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.
Background
Impairment of neurovascular coupling (NVC) was recently reported in the context of subarachnoid hemorrhage and may correlate with disease severity and outcome. However, previous techniques to evaluate NVC required invasive procedures. Retinal vessels may represent an alternative option for non-invasive assessment of NVC.
Methods
A prototype of an adapted retinal vessel analyzer was used to assess retinal vessel diameter in mice. Dynamic vessel analysis (DVA) included an application of monochromatic flicker light impulses in predefined frequencies for evaluating NVC. All retinae were harvested after DVA and electroretinograms were performed.
Results
A total of 104 retinal scans were conducted in 21 male mice (90 scans). Quantitative arterial recordings were feasible only in a minority of animals, showing an emphasized reaction to flicker light impulses (8 mice; 14 scans). A characteristic venous response to flicker light, however, could observed in the majority of animals. Repeated measurements resulted in a significant decrease of baseline venous diameter (7 mice; 7 scans, p < 0.05). Ex-vivo electroretinograms, performed after in-vivo DVA, demonstrated a significant reduction of transretinal signaling in animals with repeated DVA (n = 6, p < 0.001).
Conclusions
To the best of our knowledge, this is the first non-invasive study assessing murine retinal vessel response to flicker light with characteristic changes in NVC. The imaging system can be used for basic research and enables the investigation of retinal vessel dimension and function in control mice and genetically modified animals.
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.
Purpose: Image analysis by the retinal vessel analyzer (RVA) observes retinal vessels in their dynamic state online noninvasively along a chosen vessel segment. It has been found that high-frequency diameter changes in the retinal artery blood column along the vessel increase significantly in anamnestically healthy volunteers with increasing age and in patients with glaucoma during vascular dilation. This study was undertaken to investigate whether longitudinal sections of the retinal artery blood column are altered in systemic hypertension.
Methods: Retinal arteries of 15 untreated patients with essential arterial hypertension (age, 50.9 ± 11.9 years) and of 15 age-matched anamnestically healthy volunteers were examined by RVA. After baseline assessment, a monochromatic luminance flicker (530–600 nm; 12.5 Hz; 20 s) was applied to evoke retinal vasodilation. Differences in amplitude and frequency of spatial artery blood column diameter change along segments (longitudinal arterial profiles) of 1 mm in length were measured and analyzed using Fourier transformation.
Results: In the control group, average reduced power spectra (ARPS) of longitudinal arterial profiles did not differ when arteries changed from constriction to dilation. In the systemic hypertension group, ARPS during constriction, baseline, and restoration were identical and differed from ARPS during dilation (P < 0.05). Longitudinal arterial profiles in both groups showed significant dissimilitude at baseline and restoration (P < 0.05).
Conclusions: The retinal artery blood column demonstrates microstructural alterations in systemic hypertension and is less irregular along the vessel axis during vessel dilation. These microstructural changes may be an indication of alterations in vessel wall rigidity, vascular endothelial function, and smooth muscle cells in this disease, leading to impaired perfusion and regulation.
The present article describes a standard instrument for the continuous online determination of retinal vessel diameters, the commercially available retinal vessel analyzer. This report is intended to provide informed guidelines for measuring ocular blood flow with this system. The report describes the principles underlying the method and the instruments currently available, and discusses clinical protocol and the specific parameters measured by the system. Unresolved questions and the possible limitations of the technique are also discussed.