Exploring the Phenotype and Possible Mechanisms of Palinopsia in Visual Snow Syndrome.

Purpose: Palinopsia (persistent afterimages and/or trailing) is a common but poorly understood symptom of the neurological condition visual snow syndrome. This study aimed to collect a phenotypical description of palinopsia in visual snow syndrome and probe for abnormalities in temporal visual processing, hypothesizing that palinopsia could arise from increased visibility of normal afterimage signals or prolonged visible persistence. Methods: Thirty controls and 31 participants with visual snow syndrome (18 with migraine) took part. Participants completed a palinopsia symptom questionnaire. Contrast detection thresholds were measured before and after brief exposure to a spatial grating because deficient contrast adaptation could increase afterimage visibility. Temporal integration and segregation were assessed using missing-element and odd-element tasks, respectively, because prolonged persistence would promote integration at wide temporal offsets. To distinguish the effects of visual snow syndrome from comorbid migraine, 25 people with migraine alone participated in an additional experiment. Results: Palinopsia was common in visual snow syndrome, typically presenting as unformed images that were frequently noticed. Contrary to our hypotheses, we found neither reduced contrast adaptation (F(3.22, 190.21) = 0.71, P = 0.56) nor significantly prolonged temporal integration thresholds (F(1, 59) = 2.35, P = 0.13) in visual snow syndrome. Instead, participants with visual snow syndrome could segregate stimuli in closer succession than controls (F(1, 59) = 4.62, P = 0.04, ηp2 = 0.073) regardless of co-occurring migraine (F(2, 53) = 1.22, P = 0.30). In contrast, individuals with migraine alone exhibited impaired integration (F(2, 53) = 4.44, P = 0.017, ηp2 = 0.14). Conclusions: Although neither deficient contrast adaptation nor prolonged visible persistence explains palinopsia, temporal resolution of spatial cues is enhanced and potentially more flexible in visual snow syndrome.

The relationship between ON-OFF function and OCT structural and angiographic parameters in early diabetic retinal disease.

PURPOSE: This study measured associations between ON and OFF functional indicators and structural optical coherence tomography (OCT) and OCT angiography (OCTA) markers in diabetic retinal disease. METHODS: Fifty-four participants with type 1 or type 2 diabetes (mean age = 34.1 years; range 18-60) and 48 age-matched controls (mean age = 35.4 years, range 18-59) underwent visual psychophysical testing, OCT and OCTA retinal imaging. Psychophysical tasks measuring (A) contrast increment and decrement sensitivity and (B) response times to increment and decrement targets were assessed as surrogate measures of ON and OFF retinal ganglion cell function. RESULTS: The group with diabetes had worse foveal contrast increment and decrement thresholds (p = 0.04) and were slower to search for increment and decrement targets relative to controls (p = 0.009). Individuals with diabetes had a less circular foveal avascular zone (FAZ) (p < 0.001) but did not differ from controls in foveal vessel density and FAZ area. Functional and structural outcome measures related to the peripheral retina were also comparable between those with and without diabetes. Functional responses to increments and decrements were not significantly correlated with FAZ circularity or vessel density in individuals with diabetes. CONCLUSIONS: Diabetic retinal disease results in impaired performance on measures of inferred ON and OFF pathway function in addition to vascular deficits measurable with OCTA. Future longitudinal studies may determine the temporal relationship between these deficits, and whether they predict future diabetic retinopathy.

Eccentricity Dependency of Retinal Electrophysiological Deficits in People With Episodic Migraine.

