatic left eye showed the presence of a “hammered silver” appearance of the endothelium on slit-lamp biomicroscopy and the IVCM images of the endothelium revealed definitive evidence of “ICE cells” which were remarkably different in morphology from those seen in the right eye. The nipple-like evaginations of endothelial cells and cells having central craters with hyperreflective rims, seen interspersed amongst a regular hexagonal endothelial mosaic by IVCM in our case, are similar to findings demonstrated on SEM by Sherrard et al10 and provide further support to their proposal that blister formation and rupture are seen in the endothelial cells in ICE syndrome, and the convex and concave surfaces produced respectively are responsible for the specular or confocal microscopic images of ICE tissue. Sherrard et al10 have also postulated
that a variety of cell types found in histopathologic specimens of ICE syndrome may reflect the timing of acquisition of the specimens relative to the disease process. If the level of endothelial histopathologic change reflects the progression of the disease, the findings by Hirst et al6 of “pathognomonic endothelial changes and no areas of normal endothelial mosaic” in the affected eye and “frequent endothelial cell pleomorphism incommensurate with the patient’s age” in the clinically uninvolved contralateral eye may represent heterogeneity, although pathognomonic “ICE” tissue was not reported by them in the contralateral eye. To the best of our knowledge, this is the first case reported in the literature where IVCM was used to demonstrate such morphologic diversity between the endothelium of the 2 eyes in clinically unilateral ICE syndrome. This case might represent advanced disease OD and presymptomatic disease OS—a “gray zone” between nonspecific and pathognomonic signs. Longitudinal follow-up of the patient is necessary to determine if these subtle but definitive
FIGURE 3. IVCM images of the endothelium of the left eye: the nipple-like evaginations (white arrows) of the endothelial cells with the “light dark reversal pattern” (black arrow) of a few cells (A), the cells with a central crater-like concavity and hyperreflective rim (white arrows) (B), and the areas where the individual cell boundaries could not be well delineated (white arrowhead) (C).
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Ó 2014 Lippincott Williams & Wilkins
Cornea Volume 33, Number 6, June 2014
endothelial changes in the left eye reflect incomplete or arrested ICE syndrome or whether these progress to manifest clinically definitive disease. Ophthalmologists treating patients with apparently unilateral ICE syndrome should keep in mind the possibility that the disease may be bilateral, although asymmetrical. REFERENCES 1. Campbell DG, Shields MB, Smith TR. The corneal endothelium and the spectrum of essential iris atrophy. Am J Ophthalmol. 1978;86:317–324. 2. Levy SG, Kirkness CM, Moss J, et al. The histopathology of the iridocorneal-endothelial syndrome. Cornea. 1996;15:46–54. 3. Shields MB. Progressive essential iris atrophy, Chandler’s syndrome, and the iris nevus (Cogan-Reese) syndrome: a spectrum of disease. Surv Ophthalmol. 1979;24:3–20. 4. Hemady RK, Patel A, Blum S, et al. Bilateral iridocorneal endothelial syndrome: case report and review of the literature. Cornea. 1994;13: 368–372.
Ó 2014 Lippincott Williams & Wilkins
Heterogeneity of Corneal Endothelium in ICE Syndrome
5. Lucas-Glass TC, Baratz KH, Nelson LR, et al. The contralateral corneal endothelium in the iridocorneal endothelial syndrome. Arch Ophthalmol. 1997;115:40–44. 6. Hirst LW, Quigley HA, Stark WJ. Specular microscopy of iridocorneal endothelialsyndrome. Am J Ophthalmol. 1980;89:11–21. 7. Chiou AG, Kaufman SC, Beuerman RW, et al. Confocal microscopy in the iridocorneal endothelial syndrome. Br J Ophthalmol. 1999;83:697–702. 8. Cavanagh HD, Petroll WM, Alizadeh H, et al. Clinical and diagnostic use of in vivo confocal microscopy in patients with corneal disease. Ophthalmology. 1993;100:1444–1454. 9. Grupcheva CN, McGhee CN, Dean S, et al. In vivo confocal microscopic characteristics of iridocorneal endothelial syndrome. Clin Experiment Ophthalmol. 2004;32:275–283. 10. Sherrard ES, Frangoulis MA, Muir MG. On the morphology of cells of posterior cornea in the iridocorneal endothelial syndrome. Cornea. 1991; 10:233–243. 11. Garibaldi DC, Schein OD, Jun A. Features of the iridocorneal endothelial syndrome on confocal microscopy. Cornea. 2005;24:349–351. 12. Liu YK, Wang IJ, Hu FR, et al. Clinical and specular microscopic manifestations of iridocorneal endothelial syndrome. Jpn J Ophthalmol. 2001;45:281–287.
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