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.

Comparison of DTL and gold cup skin electrodes for recordings of the multifocal electroretinogram.

OBJECTIVE: To compare mfERG recordings with the Dawson-Trick-Litzkow (DTL) and gold cup skin electrode in healthy young and old adults and to test the sensitivity of both electrodes to age-related changes in the responses. METHODS: Twenty participants aged 20-27 years ("young") and 20 participants aged 60-75 ("old") with a visual acuity of ≤ 0 logMAR were included. The mfERG responses were recorded simultaneously using DTL and skin electrodes. P1 amplitudes, peak times and signal-to-noise ratios (SNRs) were compared between both electrodes and across age groups, and correlation analyses were performed. The electrode's performance in discriminating between age groups was assessed via area under curve (AUC) of receiver operating characteristics. RESULTS: Both electrodes reflected the typical waveform of mfERG recordings. For the skin electrode, however, P1 amplitudes were significantly reduced (p < 0.001; reduction by over 70%), P1 peak times were significantly shorter (p < 0.001; by approx. 1.5 ms), and SNRs were reduced [(p < 0.001; logSNR ± SEM DTL young (old) vs gold cup: 0.79 ± 0.13 (0.71 ± 0.15) vs 0.37 ± 0.15 (0.34 ± 0.13)]. All mfERG components showed strong significant correlations (R2 ≥ 0.253, p < 0.001) between both electrodes for all eccentricities. Both electrodes allowed for the identification of age-related P1 changes, i.e., P1-amplitude reduction and peak-time delay in the older group. There was a trend to higher AUC for the DTL electrode to delineate these differences between age groups, which, however, failed to reach statistical significance. CONCLUSIONS: Both electrode types enable successful mfERG recordings. However, in compliant patients, the use of the DTL electrode appears preferable due to the larger amplitudes, higher signal-to-noise ratio and its better reflection of physiological changes, i.e., age effects. Nevertheless, skin electrodes appear a viable alternative for mfERG recordings in patients in whom the use of corneal electrodes is precluded, e.g., children and disabled patients.

Structure-Function Relationship of Retinal Ganglion Cells in Multiple Sclerosis.

The retinal ganglion cells (RGC) may be considered an easily accessible pathophysiological site of degenerative processes in neurological diseases, such as the RGC damage detectable in multiple sclerosis (MS) patients with (HON) and without a history of optic neuritis (NON). We aimed to assess and interrelate RGC functional and structural damage in different retinal layers and retinal sites. We included 12 NON patients, 11 HON patients and 14 healthy controls for cross-sectional multifocal pattern electroretinography (mfPERG) and optical coherence tomography (OCT) measurements. Amplitude and peak times of the mfPERG were assessed. Macula and disc OCT scans were acquired to determine macular retinal layer and peripapillary retinal nerve fiber layer (pRNFL) thickness. In both HON and NON patients the foveal N2 amplitude of the mfPERG was reduced compared to controls. The parafoveal P1 peak time was significantly reduced in HON only. For OCT, parafoveal (pfGCL) and perifoveal (pGCL) ganglion cell layer thicknesses were decreased in HON vs. controls, while pRNFL in the papillomacular bundle sector (PMB) showed reductions in both NON and HON. As the mfPERG derived N2 originates from RGC axons, these findings suggest foveal axonal dysfunction not only in HON, but also in NON patients.

Diagnostic performance of multifocal photopic negative response, pattern electroretinogram and optical coherence tomography in glaucoma.

