Trans-Synaptic Degeneration in the Visual Pathway in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

BACKGROUND AND OBJECTIVES: We aimed to assess the presence of retinal neurodegeneration independent of optic neuritis (ON) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the development of trans-synaptic anterograde degeneration in these patients after ON. METHODS: Cross-sectional, retrospective study of 34 adult patients with MOGAD and 23 healthy controls (HC). Clinical, optical coherence tomography (OCT), and MRI data were collected. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell inner plexiform layer (GCIPL) were obtained using Heidelberg Spectralis. FreeSurfer7 was used to obtain the lateral geniculate nucleus (LGN), occipital volume fractions (to total estimated intracranial volume), and occipital cortical thickness. For the anterior visual pathway, the analysis was conducted using eyes, classified based on the history of ON (Eye-ON and Eye-NON) and compared with Eye-HC. The analysis of OCT and brain volumetric measures was conducted comparing MOGAD-ON, MOGAD-NON, and HC groups. The analysis of covariance with a Bonferroni-adjusted post hoc test was used to test differences between groups and linear regression analysis to evaluate OCT/MRI associations; age and sex were considered as covariates. RESULTS: 24 (70.5%) patients had a prior ON. Median pRNFL and GCIPL thickness (um) was significantly reduced in Eye-ON vs EyeNON and HC (pRNFL: 69.4 (17.3), 89.6 (13.7), 98.2 (11.7), p < 0.001; GCIPL: 55.8 (8.7), 67.39 (8.7), 72.6 (4.5), p < 0.001). pRNFL and GCIPL thickness had a negative correlation with the number of ON episodes (p = 0.025 and p = 0.031, respectively). LGN volume fraction was significantly lower in patients with MOGAD-ON than in HC (0.33 (0.05) vs 0.39 (0.04), p = 0.002). The occipital cortical thickness was lower in MOGAD-ON compared with MOGAD-NON and HC (p = 0.010). In patients with MOGAD-ON, pRNFL correlated with LGN volume (p = 0.006), occipital thickness (p = 0.002), and the medial occipital cortex (p = 0.002), but not the lateral occipital lobe. DISCUSSION: Compared with HC, MOGAD-ON exhibits reduced retinal thickness, primarily influenced by the presence and the number of prior ON episodes. Moreover, MOGAD-ON demonstrates significant atrophy in the retinal, subcortical, and cortical regions of the visual pathway, distinguishing them from MOGAD-NON and HC. These findings suggest that in patients with MOGAD neurodegeneration is tightly correlated with damage to the involved pathway.

Neurophysiological Alterations of the Visual Pathway in Posterior Cortical Atrophy: Systematic Review and a Case Series.

Background: The clinical features of posterior cortical atrophy (PCA), a rare condition often caused by Alzheimer's disease, have been recently defined, while little is known about its neurophysiological correlates. Objective: To describe neurophysiological alterations of the visual pathway as assessed using visual field test (VF), visual evoked potentials (VEP), and electroretinogram (ERG) in PCA patients. Methods: Studies reporting VF, VEPs, and ERG in PCA patients were selected according PRISMA method. Of the 323 articles that emerged from the literature, 17 included the outcomes of interest. To these data, we added those derived from a patient cohort enrolled at our clinic. Results: The literature review included 140 patients, half of them (50%) presented with homonymous hemianopia or quadrantanopia. VEPs were available in 4 patients (2 normal findings, 1 decreased amplitude, and 1 increased latency) and ERG in 3 patients (substantially normal findings). Our case series included 6 patients, presenting with homonymous lateral hemianopia in 50% and contralateral cortical atrophy. VEPs showed normal amplitude in 66-83% according to the stimulation check, and increased latency in 67% in absence of myelin damage on MRI. Latency was increased in both eyes in 50% and only on one side in the other 50%. Such alterations were observed in patients with more severe and symmetric atrophy. ERG showed normal findings. Conclusions: Neurophysiological investigations of the visual pathway in PCA are almost absent in literature. Alterations involve both amplitude and latency and can be also monocular. A multiple-point involvement of the optical pathway can be hypothesized.

Disrupted third visual pathway function in schizophrenia: Evidence from real and implied motion processing.