Purpose: During the non-attack period, people with migraine may show retinal dysfunction. This study builds on previous work by exploring the possibility of foveal and non-foveal visual field and electroretinographic deficits and determining the overlap in eccentricity of such localized visual deficits in people with migraine. Methods: Visual fields and multifocal electroretinography (mf-ERG) were tested in 27 people with migraine (aged 19-45 years) and 18 non-headache controls (aged 20-46 years). Data were averaged according to 5 concentric rings at < 1.5 degrees (foveal) and 5 degrees, 10 degrees, 15.5 degrees, and 22 degrees eccentricities (non-foveal). Linear mixed effects modelling was used to predict mf-ERG amplitude, mf-ERG peak time, and visual field sensitivity with fixed effects of eye, group, and eccentricity. Results: Foveal mf-ERG responses, and visual field sensitivity across all eccentricities (foveal and non-foveal) were similar between the migraine and control groups (P > 0.05). In contrast, the non-foveal mf-ERG was reduced in amplitude in people with migraine relative to controls (P < 0.001), and this group difference depended on eccentricity (P < 0.001) - most prominently, in the parafoveal region (ring 2, P = 0.001). Conclusions: Retinal electrophysiological deficits were observed in people with migraine in the parafoveal region (between 1.5 degrees and 5 degrees eccentricity), without corresponding visual field deficits. This suggests a spatially localized area of retinal neuronal dysfunction in people with migraine that is insufficient to manifest as a visual field sensitivity loss using standard perimetric methods. Our study highlights the added confound of migraine when conducting standard clinical retinal electrophysiological tests for conditions such as glaucoma, particularly non-foveally.

Contrast Discrimination and Global Form Perception in Primary Open-Angle Glaucoma and Primary Angle-Closure Glaucoma.

Purpose: This study explored early (contrast discrimination) and intermediate (global form perception) visual processing in primary subtypes of glaucoma: primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). We aimed to understand early and intermediate visual processing in POAG and PACG, matched for similar visual field defect severity. Methods: Early visual processing was measured using a contrast discrimination task described by Porkorny and Smith (1997), and intermediate processing using a global form perception task using glass pattern coherence thresholds. Thresholds were determined centrally and at a single midperipheral location (12.5°) in a quadrant without visual field defects. Controls were tested in corresponding quadrants to individuals with glaucoma. Results: Sixty participants (20 POAG, 20 PACG, and 20 age-matched controls), aged 50 to 77 years, were included. Visual field defects were matched between POAG and PACG, with mean deviation values of -6.53 ± 4.46 (range: -1.5 to -16.85) dB and -6.2 ± 4.24 (range: -1.37 to -16.42) dB, respectively. Two-Way ANOVA revealed significant differences in thresholds between the glaucoma groups and the control group for both contrast discrimination and global form perception tasks, with higher thresholds in the glaucoma groups. Post hoc analyses showed no significant contrast discrimination difference between POAG and PACG, but POAG had significantly higher thresholds than PACG for form perception. Conclusions: In form perception, POAG showed slightly worse performance than PACG, suggesting that individuals with POAG may experience more severe functional damage than PACG of similar visual field severity.

Improving Understanding of Visual Snow by Quantifying its Appearance and Effect on Vision.

Purpose: Visual snow is the hallmark of the neurological condition visual snow syndrome (VSS) but the characteristics of the visual snow percept remain poorly defined. This study aimed to quantify its appearance, interobserver variability, and effect on measured visual performance and self-reported visual quality. Methods: Twenty-three participants with VSS estimated their visual snow dot size, separation, luminance, and flicker rate by matching to a simulation. To assess whether visual snow masks vision, we compared pattern discrimination thresholds for textures that were similar in spatial scale to visual snow as well as more coarse than visual snow, in participants with VSS, and with and without external noise simulating visual snow in 23 controls. Results: Mean and 95% confidence intervals for visual snow appearance were: size (6.0, 5.8-6.3 arcseconds), separation (2.0, 1.7-2.3 arcmin), luminance (72.4, 58.1-86.8 cd/m2), and flicker rate (25.8, 18.9-32.8 frames per image at 120 hertz [Hz]). Participants with finer dot spacing estimates also reported greater visibility of their visual snow (τb = -0.41, 95% confidence interval [CI] = -0.62 to -0.13, P = 0.01). In controls, adding simulated fine-scale visual snow to textures increased thresholds for fine but not coarse textures (F(1, 22) = 4.98, P = 0.036, ηp2 = 0.19). In VSS, thresholds for fine and coarse textures were similar (t(22) = 0.54, P = 0.60), suggesting that inherent visual snow does not act like external noise in controls. Conclusions: Our quantitative estimates of visual snow constrain its likely neural origins, may aid differential diagnosis, and inform future investigations of how it affects vision. Methods to quantify visual snow are needed for evaluation of potential treatments.

