A 77-year-old woman with hypertension complained of recurrent crescendo altitudinal vision loss of the right eye culminating in a permanent loss of vision. An urgent ophthalmology opinion was sought. Retinal emboli at the bifurcation of the superior retinal artery cause a branch retinal artery occlusion (Fig. 1 left). This was the cause of the permanent superior altitudinal visual field defect (Fig. 1 right). Further workup demonstrated a 70% ipsilateral carotid stenosis with hypercholesterolemia. The patient was placed on cholesterol-lowering medication and had subsequent carotid endarterectomy. She did not have any further transient ischemic attacks.
The above case illustrates the importance of crescendo visual symptoms as a warning sign for the presentation of transient monocular visual loss as the ocular equivalent of a cerebral stroke.1 This article will review the clinical presentation, etiology, pathogenesis, investigation, and treatment of this condition (Figs. 2–9).
Transient visual loss due to retinal ischemia has an incidence of 14 per 100000 people per year.2 This increases the risk of subsequent vascular events (strokes and myocardial infarction) within the first week.3–11 It confers a 3% to 5% risk of stroke or death per year and 0.5% to 1% risk of retinal infarction resulting in permanent visual loss.12–14 This stroke rate remains high at 13% (10 times higher than the general population) for 3.5 years post-retinal ischemia.11
AMAUROSIS FUGAX AND OCULAR STROKE ANATOMY
The blood supply to the eye comes from the internal carotid artery and the first branch of the internal carotid artery is the ophthalmic artery. The ophthalmic artery follows a long course around the optic nerve and supplies the outer part of the eye globe from the long posterior ciliary artery. The long posterior ciliary arteries are on the medial and lateral side of the optic nerve. The ophthalmic artery dives into the nerve and forms the central retinal artery (CRA) to give blood supply to the retina. At the optic nerve head, the CRA is divided into a superior and inferior branch that then divides further to supply the 4 quadrants of the retina. Each branch further divides into retinal arterioles branches.
The site of vessel blockage may occur at the retinal arteriole, the branch retinal artery, the CRA, or at the level of the ophthalmic artery.15 Each of these will be described and illustrated in the following section.
Retinal emboli occur in 2% of the Australian population older than 70 years.6,16–20 The emboli are discrete plaque-like lesions composed of cholesterol, platelet-fibrin aggregates, or particles from calcified valves.16
A retinal emboli may be asymptomatic if the blockage is peripheral and not affecting the optic nerve and macular function. However, they can be the harbinger of deadly cerebrovascular or coronary vascular events. They are associated with diabetes, significant internal carotid artery stenosis of >70%,21 a two-third chance of patient having at least one undiagnosed vascular risk factor17 and an increased all-cause stroke-related mortality. Routine, properly retinal screening will not only identify patients with diabetic retinopathy but can also be an early screening tool to identify patients at risk for future ischemic events.
Uniform guidelines for the management of ocular ischemia are lacking.17,22 Consensus opinion mandates early risk factor intervention especially in the asymptomatic patient where retinal emboli are found.21 This is achieved by a multidisciplinary team involving ophthalmologists, stroke neurologists, and vascular surgeons.18
BRANCH RETINAL ARTERY OCCLUSION
A transient monocular visual loss typically lasts minutes only. This is the definition of amaurosis fugax. However if it lasts for longer, then permanent occlusion with a branch retinal artery occlusion (BRAO) or CRA occlusion (CRAO) must be suspected.
BRAO accounts for approximately 38% of all retinal artery occlusions.23–26 Studies have shown that branch retinal arteries are actually arterioles and that BRAO pathogenesis may have multiple causes. Large and small vessel disease and emboli have all been implicated as causes.27–29 Small vessel disease and microbleeds must be considered in workup. Each are risk factors for stroke and cognitive impairment.30–33
CRAO has an incidence of 1 to 2 people per 100,000 per year and is thought to increase to 10/100,000 in people older than 80 years. It accounts for 1/10,000 outpatient ophthalmology visits.26,29,34–37 Ocular stroke sufferers have a high degree of morbidity and mortality due to permanent severe vision loss. They are at increased risk of falls and hip fractures. Such events result in decreased quality of life, independence, and possibly institutional care.38
The most common cause of CRAO is thromboembolism from a distant site, most commonly an atheromatous plaque in the ipsilateral internal carotid artery, followed by the aortic arch of the heart.10
Risk factors for BRAO/CRAO are similar to cerebrovascular events and include hypertension, hyperlipidemia, and diabetes mellitus.4,24,29,39,40 A large multicentred trial evaluating acute treatment for CRAO demonstrated that 73% of patients suffered hypertension, 40% had 70% stenosis of at least one carotid artery, 22% had coronary artery disease, 19% had atrial fibrillation, and 78% had 1 new cardiovascular disease risk factor identified at the time of CRAO.4
An important differential not to miss is the young patient presenting with CRAO due to a carotid artery dissection. These patients have facial/neck pain with headache plus/minus an ipsilateral Horner syndrome.41,42 Other rarer causes include giant cell arteritis, thromobophilias, fibromuscular dysplasias, and possible external emboli including from dental and cosmetic procedures.