Impaired motion perception in schizophrenia has been associated with deficits in social-cognitive processes and with reduced activation of visual sensory regions, including the middle temporal area (MT+) and posterior superior temporal sulcus (pSTS). These findings are consistent with the recent proposal of the existence of a specific 'third visual pathway' specialized for social perception in which motion is a fundamental component. The third visual pathway transmits visual information from early sensory visual processing areas to the STS, with MT+ acting as a critical intermediary. We used functional magnetic resonance imaging to investigate functioning of this pathway during processing of naturalistic videos with explicit (real) motion and static images with implied motion cues. These measures were related to face emotion recognition and motion-perception, as measured behaviorally. Participants were 28 individuals with schizophrenia (Sz) and 20 neurotypical controls. Compared to controls, individuals with Sz showed reduced activation of third visual pathway regions (MT+, pSTS) in response to both real- and implied-motion stimuli. Dysfunction of early visual cortex and pulvinar were also associated with aberrant real-motion processing. Implied-motion stimuli additionally engaged a wide network of brain areas including parietal, motor and frontal nodes of the human mirror neuron system. The findings support concepts of MT+ as a mediator between visual sensory areas and higher-order brain and argue for greater focus on MT+ contributions to social-cognitive processing, in addition to its well-documented role in visual motion processing.

Mesoscale organization of ventral and dorsal visual pathways in macaque monkey revealed by 7T fMRI.

In human and nonhuman primate brains, columnar (mesoscale) organization has been demonstrated to underlie both lower and higher order aspects of visual information processing. Previous studies have focused on identifying functional preferences of mesoscale domains in specific areas; but there has been little understanding of how mesoscale domains may cooperatively respond to single visual stimuli across dorsal and ventral pathways. Here, we have developed ultrahigh-field 7 T fMRI methods to enable simultaneous mapping, in individual macaque monkeys, of response in both dorsal and ventral pathways to single simple color and motion stimuli. We provide the first evidence that anatomical V2 cytochrome oxidase-stained stripes are well aligned with fMRI maps of V2 stripes, settling a long-standing controversy. In the ventral pathway, a systematic array of paired color and luminance processing domains across V4 was revealed, suggesting a novel organization for surface information processing. In the dorsal pathway, in addition to high quality motion direction maps of MT, MST and V3A, alternating color and motion direction domains in V3 are revealed. As well, submillimeter motion domains were observed in peripheral LIPd and LIPv. In sum, our study provides a novel global snapshot of how mesoscale networks in the ventral and dorsal visual pathways form the organizational basis of visual objection recognition and vision for action.

Mapping the avian visual tectofugal pathway using 3D reconstruction.

Image processing in amniotes is usually accomplished by the thalamofugal and/or tectofugal visual systems. In laterally eyed birds, the tectofugal system dominates with functions such as color and motion processing, spatial orientation, stimulus identification, and localization. This makes it a critical system for complex avian behavior. Here, the brains of chicks, Gallus gallus, were used to produce serial brain sections in either coronal, sagittal, or horizontal planes and stained with either Nissl and Gallyas silver myelin or Luxol fast blue stain and cresyl echt violet (CEV). The emerging techniques of diffusible iodine-based contrast-enhanced computed tomography (diceCT) coupled with serial histochemistry in three planes were used to generate a comprehensive three-dimensional (3D) model of the avian tectofugal visual system. This enabled the 3D reconstruction of tectofugal circuits, including the three primary neuronal projections. Specifically, major components of the system included four regions of the retina, layers of the optic tectum, subdivisions of the nucleus rotundus in the thalamus, the entopallium in the forebrain, and supplementary components connecting into or out of this major avian visual sensory system. The resulting 3D model enabled a better understanding of the structural components and connectivity of this complex system by providing a complete spatial organization that occupied several distinct brain regions. We demonstrate how pairing diceCT with traditional histochemistry is an effective means to improve the understanding of, and thereby should generate insights into, anatomical and functional properties of complicated neural pathways, and we recommend this approach to clarify enigmatic properties of these pathways.

Objective Assessment of Visual Field Defects Caused by Optic Chiasm and Its Posterior Visual Pathway Injury.

