Contrast Sensitivity of ON and OFF Human Retinal Pathways in Myopia.

The human visual cortex processes light and dark stimuli with ON and OFF pathways that are differently modulated by luminance contrast. We have previously demonstrated that ON cortical pathways have higher contrast sensitivity than OFF cortical pathways and the difference increases with luminance range (defined as the maximum minus minimum luminance in the scene). Here, we demonstrate that these ON-OFF cortical differences are already present in the human retina and that retinal responses measured with electroretinography are more affected by reductions in luminance range than cortical responses measured with electroencephalography. Moreover, we show that ON-OFF pathway differences measured with electroretinography become more pronounced in myopia, a visual disorder that elongates the eye and blurs vision at far distance. We find that, as the eye axial length increases across subjects, ON retinal pathways become less responsive, slower in response latency, less sensitive, and less effective and slower at driving pupil constriction. Based on these results, we conclude that myopia is associated with a deficit in ON pathway function that decreases the ability of the retina to process low contrast and regulate retinal illuminance in bright environments.

Differential cortical and subcortical visual processing with eyes shut.

Closing our eyes largely shuts down our ability to see. That said, our eyelids still pass some light, allowing our visual system to coarsely process information about visual scenes, such as changes in luminance. However, the specific impact of eye closure on processing within the early visual system remains largely unknown. To understand how visual processing is modulated when eyes are shut, we used functional magnetic resonance imaging (fMRI) to measure responses to a flickering visual stimulus at high (100%) and low (10%) temporal contrasts, while participants viewed the stimuli with their eyes open or closed. Interestingly, we discovered that eye closure produced a qualitatively distinct pattern of effects across the visual thalamus and visual cortex. We found that with eyes open, low temporal contrast stimuli produced smaller responses across the lateral geniculate nucleus (LGN), primary (V1) and extrastriate visual cortex (V2). However, with eyes closed, we discovered that the LGN and V1 maintained similar blood oxygenation level-dependent (BOLD) responses as the eyes open condition, despite the suppressed visual input through the eyelid. In contrast, V2 and V3 had strongly attenuated BOLD response when eyes were closed, regardless of temporal contrast. Our findings reveal a qualitatively distinct pattern of visual processing when the eyes are closed-one that is not simply an overall attenuation but rather reflects distinct responses across visual thalamocortical networks, wherein the earliest stages of processing preserve information about stimuli but are then gated off downstream in visual cortex.NEW & NOTEWORTHY When we close our eyes coarse luminance information is still accessible by the visual system. Using functional magnetic resonance imaging, we examined whether eyelid closure plays a unique role in visual processing. We discovered that while the LGN and V1 show equivalent responses when the eyes are open or closed, extrastriate cortex exhibited attenuated responses with eye closure. This suggests that when the eyes are closed, downstream visual processing is blind to this information.

The execution of saccadic eye movements suppresses visual processing of both color and luminance in the early visual cortex of humans.

Our eyes execute rapid, directional movements known as saccades, occurring several times per second, to focus on objects of interest in our environment. During these movements, visual sensitivity is temporarily reduced. Despite numerous studies on this topic, the underlying mechanism remains elusive, including a lingering debate on whether saccadic suppression affects the parvocellular visual pathway. To address this issue, we conducted a study employing steady-state visual evoked potentials (SSVEPs) elicited by chromatic and luminance stimuli while observers performed saccadic eye movements. We also employed an innovative analysis pipeline to enhance the signal-to-noise ratio, yielding superior results compared to the previous method. Our findings revealed a clear suppression effect on SSVEP signals during saccades compared to fixation periods. Notably, this suppression effect was comparable for both chromatic and luminance stimuli. We went further to measure the suppression effect across various contrast levels, which enabled us to model SSVEP responses with contrast response functions. The results suggest that saccades primarily reduce response gain without significantly affecting contrast gain and that this reduction applies uniformly to both chromatic and luminance pathways. In summary, our study provides robust evidence that saccades similarly suppress visual processing in both the parvocellular and magnocellular pathways within the human early visual cortex, as indicated by SSVEP responses. The observation that saccadic eye movements impact response gain rather than contrast gain implies that they influence visual processing through a multiplicative mechanism.NEW & NOTEWORTHY The present study demonstrates that saccadic eye movements reduce the processing of both luminance and chromatic stimuli in the early visual cortex of humans. By modeling the contrast response function, the study further shows that saccades affect visual processing by reducing the response gain rather than altering the contrast gain, suggesting that a multiplicative mechanism of visual attenuation affects both parvocellular and magnocellular pathways.

