Hyperbaric Treatment of Central Retinal Artery Occlusion

Etiology

Blockage of the central retinal artery may be related to thromboembolic disease, vasospasm, and vasculitis. Risk factors for this ischemic event overlap with those for ischemic cerebrovascular accident and systemic vasculopathy, including hypertension, diabetes mellitus, hyperlipidemia, cardiovascular disease, ipsilateral carotid artery atherosclerosis, arrhythmia, smoking, obesity, older age, male sex, and coagulopathy. CRAO is classified into arteritic and nonarteritic causes. Giant cell arteritis is a potentially fatal vasculitic cause.

Epidemiology

CRAO occurs more frequently in men, with an incidence of approximately 1 in 50,000 to 100,000 and a mean age of 60 to 65 years.[1] CRAO due to arteritis is most commonly caused by giant cell arteritis, though systemic lupus erythematosus and other vasculitides, such as polyarteritis nodosa, may also cause CRAO. Most CRAOs are nonarteritic, with approximately 90% classified as such. Carotid artery disease is the most common cause of retinal artery occlusion, accounting for approximately 70% of cases.[2] Additional nonarteritic causes include cardioembolism from atrial fibrillation, thrombotic disorders associated with hypercoagulable states and hematologic malignancies, and vaso-occlusive disease, such as sickle cell disease.

CRAO is a rare emergent ocular condition and should be suspected in any patient with unilateral, sudden, painless vision loss, often limited to counting fingers or light perception. The absence of light perception suggests ophthalmic artery occlusion, which causes permanent and severe vision loss. HBOT is not appropriate in this setting due to the absence of ciliary collateral circulation required for retinal viability, though thrombolysis may be considered.

Pathophysiology

The central retinal artery is the 1st branch of the ophthalmic artery, itself a branch of the internal carotid artery. The central retinal artery perfuses the inner retinal layers via superior and inferior branches. Approximately 15% to 30% of the population also possesses a cilioretinal artery, a branch of the short posterior ciliary artery. The cilioretinal artery perfuses the fovea and preserves central visual acuity when spared. The classic cherry red spot fundus appearance develops due to edema of the ischemic inner retina, which obscures choroidal circulation. The foveola lacks inner retinal layers, allowing continued visualization of choroidal circulation as a cherry red spot surrounded by retinal edema and opacification. Inner retinal layer atrophy follows edema resolution and is associated with poor visual outcomes.

The retina has a dual blood supply, with the choroid supplying the outer retinal layers. The theory underlying HBOT is that increased fraction of inspired oxygen (FiO2) enhances oxygen diffusion from choroidal circulation to the ischemic inner retina. Increased FiO2 requires initiation prior to irreversible cellular loss and maintenance until retinal vessel recanalization. Recanalization typically occurs within 72 hours.

The most extensive published case series (Hayreh) demonstrated the natural progression of the disease without HBOT. Transient symptoms lasting minutes to hours were observed in some patients, with spontaneous resolution and minimal residual visual impairment. A variant retinal vascular supply, the cilioretinal artery, is present in nearly 50% of the population and approximately 1 in 3 eyes, with substantial variability in retinal territory perfusion.[3] Cilioretinal arteries may preserve central retinal function in selected cases. Outcomes in patients without cilioretinal arteries remain poor without HBOT, with less than 2% recovering baseline vision and approximately 80% limited to light perception, motion detection, or finger counting.[4] Patients with cilioretinal arteries demonstrate significantly more favorable outcomes.

History and Physical

CRAO presents as sudden-onset, painless vision loss. Visual acuity is often worse than 20/200, with presentation typically limited to light perception, hand motion detection, or finger counting. Absence of light perception suggests ophthalmic artery occlusion, with absence of perfusion to choroidal vessels. Preserved central visual acuity with fundoscopy consistent with CRAO suggests a cilioretinal artery blood supply. Fundoscopic findings may demonstrate a pale yellow ischemic retina. A cherry-red spot may be present at the macula but is an inconsistent and unreliable finding. The cherry-red spot is associated with poor outcomes (see Image. Central Retinal Artery Occlusion).[5]

Evaluation

CRAO represents a "stroke of the eye" and requires the same urgency as an evolving stroke or myocardial infarction. Oxygen administration by nonrebreather mask should be initiated immediately during the evaluation. Fundoscopy should be performed and documented without delay. Ophthalmology consultation, preferably with a vitreoretinal specialist, should be obtained promptly. Ocular pain, a history of trauma, flashers or floaters, and age younger than 40 years are more commonly associated with ocular trauma, retinal detachment, or vitreous hemorrhage and make CRAO less likely.

