A 70 yo man in his usual state of health on the night prior awoke the next morning at 9 am with near-complete monocular vision loss in the left eye except for a small crescent of vision in his central fields. He denied eye pain, headache, trauma. He denied temporal artery tenderness, headaches, or jaw claudication. No prior history of glaucoma. PMH of anxiety, depression, GERD, and mitral valve repair. Emergent ophthalmologic and stroke neurology consultation was performed excluding vitreous and chorioretinal hemorrhage, retinal detachment, disorders of the anterior segment of the eye (cornea and lens), and acute optic neuropathy. The diagnosis of left Central Retinal Artery Occlusion (CRAO) with macular sparing (Fig 1A-Fundoscopic OS Pre-tPA) was confirmed. As the patient awoke with his vision loss, he was beyond the 4.5-hour window and not eligible for emergent IV-tPA therapy. Emergent consultation for interventional therapy and potentially adjunctive Hyberbaric Oxygen Therapy (HBOT) was considered and pursued.
Neuro-Interventional Therapy and Hyperbaric Oxygen Therapy:
Our team performed emergent angiography of the left internal carotid artery (without significant stenosis) and left ophthalmic artery, demonstrating normal origin of the ophthalmic artery with a poor choroidal blush confirming the diagnosis of retinal ischemia (Figure 2, A+B). Super-selective angiography of the ophthalmic artery was performed followed by intra-arterial infusion of tPA at a concentration of .4 mg/cc for a total dose of 4 mg over 5-7 minutes. The patient reported significantly improved vision immediately after IA tPA therapy, with persistent lateral field cut. The patient then received post interventional hyperbaric oxygen therapy (2.0 – 2.6 atmospheres, 90-120 mins duration) for 4 sessions starting within 12 hours of diagnosis and treatment. A follow-up fundoscopic examination demonstrates improved perfusion of the retinal branches (Figure 1 B and C, immediate and 2 days post fundoscopic). MRI of the brain confirmed an embolic source of the CRAO, with additional small diffusion positive strokes within the left hemisphere. He was discharged home neurologically intact with significantly improved although not complete vision within the left eye for continued outpatient therapy and management.
Figure 2. A. Left ICA Angiogram CRaO; B. Selective infusion 4 mg tPA; C. Post IA tPA (OA-Ophthalmic Artery, CRA-Central Retinal Artery, CB-Choroidal Blush, PCA-Posterior Ciliary Artery);
Central Retinal Artery Occlusion (CRAO) represents on neuro-ophthalmologic emergency, which leads to irreversible damage to the inner layer of the retina secondary to ischemia. It is characterized by a sudden, unilateral and painless loss of vision. An ophthalmological evaluation including a dilated funduscopic examination is necessary to confirm the diagnosis of CRAO and rule out other disorders that can cause acute painless loss of vision, including vitreous and chorioretinal hemorrhage, retinal detachment, disorders of the anterior segment of the eye (cornea and lens), and acute optic neuropathy. Patients presenting with a history of sudden painless vision loss, a relative afferent pupil defect, an attached retina, and normal optic nerve strongly implicate central artery occlusion.1 As retinal ischemia, like other neurologic tissue, may rapidly progress to irreversible damage, patients presenting within the early 4.5 to 12-hour windows of symptom onset may be considered candidates for a variety of therapeutic approaches to improve functional visual outcome. (Figure 3)
The most common cause of CRAO is an embolic occlusion from the heart, aortic arch, or carotid artery. In several studies, ipsilateral carotid stenosis was found in greater than 1/3 of patients presenting with CRAO, and a similar percentage of these patients also presented with ipsilateral intracranial brain strokes.2,3, Branch retinal artery occlusions may also occur, often with less visual loss or symptoms secondary to collateral perfusion. In about one-third of eyes, a cilioretinal artery is also present and often supplies the fovea and central vision fields and originates from the posterior ciliary circulation which is often preserved in CRAO. When the cilioretinal artery is present, visual acuity may be preserved centrally after a CRAO, whereas peripheral vision will be severely impaired.4 (Figure 4)
