Multimodal retinal vessel analysis in CADASIL patients

Abstract

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 mm(3) and 8.83 ± 2.24 mm(3). 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.

Figure 1. A–D Measurement of retinal nerve fiber layer (RNFL) thickness, using a circular B-scan placed around the optic disc.

A Confocal scanning laser ophthalmoscopy infrared image shows optic disc with circular scan (diameter: 3.5 mm). B Corresponding spectral domain optical coherence tomography scan. Red marks delineate automatically borders of RNFL layer. C Presentation of RNFL thickness values for individual sectors and global measurement. D Individual measurement graphically compared to a healthy population.

Figure 2. Confocal scanning laser (cSLO) infrared image illustrating semi-automatic measurement tool.

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.

Figure 3. A–D Combined simultaneous confocal scanning laser ophthalmoscopy (cSLO) and spectral-domain optical coherence tomography (SD-OCT).

A–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. C–D 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.