Multimodal Retinal Vessel Analysis in CADASIL Patients

Purpose To further elucidate retinal findings and retinal vessel changes in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients by means of high resolution retinal imaging. Methods 28 eyes of fourteen CADASIL patients and an equal number of control subjects underwent confocal scanning laser ophthalmoscopy (cSLO), spectral-domain optical coherence tomography (SD-OCT), retinal nerve fibre layer (RNFL) measurements, fluorescein and indocyanine angiography. Three vessel measurement techniques were applied: RNFL thickness, a semiautomatic software tool based on cSLO images and manual vessel outlining based on SD- OCT. Results Mean age of patients was 56.2±11.6 years. Arteriovenous nicking was present in 22 (78.6%) eyes and venous dilation in 24 (85.7%) eyes. Retinal volume and choroidal volume were 8.77±0.46 mm3 and 8.83±2.24 mm3. RNFL measurements showed a global increase of 105.2 µm (Control group: 98.4 µm; p = 0.015). Based on semi-automatic cSLO measurements, maximum diameters of arteries and veins were 102.5 µm (106.0 µm; p = 0.21) and 128.6 µm (124.4 µm; p = 0.27) respectively. Manual SD-OCT measurements revealed significantly increased mean arterial 138.7 µm (125.4 µm; p<0.001) and venous 160.0 µm (146.9; p = 0.003) outer diameters as well as mean arterial 27.4 µm (19.2 µm; p<0.001) and venous 18.3 µm (15.7 µm; p<0.001) wall thicknesses in CADASIL patients. Conclusions The findings reflect current knowledge on pathophysiologic changes in vessel morphology in CADASIL patients. SD-OCT may serve as a complementary tool to diagnose and follow-up patients suffering from cerebral small-vessel diseases

Criteria for Blood Vessel Discrimination

Introduction The diagnostic potential of optical coherence tomography (OCT) in neurological diseases is intensively discussed. Besides the sectional view of the retina, modern OCT scanners produce a simultaneous top-view confocal scanning laser ophthalmoscopy (cSLO) image including the option to evaluate retinal vessels. A correct discrimination between arteries and veins (labeling) is vital for detecting vascular differences between healthy subjects and patients. Up to now, criteria for labeling (cSLO) images generated by OCT scanners do not exist. Objective This study reviewed labeling criteria originally developed for color fundus photography (CFP) images. Methods The criteria were modified to reflect the cSLO technique, followed by development of a protocol for labeling blood vessels. These criteria were based on main aspects such as central light reflex, brightness, and vessel thickness, as well as on some additional criteria such as vascular crossing patterns and the context of the vessel tree. Results and Conclusion They demonstrated excellent inter-rater agreement and validity, which seems to indicate that labeling of images might no longer require more than one rater. This algorithm extends the diagnostic possibilities offered by OCT investigations

Confocal scanning laser (cSLO) infrared image illustrating semi-automatic measurement tool.

<p>Three concentrial circles (blue 3.2 mm, green 3.5 mm, red 3.8 mm) are placed around the optic disc. Vessel labelling marks arteries (a) and veins (v). Measurement lines (cyan) are defined by the software user. Additional measurement lines automatically produced by the software are shown exemplary in artery two (a2; set of five lines). Yellow lines separate superior (S), inferior (I), nasal (N) and temporal (T) quadrant.</p

Semi-automated vessel measurements based on confocal scanning laser ophthalmoscopy (cSLO): healthy controls compared to CADASIL patients.

<p>(n) number of total eyes; (v) number of total vessels; (n/a) too few vessels in the respective sector to calculate p-value.</p><p>Semi-automated vessel measurements based on confocal scanning laser ophthalmoscopy (cSLO): healthy controls compared to CADASIL patients.</p

Data overview regarding manual retinal vessel measurements based on spectral-domain optical coherence tomography.

<p>(n) number of patients.</p><p>*measurements performed at 960 µm from the optic disc edge.</p>#<p>circular SD-OCT scan 3.5 mm in diameter.</p><p>Data overview regarding manual retinal vessel measurements based on spectral-domain optical coherence tomography.</p

Retinal nerve fiber layer thickness (RNFL) measured by spectral-domain optical coherence tomography: healthy controls compared to CADASIL patients.

<p>(n) number of eyes.</p><p>*superior and inferior measurements were calculated based on data from nasal superior and temporal superior quadrants and from nasal inferior and temporal inferior quadrants respectively.</p><p>Retinal nerve fiber layer thickness (RNFL) measured by spectral-domain optical coherence tomography: healthy controls compared to CADASIL patients.</p

A–D Combined simultaneous confocal scanning laser ophthalmoscopy (cSLO) and spectral-domain optical coherence tomography (SD-OCT).

<p><b>A–B</b> Infrared cSLO image centered on the optic disc of a healthy control subject (A) and a CADASIL patient (B). Green circle indicates the position of corresponding SD-OCT scan. Light green section inferiorly on the circle marks the localization of corresponding SD-OCT scan shown aside. <b>C–D</b> Magnified SD-OCT scans of healthy control subject (C) and CADASIL patient (D) show sections of major retinal vessels appearing as a group of heterogeneous reflectivities in a round-shaped configuration. Asterisks mark the inner and outer reflections of arterial vessel walls and diamonds indicate inner and outer reflections of venous vessel walls. Hyperreflectivities representing the vessel walls seem thicker and more accentuated in the CADASIL patient. Particularly in veins, demarcation of the inferior vessel wall (towards the retinal pigment epithelium) often remains challenging due to absorption effects also seen as acoustical shadow underneath the vessel (towards the retinal pigment epithelium). Note the typical hour-glass shaped configuration within the vessel lumen in both subjects. Lateral vessel walls cannot be visualized as OCT laser beam is not projected perpendicularly to them.</p

Alternate vessels with low variance of thickness and brightness.

<p>Alternate vessels with low variance of thickness and brightness.</p

Test reference agreement of the second-choice group before and after elimination of AC_1, AC_4 and AC_5.

<p>Test reference agreement of the second-choice group before and after elimination of AC_1, AC_4 and AC_5.</p

Vessels 1 (v1) and 2 (v2) are larger than vessel 3 (v3) and 4 (v4).

<p>V1 is an artery, v2 is a vein, v3 and v4 cannot be allocated clearly.</p