Human perception of flicker-fused letters that are luminance balanced.

The Talbot-Plateau law specifies what combinations of flash frequency, duration, and intensity will yield a flicker-fused stimulus that matches the brightness of a steady stimulus. It has proven to be remarkably robust in its predictions, and here we provide additional support though the use of a contrast discrimination task. However, we also find that the visual system can register flicker-fused letters when the combination of frequency and duration is relatively low. The letters are recognized even though they have the same physical luminance as background. We hypothesize that the letters elicit synchronous oscillations that encode for stimulus attributes, which prevents the letter from blending into the background.

Assessment of Visual Function with Cotoretigene Toliparvovec in X-Linked Retinitis Pigmentosa in the Randomized XIRIUS Phase 2/3 Study.

PURPOSE: Cotoretigene toliparvovec (BIIB112/AAV8-RPGR) is an investigational vector-based gene therapy designed to provide a full-length, codon-optimized retinitis pigmentosa GTPase regulator (RPGR) protein to individuals with RPGR-associated X-linked retinitis pigmentosa (XLRP). We assessed efficacy and tolerability of cotoretigene toliparvovec subretinal gene therapy. DESIGN: Part 2 of the XIRIUS trial (ClinicalTrials.gov identifier, NCT03116113) was a phase 2/3, 12-month, randomized (1:1:1) dose-expansion study. PARTICIPANTS: Male patients ≥10 years of age with RPGR-associated XLRP were included. METHODS: Participants were randomized 1:1:1 to receive low-dose subretinal cotoretigene toliparvovec (5 × 1010 vector genomes/eye), high-dose cotoretigene toliparvovec (2.5 × 1011 vector genomes/eye) or to be an untreated control participant. MAIN OUTCOME MEASURES: The primary end point was the percentage of participants meeting microperimetry responder criteria (≥ 7-dB improvement at ≥ 5 of 16 central loci). Secondary end points included change from baseline in retinal sensitivity at the central 16 loci and the entire 68 loci at 12 months and change from baseline in low-luminance visual acuity (LLVA) at 12 months, as well as the proportion of eyes with a ≥ 15-Early Treatment Diabetic Retinopathy Study ETDRS letter LLVA and ≥ 10-ETDRS letter LLVA change from baseline at month 12. RESULTS: Because of the impact of the COVID-19 pandemic, enrollment ended before reaching the initial target, leaving the trial underpowered. Twenty-nine participants were included (low-dose group, n = 10; high-dose group, n = 10; control group, n = 9). At month 12, the percentage of participants meeting microperimetry responder criteria was not significantly different between either cotoretigene toliparvovec group (low dose, 37.5% [P = 0.3181]; high dose, 25.0% [P = 0.5177]) and the control group (22.2%). However, the mean change from baseline in microperimetry sensitivity improved significantly with the low-dose group versus the control group at month 12 (P = 0.0350). Significant improvement in LLVA occurred in the low-dose group versus the control group at month 12 (33.3% difference [80% confidence interval, 14.7%-55.2%]; P = 0.0498). Three ocular-related serious adverse events (SAEs) occurred in the low-dose group versus 7 SAEs in the high-dose group. CONCLUSIONS: The primary microperimetry end point was not met. Significant improvements in LLVA and mean microperimetry were observed compared with controls and fewer SAEs occured with low-dose compared with high dose cotoretigene toliparvovec. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Development and Valuation of a Preference-Weighted Measure in Age-Related Macular Degeneration From the Vision Impairment in Low Luminance Questionnaire: A MACUSTAR Report.