Understanding and identifying visual field progression.

Detecting deterioration of visual field sensitivity measurements is important for the diagnosis and management of glaucoma. This review surveys the current methods for assessing progression that are implemented in clinical devices, which have been used in clinical trials, alongside more recent advances proposed in the literature. Advice is also offered to clinicians on what they can do to improve the collection of perimetric data to help analytical progression methods more accurately predict change. This advice includes a discussion of how frequently visual field testing should be undertaken, with a view towards future developments, such as digital healthcare outside the standard clinical setting and more personalised approaches to perimetry.

Self-motion induced environmental kinetopsia and pop-out illusion - Insight from a single case phenomenology.

Stable visual perception, while we are moving, depends on complex interactions between multiple brain regions. We report a patient with damage to the right occipital and temporal lobes who presented with a visual disturbance of inward movement of roadside buildings towards the centre of his visual field, that occurred only when he moved forward on his motorbike. We describe this phenomenon as "self-motion induced environmental kinetopsia". Additionally, he was identified to have another illusion, in which objects displayed on the screen, appeared to pop out of the background. Here, we describe the clinical phenomena and the behavioural tasks specifically designed to document and measure this altered visual experience. Using the methods of lesion mapping and lesion network mapping we were able to demonstrate disrupted functional connectivity in the areas that process flow-parsing such as V3A and V6 that may underpin self-motion induced environmental kinetopsia. Moreover, we suggest that altered connectivity to the regions that process environmental frames of reference such as retrosplenial cortex (RSC) might explain the pop-out illusion. Our case adds novel and convergent lesion-based evidence to the role of these brain regions in visual processing.

Altered Outer Retinal Structure, Electrophysiology and Visual Perception in Parkinson's Disease.

BACKGROUND: Visual biomarkers of Parkinson's disease (PD) are attractive as the retina is an outpouching of the brain. Although inner retinal neurodegeneration in PD is well-established this has overlap with other neurodegenerative diseases and thus outer retinal (photoreceptor) measures warrant further investigation. OBJECTIVE: To examine in a cross-sectional study whether clinically implementable measures targeting outer retinal function and structure can differentiate PD from healthy ageing and whether these are sensitive to intraday levodopa (L-DOPA) dosing. METHODS: Centre-surround perceptual contrast suppression, macular visual field sensitivity, colour discrimination, light-adapted electroretinography and optical coherence tomography (OCT) were tested in PD participants (n = 16) and controls (n = 21). Electroretinography and OCT were conducted before and after midday L-DOPA in PD participants, or repeated after ∼2 hours in controls. RESULTS: PD participants had decreased center-surround contrast suppression (p < 0.01), reduced macular visual field sensitivity (p < 0.05), color vision impairment (p < 0.01) photoreceptor dysfunction (a-wave, p < 0.01) and photoreceptor neurodegeneration (outer nuclear layer thinning, p < 0.05), relative to controls. Effect size comparison between inner and outer retinal parameters showed that photoreceptor metrics were similarly robust in differentiating the PD group from age-matched controls as inner retinal changes. Electroretinography and OCT were unaffected by L-DOPA treatment or time. CONCLUSIONS: We show that outer retinal outcomes of photoreceptoral dysfunction (decreased cone function and impaired color vision) and degeneration (i.e., outer nuclear layer thinning) were equivalent to inner retinal metrics at differentiating PD from healthy age-matched adults. These findings suggest outer retinal metrics may serve as useful biomarkers for PD.

Nonlinear Reduction in Hyperautofluorescent Ring Area in Retinitis Pigmentosa.

