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Background: Impaired corollary discharge (CD) signalling disrupts the ability to predict the sensory consequences of one's own actions; impaired CD signalling may be specific to schizophrenia or it may also be a transdiagnostic mechanism of psychosis. We sought to assess whether disruptions in oculomotor CD signalling are equally present in schizophrenia and bipolar disorder (BD) with psychotic features, and whether these putative CD disruptions relate to anomalous self-experiences. Methods: We recruited patients with schizophrenia and patients with BD with psychotic features, as well as healthy controls, to complete a double-step saccade task. On each trial, 2 visual targets (T1 and T2) flashed in rapid succession. For half of the trials, participants could use visual information to look at T2. For the other half, looking correctly at T2 required CD. Results: We included 66 patients with schizophrenia, 43 patients with BD with psychotic features, and 37 healthy controls. On trials requiring CD, patient groups were significantly less accurate than controls in localizing T2 (F 2,131 = 8.40, p < 0.001). This reduced accuracy was related to difficulty in compensating for variability in the first saccade (F 2,131 = 9.11, p < 0.001). Among controls, anomalous self-experiences predicted worse performance (F 1, 57 = 14.23, p < 0.001). Limitations: Our sample comprised stable outpatients with relatively low symptom scores, which may limit the generalizability of our results. Conclusion: These results suggest CD impairments may be a marker of predisposition for psychosis. However, observed inconsistencies suggest that this relationship is nuanced. [ABSTRACT FROM AUTHOR]

Gene augmentation and genome editing are promising strategies for the treatment of monogenic inherited retinal diseases. Although gene augmentation treatments are commercially available for inherited retinal diseases, there are many shortcomings that need to be addressed, like progressive retinal degeneration and diminishing efficacy over time. Innovative CRISPR-Cas9-based genome editing technologies have broadened the proportion of treatable genetic disorders and can greatly improve or complement treatment outcomes from gene augmentation. Progress in this relatively new field involves the development of therapeutics including gene disruption, ablate-and-replace strategies, and precision gene correction techniques, such as base editing and prime editing. By making direct edits to endogenous DNA, genome editing theoretically guarantees permanent gene correction and long-lasting treatment effects. Improvements to delivery modalities aimed at limiting persistent gene editor activity have displayed an improved safety profile and minimal off-target editing. Continued progress to advance precise gene correction and associated delivery strategies will establish genome editing as the preferred treatment for genetic retinal disorders. This commentary describes the applications, strengths, and drawbacks of conventional gene augmentation approaches, recent advances in precise genome editing in the retina, and promising preclinical strategies to facilitate the use of robust genome editing therapies in human patients.

Background: Tocotrienol is a vitamin E analogue that is known to exert anti-inflammatory and antioxidant effects. Hence, in the current study, the effects of TRF on the expression of pro- and anti-apoptotic proteins in the streptozotocin-induced diabetic rat retinas were investigated. The effect of TRF on the visual behaviour of rats was also studied. Methods: Diabetes was induced in rats by intraperitoneal injection of streptozotocin and was confirmed by a blood sugar level of at least 20 mmol/L, 48 h, post-injection. Diabetic rats were divided into a group treated with vehicle (DV) and the other treated with TRF (100 mg/kg; DT). A group of non-diabetic rats treated with vehicle (N) served as the control group. All treatments were administered orally for 12 weeks. Rats were then subjected to an assessment of general behaviour in an open field arena and a two-chamber mirror test to assess their visual behaviour. At the end of the experimental period, rats were sacrificed, and their retinas were isolated to measure the expression of pro- (Casp3, Bax) and anti-apoptotic (Bcl2) markers using RT-qPCR and ELISA. TUNEL staining was used to detect the apoptotic retinal cells. Results: Treatment with TRF lowered the retinal expression of Casp3 protein by 2.26-folds (p < 0.001) and Bax protein by 2.18-fold (p < 0.001) compared to vehicle-treated rats. The retinal anti-apoptotic protein Bcl2 expression was 1.87-fold higher in DT compared to DV rats (p < 0.001). Accordingly, the Bax/Bcl2 ratio in the TRF-treated group was significantly greater in DT compared to DV rats. Retinal Casp3, Bax, and Bcl2 gene expression, as determined by RT-qPCR, also showed changes corresponding to protein expression. In the open field test, DV rats showed greater anxiety-related behaviour than group N, while the behaviour of DT rats was similar to the N group of rats. DT rats and group N rats preferred the inverse mirror chamber over the mirror-containing chamber in the two-mirror chamber test (p < 0.01). Conclusion: Oral TRF therapy for 12 weeks lowers retinal cell apoptosis by decreasing pro- and increasing anti-apoptotic markers. The preservation of visual behaviour in a two-chamber mirror test supported these retinal molecular alterations in diabetic rats. [ABSTRACT FROM AUTHOR]

Diabetic macular edema (DME) has emerged as the foremost cause of vision loss in the population with diabetes. Early detection of DME is paramount, yet the prevailing screening, relying on two-dimensional and labor-intensive fundus photography (FP), results in frequent unwarranted referrals and overlooked diagnoses. Self-imaging optical coherence tomography (SI-OCT), offering fully automated, three-dimensional macular imaging, holds the potential to enhance DR screening. We conducted an observational study within a cohort of 1822 participants with diabetes, who received comprehensive assessments, including visual acuity testing, FP, and SI-OCT examinations. We compared the performance of three screening strategies: the conventional FP-based strategy, a combination strategy of FP and SI-OCT, and a simulated combination strategy of FP and manual SD-OCT. Additionally, we undertook a cost-effectiveness analysis utilizing Markov models to evaluate the costs and benefits of the three strategies for referable DR. We found that the FP + SI-OCT strategy demonstrated superior sensitivity (87.69% vs 61.53%) and specificity (98.29% vs 92.47%) in detecting DME when compared to the FP-based strategy. Importantly, the FP + SI-OCT strategy outperformed the FP-based strategy, with an incremental cost-effectiveness ratio (ICER) of $8016 per quality-adjusted life year (QALY), while the FP + SD-OCT strategy was less cost-effective, with an ICER of $45,754/QALY. Our results were robust to extensive sensitivity analyses, with the FP + SI-OCT strategy standing as the dominant choice in 69.36% of simulations conducted at the current willingness-to-pay threshold. In summary, incorporating SI-OCT into FP-based screening offers substantial enhancements in sensitivity, specificity for detecting DME, and most notably, cost-effectiveness for DR screening. [ABSTRACT FROM AUTHOR]

Introduction. Peripheral retinal refraction plays a crucial role in myopia, but the specific mechanism is not clear. We refined the retinal partitions to explore the characteristics of peripheral retinal refraction and its role in emmetropic, low, and moderate myopic children aged 6 to 12 years. Methods. A total of 814 subjects (814 eyes) were enrolled in the study. The participants were divided into three groups according to the central spherical equivalent refraction (SER), which were emmetropia group (E), low myopia group (LM) and moderate myopia group (MM). Multispectral refractive topography (MRT) was used to measure the retinal absolute and relative refractive difference value (RDV) in different regions. The range was divided into superior, inferior, temporal, and nasal RDV (SRDV, IRDV, TRDV, and NRDV) on the basis of several concentric circles extending outward from the macular fovea (RDV15, RDV30, RDV45, RDV30–15, RDV45–30, and RDV‐45). Kruskal–Wallis test was used to analyze the differences of peripheral refraction for all the regions among the three groups. Spearman rank correlation was performed to explore correlations between SER and RDV, axial length (AL) and RDV. Results. The absolute value of RDV decreased with increasing degree of myopia in all regions (P < 0.01). Subjects with different refractive degrees had different relative value of RDV. In nasal position within 45° and temporal position within 30°, the peripheral retina exhibited significantly different relative hyperopic refractive status among Group E, Group LM, and Group MM (P < 0.05). SER was negatively correlated with NRDV within 30° (especially in the range of NRDV30–15) (r = −0.141, P < 0.01), positively correlated with TRDV within 15° (r = 0.080, P = 0.023), and not significantly correlated with SRDV and IRDV when the retina was divided into four parts. AL was positively correlated with NRDV within 30° (especially in the range of NRDV30–15) (r = 0.109, P = 0.002), negatively correlated with TRDV within 15° (r = −0.095, P = 0.007). Conclusions. The peripheral defocus has significant implications for the genesis of myopia. The peripheral defocus of the horizontal direction, especially within the range of NRDV30, has greater effect on the development of myopia in children. Higher NRDV30 is associated with lower SER and longer AL. [ABSTRACT FROM AUTHOR]

