Sensitive Assessment of Acute Optic Neuritis by a New, Digital Flicker Test.

BACKGROUND: The Aulhorn flicker test (AFT) previously showed promise in diagnosing acute optic neuritis (ON) albeit with suboptimal sensitivity. A new, digitalized version of the AFT (the DFT) has not previously been examined in acute ON. OBJECTIVES: To examine the sensitivity, specificity and reproducibility of the DFT in acute ON. METHOD: The DFT assesses the subjective brightness of a flickering field (1-60 Hz). In normal subjects, brightness enhancement occurs at intermediate frequencies, whereas in acute ON darkness enhancement (DE) is hypothesized. AFT and DFT measurements were obtained in acute ON patients (≤31 days from first symptom) with DE as a quantitative covariate. Reproducibility of the DFT end point was assessed in the form of an intraclass correlation. RESULTS: 30 untreated first-time acute ON patients and 55 healthy controls were examined. AFT and DFT were performed 12.7 days (range: 4-30) following ON onset. The DFT showed a sensitivity of 0.93 (95% CI = 0.78-0.99) to a specificity of 0.96 (95% CI = 0.87-1.00). The AFT showed a sensitivity of 0.76 (95% CI = 0.56-0.90) to a specificity of 1.00 (95% CI = 0.93-1.00). No significant correlation was shown between DFT and visual acuity. The intraclass correlation of the DFT end point in healthy subjects was 0.84. CONCLUSIONS: We present a new DFT in acute ON displaying a high specificity of 0.96 and a sensitivity of 0.93. Our study indicates the DFT to be an accurate and easy-to-use tool in diagnosing acute ON, which may be especially helpful in atypical cases.

Homonymous Hemianopia in Children and Adolescents: An MRI Study.

AIM: Diagnosing homonymous hemianopia (HH) in children can be difficult due to inability to comply with perimetry. Therefore, HH can often only be suspected by magnetic resonance imaging (MRI) showing lesions to the retrochiasmatic visual pathways. The aim of our retrospective observational cross-sectional study was to improve the radiologic detection of HH. METHODS: MRIs of 21 subjects (5-17 years old) with ophthalmologically confirmed HH (14 complete, 7 incomplete hemianopias) were analyzed. In addition, we asked four questions looking at everyday problems possibly related to the HH. The questions asked for (1) problems in avoiding objects/people, (2) bumping into objects/people, (3) difficulties in judging stairs, and (4) difficulties in grasping objects. RESULTS: We found neuroanatomical correlates of the HH in all 21 participants, with the optic radiation being involved in almost all participants (20/21). Everyday problems possibly related to the HH were reported for all nine patients with postneonatally acquired complete hemianopias. In contrast, no such problems were reported for seven patients with incomplete HH (7/7) and for 3/5 patients with complete hemianopias due to pre-, peri- or neonatally acquired brain lesions. INTERPRETATION: A dedicated radiologic analysis of the retrochiasmatic optic pathway should routinely be performed in children with brain lesions to identify children with HH. Early onset and incomplete HH are predictors for successful compensation.

Eye movements during saccadic and fixation tasks in patients with homonymous hemianopia.

BACKGROUND: The aim of our study was to quantify ocular motor performance in patients with homonymous hemianopia and in healthy controls during saccadic and fixation tasks and to detect potential spontaneous adaptive mechanisms in the hemianopic patients. METHODS: Eye movements were recorded in 33 hemianopic patients (15 right, 18 left; disease duration, 0.2-29 years) and 14 healthy subjects by scanning laser ophthalmoscope allowing determination of the absolute fovea position relative to the stimulus without calibration. Landing accuracy of saccades was determined for 5° saccades, indicated by the number of dysmetric saccades (DS), and fixation stability (FS) after landing. In addition, during continuous fixation of a central cross, FS, and distribution of fixational eye movements (FEMs) were measured. Size of macular sparing was determined using custom microperimetry software (stimulus grid, 0.5°). RESULTS: Compared with controls, landing accuracy was decreased in hemianopic patients, indicated by significantly more DS (hypometric and hypermetric) to the blind side compared with the seeing side. The number of DS was greater in patients with macular sparing of <4°. DS were not correlated with age and disease duration. FS after landing was lower after saccades to the blind side. Distribution of FEM during continuous fixation was asymmetrically shifted to the blind side, especially in cases of macular sparing of <4°. CONCLUSIONS: Number of DS was not correlated with disease duration indicating insufficient spontaneous long-term adaptation. Increased number of DS and decreased FS after landing in patients with small or absent macular sparing stresses the importance of intact parafoveal vision. Asymmetric FEMs during continuous fixation indicate an advantageous adaptive mechanism to shift the visual field border towards the hemianopic side.