The photopic negative response of the electroretinogram reflects retinal ganglion cell function and consequently aids diagnosis of optic nerve diseases including glaucoma. In this study, we assessed the efficacy of stimulation parameters for electroretinographic recordings of the multifocal photopic negative response (mfPhNR) for the detection of glaucoma and compared the diagnostic accuracy of electrophysiological, structural and functional measures of glaucoma. We compared the diagnostic performance of the mfPhNR for 6 different stimulation rates in a cohort of 24 controls, 10 glaucoma suspects (GLAS ) and 16 glaucoma participants (GLAG). A cross-modal comparison of the mfPhNR/b wave ratio was performed with the pattern electroretinogram (PERG), and the peripapillary retinal nerve fiber layer (pRNFL) thickness. These analyses were based on area under curves (AUC) obtained from receiver-operating-characteristics (ROC) and step-wise regression analyses. We found that compared to the other mfPhNR-conditions, the PhNR/b-wave ratio for the fastest stimulation condition had the highest AUC for GLAS (0.84, P = 0.008, 95%CI: 0.71- 0.98), while the other modalities, i.e., PERG-amplitude and pRNFL had AUCs of 0.78 (P= 0.039), and 0.74 (P < 0.05), respectively. For GLAG , the respective AUCs were 0.78 (P= 0.004), 0.85 (P< 0.001) and 0.87 (P< 0.001). pRNFL was the significant predictor for both mfPhNR/b-wave ratio [t (48) = 4, P = 0.0002] and for PERG amplitude [t (48) = 3.4, P = 0.001]. In conclusion, fast mfPhNR protocols outperform other multifocal PhNR protocols in the identification of glaucomatous damage especially for GLAS and thus aid the early detection of glaucoma, indicating its value as a surrogate marker of early stage ganglion cell dysfunction.

[Reaching Beyond the Retina with Clinical Electrophysiology]. / Mit klinischer Elektrophysiologie hinter die Netzhaut.

Electrophysiological recordings from the retina and cortex are pivotal to reach beyond the retina for ophthalmological and neuro-ophthalmological diagnostic testing. Pattern electroretinograms (PERG) can be used to examine retinal ganglia cells and visual evoked potentials (VEP) help to investigate overall visual pathways. Thus, they support objective functional tests of visual pathways, as well as differential diagnosis. Conventional electrophysiology is of limited value in detecting local defects in the visual field. This gap is filled by applications of multifocal electrophysiology. This permits spatially resolved testing with multifocal PERG (mfPERG) and multifocal VEP (mfVEP), and eventually objective visual field testing with mfVEP. It is important for this spectrum of methods to consider possible confounds when performing the measurements and when interpreting the results. This is explained in the present article on the basis of a series of typical examples.

Assessing Visual Crowding in Participants With Preperimetric Glaucoma Using Eye Movement and Manual Response Paradigms.

Purpose: Crowding is the inability to distinguish objects in the periphery in the presence of clutter. Previous studies showed that crowding is elevated in patients with glaucoma. This could serve as an indicator of the functional visual performance of patients with glaucoma but at present appears too time-consuming and attentionally demanding. We examined visual crowding in individuals with preperimetric glaucoma to compare the potential effectiveness of eye movement-based and manual response paradigms. Methods: We assessed crowding magnitude in 10 participants with preperimetric glaucoma and 10 age-matched controls. Crowding magnitudes were assessed using four different paradigms: a conventional two-alternative forced choice (2AFC) manual, a 2AFC and a six-alternative forced choice (6AFC) eye movement, and a serial search paradigm. All paradigms measured crowding magnitude by comparing participants' orientation discrimination thresholds in isolated and flanked stimulus conditions. Moreover, assessment times and participant preferences were compared across paradigms. Results: Patients with preperimetric glaucoma exhibited elevated crowding, which was most evident in the manual-response paradigm. The serial search paradigm emerged as the fastest method for assessing thresholds, yet it could not effectively distinguish between glaucoma and control groups. The 6AFC paradigm proved challenging for both groups. Conclusions: We conclude that patients with preperimetric glaucoma demonstrate heightened binocular visual crowding. This is most effectively demonstrated via the 2AFC manual response paradigm. The additional attentional demand in eye movement paradigms rendered them less effective in the elderly population of the present study. Translational Relevance: Our findings underscore both the value and the complexity of efficiently evaluating crowding in elderly participants, including those with preperimetric glaucoma.

Navigation performance in glaucoma: virtual-reality-based assessment of path integration.

