Woman presents with morning unilateral vision blackouts

A 49-year-old white woman was referred by an outside eye provider to the glaucoma service at Tufts Medical Center for evaluation of elevated IOP in the left eye and episodes of transient vision “darkening” upon awakening for the past year.

The patient had similar episodes of darkening vision a decade ago that resolved after Ahmed tube placement in 2015. She described these episodes as a darkening of her central vision of the left eye only, lasting from seconds to all day long. Some improvement in her blackout episodes was noted after the recent initiation of aspirin for prothrombin X mutation 2 months ago.

Ocular history included glaucoma of the left eye treated with Ahmed implant in 2015, with well-controlled IOP down from an initial max of 38 mm Hg to a low to mid-teens until this year. Eye drops include brimonidine-timolol twice per day and dorzolamide twice per day in the left eye. Her medical history included Raynaud’s disease and prothrombin X mutation. Medications included aspirin 325 mg daily and metoprolol tartrate 12.5 mg twice per day. No other risk factors were noted, including family history of glaucoma, eye trauma, steroid use, migraines, nighttime antihypertensives or smoking.

Examination

Visual acuity at distance without correction was 20/25 with improvement to 20/25+2 with pinhole in the right eye and 20/40-2 with no improvement with pinhole in the left eye. IOP measured by applanation was 12 mm Hg in the right eye and 24 mm Hg in the left eye. The right pupil was round and briskly reactive to light and accommodation, while the left pupil was irregular and slowly reactive with no relative afferent pupillary defect. Extraocular motility and confrontational visual fields were full in both eyes.

Anterior segment exam of the left eye revealed iris heterochromia from 7 to 8 o’clock with a single overlying iris nevus and a superotemporal Ahmed tube in good position (Figure 1a). There was no neovascularization of the iris, no posterior synechiae, no Krukenberg spindle, no pseudoexfoliative material on the crystalline lens and no iris transillumination defects. The corneal endothelium showed a beaten bronze appearance without corneal edema (Figure 1b). The left fundus showed significant retinal venous tortuosity with an otherwise normal retina and a healthy-appearing optic nerve with a 0.4 cup-to-disc ratio and intact optic nerve rims (Figure 2). The right eye exam was normal with a 0.3 cup-to-disc ratio and intact optic nerve rims. Gonioscopy of the right eye was open to ciliary body band in all quadrants; however, the left eye showed high peripheral anterior synechiae (PAS) superiorly and was otherwise open to ciliary body band in all quadrants.

OCT scan of the macula of both eyes was normal with no macular edema (Figure 2). OCT of the retinal fiber layer and ganglion cell layer was normal and full symmetrically in both eyes (Figure 3). Humphrey visual field 24-2 tests of the left eye demonstrated stable full visual field with a few nonspecific defects and no glaucomatous changes (Figure 4).

Endothelial cell counts were normal in the right eye (2,457 cells/mm²) and significantly reduced in the left eye (755 cells/mm²) with abnormal cell architecture, including larger than normal endothelial cells, loss of hexagonal cell shape and abnormally dark cells with light borders. (Figure 5).

What is your diagnosis?

See answer below.

Unilateral vision blackouts with elevated IOP

The clinical picture of unilateral elevated IOP, beaten bronze appearance of the corneal endothelium, iris heterochromia, high PAS on gonioscopy, and abnormal endothelial cells with light-dark reversal on specular microscopy was consistent with a diagnosis of iridocorneal endothelial (ICE) syndrome. Other diagnoses to consider include Axenfeld-Rieger syndrome (iris abnormalities and elevated IOP), posterior polymorphous corneal dystrophy (corneal endothelial changes and glaucoma), Fuchs’ heterochromic iridocyclitis (heterochromia and glaucoma), aniridia (iris hypoplasia, glaucoma and corneal clouding) and malignant melanoma of the iris (iris nodule).

Regarding the recurrent episodes of transient darkening of vision in the left eye, the significant retinal venous tortuosity in the setting of prothrombin X mutation was concerning for an IOP-related issue manifesting as central retinal venous occlusion-type episodic symptoms. While the patient’s current IOP of 24 mm Hg was not extremely elevated, it was at least double her baseline, making it possible that this IOP was too high for her. This notion that the vision blackouts were IOP related was supported by her prior episodes of darkening vision years ago that improved with a glaucoma tube, and her current symptoms were somewhat improving with administration of aspirin.

Workup and management

The decision was made to pursue iCare home monitoring to elucidate whether the vision-darkening episodes correlated with IOP spikes. The patient was started on latanoprost nightly in addition to continuing brimonidine-timolol twice per day and dorzolamide twice per day in the left eye.

Fluorescein angiography of the left eye demonstrated slow filling with tortuous vessels but no blockages. The patient was referred to the neuro-ophthalmology service, which felt the visual symptoms and tortuous vessels may be secondary to her elevated IOP; however, cerebral imaging was recommended to rule out a compressive lesion or any carotid vascular issue, and both MRI and angiography of the brain and neck returned normal.

Home iCare monitoring for 2 weeks confirmed that IOP elevations up to mid-30s mm Hg occurred concurrently with changes in vision. At this point, the recommendation was made for a second tube shunt (inferonasal Baerveldt glaucoma implant), which was subsequently performed by the initial referring provider with simultaneous cataract extraction and posterior chamber IOL placement. The postoperative course was complicated by uveitis-glaucoma-hyphema syndrome (due to tube-iris contact) and cystoid macular edema, requiring repositioning of the tube to the sulcus. The patient ultimately did well with a best corrected visual acuity of 20/50, an IOP of 10 mm Hg and resolution of the vision-darkening episodes.