PURPOSE: To report baseline dimension of the autofluorescent (AF) ring in a large cohort of retinitis pigmentosa (RP) patients and to evaluate models of ring progression. DESIGN: Cohort study. PARTICIPANTS: Four hundred and forty-five eyes of 224 patients with clinical diagnosis of RP. METHODS: Autofluorescent rings from near-infrared AF (NIRAF) and short-wavelength AF (SWAF) imaging modalities in RP eyes were segmented with ring area and horizontal extent extracted from each image for cross-sectional and longitudinal analyses. In longitudinal analysis, for each eye, ring area, horizontal extent, and natural logarithm of the ring area were assessed as the best dependent variable for linear regression by evaluating R2 values. Linear mixed-effects modeling was utilized to account for intereye correlation. MAIN OUTCOME MEASURES: Autofluorescent ring size characteristics at baseline and ring progression rates. RESULTS: A total of 439 eyes had SWAF imaging at baseline with the AF ring observed in 206 (46.9%) eyes. Mean (95% confidence interval) of ring area and horizontal extent were 7.85 (6.60 to 9.11) mm2 and 3.35 (3.10 to 3.60) mm, respectively. In NIRAF, the mean ring area and horizontal extent were 7.74 (6.60 to 8.89) mm2 and 3.26 (3.02 to 3.50) mm, respectively in 251 out of 432 eyes. Longitudinal analysis showed mean progression rates of -0.57 mm2/year and -0.12 mm/year in SWAF using area and horizontal extent as the dependent variable, respectively. When ln(Area) was analyzed as the dependent variable, mean progression was -0.07 ln(mm2)/year, which equated to 6.80% decrease in ring area per year. Similar rates were found in NIRAF (area: -0.59 mm2/year, horizontal extent: -0.12 mm/year and ln(Area): -0.08 ln(mm2)/year, equated to 7.75% decrease in area per year). Analysis of R2 showed that the dependent variable ln(Area) provided the best linear model for ring progression in both imaging modalities, especially in eyes with large overall area change. CONCLUSIONS: Our data suggest that using an exponential model to estimate progression of the AF ring area in RP is more appropriate than the models assuming linear decrease. Hence, the progression estimates provided in this study should provide more accurate reference points in designing clinical trials in RP patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Short-term homeostatic visual neuroplasticity in adolescents after two hours of monocular deprivation.

In healthy adults with normal vision, temporary deprivation of one eye's visual experience produces transient yet robust homeostatic plasticity effects, where the deprived eye becomes more dominant. This shift in ocular dominance is short-lived and compensatory. Previous work shows that monocular deprivation decreases resting state gamma aminobutyric acid (GABA; inhibitory neurotransmitter) levels in visual cortex, and that those with the greatest reduction in GABA have stronger shifts due to monocular deprivation. Components of the GABAergic system in visual cortex vary with age (early childhood, early teen years, ageing); hence if GABA is critical to homeostatic plasticity within the visual system, adolescence may be a key developmental period where differences in plasticity manifest. Here we measured short-term visual deprivation effects on binocular rivalry in 24 adolescents (aged 10-15 years) and 23 young adults (aged 20-25 years). Despite differences in baseline features of binocular rivalry (adolescents showed more mixed percept p < 0.001 and a tendency for faster switching p = 0.06 compared to adults), deprived eye dominance increased (p = 0.01) similarly for adolescents and adults after two hours of patching. Other aspects of binocular rivalry - time to first switch (heralding the onset of rivalry) and mixed percept - were unaltered by patching. These findings suggest that binocular rivalry after patching can be used as a behavioral proxy for experience-dependent visual cortical plasticity in adolescents in the same way as adults, and that homeostatic plasticity to compensate for temporarily reduced visual input is established and effective by adolescence.

Suprathreshold Approaches to Mapping the Visual Field in Advanced Glaucoma.