Navigation is essential for moving between locations in our daily lives. We investigated the relationship between visual impairment in glaucoma and path-integration-based navigation. Fourteen glaucoma and 15 controls underwent ophthalmological examination (including visual acuity (logMAR), visual field sensitivity (MD: mean deviation from matched reference cohort), and peripapillary retinal nerve fiber layer (pRNFL)). Both groups navigated physically in virtual reality (VR) environments during daylight and dawn conditions. Briefly, the participants traversed a path marked by three targets, subsequently pointing back to the path's origin. Outcome measures included (i) travel-time, (ii) pointing-time, and (iii) Euclidian-distance error between indicated and starting position. Robust linear regression was conducted between visual function outcomes of the better eye and VR outcome measures. Glaucoma patients showed increase in travel-time (by 8.2 ± 1.7 s; p = 0.002) and in pointing-time (by 5.3 ± 1.6 s; p = 0.016). Predictors were MD for all outcome measures (p < 0.01) and pRNFL for travel-time (p < 0.01). The results suggest that the effect of glaucoma on the elapsed time depends on disease progression, i.e. people with stronger visual impairment need more time. This uncertainty during everyday navigation tasks may adversely affect their quality of life.

Rapid campimetry - a novel robust kinetic approach for visual field screening in glaucoma.

Purpose: To investigate the robustness and variability of a novel kinetic visual field (VF) screening method termed rapid campimetry (RC). Methods: In RC visual field (VF) screening is enabled via kinetic-based testing on any computer (10°/4.7 s at 40-cm viewing distance) and high contrast in a dark room (1 cd/cm2). In experiment (1): 30 participants [20 healthy participants (HC), 5 glaucoma patients (GLA) and 5 patients with cataract (CAT)] were included to test the intra-session variability (fatigue effect) and the following effects on RC: room illumination (140 cd/m2), ±3 D refractive errors, media opacity. In experiment (2): Inter-session variability (1-3 weeks apart) was assessed in 10 HC and 10 GLA. Since RC detects absolute scotomas, the outcome measure was the size of physiological (blindspot) and pathological (glaucoma) scotomas in degrees. A repeated measures ANOVA was employed in experiment 1 and intraclass correlation (ICC) in experiment 2. Results: Neither the size of the blindspot nor the VF defects differed significantly between the different testing conditions. For intra-session variability, the average bias of blindspot size was -0.6 ± 2.5°, limits of agreement (LOA), in comparison to 0.3 ± 1.5° for VF defects, both with ICC of 0.86 and 0.93, respectively. For the inter-session repeatability, the average bias and LOA for blindspot size was 0.2 ± 3.85° in comparison 1.6 ± 3.1° for VF defects, both with ICC of 0.87 and 0.91, respectively. Conclusion: RC was robust to suboptimal testing VF conditions and showed good-to-excellent reliability between VF testing visits holding high potential for teleophthalmology.

Rapid Campimetry in glaucoma - correspondence with standard perimetry and OCT.

