CENTRAL RETINAL ARTERY OCCLUSION

DR ARPITA

ANATOMY

• The ophthalmic artery is the first branch of the internal carotid artery and enters the orbit underneath the optic nerve through the optic canal.

• The central retinal artery is the first intraorbital branch of the ophthalmic artery, which enters the optic nerve 8-15 mm behind the globe to supply the retina.

• Short posterior ciliary arteries branch distally from the ophthalmic artery and supply the choroid.

• Anatomical variants include cilioretinal branches from the short posterior ciliary artery, which gives additional supply to the macula from the choroidal circulation

• A cilioretinal artery occurs in approximately 14% of the population

Retinal artery obstructions selectively affect the inner retina only.

• DEFINITION: An abrupt diminution of blood flow through the central retinal artery severe enough to cause ischemia of the inner retina

• A central retinal artery obstruction occurs when the blockage is within the optic nerve substance itself and therefore the site of obstruction is generally not visible on ophthalmoscopy. A branch retinal artery obstruction occurs when the site of blockage is distal to the lamina cribrosa of the optic nerve.

HISTORY• In 1859, Van Graefe first described central retinal artery

occlusion (CRAO) as an embolic event to the central retinal artery in a patient with endocarditis.

• In 1868, Mauthner suggested that spasmodic contractions could lead to retinal artery occlusion

• In1881 Samelsohn advocated treatment with nitrate inhalation

• In 1888 Mules did AC paracenteses for CRAO

EPIDEMIOLOGY

• Approximately 8.5 CASES PER 100000.• Similar to other vascular disorders, this condition is

largely seen in OLDER ADULTS but cases in children and young adults have also been reported.

• The average age at presentation is in the early sixties• MEN are affected more frequently than women. • No predilection for one eye over the other has been

reported; however, 1–2% of cases may manifest bilateral involvement

ETIOPATHOGENESIS

• THROMBOTIC-80%

• EMBOLIC -20%

CLINICAL FEATURES• SYMPTOMS• Monocular• Sudden loss of vision• severe• painless• Occurs acutely, possibly over the span of a few

seconds.• In some cases, premonitory episodes of amaurosis

fugax may be reported. Amaurosis fugax represents transient acute retinal ischemia and typically suggests an embolic source of occlusion

• SIGNS 1) Visual acuity at the time of initial presentation ranges

from counting fingers to light perception• Central visual acuity may be near normal in patients who

have a transient CRAO or a cilioretinal artery providing sufficient vascular supply to the fovea.

• The absence of light perception is rare; therefore, in such cases, concomitant choroidal circulation deficit (e.g., due to ophthalmic artery occlusion) or optic nerve involvement should be considered

• Visual acuity tends only to improve within the first week of onset with minimal chance for appreciable improvement subsequently

• Visual recovery after treatment has been shown to correlate with presenting visual acuity and the duration of visual impairment

2) RAPD3) INTRAOCULAR PRESSURE is often normal at

presentation but may become elevated in the setting of rubeosis iridis

4) FUNDUS CHANGES• Cherry-red spot (90%)• Posterior pole retinal opacity or whitening (58%), • Box-carring of retinal arteries and veins (19% and

20% respectively)• Retinal arterial attenuation (32%)• Optic disc edema (22%), and optic nerve pallor (39%)• The retinal findings were predominantly located in the

posterior pole with a normal-appearing periphery

• The retinal whitening is due to opacification of the retinal nerve fiber and ganglion cell layer as a result of cessation of axoplasmic transport caused by the acute ischemic insult.

• The opacification is visible ophthalmoscopically where the ganglion cell layer is more than one cell thick, i.e., the macula, except in the foveal region, whe cherry-red spot is seen.

• The cherry-red spot is actually normal-appearing retina and is observed in high contrast against the surrounding opacified retina because the thin retina in this location is nourished by the underlying choroidal circulation

• Similarly, the retinal periphery in CRAO cases appears normal because the retina is also thinner with a single layer of ganglion cells, such that the nutrition of the inner retinal layers can be maintained by the choroidal circulation alone.

• Typically, the retinal opacification resolves over a period of 4–6 weeks

• A patent cilioretinal artery supplying some or all of the papillomacular bundle is seen in approximately ONE-THIRD of cases

Cilioretinal arteries of varying size are found in about 20 per cent of eyes. These are part of the posterior ciliary circulation and are therefore spared in a CRAO. The patch of retina supplied by the artery is left viable; if the patient is fortunate this will include the macula. A small cilioretinal vessel is seen clearly in this patient supplying an area of retina temporal to the optic disc. Minute cholestero emboli can be seen in the inferior and superior temporal arteries and also in a smal branch artery adjacent to the macula, indicating the aetiology of the occlusion. Fluorescein angiography demonstrates the slow rate of filling of the retinal circulation and the normal filling ofthe cilioretinal artery and choroid.

