Treadmill-walking impairs visual function in early glaucoma and elderly controls.

AIMS: Impaired vision is an additional risk factor in elderly for falls. We investigated the hypothesis that treadmill (TM) walking affects visual function in both healthy elderly and those with early-moderate visual dysfunction due to glaucoma. METHODS: Thirty healthy controls (HC) aged 64-83 years and 18 glaucoma patients (GLA) aged 62-82 years participated in this cross-sectional study. The impact of TM-walking on visual function was assessed binocularly for (i) best-corrected visual acuity (BCVA) with and without crowding effect, (ii) contrast sensitivity (CS), and (iii) and visual field (mean deviation, VF-MD). Visual function was tested while participants were standing or during TM-walking for 2 speed conditions: (i) fast walking at their preferred speed and (ii) walking at a fixed speed of 3.5 km/h. RESULTS: GLA, most with early-moderate VF loss, performed equally well as HC. Independent of GROUP, an impact of SPEED on visual functions was statistically evident with large statistical effect size for (i) both types of BCVA with a mean loss of 0.02-0.05 logMAR (η2 = 0.41) and (ii) VF-MD with mean loss of 1 dB (η2 = 0.70), but not for CS. CONCLUSIONS: Here, we introduce a paradigm for the assessment of visual function during walking. We provide proof-of-concept that our approach allows for the identification of walking induced visual function loss, i.e., a deterioration of BCVA and VF-sensitivity during TM-walking in both groups. It is therefore of promise for the investigation of the relation of vision impairment and mobility, ultimately the increased frequency of falls in advanced glaucoma.

Single- and Dual-Task Gait Performance in Patients With Open-Angle Glaucoma: A Cross-sectional Study.

Purpose: To investigate gait kinematics during single- and dual-task walking in glaucoma patients compared with healthy controls. Methods: Nineteen glaucoma patients (10 females, 9 males) and 30 healthy controls (17 females, 13 males) participated in this cross-sectional study. Spatiotemporal gait parameters (e.g., stride length, velocity, minimum toe clearance [MTC]) were assessed using inertial measurement units (sampling frequency 100 Hz) during single-task walking and dual-task walking at a comfortable velocity. During dual-task walking, participants walked and concurrently performed different cognitive tasks in a random order: (i) reaction time task, (ii) N-Back-task, and (iii) letter fluency task with two difficulty levels, respectively. Repeated measures analyses of covariance (Group × Condition) were conducted to analyze the data. Results: A significant effect of group was found for the coefficient of variation (CoV) of the MTC, F(1,39) = 4.504, P = 0.040, \({\rm{\eta }}_{\rm{p}}^2\) = 0.104, with higher values in glaucoma patients. Based on the effect sizes, a main effect of group was also found for the MTC, F(1,39) = 2.668, P = 0.110, \({\rm{\eta }}_{\rm{p}}^2\) = 0.064, and the MTCCoV dual-task costs, F(1,38) = 3.225, P = 0.08, \({\rm{\eta }}_{\rm{p}}^2\) = 0.078, which was lower and higher, respectively, in glaucoma patients. Conclusions: The present study revealed a significantly higher MTC variability as well as medium effect sizes for a lower MTC and higher MTC dual-task costs in glaucoma patients compared with healthy controls, which might be related to a higher risk of falling owing to tripping. Translational Relevance: The minimum toe clearance might mirror disease-related changes in walking performance and might have prognostic value for assessing fall risk in glaucoma patients.

CHIASM-Net: Artificial Intelligence-Based Direct Identification of Chiasmal Abnormalities in Albinism.

Purpose: Albinism is a congenital disorder affecting pigmentation levels, structure, and function of the visual system. The identification of anatomical changes typical for people with albinism (PWA), such as optic chiasm malformations, could become an important component of diagnostics. Here, we tested an application of convolutional neural networks (CNNs) for this purpose. Methods: We established and evaluated a CNN, referred to as CHIASM-Net, for the detection of chiasmal malformations from anatomic magnetic resonance (MR) images of the brain. CHIASM-Net, composed of encoding and classification modules, was developed using MR images of controls (n = 1708) and PWA (n = 32). Evaluation involved 8-fold cross validation involving accuracy, precision, recall, and F1-score metrics and was performed on a subset of controls and PWA samples excluded from the training. In addition to quantitative metrics, we used Explainable AI (XAI) methods that granted insights into factors driving the predictions of CHIASM-Net. Results: The results for the scenario indicated an accuracy of 85 ± 14%, precision of 90 ± 14% and recall of 81 ± 18%. XAI methods revealed that the predictions of CHIASM-Net are driven by optic-chiasm white matter and by the optic tracts. Conclusions: CHIASM-Net was demonstrated to use relevant regions of the optic chiasm for albinism detection from magnetic resonance imaging (MRI) brain anatomies. This indicates the strong potential of CNN-based approaches for visual pathway analysis and ultimately diagnostics.

Deep Learning-Based Detection of Malformed Optic Chiasms From MRI Images.