The Rapid Campimetry (RC), a kinetic visual field test proved to reliably detect visual field defects within the central 10° degrees, the most crucial part for visual acuity and quality of life, affected even at very early stages of glaucoma, within a short measurement epoch, ~ 1 min. This study aims to further investigate RC correspondence with standard tests in glaucoma, namely standard automated perimetry (SAP) and optical coherence tomography (OCT) within 10° of visual field (VF). For this purpose, we included 41 participants, [21 glaucoma (GLA, mean age: 65.9 ± 12.4; 12 preperimetric eyes and 11 with VF defects) and 20 healthy controls (HC; mean age: 65.0 ± 10.3); 20 eyes]. At first, we compared the rate of detection/exclusion of VF defects in RC vs. SAP. Then, for those with VF defects (11 eyes), we investigated the 68-pointwise correspondence of 10 - 2 layout of RC and SAP. For functional and structural (SF) correspondence, pointwise correspondence of RC, SAP vs. OCTmacula [ macular ganglion cell thickness (GCL)] was also performed. Further, we compared sector-based correspondence of RC, SAP vs. OCTmacula accounting for GCL displacement at the fovea as well as sector-based correspondence with OCTdisc [peripapillary retinal nerve fiber layer thickness (pRNFL)]. Agreement estimates were reported along with Cohen Kappa ([Formula: see text]) statistic. For overall performance, RC and SAP showed 100% agreement ([Formula: see text]) for the exclusion of VF defects (HC and preperimetric GLA) and for detection of VF defects [11 eyes of 9 GLA, ([Formula: see text]]. Further, RC outperformed SAP in detection of arcuate scotomas, 7 vs. 5, respectively. Pointwise correspondence of VF defects (11 eyes), RC-SAP agreement reached 90% accuracy ([Formula: see text]). For SF correspondence, RC [SAP] showed 62% [69%] pointwise agreement with OCTmacula, ([Formula: see text]). For macular sector-based correspondence, SF correspondence improved and reached 83% [83%] agreement, ([Formula: see text]). For OCTdisc sector-based analysis, SF correspondence was highest, 100% [100%] agreement, ([Formula: see text]). Rapid Campimetry gave reproducible results in comparison to SAP and OCT with high potential as a screening VF method given its short testing duration, ~ 1 min in screening mode, and compatibility with telemedicine technologies upon future optimization and automation.

Effect of nystagmus on VEP-based objective visual acuity estimates.

In order to determine the effect of nystagmus on objective visual acuity (VA) estimates, we compared subjective (VApsych) and objective (VEP, VAVEP) VA estimates in participants with nystagmus. For this purpose, 20 participants with nystagmus (NY) caused by idiopathic infantile nystagmus, albinism, achiasma or acquired nystagmus were recruited in this study. Estimates of BCVA (best corrected visual acuity) were determined psychophysically (VApsych; FrACT, Freiburg visual acuity test) and electrophysiologically (VAVEP; EP2000) according to ISCEV (International Society of Clinical Electrophysiology of Vision) guidelines. For each participant the eye with the stronger fixation instability [Nidek microperimeter (MP-1), Nidek Instruments] was included for further analysis. VApsych vs VAVEP were compared via paired t-tests and the correlation of the difference between VApsych and VAVEP (∆VA) vs the degree of fixation instability was tested with Pearson correlation (r). We found VAVEP to be better than VApsych [by 0.12 Logarithm of the Minimum Angle of Resolution (logMAR); mean ± standard error (SE) of VAVEP vs VApsych: 0.176 ± 0.06 vs. 0.299 ± 0.06, P = 0.017] and ∆VA to be correlated linearly with the degree of fixation instability (r2 = 0.21,p = 0.048). In conclusion, on average we report a small VA overestimation, around 1 line, for VAVEP compared to VApsych in NY. This overestimation depended on the magnitude of the fixation instability. As a rule of thumb, a reduction of the fixation probability in the central 4° from 100 to 50% leads on average to a VAVEP overestimation of around 0.25 logMAR, i.e. 2.5 lines.

Scotopic and Photopic Conventional Visual Acuity and Hyperacuity - Binocular Summation.

Purpose: The purpose of this study was to determine and compare binocular summation (BiS) of conventional visual acuity (cVA) versus hyperacuity (hVA) for photopic and scotopic luminance conditions as a potential biomarker to assess the outcome of interventions on binocular function. Methods: Sixteen young adults (age range [years] = 21-31; 8 women; cVA logMAR < 0.0) participated in this study. The Freiburg Visual Acuity Test (FrACT) was used for VA testing and retested on another day. Both cVA and hVA were determined for dark grey optotypes on light grey background. Participants underwent 40 minutes of dark adaptation prior to scotopic VA testing. Binocular and monocular VA testing was performed. The eye with better VA over the 2 days of testing was selected, the BiS was quantified (binocular VA - better monocular VA) and repeated measures ANOVAs were performed. Results: Binocular VA exceeded monocular VA for all luminance conditions, VA-types, and sessions. We report BiS estimates for photopic and scotopic cVA and hVA, (logMAR BiS ± SEM [decimal BiS]): photopic = -0.01 ± 0.01 [1.03] and -0.06 ± 0.03 [1.15]; and scotopic = -0.05 ± 0.01 [1.12] and -0.11 ± 0.04 [1.28], respectively). Improvement for binocular vision estimates ranged from 0.01 to 0.11 logMAR. A repeated-measures ANOVA (RM ANOVA) did not reveal significant effects of LUMINANCE or VA TYPE on BiS, albeit a trend for strongest BiS for scotopic hVA (15% vs. 28%, photopic versus scotopic, respectively) and weakest for photopic cVA (3% vs. 12%, photopic versus scotopic conditions, respectively). Conclusions: Our results indicate that BiS of VA is relevant to scotopic and photopic hVA and cVA. It appears therefore a plausible candidate biomarker to assess the outcome of retinal therapies restoring rod or cone function on binocular vision. Translational Relevance: Binocular summation of visual acuity might serve as a clinical biomarker to monitor therapy outcome on binocular rod and cone-mediated vision.

