Retinal alterations in patients with Lafora disease

Abstract

Purpose Lafora disease is a genetic neurodegenerative metabolic disorder caused by insoluble polyglucosan aggregate accumulation throughout the central nervous system and body. The retina is an accessible neural tissue, which may offer alternative methods to assess neurological diseases quickly and noninvasively. In this way, noninvasive imaging may provide a means to characterize neurodegenerative disease, which enables earlier identification and diagnosis of disease and the ability to monitor disease progression. In this study, we sought to characterize the retina of individuals with Lafora disease using non-invasive retinal imaging. Methods One eye of three individuals with genetically confirmed Lafora disease were imaged with optical coherence tomography (OCT) and adaptive optics scanning light ophthalmoscopy (AOSLO). When possible, OCT volume and line scans were acquired to assess total retinal thickness, ganglion cell-inner plexiform layer thickness, and outer nuclear layer + Henle fiber layer thickness. OCT angiography (OCTA) scans were acquired in one subject at the macula and optic nerve head (ONH). AOSLO was used to characterize the photoreceptor mosaic and examine the retinal nerve fiber layer (RNFL). Results Two subjects with previous seizure activity demonstrated reduced retinal thickness, while one subject with no apparent symptoms had normal retinal thickness. All other clinical measures, as well as parafoveal cone density, were within normal range. Nummular reflectivity at the level of the RNFL was observed using AOSLO in the macula and near the ONH in all three subjects. Conclusions This multimodal retinal imaging approach allowed us to observe a number of retinal structural features in all three individuals. Most notably, AOSLO revealed nummular reflectivity within the inner retina of each subject. This phenotype has not been reported previously and may represent a characteristic change produced by the neurodegenerative process.

Ocular phenotype and electroretinogram abnormalities in Lafora disease and correlation with disease stage

“…We were not able to perform Retinal Nerve Fiber Layer (RNFL) thickness measurements in patients due to invalidating psychomotor status of patients, but a recent case series showed reduced retinal thickness in two patients [ 22 ] and due to the small sample size, we failed to identify a statistical significance for the rod photoreceptors' a-wave amplitude function in the right eye. Nevertheless, we showed that EPM2A patients display a more severe dysfunction of both cones and rods photoreceptors (Figs.…”

Lafora Disease and Alpha-Synucleinopathy in Two Adult Free-Ranging Moose (Alces alces) Presenting with Signs of Blindness and Circling

“…Histologically, in addition to the brain, cytoplasmic PGBs have been discovered in the spinal cord, sweat glands of skin, liver, and cardiac and skeletal muscles in animals and humans [7,11,12,35]. Visual impairments with retinal alterations were reported in human patients with LD [57,58]. No inclusions were noted in the ocular muscles in our study, and the other body systems of these moose were not evaluated as they were unavailable.…”

Retinal Phenotyping of a Murine Model of Lafora Disease

“…As the disease progresses, EEG demonstrates long bursts of diffuse spike-waves and fast polyspikes associated with myoclonic jerks and enhanced by photic stimulation [ 6 , 9 , 10 , 11 , 12 ]. Although, subjects with LD typically retain good visual acuity and color vision [ 13 , 14 ], retinal structure and function are often abnormal [ 13 , 14 , 15 ]. For instance, on full-field electroretinogram (ERG) testing, a generalized cone dysfunction is commonly observed [ 13 , 14 ]; additional involvement of the rod bipolar system may be seen in some patients [ 13 ].…”

“…For instance, on full-field electroretinogram (ERG) testing, a generalized cone dysfunction is commonly observed [ 13 , 14 ]; additional involvement of the rod bipolar system may be seen in some patients [ 13 ]. Optical coherence tomography (OCT), an in vivo imaging technique, shows preservation of retinal lamination [ 13 ], but regional thinning is described in some patients [ 15 ]. Further, adaptive optics scanning light ophthalmoscopy (AOSLO), a non-invasive technique capable of resolving single-cell structures, shows nummular hyperreflective structures within the retinal nerve fiber layer in LD [ 15 ].…”

“…Optical coherence tomography (OCT), an in vivo imaging technique, shows preservation of retinal lamination [ 13 ], but regional thinning is described in some patients [ 15 ]. Further, adaptive optics scanning light ophthalmoscopy (AOSLO), a non-invasive technique capable of resolving single-cell structures, shows nummular hyperreflective structures within the retinal nerve fiber layer in LD [ 15 ].…”