Delayed interval of involvement of the second eye in a male patient with bilateral Chandler's syndrome
- Correspondence toDouglas J Rhee, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114; dougrhee{at}aol.com
- Chandler's syndrome
- bilateral involvement
- specular microscopy
- chronic angle-closure glaucoma
- cornea
- intraocular pressure
- diagnostic tests/investigation
Case report
A 37-year-old man was diagnosed with angle-closure glaucoma during a routine screening by his local ophthalmologist. He reported a family history of glaucoma; medical history was unremarkable. He had a laser iridotomy in the right eye (OD). His intraocular pressure (IOP) OD continued to be elevated over 3 years, and he underwent laser trabeculoplasty. He first presented to our institution for blurred vision 1 week following laser trabeculoplasty. On examination, visual acuity (VA) was 20/60 OD and 20/20 in the left eye (OS). IOPs were 38 mmHg OD and 8 mmHg OS. There was corneal oedema and a ‘beaten-metal’ appearance to the endothelium OD. Gonioscopy revealed extensive peripheral anterior synechiae (PAS) inferiorly OD and normal angle structures OS. He had a cup-to-disc ratio of 0.8 OD and 0.6 OS. Visual field testing showed marked glaucomatous loss OD and a full field OS. Specular microscopy showed decreased endothelial cell count with significant pleomorphism OD (figure 1a) and normal endothelium OS (figure 1b). After failing maximal medical therapy, he underwent multiple glaucoma surgeries, including two trabeculectomies, a Molteno drainage implant, and Molteno implant revision surgery. He experienced corneal decompensation and cataract progression after his valve surgery and underwent a combined extracapsular cataract extraction with a penetrating keratoplasty. He was lost to follow-up for 10 years while seeking care at another institution.
(a) Specular microscopy of corneal endothelium of the right eye illustrating significant pleomorphism, decreased endothelial cell count and loss of cellular mosaic. (b) Specular microscopy of the left eye showing normal corneal endothelium initially. (c) Pathology specimen from the right eye showing Descemet-like membrane covering angle structures and anterior surface of the iris on haematoxylin and eosin stain (A) and Periodic acid-Schiff stain (B). In (A), the structures are labelled as C, cornea; D, duplication of Descemet's membrane; I, iris. In (B), the arrow denotes reduplication of Descemet's membrane on Periodic acid-Schiff stain.
On return, the patient presented with long-standing pain OD. VA was hand motion OD and 20/20 OS. IOPs were 4 mmHg OD and 16 mmHg OS. He had an opaque corneal graft and phthisis OD. The left eye appeared normal. Despite prednisolone acetate and atropine treatment, his discomfort persisted and he underwent elective enucleation (figure 1c). On follow-up visits, the VA of the left eye was unchanged, but the IOPs fluctuated between 18 and 22 mmHg. He was followed as a glaucoma suspect for 2 years without change. On a recent examination, his VA was 20/20 with an IOP of 22 mmHg. There was a ‘beaten-metal’ appearance to the endothelium. Gonioscopy demonstrated new development of low PAS. Confocal microscopy and repeated specular microscopy showed significantly decreased endothelial cell counts (cell density on confocal microscopy was 990 cells/mm2; endothelial cell density dropped from 2207 cells/mm2 in 1992 to 1041 cells/mm2 in 2008 on specular microscopy) with pleomorphism and loss of normal mosaic pattern (figure 2a,b).
(a) Specular microscopy of left eye in 2008 demonstrating significant pleomorphism, ICE cells, and loss of endothelial cell count and cellular mosaic. (b) Confocal microscopy of the left eye in 2008 demonstrating pleomorphism and loss of cellular mosaic.
Questions
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Describe the specular microscopy and pathology of the right eye.
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What is the diagnosis?
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How would you manage the left eye?
See page 146 for answers
Answers
From questions on page 134
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Describe the specular microscopy and pathology of the right eye.
The specular microscopy of the right eye illustrates significant pleomorphism and loss of the cellular mosaic compared to the normal left eye. The pathology demonstrates a reduplication of a descemet-like membrane that is growing over the angle and iris structures (figure 1).
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What is the diagnosis?
The diagnosis is bilateral Chandler's syndrome. The right eye had a beaten metal appearance to the endothelium, PAS, glaucoma that was refractory to multiple medical and surgical treatments, and pathology consistent with a descemet-like membrane covering the angle and iris structures. The left eye was initially normal, but years later also appeared to have a beaten metal appearance, PAS, and Iridocorneal endothelial (ICE) cells and significant pleomorphism on repeated specular microscopy.