Gaze behavior in open-angle glaucoma patients during visuo-cognitive-motor tasks: a cross-sectional study.

This study investigated gaze behavior during visuo-cognitive-motor tasks with a change of movement direction in glaucoma patients and healthy controls. Nineteen glaucoma patients (10 females, 9 males) and 30 healthy sighted controls (17 females, 13 males) participated in this cross-sectional study. Participants performed two visuo-cognitive-motor tasks with a change of movement direction: (i) the "Speed-Court-Test" that involved stepping on different sensors in response to a visual sign displayed on either a large or small screen (165″ and 55″, respectively); (ii) the "Trail-Walking-Test" that required walking to 15 cones labeled with numbers (1-8) or letters (A-G) in an alternately ascending order. During these tasks, the time needed for completing each task was determined and the gaze behavior (e.g., saccade duration, fixation duration) was recorded via eye tracking. Data were analyzed with repeated measures analyses of covariance (ANCOVA; GROUP × SCREEN) and one-way ANCOVA. No differences between groups were found for the time needed to complete the tasks. However, during the "Trail-Walking-Test", the fixation duration was longer for glaucoma patients than for controls (p = 0.016, η p 2  = 0.131). Furthermore, during the "Speed-Court-Test", there was a screen size effect. Irrespective of group, saccade amplitudes were lower (p < 0.001, η p 2  = 0.242) and fixation durations were higher (p = 0.021, η p 2  = 0.125) for the small screen. Fixation durations were longer in glaucoma patients during the cognitively demanding "Trail-Walking-Test", which might indicate a strategy to compensate for their visual impairment.

Temporal-to-Nasal Macular Ganglion Cell and Inner Plexiform Layer Ratios in a Large Adult Twin Cohort: Correlations With Age and Heritability.

Purpose: Temporal-to-nasal macular ganglion cell layer thickness ratios are reduced in albinism. We explored similar ratios in a large twin cohort to investigate ranges in healthy adults, correlations with age, and heritability. Methods: More than 1000 twin pairs from TwinsUK underwent macular optical coherence tomography (OCT) scans. Automated segmentation yielded thicknesses for the combined ganglion cell and inner plexiform layer (GCIPL) in Early Treatment of Diabetic Retinopathy Study subfields. Participants with diseases likely to affect these layers or segmentation accuracy were excluded. Inner and outer ratios were defined as the ratio of temporal-to-nasal GCIPL thickness for inner and outer subfields respectively. Corresponding ratios were obtained from a smaller cohort undergoing OCTs with a different device (three-dimensional (3D)-OCT, Topcon, Japan). Results: Scans from 2300 twins (1150 pairs) were included (mean [SD] age, 53.9 (16.5) years). Mean (SD) inner and outer ratios were 0.89 (0.09) and 0.84 (0.11), correlating negatively with age (coefficients, -0.17 and -0.21, respectively). In males (150 pairs) ratios were higher and did not correlate significantly with age. Intrapair correlation coefficients were higher in monozygotic than dizygotic pairs; age-adjusted heritability estimates were 0.20 and 0.23 for inner and outer ratios, respectively. For the second cohort (n = 166), mean (SD) ratios were 0.93 (0.08) and 0.91 (0.09), significantly greater than for the larger cohort. Conclusions: Our study gives reference values for temporal-to-nasal macular GCIPL subfield ratios. Weak negative correlations with age emerged. Genetic factors may contribute to ∼20% to 23% of the variance in healthy individuals. The ratios differ according to the OCT platform used.

