Hollenhorst Plaque

Etiology

HPs tend to originate from carotid arteries or the aorta. This finding is consistent with carotid disease originating from atherosclerotic lesions. Upon discovering an HP, eye care professionals initially assumed that it originated from the stenosed, ipsilateral internal carotid artery (ICA). The direct anatomical route between the ICA and the central retinal artery (CRA) supports this assumption. The ophthalmic artery is the first branch of the ICA, which then leads into the CRA.[5][6]

Epidemiology

The Blue Mountains Eye study stated that the prevalence of retinal emboli is 1.4% in the general population older than 49 years.[7] The prevalence increases with age. Retinal emboli are significantly more prevalent in men than in women. HPs make up 80% of retinal emboli. An estimated 10% of carotid emboli reach the retinal arteries.[8]

In the Beaver Dam Eye Study, comprising almost 5000 patients, the prevalence of HPs was 1.3%, and the 5-year incidence was 0.9%.[9] In a study of 130 consecutive patients with a diagnosis of HP alongside central or branch RAO, the mean age of the patients was 68 ± 16 years, and the incidence of symptomatic patients was 61%.[10]

The incidence of asymptomatic retinal emboli is 1.4%. Cholesterol emboli are more prevalent in men than women (2.2% vs 0.8%).[11][12] Eighty percent of all retinal emboli are of the cholesterol type.[4][11] Significant links with hypertension (odds ratio [OR], -2.2), vascular disease (OR, -2.4), past vascular surgery (OR, -3.5), and current smoking history (OR, -2.2) or any smoking history (OR, -2.6) have been observed.[11]

Pathophysiology

Ulcerated plaques just distal to the bifurcation of the common carotid artery into its external and internal branches may be a source of retinal emboli that can be asymptomatic or produce transient monocular blindness.[13][14] Cholesterol plaques are seen in the retina owing to their relatively small size and decreased velocity while traveling through the internal carotid system.

History and Physical

HP is a marker of past embolic events but is a poor predictor of future events. These plaques may or may not cause an RAO. The discovery of asymptomatic emboli has a greater concern for a patient’s systemic health than visual health. Most HPs are discovered incidentally during funduscopy. They often dislodge and are not noted on subsequent fundus examinations.

An HP is a clinical sign, commonly a contributing factor in diagnosing RAO. The plaque must completely obstruct the vessel for an HP to cause an RAO. RAOs can occur in the central retinal artery (CRAO) or one of its branches (BRAO). HP is a possible cause of a CRAO/BRAO and should not be considered synonymous.

As noted in the differential diagnosis, other types of emboli can occlude the relevant vessels. There are also nonembolic causes of RAO, including nocturnal arterial hypotension and transient vasospasm. HP, like other types of retinal emboli, may not stay in 1 place. The plaque may dislodge and move to a smaller diameter vessel before it gets lodged again, or the plaque may dissolve completely. The presence of an HP is a confirming diagnosis; however, the absence of a plaque does not rule out the possibility of embolic occlusion.

If an RAO occurs, the most common symptom is sudden, painless vision loss. The fundus will display typical ischemic signs, such as retinal whitening around the occluded vessel (see Images. Hollenhorst Plaques). The macular area will remain “cherry-red” due to its secondary outer retinal blood supply. If the plaque only partially occludes the vessel, blood can still flow through the lumen, and no damage occurs. A single eye can undergo more than 1 transient RAO. 