Influence of open-source virtual-reality based gaze training on navigation performance in Retinitis pigmentosa patients in a crossover randomized controlled trial.

METHODS: A group of RP patients (n = 8, aged 20-60) participated in a study consisting of two 4-week-phases, both carried out by the same patient group in randomized order: In the 'training phase', participants carried out a Virtual-Reality gaze training for 30 minutes per day; In the 'control phase', no training occurred. Before and after each phase, participants were tasked to move through a randomized real-world obstacle course. Navigation performance in the obstacle course as well as eye-tracking data during the trials were evaluated. The study is registered at the German Clinical Trials Register (DRKS) with the ID DRKS00032628. RESULTS: On average, the time required to move through the obstacle course decreased by 17.0% after the training phase, the number of collisions decreased by 50.0%. Both effects are significantly higher than those found in the control phase (p < 0.001 for required time, p = 0.0165 for number of collisions), with the required time decreasing by 5.9% and number of collisions decreasing by 10.4% after the control phase. The average visual area observed by participants increases by 4.41% after training, however the effect is not found to be significantly higher than in the control phase (p = 0.394). CONCLUSION: The performance increase over the training phase significantly surpasses the natural learning effect found in the control phase, suggesting that Virtual-Reality based gaze training can have a positive effect on real-world navigation tasks for patients with RP. The training is available as work-in-progress open-source software.

Evidence that global processing does not limit thresholds for RF shape discrimination.

In studies of shape processing, a crucial distinction is made between the global stages, which integrate across features to define shape, and earlier stages that encode individual components. We investigate whether shape discrimination thresholds for radial frequency (RF) patterns are limited at this global stage or whether the information in individual components supports threshold. We use achromatic and chromatic (L/M- and S-cone opponent) radial frequency (RF) patterns of different contour thicknesses (0.75-6 cpd). First, we show using sections of an RF4 that shape discrimination thresholds are invariant with cycle number from 1 to the complete pattern. Performance for a single cycle displayed alone is as good as for the whole RF, indicating that information within a single RF cycle is sufficient to support the whole shape discrimination threshold, arguing against an influence of global processing. Second, we find similar thresholds for the discrimination of RF patterns and modulated line stimuli, also arguing against global effects. Third, we calculate a metric for the intrinsic orientation variation in a stimulus cycle at threshold and show that this potentially accounts for the improvement in shape and line discrimination thresholds with modulation frequency from RF1 to RF6. Higher threshold discrimination for chromatic compared to achromatic patterns may reflect the poorer orientation discrimination of color vision, rather than a deficit for global processing. We propose that the global stages of shape processing are not revealed at threshold but are enabled only for well-defined shapes at suprathreshold modulations.

Influence of Systematic Gaze Patterns in Navigation and Search Tasks with Simulated Retinitis Pigmentosa.

People living with a degenerative retinal disease such as retinitis pigmentosa are oftentimes faced with difficulties navigating in crowded places and avoiding obstacles due to their severely limited field of view. The study aimed to assess the potential of different patterns of eye movement (scanning patterns) to (i) increase the effective area of perception of participants with simulated retinitis pigmentosa scotoma and (ii) maintain or improve performance in visual tasks. Using a virtual reality headset with eye tracking, we simulated tunnel vision of 20° in diameter in visually healthy participants (n = 9). Employing this setup, we investigated how different scanning patterns influence the dynamic field of view-the average area over time covered by the field of view-of the participants in an obstacle avoidance task and in a search task. One of the two tested scanning patterns showed a significant improvement in both dynamic field of view (navigation 11%, search 7%) and collision avoidance (33%) when compared to trials without the suggested scanning pattern. However, participants took significantly longer (31%) to finish the navigation task when applying this scanning pattern. No significant improvements in search task performance were found when applying scanning patterns.