Purpose: Measuring the spatial extent of defects may be advantageous in advanced glaucoma where conventional perimetric sensitivity measurements are unreliable. We test whether suprathreshold tests on a higher density grid can more efficiently map advanced visual field loss. Methods: Data from 97 patients with mean deviation < -10 dB were used in simulations comparing two suprathreshold procedures (on a high-density 1.5° grid) to interpolated Full Threshold 24-2. Spatial binary search (SpaBS) presented 20-dB stimuli at locations bisecting seen/unseen points until the seen status of all neighbors matched or until tested points were adjacent. The SupraThreshold Adaptive Mapping Procedure (STAMP) presented 20-dB stimuli where entropy was maximal and modified the status of all points after each presentation, stopping after a fixed number of presentations (estimated as 50%-100% of the presentation number of a current procedure). Results: With typical response errors, SpaBS had worse mean accuracy and repeatability than Full Threshold (both P < 0.0001). Compared to Full Threshold, mean accuracy (Full Threshold: median, 91%; interquartile range [IQR], 87%-94%) was slightly better with STAMP for all stopping criteria, although this was not statistically significant until 100% of conventional test presentations were used. Mean repeatability for STAMP was similar for all stopping criteria (P ≥ 0.02) compared to Full Threshold (Full Threshold: median, 89%; IQR, 82%-93%). Conclusions: STAMP accurately and repeatably maps the spatial extent of advanced visual field defects in as few as 50% of conventional perimetric test presentations. Further work is needed to test STAMP in human observers and in progressive loss. Translational Relevance: New perimetric approaches may improve information available for advanced glaucoma management and may potentially be more acceptable to patients.

The relationship between central and mid-peripheral motion perception and the hazard perception test in younger and older adults.

INTRODUCTION: Vision standards for driving are typically based on visual acuity, despite evidence that it is a poor predictor of driving safety and performance. However, visual motion perception is potentially relevant for driving, as the vehicle and surroundings are in motion. This study explored whether tests of central and mid-peripheral motion perception better predict performance on a hazard perception test (HPT), which is related to driving performance and crash risk, than visual acuity. Additionally, we explored whether age influences these associations, as healthy ageing impairs performance on some motion sensitivity tests. METHODS: Sixty-five visually healthy drivers (35 younger, mean age: 25.5; SD 4.3 years; 30 older adults, mean age: 71.0; SD 5.4 years) underwent a computer-based HPT, plus four different motion sensitivity tests both centrally and at 15° eccentricity. Motion tests included minimum displacement to identify motion direction (Dmin ), contrast detection threshold for a drifting Gabor (motion contrast), coherence threshold for a translational global motion stimulus and direction discrimination for a biological motion stimulus in the presence of noise. RESULTS: Overall, HPT reaction times were not significantly different between age groups (p = 0.40) nor were maximum HPT reaction times (p = 0.34). HPT response time was associated with motion contrast and Dmin centrally (r = 0.30, p = 0.02 and r = 0.28, p = 0.02, respectively) and with Dmin peripherally (r = 0.34, p = 0.005); these associations were not affected by age group. There was no significant association between binocular visual acuity and HPT response times (r = 0.02, p = 0.29). CONCLUSIONS: Some measures of motion sensitivity in central and mid-peripheral vision were associated with HPT response times, whereas binocular visual acuity was not. Peripheral testing did not show an advantage over central testing for visually healthy older drivers. Our findings add to the growing body of evidence that the ability to detect small motion changes may have potential to identify unsafe road users.

Perceptual Center-Surround Contrast Suppression in Adolescence.

Purpose: Center-surround contrast suppression-typically induced when a center pattern is surrounded by another pattern with similar spatial features-is considered a perceptual analogue of center-surround neurophysiology in the visual system. Surround suppression strength is altered in a range of brain conditions affecting young people (e.g., schizophrenia, depression, migraine) and is modulated by various neurotransmitters. The early teen years are associated with neurotransmitter changes in the human visual cortex, which could impact on excitation-inhibition balance and center-surround antagonistic effects. Hence, we predict that early adolescence is associated with perceptual changes in center-surround suppression. Methods: In this cross-sectional study, we tested 196 students at every age from 10 to 17 years and 30 adults (aged 21-34 years) to capture the preteen, adolescent, and adult periods. Contrast discrimination thresholds were measured for a central, circular, vertical sinusoidal grating pattern (0.67° radius, 2 cyc/deg spatial frequency, 2 deg/s drift rate) with and without the surround (4° radius, otherwise same spatial properties as the center). Individual suppression strength was determined by comparing the perceived contrast of the target with and without the surround. Results: After excluding unreliable data (7% of total), we found an effect of age on perceptual center-surround contrast suppression strength, F(8,201) = 2.30, P = 0.02, with weaker suppression in the youngest adolescents relative to adults (Bonferroni pairwise comparisons between adults vs 12-year-olds P = 0.01; adults vs 13-year-olds P = 0.002). Conclusions: Our data demonstrate different center-surround interactions in the visual system-a key building block for visual perception-in early adolescence relative to adulthood.