OBJECTIVES: To investigate the characteristics and objective assessment method of visual field defects caused by optic chiasm and its posterior visual pathway injury. METHODS: Typical cases of visual field defects caused by injuries to the optic chiasm, optic tracts, optic radiations, and visual cortex were selected. Visual field examinations, visual evoked potential (VEP) and multifocal visual evolved potential (mfVEP) measurements, craniocerebral CT/MRI, and retinal optical coherence tomography (OCT) were performed, respectively, and the aforementioned visual electrophysiological and neuroimaging indicators were analyzed comprehensively. RESULTS: The electrophysiological manifestations of visual field defects caused by optic chiasm injuries were bitemporal hemianopsia mfVEP abnormalities. The visual field defects caused by optic tract, optic radiation, and visual cortex injuries were all manifested homonymous hemianopsia mfVEP abnormalities contralateral to the lesion. Mild relative afferent pupil disorder (RAPD) and characteristic optic nerve atrophy were observed in hemianopsia patients with optic tract injuries, but not in patients with optic radiation or visual cortex injuries. Neuroimaging could provide morphological evidence of damages to the optic chiasm and its posterior visual pathway. CONCLUSIONS: Visual field defects caused by optic chiasm, optic tract, optic radiation, and visual cortex injuries have their respective characteristics. The combined application of mfVEP and static visual field measurements, in combination with neuroimaging, can maximize the assessment of the location and degree of visual pathway damage, providing an effective scheme for the identification of such injuries.

Neural segregation and integration of sensory, decision, and action processes during object categorization.

Neural and computational evidence suggests that perceptual decisions depend on an evidence accumulation process. The gradual reveal fMRI method, which prolongs a decision to match the slow temporal resolution of fMRI measurements, has classified dorsal visual stream regions as "Action" (alternatively, "Moment of Recognition" or "Commitment") and ventral visual stream regions as "Accumulator." Previous gradual reveal fMRI studies, however, only tested actions that were in response to decisions and, thus, related to evidence accumulation. To fully dissociate the contribution of sensory, decision, and motor components to Action and Accumulator regions in the dorsal and ventral visual streams, we extended the gradual reveal paradigm to also include responses made to cues where no decision was necessary. We found that the lateral occipital cortex in the ventral visual stream showed a highly selective Accumulator profile, whereas regions in the fusiform gyrus were influenced by action generation. Dorsal visual stream regions showed strikingly similar profiles as classical motor regions and also as regions of the salience network. These results suggest that the dorsal and ventral visual streams may appear highly segregated because they include a small number of regions that are highly selective for Accumulator or Action. However, the streams may be more integrated than previously thought and this integration may be accomplished by regions with graded responses that are less selective (i.e., more distributed).

Evidence for adaptive myelination of subcortical shortcuts for visual motion perception in healthy adults.

Conscious visual motion information follows a cortical pathway from the retina to the lateral geniculate nucleus (LGN) and on to the primary visual cortex (V1) before arriving at the middle temporal visual area (MT/V5). Alternative subcortical pathways that bypass V1 are thought to convey unconscious visual information. One flows from the retina to the pulvinar (PUL) and on to medial temporal visual area (MT); while the other directly connects the LGN to MT. Evidence for these pathways comes from non-human primates and modest-sized studies in humans with brain lesions. Thus, the aim of the current study was to reconstruct these pathways in a large sample of neurotypical individuals and to determine the degree to which these pathways are myelinated, suggesting information flow is rapid. We used the publicly available 7T (N = 98; 'discovery') and 3T (N = 381; 'validation') diffusion magnetic resonance imaging datasets from the Human Connectome Project to reconstruct the PUL-MT (including all subcompartments of the PUL) and LGN-MT pathways. We found more fibre tracts with greater density in the left hemisphere. Although the left PUL-MT path was denser, the bilateral LGN-MT tracts were more heavily myelinated, suggesting faster signal transduction. We suggest that this apparent discrepancy may be due to 'adaptive myelination' caused by more frequent use of the LGN-MT pathway that leads to greater myelination and faster overall signal transmission.

Age-related changes in the healthy adult visual pathway: evidence from diffusion tensor imaging with fixel-based analysis.