Purpose: To determine the physiological status of the retina by electroretinography (ERG) using skin electrodes and the RETevalTM system in eyes that had undergone pars plana vitrectomy (PPV) with silicone oil (SO) tamponade. The vitrectomy was performed for a retinal detachment and proliferative diabetic retinopathy (PDR). Design: Retrospective case series. Methods: ERGs were recorded with the RETevalTM system (LKC Technologies Inc. Gaithersburg, MD; Welch Allyn, Inc. Skaneateles Falls, NY) from eight eyes with PDR before and after the SO removal. The amplitudes and implicit times of the a- and b-waves of the ERGs before the SO removal were compared to that after the SO removal. Results: ERGs were recordable in four eyes before and after the SO removal and the a- and b-amplitudes improved in three eyes and worsened in one eye after the SO removal. In the remaining four eyes, ERGs were non-recordable both before and after the SO removal. Conclusion: These results indicate that ERGs picked up by skin electrodes can be used to assess the physiology of the retina in eyes with a SO tamponade. The flat ERGs in the SO-filled eye indicated the presence of diffuse retinal damage which was confirmed by the flat ERGs after the SO removal. Plain Language Summary: There has been an increasing number of reports on evaluating the retinal function using electroretinography (ERG) with skin electrodes. The main advantage of this system is the ability to record ERGs with a skin electrode that does not touch the cornea and ocular surface. This reduces the risk of infection especially in the postoperative period and in clinical situations where infection is suspected. In addition, there have been only a few reports evaluating the function of the retina by ERG in SO-filled eyes. We recorded ERGs with the RETeval (LKC Technologies Inc. Gaithersburg, MD; Welch Allyn Inc. Skaneateles Falls, NY) device, a relatively new ERG recording system that uses skin electrodes and is less invasive. We recorded ERGs from eight SO-filled eyes with proliferative diabetic retinopathy (PDR). In 4 SO filled eyes, the amplitudes increased in three eyes after the SO removal. In the other four eyes, ERGs were non-recordable before and after the SO removal. These results suggest that the RETeval system that uses skin electrodes can be used to assess the retinal function in PDR eyes with a SO tamponade. We suggest that the absence of ERGs in the SO filled eyes was not due to the electrical non-conductive effects of SO but may indicate the presence of diffuse retinal damage which was confirmed after the SO removal. [ABSTRACT FROM AUTHOR]

Spectral-domain optical coherence tomography (SDOCT) is the gold standard of imaging the eye in clinics. Penetration depth with such devices is, however, limited and visualization of the choroid, which is essential for diagnosing chorioretinal disease, remains limited. Whereas swept-source OCT (SSOCT) devices allow for visualization of the choroid these instruments are expensive and availability in praxis is limited. We present an artificial intelligence (AI)-based solution to enhance the visualization of the choroid in OCT scans and allow for quantitative measurements of choroidal metrics using generative deep learning (DL). Synthetically enhanced SDOCT B-scans with improved choroidal visibility were generated, leveraging matching images to learn deep anatomical features during the training. Using a single-center tertiary eye care institution cohort comprising a total of 362 SDOCT-SSOCT paired subjects, we trained our model with 150,784 images from 410 healthy, 192 glaucoma, and 133 diabetic retinopathy eyes. An independent external test dataset of 37,376 images from 146 eyes was deployed to assess the authenticity and quality of the synthetically enhanced SDOCT images. Experts' ability to differentiate real versus synthetic images was poor (47.5% accuracy). Measurements of choroidal thickness, area, volume, and vascularity index, from the reference SSOCT and synthetically enhanced SDOCT, showed high Pearson's correlations of 0.97 [95% CI: 0.96–0.98], 0.97 [0.95–0.98], 0.95 [0.92–0.98], and 0.87 [0.83–0.91], with intra-class correlation values of 0.99 [0.98–0.99], 0.98 [0.98–0.99], and 0.95 [0.96–0.98], 0.93 [0.91–0.95], respectively. Thus, our DL generative model successfully generated realistic enhanced SDOCT data that is indistinguishable from SSOCT images providing improved visualization of the choroid. This technology enabled accurate measurements of choroidal metrics previously limited by the imaging depth constraints of SDOCT. The findings open new possibilities for utilizing affordable SDOCT devices in studying the choroid in both healthy and pathological conditions. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether 0.025% povidone-iodine (0.025% PI) in the irrigation solution during vitrectomy for endophthalmitis is safe. Methods: Two cases of bleb-associated endophthalmitis were treated with vitrectomy using 0.025% PI in the irrigation solution. The RETevel electroretinographic (ERG) system with skin electrodes was used to assess the physiology of the retina pre- and postoperatively. Case: Case 1 was a 46-year-old man who had atopic keratoconjunctivitis and underwent trabeculectomy with the creation of a bleb after there was a rise in the intraocular pressure. One month postoperatively, a mild filtering bleb-associated endophthalmitis developed, and the eye was treated with intravitreal and subconjunctival injections of vancomycin (VCM) and ceftazidime (CAZ). After three days, the fundus was not visible and B-mode echography showed an area of high brightness in the retina. Vitrectomy with irrigation with VCM and CAZ, and 0.025% PI was performed successfully. Pre- and postoperative ERGs showed an improvement in both the a- and b-wave amplitudes and the b/a ratio was stable at 2.0. Case 2 was a 63-year-old man who had undergone trabeculectomy for glaucoma. Five years later, the eye developed blebitis which was treated with topical and subconjunctival injections of VCM and CAZ. Three days later, vitreous opacities appeared and a high brightness area was seen in the B-mode echographic images. Vitrectomy with VCM and CAZ, and 0.025% PI irrigation was successfully performed. Comparisons of the pre- and postoperative ERGs found that the a- and b- wave amplitudes of the ERGs increased and the b/a ratio was stable at approximately 1.5. Conclusion: Vitrectomy with 0.025% PI irrigation is safe and ERG recordings with skin electrodes can be used to evaluate the pre- and postoperative retinal physiology safely. Plain Language Summary: We report our findings in two cases of bleb-related endophthalmitis that underwent pars plana vitrectomy (PPV) with irrigation with 0.025% povidone-iodine (PI)-Balanced Salt Solution (BSS) PLUS (Alcon Laboratories, Fort Worth, TX). The retinal function was evaluated by full-field electroretinograms (ERGs) recorded with skin electrodes before and after the vitrectomy. At present, there is no consensus on whether patients with bleb-related endophthalmitis should be treated with PPV or treated solely by intravitreal antibiotics. It was recently reported that vitrectomy using an irrigation solution containing 0.025% PI followed by postoperative antibiotics was effective and safe for the treatment of endogenous endophthalmitis and postoperative endophthalmitis. However, iodine is known to be retinotoxic depending on its concentration. Electroretinography is a useful method to evaluate the safety of medications because it represents the physiology of the entire retina. However, conventional recording procedures with contact lens electrodes cannot be used in eyes with bleb associated endophthalmitis. Therefore, we performed ERG using skin electrodes which were introduced relatively recently. As a result, electroretinographic response showed that retinal function was not altered after surgery in these two cases. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the retinal morpho‐functional characteristics of patients with neovascular wet age‐related macular degeneration (nAMD) treated with intravitreal injection (IV) of aflibercept (AFL). Methods: The study was conducted on 35 patients previously diagnosed with type 1 nAMD who received a fixed‐dosing regimen of aflibercept injections over 12 months. The goal was to assess trends in visual abilities over time by measuring visual acuity (VA), contrast sensitivity (CS), visual evoked potentials (VEPs), and spectral domain‐optical coherence tomography (SD‐OCT). The same psychophysical, electro‐functional, and morphological tests administered at baseline (T0) were repeated 4 to 8 weeks after the last aflibercept injection (Tn), resulting in a total of six examinations. Results: At Tn, all subjects exhibited improved VA for both far and near distances compared to values detected at T0. Similarly, VEP amplitude and latency values at Tn showed a greater P100 improvement than those observed at T0. Additionally, the CS examination at Tn demonstrated improvement, particularly at high spatial stimulation frequencies. The Tn SD‐OCT results highlighted a reduction in macular thickness compared to T0 values. Conclusions: This exploratory research indicates that intravitreal injections of AFL, following a fixed‐dosing regimen, represent a valuable therapeutic approach for enhancing visual performance. This conclusion is supported by comprehensive statistical analysis of psychophysical, electro‐functional, and morphological examinations within the same group of patients with nAMD, as demonstrated for the first time. [ABSTRACT FROM AUTHOR]

