November 15, 2017
6 min read
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Middle-age man experiences unilateral, episodic, blurred vision

Gonioscopy revealed high peripheral anterior synechiae in the right eye.

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A 50-year-old man was referred to the New England Eye Center for 2 years of episodic blurry vision and right eye irritation. He previously saw an ophthalmologist a year ago who attributed his blurry vision and right eye irritation to allergies and dry eyes. For the past year, he has tried artificial tears and allergy eye drops without improvement of symptoms. He currently reported right eye glare at night and foreign body sensation in his right eye. He said the right eye discomfort and blurred vision can sometimes be triggered during times of stress or exertion. In addition, he sometimes has discomfort early in the morning when he wakes up. He denied current eye pain, flashes or floaters. He wears glasses for myopia and had one corneal abrasion many years ago that resolved.

His medical history was positive for remote alcohol abuse with seizure disorders and seasonal allergies. The patient reported he has not had a seizure in more than 12 years since he quit drinking and he is compliant with daily oral phenytoin. He uses a nasal spray for seasonal allergies. He has no known drug allergies. He denied smoking, illicit drugs and current alcohol use. He has no family history of ocular disorders or health problems.

Examination

The patient was alert and oriented to person, place and time with normal mood and affect. Visual acuity with correction was 20/70 (wearing –1.25 + 1.25 × 005) in the right eye and 20/20 in the left eye (wearing –2.00 sphere). There was no evidence of an afferent pupillary defect. The right pupil was noted to be irregularly shaped in both dim and bright light. The left pupil was round and 3 mm in dim light and 2 mm in bright light. IOP was 14 mm Hg in the right eye and 13 mm Hg in the left eye. Visual fields were full to confrontation bilaterally. Extraocular movements were full bilaterally. The external lids and lacrimal system were within normal limits.

Figure 1. Slit lamp examination of the right eye demonstrates an irregularly shaped pupil (a). Slit lamp examination of the left eye demonstrates a normal-appearing pupil (b).

Source: Huan Meng Mills, MD, and Chandru Krishnan, MD

Figure 2. Gonioscopy of the right eye demonstrates high peripheral anterior synechiae.

The right conjunctiva had 1+ injection, and the left conjunctiva was white. The right cornea had endothelial changes with mild anterior stromal haze. The left cornea was clear without scars or guttata. No iris transillumination defects were noted. Central corneal thickness was 607 µm in the right eye and 598 µm in the left eye. The anterior chamber was quiet. The right iris was ovoid shaped (Figure 1a), and the left iris was normal appearing (Figure 1b). The right lens had trace to 1+ nuclear sclerotic cataract, and the left eye had trace nuclear sclerotic cataract. The vitreous was clear without cells. Gonioscopy revealed high peripheral anterior synechiae (PAS) in the right eye (Figure 2) extending up to Schwalbe’s line throughout with ciliary body/scleral spur only visible at 4, 6 and 12 o’clock. There was no posterior embryotoxon. The left angle was open without PAS. Optic nerves were pink and sharp with small cups bilaterally. The macula and vessels were normal in both eyes.

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Peripheral anterior synechiae

Differential diagnoses considered include iridocorneal endothelial, or ICE, syndrome, posterior polymorphous corneal dystrophy and Axenfeld-Rieger syndrome. Endothelial changes and PAS can be present in all three of these disorders. The major difference between ICE syndrome and these other disorders is ICE syndrome tends to be unilateral whereas posterior polymorphous corneal dystrophy and Axenfeld-Rieger syndrome are usually bilateral and inherited in an autosomal dominant fashion. Posterior polymorphous corneal dystrophy is an autosomal dominant disease that results in abnormal development of Descemet’s membrane and endothelium. This disease classically presents with bilateral vesicular lesions of the corneal endothelium. Axenfeld-Rieger syndrome is a congenital disorder that has similar iris and iridocorneal angle alterations to ICE syndrome, but these changes are secondary to the presence of a primordial endothelial layer instead of migration of abnormal corneal endothelial cells. The presence of posterior embryotoxon is a key clinical finding of Axenfeld-Rieger syndrome.

Figure 3. Specular microscopy of the right eye reveals abnormally shaped corneal endothelial cells with irregular cell borders (a). Specular microscopy of the left eye reveals a monolayer of normal hexagonal corneal endothelial cells (b).