BACKGROUND AND PURPOSE: Fixel-based analysis (FBA) is a new method that overcomes the technical limitations of diffusion tensor imaging (DTI) by enabling the characterization of multiple fiber populations within a voxel, and provides biologically meaningful indicators. This study aimed to explore age-related changes in the visual pathway in healthy adults and to observe differences in imaging quality between data collected using different b­values. METHODS: In this prospective cross-sectional study, brain DTI scans which were collected with more than six uniformly distributed gradient directions and higher b­values (up to 2000 s/mm2) than traditional DTI were performed in 72 healthy adults across the adult lifespan (20-79 years). After image preprocessing, FBA was used to process the dataset. At the same time, conventional DTI metrics were also calculated. RESULTS: Pearson's correlation analysis showed that DTI parameters of white matter (optic nerve, optic chiasma, optic tract, and optic radiation) in the optic pathway were correlated with age. FA values were negatively correlated with age, while MD/AD/RD showed a positive correlation (P < 0.05). FBA showed that the index including FD/FC/FDC tended to decline with age (P < 0.05). Linear regression analysis showed a linear relationship between DTI metrics of the dataset collected by b­values of 1000 and 2000 s/mm2 (P < 0.05). CONCLUSION: FBA provides a useful method to assess age-related changes in the visual pathway, which is sensitive to diffusion. In addition, the b­value influences DTI parameters and signal-to-noise ratio of the image.

Category-specific and category-general neural codes of recognition memory in the ventral visual pathway.

Researchers have identified category-specific brain regions, such as the fusiform face area (FFA) and parahippocampal place area (PPA) in the ventral visual pathway, which respond preferentially to one particular category of visual objects. In addition to their category-specific role in visual object identification and categorization, regions in the ventral visual pathway play critical roles in recognition memory. Nevertheless, it is not clear whether the contributions of those brain regions to recognition memory are category-specific or category-general. To address this question, the present study adopted a subsequent memory paradigm and multivariate pattern analysis (MVPA) to explore category-specific and category-general neural codes of recognition memory in the visual pathway. The results revealed that the right FFA and the bilateral PPA showed category-specific neural patterns supporting recognition memory of faces and scenes, respectively. In contrast, the lateral occipital cortex seemed to carry category-general neural codes of recognition memory. These results provide neuroimaging evidence for category-specific and category-general neural mechanisms of recognition memory in the ventral visual pathway.

Assessing the structure of the posterior visual pathway in bilateral macular degeneration.

Macular degeneration (MD) embodies a collection of disorders causing a progressive loss of central vision. Cross-sectional MRI studies have revealed structural changes in the grey and white matter in the posterior visual pathway in MD but there remains a need to understand how such changes progress over time. To that end we assessed the posterior pathway, characterising the visual cortex and optic radiations over a ~ 2-year period in MD patients and controls. We performed cross-sectional and longitudinal analysis of the former. Reduced cortical thickness and white matter integrity were observed in patients compared to controls, replicating previous findings. While faster, neither the rate of thinning in visual cortex nor the reduction in white matter integrity during the ~ 2-year period reached significance. We also measured cortical myelin density; cross-sectional data showed this was higher in patients than controls, likely as a result of greater thinning of non-myelinated tissue in patients. However, we also found evidence of a greater rate of loss of myelin density in the occipital pole in the patient group indicating that the posterior visual pathway is at risk in established MD. Taken together, our results revealed a broad decline in grey and white matter in the posterior visual pathway in bilateral MD; cortical thickness and fractional anisotropy show hints of an accelerated rate of loss also, with larger effects emerging in the occipital pole.

Traumatic Brain Injury and Vision.

Traumatic brain injury disrupts the complex anatomy of the afferent and efferent visual pathways. Injury to the afferent pathway can result in vision loss, visual field deficits, and photophobia. Injury to the efferent pathway primarily causes eye movement abnormalities resulting in ocular misalignment and double vision. Injury to both the afferent and efferent systems can result in significant visual disability.

Spikiness and animacy as potential organizing principles of human ventral visual cortex.

