Central Retinal Artery Occlusion (CRAO)

Central Retinal Artery Occlusion (CRAO) is an ophthalmologic emergency that may result in a complete vision loss that is frequently irreversible. It is considered as having a stroke of the eye

Introduction

  • Opthalmological Emergency
  • Complete vision loss in one eye
  • Analoguous to Acute Ischemic Stroke
 
Central Retinal Artery Occlusion (CRAO) is an ophthalmologic emergency that may result in a complete vision loss that is frequently irreversible. It is considered as having a stroke of the eye.

Epidemiology

  • Occurs in an estimated 1 in 100,000 people
  • Occurs in 1.90 per 100,000 in the United States white population
  • Accounts for 1 in 10,000 ophthalmologic outdoor visits
  • 80% of patients have a visual acuity of 20/400 or worse
  • Incidence in men is 1.47 times higher than in women
  • <2% patients present with bilateral involvement
  • Mean age of presentation is early 60s

Anatomy

  • Central retinal artery originates from the intra-orbital part of the ophthalmic artery which is the first branch of internal carotid artery
  • Arises medial to the ciliary ganglion
  • Usually, the first branch of the ophthalmic artery (67%), may present as a second branch (28%)
  • Follows a tortuous path inside the orbital cavity
  • Enters optic sheath 18.6 mm from the distal end of the optic canal, 8.0 mm behind the posterior pole of the globe
  • Penetrates lower surface of the dura matter in an oblique manner 1 cm behind the eyeball on the inferomedial side of the optic nerve
  • Courses through the meninges and crosses the cranial nerve to be located in its center
  • Reaches the optical papilla where it divides to give branches
  • Cilioretinal artery is present in 49.5% of patients and it supplies the papillomacular bundle

Figure 1: Ophthalmic artery and its branches

notion image

Microsurgical Anatomy

  • Has narrowing at the level of the dural sheath and at the level of the cribriform plate
  • Distance Between the dural perforation point of the Central retinal artery and the optic disc is 8.36 mm
  • The average diameter is 0.4 mm

Figure 2: Cilioretinal retinal artery

notion image

Risk Factors

  • Hypertension
  • Hyperlipidemia
  • Smoking
  • Diabetes Mellitus
  • Hyperhomocysteinemia
  • Family history of vascular disease
  • Use of cocaine
  • Polycythemia vera
  • Vasculitis
  • Thrombophilia
  • Sickle cell anemia
  • Multiple myeloma
  • Systemic lupus erythematosus
  • Prothrombin III mutation
  • Giant Cell Arteritis
  • Intravitreal Injection of VEGF Therapy
  • Orbital or Head Injuries

Types of Central Retinal Artery Occlusion

Central retinal artery occlusion can be classified into four types as follows:

1. Non-arteritic permanent CRAO

  • This accounts for >2/3rd of cases of CRAO.
  • Non-arteritic permanent CRAO occurs when a thrombus or embolus, as a result of atherosclerotic disease, blocks the central retinal artery.

2. Non-arteritic transient CRAO

  • This accounts for 15–17% of cases of CRAO.
  • According to a proposed mechanism, transient vasospasm occurs due to serotonin release from platelets on atherosclerotic plaque. This vasospasm is reversible hence this form of CRAO has the best prognosis.

3. Non-arteritic CRAO with cilioretinal sparing

  • Preserved perfusion of the macula by the cilioretinal artery, which is present in 49.5% of the population, results in macular sparing.

4. Arteritic CRAO

  • This accounts for 4.5-5% of cases of CRAO.
  • This is caused by vasculitides, which in almost all cases is Giant Cell Arteritis.

