Bilateral Ocular Ischemic Syndrome in the Setting of Chronic Angle Closure Glaucoma.

We report novel case of a 57-year-old woman who developed bilateral ocular ischemic syndrome in the setting of chronic angle closure glaucoma without associated angle neovascularization. Detailed is a course in which markedly prolonged, elevated intraocular pressure led to significantly reduced arterial perfusion at the level of the central retinal artery, leading to the clinical picture of ocular ischemic syndrome.

O cular ischemic syndrome (OIS) occurs in the setting of arterial insufficiency with symptoms such as gradual vision loss, eye pain, amaurosis fugax, and prolonged light recovery. 1 Patients with OIS typically present with carotid stenosis of at least 90% occlusion of the ipsilateral carotid artery, though mild to no stenosis has also been reported. 2,3 Other sources of disrupted flow may lead to this syndrome, such as significant flow limitation of the ophthalmic artery. 4 At presentation, iris neovascularization (NVA) as a result of limited tissue perfusion is present in approximately two-thirds of cases of OIS. 2 Even with this predisposition for angle NVA, increased eye pressure is observed in less than half of eyes as decreased arterial perfusion is believed to lead to ciliary body hypofunction. 1,3,4 Anterior chamber inflammation is noted in ∼20% of eyes and is usually no greater than grade 2+. 2 Midperipheral retinal hemorrhages are the most common posterior segment manifestation occurring in ∼80% of patients. Other nonspecific retinal findings such as cherry-red spot, cotton wool spots, and spontaneous retinal arterial pulsations may also occur. Fluorescein angiography (FA) may show prolonged retinal arteriovenous transit time with vascular staining, delayed/patchy choroidal filling, and retinal capillary nonperfusion. Computed tomography angiography or magnetic resonance angiographyare often required to diagnose intracranial or extracranial arterial stenosis. 5 Here, we report a case of a 57-year-old woman who presented with bilateral chronic angle closure glaucoma (CACG) causing elevated intraocular pressures (IOPs) which led to the clinical picture of bilateral OIS.

CASE PRESENTATION
A 57-year-old woman presented with a 3-month history of slowly progressive bilateral vision loss. She endorsed light-induced amaurosis and seeing haloes with no history of eye pain. Her past medical history included an excised cutaneous melanoma from her right naris and a traumatic intracranial hemorrhage that required craniotomy. She was a current smoker with a 50-pack year history. Her visual acuity was light perception in both eyes. Her IOPs were 79 and 74 mm Hg in the right and left eyes, respectively. Both pupils were mid-dilated and nonreactive. She had mild diffuse corneal microcystic edema in both eyes. Her iris showed no rubeosis. Gonioscopy revealed a universally closed angle bilaterally without evidence of angle NVA. Her lenses had 2+ nuclear sclerosis bilaterally and she was not in pupillary block. Her dilated fundus exam showed spontaneous arterial pulsations ( Fig. 1), marked cupping of both optic nerves, mild venous tortuosity, and 360 degrees midperipheral intraretinal hemorrhages in both eyes (Fig. 2 She was started on acetazolamide 500 mg twice a day, timolol, brinzolamide/brimonidine tartrate, and travoprost in both eyes. CT angiogram of the neck and brain showed no abnormalities, specifically no evidence of vascular stenosis.
Two days later, her IOP had decreased significantly to 9 mm Hg in the right and 7 mm Hg in the left eye. Her visual acuity improved to 20/80 right eye and 20/250 in the left eye. Her pupils remained minimally reactive and mid-dilated. At this time she no longer showed spontaneous arterial pulsations and her corneal microcystic edema resolved. Her acetazolamide was discontinued and her IOPs 5 days later were 12 and 10 mm Hg in the right and left eye, respectively. She ran out of her glaucoma drops and did not refill them for financial reasons.
Two weeks following her presentation, she experienced a pressure spike of > 50 mm Hg in both eyes. Her visual acuity declined to hand motion in the right eye and light perception in the left eye. She continued to endorse daily waxing and waning vision changes. She underwent emergent cataract extraction and intraocular lens placement, goniosynechialysis, and Ahmed (New World Medical, Rancho Cucamonga, CA) tube placement in the right eye followed by micropulse cyclophotocoagulation laser of the left eye. She subsequently underwent Ahmed tube placement in the left eye 1 week later.
Two months after her initial surgery, her fundoscopic findings including midperipheral hemorrhages had resolved. Macular OCT showed 1 to 2+ cystoid macular edema, trace subretinal fluid, and a trace epiretinal membrane in both eyes. Repeat FA showed normal filling, mild cystoid macular edema, mild peripheral leakage/possible trace ischemia, peripheral microaneurysms, and optic nerve head staining in both eyes. She was started on topical prednisolone drops 8 times a day for suspected Irvine-Gass syndrome.
Her most recent best-corrected visual acuity 5 months following her presentation was 20/70 in the right eye and hand motion in the left eye. Her IOPs were 15 and 14.

