Approach Considerations
The most important tenet of treatment is rapid identification of central retinal artery occlusion (CRAO), which depends on logistic challenges specific to each care center.
Medical Care
There is no standard treatment for CRAO. [12]
Among the suggested treatments are noninvasive and more invasive treatments. Some of the noninvasive treatments include ocular massage, hyperbaric oxygen (HBO) therapy, carbogen inhalation therapy, intraocular pressure reduction (with systemic or local agents), anticoagulation therapy, sublingual isosorbide therapy, and systemic steroid therapy. The goal of each is to increase blood flow and blood oxygen content.
Invasive procedures include anterior chamber paracentesis, laser embolectomy, pars plana vitrectomy, and intraarterial thrombolysis. Most invasive procedures are aimed to reducing intraocular pressure and lyse/dislodge the obstructive embolus, although none of the treatments has enough supportive evidence to become the standard of care. Recent publications demonstrated that intraarterial thrombolysis may be an alternative to recover blood flow and vision after embolic CRAO. [33]
Ocular massage
Ocular massage can dislodge the embolus to a point further down the arterial circulation and improve retinal perfusion.
Anterior chamber paracentesis
This procedure involves letting out aqueous from the anterior chamber, which causes a decrease in intraocular pressure. This is believed to allow greater perfusion, pushing emboli further down the vascular tree. However, according to one study, anterior chamber paracentesis added no gain in visual acuity, regardless of the interval between onset of symptoms and time of treatment. [34]
Medical reduction of intraocular pressure
Acetazolamide 500 mg IV or 500 mg PO can be administered to immediately lower intraocular pressure.
Topical medications are also used to lower intraocular pressure.
Laser embolectomy
Lysis of the emboli can be achieved with Nd:YAG laser. [35, 36, 37] Retinal perfusion with gain of visual function can be achieved. However, complications such as creation of false aneurysms and vitreous hemorrhage may arise.
Pars plana vitrectomy with direct central retinal artery massage
A probe was designed to apply direct gentle pressure/massage over the CRA and the optic nerve head. Of 10 patients, circulation was restored in only 4. [38]
Intra-arterial fibrinolysis
CRAO is one of the few ophthalmology emergencies in which management depends on time of onset. Intraarterial thrombolysis has been used anywhere from 1 hour to up to 24 hours, although this procedure is very controversial. [39]
Dumitrascu calls for nonarteritic CRAO patients to be treated the same as patients with acute cerebral ischemia, and for these patients to receive the same thrombolytic therapies, in the same time frame. [40]
However, according the American Academy of Ophthalmology Preferred Practice Pattern, no level I data exists to support any single specific therapy, and in the absence of strong evidence-based data, more aggressive treatments, such as thrombolysis, have associated risks and cannot be recommended.
Thrombolytic agents that have been studied for CRAO treatment include intra-arterial tissue plasminogen activator (tPA) and urokinase.
According to Wang et al, digital subtraction angiography (DSA)–guided superselective ophthalmic artery or selective carotid thrombolysis remains the preferred treatment method for CRAO. [41] More recently, branch retrograde thrombolytic intervention of the ophthalmic artery (urokinase and papaverine) was shown to be effective for CRAO. [41] Mercier et al reported that fibrinolysis was more effective than conservative management in 16 patients with CRAO. [42] In 11 patients, Nedelmann et al found clinically relevant visual improvement with thrombolysis in patients with CRAO only in the absence of a “spot sign,” an ultrasonographic sign they hypothesize may indicate calcified intra-arterial emboli due to atherosclerotic plaques. [43]
Conversely, Pielen et al found no clear benefit from intra-arterial fibrinolysis, even in otherwise ideal candidates (ie, young age, without history of coronary heart disease, and early treatment). [44] Ahn et al showed that approximately 40% of patients undergoing intra-arterial thrombolysis showed a no-reflow phenomenon, and those with the no-reflow phenomenon suffered a worse visual outcome, with more retinal atrophy and disruption of photoreceptors. [45] However, in a separate study, Ahn et al concluded that intra-arterial thrombolysis may help patients with incomplete CRAO. [46]
McLeod and Beatty reported that, once CRAO exceeds 2 hours, emergency fibrinolytic therapy is inappropriate. [47]
Systemic complications of fibrinolytic therapy include transient ischemic attack (TIA), stroke, intra-cerebral hemorrhage, and hematoma.