Eye movement characteristics are not significantly influenced by psychiatric comorbidities in people with visual snow syndrome.

Visual snow syndrome (VSS) is a neurological disorder primarily affecting the processing of visual information. Using ocular motor (OM) tasks, we previously demonstrated that participants with VSS exhibit altered saccade profiles consistent with visual attention impairments. We subsequently proposed that OM assessments may provide an objective measure of dysfunction in these individuals. However, VSS participants also frequently report significant psychiatric symptoms. Given that that these symptoms have been shown previously to influence performance on OM tasks, the objective of this study was to investigate whether psychiatric symptoms (specifically: depression, anxiety, fatigue, sleep difficulties, and depersonalization) influence the OM metrics found to differ in VSS. Sixty-one VSS participants completed a battery of four OM tasks and a series of online questionnaires assessing psychiatric symptomology. We revealed no significant relationship between psychiatric symptoms and OM metrics on any of the tasks, demonstrating that in participants with VSS, differences in OM behaviour are a feature of the disorder. This supports the utility of OM assessment in characterising deficit in VSS, whether supporting a diagnosis or monitoring future treatment efficacy.

Impact of Victorian COVID-19 restrictions on emergency department presentations and hospital admissions for ophthalmic conditions.

CLINICAL RELEVANCE: Assessing the extent to which COVID-19 impacted hospitals can provide important learnings for future pandemics. BACKGROUND: This study aims to determine the impact of the 7-month duration COVID-19 pandemic-related lockdown orders on ophthalmology-related hospital admissions and emergency department (ED) presentations, during 2020 in Victoria, Australia. METHODS: Analysis was performed on Victorian statewide data from the Victorian Emergency Minimum Dataset (VEMD) and Victorian Admitted Episodes Dataset (VAED), between 1 January 2018 and 31 October 2020. Numbers of presentations and admissions for key ophthalmic conditions were stratified by age, socioeconomic status, location (metropolitan versus rural), and triage category. From the observations occurring in the pre-pandemic period (January 2018 to March 2020), a linear regression prediction model was built for each diagnosis which predicted what the presentation number in the COVID-19 period would have been if the pandemic had not occurred. RESULTS: Based on pre-COVID-19 trends, the largest decreases in expected admissions were for glaucoma (32.9%) and retinal breaks and detachments (21.2%). For the ED data, the most apparent changes were: an increase in presentations for foreign bodies (22.6%); a decrease in retinal detachments (35.5%); and a decrease in keratitis (18.4%) relative to predictions. CONCLUSIONS: Hospital admissions decreased and patterns of ED attendances changed during lockdown. The findings suggest the need for the following: increased safety messaging to avoid eye injuries around the home; improved pathways for safe and rapid triaging of eye conditions in the community to ensure effective use of ED resources; and messaging to ensure that people do not delay care when they notice signs of sight-threatening conditions such as retinal detachment.

Primary eyecare provision for people living with dementia: what do we need to know?

Dementia comprises a group of brain disorders characterised by loss of cognitive function. Sensory loss, predominantly vision (the focus of this review) and hearing, is a significant problem for people living with dementia. Eyecare practitioners such as optometrists therefore play an important role in identifying and addressing vision-related care needs. To support provision of high quality "dementia-friendly" eyecare, this scoping review summarises recent primary research findings and available clinical practice guidelines, to identify research gaps relating to vision and dementia, and make recommendations for future research and clinical practice. The review set a priori guidelines for the population, concept and context based on the review questions. Primary research papers (2016-2021) were included via 3-step search strategy: preliminary search to index terms, full search, search reference lists of included articles for further inclusions. Additionally, websites of eyecare professional bodies in English-speaking countries were searched to identify current clinical eyecare practice guidelines relating to dementia. Study characteristics (e.g. country, study design) were reported descriptively. Patterns within findings/recommendations from included sources were identified using thematic analysis and reported as themes. 1651 titles/abstracts and 161 full-text articles were screened for eligibility. Three clinical practice guidelines were also identified. The final review included 21 sources: 18 primary research papers and 3 clinical practice guidelines. The thematic analysis reported five key themes: Diagnosis/Screening, dementia progression, findings on clinical visual testing, tailored approach to care, improving care. This scoping review demonstrated limited information about current practices of optometrists working with people living with dementia. Recent evidence reinforces the continuing need for improved eyecare for people living with dementia, taking into account their specific needs with an individualised approach. Up-to-date practical recommendations are synthesised for eyecare providers before, during and after a consultation with a person living with dementia, to better support their care.