OBJECTIVES: This study generates VILL-UI (Vision Impairment in Low Luminance - Utility Index), a preference-weighted measure (PWM) derived from the VILL-33 measure for use in patients with age-related macular degeneration (AMD) and valued to generate United Kingdom and German preference weights. METHODS: A PWM consists of a classification system to describe health and utility values for every state described by the classification. The classification was derived using existing data collected as part of the MACUSTAR study, a low-interventional study on AMD, conducted at 20 clinical sites across Europe. Items were selected using psychometric and Rasch analyses, published criteria around PWM suitability, alongside instrument developer views and concept elicitation work that informed VILL-33 development. An online discrete choice experiment (DCE) with duration of the health state was conducted with the United Kingdom and German public. Responses were modeled to generate utility values for all possible health states. RESULTS: The classification system has 5 items across the 3 domains of VILL-33: reading and accessing information, mobility and safety, and emotional well-being. The DCE samples (United Kingdom: n = 1004, Germany: n = 1008) are broadly representative and demonstrate good understanding of the tasks. The final DCE analyses produce logically consistent and significant coefficients. CONCLUSIONS: This study enables responses to VILL-33 to be directly used to inform economic evaluation in AMD. The elicitation of preferences from both United Kingdom and Germany enables greater application of VILL-UI for economic evaluation throughout Europe. VILL-UI fills a gap in AMD in which generic preference-weighted measures typically lack sensitivity.

Ambient lighting alters pattern electroretinogram P50 peak time and spatial sensitivity.

PURPOSE: Our aim was to explore the effect of ambient lighting on the pattern ERG (PERG). METHODS: We compared PERGs recorded in two conditions; room lights on and room lights off. PERGs from 21 adult participants were recorded from each eye to high contrast checks of 50' side width, reversing 3rps in a large (30°) and then standard (15°) field. This was performed first in lights-ON conditions, then 2 min after the room lights were switched off. A minimum of 2 averages of 300 trials were acquired for each condition. A subset of 10 participants had PERGs recorded to a 50' check width with a range of stimulus contrasts (96-18%), also to a range of different check widths (100'-12') at high contrast in both ambient lighting conditions in a 30° field. RESULTS: The lights-ON P50 median peak time (PT) was 3 ms earlier than the lights-OFF P50 from the 30° field (range 0-5 ms) and 15° field (range 0-6 ms). The earlier lights-ON P50 PT was evident at different stimulus contrasts, even after accounting for stimulus contrast reductions associated with stray ambient lighting in lights-ON conditions. Lights-OFF and lights-ON P50 PT were similar to different check widths; the lights-OFF P50 PT to a 50' check width matched the lights-ON P50 PT to a 25' check width. CONCLUSION: PERG P50 PT in lights-ON ambient light conditions can be earlier than in lights-OFF ambient light conditions. The difference in P50 PT with ambient light may reflect alterations in spatial sensitivity associated with retinal adaptation. These results emphasise the clinical importance of consistent ambient lighting for PERG recording and calibration.

Retinex theory-based nonlinear luminance enhancement and denoising for low-light endoscopic images.