Pathophysiology

  • Most common cause: Thromboembolic
    • Central retinal artery occlusion is embolism formed due to atherosclerotic plaques derived from carotid artery
      • Cholesterol (74%)
      • Fibrin (15.5%) and
      • Calcific material (10.5%)
  • Most common Artertic Process: Giant Cell Arteritis. GCA causes nodular granulomatous inflammation of medium and large sized arteries leading to the development of a fragmented internal elastic lamina and FFA in patients show occlusion of posterior ciliary artery which supply the optic nerve head and cilio-retinal arteries resulting in arteritic anterior ischemic neuropathy
  • Occlusion of central retinal artery leads to hypoperfusion of retina, retinal cell damage and eventually necrosis
  • Central retinal artery occlusion of about 240 minutes results in irreversible retinal damage
  • Other less common sources of emboli include
    • Tumor emboli from cardiac myxoma
    • Fat emboli from bone fractures
    • Bacterial endocarditis induced emboli and
    • Septicemia induced septic emboli
  • Thrombi due to atherosclerotic disease, collagen-vascular diseases, inflammatory or hypercoagulable diseases can cause central retinal artery occlusion
  • Other causes of occlusion include a foreign body, migraine, spasm of the central retinal artery, or encephalitis

Clinical Presentation

Clinical Features

  • Presents as a transient , painless monocular vision loss (amaurosis fugax) and an afferent pupillary defect
  • May be preceded by transient visual obscurations ( migrating embolism or giant cell arteritis )
  • May complain of a purplish hue to the blur
  • May complain of hallucinations
  • Simultaneous onset of CRAO in both eyes is rare
  • Central vision may be preserved if cilioretinal artery is present
  • Visual acuity may vary from loss of light perception to finger counting

Figure 3: Cherry red spot , retinal edema and vessel attenuation visible in CRAO

Source : Figure 1 Fieß, A., Cal, Ö., Kehrein, S. et al. Anterior chamber paracentesis after central retinal artery occlusion: a tenable therapy?. BMC Ophthalmol 14, 28 (2014). https://doi.org/10.1186/1471-2415-14-28
Source : Figure 1 Fieß, A., Cal, Ö., Kehrein, S. et al. Anterior chamber paracentesis after central retinal artery occlusion: a tenable therapy?. BMC Ophthalmol 14, 28 (2014). https://doi.org/10.1186/1471-2415-14-28
 

Ocular Evaluation in different types of CRAO

Table 1: Ocular Evaluation in different types of CRAO
Changes
Permanent CRAO
Permanent CRAO with cilioretinal artery sparing
Transient CRAO
Cherry red spot present , Diffuse retinal opacity present in the posterior fundus or macular region , Retina in the macular region becomes atrophic after retinal opacity resolves
Cherry-red spot, retinal opacity and cotton-wool spots are present in 3% patients within 7 days of onset
Retinal pigment epithelial changes is present in 13% of patients
Box-carring (cattle trucking) is present in 19% of patients within 7 days of onset
Box-carring is present in 16% of patients within 7 days of onset
Box-carring is not present
Retinal venous attenuation is present in 18% of patients within 1 month of onset
Retinal venous attenuation is present in 29% of patients within 1 month of onset
Retinal venous attenuation is present in 6% of patients within 1 month of onset
Disk edema is always present in arteritic CRAO Disk is pale in 39% of NA-CRAO patients
Disk edema is present in 6% patients Disk is pale in 75% of patients within 2 months of onset
Disk edema is present in 6% patients
Present in 25% patients
Present in 6% patients
Present in 13% patients

Visual Field Defects In Central retinal Artery Occlusion

  • Temporal island (59%)
  • Central and centrocecal scotoma (19%)
  • Complete blindness (10%)
  • Peripheral constriction (8%)
  • Paracentral scotoma (3%)

Differential Diagnosis

  • Retinal vein occlusion
  • Retinal detachment
  • Giant cell arteritis
  • Multiple sclerosis
  • Acute angle-closure glaucoma
  • Papilledema
  • Globe rupture
  • Sickle cell anemia
  • Epilepsy

Investigations

  • Complete blood count and coagulation assays (PT/INR, PTT)
  • ESR and CRP (more reliable) levels to rule out giant cell arteritis
  • CT head without contrast to rule out intracranial hemorrhage
  • Fluorescein angiography for the presence of posterior ciliary artery occlusion
  • Trans esophageal echocardiography to evaluate heart lesions which can be a source of emboli
  • Lipid profile(LDLs should be not more than 70s mg/dL)
  • Thrombophilia evaluation by a thrombophilia screen
  • Consider intravenous fluorescein angiography to confirm the diagnosis

Management

  • Distinguish complete from incomplete CRAO to identify patients that might benefit from treatment
  • Advise the patient to have a low-fat diet rich in fruits, vegetables, fish and lean meats for secondary prevention