Twenty-seven glaucoma patients (54 eyes in total) with well-controlled intraocular pressure were trained with binocular virtual reality visual software for 3 months to investigate whether virtual reality visual perceptual plastic training promotes macular retinal structure and macular function recovery in glaucoma patients. The thickness of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer-inner plexiform layer (mGCIPL), and mean macular sensitivity (mMS) were evaluated 3 months after training. The mean value of pRNFL thickness in glaucoma patients did not change significantly (Z = 0.642, p = 0.521), nor did the mean value (t = 1.916, p = 0.061) and minimum value (Z = 1.428, p = 0.153) of mGCIPL after 3 months. However, the significant increases were found in superior temporal mGCIPL thickness (t = 2.430, p = 0.019) as well as superior mGCIPL thickness (t = 2.262, p = 0.028). Additionally, the mMS was increased (Z = 2.259, p < 0.05), with the inferior square to be a more pronounced mMS increase (Z = 2.070, p = 0.038). In conclusion, virtual reality visual perceptual plastic training can increase the thickness of retinal ganglion cells complexes in the macular area of glaucoma patients and improve the macular function of the corresponding area. Clinical Trial registration number: ChiCTR1900027909. [ABSTRACT FROM AUTHOR]

Background: Amiodarone is widely used for heart arrhytmia. Previous studies have suggested the possibility of optic neuropathy with the chronic use of this drug. Objectives: To identify structural or functional changes in the retina and optic nerve in patients on chronic amiodarone therapy without visual complaints. Methods: This observational study included 15 eyes of 15 patients with cardiac arrythmia on chronic amiodarone treatment and 15 healthy matched subjects as a control group. All subjects underwent electrophysiological tests [pattern visual evoked potential (PVEP), pattern electroretinogram (PERG), multifocal electroretinogram (mfERG), and optical coherence tomography (OCT) and angiography (OCTA)]. Results: There were no statistically significant differences between the two groups regarding the PVEP, PERG, and the mfERG parameters. Macular and optic nerve head OCT and OCTA have not shown statistically significant differences except for the morphological parameters of the optic disc (p = 0.008 for the horizontal and p = 0.013 for vertical cup/disc ratio and p = 0.045 for rim area). Conclusion: Patients on chronic amiodarone therapy have not shown evident structural or functional changes in the retinal or optic nerve as demonstrated by electrophysiological tests, OCT, and OCTA results compared to controls. [ABSTRACT FROM AUTHOR]

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Background. The change in refraction caused by accommodation inevitably affects the peripheral defocus state and thus may influence the effect of retinal peripheral myopic defocus measures in myopia control. This study investigated accommodation changes in different peripheral retinas under cycloplegia to help improve myopia control. Methods. Fifty-six eyes of fifty-six myopic subjects were recruited for this prospective study. The center and peripheral retina refractions were measured using multispectral refractive topography. The subjects were divided into low-to-moderate myopia group (range: −1.25 D to −6.00 D) and high myopia group (range: −6.25 D to −9.75 D) according to spherical equivalent (SE). The compound tropicamide (0.5% tropicamide and 0.5% phenylephrine) was used to relax the accommodation. The difference between cycloplegia and non-cycloplegia peripheral retinal refraction was analyzed using the t-test. The correlation between eccentricity and changes in peripheral refraction was analyzed using Pearson's correlation analysis. Results. The manifest refraction of the retina significantly decreased with an increase in eccentricity after cycloplegia. The annular refraction difference value at 50°–53° (ARDV 50–53) showed the largest refraction decrease of 1.31 D compared with the central retinal refraction decrease of 0.84 D. The inferior quadrantal refraction difference value had the least change compared to the other quadrants. The relative peripheral refraction (RPR) changes in refraction difference value (RDV) at 15° (RDV-15), RDV-30, and RDV-45 were less than 0.15 D. When the range of annulus narrowed to 5°, the narrower annulus showed faster change with eccentricity increase in ARDV 30–35, ARDV 35–40, ARDV 40–45, ARDV 45–50, and ARDV 50–53. The RPR was highly correlated with eccentricity (R = 0.938 and P < 0.001). The high myopia group had a greater hyperopic shift in the periphery than the low-to-moderate group after cycloplegia. Conclusions. Peripheral refraction showed a significant hyperopic shift after cycloplegia with an increase in eccentricity. The RPR became more hyperopic than the central refraction. The high myopia group showed more hyperopic shifts in the peripheral region. Accommodation should be taken into consideration in peripheral defocus treatment. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the most serious neurodegenerative diseases in the globe. As a result, there is an acute need to discover indications that allow for early disease detection. There is growing scientific data showing the similarities between the eye and other central nervous system components, suggesting that information obtained in ophthalmic research might be valuable in the study and diagnosis of AD. Fifty male albino Wistar rats were separated into five groups: the first group served as control, and the other four groups of animals were administrated aluminium chloride (AlCl3) in a dose of 100 mg/kg body weight (b.w.) for 2, 4, 6, and 8 weeks, respectively. Insights into the function of the retina by electroretinogram (ERG) and the changes thought to have occurred in the molecular structure of the retina and brain using Fourier transform infrared spectroscopy (FTIR) as a result of AD progression induced by AlCl3 in rats were done. Moreover, the measurement of acetylcholinesterase (AchE) was done. After 6 and 8 weeks of AlCl3 injection, there was a substantial reduction (p ≤ 0.05) in a- and b-wave amplitudes and a significant rise (p ≤ 0.05) in implicit time compared to controls. A significant elevation (p ≤ 0.05) of AchE content was observed after 4, 6, and 8 weeks. FTIR revealed a significant increase (p ≤ 0.05) of β-turn and β-sheet content associated with significant decrease (p ≤ 0.05) of α-helix content for all groups administrated with AlCl3. Our findings suggest that retinal biomarkers such as ERG of the retina may be used as a screening tool for detection of AD. Secondary structural changes in the proteins of the retina and the brain were similar in AD rats' model and precede retinal dysfunction. [ABSTRACT FROM AUTHOR]

Perception and action are inherently entangled: our world view is shaped by how we explore our environment through complex and variable self-motion. Even when fixating stable stimuli, our eyes undergo small, involuntary movements. Fixational eye movements (FEM) render a stable world jittery on our retinae, which can be expected to harm neural coding. Yet, empirical evidence suggests that FEM help rather than harm human perception of fine detail. Here, we elucidate this paradox by uncovering under which conditions FEM improve or impair retinal coding and human acuity. We combine theory and experiment: model accuracy is directly compared to that of healthy human subjects in a visual acuity task. Acuity is modeled by applying an ideal Bayesian classifier to simulations of retinal spiking activity in the presence of FEM. In addition, empirical FEM are monitored using high-resolution eye-tracking by an adaptive optics scanning laser ophthalmoscope. FEM introduce variability in retinal ganglion cell activity, but they also effectively preprocess inputs to facilitate retinal information encoding. Based on an interplay of these mechanisms, our model predicts a relation between visual acuity, FEM amplitude, and single-trial stimulus size that quantitatively accounts for experimental observations and captures the beneficial effect of FEM. Moreover, we observe that while human subjects' FEM statistics vary with stimulus size, our model suggests that subjects' FEM amplitude remains within a near-optimal range, where acuity is enhanced compared to much larger or smaller amplitudes. Overall, our findings indicate that perception benefits from action even at the fine spatiotemporal scale of FEM., Competing Interests: Competing interests statement:The authors declare no competing interest.