Considerable research has been devoted to understanding the fundamental organizing principles of the ventral visual pathway. A recent study revealed a series of 3-4 topographical maps arranged along the macaque inferotemporal (IT) cortex. The maps articulated a two-dimensional space based on the spikiness and animacy of visual objects, with "inanimate-spiky" and "inanimate-stubby" regions of the maps constituting two previously unidentified cortical networks. The goal of our study was to determine whether a similar functional organization might exist in human IT. To address this question, we presented the same object stimuli and images from "classic" object categories (bodies, faces, houses) to humans while recording fMRI activity at 7 Tesla. Contrasts designed to reveal the spikiness-animacy object space evoked extensive significant activation across human IT. However, unlike the macaque, we did not observe a clear sequence of complete maps, and selectivity for the spikiness-animacy space was deeply and mutually entangled with category-selectivity. Instead, we observed multiple new stimulus preferences in category-selective regions, including functional sub-structure related to object spikiness in scene-selective cortex. Taken together, these findings highlight spikiness as a promising organizing principle of human IT and provide new insights into the role of category-selective regions in visual object processing.

Optic radiations representing different eccentricities age differently.

The neural pathways that carry information from the foveal, macular, and peripheral visual fields have distinct biological properties. The optic radiations (OR) carry foveal and peripheral information from the thalamus to the primary visual cortex (V1) through adjacent but separate pathways in the white matter. Here, we perform white matter tractometry using pyAFQ on a large sample of diffusion MRI (dMRI) data from subjects with healthy vision in the U.K. Biobank dataset (UKBB; N = 5382; age 45-81). We use pyAFQ to characterize white matter tissue properties in parts of the OR that transmit information about the foveal, macular, and peripheral visual fields, and to characterize the changes in these tissue properties with age. We find that (1) independent of age there is higher fractional anisotropy, lower mean diffusivity, and higher mean kurtosis in the foveal and macular OR than in peripheral OR, consistent with denser, more organized nerve fiber populations in foveal/parafoveal pathways, and (2) age is associated with increased diffusivity and decreased anisotropy and kurtosis, consistent with decreased density and tissue organization with aging. However, anisotropy in foveal OR decreases faster with age than in peripheral OR, while diffusivity increases faster in peripheral OR, suggesting foveal/peri-foveal OR and peripheral OR differ in how they age.

Functional topography of pulvinar-visual cortex networks in macaques revealed by INS-fMRI.

The pulvinar in the macaque monkey contains three divisions: the medial pulvinar (PM), the lateral pulvinar (PL), and the inferior pulvinar (PI). Anatomical studies have shown that connections of PM are preferentially distributed to higher association areas, those of PL are biased toward the ventral visual pathway, and those of PI are biased with the dorsal visual pathway. To study functional connections of the pulvinar at mesoscale, we used a novel method called INS-fMRI (infrared neural stimulation and functional magnetic resonance imaging). This method permits studies and comparisons of multiple pulvinar networks within single animals. As previously revealed, stimulations of different sites in PL and PI produced topographically organized focal activations in visual areas V1, V2, and V3. In contrast, PM stimulation elicited little or diffuse response. The relative activations of areas V1, V2, V3A, V3d, V3v, V4, MT, and MST revealed that connections of PL are biased to ventral pathway areas, and those of PI are biased to dorsal areas. Different statistical values of activated blood-oxygen-level-dependent responses produced the same center of activation, indicating stability of connectivity; it also suggests possible dynamics of broad to focal responses from single stimulation sites. These results demonstrate that infrared neural stimulation-induced connectivity is largely consistent with previous anatomical connectivity studies, thereby demonstrating validity of our novel method. In addition, it suggests additional interpretations of functional connectivity to complement anatomical studies.

A unified global tractography framework for automatic visual pathway reconstruction.