Vessel Evaluation in Patients with Primary Open-Angle Glaucoma, Normal Tension Glaucoma and Healthy Controls.

PURPOSE: To compare changes in central retinal arterial equivalent (CRAE), central retinal vein equivalent (CRVE), arteriovenous ratio (AVR), tortuosity and fractal dimension in primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG) and in a control group (CG) on fundus photographs. Further, to provide further evidence of vascular change in glaucoma patients using a novel method of tortuosity. PATIENTS AND METHODS: The primary endpoint was the change in CRAE, CRVE, AVR, fractal dimension and tortuosity of the retinal vasculature from baseline, retrospectively analyzed from 2011 to 2017 at the University Eye Hospital Tuebingen. Fundus photos of POAG (N = 49), NTG (N = 38) and CG (N = 18) were computer evaluated and analyzed in the quantities mentioned above. RESULTS: CRAE in NTG and POAG and CRVE in NTG significantly decreased (P = 0.02, P = 0.01; P = 0.03) whereas CRVE in POAG increased insignificantly (P = 0.72). In NTG, AVR decreased significantly (P = 0.05), but to a lesser extent than in POAG (P < 0.001). In CG, CRAE decreased insignificantly (P = 0.10), CRVE decreased significantly (P = 0.03) and AVR increased insignificantly (P = 0.77). In POAG tortuosity calculated using standard methods as well as our novel method, increased significantly (P = 0.015-0.04), whereas it did not occur in NTG (P = 0.18-0.57) and CG (P = 0.11-0.21). Fractal dimensions in POAG decreased significantly (P = 0.001-0.002), whereas in NTG and CG changes were insignificant (P = 0.33-0.92). CONCLUSION: Based on a retrospective analysis of fundus photographs, specific retinal vasculature features of the retinal vasculature display significant alterations associated with NTG and POAG. The assessment of tortuosity using our novel method was consistent with previously established methods for analyzing tortuosity.

The inner clock-Blue light sets the human rhythm.

Visible light synchronizes the human biological clock in the suprachiasmatic nuclei of the hypothalamus to the solar 24-hour cycle. Short wavelengths, perceived as blue color, are the strongest synchronizing agent for the circadian system that keeps most biological and psychological rhythms internally synchronized. Circadian rhythm is important for optimum function of organisms and circadian sleep-wake disruptions or chronic misalignment often may lead to psychiatric and neurodegenerative illness. The beneficial effect on circadian synchronization, sleep quality, mood, and cognitive performance depends not only on the light spectral composition but also on the timing of exposure and its intensity. Exposure to blue light during the day is important to suppress melatonin secretion, the hormone that is produced by the pineal gland and plays crucial role in circadian rhythm entrainment. While the exposure to blue is important for keeping organism's wellbeing, alertness, and cognitive performance during the day, chronic exposure to low-intensity blue light directly before bedtime, may have serious implications on sleep quality, circadian phase and cycle durations. This rises inevitably the need for solutions to improve wellbeing, alertness, and cognitive performance in today's modern society where exposure to blue light emitting devices is ever increasing.

Ultraviolet radiation oxidative stress affects eye health.

In the eye, ultraviolet radiation (UVR) is not known to contribute to visual perception but to mainly damage multiple structures. UVR carries higher energy than visible light and high dose exposure to UVR causes direct cellular damage, which has an important role in the development of cancer. This review provides an overview on the most recent knowledge on the role of UVR in oxidative stress (OS) in relation to noncancer ocular pathologies: various corneal pathologies, cataract, glaucoma and age-related macular degeneration. Possible OS signaling streams and mechanisms in the aging eye are discussed. Excessive exposure to UVR through live may seriously contribute to increase in OS of various eye tissues and thus lead to the advancement of serious ocular pathologies. Children are especially vulnerable to UVR because of their larger pupils and more transparent ocular media: up to 80% of a person's lifetime exposure to UVR is reached before the age of 18. Therefore, efficient everyday protection of the sensitive tissues of the eye by wearing of sunglasses, clear UVR-blocking spectacles or contact lenses should be considered from early age on. Many initiatives are taken worldwide to inform and raise the population's awareness about these possible UVR hazards to the eye.