Visual processing involves numerous neuro-ophthalmic pathways that enable humans to perceive and interact with the world. These visual pathways can negatively impact visual perception and decision-making. The Vestibulo-Ocular Reflex (VOR) is a compensatory mechanism that stabilizes gaze on a target during head movement, such as running or turning. However, inadequate VOR stabilization can lead to retinal slip, reducing visual acuity. In the National Football League (NFL), officials require exceptional visual training and performance. NFL officiating utilize rapid visual processing, strategic movements, and precise judgement to make accurate penalty calls in real-time. Retinal slip can adversely affect play calling and penalty assessment by NFL officials. Despite these challenges, NFL officials achieve high precision and accuracy in up to 98.9% of plays. To maintain such high standards, the NFL has implemented a standardized curriculum to mitigate the effects of VOR and retinal slip. This manuscript outlines the basics of VOR function and explores countermeasures to minimize retinal slip in NFL officiating. We believe that these scientific endeavours can improve both penalty assessment accuracy and precision. The use of these general principles might also be potentially applicable to other sports., Competing Interests: Competing interests: AGL serves as a consultant for the National Football League (NFL). Dr. Lee is on the Speakers’ Bureau for Amgen and Alexion and is on the Advisory Board for Viridian and Stoke and serves as a consultant for Bristol Myers Squibb and Astrazeneca. Dr. Lee serves on the Editorial board of Eye., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Detecting small moving objects in complex backgrounds from an overhead perspective is a highly challenging task for machine vision systems. As an inspiration from nature, the avian visual system is capable of processing motion information in various complex aerial scenes, and the Retina-OT-Rt visual circuit of birds is highly sensitive to capturing the motion information of small objects from high altitudes. However, more needs to be done on small object motion detection algorithms based on the avian visual system. In this paper, we conducted mathematical description based on extensive studies of the biological mechanisms of the Retina-OT-Rt visual circuit. Based on this, we proposed a novel tectum small object motion detection neural network (TSOM). The TSOM neural network includes the retina, SGC dendritic, SGC Soma, and Rt layers, each corresponding to neurons in the visual pathway for precise topographic projection, spatial-temporal encoding, motion feature selection, and multi-directional motion integration. Extensive experiments on pigeon neurophysiological experiments and image sequence data showed that the TSOM is biologically interpretable and effective in extracting reliable small object motion features from complex high-altitude backgrounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Subretinal injection of gene products is the only treatment option for inherited retinal diseases. However, this procedure induces localized high multiaxial deformations, potentially causing irreversible tissue damage due to retinal overstretching and tearing. Comprehensive characterization of retinal mechanical behavior is essential for performing safe injections. Although uniaxial tensile test has been used in the literature, it has many limitations for retinal characterization. To date, retinal mechanical properties are poorly understood due to the lack of standardized testing protocol. This study aimed to introduce a combined experimental-computational approach using small punch testing and finite element simulations to investigate retina elastic behavior under biaxial deformations. To develop a suitable testing protocol for retinal samples, we evaluated the impact of environmental conditions on retinal elasticity by performing uniaxial tensile tests on porcine retinal strips in air, in a saline bath, and at different temperatures. The results showed that conditions did not significantly affect the elastic modulus. We then developed an easy and reproducible small punch test protocol, allowing to measure for the first time the load-displacement response of the retina under biaxial deformations. Computational simulations enabled the analysis of retinal deformations and the identification of its elastic modulus (5.5 kPa). The outcomes of this study highlight the great potential of the combined approach as a viable alternative to uniaxial tensile test to advance the understanding of retinal biomechanics. This is essential not only for minimizing sight-threatening surgical complications during injections, but also for building predictive in silico models, and developing biomimetic scaffolds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Current vision-inspired spiking neural networks (SNNs) face key challenges due to their model structures typically focusing on single mechanisms and neglecting the integration of multiple biological features. These limitations, coupled with limited synaptic plasticity, hinder their ability to implement biologically realistic visual processing. To address these issues, we propose Spike-VisNet, a novel retina-inspired framework designed to enhance visual recognition capabilities. This framework simulates both the functional and layered structure of the retina. To further enhance this architecture, we integrate the FocusLayer-STDP learning rule, allowing Spike-VisNet to dynamically adjust synaptic weights in response to varying visual stimuli. This rule combines channel attention, inhibition mechanisms, and competitive mechanisms with spike-timing-dependent plasticity (STDP), significantly improving synaptic adaptability and visual recognition performance. Comprehensive evaluations on benchmark datasets demonstrate that Spike-VisNet outperforms other STDP-based SNNs, achieving precision scores of 98.6% on MNIST, 93.29% on ETH-80, and 86.27% on CIFAR-10. These results highlight its effectiveness and robustness, showcasing Spike-VisNet's potential to simulate human visual processing and its applicability to complex real-world visual challenges., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Study the scotopic oscillatory potentials (OPs) in mice over a wide range of flash luminance levels using the Hilbert transform (HT) to extract new features of the high frequency components of the electroretinogram (ERG)., Methods: Scotopic ERGs [Intensity: - 6.3 to 0.9 log cd∙s∙m -2 ; 12 h of dark-adaptation] were obtained from adult mice (C57BL/6; n = 7). The Hilbert transform (HT) was obtained within 3 consecutive frequency bands (65-90 Hz, 90-115 Hz and 115-140 Hz), with OPs being denoised, automatically identified and analyzed. Measurements included: number of OPs, duration of the OP response, surface-under-the-curve (SUC) of the HT envelopes, implicit times, and instantaneous frequency at the HT envelope peak, mean peak time differences (PTD) between the envelopes of each frequency band (measuring their synchrony), correlation coefficient and lag between consecutive HT envelopes, as well as the number of peaks on the HT envelopes., Results: The OP response duration, number of OPs and PTD all peaked for flashes between the level corresponding to the RodVmax (maximal b-wave amplitude of the rod ERG; i.e., the first asymptote of the scotopic luminance-response curve) and K (the flash luminance at which the amplitude of the b-wave is half of that of the RodVmax;), i.e., between -3.9 and -2.4 log cd∙s∙m -2 . The correlation between consecutive envelopes is close to 1 at flashes > -1.2 log cd∙s∙m -2 , with small lags (min. = 1.93 ± 0.45 ms at - 1.2 log cd∙s∙m -2 ), then gradually drops to 0.81 ± 0.02 at the dimmest flash intensity (with a max. lag = 14.76 ± 8.92 ms at - 5.1 log cd∙s∙m -2 ). Finally, we found that the single OP burst (i.e., a single HT envelope peak) seen at flash intensities >  - 1.2 log cd∙s∙m -2 progressively divided in two (or more) OP bursts (i.e., multiple HT envelope peaks) with gradually dimmer flashes., Conclusions: Our HT method enabled the analysis of the OP response without the subjective interpretation of the experimenter. Analysis of the scotopic OPs at dim flashes with the HT revealed a novel feature of the OP response not yet reported elsewhere, namely: a split of the OP response into two (or more) distinct bursts. Furthermore, the synchrony peak (measured with the PTD) matched the peak in OP response duration between K and RodVmax, suggesting a disorganization (or dephasing) of the retinal signal in ERGs evoked for weaker flashes. The increased synchronization and correlation of the single burst observed for the strongest flashes could suggest an optimization or saturation of the retinal response. We believe that these novel features of the OP components of the ERG went unnoticed given that previous studies did not use weak enough flashes and failed to recognize the added value that time and frequency domain analysis of the ERG (such as what is achieved with the HT) brings to the interpretation (and our understanding) of the retinal response., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To explore changes in the electroretinogram (ERG) following methylphenidate use in attention-deficit/hyperactivity disorder (ADHD)., Methods: Light adapted ERGs were recorded in five individuals (3 male and 2 female, age range 13.6-21.8 years) with a diagnosis of ADHD. Six flash strengths ranging from 71 to 446 Td.s were qualitatively evaluated following a minimum of 24 h without any medication and from 2 to 6 h following the individuals' standard slow-release (XL) methylphenidate dose that ranged from 18 to 60 mg., Results: Of the six flash strengths, the 178 Td.s strength revealed changes in four of the five participants with a median 27.4% increase in b-wave amplitude. For three individuals there was an increase in the a-wave amplitude and for two of the same individuals there was also a noticeable pronouncement of the oscillatory potentials. The a-wave amplitude showed a greatest median increase at the 446 Td.s flash strength of 25.8%. One individual - on the highest dose (60 mg) exhibited no morphologically distinct changes in the ERG. No differences in the time to peaks of the a- and b-wave were observed for any individual., Conclusion: The a- and b-wave amplitudes of the light adapted ERG could provide insights into the effect of methylphenidate in ADHD., Competing Interests: Declarations. Conflicts of interest: DT is an associate editor for Documenta Ophthalmologica but had no part in the peer review process for this article. The authors declare no other conflicts of interest. Ethical approval: The study was was approved by the Southeast Scotland Research Ethics Committee UK. Consent to participate: Written informed consent obtained from the parents/caregivers of children under the age of 16 or from the participants if aged over 16 years of age. Consent to publish: All participants gave consent to publish anonymised data obtained in the study. Informed consent: Informed consent was obtained from all participants in the study. Statement of human rights: All procedures performed in study involving human participants were in accordance with the ethical standards of institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Statement on the welfare of animals: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective. Neural interfaces are designed to evoke specific patterns of electrical activity in populations of neurons by stimulating with many electrodes. However, currents passed simultaneously through multiple electrodes often combine nonlinearly to drive neural responses, making evoked responses difficult to predict and control. This response nonlinearity could arise from the interaction of many excitable sites in each cell, any of which can produce a spike. However, this multi-site activation hypothesis is difficult to verify experimentally. Approach. We developed a biophysical model to study retinal ganglion cell responses to multi-electrode stimulation and validated it using data collected from ex vivo preparations of the macaque retina using a microelectrode array (512 electrodes; 30 µ m pitch; 10 µ m diameter). Results. First, the model was validated by using it to reproduce essential empirical findings from single-electrode recording and stimulation, including recorded spike voltage waveforms at multiple locations and sigmoidal responses to injected current. Then, stimulation with two electrodes was modeled to test how the positioning of the electrodes relative to the cell affected the degree of response nonlinearity. Currents passed through pairs of electrodes positioned near the cell body or far from the axon (>40 µ m) exhibited approximately linear summation in evoking spikes. Currents passed through pairs of electrodes close to the axon summed linearly when their locations along the axon were similar, and nonlinearly otherwise. Over a range of electrode placements, several distinct, localized spike initiation sites were observed, and the number of these sites covaried with the degree of response nonlinearity. Similar trends were observed for three-electrode stimuli. All of these trends in the simulation were consistent with experimental observations. Significance. These findings support the multi-site activation hypothesis for nonlinear activation of neurons, providing a biophysical interpretation of previous experimental results and potentially enabling more efficient use of multi-electrode stimuli in future neural implants., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objective: To present a remodeling of the electroretinogram waveform using a covariance matrix to identify regions of interest and distinction between a control and attention deficit/hyperactivity disorder (ADHD) group. Electroretinograms were recorded in n = 25 ADHD (16 male; age 11.9 ± 2.7 years) and n = 38 (8 male; age 10.4 ± 2.8 years neurotypical control participants as part of a broad study into the determining if the electroretinogram could be a biomarker for ADHD. Flash strengths of 0.6 and 1.2 log cd.s.m - 2 on a white 40 cd.m - 2 background were used. Averaged waveforms from each eye and flash strength were analyzed with Bayesian regularization of the covariance matrices using 100 equal length time intervals. The eigenvalues of the covariance matrices were ranked for each group to indicate the degree of complexity within the regularized waveforms., Results: The correlation matrices indicated less correlation within the waveforms for the ADHD group in time intervals beyond 70 msec. The eigenvalue plots suggest more complexity within the ADHD group compared to the control group. Consideration of the correlation structure between ERG waveforms from different populations may reveal additional features for identifying group differences in clinical populations., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Flinders University Human Research Ethical Committee (application number: 4606) and conformed to the principles of the declaration of Helsinki. Written informed consent was obtained from the parent/guardian for participants aged under 16 years of age or if older than 16 years of age from the individual. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Sensory neurons continually adapt their response characteristics according to recent stimulus history. However, it is unclear how such a reactive process can benefit the organism. Here, we test the hypothesis that adaptation actually acts proactively in the sense that it optimally adjusts sensory encoding for future stimuli. We first quantified human subjects' ability to discriminate visual orientation under different adaptation conditions. Using an information theoretic analysis, we found that adaptation leads to a reallocation of coding resources such that encoding accuracy peaks at the mean orientation of the adaptor while total coding capacity remains constant. We then asked whether this characteristic change in encoding accuracy is predicted by the temporal statistics of natural visual input. Analyzing the retinal input of freely behaving human subjects showed that the distribution of local visual orientations in the retinal input stream indeed peaks at the mean orientation of the preceding input history (i.e., the adaptor). We further tested our hypothesis by analyzing the internal sensory representations of a recurrent neural network trained to predict the next frame of natural scene videos (PredNet). Simulating our human adaptation experiment with PredNet, we found that the network exhibited the same change in encoding accuracy as observed in human subjects. Taken together, our results suggest that adaptation-induced changes in encoding accuracy prepare the visual system for future stimuli., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Mao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fish with unique life cycles offer valuable insights into retinal plasticity, revealing mechanisms of environmental adaptation, cell proliferation, and thus, potentially regeneration. The variability of the environmental factors to which Austrolebias annual fishes are exposed has acted as a strong selective pressure shaping traits such as nervous system plasticity. This has contributed to adaptation to their extreme conditions including the decreased luminosity as ponds dry out. In particular, the retina of A. charrua has been shown to respond to 30 days of decreased luminosity by exacerbating cell proliferation Now, we aimed to determine the cellular component of the retina involved in shorter-term responses. To this end, we performed 5-bromo-2'-deoxyuridine (BrdU) experiments, exposing adult fish to a short period (11 days) of constant darkness. Strikingly, in control conditions, neurogenesis in the inner nuclear and ganglion cell layer in the differentiated retina was detected. In constant darkness, we observed an effect on inner nuclear layer cell proliferation and changes in retinal cytoarchitecture of the retina with cell clusters located in the inner plexiform layer. Additionally, increased BLBP (brain lipid-binding protein) presence was detected in darkness, which has been previously associated with immature and reactivated Müller glia. Thus, our results suggest that the A. charrua retina can respond to environmental changes via rapid activation of progenitor cells in the INL, namely the Müller glia This leads us to hypothesize, that cell proliferation and neurogenesis might contribute to the responses to the functional needs of organisms, potentially playing an adaptive role., Competing Interests: Declaration of competing interest All authors have read and are abided by the statement of ethical standards for the present manuscripts. The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Primate vision relies on retinotopically organized cortical parcels defined by representations of hemifield (upper vs lower visual field), eccentricity (fovea vs periphery), and area (V1, V2, V3, V4). Here we test for functional signatures of these organizing principles. We used functional magnetic resonance imaging to measure responses to gratings varying in spatial frequency, color, and saturation across retinotopically defined parcels in two macaque monkeys, and we developed a Sparse Supervised Embedding (SSE) analysis to identify stimulus features that best distinguish cortical parcels from each other. Constraining the SSE model to distinguish just eccentricity representations of the voxels revealed the expected variation of spatial frequency and S-cone modulation with eccentricity. Constraining the model according to the dorsal/ventral location and retinotopic area of each voxel provided unexpected functional signatures, which we investigated further with standard univariate analyses. Posterior parcels (V1) were distinguished from anterior parcels (V4) by differential responses to chromatic and luminance contrast, especially of low-spatial-frequency gratings. Meanwhile, ventral parcels were distinguished from dorsal parcels by differential responses to chromatic and luminance contrast, especially of colors that modulate all three cone types. The dorsal/ventral asymmetry not only resembled differences between candidate dorsal and ventral subdivisions of human V4 but also extended to include all retinotopic visual areas, starting in V1 and increasing from V1 to V4. The results provide insight into the functional roles of different retinotopic areas and demonstrate the utility of SSE as a data-driven tool for generating hypotheses about cortical function and behavior., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Loggia et al.)

