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.

Reproducibility of consecutive automated telemetric noctodiurnal IOP profiles as determined by an intraocular implant.

BACKGROUND: Intraocular pressure (IOP) monitoring in glaucoma management is evolving with novel devices. We investigated the reproducibility of 24 hour profiles on two consecutive days and after 30 days of self-measurements via telemetric IOP monitoring. METHODS: Seven primary patients with open-angle glaucoma previously implanted with a telemetric IOP sensor in one eye underwent automatic measurements throughout 24 hours on two consecutive days ('day 1' and 'day 2'). Patients wore an antenna adjacent to the study eye connected to a reader device to record IOP every 5 min. Also, self-measurements in six of seven patients were collected for a period of 30 days. Analysis included calculation of hourly averages to correlate time-pairs of day 1 versus day 2 and the self-measurements vers day 2. RESULTS: The number of IOP measurements per patient ranged between 151 and 268 on day 1, 175 and 268 on day 2 and 19 and 1236 during 30 days of self-measurements. IOP time-pairs of automatic measurements on day 1 and day 2 were significantly correlated at the group level (R=0.83, p<0.001) and in four individual patients (1, 2, 6 and 7). IOP time-pairs of self-measurements and day 2 were significantly correlated at the group level (R=0.4, p<0.001) and in four individual patients (2, 5, 6 and 7). CONCLUSIONS: Twenty-four hour automatic measurements of IOP are correlated on consecutive days and, though to a lesser degree, with self-measurements. Therefore a virtual 24-hour IOP curve might be constructed from self-measurements. Both options provide an alternative to frequent in-office IOP measurements.

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.

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.

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.

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

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

Achromatopsia-Visual Cortex Stability and Plasticity in the Absence of Functional Cones.

Purpose: Achromatopsia is a rare inherited disorder rendering retinal cone photoreceptors nonfunctional. As a consequence, the sizable foveal representation in the visual cortex is congenitally deprived of visual input, which prompts a fundamental question: is the cortical representation of the central visual field in patients with achromatopsia remapped to take up processing of paracentral inputs? Such remapping might interfere with gene therapeutic treatments aimed at restoring cone function. Methods: We conducted a multicenter study to explore the nature and plasticity of vision in the absence of functional cones in a cohort of 17 individuals affected by autosomal recessive achromatopsia and confirmed biallelic disease-causing CNGA3 or CNGB3 mutations. Specifically, we tested the hypothesis of foveal remapping in human achromatopsia. For this purpose, we applied two independent functional magnetic resonance imaging (fMRI)-based mapping approaches, i.e. conventional phase-encoded eccentricity and population receptive field mapping, to separate data sets. Results: Both fMRI approaches produced the same result in the group comparison of achromatopsia versus healthy controls: sizable remapping of the representation of the central visual field in the primary visual cortex was not apparent. Conclusions: Remapping of the cortical representation of the central visual field is not a general feature in achromatopsia. It is concluded that plasticity of the human primary visual cortex is less pronounced than previously assumed. A pretherapeutic imaging workup is proposed to optimize interventions.

[Achromatopsia : Clinical aspects, diagnostics, genes, brain and quality of life]. / Achromatopsie : Klinik, Diagnostik, Gene, Gehirn und Lebensqualität.

Achromatopsia or rod monochromatism is a congenital autosomal recessive retinal dystrophy which leads to dysfunctional cones, with decreased visual acuity, extremely limited color vision, nystagmus and photophobia. Due to the initially normally appearing ocular morphology, the diagnosis is often delayed. With imaging procedures, e.g., fluorescence-autofluorescence (FAF) and optical coherence tomography (OCT), different morphological forms of achromatopsia can be discriminated that do not seem to have a differential effect on visual function. Crucial is the provision of specific edge filters. Mutations in six genes are known to cause achromatopsia. For the two most frequent genes, CNGA3 and CNGB3, gene addition therapies are currently being tested. Such future approaches should be applied before the manifestation of sensory-related amblyopia in the visual cortex. Accordingly, state of the art management of achromatopsia should provide a diagnosis in early childhood including genotyping.

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.

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.

Effect of eyelid muscle action and rubbing on telemetrically obtained intraocular pressure in patients with glaucoma with an IOP sensor implant.

BACKGROUND: Patients with glaucoma on topical glaucoma medication are often affected by dry eye symptoms and thus likely to rub or squeeze their eyelids. Here, we telemetrically measure peak intraocular pressure (IOP) during eyelid manoeuvres and eyelid rubbing. METHODS: Eleven patients with primary open-angle glaucoma (POAG) previously implanted with a telemetric IOP sensor (Eyemate-IO) were instructed to look straight ahead for 1 min as a baseline measurement. Next, 6 repeats of blinking on instruction with 10 s intervals in between were performed. In addition, 5 repeats of eyelid closure (n=9), eyelid squeezing and eyelid rubbing (n=7) were performed with 15 s intervals in between. IOP was recorded via an external antenna placed around the study eye. Average peak IOP increases from baseline were analysed and tested against zero (no change) with one-sample t-tests. RESULTS: For eyelid rubbing, the average peak ∆ IOP increase (mean±SEM) was 59.1±9.6 mm Hg (p<0.001) from baseline. It was 42.2±5.8 mm Hg (p<0.0001) for eyelid squeezing, 3.8±0.6 mm Hg (n=9, p<0.01) for eyelid closure and 11.6±2.4 mm Hg (p<0.001) for voluntary blinking. No IOP change except for a short irregularity in the ocular pulse was observed during involuntary blinking. CONCLUSION: Eyelid manoeuvres in patients with POAG elicited brief increases in IOP that were particularly large with squeezing and rubbing. Further investigation of the potential implications for glaucoma progression is warranted.