Effects of visual search training in children with hemianopia.

BACKGROUND: This study investigates the effect of a new computer-based visual search training (VST) that was adapted for children with homonymous hemianopia (HH). METHODS: 22 children with HH (median age 11 years, 8 months: 6y6m-19y2m) trained at home for 15 minutes twice/day, 5 days/week, for 6 weeks. To assess performance before training (T1), directly after training (T2) and 6 weeks after the end of training (T3), we measured search times (STs) during on-screen search (with eye tracking), and in a real life search task. Additional variables analyzed during on-screen search were numbers, amplitudes, and durations of saccades, their directional patterns and the proportional number of saccades into the non-seeing field. The latter was the main variable during free viewing. Sixteen healthy age-matched children, who did not undergo the training, served as comparison group. Quality of Life (QoL)-questionnaires were also applied. RESULTS: STs of the patients decreased significantly during the training and all search performance tests. This improvement persisted 6 weeks after the end of the training. Saccade amplitudes increased, total number of saccades to find the target decreased, and the proportional number of saccades to the non-seeing side increased. These changes were maintained at T3. Saccade durations did not change. During free viewing, saccades were equally distributed to both sides before and after training. Patients reported improvements in QoL and activities of daily living. Performance in the healthy children did not change by simply repeating the visual search test. CONCLUSIONS: The improvement in STs in all search tasks, larger and fewer saccades, and an improved search strategy after VST suggests that the children with HH benefited from the training. The maintained improvement at T3 and the improvement in the real life search task indicate that the newly developed search strategy persists and can be applied to everyday life.

Can positions in the visual field with high attentional capabilities be good candidates for a new preferred retinal locus?

The sustained component of visual attention lowers the perceptual threshold of stimuli located at the attended region. Attentional performance is not equal for all eccentric positions, leading to variations in perception. The location of the preferred retinal locus (PRL) for fixation might be influenced by these attentional variations. This study investigated the relation between the placement of sustained attention and the location of a developed PRL using simulations of central scotoma. Thirteen normally sighted subjects participated in the study. Monocular sustained attention was measured in discrete eccentric locations of the visual field using the dominant eye. Subsequently, a six degrees macular scotoma was simulated and PRL training was performed during eight ten-minutes blocks of trials. After training, every subject developed a PRL. Subjects with high attentional capabilities in the lower hemifield generally developed PRLs in the lower hemifield (n=10), subjects with high attentional capabilities in the upper hemifield developed PRLs in the upper hemifield (n=2) and one subject with similar attentional capabilities in the upper and lower hemifield developed the PRL on the upper hemifield. Analyzed individually, the results showed that 70% of the subjects had a PRL location in the hemifield where high attentional performance was achieved. These results suggest that attentional capabilities can be used as a predictor for the development of the PRL and are of significance for low vision rehabilitation and for the development of new PRL training procedures, with the option for a preventive attentional training in early macular disease to develop a favorable PRL.

Quality and learning curve of handheld versus stand-alone non-mydriatic cameras.

PURPOSE: Nowadays, complex digital imaging systems allow detailed retinal imaging without dilating patients' pupils. These so-called non-mydriatic cameras have advantages in common circumstances (eg, for screening or emergency purposes) but present limitations in terms of image quality and field of view. We compare the usefulness of two non-mydriatic camera systems (ie, a handheld versus a stand-alone device) for fundus imaging. The primary outcome was image quality. The secondary outcomes were learning effects and quality grade-influencing factors. METHODS: The imaging procedures followed standard protocol and were all performed by the same investigator. Camera 1 (DRS®) was a stand-alone system, while Camera 2 (Smartscope® PRO) was a mobile system. In order to evaluate possible learning effects, we selected an examiner with no prior training in the use of these systems. The images were graded separately by two experienced and "blinded" ophthalmologists following a defined protocol. RESULTS: In total, 211 people were enrolled. Quality grade comparisons showed significantly better grades for Camera 1. Both systems achieved better quality grades for macular images than for disc-centered images. No remarkable learning effects could be demonstrated. CONCLUSIONS: Both camera systems are useful for fundus imaging. The greater mobility of Camera 2 was associated with lower image quality. For screening scenarios or telemedicine, it must be determined whether image quality or mobility is more important.