BACKGROUND: The quality of low-light endoscopic images involves applications in medical disciplines such as physiology and anatomy for the identification and judgement of tissue structures. Due to the use of point light sources and the constraints of narrow physiological structures, medical endoscopic images display uneven brightness, low contrast, and a lack of texture information, presenting diagnostic challenges for physicians. METHODS: In this paper, a nonlinear brightness enhancement and denoising network based on Retinex theory is designed to improve the brightness and details of low-light endoscopic images. The nonlinear luminance enhancement module uses higher-order curvilinear functions to improve overall brightness; the dual-attention denoising module captures detailed features of anatomical structures; and the color loss function mitigates color distortion. RESULTS: Experimental results on the Endo4IE dataset demonstrate that the proposed method outperforms existing state-of-the-art methods in terms of Peak Signal-to-Noise Ratio (PSNR), Structural Similarity (SSIM), and Learned Perceptual Image Patch Similarity (LPIPS). The PSNR is 27.2202, SSIM is 0.8342, and the LPIPS is 0.1492. It provides a method to enhance image quality in clinical diagnosis and treatment. CONCLUSIONS: It offers an efficient method to enhance images captured by endoscopes and offers valuable insights into intricate human physiological structures, which can effectively assist clinical diagnosis and treatment.

Field comparison of broad-spectrum white LED-baited traps with narrow-spectrum green LED-baited traps in the capture of Anopheles mosquitoes (Diptera: Culicidae).

Light-Emitting Diodes (LEDs) have been effective light sources in attracting Anopheles mosquitoes, but the broad-spectrum white light, even with a wide-ranging application in lighting, have not been evaluated yet. In this study, the white light was field evaluated against the green one in the light trapping of anopheline mosquitoes by using two non-suction Silva traps and two CDC-type suction light traps. Anopheline mosquitoes were captured for two 21-night periods of collecting (2022 and 2023). In the first period, two LEDs were used per Silva trap, but three were used in the second one to increase the luminance/illuminance at traps. A CDC-type suction light trap equipped with an incandescent lamp was used in 2022 and a CDC-type suction light trap equipped with a 6 V-white light (higher luminance/illuminance) in 2023. A total of eight species and 3,289 specimens were captured in both periods. The most frequent species were Anopheles triannulatus s.l., An. goeldii, An. evansae and An. argyritarsis. In 2022, white LEDs were less attractive to anopheline mosquitoes than the other light sources, but without statistical difference among treatments (F = 2.703; P = 0.0752; df = 2). In 2023, even with an increased luminance/illuminance at traps, no statistical difference was found between the two LED-baited Silva traps (F = 6.690; P = 0.0024; df = 2), but rather between the 6 V-white-baited CDC-type suction light trap and green-baited Silva traps. Due to some drawbacks and the lower abundance of individuals caught by using white LEDs, the narrow-banded green LEDs is preferable to white ones for attracting anophelines.

Optical design of low-location illumination based on asymmetric double freeform surfaces.

The development of optical optics for low-location road lighting is a challenging problem in providing high luminance and uniformity of illumination and meeting many other specific requirements. This study proposes an optical design method of low-location illumination based on an asymmetric double freeform surface lens. The ray emitted from the light source is refracted and reflected through the different surface types to the corresponding area of the receiving surface. In the design example, the road has dual-side mounted luminaires and a width of 6 m, and a height of 0.8 m. Simulation results indicate that, compared with conventional high-pole streetlights, the luminance uniformity had increased from 0.60 to 0.66, the illuminance uniformity had improved from 0.75 to 0.86, and the glare had been reduced.

Estimation of spectral similarities utilizing segmented regions' probability distribution in the block-optimized pan-sharpened image for material classification.

Pan-sharpening is an image fusion approach that combines the spectral information in multispectral (MS) images with the spatial properties of PAN (Panchromatic) images. This vital technique is used in categorization, detection, and other remote sensing applications. In the first step, the article focuses on increasing the finer spatial details in the MS image with PAN images using two levels of fusion without causing spectral deterioration. The suggested fusion method efficiently utilizes image transformation techniques and spatial domain image fusion methods. The luminance component of MS images typically contains spatial features that are not as detailed as the PAN images. A multiscale transform is applied to the intensity/luminance component and PAN image to introduce features into the intensity component. In the first level of processing, coefficients obtained from the non-subsampled contourlet transform are subjected to particle swarm optimization weighted block-based fusion. The second level of fusion is carried out using the concept of spatial frequency to reduce spectral distortion. Numerous reference and non-reference parameters are used to evaluate the sharpened image's quality. In the next step, the article focuses on designing an evaluation metric for analysing spectral distortion based on the Bhattacharyya coefficient and distance. The Bhattacharyya coefficient and distance are calculated for each segmented region to assess the sharpened images' quality. Spectral degradation analysis using proposed techniques can also be useful for analysing materials in the segmented regions. The research findings demonstrate that the spatial features of fused images obtained from the proposed technique increased with the least spectral degradation.