• Box-carring or segmentation of the blood column of both the arteries and veins occurs secondary to separation of blood serum from erythrocytes in a stacked or rouleaux formation

• Retinal emboli are visible in 20–40% of eyes with CRAO .The most common variant is a yellow, refractile cholesterol embolus (Hollenhorst plaque)

• Retinal emboli consist of CHOLESTEROL in 74% of cases, CALCIFIED MATERIAL in 15.5%, and PLATELET AND FIBRIN in 15.5%

• 1 Cholesterol emboli (Hollenhorst plaques) appear as intermittent showers of minute, bright, refractile, golden to yellow-orange crystals, often located at arteriolar bifurcations They rarely cause significant obstruction to the retinal arterioles and are frequently asymptomatic.   2    Calcific emboli may originate from atheromatous plaques in the ascending aorta or carotid arteries, as well as from calcified heart valves. They are usually single, white, non-scintillating and often on or close to the disc When located on the disc itself, they may be easily overlooked as they tend to merge with the disc. They may cause permanent occlusion of the central retinal artery or one of its main branches.   3    Fibrin-platelet emboli are dull grey, elongated particles which are usually multiple and occasionally fill the entire lumen They may cause a retinal transient ischaemic attack (TIA), with resultant amaurosis fugax, and occasionally complete obstruction.

• Ophthalmologist plays an important role in the management of these patients by referring them for prophylactic medical or surgical treatment to forestall the development of permanent neurological sequelae as patients with retinal embolization have an increased risk of developing a permanent stroke over the next few months and the risk is substantially increased if the amaurosis fugax is accompanied by signs of transient cerebral ischaemia or an embolus is visible in the retina

• It should be noted that the leading cause of death in patients with retinal arterial obstruction is cardiovascular disease

• The optic nerve is acutely edematous in nearly all cases of arteritic CRAO as a result of the associated anterior ischemic optic neuropathy that is typically observed in these patients. In the acute phase of nonarteritic CRAO, the disc may be normal, hyperemic, edematous, and, rarely, pale.

• Months after an acute CRAO, cilioretinal collaterals may develop as a result of a compensatory enlargement of capillary anastomoses between retinal capillaries on the surface of the disc and ciliary capillaries in deeper parts of the optic nerve head.

• The most frequent findings in the CHRONIC STAGE of eyes with CRAO are

• optic atrophy (91%),• retinal arterial attenuation (58%), • cilioretinal collaterals (18%), • macular RPE changes (11%), and • cotton-wool spots (3%)

ANCILLARY STUDIES• 1) OCT• In the acute stage, optical coherence tomography (OCT)

shows an irregular macular contour with increased reflectivity of the inner retina. This corresponds to intracellular edema and explains the lack of intraretinal, hyporeflective fluid spaces in cases of CRAO or BRAO. The reflectivity of the outer retinal layers and RPE is blocked by the highly reflective inner retinal layer.

• OCT can be helpful in cases of chronic CRAO where the fundus may appear featureless but the OCT shows inner retinal atrophy with preservation of the outer retina

• 2)FFA• Initially shows some variable residual retinal circulation

with delayed and sluggish filling of the retinal vasculature. Complete absence of retinal filling is rare

• Areas of delayed choroidal perfusion, may be seen in about 11% of eyes with acute CRAO.

• Leakage of fluorescein dye at the level of the RPE is generally not seen with CRAO unless the choroidal circulation is involved

• 3) ERG• Typically demonstrates more severe attenuation of the b-

wave than the a-wave since the inner retinal layers are more affected – this produces a characteristic negative waveform

• Diminution of the a-wave and b-wave may suggest outer retinal damage secondary to choroidal vascular hypoperfusion in the setting of an ophthalmic artery occlusion in addition to a CRAO

4) AUTOFLUORESCENCE Imaging in the area supplied by the occluded retinal

artery acutely shows decreased autofluorescence due to blockage of the normal autofluorescence of the RPE by the thickened inner retina.

5) VISUAL FIELDS• Central scotoma is the most common defect observed

on macular visual field testing followed by paracentral scotoma.

• Patients with cilioretinal sparing show a preserved central island of vision corresponding to the area perfused by the patent cilioretinal artery. Peripheral constriction is the most common visual field deficit noted in these patients

SYSTEMIC ASSOCIATIONS

EVALUATION• The only true emergency in such a circumstance would

be to rule out giant cell arteritis in patients older than 50 years with a positive review of systems. Evaluation for giant cell arteritis includes compete blood count, including platelets, erythrocyte sedimentation rate, and C-reactive protein. If suspicion is high, the patient should be started on steroid therapy and scheduled for a temporal artery biopsy.

• In other cases etiologic workup is generally recommended on an outpatient basis along with a primary care physician.

• The evaluation of embolic source often includes carotid Doppler imaging and echocardiography since the most common sources of retinal emboli are from the carotid artery or the heart and chronic anticoagulation may be indicated to prevent more serious adverse events.