The human visual pathway starts from the retina, passes through the retinogeniculate visual pathway, the optic radiation, and finally connects to the primary visual cortex. Diffusion MRI tractography is the only technology that can noninvasively reconstruct the visual pathway. However, complete and accurate visual pathway reconstruction is challenging because of the skull base environment and complex fiber geometries. Specifically, the optic nerve within the complex skull base environment can cause abnormal diffusion signals. The crossing and fanning fibers at the optic chiasm, and a sharp turn of Meyer's loop at the optic radiation, contribute to complex fiber geometries of the visual pathway. A fiber trajectory distribution (FTD) function-based tractography method of our previous work and several high sensitivity tractography methods can reveal these complex fiber geometries, but are accompanied by false-positive fibers. Thus, the related studies of the visual pathway mostly applied the expert region of interest selection strategy. However, interobserver variability is an issue in reconstructing an accurate visual pathway. In this paper, we propose a unified global tractography framework to automatically reconstruct the visual pathway. We first extend the FTD function to a high-order streamline differential equation for global trajectory estimation. At the global level, the tractography process is simplified as the estimation of global trajectory distribution coefficients by minimizing the cost between trajectory distribution and the selected directions under the prior guidance by introducing the tractography template as anatomic priors. Furthermore, we use a deep learning-based method and tractography template prior information to automatically generate the mask for tractography. The experimental results demonstrate that our proposed method can successfully reconstruct the visual pathway with high accuracy.

Multiple cortical visual streams in humans.

The effective connectivity between 55 visual cortical regions and 360 cortical regions was measured in 171 HCP participants using the HCP-MMP atlas, and complemented with functional connectivity and diffusion tractography. A Ventrolateral Visual "What" Stream for object and face recognition projects hierarchically to the inferior temporal visual cortex, which projects to the orbitofrontal cortex for reward value and emotion, and to the hippocampal memory system. A Ventromedial Visual "Where" Stream for scene representations connects to the parahippocampal gyrus and hippocampus. An Inferior STS (superior temporal sulcus) cortex Semantic Stream receives from the Ventrolateral Visual Stream, from visual inferior parietal PGi, and from the ventromedial-prefrontal reward system and connects to language systems. A Dorsal Visual Stream connects via V2 and V3A to MT+ Complex regions (including MT and MST), which connect to intraparietal regions (including LIP, VIP and MIP) involved in visual motion and actions in space. It performs coordinate transforms for idiothetic update of Ventromedial Stream scene representations. A Superior STS cortex Semantic Stream receives visual inputs from the Inferior STS Visual Stream, PGi, and STV, and auditory inputs from A5, is activated by face expression, motion and vocalization, and is important in social behaviour, and connects to language systems.

Visual Pathway Involvement in NMDA Receptor Encephalitis: A Clinical, Optical Coherence Tomography, and 18-Fluorodeoxyglucose PET/CT Approach.

BACKGROUND: Anti-NMDA receptor (NMDAR) encephalitis patients have been reported to exhibit visual dysfunction without retinal thinning. The objective of our study was to examine the involvement of the visual pathway structure and function in anti-NMDAR encephalitis by assessing postrecovery visual function and retinal structure, and acute-phase occipital cortex function. METHODS: In this cross-sectional study, patients diagnosed with anti-NMDAR encephalitis per consensus criteria underwent postrecovery visual acuity (VA) testing and optical coherence tomography (OCT) with automated retinal layer segmentation. Clinical data and acute-phase brain 18F-fluorodeoxyglucose (FDG) PET/CT (performed within 90 days of symptom onset, assessed qualitatively and semi-quantitatively) were retrospectively analyzed. VA and OCT measures were compared between anti-NMDAR and age, sex, and race-matched healthy controls (HC). When available, FDG-PET/CT metabolism patterns were analyzed for correlations with VA, and OCT measures. RESULTS: A total of 16 anti-NMDAR (32 eyes) and 32 HC (64 eyes) were included in the study. Anti-NMDAR exhibited lower low-contrast VA (2.5% contrast: -4.4 letters [95% CI; -8.5 to -0.3]; P = 0.04, 1.25% contrast: -6.8 letters [95%CI; -12 to -1.7]; P = 0.01) compared with HC, but no differences were found on OCT-derived retinal layer thicknesses. Acute-phase FDG-PET/CT medial occipital cortex metabolism did not correlate with follow-up low-contrast VA or ganglion cell/inner plexiform layer thickness (GCIPL) (n = 7, 2.5% contrast: r = -0.31; P = 0.50, 1.25% contrast: r = -0.34; P = 0.45, GCIPL: r = -0.04; P = 0.94). CONCLUSIONS: Although the visual system seems to be involved in anti-NMDAR encephalitis, no retinal structural or occipital cortex functional abnormalities seem to be responsible for the visual dysfunction. When detected acutely, occipital lobe hypometabolism in anti-NMDAR encephalitis does not seem to associate with subsequent retrograde trans-synaptic degenerative phenomena, potentially reflecting reversible neuronal/synaptic dysfunction in the acute phase of the illness rather than neuronal degeneration.