Lower IOP

  • Perform an emergency anterior chamber paracentesis
  • Perform ocular massage using a three-mirror contact lens by compressing the gobe for 10 seconds followed by a 5 second release or over closed eyelids for 15–20 minutes
  • Treat with intravenous mannitol 1.5–2 g/ Kg over 30–60 min . Contraindicated if the patient is hypersensitive, severely dehydrated, or has progressive renal disease
  • Inject Intravenous acetazolamide 500 stat / 250 mg every 4 hours for 24 h . Contraindicated if the patient is hypokalemic , hyponatremic and suffers from a sulfa allergy or liver, renal disease
  • Treat with timolol 0.25% ophthalmic solution 1 gtt every 12 hours . If it is not effective then increase to 0.5% 1 gtt every 12 hours

Vasodilators

  • Treat with Pentoxifylline 600 mg TDS (vasodilator) if the patient is not allergic to theophylline or caffeine
  • Start hyperbaric oxygen 2–2.5 atm for 90 min within 8 hours of onset
  • Treat with sublingual isosorbide dinitrate 10 mg. Contraindicated if patient is hypersensitive, anemic or has a recent use of phosphodiesterase inhibitors
  • Start carbogen inhalation for 10 min per hour when awake and 10 min every 4 hours at night. Continue for 48–72 hours

Reduce Retinal Edema

  • Treat with a single dose of 1g intravenous methylprednisolone. Not recommended for non-arteritic permanent CRAO

Dislodge the Clot

  • Use Nd YAG laser 0.8–1.1 mJ intensity focused on arterial wall behind embolus to dislodge the embolus
  • Perform a pars plana vitrectomy followed by embolus removal

Embolus Thrombolysis

  • Administer intra arterial continuous infusion of tPA 40–80 mg or urokinase in a dose range of 300,000 to 1 million units . Contraindicated if patient has an evidence of intracerebral hemorrhage, a suspicion of subarachnoid hemorrhage, myocardial infarction, intracranial or intraspinal surgery , serious head trauma or stroke in the last 3 months , gastrointestinal or genitourinary hemorrhage in the previous 3 weeks, a history of intracerebral hemorrhage and uncontrolled hypertension at time of treatment or a blood glucose >22.22 mmol
  • Perform follow-up ophthalmic examination 1-4 weeks after the event to check for neovascularization

Factors Which Influence the Visual Outcome

Site of Occlusion Of Central Retinal Artery

  • Determines the amount of residual retinal circulation

Dural sheath

  • Pial and intraneural collaterals are intact and establish residual retinal circulation

Lamina cribrosa

  • No collaterals present to establish retinal circulation

Causes of Occlusion

  • Giant cell arteritis involves the posterior ciliary artery
  • When the common trunk is occluded , both arteries are occluded which is characteristic of arteritic CRAO but rare in NA-CRAO
  • The combined occlusion has a much worse visual loss than in NA-CRAO

Length of CRAO

  • Central retinal artery occlusion of upto 97 min has no detectable damage
  • Central retinal artery occlusion of about 240 minutes results in irreversible retinal damage
  • Increased duration of ischemia results in increased duration before any improvement of function occurs after circulation is restored

Patent Cilioretinal Artery

  • If it supplies the foveal region, visual acuity is almost always normal
  • If its supply just reaches the foveola , there is an initial marked fall of visual acuity but it improves markedly within 2–3 weeks
  • If it supplies a small peripapillary region , a small visual field is present with poor visual acuity

Conclusion

  • Although an accepted evidence-based therapy for CRAO does not exist , a quick diagnosis , ruling out giant cell arteritis and management to prevent further end-organ ischaemia within 6 hours of onset of symptoms must be done pending future management guidelines

Further Reading

  • Argyrios Chronopoulos, James S. Schutz, Central retinal artery occlusion—A new, provisional treatment approach, Survey of Ophthalmology, Volume 64, Issue 4, 2019
  • Dumitrascu, Oana M. MD, MSc; Newman, Nancy J. MD; Biousse, Valérie MD Thrombolysis for Central Retinal Artery Occlusion in 2020: Time Is Vision!, Journal of Neuro-Ophthalmology: September 2020 - Volume 40 - Issue 3 - p 333-345 doi: 10.1097/WNO.0000000000001027

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