The natural history for spontaneous recovery or improvement of CRAO with conservative measures (including paracentesis, acetazolamide, anticoagulation and/or antiplatelets) remains poor, with a recent meta-analysis demonstrating functional visional improvement in less than 20%.5 Unilateral uncorrectable visual loss is associated with an increased likelihood of falls and functional dependence and may be disabling enough to warrant placement in a long-term care facility.6 Surveys of adults with normal vision evaluating their preference for the treatment of CRAO, revealed that 39% of surveyed adults would accept some risk of stroke and 37% would even accept some risk of death to triple the chances of recovering 20/100 visual acuity in 1 eye when the unaffected eye is sighted. More than 80% of individuals would accept these risks if the unaffected eye were not sighted.7
Intravenous tPA has become the standard of care for many stroke patients presenting within 4.5 hours of their symptoms. Although there are currently no adequate randomized clinical trials of IV tPA for CRAO, several observational studies including a patient-level meta-analysis suggested that as many as 50% of patients treated with IV tPA may recover visual acuity of 20/100 or better if treated within 4.5 hours, with low risks of hemorrhagic complications (especially without concomitant anticoagulation)5 These early cohort studies have provided support for conducting several prospective randomized trials that are currently ongoing in the <4.5 hour window (THEIA, REVISION, Ten-CRAOS). Beyond the 4.5-hour window, IV tPA is generally not recommended, as the benefits for recovery decrease and risks of hemorrhage in the presence of a brain stroke increase.1
IA-tPA and HBOT:
Unfortunately, many if not most patients present outside of the 4.5 hour window or with “wake-up” vision loss precluding IV tPA administration, Intra-arterial tPA delivery has long been considered and performed selectively with promising results. The benefits of intra-arterial delivery include limiting the dose and systemic exposure of the thrombolytic and its hemorrhagic complications, especially within the expanded windows beyond 4.5 hours. In studies comparing selective thrombolysis with conservative therapy, Schmidt et al. reported 58% of the interventional therapy group compared with 29% of the control group demonstrated partial improvement in visual acuity, with 77% vs. 26% if treated within 6 hours.8 Additional studies delivering lower doses of tPA within 4 hours of onset published by Aldrich and colleagues demonstrated significant improvement in visual acuity (at least 1 line on the Snellen chart) in 76% of patients receiving intra-arterial therapy versus 33% of patients in the control group. The Interventional group was 13 times more likely to have improvement in visual acuity of 3 lines or more and 4.9 times more likely to have a visual acuity of 20/200 or better.9 Although limited due to the heterogeneity of the presentations and therapeutic regimens applied, early experiences suggest opportunities for improved outcomes. The only prospective randomized controlled study (EAGLE) enrolled patients up to 20 hours with a mean time to treatment of 13 hours and was halted early secondary to absence of benefit and risks within this prolonged window.3
In addition to the retinal vascular perfusion networks, >50% of the retinal oxygen supply may be derived from the passive diffusion from the choroidal circulation. Hyperbaric Oxygen Therapy (HBOT) may significantly increase passive diffusion of oxygen to the retina has been associated with visual improvement in retrospective studies.10 HBOT can maintain oxygenation of the retina through the choroidal blood supply, decrease edema and preserve compromised tissue adjacent to ischemic area. Important key factors for improvement include early therapy (<4-12 hours), degree of vessel occlusion, type of vessel occluded and presence of an adequate PaO2 of oxygen.11
Our patient experienced the most severe form of CRAO with complete vision loss with only light perception. Despite this critical presentation, with a combination of early Neurointerventional therapy with intra-arterial thrombolysis directed to provide primary revascularization and Hyperbaric Oxygen Therapy to improve collateral and retinal perfusion, he was able to achieve early functional visual improvement of movement, objects, and color in his lateral fields. CRAO represents an ocular emergency with devastating outcomes. Poor outcomes are more commonly observed with delayed presentation, complete vision loss, and conservative management. Early recognition and potential multi-disciplinary treatment plans may offer patients an opportunity for improved functional outcomes and restoration of vision for these ophthalmologic emergencies and impending strokes of the eyes.
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