Retinal artery occlusion presents with painless visual dysfunction with a reduction in both visual acuity and/or visual fields with a relative afferent pupillary defect. The subjective experience is one of a rapid onset, with black, dark, or hazy vision of one eye. A patient will often describe the visual loss as altitudinal in nature similar to a “descending curtain.” Vision loss often occurs from the superior visual field but can be patchy or sectoral and can respect horizontal or vertical meridians.43
Visual acuity after BRAO/CRAO ranges from near normal to counting fingers or worse.44–46 However, often it is the latter. BRAO is often associated with less severe visual dysfunction than CRAO.44–47
The visual outcome after CRAO/BRAO is determined by the type of embolus, the presence of a cilioretinal artery, and the length of time a central or branch retinal artery is occluded. Studies in primate models have shown that at 240 minutes of occlusion, massive irreversible retinal damage occurs.1,48
The majority of CRAO are due to thromboembolic cause but a small percentage may be due to vasculitic cause from giant cell arteritis. Giant cell arteritis is a rare vasculitic cause of visual loss affecting patients older than 50 years. These patients present with temporal headaches, temporal artery tenderness on palpitation, and jaw claudication. This constellation of symptoms warrants urgent referral to a tertiary center with an ophthalmologist. Biomarkers such as C-reactive protein and erythrocyte sedimentation rate must be ordered with temporal artery biopsy to be performed followed by high-dose intravenous steroids.2,23,39,49,50–55
OCULAR ISCHAEMIC SYNDROME
Ocular ischemic syndrome (OIS) is a rare condition with an incidence of 7.5 per million per year. It is due to ocular hypoperfusion from stenosis or occlusion of the internal carotid arteries, due most commonly to atherosclerosis. Less common causes for OIS include giant cell arteritis, Takayasu arteritis, fibrovascular dysplasia, dissecting aneurysm of the carotid artery, hyperviscosity syndrome from genetic or iatrogenic causes, and trauma or inflammation causing stenosis of the carotid arteries.15
It occurs mainly in the elderly, has a mean age of 65 years, and rarely occurs in those younger than 50 years. There is a 2:1 male to female ratio, thought to be due to the increased incidence of coronary artery disease in men. In 20% of cases, OIS occurs bilaterally.56
The most common symptom in patients with OIS is slow progressive loss of vision, although about 10% of patients describe a sudden visual decline, and a few present with amaurosis fugax only.5,6 Pain is a presenting feature in about 40% of patients. One of the important clinical symptom in OIS is light induced amaurosis. The patients describe transient loss of vision after exposure to a bright light. This is because the OIS supplies both the internal retinal layers from the CRA and the external choroidal layers from the long posterior ciliary artery and cause from photoreceptor ischemia which cannot regenerate after exposure to bright light.
Patients with OIS usually have a >90% occlusion of the ipsilateral carotid artery with complete occlusion occurring 50% of the time. Such occlusion reduces perfusion pressure in the CRA by approximately 50%. OIS usually occurs in patients with poor collateral circulation. If a patient has poor collateral supply as little as 50%, stenosis can cause OIS. The mortality rate is up to 40% within 5 years, with cardiovascular disease and then stroke the most common causes of death. Risk factors are similar to that of CRAO/BRAO; hypertension and diabetes are found in 73% and 56% of patients, respectively.
APPROACH TO HISTORY IN TRANSIENT OR PERMANENT VISUAL LOSS
A clear, deliberate approach to clinical history taking and physical examination will help GP's make an accurate diagnosis when assessing patients with transient monocular and permanent visual loss. Specific history of the pattern, timing, provoking factors, and associated symptoms will provide clues to the etiology of visual loss.
The pattern of visual loss may be altitudinal like a curtain coming down. A patient with altitudinal visual loss is more likely to have a carotid or cardiac embolic source compared with patients with diffuse or constricting patterns of vision loss. About 40% of patients with an altitudinal defect at the start of visual loss progress to a diffuse or total vision loss. Therefore, it is important to specifically ask how the symptom was perceived at its onset.
PHYSICAL EXAMINATION IN TRANSIENT AND PERMANENT VISUAL LOSS
The purpose of the physical examination is the following:
Confirmation of the Diagnosis
The standard ocular examination with determination of visual acuity with a hand-held Snellen chart, determination of visual field to confrontation, and the demonstration of an afferent pupillary defect. The visual acuity and visual fields are determinants of an individual's ability to function independently.