Evaluation

Diagnostic tools which may be employed in the evaluation of HPs include the following:

Auscultation of the ipsilateral carotid for the presence of a bruit.                                                                 

Blood pressure measurement to rule out hypertension or hypotension.                                                          

Electrocardiogram (ECG) for atrial fibrillation (AF).                                                                                       

Carotid duplex study- A significant stenosis is characterized by a diameter reduction of 80% to 99%, a peak systolic velocity of >125cm/sec, and an end-diastolic velocity of>140cm/sec alongside extensive spectral broadening. Carotid bifurcation stenosis was <30% in 68% of the patients, between 30% and 60% in 22% of the patients, and >60% in only 8% of the patients.[10] Significant carotid internal artery stenosis was detected in 7% to 20% of patients with asymptomatic retinal emboli and 20% to 25% of patients with BRAOs.[15]                                                                                                                              

Echocardiography (ECHO) study for determining the cardio-embolic source.                                                    

CT or MRI 4-vessel carotid angiography to evaluate for stenosis, dissection, and/or dysplasia. CT angiography has a sensitivity of 85% and a specificity of 93%.[16]                                                                                                      

Blood test for ruling out any hypercoagulopathy.                                                                                          

Fluorescein angiography shows delayed or absent fill in the retinal artery (most specific sign), prolonged arteriovenous transit time (most sensitive sign), and capillary nonperfusion (loss of endothelial cells, pericytes, and lumen obliteration). Staining of retinal vessels (endothelial cell damage due to chronic ischemia), macular edema, and hyperfluorescence within the optic disk in OIS are also observed, caused by leakage from the disk and capillaries.[3][17] Indocyanine green angiography shows prolonged arm-to-choroid and intrachoroidal circulation times and slow filling of the watershed zones.[3]

Visual-evoked potentials (VEP), electroretinography (ERG), and ophthalmo-tonometry are seldom used.[3] Electroretinography shows reduced amplitudes of both the a- and b-waves.[18]                                             

Optical coherence tomography (OCT) shows thick, hyperreflective inner retinal layers with blocked outer retina reflectivity. Eventually, the retina is thinned out and appears atrophic. This also demonstrates a reduction in the foveal avascular zone and improved vessel density in all retinal layers after carotid artery stenting for OIS.[19]

B-scan ultrasonography or orbital computed tomography (CT) scan to rule out compressive lesions.

Treatment / Management

Immediate ocular massage may help dislodge the emboli.[17] Irreversible retinal damage occurs within 240 minutes of central RAO.

Surgical embolus removal was first attempted in 1990 by Peyman and Gremillion. This was achieved in 87.5% with reperfusion and improved visual acuity in 4 of 6 patients in 1 study.[17]

The treatment decision for carotid stenosis is primarily based on the degree of stenosis and associated symptomatology.

For patients with <50% stenosis - antiplatelet therapy is advocated in the form of:

• Cyclooxygenase-2 (COX-2) inhibitor- Aspirin
• Adenosine diphosphate (ADP) receptor inhibitor- Clopidogrel and
• ADP reuptake inhibitor- Dipyridamole

This minimizes the risk of a 5-year stroke rate by almost 50%. Subgroup analysis in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial revealed that atorvastatin reduced the risk of both cerebrovascular and cardiovascular adverse events.[20]

For patients with >70% stenosis - are considered for surgical interventions in the form of either CEA or carotid angioplasty and stenting (CAS). Both are safe and effective, with increased odds of myocardial infarction following CEA and an increased risk of stroke following CAS. They also have a comparable risk for fatal or disabling stroke.[21] Evidence is poor for purely ocular transient ischemic attacks (TIAs).(A1)

North American Symptomatic Carotid Endarterectomy Trial (NASCET) showed that surgical intervention was markedly effective with cohorts with 70% to 99% stenosis.[22] This significantly reduced the 2-year risk of ipsilateral stroke rate compared to medical management alone (9% vs 26%)  among symptomatic cohorts presenting with transient monocular visual loss, transient ischemic attack, or nondisabling strokes. Comparable findings were observed among symptomatic patients within the European Carotid Surgical Trial.[23] A meta-analysis comprising 5223 patients with asymptomatic moderate to severe stenosis and low perioperative risks favored CEA (relative risk, 0.69). CAS is also comparable to endarterectomy in terms of risk of procedural stroke (2.9 vs 1.7%) and survival (87.1% vs 89.4%). The 5-year stroke-free survival was similar (93.1% vs 94.7%).[24](A1)

For patients with 50% to 69% stenosis - there was a considerable drop in the benefits following surgery.