• Since the cardiac morbidity and mortality are significant in patients with retinal artery occlusion, a baseline electrocardiogram is recommended

• A hypercoagulability evaluation should be considered for patients less than 50 years of age with a suggestive history (e.g.,prior thrombosis, miscarriage, or family history) or unknown embolic source

• Other tests for monoclonal gammopathy, cancer,• infection, and disseminated intravascular coagulation

may be ordered depending on the clinical circumstance

TREATMENT• Adoption of a supine posture might improve ocular

perfusion• Ocular massage• sublingual isosorbide dinitrate• intravenous acetazolamide,• intravenousmannitol or oral glycerol,• anterior-chamber paracentesis,• Intravenous methylprednisolone, streptokinase, and

• Hayreh has shown that irreversible cell injury occurs after 90-100 minutes of total CRAO in the primate model.

Controversy exists regarding the optimal window of treatment in humans, but the conservative approach involves treatment up to 24 hours.

• Ocular massage is performed using either a Goldmann contact lens or digital massage to apply ocular pressure with an in-andout movement to dislodge a possibly obstructing embolus.

• Repeated massage with 10–15 seconds of pressure followed by a sudden release is recommended. This maneuver can produce retinal arterial vasodilation, thereby improving retinal blood flow

• A mixture of 95% oxygen and 5% carbon dioxide (carbogen) can be provided to induce vasodilation and improve oxygenation, but efficacy has not been proven

• Hyperbaric oxygen provides oxygen at levels of atmospheric pressure. The purpose of hyperbaric oxygen is to preserve the retina in an oxygenated state until recanalization and reperfusion occur, typically at 72 hours. The hyperbaric oxygen increases the arterial oxygen pressure and thereby increases nitric oxide synthesis, leading to vasodilation

• ‘Rebreathing’ into a paper bag in order to elevate blood carbon dioxide and respiratory acidosis, as this may promote vasodilation

• Anterior-chamber paracentesis causes a sudden decrease in intraocular pressure, possibly causing the arterial perfusion pressure behind the obstruction to force an obstructing embolus downstream

• Topical timolol 0.5% and intravenous acetazolamide 500 mg to achieve a more sustained lowering of intraocular pressure

• Hyperosmotic agents. Mannitol or glycerol have been used for their possibly more rapid IOP-lowering

• Vasodilating medications that have been utilized to increase retinal blood flow in retinal arterial occlusion include pentoxifylline, nitroglycerin, and isosorbide dinitrate

• (Nd- YAG) laser arteriotomy in patients with CRAO has been reported to result in extrusion of an embolus, reopening of the central retinal artery, and return of vision. A fundus contact lens is used with the laser in single-burst mode.

• Pulses are delivered directly to the emboli, beginning with the lowest power setting and then with increasing energy until either (1) achieving photofragmentation of the embolus within the arteriole without creating an opening in the vessel wall and without vitreous hemorrhage or (2) creating visible removal of the embolus from within arteriole into the vitreous cavity, typically associated with a limited vitreous hemorrhage.

• Digital pressure can be applied to the globe to help stop bleeding, if it occurs

• Corticosteroids should only be used when arteritic CRAO from giant cell arteritis is suspected. Anticoagulants should be reserved for secondary prevention of cerebral and ocular infarction in those rare patients who have an underlying systemic disease such as atrial fibrillation, acute internal carotid artery dissection, or a hypercoagulable condition

• In 2010 the European Assessment Group for Lysis in the Eye (EAGLE) study group published the results of the first prospective, randomized clinical trial evaluating the effect of intra-arterial t-PA compared with conservative treatment.

• At 1 month, the mean best-corrected visual acuity improved significantly in both groups but no significant difference was noted between groups

• Iris neovascularization develops after acute CRAO in approximately 18% of eyes, with a mean time interval of approximately 4- 5 weeks -typically earlier than in CRVO 3 months), and along with very poor vision may indicate ophthalmic artery occlusion. Full-scatter PRP is effective in eradicating the new iris vessels in about two thirds of cases

• Neovascularization of the disc occurs in 2-3% of patients. Panretinal photocoagulation is effective for optic disc neovascularization.

• Intravitreal injection of an anti-VEGF agent is first-line therapy for iris, trabecular meshwork, or optic disc neovascularization

• Treatment of carotid disease In patients with a localized stenosis of the artery,

endarterectomy significantly reduces the risk of subsequent stroke. In experienced hands this operation carries a mortality of less than 1%, although the incidence of morbidity is higher.

• If endarterectomy is contraindicated, medical treatment with drugs that reduce platelet stickiness (aspirin, dipyridamole) or anticoagulants may be used to reducing the frequency of transient ischaemic attacks and the risk of a major stroke.

FOLLOW-UP

• The patient should be seen by an ophthalmologist in 3–4 weeks and again a month later in order to detect incipient neovascularization, particularly of the anterior segment.

• In the minority of cases where referral to a specialist vascular team is not indicated, it should be ensured that the results of systemic investigations have been reviewed and necessary systemic treatment initiated.

PROGNOSIS• Patients with visualized retinal artery emboli, whether or

not obstruction is present, have a 56% mortality rate over 9 years, compared to 27% for an age-matched population without retinal artery emboli.

• Life expectancy of patients with CRAO is 5.5 years compared to 15.4 years for an age-matched population without CRAO