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.

The retinal pigmentation pathway in human albinism: Not so black and white.

Albinism is a pigment disorder affecting eye, skin and/or hair. Patients usually have decreased melanin in affected tissues and suffer from severe visual abnormalities, including foveal hypoplasia and chiasmal misrouting. Combining our data with those of the literature, we propose a single functional genetic retinal signalling pathway that includes all 22 currently known human albinism disease genes. We hypothesise that defects affecting the genesis or function of different intra-cellular organelles, including melanosomes, cause syndromic forms of albinism (Hermansky-Pudlak (HPS) and Chediak-Higashi syndrome (CHS)). We put forward that specific melanosome impairments cause different forms of oculocutaneous albinism (OCA1-8). Further, we incorporate GPR143 that has been implicated in ocular albinism (OA1), characterised by a phenotype limited to the eye. Finally, we include the SLC38A8-associated disorder FHONDA that causes an even more restricted "albinism-related" ocular phenotype with foveal hypoplasia and chiasmal misrouting but without pigmentation defects. We propose the following retinal pigmentation pathway, with increasingly specific genetic and cellular defects causing an increasingly specific ocular phenotype: (HPS1-11/CHS: syndromic forms of albinism)-(OCA1-8: OCA)-(GPR143: OA1)-(SLC38A8: FHONDA). Beyond disease genes involvement, we also evaluate a range of (candidate) regulatory and signalling mechanisms affecting the activity of the pathway in retinal development, retinal pigmentation and albinism. We further suggest that the proposed pigmentation pathway is also involved in other retinal disorders, such as age-related macular degeneration. The hypotheses put forward in this report provide a framework for further systematic studies in albinism and melanin pigmentation disorders.

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.

Structural changes to primary visual cortex in the congenital absence of cone input in achromatopsia.

Autosomal recessive Achromatopsia (ACHM) is a rare inherited disorder associated with dysfunctional cone photoreceptors resulting in a congenital absence of cone input to visual cortex. This might lead to distinct changes in cortical architecture with a negative impact on the success of gene augmentation therapies. To investigate the status of the visual cortex in these patients, we performed a multi-centre study focusing on the cortical structure of regions that normally receive predominantly cone input. Using high-resolution T1-weighted MRI scans and surface-based morphometry, we compared cortical thickness, surface area and grey matter volume in foveal, parafoveal and paracentral representations of primary visual cortex in 15 individuals with ACHM and 42 normally sighted, healthy controls (HC). In ACHM, surface area was reduced in all tested representations, while thickening of the cortex was found highly localized to the most central representation. These results were comparable to more widespread changes in brain structure reported in congenitally blind individuals, suggesting similar developmental processes, i.e., irrespective of the underlying cause and extent of vision loss. The cortical differences we report here could limit the success of treatment of ACHM in adulthood. Interventions earlier in life when cortical structure is not different from normal would likely offer better visual outcomes for those with ACHM.

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

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

CHIASM, the human brain albinism and achiasma MRI dataset.

We describe a collection of T1-, diffusion- and functional T2*-weighted magnetic resonance imaging data from human individuals with albinism and achiasma. This repository can be used as a test-bed to develop and validate tractography methods like diffusion-signal modeling and fiber tracking as well as to investigate the properties of the human visual system in individuals with congenital abnormalities. The MRI data is provided together with tools and files allowing for its preprocessing and analysis, along with the data derivatives such as manually curated masks and regions of interest for performing tractography.

Structural Differences Across Multiple Visual Cortical Regions in the Absence of Cone Function in Congenital Achromatopsia.

Most individuals with congenital achromatopsia (ACHM) carry mutations that affect the retinal phototransduction pathway of cone photoreceptors, fundamental to both high acuity vision and colour perception. As the central fovea is occupied solely by cones, achromats have an absence of retinal input to the visual cortex and a small central area of blindness. Additionally, those with complete ACHM have no colour perception, and colour processing regions of the ventral cortex also lack typical chromatic signals from the cones. This study examined the cortical morphology (grey matter volume, cortical thickness, and cortical surface area) of multiple visual cortical regions in ACHM (n = 15) compared to normally sighted controls (n = 42) to determine the cortical changes that are associated with the retinal characteristics of ACHM. Surface-based morphometry was applied to T1-weighted MRI in atlas-defined early, ventral and dorsal visual regions of interest. Reduced grey matter volume in V1, V2, V3, and V4 was found in ACHM compared to controls, driven by a reduction in cortical surface area as there was no significant reduction in cortical thickness. Cortical surface area (but not thickness) was reduced in a wide range of areas (V1, V2, V3, TO1, V4, and LO1). Reduction in early visual areas with large foveal representations (V1, V2, and V3) suggests that the lack of foveal input to the visual cortex was a major driving factor in morphological changes in ACHM. However, the significant reduction in ventral area V4 coupled with the lack of difference in dorsal areas V3a and V3b suggest that deprivation of chromatic signals to visual cortex in ACHM may also contribute to changes in cortical morphology. This research shows that the congenital lack of cone input to the visual cortex can lead to widespread structural changes across multiple visual areas.

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

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

Functional Dynamics of Deafferented Early Visual Cortex in Glaucoma.

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