Convolutional neural network (CNN) models are of great promise to aid the segmentation and analysis of brain structures. Here, we tested whether CNN trained to segment normal optic chiasms from the T1w magnetic resonance imaging (MRI) image can be also applied to abnormal chiasms, specifically with optic nerve misrouting as typical for human albinism. We performed supervised training of the CNN on the T1w images of control participants (n = 1049) from the Human Connectome Project (HCP) repository and automatically generated algorithm-based optic chiasm masks. The trained CNN was subsequently tested on data of persons with albinism (PWA; n = 9) and controls (n = 8) from the CHIASM repository. The quality of outcome segmentation was assessed via the comparison to manually defined optic chiasm masks using the Dice similarity coefficient (DSC). The results revealed contrasting quality of masks obtained for control (mean DSC ± SEM = 0.75 ± 0.03) and PWA data (0.43 ± 0.8, few-corrected p = 0.04). The fact that the CNN recognition of the optic chiasm fails for chiasm abnormalities in PWA underlines the fundamental differences in their spatial features. This finding provides proof of concept for a novel deep-learning-based diagnostics approach of chiasmal misrouting from T1w images, as well as further analyses on chiasmal misrouting and their impact on the structure and function of the visual system.

Mapping Visual Field Defects With fMRI - Impact of Approach and Experimental Conditions.

Current initiatives to restore vision emphasize the need for objective assessments of visual field (VF) defects as pursued with functional magnetic resonance imaging (fMRI) approaches. Here, we compared population receptive field (pRF) mapping-based VF reconstructions to an fMRI method that uses more robust visual stimulation (on-off block design) in combination with individualized anatomy-driven retinotopic atlas-information (atlas-based VF). We investigated participants with sizable peripheral VF-deficits due to advanced glaucoma (n = 4) or retinitis pigmentosa (RP; n = 2) and controls (n = 6) with simulated scotoma. We obtained (1) standard automated perimetry (SAP) data as reference VFs and 3T fMRI data for (2) pRF-mapping [8-direction bar stimulus, fixation color change task] and (3) block-design full-field stimulation [8-direction drifting contrast patterns during (a) passive viewing (PV) and (b) one-back-task (OBT; reporting successions of identical motion directions) to probe the impact of previously reported task-related unspecific visual cortex activations]. Correspondence measures between the SAP and fMRI-based VFs were accuracy, assisted by sensitivity and specificity. We found an accuracy of pRF-based VF from V1 in patients [median: 0.62] that was similar to previous reports and increased by adding V2 and V3 to the analysis [0.74]. In comparison to the pRF-based VF, equivalent accuracies were obtained for the atlas-based VF for both PV [0.67] and, unexpectedly, the OBT [0.59], where, however, unspecific cortical activations were reflected by a reduction in sensitivity [0.71 (PV) and 0.35 (OBT)]. In conclusion, in patients with peripheral VF-defects, we demonstrate that previous fMRI procedures to obtain VF-estimates might be enhanced by: (1) pooling V1-V3 to enhance accuracy; (2) reporting sensitivity and specificity measures to increase transparency of the VF-reconstruction metric; (3) applying atlas-based procedures, if pRF-based VFs are not available or difficult to obtain; and (4) giving, counter-intuitively, preference to PV. These findings are expected to provide guidance to overcome current limitations of translating fMRI-based methods to a clinical work-up.

Functional Dynamics of Deafferented Early Visual Cortex in Glaucoma.

In advanced retinitis pigmentosa with retinal lesions, the lesion projection zone (LPZ) in the early visual cortex can be driven during visual tasks, while it remains unresponsive during passive viewing. We tested whether this finding translates to advanced glaucoma, a major cause of acquired blindness. During visual stimulation, 3T fMRI scans were acquired for participants with advanced glaucoma (n = 4; age range: 51-72) and compared to two reference groups, i.e., advanced retinitis pigmentosa (n = 3; age range: 46-78) and age-matched healthy controls with simulated defects (n = 7). The participants viewed grating patterns drifting in 8 directions (12 s) alternating with uniform gray (12 s), either during passive viewing (PV), i.e., central fixation, or during a one-back task (OBT), i.e., reports of succeeding identical motion directions. As another reference, a fixation-dot task condition was included. Only in glaucoma and retinitis pigmentosa but not in controls, fMRI-responses in the lesion projection zone (LPZ) of V1 shifted from negative for PV to positive for OBT (p = 0.024 and p = 0.012, respectively). In glaucoma, these effects also reached significance in V3 (p = 0.006), while in V2 there was a non-significant trend (p = 0.069). The general absence of positive responses in the LPZ during PV underscores the lack of early visual cortex bottom-up plasticity for acquired visual field defects in humans. Trends in our exploratory analysis suggesting the task-dependent LPZ responses to be inversely related to visual field loss, indicate the benefit of patient stratification strategies in future studies with greater sample sizes. We conclude that top-down mechanisms associated with task-elicited demands rather than visual cortex remapping appear to shape LPZ responses not only in retinitis pigmentosa, but also in glaucoma. These insights are of critical importance for the development of schemes for treatment and rehabilitation in glaucoma and beyond.