Human Vision-Motivated Algorithm Allows Consistent Retinal Vessel Classification Based on Local Color Contrast for Advancing General Diagnostic Exams.

PURPOSE: Abnormalities of blood vessel anatomy, morphology, and ratio can serve as important diagnostic markers for retinal diseases such as AMD or diabetic retinopathy. Large cohort studies demand automated and quantitative image analysis of vascular abnormalities. Therefore, we developed an analytical software tool to enable automated standardized classification of blood vessels supporting clinical reading. METHODS: A dataset of 61 images was collected from a total of 33 women and 8 men with a median age of 38 years. The pupils were not dilated, and images were taken after dark adaption. In contrast to current methods in which classification is based on vessel profile intensity averages, and similar to human vision, local color contrast was chosen as a discriminator to allow artery vein discrimination and arterial-venous ratio (AVR) calculation without vessel tracking. RESULTS: With 83% ± 1 standard error of the mean for our dataset, we achieved best classification for weighted lightness information from a combination of the red, green, and blue channels. Tested on an independent dataset, our method reached 89% correct classification, which, when benchmarked against conventional ophthalmologic classification, shows significantly improved classification scores. CONCLUSIONS: Our study demonstrates that vessel classification based on local color contrast can cope with inter- or intraimage lightness variability and allows consistent AVR calculation. We offer an open-source implementation of this method upon request, which can be integrated into existing tool sets and applied to general diagnostic exams.

Eye Movement Training and Suggested Gaze Strategies in Tunnel Vision - A Randomized and Controlled Pilot Study.

PURPOSE: Degenerative retinal diseases, especially retinitis pigmentosa (RP), lead to severe peripheral visual field loss (tunnel vision), which impairs mobility. The lack of peripheral information leads to fewer horizontal eye movements and, thus, diminished scanning in RP patients in a natural environment walking task. This randomized controlled study aimed to improve mobility and the dynamic visual field by applying a compensatory Exploratory Saccadic Training (EST). METHODS: Oculomotor responses during walking and avoiding obstacles in a controlled environment were studied before and after saccade or reading training in 25 RP patients. Eye movements were recorded using a mobile infrared eye tracker (Tobii glasses) that measured a range of spatial and temporal variables. Patients were randomly assigned to two training conditions: Saccade (experimental) and reading (control) training. All subjects who first performed reading training underwent experimental training later (waiting list control group). To assess the effect of training on subjects, we measured performance in the training task and the following outcome variables related to daily life: Response Time (RT) during exploratory saccade training, Percent Preferred Walking Speed (PPWS), the number of collisions with obstacles, eye position variability, fixation duration, and the total number of fixations including the ones in the subjects' blind area of the visual field. RESULTS: In the saccade training group, RTs on average decreased, while the PPWS significantly increased. The improvement persisted, as tested 6 weeks after the end of the training. On average, the eye movement range of RP patients before and after training was similar to that of healthy observers. In both, the experimental and reading training groups, we found many fixations outside the subjects' seeing visual field before and after training. The average fixation duration was significantly shorter after the training, but only in the experimental training condition. CONCLUSIONS: We conclude that the exploratory saccade training was beneficial for RP patients and resulted in shorter fixation durations after the training. We also found a significant improvement in relative walking speed during navigation in a real-world like controlled environment.

The role of the foreshortening cue in the perception of 3D object slant.

