Hyperreflective dots in the avascular outer retina in relapsing-remitting multiple sclerosis.

BACKGROUND: Hyperreflective granular elements with a transient presence in the retina can be detected non-invasively by optical coherence tomography (OCT). Such foci or dots may represent aggregates of activated microglia. However, in multiple sclerosis an increased number of hyperreflective foci has so far not been demonstrated in the intrinsically hyporeflective and avascular outer nuclear layer of the retina where there are no fixed elements in healthy eyes. Therefore, the present study intended to investigate the presence of hyperreflective foci in the outer nuclear layer in patients with relapsing- remitting multiple sclerosis (RRMS) by using a high-resolution OCT scanning protocol. METHODS: This cross-sectional exploratory study examined 88 eyes in 44 RRMS patients and 106 eyes in 53 age- and sex-matched healthy subjects. None of the patients had any sign of retinal disease. All patients and healthy subjects each underwent one session of spectral domain OCT imaging. A total of 23,200 B-scans extracted from 8 × 8 mm blocks of linear B-scans at 60 µm intervals were analysed for hyperreflective foci in the outer nuclear layer of the retina. Analyses were made of the total block scan and a circular 6-mm diameter fovea-centered field in each eye. Multivariate logistic regression analysis was used to assess associations between parameters. RESULTS: Hyperreflective foci were observed in 31 out of 44 (70.5 %) multiple sclerosis patients compared to 1 out of 53 (1.8%) healthy subjects (p < 0.0001). From analyses of the total block scans, the median number of hyperreflective foci in the outer nuclear layer was 1 (range 0-13) in patients and 0 (range 0-2) in healthy subjects (p < 0.0001). In total, 66.2% of all hyperreflective foci were located within 6 mm of the center of the macula. There was no detectable association between the presence of hyperreflective foci and retinal nerve fiber layer or ganglion cell layer thickness. CONCLUSION: Hyperreflective granular foci in the avascular outer nuclear layer of the retina seen by OCT were almost completely absent in healthy subjects, whereas they were found, albeit at low density, in the majority of patients with RRMS. Hyperreflective foci can be repeatedly examined by non-invasive means and without pupil dilation, which opens a new field of investigation of infiltrating elements in an unmyelinated part of the central nervous system.

Characterization of Hyperreflective Dots by Structural and Angiographic Optical Coherence Tomography in Patients with Diabetic Retinopathy and Healthy Subjects.

Hyperreflective dots are a common but highly variable feature of optical coherence tomography (OCT) scans of the retina. We studied the spatial characteristics and perfusion of hyperreflective dots using both structural and angiographic OCT B-scans of the macula in 16 eyes in 8 healthy subjects and 8 patients with diabetic retinopathy without macular edema. Hyperreflective dots were manually graded in a 1000 µm parafoveal area by number, diameter, location and perfusion status and traced through adjacent B-scans at 11 µm intervals to determine their length. Thereby, this study defined a procedure to identify granular and elongated hyperreflective elements and differentiate between presumably perfused and occluded capillaries. The latter were only found in the diabetic patients. This classification can potentially be automated to non-invasively identify capillary non-perfusion in vivo.

Multi-modal and multi-scale clinical retinal imaging system with pupil and retinal tracking.

We present a compact multi-modal and multi-scale retinal imaging instrument with an angiographic functional extension for clinical use. The system integrates scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT) and OCT angiography (OCTA) imaging modalities and provides multi-scale fields of view. For high resolution, and high lateral resolution in particular, cellular imaging correction of aberrations by adaptive optics (AO) is employed. The entire instrument has a compact design and the scanning head is mounted on motorized translation stages that enable 3D self-alignment with respect to the subject's eye by tracking the pupil position. Retinal tracking, based on the information provided by SLO, is incorporated in the instrument to compensate for retinal motion during OCT imaging. The imaging capabilities of the multi-modal and multi-scale instrument were tested by imaging healthy volunteers and patients.

Migration of an outer retinal element in a healthy child followed by longitudinal multimodal imaging.

PURPOSE: To describe the migration of an outer retinal element using longitudinal multimodal imaging. OBSERVATIONS: In the retina of a healthy 7-year-old girl, movement of a hyperreflective element of 15 µm extent was seen using optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy (cSLO), and adaptive optics fundus photography (AO). On the OCT B-scan, the element initially appeared at the level of the outer limiting membrane with an umbra reaching the retinal pigment epithelium from where it gradually diminished and disappeared over 33 days. A corresponding disruption of the photoreceptor pattern on AO diminished over 52 days. CONCLUSIONS AND IMPORTANCE: This non-invasive observation of an isolated, cell-sized, migrating element in the human retina was made in vivo in the absence of confounding retinal disease or similar nearby elements. Based on prior preclinical observations we hypothesize that such a migrating element could be a macrophage. The case provides information about the time-scale and resolution needed for the monitoring of infiltrative processes in the retina.