Multimodal dynamic retinal vessel analysis offers new insights in microvascular defects in Fabry's disease.

Fabry's Disease (FD) is one of many disorders that result in altered vascular function. With the Dynamic Vessel Analyzer (DVA, IMEDOS Systems), retinal vessels can be recorded non-invasively in real time and dynamic responses to stimuli that affect vessel diameter can be directly visualized. The data obtained can be further mathematically evaluated in terms of dynamic time- and location-dependent vessel behavior. This principle of multimodal analysis of dynamic retinal vascular behavior has been applied to demonstrate specific structural and functional retinal microvascular changes in Fabry's disease. The retinal vascular response was examined with DVA in 10 patients with FD, 4 women, 6 men including 1 child aged 42.5 (34.3-57.3) years (median (1st quartile-3rd quartile)) and in 10 age- and sex-matched healthy participants. The vessel width of an arterial and a venous retinal vessel segment of ~ 1 mm in length was examined in all participants. After 50 s of baseline observation, a monochromatic rectangular luminance flicker (530-600 nm; of 12.5 Hz frequency) was applied three times for 20 s. The vascular response to flicker light was analyzed. Using mathematical signal analysis, the longitudinal microstructure of retinal vessels was assessed and unstimulated vessel wall oscillations were characterized. Group comparisons were performed exploratively using Mann-Whitney-U test. The entire patient group showed no significant difference in response to the flicker light compared to the control group. After dividing the patient group by sex, male patients with FD showed significantly larger arterial dilatation of 6.3 (5.6-7.9)% compared to age-matched controls: 3.3 (2.5-4.1)%, p < 0.01. In contrast, female patients showed a reduced arterial response of 3.4 (3.1-3.7)% compared to age-matched controls: 5.4 (4.0-6.7)%, p = 0.1. When analyzing the periodicity of the spontaneous unstimulated vessel wall modulation, female Fabry patients had a higher and less scattered periodicity of vasomotions in arteries and veins, while male patients showed lower periodicity of vasomotions in arteries with more scattered periods and longer more scattered periods in veins, compared to age-matched controls. The cardiac rhythm was more aperiodic and less pronounced in male patients. In addition, the longitudinal microstructure of retinal arteries and veins in FD was structurally and functionally altered. This was particularly notable in veins at all stages of the vascular reaction and in arteries at all stages except the baseline by more pronounced waves with periods of ~ 50-100 µm. Multimodal dynamic retinal vessel analysis conveys information about different aspects of vascular regulatory potential. The flicker provoked retinal arterial response is more pronounced in male patients with FD. This reaction is nitric oxide (NO) mediated and conveyed by the vascular endothelial cells. With an altered baseline smooth muscle activity in vessel walls subsequent reactions to vascular stimuli such as flicker light for the retina may be more pronounced in the imbalanced system of male Fabry patients. Spontaneous retinal vessel oscillations are altered in Fabry's disease. These alterations are more dramatic in male patients, and are especially characterized with less periodic vessel behavior over the large frequency range. This is a result of altered smooth muscle reaction potentially due to disease mediated altered potassium channel activity. Both arterial and venous retinal vessel walls in FD show peculiar microstructural changes. The characteristic microirregularities of retinal vessels are of functional nature in arteries and rather of structural nature in veins. The DVA examination with multimodal retinal vessel analysis represents a practical possibility to investigate central microvascular status of Fabry's disease in more detail and might elucidate the effect of potential therapeutic interventions.