Altered Perception of the Bistable Motion Quartet in Albinism.

Purpose: Perception of the motion quartet (MQ) alternates between horizontal and vertical motion, with a bias toward vertical motion. This vertical bias has been explained by the dominance of intrahemispheric processing. In albinism, each hemisphere receives input from both visual hemifields owing to enhanced crossing of the optic nerves at the optic chiasm. This might affect the perception of the ambiguous MQ and particularly the vertical bias. Methods: The effect of optic nerve misrouting in persons with albinism and nystagmus (PWA, n = 14) on motion perception for MQ was compared with healthy controls (HC; n = 11) and with persons with nystagmus in the absence of optic nerve misrouting (PWN; n = 12). We varied the ratio of horizontal and vertical distances of MQ dots (aspect ratio [AR]) between 0.75 and 1.25 and compared the percentages of horizontal and vertical motion percepts as a function of AR between groups. Results: For HC, the probability of vertical motion perception increased as a sigmoid function with increasing AR exhibiting the expected vertical percept bias (mean, 58%; median, 54%; vertical motion percepts). PWA showed a surprisingly strong horizontal bias independent of the AR with a mean of 11% (median, 10%) vertical motion percepts. The PWN was in between PWA and HC, with a mean of 34% (median, 47%) vertical perception. Nystagmus alone is unlikely to explain this pattern of results because PWA and PWN had comparable fixation stabilities. Conclusions: The strong horizontal bias observed in PWA and PWN might partly result from the horizontal nystagmus. The even stronger horizontal bias in PWA indicates that the intrahemispherical corepresentation of both visual hemifields may play an additional role. The altered perception of the MQ in PWA opens opportunities to (i) understand the interplay of stability and plasticity in altered visual pathway conditions and (ii) identify visual pathway abnormalities with a perception-based test using the MQ.

Functional and structural readouts for early detection of retinal involvement in multiple sclerosis.

Introduction: The retina, a window into the brain, allows for the investigation of many disease-associated inflammatory and neurodegenerative changes affecting the central nervous system (CNS). Multiple sclerosis (MS), an autoimmune disease targeting the CNS, typically impacts on the visual system including the retina. Hence, we aimed to establish innovative functional retinal measures of MS-related damage, e.g., spatially resolved non-invasive retinal electrophysiology, backed by established morphological retinal imaging markers, i.e., optical coherence tomography (OCT). Methods: 20 healthy controls (HC) and 37 people with MS [17 without history of optic neuritis (NON) and 20 with (HON) history of optic neuritis] were included. In this work, we differentially assessed photoreceptor/bipolar cells (distal retina) and retinal ganglion cell (RGC, proximal retina) function besides structural assessment (OCT). We compared two multifocal electroretinography-based approaches, i.e., the multifocal pattern electroretinogram (mfPERG) and the multifocal electroretinogram to record photopic negative response (mfERG PhNR ). Structural assessment utilized peripapillary retinal nerve fiber layer thickness (pRNFL) and macular scans to calculate outer nuclear thickness (ONL) and macular ganglion cell inner plexiform layer thickness (GCIPL). One eye was randomly selected per subject. Results: In NON, photoreceptor/bipolar cell layer had dysfunctional responses evidenced by reduced mfERG PhNR -N1 peak time of the summed response, but preserved structural integrity. Further, both NON and HON demonstrated abnormal RGC responses as evidenced by the photopic negative response of mfERG PhNR (mfPhNR) and mfPERG indices (P < 0.05). Structurally, only HON had thinned retina at the level of RGCs in the macula (GCIPL, P < 0.01) and the peripapillary area (pRNFL, P < 0.01). All three modalities showed good performance to differentiate MS-related damage from HC, 71-81% area under curve. Conclusion: In conclusion, while structural damage was evident mainly for HON, functional measures were the only retinal read-outs of MS-related retinal damage that were independent of optic neuritis, observed for NON. These results indicate retinal MS-related inflammatory processes in the retina prior to optic neuritis. They highlight the importance of retinal electrophysiology in MS diagnostics and its potential as a sensitive biomarker for follow-up in innovative interventions.