Underwater Image Enhancement Based on Luminance Reconstruction by Multi-Resolution Fusion of RGB Channels.

Underwater image enhancement technology is crucial for the human exploration and exploitation of marine resources. The visibility of underwater images is affected by visible light attenuation. This paper proposes an image reconstruction method based on the decomposition-fusion of multi-channel luminance data to enhance the visibility of underwater images. The proposed method is a single-image approach to cope with the condition that underwater paired images are difficult to obtain. The original image is first divided into its three RGB channels. To reduce artifacts and inconsistencies in the fused images, a multi-resolution fusion process based on the Laplace-Gaussian pyramid guided by a weight map is employed. Image saliency analysis and mask sharpening methods are also introduced to color-correct the fused images. The results indicate that the method presented in this paper effectively enhances the visibility of dark regions in the original image and globally improves its color, contrast, and sharpness compared to current state-of-the-art methods. Our method can enhance underwater images in engineering practice, laying the foundation for in-depth research on underwater images.

An Adaptive Vehicle Detection Model for Traffic Surveillance of Highway Tunnels Considering Luminance Intensity.

Vehicle detection is essential for road traffic surveillance and active safety management. Deep learning methods have recently shown robust feature extraction capabilities and achieved improved detection results. However, vehicle detection models often perform poorly under abnormal lighting conditions, especially in highway tunnels. We proposed an adaptive vehicle detection model that accounts for varying luminance intensities to address this issue. The model categorizes the image data into abnormal and normal luminance scenarios. We employ an improved CycleGAN with edge loss as the adaptive luminance adjustment module for abnormal luminance scenarios. This module adjusts the brightness of the images to a normal level through a generative network. Finally, YOLOv7 is utilized for vehicle detection. The experimental results demonstrate that our adaptive vehicle detection model effectively detects vehicles under abnormal luminance scenarios in highway tunnels. The improved CycleGAN can effectively mitigate edge generation distortion. Under abnormal luminance scenarios, our model achieved a 16.3% improvement in precision, a 1.7% improvement in recall, and a 9.8% improvement in mAP_0.5 compared to the original YOLOv7. Additionally, our adaptive luminance adjustment module is transferable and can enhance the detection accuracy of other vehicle detection models.

Optimum display luminance and contrast polarity of desktop head-up display under office lighting level based on visual ergonomic study.

New type desktop head-up display (HUD) can reduce visual fatigue and protect vision through long viewing distance. In this study, participants evaluated visual performance, fatigue, and discomfort of desktop HUD under two contrast polarity (N = 36) and five display luminance levels (N = 21). A positive polarity advantage was found over negative in visual fatigue and discomfort (p < .05). Statistically significant effect of luminance was found on visual performance, fatigue, and discomfort (p < .05). The calculated optimum display luminance by the proposed inverted-U fitted model was 153 cd/m2 under 300 lx, higher than that of traditional desktop displays. It is speculated that higher luminance is required to offset the reduction in contrast sensitivity due to smaller target angular size, which caused by longer viewing distance. These findings suggest that positive polarity and 153 cd/m2 can be used to improve performance and avoid fatigue and discomfort when utilising desktop HUD under 300 lx.

A visual ergonomic study was conducted on new type desktop HUD. With visual performance, fatigue, and discomfort as optimisation goals, positive polarity and 153 cd/m² was recommended under 300 lx. Compared with traditional desktop displays, higher luminance was required in desktop HUD under the same illumination.