Detecting glaucoma from multi-modal data using probabilistic deep learning.

Objective: To assess the accuracy of probabilistic deep learning models to discriminate normal eyes and eyes with glaucoma from fundus photographs and visual fields. Design: Algorithm development for discriminating normal and glaucoma eyes using data from multicenter, cross-sectional, case-control study. Subjects and participants: Fundus photograph and visual field data from 1,655 eyes of 929 normal and glaucoma subjects to develop and test deep learning models and an independent group of 196 eyes of 98 normal and glaucoma patients to validate deep learning models. Main outcome measures: Accuracy and area under the receiver-operating characteristic curve (AUC). Methods: Fundus photographs and OCT images were carefully examined by clinicians to identify glaucomatous optic neuropathy (GON). When GON was detected by the reader, the finding was further evaluated by another clinician. Three probabilistic deep convolutional neural network (CNN) models were developed using 1,655 fundus photographs, 1,655 visual fields, and 1,655 pairs of fundus photographs and visual fields collected from Compass instruments. Deep learning models were trained and tested using 80% of fundus photographs and visual fields for training set and 20% of the data for testing set. Models were further validated using an independent validation dataset. The performance of the probabilistic deep learning model was compared with that of the corresponding deterministic CNN model. Results: The AUC of the deep learning model in detecting glaucoma from fundus photographs, visual fields, and combined modalities using development dataset were 0.90 (95% confidence interval: 0.89-0.92), 0.89 (0.88-0.91), and 0.94 (0.92-0.96), respectively. The AUC of the deep learning model in detecting glaucoma from fundus photographs, visual fields, and both modalities using the independent validation dataset were 0.94 (0.92-0.95), 0.98 (0.98-0.99), and 0.98 (0.98-0.99), respectively. The AUC of the deep learning model in detecting glaucoma from fundus photographs, visual fields, and both modalities using an early glaucoma subset were 0.90 (0.88,0.91), 0.74 (0.73,0.75), 0.91 (0.89,0.93), respectively. Eyes that were misclassified had significantly higher uncertainty in likelihood of diagnosis compared to eyes that were classified correctly. The uncertainty level of the correctly classified eyes is much lower in the combined model compared to the model based on visual fields only. The AUCs of the deterministic CNN model using fundus images, visual field, and combined modalities based on the development dataset were 0.87 (0.85,0.90), 0.88 (0.84,0.91), and 0.91 (0.89,0.94), and the AUCs based on the independent validation dataset were 0.91 (0.89,0.93), 0.97 (0.95,0.99), and 0.97 (0.96,0.99), respectively, while the AUCs based on an early glaucoma subset were 0.88 (0.86,0.91), 0.75 (0.73,0.77), and 0.92 (0.89,0.95), respectively. Conclusion and relevance: Probabilistic deep learning models can detect glaucoma from multi-modal data with high accuracy. Our findings suggest that models based on combined visual field and fundus photograph modalities detects glaucoma with higher accuracy. While probabilistic and deterministic CNN models provided similar performance, probabilistic models generate certainty level of the outcome thus providing another level of confidence in decision making.

The Effects of Glare on the Perception of Visual Motion as a Function of Age.

