Retinal Vessel Analysis (RVA) in the context of subarachnoid hemorrhage: A proof of concept study
(2016)
Background
Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH.
Methods
In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2–14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling.
Results
Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion.
Conclusion
RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort.
Purpose: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself.
Methods: A total of 12 young 25.5-year-old (24.0–28.8) [median(1st quartile–3rd quartile)] and 12 senior 68.5-year-old (63.8–71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8–65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5–35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated.
Results: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280–500] RU/s) and in validated healthy seniors (400 [320–510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains.
Conclusions: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV.
Patients after coarctation repair still have an increased risk of cardiovascular or cerebrovascular events. This has been explained by the persisting hypertension and alterations in the peripheral vessels. However, involvement of the central vessels such as the retinal arteries is virtually unknown. A total of 34 patients after coarctation repair (22 men and 12 women; 23 to 58 years old, age range 0 to 32 years at surgical repair) and 34 nonhypertensive controls underwent structural and functional retinal vessel analysis. Using structural analysis, the vessel diameters were measured. Using functional analysis, the endothelium-dependent vessel dilation in response to flicker light stimulation was assessed. In the patients after coarctation repair, the retinal arteriolar diameter was significantly reduced compared to that of the controls (median 182 μm, first to third quartile 171 to 197; vs 197 μm, first to third quartile 193 to 206; p <0.001). These findings were independent of the peripheral blood pressure and age at intervention. No differences were found for venules. The functional analysis findings were not different between the patients and controls (maximum dilation 3.5%, first to third quartile 2.1% to 4.5% vs 3.6%, first to third quartile 2.2% to 4.3%; p = 0.81), indicating preserved autoregulative mechanisms. In conclusion, the retinal artery diameter is reduced in patients after coarctation repair, independent of their current blood pressure level and age at intervention. As a structural marker of chronic vessel damage associated with past, current, or future hypertension, retinal arteriolar narrowing has been linked to stroke incidence. These results indicate an involvement of cerebral microcirculation in aortic coarctation, despite timely repair, and might contribute to explain the increased rate of cerebrovascular events in such patients.
Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and can lead to infarction and poor clinical outcome. The underlying mechanisms are still incompletely understood, but animal models indicate that vasoactive metabolites and inflammatory cytokines produced within the subarachnoid space may progressively impair and partially invert neurovascular coupling (NVC) in the brain. Because cerebral and retinal microvasculature are governed by comparable regulatory mechanisms and may be connected by perivascular pathways, retinal vascular changes are increasingly recognized as a potential surrogate for altered NVC in the brain. Here, we used non-invasive retinal vessel analysis (RVA) to assess microvascular function in aSAH patients at different times after the ictus.