Discussion

ICE syndrome is a sporadic ophthalmic disorder that typically manifests in women aged 20 to 50 years old as unilateral glaucoma (however, 10% of cases are bilateral), corneal decompensation and/or iris atrophy (Chandran and colleagues). The pathophysiology of ICE syndrome involves replacement of the corneal endothelium by more epithelial-like cellular behavior with migratory characteristics (Sacchetti and colleagues). Posterior migration of the altered endothelium occurs beyond Schwalbe’s line onto the trabecular meshwork and sometimes onto the peripheral iris. Contraction of this tissue membrane in the angle and iris leads to high PAS with secondary angle-closure glaucoma and characteristic iris changes. Corneal edema may occur as a result of poor pump function of the altered corneal endothelium or from elevated IOP due to secondary angle-closure glaucoma. Although the true etiology of ICE syndrome is not well understood, there is evidence to suggest that an underlying viral infection with herpes simplex virus or Epstein-Barr virus may play a role in inducing inflammation of the corneal endothelium, resulting in the epithelial-like changes (Alvarado and colleagues).

Clinical findings on presentation include unilateral elevated IOP with beaten bronze appearance of the corneal endothelium; corneal edema; iris changes such as heterochromia, ectropion uveae, corectopia, polycoria, iris hole formation and iris atrophy; and gonioscopy showing high PAS. Three phenotypic variants exist: Chandler syndrome, essential iris atrophy and Cogan-Reese syndrome. Chandler syndrome is the most common, accounting for 50% of cases, and typically is isolated to corneal involvement with associated corneal edema and high PAS, whereas the iris changes are rarer. Essential iris atrophy often displays robust iris involvement including polycoria, corectopia, iris hole formation, iris atrophy and ectropion uveae. Cogan-Reese syndrome is characterized by tan pedunculated nodules of the iris or diffuse pigmented iris lesions without iris atrophy.

Diagnostic evaluation involves a detailed slit lamp exam, gonioscopy and dilated fundus exam. Routine evaluation for glaucoma should be performed via measurement of IOP, visual field analysis and optic nerve fiber layer assessment on OCT. Specular microscopy is an additional important diagnostic test to demonstrate unilateral endothelial cell loss with an atypical endothelial cell morphology characterized by loss of hexagonal shape, pleomorphic appearance, and light-dark reversal displayed as a dark cell with a bright central spot and light cellular borders (Laganowski and colleagues).

First-line therapy for management of ICE syndrome includes topical IOP-lowering medication. Because of the theorized role of herpes simplex virus in ICE, prostaglandin analogs are not first line. Topical hypertonic saline gels can be used to improve corneal edema. When medical therapy fails to control IOP, filtration surgery or a drainage implant may be necessary. Long-term outcomes in ICE syndrome have been shown to be slightly better with tube shunts compared with trabeculectomy (Doe and colleagues). Unfortunately, IOP is often difficult to control in ICE syndrome due to the progressive nature of the disease. In some cases, these obstructive membranes can be treated with a Nd:YAG laser to reopen the fistula. If initial surgical interventions fail in the long term in the case of intractable glaucoma, laser cyclophotocoagulation can be pursued. At times, corneal decompensation requires treatment with corneal transplantation to replace the abnormal corneal endothelial cells and improve corneal function.

This case highlights the role of IOP home monitoring devices to assist in the discovery of occult IOP spikes that correlated with the patient’s symptoms of episodic visual darkening, ultimately guiding surgical management with successful improvement in her IOP control and symptoms. Home monitoring of IOP has been shown to provide good assessment of IOP mean values, IOP spikes and tailored treatment modifications for patients with glaucoma (Rosenfeld and colleagues). Clinical scenarios in which home monitoring of IOP may be clinically useful include accessibility for patients unable to attend an office visit purely for an IOP check; unmasking of IOP fluctuations/spikes/peaks such as in the case of glaucoma progression despite no change of in-office IOP measurements; or in the case of ocular symptoms suggestive of IOP spikes despite normal in-office IOP measurements. It is worth noting that home tonometer devices do raise several challenges, including technical difficulty for patients to accurately use the device on their own, managing the data overload burdening the physician, and financial concerns for renting or buying the devices (Mali and colleagues). Overall, home IOP monitoring has displayed promising results, and for carefully selected patients such as the current case, it may provide a better overall picture of IOP fluctuations to help guide glaucoma management.

• References:
• Alvarado JA, et al. Arch Ophthalmol. 1994;doi:10.1001/archopht.1994.01090240107034.
• Chandran P, et al. PLoS One. 2017;doi:10.1371/journal.pone.0171884.
• Doe EA, et al. Ophthalmology. 2001;doi:10.1016/s0161-6420(01)00725-4.
• Laganowski HC, et al. Arch Ophthalmol. 1992;doi:10.1001/archopht.1992.01080150044025.
• Mali YP, et al. J AAPOS. 2018;doi:10.1016/j.jaapos.2018.01.004.
• Rosenfeld E, et al. Int J Ophthalmol. 2021;doi:10.18240/ijo.2021.03.12.
• Sacchetti M, et al. Biomed Res Int. 2015;doi:10.1155/2015/763093.

• For more information:
• Edited by William W. Binotti, MD, and Julia Ernst, MD, PhD, of New England Eye Center, Tufts University School of Medicine. They can be reached at william.binotti@tuftsmedicine.org and julia.ernst@tuftsmedicine.org.

Published by:

Read more about

This post was originally published on this site