Faster Detection of "Darks" than "Brights" by Monkey Superior Colliculus Neurons.

Visual processing is segregated into ON and OFF channels as early as in the retina, and the superficial (output) layers of the primary visual cortex (V1) are dominated by neurons preferring dark stimuli. However, it is not clear how the timing of neural processing differs between "darks" and "brights" in general, especially in light of psychophysical evidence; it is also equally not clear how subcortical visual pathways that are critical for active orienting represent stimuli of positive (luminance increments) and negative (luminance decrements) contrast polarity. Here, we recorded from all visually-responsive neuron types in the superior colliculus (SC) of two male rhesus macaque monkeys. We presented a disk (0.51° radius) within the response fields (RFs) of neurons, and we varied, across trials, stimulus Weber contrast relative to a gray background. We also varied contrast polarity. There was a large diversity of preferences for darks and brights across the population. However, regardless of individual neural sensitivity, most neurons responded significantly earlier to dark than bright stimuli. This resulted in a dissociation between neural preference and visual response onset latency: a neuron could exhibit a weaker response to a dark stimulus than to a bright stimulus of the same contrast, but it would still have an earlier response to the dark stimulus. Our results highlight an additional candidate visual neural pathway for explaining behavioral differences between the processing of darks and brights, and they demonstrate the importance of temporal aspects in the visual neural code for orienting eye movements.SIGNIFICANCE STATEMENT Objects in our environment, such as birds flying across a bright sky, often project shadows (or images darker than the surround) on our retina. We studied how primate superior colliculus (SC) neurons visually process such dark stimuli. We found that the overall population of SC neurons represented both dark and bright stimuli equally well, as evidenced by a relatively equal distribution of neurons that were either more or less sensitive to darks. However, independent of sensitivity, the great majority of neurons detected dark stimuli earlier than bright stimuli, evidenced by a smaller response latency for the dark stimuli. Thus, SC neural response latency can be dissociated from response sensitivity, and it favors the faster detection of dark image contrasts.

Identifying the severity of diabetic retinopathy by visual function measures using both traditional statistical methods and interpretable machine learning: a cross-sectional study.

AIMS/HYPOTHESIS: To determine the extent to which diabetic retinopathy severity stage may be classified using machine learning (ML) and commonly used clinical measures of visual function together with age and sex. METHODS: We measured the visual function of 1901 eyes from 1032 participants in the Northern Ireland Sensory Ageing Study, deriving 12 variables from nine visual function tests. Missing values were imputed using chained equations. Participants were divided into four groups using clinical measures and grading of ophthalmic images: no diabetes mellitus (no DM), diabetes but no diabetic retinopathy (DM no DR), diabetic retinopathy without diabetic macular oedema (DR no DMO) and diabetic retinopathy with DMO (DR with DMO). Ensemble ML models were fitted to classify group membership for three tasks, distinguishing (A) the DM no DR group from the no DM group; (B) the DR no DMO group from the DM no DR group; and (C) the DR with DMO group from the DR no DMO group. More conventional multiple logistic regression models were also fitted for comparison. An interpretable ML technique was used to rank the contribution of visual function variables to predictions and to disentangle associations between diabetic eye disease and visual function from artefacts of the data collection process. RESULTS: The performance of the ensemble ML models was good across all three classification tasks, with accuracies of 0.92, 1.00 and 0.84, respectively, for tasks A-C, substantially exceeding the accuracies for logistic regression (0.84, 0.61 and 0.80, respectively). Reading index was highly ranked for tasks A and B, whereas near visual acuity and Moorfields chart acuity were important for task C. Microperimetry variables ranked highly for all three tasks, but this was partly due to a data artefact (a large proportion of missing values). CONCLUSIONS/INTERPRETATION: Ensemble ML models predicted status of diabetic eye disease with high accuracy using just age, sex and measures of visual function. Interpretable ML methods enabled us to identify profiles of visual function associated with different stages of diabetic eye disease, and to disentangle associations from artefacts of the data collection process. Together, these two techniques have great potential for developing prediction models using untidy real-world clinical data.