Retinal ganglion cells (RGCs) typically respond to light stimulation over their spatially restricted receptive field. Using large-scale recordings in the mouse retina, we show that a subset of non- direction-selective (DS) RGCs exhibit asymmetric activity, selective to motion direction, in response to a stimulus crossing an area far beyond the classic receptive field. The extraclassical response arises via inputs from an asymmetric distal zone and is enhanced by desensitization mechanisms and an inherent DS component, creating a network of neurons responding to motion toward the optic disc. Pharmacological manipulations revealed the necessity of glycinergic amacrine cells for this response. Using in vivo recordings, we identified similar extraclassical responses in lateral geniculate nucleus neurons, suggesting such non conventional DS information is transferred to downstream structures. Our results suggest a complex integration of motion direction processing across the visual field, which arises beyond the classical receptive field boundaries., Competing Interests: Competing interests statement:The authors declare no competing interest.

Motion perception is crucial to animal survival and effective environmental interactions. In mammals, detection of movement begins in the retina. Directionally selective (DS) retinal ganglion cells were first discovered in the rabbit eye, 1 and they have since been found in mouse, 2 , 3 cat, 4 and monkey. 5 , 6 These DS retinal neurons contact a small population of neurons in the visual thalamus (dorsal lateral geniculate nucleus [LGN]) that are highly DS. 7 , 8 , 9 , 10 The primary visual cortex (V1) also contains DS neurons, but whether directional selectivity in V1 emerges de novo 11 , 12 , 13 or is inherited from DS thalamic inputs 14 , 15 , 16 remains unclear. We previously found that LGN-DS neurons generate strong and focal synaptic currents in rabbit V1, similar to those generated by LGN concentric cells. 17 Thus, the synaptic drive generated by LGN-DS neurons in V1 is spatially well situated to influence the firing of layer 4 (L4) simple cells, most of which show strong directional selectivity. 18 However, two important questions remain: do LGN-DS neurons synaptically target DS simple cells in L4, and, if so, do they contribute to the directional preferences of these V1 DS neurons? We used spike-train cross-correlation analysis of pairs of LGN-DS and L4 simple cells to address these questions. We found that LGN-DS neurons do target L4 DS simple cells and that the targeting is highly selective, largely following a simple set of "connectivity rules." We conclude that this highly selective thalamocortical connectivity of LGN-DS neurons contributes to the sharp directional selectivity of cortical simple cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The neurovascular unit (NVU), comprising vascular, glial, and neural elements, supports the energetic demands of neural computation, but this aspect of the retina's trilaminar vessel network is poorly understood. Only the innermost vessel layer-the superficial vascular plexus (SVP)-is associated with astrocytes, like brain capillaries, whereas radial Müller glia interact with vessels in the other layers. Using serial electron microscopic reconstructions from mouse and primate retina, we find that Müller processes cover capillaries in a tessellating pattern, mirroring the wrapping of brain capillaries by tiled astrocytic endfeet. Gaps in the Müller sheath, found mainly in the intermediate vascular plexus (IVP), permit diverse neuron types to contact pericytes and the endothelial cells directly. Pericyte somata are a favored target, often at spine-like structures with reduced or absent vascular basement lamina. Focal application of ATP to the vitreal surface evoked Ca 2+ signals in Müller sheaths in all three vascular layers. Pharmacological experiments confirmed that Müller sheaths express purinergic receptors that, when activated, trigger intracellular Ca 2+ signals that are amplified by inositol triphosphate (IP 3 )-controlled intracellular Ca 2+ stores. When rod photoreceptors die in a mouse model of retinitis pigmentosa (rd10), Müller sheaths dissociate from the deep vascular plexus (DVP) but are largely unchanged within the IVP or SVP. Thus, Müller glia interact with retinal vessels in a laminar, compartmentalized manner: glial sheaths are virtually complete in the SVP but fenestrated in the IVP, permitting direct neurovascular contacts. In the DVP, the glial sheath is only modestly fenestrated and is vulnerable to photoreceptor degeneration., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

The human body is an intricate system, where diverse and complex signaling among different organs sustains physiological activities. The eye, as a primary organ for information acquisition, not only plays a crucial role in visual perception but also, as increasing evidence suggests, exerts a broad influence on the entire body through complex circuits upon receiving light signals which is called non-image-forming vision. However, the extent and mechanisms of light's impact on the body through the eyes remain insufficiently explored. There is also a dearth of comprehensive reviews elucidating the intricate interplay between light, the eye, and the systemic connections to the entire body. Herein, we propose the concept of the light-eye-body axis to systematically encapsulate the extensive non-image-forming effects of light signals received by the retina on the entire body. We reviewed the visual-neural structure basis of the light-eye-body axis, summarized the mechanism by which the eyes regulate the whole body and the current research status and challenges within the physiological and pathological processes involved in the light-eye-body axis. Future research should aim to expand the influence of the light-eye-body axis and explore its deeper mechanisms. Understanding and investigating the light-eye-body axis will contribute to improving lighting conditions to optimize health and guide the establishment of phototherapy standards in clinical practice., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Neuroprosthetics equipped with artificial synapses hold promise to address some most intricate medical problems, such as human sensory disorders. Yet, it is necessitated and of paramount importance for neuroprosthetics to be able to differentiate significant and insignificant signals. Here, we present an information-filterable artificial retina system that integrates artificial synapses with a signal-integration device for signal perception and processing with attention. The synaptic weight modulation is rendered through metal-organic framework (MOF) layers, where distinct short-term and long-term properties are predominantly determined by MOF's pore diameter and functionality. Specifically, four types of isoreticular Zr-based MOFs that share Zr 6 O 4 (OH) 4 secondary building units have been systematically examined. It is demonstrated that small pore diameters enhance short-term properties, while large pores, which are characterized by increased ion affinity, sustain long-term properties. Moreover, we demonstrated a 6 × 6 pixel artificial retina by incorporating both short-term and long-term artificial synapses with a signal-integration device. Signal summation by the signal-integration device enables attention-based information processing. The information-filterable artificial retina system developed here emulates human perception processes and holds promise in the fields of neuroprosthetics and advanced artificial intelligence., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Mammals do not possess the ability to spontaneously repair or regenerate damaged retinal tissue. In contrast to teleost fish which are capable of retina regeneration through the action of Müller glia, mammals undergo a process of reactive gliosis and scarring that inhibits replacement of lost neurons. Thus, it is important to discover novel methods for stimulating mammalian Müller glia to dedifferentiate and produce progenitor cells that can replace lost retinal neurons. Inducing an endogenous regenerative pathway mediated by Müller glia would provide an attractive alternative to stem cell injections or gene therapy approaches. Extracellular vesicles (EVs) are now recognized to serve as a novel form of cell-cell communication through the transfer of cargo from donor to recipient cells or by the activation of signaling cascades in recipient cells. EVs have been shown to promote proliferation and regeneration raising the possibility that delivery of EVs could be a viable treatment for visual disorders. Here, we provide protocols to isolate EVs for use in retina regeneration experiments., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The role of the vertebrate retina in early vision is generally described by the efficient coding hypothesis 1,2 , which predicts that the retina reduces the redundancy inherent in natural scenes 3 by discarding spatiotemporal correlations while preserving stimulus information 4 . It is unclear, however, whether the predicted decorrelation and redundancy reduction in the activity of ganglion cells, the retina's output neurons, hold under gaze shifts, which dominate the dynamics of the natural visual input 5 . We show here that species-specific gaze patterns in natural stimuli can drive correlated spiking responses both in and across distinct types of ganglion cells in marmoset as well as mouse retina. These concerted responses disrupt redundancy reduction to signal fixation periods with locally high spatial contrast. Model-based analyses of ganglion cell responses to natural stimuli show that the observed response correlations follow from nonlinear pooling of ganglion cell inputs. Our results indicate cell-type-specific deviations from efficient coding in retinal processing of natural gaze shifts., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

To track moving targets, humans move their eyes using both saccades and smooth pursuit. If pursuit eye movements fail to accurately track the moving target, catch-up saccades are initiated to rectify the tracking error. It is well known that retinal position and velocity errors determine saccade latency and amplitude, but the extent to which retinal acceleration error influences these aspects is not well quantified. To test this, 13 adult human participants performed an experiment where they pursued accelerating/decelerating targets. During the ongoing pursuit, we introduced a randomly sized target step to evoke a catch-up saccade and analyzed its latency and amplitude. We observed that retinal acceleration error (computed over a 200 ms range centered 100 ms before the saccade) was a statistically significant predictor of saccade amplitude and latency. A multiple linear regression supported our hypothesis that retinal acceleration errors influence saccade amplitude in addition to the influence of retinal position and velocity errors. We also found that saccade latencies were shorter when retinal acceleration error increased the tracking error and vice versa. In summary, our findings support a model in which retinal acceleration error is used to compute a predicted position error ∼100 ms into the future to trigger saccades and determine saccade amplitude. NEW & NOTEWORTHY When visually tracking object motion, humans combine smooth pursuit and saccadic eye movements to maintain the target image on the fovea. Retinal position and velocity errors are known to determine catch-up saccade amplitude and latency, however, it is unknown if retinal acceleration error is also used to predict future target position. This study provides evidence of a small but statistically significant contribution of retinal acceleration error in determining saccade amplitude and latency.

Deciphering the connectome, the ensemble of synaptic connections that underlie brain function, is a central goal of neuroscience research. Here we report the in vivo mapping of connections between presynaptic and postsynaptic partners in zebrafish, by adapting the trans-Tango genetic approach that was first developed for anterograde transsynaptic tracing in Drosophila. Neural connections were visualized between synaptic partners in larval retina, brain and spinal cord and followed over development. The specificity of labeling was corroborated by functional experiments in which optogenetic activation of presynaptic spinal cord interneurons elicited responses in known motor neuronal postsynaptic targets, as measured by trans-Tango-dependent expression of a genetically encoded calcium indicator or by electrophysiology. Transsynaptic signaling through trans-Tango reveals synaptic connections in the zebrafish nervous system, providing a valuable in vivo tool to monitor and interrogate neural circuits over time., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The midget pathway of the primate retina provides the visual system with the foundations for high spatial resolution and color perception. An essential contributor to these properties is center-surround organization, in which responses from the central area of a cell's receptive field are antagonized by responses from a surrounding area. Two key questions about center-surround organization are unresolved. First, the surround is largely or completely due to negative feedback from horizontal cells to cones: how can this feedback be reconciled with the popular difference of Gaussians (DOG) model, which implies feedforward inhibition? Second, can the spatial extent of center and surround be predicted from the components-optics, horizontal cell receptive field, ganglion cell dendrites-that give rise to them? We address these questions with a computational model of midget pathway signal processing in macaque retina; model parameters are derived from published literature. We show that, contrary to the DOG model, the surround's effect is better treated as divisive. A simplified version of our model-a ratio of Gaussians (ROG) model-has practical advantages over the DOG, such as accounting for spatiotemporal interactions and pulse responses. The ROG model also shows that both center and surround radii can be calculated from a sum of squared radii of their components. Finally, chromatic antagonism between center and surround in the full model predicts cone opponency as a function of eccentricity. We suggest that a signal-processing model gives new insight into retinal function. NEW & NOTEWORTHY We simulated signal processing from cones to midget ganglion cells in the monkey retina and found that: 1 ) center/surround structure is better described as a ratio of Gaussian functions than as the traditional difference of Gaussians; 2 ) ganglion cell center and surround radii can be calculated from a sum of squares of radii in upstream stages; 3 ) the model can predict chromatic dominance in the center and surround mechanisms as a function of eccentricity.

