Patients with MVL often present to physicians with isolated visual symptoms. The present study demonstrates that MVL does not always represent an isolated disruption of the retinal circulation; approximately one out of every four patients with MVL presumed to be caused by ischemia in the retinal arterial system demonstrate DWI positive brain infarcts that have occurred either concurrently or closely related in time. These infarcts are typically small, often multiple, frequently occur in the hemisphere ipsilateral to the involved eye, and tend to remain asymptomatic. The probability of concurrent brain infarcts is higher in MVL presumed to be caused by an embolic mechanism as compared to non-embolic events and in permanent visual loss as compared to transient symptoms. The current study also shows that the identification of concurrent acute brain infarcts in a patient with MVL is important because it suggests the patient has an elevated risk of harboring a major underlying etiology that might be amenable to urgent treatment; patients with concurrent brain infarcts had approximately 50% higher risk of having a major etiology as compared to patients with normal brain imaging.
The course of the embolic material after it enters into the carotid circulation is one of the key determinants of the clinical symptoms – retinal, cerebral or both – that the patient is going to present with. It has been suggested that embolic particles enter into the ophthalmic artery, the first major branch off of the internal carotid artery, only when they are “small” enough to travel along the walls of the internal carotid artery.12
Suspended particles in the bloodstream are distributed along a radial gradient where large particles are more concentrated in the axial stream and small particles are in the peripheral streamline (Fahraeus-Lindqvist effect).5, 13
In a human cadaveric perfusion model, selective distribution to regions supplied by the most axial stream (watershed zones) was observed when particles around 200 micrometers were injected into the ICA.14
In contrast, there was no selective distribution to axial branches when particles less than 150 micrometers were injected. In another experiment, in an in-vitro model of unevenly bifurcating system, perfusion with 200 micrometer particles resulted in lower concentration of particles in smaller branches while particles less than 100 micrometers showed no relative concentration shift across branches of different size.14
Published evidence, thus, suggests that the critical size that determines selective distribution of embolic material into an unevenly branching artery (such as the ophthalmic artery) is around 150 micrometers. The size of most of the major arteries in the retinal circulation is, however, larger than 150 micrometers; the vascular diameter is 1600 micrometers (1500–1800 micrometers) at the origin of the ophthalmic artery from the ICA, 200 micrometers (100–400 micrometers) at the proximal central retinal artery, and 110 micrometers (60–160) at the major retinal branch arteries.3, 15
Thus, embolic particles that are large enough to preferentially travel in the axial streamline along the ICA can sometimes lodge into the retinal circulation causing concurrent retinal symptoms and brain lesions. In contrast, emboli small enough to travel in the peripheral streamline are preferentially distributed to the ophthalmic artery, occlude branch retinal arteries, and often cause partial, transient, and isolated MVL. It is possible that such small particles are also distributed into the hemispheric circulation. Nevertheless, they only rarely cause infarcts detectable by MRI possibly due to rapid spontaneous resolution or rich pial anastomoses,16
while their counterparts entering into the ophthalmic circulation lead to retinal symptoms.
Strengths of the present study include consecutive recruitment of subjects, stringent ascertainment of the diagnosis of MVL by detailed ophthalmologic and neurological assessment, and thorough diagnostic investigation for the underlying mechanism of MVL. Limitations include retrospective design and failure to obtain brain imaging in every patient. Although we collected data retrospectively through chart reviews, this is unlikely to have caused a systematic bias towards selection of a particular population because all patients admitted with the complaint of MVL underwent a standard battery of laboratory tests and physical examination. Even though we excluded 21 patients due to unavailability of DWI, baseline patient characteristics and MVL features (listed in ) were similar between patients with and without MRI, arguing against a potential selection bias. Incidental small DWI lesions can occur in up to 15% of patients with diffuse small vessel disease associated with ischemic leukoaraiosis, amyloid angiopathy, or CADASIL. 17, 18
Nonetheless, the presence of a temporal relationship with MVL, the existence of a high-risk cardiac or arterial mechanism in the majority, and inappropriate location of most infarcts for small vessel disease make it unlikely that DWI lesions observed in the current study were incidental. Finally, it should be acknowledged that contamination of studies such as the present one by retinal ischemic events due to non-embolic mechanisms (such as hemodynamic failure or retinal vasospasm) is inevitable and such contamination obviously blurs the relationship between MVL and concurrent brain infarcts.
Our findings have implications for a wide range of physicians (including but not limited to primary care physicians, emergency physicians, ophthalmologists, neuro-ophthalmologists, internists, neurologists) involved in the care of patients with MVL by highlighting the need for urgency in obtaining brain imaging and performing a full diagnostic work-up in patients suspected to have had ischemic MVL. Although recent American Heart Association/American Stroke Association guidelines recommend that all patients with suspected brain or retinal ischemia should undergo urgent brain imaging and etiologic testing,19
the current practice in MVL does not a priori require brain imaging as a part of the diagnostic work-up.20, 21
A recent survey among US physicians shows that there is significant reluctance even in referring patients with MVL due to central retinal artery occlusion to an emergency room for urgent assessment;22
only 35% of ophthalmologists and 73% of neurologist reported sending such patients for immediate evaluation. In a study conducted in the Netherlands, only 72% of patients with transient MVL were referred by general practitioners to a specialist.23
Our findings suggest that patients presenting with symptoms consistent with ischemic MVL, whether it is isolated or accompanied by other neurologic symptoms, should be referred urgently for brain imaging to exclude concurrent brain ischemia. Given that up to 12% of untreated patients with brain ischemia develop a recurrent stroke in two weeks,24
urgent work-up of imaging positive patients with MVL would facilitate timely identification of the underlying etiology, early institution of specific preventive treatments, and reduction in risk a subsequent devastating stroke. Future studies are needed to elucidate whether MVL associated with concurrent brain infarcts poses a higher risk of subsequent stroke as compared to MVL without accompanying acute brain infarcts.