Keeping an eye on vascular disease

Coronary microvascular dysfunction can be challenging to identify by epicardial coronary angiography and is better appreciated by the more sensitive imaging modality of myocardial perfusion scintigraphy. Similarly, manifestations of atherosclerotic peripheral vascular disease (PVD) – which may escape even an alert and educated clinician – may at least passively be apparent to the optometrist or ophthalmologist performing indirect ophthalmoscopy during a routine eye examination. The retina is a magnificent storyteller, often providing microvascular evidence of disease in more distant vascular beds. ¹ This (usually noninvasive) examination, however, takes a certain degree of skill and practice to conduct during a routine office evaluation by direct ophthalmoscopy. ¹

Clinicians who routinely conduct a funduscopic exam are attuned to retinal manifestations of systemic atheroembolic disease – typically from the ipsilateral internal carotid artery or one of the great cardiac vessels in the form of refractile cholesterol particles. So it seems that Robert W Hollenhorst, MD, who reported this observation in 1961 in the American Journal of Ophthalmology, was ahead of his time in believing the eye is a window to evaluate remote vascular disease. ² Though most vascular specialists are familiar with the term ‘Hollenhorst plaques’, they may be less familiar with the term ‘Hollenhorst syndrome’, a form of unilateral blindness related to increased intraocular pressure and decreased systemic arterial pressure from general anesthesia that was reported even earlier in 1954. ³ Atheroembolism from a proximal arterial bed to the retina often manifests as branch retinal artery occlusion (BRAO) or the more serious central retinal artery occlusion (CRAO). According to an expert consensus statement from the American Heart Association (AHA) and American Stroke Association (ASA), retinal ischemia should be treated with similar urgency as one would for a patient presenting with transient ischemia attack (TIA). ⁴ CRAO and BRAO fall under the umbrella of ocular ischemic syndromes (OIS) and are associated with an increased risk of symptomatic stroke. ⁵ On the venous side of the retinal vasculature, central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) have been associated with systemic hypertension and, somewhat surprisingly, atrial fibrillation. ⁶ Once again, this presents the vascular specialist with an opportunity to engage patients in a therapeutic relationship and further attempt to reduce risk factors associated with stroke.

With advances in imaging modalities and the introduction of artificial intelligence (AI) into diagnostic medicine, it has never been easier to serve our patients with vascular disease. As tangible evidence of the latter concept, it was demonstrated using anatomic features of a single funduscopic retinal image in 284,000 patients that deep learning models accurately predict previously undetected cardiovascular risk factors by examination of the retina. ⁷ Recently, Yang and colleagues reported data from the Atherosclerosis Risk in Communities (ARIC) registry over an observational period of almost 19 years that pathological retinal findings by funduscopic evaluation including hard and soft exudates, as well as microaneurysms, strongly predict the development of peripheral artery disease (PAD). These observations held true even after adjusting for confounders such as diabetes. ⁸ These data present the vascular specialist with another opportunity to employ medical therapy to mitigate the risk of developing PVD and progression of PVD. Narrowing of retinal arteries was found to predict coronary microvascular disease as determined by magnetic resonance imaging (MRI). ⁹ Similarly, Allon and colleagues more recently reported data from 11 prospective studies that anatomic divergence from normal caliber retinal vasculature including the appearance of dilated retinal veins, narrowed retinal arteries, and tortuosity (seen frequently by our colleagues in optometry and ophthalmology) predict systemic cardiovascular disease. ¹⁰

Every vascular medicine physician is familiar – at least in principle– with transcranial Doppler (TCD) to interrogate the cerebrovascular circulation. Few will be as familiar with the concept of imaging the retina directly via the transorbital acoustic window. In this issue of Vascular Medicine, Dr Ruiz-Ares and colleagues from La Paz University Hospital in Madrid took an innovative approach in using transorbital duplex to interrogate the ophthalmic artery and the central retinal artery. ¹¹ In a 7-year observational period, the authors evaluated patients with transient or permanent monocular blindness and reduced blood flow in the ophthalmic artery or central retinal artery, with the aim of determining if this imaging technique could clarify the etiology of CRAO. Using an insonation angle of 30 degrees and a 7.5-MHz linear array transducer with a 2-mm sampling gate, the authors evaluated the ophthalmic artery and the central retinal artery. Receiver operating characteristic (ROC) analysis was utilized and identified a cut-point peak-systolic velocity (PSV) of < 10.0 cm/second, with sensitivity of 80% and specificity of 73% (area under the curve, 84%) for confirming a diagnosis of CRAO. Carotid duplex imaging to determine the presence of ipsilateral carotid atheroma, age, and the presence of hypertension were used in a logistic regression model to validate the authors’ data. The authors concluded that transorbital imaging can distinguish CRAO from other causes of monocular vision loss. Given the training and well-developed skill set vascular medicine specialists have in ultrasound, transorbital evaluation of the retina certainly offers an additional noninvasive approach to assess the progression of a patient after reperfusion of the retina when, for example, the obstructive material causing CRAO clears. Certainly, in the practice of vascular medicine, this technique would be more practical than slit lamp ophthalmoscopy following a diagnosis of CRAO. Since retinal blood flow is almost always assessed by an optometrist or ophthalmologist and issues with orbital blood flow are managed more often by vascular medicine specialists or vascular neurologists, the capability of transorbital ultrasound to evaluate both offers a more comprehensive evaluation. The authors are to be congratulated on the results of this preliminary study.

Vascular medicine specialists now have the opportunity to explore the eye as an auspicious storyteller of active and impending systemic vascular disease. Collaborative patient care has always been a strength of the vascular medicine physician. ¹² Partnering with medical professionals, such as optometrists and ophthalmologists who may traditionally have less contact with vascular medicine specialists, can positively impact patient care. Just as the vasculature unifies every organ system, the vascular medicine specialist continues to unify multiple medical specialties, bridging gaps in medical care.