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.

Optical Coherence Tomography as a Biomarker for Differential Diagnostics in Nystagmus: Ganglion Cell Layer Thickness Ratio.

In albinism, with the use of optical coherence tomography (OCT), a thinning of the macular ganglion cell layer was recently reported. As a consequence, the relevant OCT measure, i.e., a reduction of the temporal/nasal ganglion cell layer thickness quotient (GCLTQ), is a strong candidate for a novel biomarker of albinism. However, nystagmus is a common trait in albinism and is known as a potential confound of imaging techniques. Therefore, there is a need to determine the impact of nystagmus without albinism on the GCLTQ. In this bi-center study, the retinal GCLTQ was determined (OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany) for healthy controls (n = 5, 10 eyes) vs. participants with nystagmus and albinism (Nalbinism, n = 8, 15 eyes), and with nystagmus of other origins (Nother, n = 11, 17 eyes). Macular OCT with 25 horizontal B scans 20 × 20° with 9 automated real time tracking (ART) frames centered on the retina was obtained for each group. From the sectoral GCLTs of the early treatment diabetic retinopathy study (ETDRS) circular thickness maps, i.e., 3 mm and 6 mm ETDRS rings, GCLTQ I and GCLTQ II were determined. Both GCLTQs were reduced in Nalbinism (GCLTQ I and II: 0.78 and 0.77, p < 0.001) compared to Nother (0.91 and 0.93) and healthy controls (0.89 and 0.95). The discrimination of Nalbinism from Nother via GCLTQ I and II had an area under the curve of 80 and 82% with an optimal cutoff point of 0.86 and 0.88, respectively. In conclusion, lower GCLTQ in Nalbinism appears as a distinguished feature in albinism-related nystagmus as opposed to other causes of nystagmus.

Rapid Campimetry-A Novel Screening Method for Glaucoma Diagnosis.

One of the most important functions of the retina-the enabling of perception of fast movements-is largely suppressed in standard automated perimetry (SAP) and kinetic perimetry (Goldmann) due to slow motion and low contrast between test points and environment. Rapid campimetry integrates fast motion (=10°/4.7 s at 40 cm patient-monitor distance) and high contrast into the visual field (VF) examination in order to facilitate the detection of absolute scotomas. A bright test point moves on a dark background through the central 10° VF. Depending on the distance to the fixation point, the test point automatically changes diameter (≈0.16° to ≈0.39°). This method was compared to SAP (10-2 program) for six subjects with glaucoma. Rapid campimetry proved to be comparable and possibly better than 10-2 SAP in identifying macular arcuate scotomas. In four subjects, rapid campimetry detected a narrow arcuate absolute scotoma corresponding to the nerve fiber course, which was not identified as such with SAP. Rapid campimetry promises a fast screening method for the detection of absolute scotomas in the central 10° visual field, with a potential for cloud technologies and telemedical applications. Our proof-of-concept study motivates systematic testing of this novel method in a larger cohort.

Non-invasive electrophysiology in glaucoma, structure and function-a review.

Glaucoma, its early diagnosis, and monitoring of interventions remain an ongoing challenge. We here review developments in functional assessment and its relation to morphology, evaluating recent insights in electrophysiology in glaucoma and highlighting how glaucoma research and diagnostics benefit from combined approaches of OCT and electrophysiological investigations. After concise overviews of OCT and non-invasive electrophysiology in glaucoma, we evaluate commonalities and complementarities of OCT and electrophysiology for our understanding of glaucoma. As a specific topic, the dynamic range (floor effects) of the various techniques is discussed.

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.