[Neuro-computational approaches for objective assessment of visual function]. / Neurocomputationelle Ansätze zur objektiven Funktionsüberprüfung des Sehens.

BACKGROUND: Retinal pathologies affect the structure and function of post-retinal visual pathways. These post-retinal alterations bear the potential to obstruct the aim of innovative retinal treatment to restore visual function. OBJECTIVE: Current developments in the field of neuroimaging and the associated neurocomputational approaches enable a detailed assessment of this interrelationship. As a consequence, they open up the possibility to anticipate the success of treatment. METHODS: This review article demonstrates how innovations particularly in magnetic resonance imaging (MRI)-based anatomical, functional, and diffusion imaging can guide visual pathway assessments that are relevant for ophthalmological applications. RESULTS: Specific examples of retinal and visual pathway pathologies in the context of a detailed analysis of the visual pathway are described. CONCLUSION: A concept is introduced of how to translate the meaningful but technically and computationally challenging neuroimaging procedures into a clinical setting in order to effectively connect these procedures to innovative treatment approaches.

Combined Multi-Modal Assessment of Glaucomatous Damage With Electroretinography and Optical Coherence Tomography/Angiography.

Purpose: To compare the diagnostic performance and to evaluate the interrelationship of electroretinographical and structural and vascular measures in glaucoma. Methods: For 14 eyes of 14 healthy controls and 15 eyes of 12 patients with glaucoma ranging from preperimetric to advanced stages optical coherence tomography (OCT), OCT-angiography (OCT-A), and electrophysiological measures (multifocal photopic negative response ratio [mfPhNR] and steady-state pattern electroretinography [ssPERG]) were applied to assess changes in retinal structure, microvasculature, and function, respectively. The diagnostic performance was assessed via area-under-curve (AUC) measures obtained from receiver operating characteristics analyses. The interrelation of the different measures was assessed with correlation analyses. Results: The mfPhNR, ssPERG amplitude, parafoveal (pfVD) and peripapillary vessel density (pVD), macular ganglion cell inner plexiform layer thickness (mGCIPL) and peripapillary retinal nerve fiber layer thickness (pRNFL) were significantly reduced in glaucoma. The AUC for mfPhNR was highest among diagnostic modalities (AUC: 0.88, 95% confidence interval: 0.75-1.0, P < 0.001), albeit not statistically different from that for macular (mGCIPL: 0.76, 0.58-0.94, P < 0.05; pfVD: 0.81, 0.65-0.97, P < 0.01) or peripapillary imaging (pRNFL: 0.85, 0.70-1.0, P < 0.01; pVD: 0.82, 0.68-0.97, P < 0.01). Combined functional/vascular measures yielded the highest AUC (mfPhNR-pfVD: 0.94, 0.85-1.0, P < 0.001). The functional/structural measure correlation (mfPhNR-mGCIPL correlation coefficient [rs]: 0.58, P = 0.001; mfPhNR-pRNFL rs: 0.66, P < 0.001) was stronger than the functional-vascular correlation (mfPhNR-pfVD rs: 0.29, P = 0.13; mfPhNR-pVD rs: 0.54, P = 0.003). Conclusions: The combination of ERG measures and OCT-A improved diagnostic performance and enhanced understanding of pathophysiology in glaucoma. Translational Relevance: Multimodal assessment of glaucoma damage improves diagnostics and monitoring of disease progression.

Foveal pRF properties in the visual cortex depend on the extent of stimulated visual field.

Previous studies demonstrated that alterations in functional MRI derived receptive field (pRF) properties in cortical projection zones of retinal lesions can erroneously be mistaken for cortical large-scale reorganization in response to visual system pathologies. We tested, whether such confounds are also evident in the normal cortical projection zone of the fovea for simulated peripheral visual field defects. We applied fMRI-based visual field mapping of the central visual field at 3 T in eight controls to compare the pRF properties of the central visual field of a reference condition (stimulus radius: 14°) and two conditions with simulated peripheral visual field defect, i.e., with a peripheral gray mask, stimulating only the central 7° or 4° radius. We quantified, for the cortical representation of the actually stimulated visual field, the changes in the position and size of the pRFs associated with reduced peripheral stimulation using conventional and advanced pRF modeling. We found foveal pRF-positions (≤3°) to be significantly shifted towards the periphery (p<0.05, corrected). These pRF-shifts were largest for the 4° condition [visual area (mean eccentricity shift): V1 (0.9°), V2 (0.9°), V3 (1.0°)], but also evident for the 7° condition [V1 (0.5°), V2 (0.5°), V3 (0.9°)]. Further, an overall enlargement of pRF-sizes was observed. These findings indicate the dependence of foveal pRF parameters on the spatial extent of the stimulated visual field and are likely associated with methodological biases and/or physiological mechanisms. Consequently, our results imply that, previously reported similar findings in patients with actual peripheral scotomas need to be interpreted with caution and indicate the need for adequate control conditions in investigations of visual cortex reorganization.