Prognostic Value of Optical Coherence Tomography Characteristics in Anterior Visual Pathway Meningiomas.

BACKGROUND: Anterior visual pathway meningiomas (AVPM) represent 2.5%-18% of all meningiomas. They may affect visual function, including visual acuity (VA) and visual field (VF). The principal modes of treatment are surgery and radiotherapy. The prognostic value of macular ganglion cell complex count (GCC) thickness has not been assessed in the literature thus far. The purpose of this study was to evaluate the prognostic value of pre-treatment optical coherence tomography (OCT) parameters (retinal nerve fiber layer and GCC) for visual outcomes in patients with AVPM. METHODS: We retrospectively reviewed the medical records of all patients with AVPM who were treated in the Sheba Medical Center between 2011 and 2020. Included were patients with valid data containing preintervention OCT findings on the CIRRUS device and a minimum follow-up of 6 months. Preintervention and postintervention data on comprehensive ophthalmic examinations and OCT parameters of the affected eyes were retrieved. The correlation between preintervention OCT parameters and the visual outcome was assessed. The patients were also divided into 2 groups according to preintervention GCC (thin vs normal), and the visual outcome was compared between groups. RESULTS: In total, 186 patients' medical records were analyzed, and 38 patients who met the inclusion criteria were included in the study (mean age at diagnosis 52.8 ± 12.2 years, 28 women). Twenty-nine patients had 1 affected eye, and 9 had bilateral insult. A higher preinterventional average GCC was associated with better VA at 6 months, 1 year, and 2 years after intervention (r = -0.5, P ≤ 0.004, 0.005, and 0.03, respectively). There was a significant correlation between preinterventional GCC and VF mean deviation 2 years after intervention (r = 0.7, P ≤ 0.001). The thinner the GCC, the more prominent was the change in VA from before intervention to 2 years after intervention ( P ≤ 0.008). Correction for multiple comparisons with the Benjamini-Hochberg procedure did not change the significance of our findings. CONCLUSIONS: OCT parameters (GCC) have a predictive value in AVPM. There is strong correlation between preinterventional GCC and VA shortly after the intervention. Although a thin GCC is generally considered a negative prognostic factor, improvement in clinical parameters was also evident in patients with thin GCC. The potential of improvement despite preinterventional GCC thinning can add to the clinical discussion of the prognosis, and therefore, we recommend the patients with AVPM to undergo OCT and to be advised that GCC thinning alone should not be used as a major criterion in deciding whether treatment should be pursued.

Multimodal Analysis of the Visual Pathways in Friedreich's Ataxia Reveals Novel Biomarkers.

BACKGROUND: Optic neuropathy is a near ubiquitous feature of Friedreich's ataxia (FRDA). Previous studies have examined varying aspects of the anterior and posterior visual pathways but none so far have comprehensively evaluated the heterogeneity of degeneration across different areas of the retina, changes to the macula layers and combined these with volumetric MRI studies of the visual cortex and frataxin level. METHODS: We investigated 62 genetically confirmed FRDA patients using an integrated approach as part of an observational cohort study. We included measurement of frataxin protein levels, clinical evaluation of visual and neurological function, optical coherence tomography to determine retinal nerve fibre layer thickness and macular layer volume and volumetric brain MRI. RESULTS: We demonstrate that frataxin level correlates with peripapillary retinal nerve fibre layer thickness and that retinal sectors differ in their degree of degeneration. We also shown that retinal nerve fibre layer is thinner in FRDA patients than controls and that this thinning is influenced by the AAO and GAA1. Furthermore we show that the ganglion cell and inner plexiform layers are affected in FRDA. Our MRI data indicate that there are borderline correlations between retinal layers and areas of the cortex involved in visual processing. CONCLUSION: Our study demonstrates the uneven distribution of the axonopathy in the retinal nerve fibre layer and highlight the relative sparing of the papillomacular bundle and temporal sectors. We show that thinning of the retinal nerve fibre layer is associated with frataxin levels, supporting the use the two biomarkers in future clinical trials design. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.