Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL)

A 44-year-old Caucasian man presented with seizures and cognitive impairment. He had marked retinal drusen, and MR brain scan showed features of cerebral small vessel disease; he was diagnosed with a leukoencephalopathy of uncertain cause. He died at the age of 46 years and postmortem brain examination showed widespread small vessel changes described as a vasculopathy of unknown cause. Seven years postmortem, whole-genome sequencing identified a homozygous nonsense HTRA1 mutation (p.Arg302Ter), giving a retrospective diagnosis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy.

Visual Function and Macular Carotenoid Changes in Eyes with Retinal Drusen—An Open Label Randomized Controlled Trial to Compare a Micronized Lipid-Based Carotenoid Liquid Supplementation and AREDS-2 Formula

Purpose: To compare the changes in visual and ocular parameters in individuals with retinal drusen who were treated with two commercially available nutritional supplements. Methods: An open-label, single-center, randomized, parallel-treatment with an observational control group design was utilized. The treatment groups included individuals with fine retinal drusen sub-clinical age-related macular degeneration (AMD), while the control group consisted of ocular normal individuals. The treatment groups were randomly assigned to the micronized lipid-based carotenoid supplement, Lumega-Z (LM), or the PreserVision Age-Related Eye Disease Study 2 (AREDS-2) soft gel (PV). Visual performance was evaluated using the techniques of visual acuity, dark adaptation recovery and contrast sensitivity, at baseline, three months, and six months. Additionally, the macular pigment optical density (MPOD) was measured. The control group was not assigned any carotenoid supplement. The right eye and left eye results were analyzed separately. Results: Seventy-nine participants were recruited for this study, of which 68 qualified and 56 participants had useable reliable data. Of the individuals who completed this study, 25 participants belonged to the LM group, 16 belonged to the PV group, and 15 to the control group. The LM group demonstrated statistically significant improvements in contrast sensitivity function (CSF) in both eyes at six months (p < 0.001). The LM group displayed a positive linear trend with treatment time in CSF (p < 0.001), with benefits visible after just three months of supplementation. Although there was a trend showing improvement in CSF in the PV group, the change was not significant after a Bonferroni-corrected p-value of p < 0.00625. Visual acuity, dark adaptation recovery and MPOD did not significantly improve in either treatment groups. Conclusion: The LM group demonstrated greater and faster benefits in visual performance as measured by CSF when compared to the PV group. This trial has been registered at clinicaltrials.gov (NCT03946085).

Quantum-Assisted Retinal Drusen Detection Algorithm using Entropy-Based Image Processing Techniques

Drusen identification is the fundamental operation in the automated diagnosis of eye diseases. Manual and automatic detection of the drusen in the retinal fundus images has been developed recently in the classical manner only. This work provides the quantum-based retinal drusen detection method using entropy-based image processing techniques. This algorithm is the composite system of two channels, classical and quantum channels for the preprocessing and drusen detection respectively. This research work has been evaluated with the databases of DRIVE, STARE, MESSIDOR, E-Optha-Ex and ONH-Hunter. This quantum-based approach will be analyzed with the results of the existing classical methods and proves its efficiency from the calculations of sensitivity, specificity, accuracy and execution time.

Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration

Drusen are lipid-, mineral-, and protein-containing extracellular deposits that accumulate between the basal lamina of the retinal pigment epithelium (RPE) and Bruch’s membrane (BrM) of the human eye. They are a defining feature of age-related macular degeneration (AMD), a common sight-threatening disease of older adults. The appearance of heterogeneous internal reflectivity within drusen (HIRD) on optical coherence tomography (OCT) images has been suggested to indicate an increased risk of progression to advanced AMD. Here, in a cohort of patients with AMD and drusen, we show that HIRD indicated an increased risk of developing advanced AMD within 1 year. Using multimodal imaging in an independent cohort, we demonstrate that progression to AMD was associated with increasing degeneration of the RPE overlying HIRD. Morphological analysis of clinically imaged cadaveric human eye samples revealed that HIRD was formed by multilobular nodules. Nanoanalytical methods showed that nodules were composed of hydroxyapatite and that they differed from spherules and BrM plaques, other refractile features also found in the retinas of patients with AMD. These findings suggest that hydroxyapatite nodules may be indicators of progression to advanced AMD and that using multimodal clinical imaging to determine the composition of macular calcifications may help to direct therapeutic strategies and outcome measures in AMD.

Multimodal imaging of small hard retinal drusen in young healthy adults

BackgroundSmall hard macular drusen can be observed in the retina of adults as young as 18 years of age. Here, we seek to describe the in vivo topography and geometry of these drusen.MethodsRetinal images were acquired in young, healthy adults using colour fundus photography, spectral domain optic coherence tomography (SD-OCT), reflectance flood-illuminated adaptive optic ophthalmoscopy (AO flood) and reflectance adaptive optic scanning light ophthalmoscopy (AOSLO) in both confocal and non-confocal split-detection modalities. Small bright yellow hard drusen within a 10 degree radius from the foveal centre were characterised.ResultsSmall hard drusen were seen on colour photographs in 21 out of 97 participants and 26 drusen in 12 eyes in 11 participants were imaged using the full protocol. Drusen were easily identifiable in all modalities, except a few very small ones, which were not visible on SD-OCT. On AOSLO images, these drusen appeared as round, oval or lobular areas (up to three lobules) of diameter 22–61 µm where cone photoreceptor reflectivity and density was decreased (p=0.049). This was usually associated with discrete thickening of the retinal pigment epithelium (RPE) complex.ConclusionHigh lateral resolution imaging of small lobular hard retinal drusen suggests formation through the confluence of two or more smaller round lesions. The outline and size of these smaller lesions corresponds to 1–4 RPE cells. Prospective longitudinal studies are needed to determine the ultimate fate of small hard drusen and their potential relation to age-related macular degeneration.