Slant is the degree to which a surface recedes or slopes away from the observer about the horizontal axis. The perception of surface slant may be derived from static monocular cues, including linear perspective and foreshortening, applied to single shapes or to multi-element textures. It is still unclear the extent to which color vision can use these cues to determine slant in the absence of achromatic contrast. Although previous demonstrations have shown that some pictures and images may lose their depth when presented at isoluminance, this has not been tested systematically using stimuli within the spatio-temporal passband of color vision. Here we test whether the foreshortening cue from surface compression (change in the ratio of width to length) can induce slant perception for single shapes for both color and luminance vision. We use radial frequency patterns with narrowband spatio-temporal properties. In the first experiment, both a manual task (lever rotation) and a visual task (line rotation) are used as metrics to measure the perception of slant for achromatic, red-green isoluminant and S-cone isolating stimuli. In the second experiment, we measure slant discrimination thresholds as a function of depicted slant in a 2AFC paradigm and find similar thresholds for chromatic and achromatic stimuli. We conclude that both color and luminance vision can use the foreshortening of a single surface to perceive slant, with performances similar to those obtained using other strong cues for slant, such as texture. This has implications for the role of color in monocular 3D vision, and the cortical organization used in 3D object perception.

The role of local features in shape discrimination of contour- and surface-defined radial frequency patterns at low contrast.

Shape processing involves a progression from local to global analysis. A key aspect of this is the binding of distributed local features into an overall form followed by the extraction of the shape independently of its local contrast and spatial scales, so enabling the shape to be encoded based on its proportions without reference to its exact size or retinal location. Here we use contour- and surface-defined radial frequency (RF) patterns in a shape discrimination task, previously thought to reflect a global processing stage that has reached contrast and scale invariance. We compare performance across different spatial scales for a wide range of RF patterns (contour spatial frequencies of 0.7-10.0cpd, pattern radii of 0.5-10.5°), and sharp- and smooth-edged surface-RF patterns, all at low contrast (5× detection threshold). We show that shape discrimination thresholds for RF patterns have a complex series of dependencies on stimulus size (radius), contour spatial frequency (thickness) and contrast, with no scale invariance. Our results are at odds with earlier work showing no effect of radius and spatial frequency on discrimination thresholds. We show that this discrepancy can be accounted for by a differential effect of contrast on shape discrimination, with shape invariance only stabilizing at higher contrasts (10-20× threshold).

Effects on colour discrimination during long term exposure to high altitudes on Mt Everest.

AIM: To investigate changes in colour discrimination as a result of chronic hypoxic exposure induced by extreme altitudes (above 8000 m) during an expedition to Mt Everest. METHODS: Colour discrimination thresholds for tritan, protan and deutan axes were measured extensively in two male participants (four eyes) during an expedition to Mt Everest, using a quantitative, computer controlled psychophysical colour vision test (modified version of the Cambridge Colour Test). The tests were carried out over a period of 54 days at altitudes of 1300 m, 3450 m, 4410 m, 5060 m, 5300 m, 6450 m, 7200 m and 8000 m. RESULTS: Colour vision tests 1 week before and 6 months after the expedition indicated normal colour discrimination in both participants. With increasing altitude, colour discrimination thresholds were found to rise, predominantly for the tritan (blue) axes in both observers. Deutan (green) thresholds were minimally elevated at high altitude, whereas protan (red) was altered in one observer. Tritan colour discrimination thresholds decreased as a function of time spent at a given altitude and normalised upon return to low altitude. CONCLUSIONS: Chronic hypoxia induced by high altitude exposure transiently affects colour discrimination, in particular tritan axis discrimination. Decreased tritan discrimination is partly reversible upon physiological adaptation to high altitude and completely normalised upon return to low altitude.

Colour in action: evidence for a redundancy signal effect when driving motor responses by combined colour and spatial cues

Several studies have demonstrated that either chromatic or spatial information can guide motor behaviour, but so far interactions between these two visual features are little understood. Here we addressed this issue by measuring reaction times (RT) for pointing hand movements which were instructed by either cues for spatial (thought to be predominantly processed in the dorsal visual stream), colour (thought to be predominantly processed in the ventral visual stream) or redundant (combination of colour and spatial information) conditions. While faster responses were found for spatial than for colour cues, most importantly, the shortest RTs were measured for the combined cues (redundancy signal effect, RSE). The data are inconsistent with the predictions of the race model which assumes parallel and independent input from the two streams to the motor system. Instead, the data are better explained by the coactivation model, which proposes combined sensory information from the different stimuli and detection process from the sum of the signals. Here, the redundancy signal effect results from the combination of colour and spatial information. The results provide behavioural evidence for an integration of colour and spatial cues when guiding hand movements.