Signal amplitudes obtained from retinal scanning depend on numerous factors. Working with polarized light to interrogate the retina, large parts of which are birefringent, is even more prone to artifacts. This article demonstrates the necessity of using normalization when working with retinal birefringence scanning signals in polarization-sensitive ophthalmic instruments. After discussing the pros and cons of employing a normalization signal obtained by means of added optoelectronic hardware, the study shifts over and focuses on a numerical normalization method based on merely the s - and p -polarization components without additional optical or electronic hardware. This minimizes the adverse effects of optical asymmetries, the presence of certain instrumental noise, device-to-device variability, pupil diameter, retinal reflectivity, subject-to-subject variations, the position of the eye in the exit pupil of the device, and even signal degradation by cataracts. Results were experimentally and numerically tested on human data from 15 test subjects and clearly demonstrated the signal standardization achieved by numerical normalization. This is expected to lead to substantial improvement in algorithms and decision-making software, especially in ophthalmic screening instruments for pediatric applications, without added hardware cost. The proposed normalization method is also applicable to other polarization-sensitive optical instruments.

Everything that the brain sees must first be encoded by the retina, which maintains a reliable representation of the visual world in many different, complex natural scenes while also adapting to stimulus changes. This study quantifies whether and how the brain selectively encodes stimulus features about scene identity in complex naturalistic environments. While a wealth of previous work has dug into the static and dynamic features of the population code in retinal ganglion cells (RGCs), less is known about how populations form both flexible and reliable encoding in natural moving scenes. We record from the larval salamander retina responding to five different natural movies, over many repeats, and use these data to characterize the population code in terms of single-cell fluctuations in rate and pairwise couplings between cells. Decomposing the population code into independent and cell-cell interactions reveals how broad scene structure is encoded in the retinal output. while the single-cell activity adapts to different stimuli, the population structure captured in the sparse, strong couplings is consistent across natural movies as well as synthetic stimuli. We show that these interactions contribute to encoding scene identity. We also demonstrate that this structure likely arises in part from shared bipolar cell input as well as from gap junctions between RGCs and amacrine cells., Competing Interests: Competing interests statement:The authors declare no competing interest.

Eye tracking has emerged as a key method for understanding how animals process visual information, identifying crucial elements of perception and attention. Traditional fish eye tracking often alters animal behavior due to invasive techniques, while non-invasive methods are limited to either 2D tracking or restricting animals after training. Our study introduces a non-invasive technique for tracking and reconstructing the retinal view of free-swimming fish in a large 3D arena without behavioral training. Using 3D fish bodymeshes reconstructed by DeepShapeKit, our method integrates multiple camera angles, deep learning for 3D fish posture reconstruction, perspective transformation, and eye tracking. We evaluated our approach using data from two fish swimming in a flow tank, captured from two perpendicular viewpoints, and validated its accuracy using human-labeled and synthesized ground truth data. Our analysis of eye movements and retinal view reconstruction within leader-follower schooling behavior reveals that fish exhibit negatively synchronised eye movements and focus on neighbors centered in the retinal view. These findings are consistent with previous studies on schooling fish, providing a further, indirect, validation of our method. Our approach offers new insights into animal attention in naturalistic settings and potentially has broader implications for studying collective behavior and advancing swarm robotics., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Orientation is one of the most salient features in visual scenes. Neurons at multiple levels of the visual system detect orientation, but in many cases, the underlying biophysical mechanisms remain unresolved. Here, we studied mechanisms for orientation detection at the earliest stage in the visual system, in B/K wide-field amacrine cells (B/K WACs), a group of giant, nonspiking interneurons in the mouse retina that coexpress Bhlhe22 (B) and Kappa Opioid Receptor (K). B/K WACs exhibit orientation-tuned calcium signals along their long, straight, unbranching dendrites, which contain both synaptic inputs and outputs. Simultaneous dendritic calcium imaging and somatic voltage recordings reveal that individual B/K dendrites are electrotonically isolated, exhibiting a spatially confined yet extended receptive field along the dendrite, which we term "compartmentalized pooling." Further, the receptive field of a B/K WAC dendrite exhibits center-surround antagonism. Phenomenological receptive field models demonstrate that compartmentalized pooling generates orientation selectivity, and center-surround antagonism shapes band-pass spatial frequency tuning. At the microcircuit level, B/K WACs receive excitation driven by one contrast polarity (e.g., "ON") and glycinergic inhibition driven by the opposite polarity (e.g., "OFF"). However, this "crossover" inhibition is not essential for generating orientation selectivity. A minimal biophysical model reproduced compartmentalized pooling from feedforward excitatory inputs combined with a substantial increase in the specific membrane resistance between somatic and dendritic compartments. Collectively, our results reveal the biophysical mechanism for generating orientation selectivity in dendrites of B/K WACs, enriching our understanding of the diverse strategies employed throughout the visual system to detect orientation., Competing Interests: Competing interests statement:The authors declare no competing interest.

Determining the location of objects relative to ourselves is essential for interacting with the world. Neural activity in the retina is used to form a vision-independent model of the local spatial environment relative to the body. For example, when an animal navigates through a forest, it rapidly shifts its gaze to identify the position of important objects, such as a tree obstructing its path. This seemingly trivial behavior belies a sophisticated neural computation. Visual information entering the brain in a retinocentric reference frame must be transformed into an egocentric reference frame to guide motor planning and action. This, in turn, allows the animal to extract the location of the tree and plan a path around it. In this review, we explore the anatomical, physiological, and computational implementation of retinocentric-to-egocentric reference frame transformations - a research area undergoing rapid progress stimulated by an ever-expanding molecular, physiological, and computational toolbox for probing neural circuits. We begin by summarizing evidence for retinocentric and egocentric reference frames in the brains of diverse organisms, from insects to primates. Next, we cover how distance estimation contributes to creating a three-dimensional representation of local space. We then review proposed implementations of reference frame transformations across different biological and artificial neural networks. Finally, we discuss how an internal egocentric model of the environment is maintained independently of the sensory inputs from which it is derived. By comparing findings across a variety of nervous systems and behaviors, we aim to inspire new avenues for investigating the neural basis of reference frame transformation, a canonical computation critical for modeling the external environment and guiding goal-directed behavior., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: High density microelectrode arrays (HD-MEAs) are now widely used for both in-vitro and in-vivo recordings, as they allow spikes from hundreds of neurons to be recorded simultaneously. Since extracellular recordings do not allow visualization of the recorded neurons, algorithms are needed to estimate their physical positions, especially to track their movements when the are drifting away from recording devices., New Method: The objective of this study was to evaluate the performance of multiple algorithms for neuron localization solely from extracellular traces (MEA recordings), either artificial or obtained from mouse retina. The algorithms compared included center-of-mass, monopolar, and grid-based algorithms. The first method is a barycenter calculation. The second algorithm infers the position of the cell using triangulation with the assumption that the neuron behaves as a monopole. Finally, grid-based methods rely on comparing the recorded spike with a projection of spikes of hypothetical neurons with different positions., Results: The Grid-Based algorithm yielded the most satisfactory outcomes. The center-of-mass exhibited a minimal computational cost, yet its average localization was suboptimal. Monopolar algorithms gave cell localizations with an average error of less than 10μm, but they had considerable variability and a high computational cost. For the grid-based method, the variability was smaller, with satisfactory performance and low computational cost., Comparison With Existing Method(s): The accuracy of the different localization methods benchmarked in this article had not been properly tested with ground-truth recordings before., Conclusion: The objective of this article is to provide guidance to researchers on the selection of optimal methods for localizing neurons based on MEA recordings., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The evolutionary origin of the inverted retina in the vertebrate eye is unknown. This paper explores a hypothetical evolutionary scenario that explains the unique orientation of the photoreceptors in the vertebrate retina. The proposed scenario follows the scientific accepted scenario for eye evolution and gradually builds up towards an eye prototype by considering light direction detection and increase in achievable spatial resolution as the driving forces. It suggests that eye retinas developed along two different morphological processes, an evagination process that results in the inverted retina in vertebrate eyes and an invagination process that results in a verted retina in cephalopod eyes. The development of the inverted vertebrate retina and eye prototype morphology is strongly substantiated by physics of vision. The proposed evolutionary sequence for vertebrate eye development is simple and has the full potential to explain the origin of the inverted retina and leads to an eye prototype enabling visual detection and orientation. It allows the emergence of eye structures like, extraocular muscles, tapetum lucidum, biconvex lens, cornea, and pupil. This study supports the suggestion that a primitive inverted retina in the predecessor of vertebrates is of ectodermal origin and available before neurulation occurred., (© 2024. The Author(s).)