Treatment / Management

General Treatment

Immediate management includes administration of supplemental oxygen at the highest available normobaric FiO2. Ophthalmology consultation should be obtained without delaying treatment when HBOT is readily available. Baseline laboratory evaluation includes complete blood count, erythrocyte sedimentation rate, C-reactive protein, prothrombin time, partial thromboplastin time, and international normalized ratio in patients receiving warfarin. Electrocardiography should also be performed. Carotid ultrasound, magnetic resonance imaging, and echocardiography may be performed later as part of a comprehensive evaluation for vascular risk factor modification, similar to stroke assessment. Symptom onset within 24 hours of presentation and lack of response to normobaric hyperoxia after 15 minutes warrant emergency hyperbaric medicine consultation.[6](B3)

Hyperbaric Oxygen Treatment Protocol

HBOT in CRAO is initiated with compression to 2 atmospheres absolute (ATA). Significant visual improvement at 2 ATA warrants treatment at that depth for 90 minutes. Absence of visual improvement after 30 minutes at 2 ATA necessitates compression to 2.4 ATA, followed by treatment at that depth for 90 minutes if vision improves. Failure to improve at 2.4 ATA warrants compression to 2.8 ATA and administration of the US Navy Treatment Table No. 6

Lack of improvement after the initial US Navy Treatment Table No. 6 is an indication for treatment discontinuation, use of normobaric oxygen therapy, or 2 additional treatments at 2.8 ATA for 90 minutes with 5-minute air breaks every 30 minutes twice daily, followed by reassessment after 4 to 6 days. Most patients reach a treatment plateau beyond which further improvement in visual acuity does not occur, at which point treatment may be discontinued. Some patients require up to 8 treatments before visual acuity improves, although response beyond that point is uncommon.[7]

A simpler protocol associated with favorable outcomes consists of treatment at 2.5 ATA for 90 minutes with 5-minute air breaks every 30 minutes twice daily for 2 to 3 weeks.[8] Fluorescein angiography provides a safe and valuable method for assessing successful central retinal artery recanalization.[9]

Differential Diagnosis

The differential diagnosis for acute painless vision loss includes central retinal vein occlusion, vitreous hemorrhage, retinal detachment, posterior circulation stroke, ischemic optic neuropathy, and amaurosis fugax. Overlapping clinical features necessitate exclusion of these conditions during the initial evaluation.

Pertinent Studies and Ongoing Trials

An unfavorable meta-analysis published in 2002 failed to demonstrate significant improvement in CRAO outcomes with HBOT despite treatment initiation within 12 hours of symptom onset in most patients.[10] Another equivocal study compared outcomes between 2 hospitals, one using HBOT and the other not. Although HBOT was associated with better outcomes, clinical significance was minimal, and no significant difference was observed in the proportion of patients achieving visual acuity better than 20/200.[11] HBOT has also been explored for central retinal vein occlusion, although published evidence is limited to case reports and small case series. Case reports describing favorable outcomes despite delayed treatment initiation are encouraging.[12] [Source: Assaf-Harofeh Medical Center. Hyperbaric Chamber for Central Retinal Vein Occlusion (CRVO) Patients. 2015]

Prognosis

HBOT initiated within 8 hours of symptom onset is associated with an 83% likelihood of improving visual acuity by at least 3 Snellen lines.[13] A case series of 39 patients with CRAO reported visual improvement in 72% of patients, with a mean gain of 5 lines on a modified Snellen chart.

Complications

Neovascularization may develop after CRAO, particularly in patients with diabetes mellitus. Neovascularization may result in progressive visual loss, neovascular glaucoma, and vitreous hemorrhage despite initial visual salvage with HBOT.[14] The effects of HBOT on this process are unknown.[15] HBOT is generally well tolerated, although confinement anxiety and otic barotrauma may occur. Other complications are uncommon.