Purpose: The purpose of this study was to determine the impact of glare, that simulated the effects of oncoming vehicle headlights, and age on different aspects of motion perception in central and peripheral vision. Methods: Twenty younger (mean age = 25 years, range = 20-32 years) and 20 older (mean age = 70 years, range = 60-79 years) visually healthy adults completed four visual motion tasks. Stimuli were presented centrally and at 15 degrees horizontal eccentricity for 2 viewing conditions: glare (continuous, off-axis) versus no glare. Motion tasks included minimum Gabor contrast required to discriminate direction of motion, translational global motion coherence, minimum duration of a Gabor to determine direction of motion (2 different size Gabors to determine spatial surround suppression), and biological motion detection in noise. Intraocular straylight was also measured (C-Quant). Results: Older adults had increased intraocular straylight compared with younger adults (P < 0.001). There was no significant effect of glare on motion thresholds in either group for motion contrast (P = 0.47), translational global motion (P = 0.13), biological motion (P = 0.18), or spatial surround suppression of motion (P = 0.29). Older adults had elevated thresholds for motion contrast (P < 0.001), biological motion (P < 0.001), and differences in surround suppression of motion (P = 0.04), relative to the younger group, for both the glare and no-glare conditions. Conclusions: Although older adults had elevated thresholds for some motion perception tasks, glare from a continuous off-axis light source did not further elevate these thresholds either in central or peripheral vision. Translational Relevance: A glare source that simulated the effect of oncoming headlights, did not impact motion perception measures relevant to driving.

A Method for Reducing the Number of Presentations in Perimetric Test Procedures.

Purpose: To introduce a new method (ARBON) for decreasing the test time of psychophysical procedures and examine its application to perimetry. Methods: ARBON runs in parallel with an existing psychophysical procedure injecting occasional responses of seen or unseen into that procedure. Using computer simulation to mimic human responses during perimetry, we assess the performance of ARBON relative to an underlying test procedure and a version of that procedure truncated to be faster. Simulations used 610 normal eyes (age 20 to 80 years) and 163 glaucoma eyes (median mean deviation = -1.81 dB, 5th percentile = +2.14 dB, 95th percentile = -22.55 dB). Outcome measures were number of presentations and mean absolute error in threshold estimation. We also examined the probability distribution of measured thresholds. Results: ARBON and the Truncated procedure reduced presentations by 16% and 18%, respectively. Mean error was increased by 8% to 10% for the Truncated procedure but decreased by 5% to 7% for ARBON. The probability distributions of measured thresholds using ARBON overlapped with the Underlying procedure by over 80%, whereas the Truncated procedure overlapped by 50%. Conclusions: ARBON offers a principled method for reducing test time. ARBON can be added to any existing psychophysical procedure without requiring any change to the logic or parameters controlling the procedure, resulting in distributions of measured thresholds similar to those of the underlying procedure. Translational Relevance: ARBON can be added to a perimetry test procedure to speed up the test while largely preserving the distribution of returned sensitivities, thus producing normative data similar to the data for the original, underlying perimetric test.

Relating the cortical visual contrast gain response to spectroscopy-measured excitatory and inhibitory metabolites in people who experience migraine.

OBJECTIVE: This study aimed to determine whether the visual response to flickering checkerboard patterns measured using electroencephalography (EEG) relate to excitatory or inhibitory metabolite levels measured using ultra-high (7Tesla/7T) magnetic resonance spectroscopy (MRS). BACKGROUND: Electrophysiological studies have shown altered visual cortical response amplitudes and contrast gain responses to high contrast flickering patterns in people with migraine. These contrast response anomalies have been argued to represent an imbalance between cortical inhibition and excitation, however the specific mechanism has not been elucidated. METHODS: MRS-measured metabolite levels were obtained from the occipital cortex of 18 participants with migraine and 18 non-headache controls. EEG contrast gain response functions were collected on separate days from a subset of 10 participants with migraine and 12 non-headache controls. Case-control outcome measures were statistically compared between groups both before and after checkboard exposure. RESULTS: No significant difference in GABA and glutamate levels were found between groups nor checkerboard timepoint. Glucose levels were significantly reduced after checkerboard exposure in both participant groups. There was no metabolic signature in visual cortex in response to high-contrast flickering checkboards that distinguished those with migraine and without. There was also no correlation between MRS and EEG measurements in response to the flickering checkerboard. CONCLUSION: Our findings suggest that the mechanisms driving contrast-flickering stimulus aversion are not simplistically reflected by gross changes in metabolic activity in the primary visual cortex.