Saccadic eye movements successively project the saccade target on two retinal locations: a peripheral one before the saccade, and the fovea after the saccade. Typically, performance in discriminating stimulus features changes between these two projections is very poor. However, a short (∼200 ms) blanking of the target upon saccade onset drastically improves performance, demonstrating that a precise signal of the peripheral projection is retained during the saccade. Although little is known about the nature of that transsaccadic signal, previous reports conjectured that it relies on information processed by the magnocellular system. Across two experiments, we investigated the feature blanking effect for a wide range of spatial frequencies (0.5-8 cycles per degree of visual angle, dva), stimulus sizes (1-4 dva), and eccentricities (6-10 dva). In each trial, participants executed a saccade to a high-contrast grating presented either left or right of fixation. During the saccade, the grating changed orientation (clockwise or counter-clockwise) either instantaneously or after a 200-ms blank, and participants reported the change's direction. We contrasted this saccade condition with a trans-retinal fixation condition mimicking the peripheral-then-foveal sequence of the target stimulus occurring across a saccade. Remarkably, blanking improved performance reliably for each spatial frequency, stimulus size, and eccentricity, but only in the saccade condition. Performance with blanking in saccade trials systematically exceeded performance in the fixation condition. Our results demonstrate a robust feature blanking effect across saccades, suggesting that transsaccadic processes involve low-level visual features beyond those processed in the magnocellular system. NEW & NOTEWORTHY Across a saccadic eye movement, the visual system is able to keep track of the signals carrying the visual features of a saccade target. We provide evidence that these signals are sensitive to a wide range of stimulus sizes, can use a wide range spatial frequencies channels and, operate at various saccade amplitudes. Our results suggest an underlying mechanism operating beyond the magnocellular pathway that is contingent to saccade execution.

Clinical results with photovoltaic subretinal prosthesis (PRIMA) demonstrated restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution matching the 100 μm pixel size. Since scaling the pixels below 75 μm in the current bipolar planar geometry will significantly limit the penetration depth of the electric field and increase stimulation threshold, we explore the possibility of using smaller pixels based on a novel 3-dimensional honeycomb-shaped design. We assessed the long-term biocompatibility and stability of these arrays in rats by investigating the anatomical integration of the retina with flat and 3D implants and response to electrical stimulation over lifetime - up to 32-36 weeks post-implantation in aged rats. With both flat and 3D implants, signals elicited in the visual cortex decreased after the day of implantation by more than 3-fold, and gradually recovered over the next 12-16 weeks. With 25 μm high honeycomb walls, the majority of bipolar cells migrate into the wells, while amacrine and ganglion cells remain above the cavities, which is essential for selective network-mediated stimulation of the retina. Retinal thickness and full-field stimulation threshold with 40 μm-wide honeycomb pixels were comparable to those with planar devices - 0.05 mW/mm 2 with 10 ms pulses. However, fewer cells from the inner nuclear layer migrated into the 20 μm-wide wells, and stimulation threshold increased over 12-16 weeks, before stabilizing at about 0.08 mW/mm 2 . Such threshold is still significantly lower than 1.8 mW/mm 2 with a previous design of flat bipolar pixels, confirming the promise of the 3D honeycomb-based approach to high resolution subretinal prosthesis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Daniel Palanker reports financial support was provided by National Institutes of Health. Daniel Palanker reports financial support was provided by U.S. Department of Defense. Daniel Palanker reports financial support was provided by Air Force Office of Scientific Research. Daniel Palanker reports a relationship with Pixium Vision that includes: consulting or advisory. Ted Kamins reports a relationship with Pixium Vision that includes: consulting or advisory. Daniel Palanker has patent licensed to Pixium Vision. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

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Diabetic retinopathy (DR) is one of the leading causes of blindness in the world. While there is a major focus on the study of juvenile/adult DR, the effects of hyperglycemia during early retinal development are less well studied. Recent studies in embryonic zebrafish models of nutritional hyperglycemia (high-glucose exposure) have revealed that hyperglycemia leads to decreased cell numbers of mature retinal cell types, which has been related to a modest increase in apoptotic cell death and altered cell differentiation. However, how embryonic hyperglycemia impacts cell proliferation in developing retinas still remains unknown. Here, we exposed zebrafish embryos to 50 mM glucose from 10 h postfertilization (hpf) to 5 days postfertilization (dpf). First, we confirmed that hyperglycemia increases apoptotic death and decreases the rod and Müller glia population in the retina of 5-dpf zebrafish. Interestingly, the increase in cell death was mainly observed in the ciliary marginal zone (CMZ), where most of the proliferating cells are located. To analyze the impact of hyperglycemia in cell proliferation, mitotic activity was first quantified using pH3 immunolabeling, which revealed a significant decrease in mitotic cells in the retina (mainly in the CMZ) at 5 dpf. A significant decrease in cell proliferation in the outer nuclear and ganglion cell layers of the central retina in hyperglycemic animals was also detected using the proliferation marker PCNA. Overall, our results show that nutritional hyperglycemia decreases cellular proliferation in the developing retina, which could significantly contribute to the decline in the number of mature retinal cells. [ABSTRACT FROM AUTHOR]

Objectives: Myopia is a common ocular disorder worldwide, leading to degenerative changes in the retina which is highly susceptible to vascular impairment. The aim of the study was to investigate the effects of pathological retinal changes on the retinal capillary structures using optical coherence tomography angiography (OCTA) in myopic patients. Methods: Thirty-two patients with high myopia (HM), 29 patients with pathological myopia (PM), and 38 healthy subjects with emmetropia (EM) were enrolled in this study. OCTA was performed to measure the following parameters: Foveal avascular zone (FAZ) area; FAZ perimeter; FAZ acircularity index (AI); and superficial, deep, and radial peripapillary capillary (RPC) vessel densities. Axial length (AL), spherical equivalent, and anterior chamber depth were evaluated. Results: Significant differences in the mean AL values were observed between the EM group and the other groups (p<0.001 for all); however, no significant differences were observed between the HM and PM groups (p=0.135). Significant differences in FAZ parameters, except for AI, were found among the three groups (p<0.05 for all). In all regions, except for the fovea and inside disc, the capillary plexus vessel densities were significantly lower in the PM group than in the other groups and were lower in the HM group than in the EM group (p<0.05 for all). Conclusion: Significant differences identified in capillary densities between the HM and PM groups, both of which present similar AL measurements, suggest that pathological retinal findings have significant effects on retinal perfusion independent of the effect of AL. [ABSTRACT FROM AUTHOR]

Detecting 3D symmetry is important for the human visual system because many objects in our everyday life are 3D symmetrical. Many are 3D mirror-symmetrical and others are 3D rotational-symmetrical. But note that their retinal images are 2D symmetrical only in degenerate views. It has been suggested that a human observer can detect 3D mirror-symmetry even from a 2D retinal image of a 3D mirror-symmetrical pair of contours. There are model-based invariants of the 3D mirror-symmetrical pair of contours in the retinal image and there are additional invariant features when the contours are individually planar. There are also model-based invariants of a 3D rotational-symmetrical pair of contours. These invariant features of 3D mirror-symmetry and rotational-symmetry are analogous to one another but the features of 3D rotational-symmetry are computationally more difficult than the features of 3D mirror-symmetry. Experiment 1 showed that only 3D mirror-symmetry could be detected reliably while the detection of 3D rotational-symmetry was close to chance-level. Experiment 2 showed that the detection of 3D mirror-symmetry is partly based on the model-based invariants of 3D mirror-symmetry and the planarity of the contours. These results show that the visual system has evolved to favour the perception of 3D mirror-symmetry. [ABSTRACT FROM AUTHOR]