DISCUSSION
We present an unusual case of bilateral vision loss and fundus findings consistent with bilateral OIS in the setting of bilateral CACG without associated angle NVA. The midperipheral hemorrhages argue strongly enough for OIS that neuroimaging was performed. It is believed that OIS occurs as a result of chronic insufficient arterial perfusion, most commonly from > 90% carotid stenosis. Bilateral OIS is usually associated with bilateral carotid stenosis or systemic inflammatory disorders, such as giant cell arteritis, moyamoya syndrome, Takayasu arteritis, and increased homocysteine/CRP levels. [6][7][8][9] One report described bilateral OIS without evidence of carotid stenosis, but failed to include details of IOP on initial presentation or final visual acuity. While OIS can cause CACG from NVA, our case uniquely describes CACG without NVA causing OIS. 10 There was no evidence of vascular stenosis or systemic inflammatory disorder and both eyes responded to IOP lowering medications.
To our knowledge, CACG itself has not been reported as a cause of OIS. Rao et al describe a patient with bilateral NLP vision, unilateral macular hemorrhages, bilateral angle closure, and IOP of 6 and 10 mm Hg. The clinical description is not consistent with OIS and the authors do not posit how OIS could occur in this patient with relative hypotony. 11 Our case showed classic features of OIS and high-IOPs. It is plausible that central retinal arterial vascular compromise from high-IOPs secondary to poor aqueous outflow contributed to the appearance of OIS in this patient. This is consistent with the hypothesis proposed by Song and colleagues who demonstrate that the sudden increase in IOP in acute angle closure glaucoma results in decreased choroidal thickness which may be evidence of compression of the choroidal blood vessels. The compressed choroidal blood vessels may in turn result in ischemic retinal injury. 12 The presence of spontaneous central retinal arterial pulsations at extremely high-IOPs, combined with her unusual delay before seeking treatment (3 months), argues that chronic arterial hypoperfusion was present in both eyes. OIS may initially present with intraocular hypotension secondary to decreased ciliary body blood supply and subsequent hypofunction, however, in the setting of bilateral angle closure with nonfunctioning outflow, high pressures will prevail as they did initially in this patient. The restoration of central retinal arterial perfusion following the lowering of IOP led to the resolution of the clinical findings of OIS.
We strongly considered central retinal venous occlusion and diabetic retinopathy in this case. While the patient showed mild venous tortuosity, she did not have other features consistent with central retinal venous occlusion including hemorrhages in the posterior pole, swollen optic nerves or late venous staining on FA.
In conclusion, we report a patient who developed bilateral OIS in the setting of bilateral CACG with markedly prolonged, elevated IOP. We postulate that this occurred as a result of chronically reduced arterial outflow at the level of the central retinal artery. To our knowledge, this association has not been described previously in literature.