Our patient was ultimately diagnosed with ICE syndrome. The clinical finding that led to this diagnosis was the presence of unilateral broad PAS on gonioscopy. The lack of posterior embryotoxon helped rule out Axenfeld-Rieger syndrome. Corneal endothelial imaging also helped to solidify the diagnosis. Specular imaging of the affected right eye demonstrated abnormal corneal endothelial cells (Figure 3a) with a reduced corneal endothelial cell density. An accurate cell count could not be obtained due to the abnormal morphology and indistinct cell borders. In contrast, the left unaffected eye had completely normal corneal endothelial cell morphology (Figure 3b) with a normal corneal endothelial cell density of 2,941 cells/mm2. Unilateral corneal findings are characteristic of ICE syndrome. Posterior polymorphous corneal dystrophy usually presents with bilateral corneal endothelial abnormalities whereas corneal endothelial cell morphology is normal in Axenfeld-Rieger syndrome. The likely cause of the intermittent blurry vision was thought to be due to intermittent pressure spikes caused by high PAS-obstructing aqueous outflow.

Discussion

ICE syndrome is a rare, sporadic disease with a predisposition for women and is most often diagnosed in the third to fifth decade of life. The hallmark features of ICE syndrome are unilateral (rarely bilateral) corneal endothelial cell dysfunction, PAS and varying degrees of iris changes.

There are three clinical variants of ICE syndrome: Chandler syndrome, progressive iris atrophy and Cogan-Reese syndrome. Chandler syndrome is the most common of the three variants, representing 50% of patients with ICE syndrome, and it usually presents with unilateral corneal edema with minimal iris alterations. Progressive iris atrophy is another variant that presents with iris atrophy, corectopia and ectropion uvea. The prominent feature of Cogan-Reese syndrome is multiple, pigmented, pedunculated iris nodules that are composed of iris stroma surrounded by endothelial tissue.

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The cause of ICE syndrome is currently unknown. One hypothesis proposes that infection of corneal endothelial cells with herpes simplex virus is the trigger of low-grade inflammation and endothelial damage. In the normal eye, corneal endothelial cells form a uniform, hexagonal monolayer that makes up the posterior corneal surface. The normal function of corneal endothelium is to maintain deturgescence and clarity of the cornea. Humans are normally born with approximately 6,000 cells/mm2, and the endothelial cell density declines steadily with age. At age 15 years, the average endothelial cell count is 3,400 cells/mm2, and by age 85 years, the average endothelial cell count is only 2,300 cells/mm2. Endothelial damage is associated with loss of function and cell death, causing corneal edema. Additionally, in ICE syndrome, endothelial cells acquire epithelial-like activity. Aberrant endothelial cells migrate throughout the anterior segment of the eye and invade the iridocorneal angle and iris, causing broad PAS, secondary angle closure glaucoma and iris atrophy. Broad PAS often extends to Schwalbe’s line on gonioscopy (Figure 2).

The most frequent causes of vision loss in patients with ICE syndrome are glaucoma and corneal decompensation. Upward of 82% of patients with ICE syndrome develop glaucoma. Initial medical therapy for glaucoma includes aqueous suppressants, but as more PAS develops, the patient can develop angle closure, which necessitates surgery to lower the pressure. Surgical options include trabeculectomy with antifibrosis agents and glaucoma drainage implants. Some studies suggest a guarded prognosis with trabeculectomy due to increased scarring propensity in younger individuals. Abnormal endothelial cell growth can obstruct filtering and cause bleb failure. Cyclophotocoagulation can be used to decrease IOP when surgery fails.

Mild corneal edema due to endothelial pump dysfunction can initially be treated symptomatically with hypertonic saline and contact lens for comfort; however, corneal decompensation requires Descemet’s stripping endothelial keratoplasty, Descemet’s stripping automated endothelial keratoplasty or full-thickness penetrating keratoplasty. Cornea transplantation has been shown to have good short-term visual outcomes; however, long-term graft survival is poor due to late endothelial failure. Inflammation and graft rejection are also more common in patients with ICE syndrome.

Clinical course continued

Our patient likely had the Chandler variant of ICE syndrome given the absence of atrophic iris changes and iris nodules. Early progressive iris atrophy could also be possible given mild right corectopia on exam. Baseline glaucoma testing including OCT of the optic nerve head and visual fields was reliable and normal in both eyes. Despite normal pressures of 14 mm Hg at this visit, the patient was started on dorzolamide 2%/timolol 0.5% one drop in the right eye twice a day for prevention of future pressure spikes. At a 2-month follow-up visit, the patient’s IOP in the right eye was 9 mm Hg. He reported tolerating the dorzolamide-timolol drops without any adverse side effects. He also denied any new episodes of right eye discomfort or change in vision. Best corrected visual acuity remained 20/70 in the right eye and 20/20 in the left eye. The patient will need regular follow-up going forward to assess for worsening corneal edema and development of secondary glaucoma.