In a meta-analysis, Schrag et al suggested that early systemic intravenous fibrinolytic therapy might be helpful in CRAO and called for a clinical trial. [48]
The European Assessment Group for Lysis in the Eye (EAGLE) [49] trial was a multicenter, randomized, controlled trial involving 82 patients with acute CRAO (< 20 hours). EAGLE compared the effect of intra-arterial tPA to “conservative” treatments (eg, IOP lowering medications, IV heparin, hemodilution, ocular massage, daily ASA therapy). In this trial, 42 patients (51.2%) received localized intra-arterial tPA in either the ophthalmic artery or external carotid artery collaterals feeding into the ophthalmic artery. There was no statistically significant improvement in visual acuity after intra-arterial tPA administration compared to conservative treatment. Interestingly, 60% of patients in the conservative treatment group and 57% of patients in the thrombolysis group experienced 3 or more lines of improvement in visual acuity. However, 37.1% of the thrombolysis group (versus only 4.3% of the conservative treatment group) experienced adverse reactions (eg, epistaxis, oral hemorrhage, dizziness, headaches, intracranial hemorrhages, hemiparesis, postprocedural hemorrhage). The study was terminated at the first interim analysis because of the increased incidence of adverse events in the tPA treatment group.
A second placebo-controlled randomized trial studying the effect of intravenous (IV) tPA on visual outcome in 8 patients with CRAO also did not show a significant improvement. One patient in the IV tPA cohort developed intracranial hemorrhage.
A meta-analysis of studies comparing standard therapy with intra-arterial thrombolysis included 5 retrospective studies and one randomized controlled trial (ie, EAGLE study). Pooled data from these studies favored use of intra-arterial thrombolysis over standard therapy, with 50.4% of those treated with intra-arterial thrombolysis demonstrating improved visual acuity versus 31.8% of those treated with standard therapy (P < 0.005). This was despite the fact that the EAGLE study did not show any statistical significance in improvement of best-corrected visual acuity (BCVA) among the two groups. However, the included studies showed dramatic variations in the efficacy of both intra-arterial thrombolysis (23.5%-80% in visual acuity improvement) and conservative therapies. The EAGLE study design has been questioned owing to its broad inclusion criteria, as it included patients with incomplete, subtotal, and complete occlusion. The treatment outcomes vary significantly depending on the type of presentation. Clinically significant visual outcomes can be expected in patients with incomplete or subtotal occlusion, as opposed to those with complete occlusion.
More randomized controlled studies, including limiting the study group to incomplete or subtotal CRAO, as opposed to including those with complete occlusion, which by itself has a poor prognostic outcome, would be a better design to analyze and compare the efficacy of standard therapy with intra-arterial thrombolysis. [50]
Hyperbaric Medicine
Early treatment (< 2 hours from onset of symptoms) with hyperbaric oxygen (HBO) therapy may be associated with increased visual recovery, but HBO therapy can be considered if the duration of visual loss is less than 12 hours.
Inhalation of 100% oxygen at 2 atmospheric absolute provides an arterial pO2 of 1000-1200 mm Hg, resulting in a 3-fold increase in oxygen diffusion distance through ischemic retinal tissues. Some studies show a 40% improvement of 2 or more levels of visual acuity.
One study shows that HBO decreased neovascularization from 30% to 20% in patients with CRAO. [51]
Inpatient Care
Inpatient care is indicated only if comorbid disease is present. Acute cases may require in-hospital evaluation for stroke risk factors. In a 2009 survey of US ophthalmologists in Georgia, only 35% reported referring patients with CRAO to the hospital. Another US-based vitreoretinal specialist and neurologist survey revealed that, for a hypothetical patient with a CRAO (< 12 hours), only 18% of vitreoretinal specialists would pursue hospital admission to a stroke unit or ER referral. In contrast, 75% of neurologists would refer to the hospital. Only 46% of neurologists and 8% of vitreoretinal specialists would pursue hospital evaluation for CRAO onset between 24 and 48 hours.
Transfer
Transfer to a hyperbaric facility is necessary if HBOT is to be administered.
Prevention
Patients should control their blood pressure, lower their cholesterol, avoid intravenous drugs, and take their medication.
Long-Term Monitoring
A follow-up ophthalmic examination should be performed 1-4 weeks after the event to check for neovascularization of the disc or iris. Intravitreal injection of an anti-VEGF agent is first-line therapy for neovascularization of the iris, trabecular meshwork, or optic disc. Neovascularization of the iris occurs in 20% of patients at an average of 4-5 weeks after the event. Panretinal photocoagulation is effective in causing regression of iris neovascularization in 65% of patients. Neovascularization of the disc occurs in 2-3% of patients. Panretinal photocoagulation is effective for optic disc neovascularization.
A complete systemic workup should be performed by a primary care provider. Hospital admission, cranial MRI (including diffusion weighted imaging) and MRA, and consultation with the neurology stroke service may be useful, especially in acute cases.
If hyperbaric oxygen therapy (HBOT) is to be used, several treatments may be necessary, although this treatment is unproven.
