Detection of capillary abnormalities in early diabetic retinopathy using scanning laser ophthalmoscopy and optical coherence tomography combined with adaptive optics.

This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Using AO-SLO, capillary looping, inflections and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion. In one patient with moderate NPDR, non-perfused capillaries, also called ghost vessels, were identified by alignment of corresponding en face AO-OCT and AO-OCTA images. The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in diabetic retinopathy earlier and more detailed than conventional fundus imaging devices.

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.

Automated detection of hyperreflective foci in the outer nuclear layer of the retina.

PURPOSE: Hyperreflective foci are poorly understood transient elements seen on optical coherence tomography (OCT) of the retina in both healthy and diseased eyes. Systematic studies may benefit from the development of automated tools that can map and track such foci. The outer nuclear layer (ONL) of the retina is an attractive layer in which to study hyperreflective foci as it has no fixed hyperreflective elements in healthy eyes. In this study, we intended to evaluate whether automated image analysis can identify, quantify and visualize hyperreflective foci in the ONL of the retina. METHODS: This longitudinal exploratory study investigated 14 eyes of seven patients including six patients with optic neuropathy and one with mild non-proliferative diabetic retinopathy. In total, 2596 OCT B-scan were obtained. An image analysis blob detector algorithm was used to detect candidate foci, and a convolutional neural network (CNN) trained on a manually labelled subset of data was then used to select those candidate foci in the ONL that fitted the characteristics of the reference foci best. RESULTS: In the manually labelled data set, the blob detector found 2548 candidate foci, correctly detecting 350 (89%) out of 391 manually labelled reference foci. The accuracy of CNN classifier was assessed by manually splitting the 2548 candidate foci into a training and validation set. On the validation set, the classifier obtained an accuracy of 96.3%, a sensitivity of 88.4% and a specificity of 97.5% (AUC 0.989). CONCLUSION: This study demonstrated that automated image analysis and machine learning methods can be used to successfully identify, quantify and visualize hyperreflective foci in the ONL of the retina on OCT scans.

Anti-myelin oligodendrocyte glycoprotein antibodies in a girl with good recovery after five episodes of prior idiopathic optic neuritis.

PURPOSE: To describe the clinical, radiological, immunological and electrophysiological features of a myelin oligodendrocyte glycoprotein (MOG)-IgG positive girl with five prior episodes of idiopathic bilateral optic neuritis (ON). OBSERVATIONS: We report a Danish girl who has been followed by pediatricians and pediatric neurologists since the age of 10 with recurrent episodes of idiopathic bilateral ON. Since the age of 15 there has been no recurrence of ON, and the patient has been thoroughly investigated for Multiple Sclerosis (MS) several times, but with negative findings. At the age of 19 the patient was referred to the Clinic of Optic Neuritis where she was tested seropositive for antibodies against MOG (MOG- IgG) on a conventionally cell-based assay. Despite 5 previous episodes of ON, the latency and amplitude signals of pattern-reversal visual evoked potentials (pVEP) including multifocal VEP were detected within the normal range. CONCLUSION: The clinical implications of MOG- IgG are not yet clear, but in cases where the diagnosis of MS is less likely and where ON is the main symptom, testing for both IgG antibodies against AQP4 and MOG while having atypical optic neuropathies in mind is important. MOG-IgG positive patients may have a good prognosis with regards to visual function.

Functional-structural assessment of the optic pathways in patients with optic neuritis.

BACKGROUND: The pattern-reversal visual evoked potential (pVEP) is widely used for the diagnosis of Optic Neuritis (ON), but this method has some limitations. The aim of this study was to examine the added value of multifocal visual evoked potentials (mfVEP) and spectral-domain optical coherence tomography (SD-OCT) in the diagnosis of ON in patients that exhibit a normal pVEP. METHOD: Thirty-three patients with a history of having ON and 30 sex- and age-matched healthy controls (HC) were investigated. We included patients who were suspected of having a first-time ON and in whom pVEP showed normal results. Both eyes of the patients and HC were systematically investigated with SD-OCT, visual acuity, pVEP and mfVEP. The ON-affected eyes of the patients were compared with only one randomly selected eye per person in the HC group. The fellow "non-affected" eye of patients was held as a separate group. Statistical analyses were performed (including t test, Spearman's rank-order correlation test) using SPSS Statistics, Version 24.0. RESULTS: A significant difference was found in OCT mean retinal nerve fibre layer thickness (RNFLt) between patients and HC (p = 0.013) (i.e. 84.24 (± 17.00) µm versus 93.48(± 6.44) µm). An association was detected in patients between mean inter-eye asymmetry of the RNFLt and global (averaged) mfVEP amplitude (r = 0.565, p = 0.002). When analysing mfVEP signals from sectors in the upper hemifield, a significant difference was found in mean mfVEP amplitude between patients and HC (p = 0.005). CONCLUSIONS: Abnormality is potentially measurable (via reduced RNFLt and focal analyses with mfVEP amplitude) in patients suspected of having a first episode of ON where pVEP reports no abnormality. The mfVEP and SD-OCT may together be of value as supplementary tools in diagnosing ON in this patient group.

Multifocal visual evoked potentials in optic neuritis and multiple sclerosis: A review.

Multifocal visual evoked potential (mf-VEP) represents a new approach to the classical full field (ff-)VEP with separate responses from up to 60 sectors of the visual field. A thorough literature survey of the use of mf-VEP in optic neuritis (ON) and multiple sclerosis (MS) is presented (38 published studies were retrieved). Mf-VEP provides direct topographical information of specific lesions and facilitates investigations on structural-functional correlations thus providing new methods for exploring the interplay between demyelination, atrophy and remyelination in MS. Good correlation was shown between mf-VEP and OCT, ff-VEP, MRI (MTR, DTI), 30-2 standard automated perimetry and low-contrast-visual acuity. All but one study showed superior sensitivity and specificity compared to ff-VEP, especially with regards to small, peripheral lesions or lesions of the upper visual field. Mf-VEP has shown superior sensitivity and specificity than established methods in diagnosing optic nerve lesions and tracking functional recovery following lesions. Abnormal mf-VEP responses in the fellow, non-ON afflicted eye may predict MS risk in ON patients. No standardization currently exists and no direct comparisons in ON and MS between at least 5 different commercially available mf-VEP systems have so far been published. Despite these limitations, mf-VEP is a promising new tool of diagnostic and prognostic value of mf-VEP in ON and MS.