Often the funduscopic examination may show evidence of optic nerve compromise, with edema of the nerve. Fundoscopic findings depend on the duration and degree of retinal ischemia from the arterial occlusion. Early findings may show retinal opacity in the posterior pole in the area of infarction or presence of the retinal emboli, cherry red spot in acute CRA occlusion, box carring, or retinal arterial attenuation. Late findings may include optic atrophy, retinal arterial attenuation, cilioretinal collaterals, and macula pigment epithelial changes.
A fundus fluoresceine angiogram may help determine the site of the arterial occlusion and also define whether there are other vascular territories affected. Fundus Fluorescein angiography will show delayed filling of the affected vessels, reduced arterial caliber, and sometimes presence of retinal emboli. Optical coherence tomography may demonstrate an increased inner retinal layer thickness in the acute phase of CRA occlusion due to the retinal edema and optic nerve swelling.11
Imaging of the Carotid Artery
Ocular ischemia may result from compromise of the ophthalmic artery, the first branch of the internal carotid artery. Therefore, the presence of internal carotid artery stenosis is important in terms of re-vascularisation with a carotid endarterectomy. This would be indicated in the presence of >50% or greater stenosis of the symptomatic carotid artery.
The easiest way to determine a carotid stensosis is ultrasonagraphy although the most accurate way would be angiography. The computerized tomography angiogram would be an ideal choice for a primary care physician.
Determination of Vascular Risk Factors
Standard vascular workup including fasting blood sugar and lipid levels should be performed. Depending upon the clinical suspicion of an arthritic or inflammatory aetiology, such as giant cell arteritis, erythrocyte sedimentation rate, and C-reactive protein can easily be added on as test.
The 12-lead electrocardiogram for determination of atrial fibrillation should be done. If this shows sinus rhythm, due consideration should be given for proceeding on to a 24-hour Holter monitor. The presence of atrial fibrillation alters management as anticoagulation would be considered in favor of antiplatelet therapy (Table 1).
The management of retinal arterial occlusion should be divided into:
- a. Acute: attempt to restore ocular perfusion to the retinal artery
- b. Subacute: preventing secondary neovascular complications to the eye
- c. Long term: preventing other vascular ischemic events to the eye or other end organ.
There are currently no guideline-level data for the treatment of retinal artery occlusion. Referral to an ophthalmologist is suggested.
Subacute Preventing Ocular Neovascularization Complication in the Eye
Another complication of CRAO and OIS is the risk of neovascularization and subsequent glaucoma. There is debate in the literature regarding its prevalence and etiology after CRAO. As such, there is no consensus on the best follow-up regimen post-CRAO to detect the ocular neovascular complications and optimally manage CRAO. The reported prevalence is 2.5% to 31.6%. Rudkin et al3 noted a 18.2% prevalence of ocular neovascularisation and the mean time from CRAO to observed neovascularization was 8.5 weeks (range 2–16 weeks). No patient had diabetic retinopathy or other causes of neovascularization. There was a definite temporal relationship between the CRAO and neovascularization events, with no other causes of neovascularization demonstrable in this cohort of patients. In the majority of cases of neovascularization, there were no clinical features of ocular ischemia, and no association with a hemodynamically significant stenosis of the carotid artery. Given the association between neovascularization and CRAO and OIS, prudent clinical practice would be to review all patients with acute CRAO and OIS at regular intervals as early as 2 weeks then monthly up to 4 months post-CRAO.
Chronic Secondary Prevention
Essentially this is no different from the treatment of cerebral stroke and is as follows:
- Patients whether normotensive or hypertensive should receive blood pressure-lowering therapy unless contraindicated.
- Therapy with a statin should be commenced.
- Long-term anti-platelet therapy via aspirin and dipyridamole or clopidogrel should be prescribed to all patients based on comorbidities that do not need anti-coagulation.
- Anticoagulation should be used in patients with atrial fibrillation or cardioembolic stroke/transient ischemic attacks.
- Eligible patients should undergo carotid endarterectomy as soon as possible after ischemic event (within 2 weeks).
- Patients with diabetes mellitus should be managed as per the national guidelines.
- Smoking cessation via nicotine replacement therapy, bupropion or nortryptiline, and or behavioral therapy.
- Diet low in fat and sodium but high in fruit and vegetables.
- Increase exercise in line with national guidelines (30 minutes 5 days a week moderate intensity).
- Ensure adherence to treatment (medications) via reminders, self-moitoring, telephone follow-up, family therapy, dose administration aids.
A sound understanding of transient and permanent visual loss from ischemia is underpinned by knowledge of the relevant neuroanatomy and how it relates to patient's history and physical examination. Once an ophthalmologist suspects an ischemic cause for visual loss, the common etiologies, risk factors, investigations, and referral protocols should be in their minds or easily accessible.
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