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How would you manage the left eye?
The left eye has not developed elevated IOP requiring medical treatment; however, given the patient's monocular status, this eye should be monitored very carefully for the development of glaucoma related to Chandler's syndrome.
Discussion
ICE syndrome is a spectrum of diseases, which includes essential (progressive) iris atrophy, Cogan–Reese (iris nevus), and Chandler's syndrome. ICE is typically unilateral, acquired in the fourth or fifth decade, and predominantly found in women. There have been varying reports of the ratios of female to male patients with ICE syndrome, including ranges from 2:1 to 5:1.1 In each of three large studies of patients with ICE syndrome, the percentage of female patients was over 60%.2 Of the 22 patients with bilateral ICE syndrome reported in the literature, only four patients were male and all had atypical features of ICE syndrome.3–8 Three patients had bilateral iris atrophy findings at the time of diagnosis. The fourth male patient had unilateral findings of iris atrophy initially and subsequently developed clinical findings in the other eye 3 years later.8 Our patient developed involvement of his contralateral eye over 10 years after involvement of his first.
There are several studies which have documented endothelial abnormalities in the contralateral eye in patients with ICE syndrome.2 9 10 In a study by Kupfer, six patients had decreased endothelial cell counts and some degree of pleomorphism on specular microscopic examination of the contralateral eye in patients with ICE syndrome.9 On average, these patients were followed for less than 7 years. Another study reported 28 patients with subclinical endothelial abnormalities, including increased variation of cell area and decreased percentage of hexagonal cells compared with normal controls.10 The presence of endothelial abnormalities in the asymptomatic eyes of patient's with ICE raises the question as to whether this can truly be called a unilateral disease process. One study emphasises that these subclinical changes in the contralateral eye do not imply that ICE syndrome is a bilateral process because the clinically uninvolved eyes lack other findings such as ICE cells on specular microscopy and angle or iris abnormalities.10 While specular microscopy has been used to aid in diagnosis and differentiate ICE syndrome from other endothelial disorders, confocal microscopy offers further information on polymegathism and pleomorphic cells that specular microscopy does not provide. Confocal microscopy is superior to specular microscopy in cases of oedematous or scarred corneas.11 12 In our case, the use of specular and confocal microscopy provided confirmation of the clinical exam findings and helped to establish the diagnosis of Chandler's syndrome in the contralateral eye, but is not required to establish the diagnosis.
Chandler originally described a syndrome where abnormalities of the posterior aspect of the cornea were present with minimal iris atrophy and no hole formation.1 13 The pathogenesis of ICE syndrome is related to abnormal endothelial cells which create a membrane that grows over the angle structures and causes atrophy of the iris.1 With regard to the histopathologic findings from the enucleated eye, the endothelial cell count and corneal stromal oedema could have been further compromised from the multiple prior glaucoma surgeries including two trabeculectomies and glaucoma drainage device as this consequence has been documented by other investigators.14 If there are endothelial abnormalities in both eyes, it is unknown why the endothelial changes in one eye are confined to the subclinical level. It has been hypothesised that ICE syndrome may have a viral origin; a study by Alvarado demonstrated the presence of HSV-DNA in a significant number of patients with ICE syndrome compared with control subjects using PCR.15 Furthermore, a differential immune response to HSV in one eye may prevent full clinical presentation in the other eye.3 15 A combination of a viral origin with a two-hit hypothesis has been proposed for the development of ICE syndrome.10 Patients may have a genotype which may be susceptible to further injury from a virus resulting in clinical manifestations of ICE syndrome; the subclinical findings may be a reflection of the ‘first hit.’10 Our patient initially had a normal specular microscopy, but later developed clinical findings consistent with Chandler's syndrome, including endothelial abnormalities on slit-lamp examination and specular microscopy and PAS on gonioscopy. This case suggests that patients with unilateral ICE syndrome should have careful monitoring of their contralateral eye for the delayed onset of ICE syndrome years later. This case also raises the important point that even without subclinical abnormalities in the contralateral eye, patients may eventually develop the actual disease process years later. We recommend annual examinations of the contralateral eye, including anterior segment evaluation, gonioscopy and tonometry. Specular and confocal microscopy may also be useful adjunctive tests for confirming the diagnosis in cases of bilateral Chandler's syndrome.
Footnotes
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Competing interests None to declare.
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Patient consent Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