The Asymptomatic Carotid Atherosclerosis Study and Asymptomatic Carotid Surgery Trial showed a risk reduction of 53% and 46% among cohorts with 60% stenosis with CEA.[25] Guidelines recommend CEA when the risk of perioperative stroke, myocardial infarction, or mortality is considerably low.(A1)

No ocular treatment is necessary unless an HP completely obstructs a vessel, causing an RAO. All patients with retinal emboli should be referred to the patient’s primary care provider for a bilateral carotid duplex study. The management considers the following:

• Patient education on HA as primarily an underlying etiology
• Lifestyle modifications and combating risk variables (diabetes, hypertension, hyperlipidemia, sedentary lifestyles, obesity, cigarette smoking) and
• Aspirin for arteriosclerosis

Differential Diagnosis

Types of Retinal Emboli:

• Calcific emboli- appear whitish, involve the central retinal artery, do not dissolve, and originate from cardiac valves or aorta calcification.                                                                                                                    
• Fibrinoplatelet emboli- appear dull white within the retinal arteriole and arise from carotid thrombus.                   

• Talc emboli- observed in patients with an intravenous drug and/or cocaine addiction, are relatively small and appear parafoveally.[26]                                                                                                                                      
• Metastatic tumor cells                                                                                                                             

• Septic emboli- following bacterial endocarditis                                                                                           

• Fat emboli- occur following long bone fractures and have concomitant scattered retinal microinfarcts and hemorrhages.[27]                                                                                                                                                 
• Amniotic fluid emboli [28]                                                                                                                                                                                                                                                                                
• Air emboli [17][29]

Prognosis

The atheromatous disease of the ICA can be associated with HPs and is usually an indicator of potential stroke. Carotid stenosis increases stroke risk by 1.18 times for every 10% increase in stenosis. This risk of stroke rises <1% per year for a vessel that is <80% stenosed. On the contrary, a vessel >90% stenosed raises the stroke risk by 4.8% per year.

Almost 75% of HPs are asymptomatic. Asymptomatic HP, however, is a poor predictor of future embolic events.[12] However, 25% of these cohorts have carotid stenosis of >40%.[4] Symptomatic patients were more likely to harbor carotid stenosis >69% when compared with asymptomatic patients (25% vs 9.2%).[12]

Patients with retinal cholesterol plaques had a higher incidence of stroke compared to their healthy counterparts (8.5% vs 0.8%).[12] Cholesterol emboli have a 15% risk of mortality at 1 year, 29% at 3 years, and 54% at 7 years.[12] Hollenhorst observed that survival reduced by almost 15% and 40% at 1 and 8 years, respectively, in patients with retinal cholesterol embolism.[4] These patients have increased odds of stroke-related deaths (hazard ratio, 2.61).[9] The cumulative mortality was 56% with retinal emboli and 30% without retinal emboli.[4] The risk of nonfatal myocardial infarction or vascular death was 7.7% (4.9% among controls).[30]

Asymptomatic retinal cholesterol embolism is a risk variable for cerebral infarction.[30] In a meta-analysis of 1343 patients with asymptomatic cholesterol emboli, 17.8% had a history of either cerebrovascular accident (CVA) or TIAs at presentation. Twelve percent of these patients evolved to stroke, TIAs, or death during their follow-up.[31] The evidence suggests that these patients warrant referral for medical optimization of pertinent cardiovascular risk factors.

Currently, no recommendation exists to support CEA in patients with HPs or retinal emboli alone.[31] In a study with 159 patients with CRAO, 284 with BRAO, and 85 with HP, mortality and cerebrovascular events were statistically significantly higher in only the CRAO and BRAO groups.

Complications

Complications of HPs include the following:

• Central retinal artery occlusion (CRAO)
• Branch retinal artery occlusion (BRAO)
• Ischemic strokes [32]