Diagnosis: Central retinal artery occlusion (CRAO)
CRAO is an ocular emergency that presents classically with monocular, painless vision loss and can be a warning sign for an impending cerebrovascular emergency. Lack of pain is an important feature in CRAO to distinguish it from other causes of vision loss. It generally results from an atherosclerotic plaque embolism originating from the ipsilateral carotid artery. This causes cessation of blood flow through the central retinal artery, depriving the inner retina of blood supply, leading to ischemic vision loss. The occlusive, embolic plaques can often be seen in the retinal arterioles, typically at bifurcations, and are referred to as Hollenhorst plaques. Keep in mind the anatomy at play: the ophthalmic artery branches at a sharp angle off of the internal carotid artery, and supplies the central retinal artery, which travels in the optic nerve and supplies the inner retina. (Above left image credit: Häggström, Mikael (2014). “Medical gallery of Mikael Häggström 2014“. WikiJournal of Medicine 1 (2).; Bottom right image credit: This image was originally published in the Retina Image Bank. John T. Thompson, MD. Hollenhorst Plaque. Retina Image Bank. 2016; 26741. © the American Society of Retina Specialists.)
CRAO can also occur due to a cardioembolic source in the setting of arrhythmia, notably atrial fibrillation. Rarely, Giant cell arteritis can lead to the development of an arteritic CRAO. Diagnosis is made by fundoscopic exam which reveals diffuse retinal whitening, consistent with ischemia, the appearance of a cherry red spot, and can sometimes be accompanied by optic disc edema. The appearance of a cherry red spot is caused by the choroidal vasculature beneath the fovea, appearing more prominent against the ischemic, white retina. Cherry red spots can also be see in Tay-Sachs and Niemann-Pick Disease, but in these cases the appearance is due to metabolic changes rather than ischemia. A relative or complete afferent pupillary defect is typically present in the affected eye due the significant ocular ischemia. It is important to remember that these findings may be absent early in the disease course, so one must have a high degree of clinical suspicion.
The European Assessment Group for Lysis in the Eye (EAGLE) study suggested that a majority (78%) of patients presenting with CRAO have an underlying, undiagnosed risk factor. Among patients with CRAO, the most common previously undiagnosed risk factor is severe carotid artery stenosis (>70%). Patients with CRAO should undergo emergent evaluation for carotid stenosis with CT or MR angiogram or Doppler ultrasound of the carotid arteries to assess for degree of stenosis along with evaluation for the presence of undiagnosed risk factors. However, CRAO is considered a form of stroke and the entire cerebrovascular risk factor profile should be evaluated in the same way: admit to hospital, telemetry monitoring, neurovascular imaging, MRI brain, echocardiography, evaluation for hypertension, hyperlipidemia, and diabetes, and assessment of lifestyle factors such as smoking, diet, and physical activity. Patients without vascular risk factors, especially if they are young, may warrant additional testing such as screening for an underlying hypercoagulability disorder.
Risk factors for CRAO include those known to cause vasculopathy: hypertension, diabetes, coronary artery disease, carotid atherosclerosis, smoking, and hypercoagulability.
CRAO carries a poor prognosis with respect to recovering visual loss. Irreversible vision loss can occur within 100 minutes of blocked blood flow to the central retinal artery. Treatment necessitates immediate attempt to restore perfusion to the retina in order to recover vision loss. The quickest method is through ocular massage, which aims to manually displace the embolus obstructing blood flow. Rebreathing of expired CO2 and hyperbaric oxygen, as well as isosorbide mononitrate treatment have shown benefit in causing vasodilation of the central retinal artery. Other treatment options include anterior chamber paracentesis or medical therapies to reduce intraocular pressure, such as acetazolamide or mannitol, which are thought to help move the embolus. Some centers include CRAO in the acute stroke protocol and consider intraarterial thrombolysis on a case by case basis, with suggestion of greater benefit from earlier treatment in the EAGLE trial. However, conclusive data for the benefit of intraarterial thrombolysis are lacking.
In terms of long term management and further disease prevention, medications aimed at the specific cause of CRAO must be initiated. For management of atherosclerotic disease, patients should start antiplatelet (eg aspirin) and high intensity statin therapy. For those with symptomatic high grade stenosis, carotid revascularization is indicated. If atrial fibrillation is detected, it may be necessary to initiate long term anticoagulation. All patients should receive counseling on lifestyle modifications as secondary prevention.
While visual prognosis for CRAO is often poor even with timely interventions, some individuals have a cilioretinal artery which provides collateral flow to the macula, and if present, vision may be significantly preserved.
CRAO can be complicated by the development of neovascular glaucoma. This form of secondary glaucoma can develop in eyes affected by significant ischemic changes. It can cause acute elevation of intraocular pressure and severe pain, and may threaten any remaining vision if not treated urgently (see Case 6, part 2 for more information on neovascular glaucoma).
In contrast to a CRAO, central retinal venous occlusion (CRVO) is characterized by scattered hemorrhages throughout the macula and can often be accompanied by macular edema and optic disc swelling (see image on left). If the degree of ischemia caused by venous occlusion isn’t severe, the visual prognosis can be better, with use of treatments such as anti-VEGF injections. (Left image credit, License CC A 4.0 International)
References and Additional Resources:
1. Feltgen N, Neubauer A, Jurklies B et al – EAGLE Study Group. Multicenter Study of the European Assessment Group for Lysis in the Eye (EAGLE) for the Treatment of Central Retinal Artery Occlusion: Design Issues and Implications. Graefes Arch Clin Exp Ophthalmol. 2006;244(8):950-6.
2. Mehta N, Marco RD, Goldhardt R., Modi Y. Central Retinal Artery Occlusion: Acute Management and Treatment. Curr Ophthalmol Rep. 2017;149–159.
3. Hedges TR III. (2018). Central and branch retinal artery occlusion. Brazis PW, Trobe J, & Wilterdink JR (Eds), UptoDate. Available at: https://www.uptodate.com/contents/central-and-branch-retinal-artery-occlusion.
4. “EyeWiki: Retinal Artery Occlusion.” Avaiable at: https://eyewiki.aao.org/Retinal_Artery_Occlusion#Management.
5. “Cherry Red Spot.” Available at: https://en.wikipedia.org/wiki/Cherry-red_spot.
6. Biousse V, Nahab F, Newman NJ. Management of Acute Retinal Ischemia: Follow the Guidelines! Ophthalmology. 2018;125(10):1597-1607.
Neuro-oph Case 1 Index