Evaluation of correlation between Diopsys® NOVA™ fixed-luminance flicker ERG and Diagnosys® Espion 2™ flicker ERG parameters.

PURPOSE: Diopsys® NOVA™ is a novel full-field electroretinography (ffERG) device that can make rapid measurements of retinal electrophysiologic function. Diagnosys® Espion 2™ is a clinical gold-standard ERG device. This study aimed to investigate whether light-adapted Diopsys® NOVA™ fixed-luminance flicker ffERG magnitude and implicit time (converted from phase) measurements correlate with light-adapted Diagnosys® Espion 2™ flicker ffERG amplitude and implicit time measurements, respectively. METHODS: Twelve patients (22 eyes) with various retinal and uveitic diseases underwent light-adapted Diagnosys® Espion 2™ and Diopsys® NOVA™ fixed-luminance flicker testing. Diopsys® magnitude and implicit time (converted from phase) measurements were compared to Diagnosys® amplitude and implicit time measurements, and a Pearson correlation was used to evaluate any existing correlation. Groups were also compared using generalized estimating equations. Bland-Altman plots were utilized to determine agreement between the comparison groups. RESULTS: Age of patients ranged from 14 to 87 years. 58% (n = 7/12) of patients were female. A significant, positive correlation (r = 0.880, P < 0.001) was observed between magnitude (Diopsys®) and amplitude (Diagnosys®) measurements. Amplitude increases by 6.69 µV for each 1 µV increase in Magnitude (p-value < 0.001). A statistically significant, strong positive correlation was observed between Diopsys® implicit time measurements (converted from phase) and Diagnosys® implicit time measurements (r = 0.814, p-value < 0.001). For each 1 ms increase in Diopsys® implicit time, Diagnosys® implicit time increases by 1.13 ms (p-value < 0.001). CONCLUSIONS: There is a statistically significant positive correlation between light-adapted Diopsys® NOVA™ fixed-luminance flicker amplitude and Diagnosys® flicker magnitude values. Additionally, there is a statistically significant positive correlation between Diopsys® NOVA™ fixed-luminance flicker implicit time (converted from phase) and Diagnosys® flicker implicit time values. These results imply that the Diopsys® NOVA™ module, which utilizes the nonstandard shortened International Society for Clinical Electrophysiology of Vision (ISCEV) ERG protocol, can produce reliable light-adapted flicker ffERG measurements.

A cross-sectional study to assess the clinical utility of modern visual function assessments in patients with inherited retinal disease: a mixed methods observational study protocol.

BACKGROUND: Treatment options for patients with inherited retinal disease are limited, although research into novel therapies is underway. To ensure the success of future clinical trials, appropriate visual function outcome measures that can assess changes resulting from therapeutic interventions are urgently required. Rod-cone degenerations are the most common type of inherited retinal disease. Visual acuity is a standard measure but is typically preserved until late disease stages, frequently making it an unsuitable visual function marker. Alternative measures are required. This study investigates the clinical utility of a range of carefully selected visual function tests and patient reported outcome measures. The aim is to identify suitable outcome measures for future clinical trials that could be considered for regulatory approval. METHODS: This cross-sectional study involves two participant groups, patients with inherited retinal disease (n = 40) and healthy controls (n = 40). The study has been designed to be flexible and run alongside NHS clinics. The study is split into two parts. Part one includes examining standard visual acuity, low luminance visual acuity, the Moorfields acuity chart visual acuity, mesopic microperimetry and three separate patient reported outcome measures. Part two involves 20 min of dark adaptation followed by two-colour scotopic microperimetry. Repeat testing will be undertaken where possible to enable repeatability analyses. A subset of patients with inherited retinal disease will be invited to participate in a semi-structured interview to gain awareness of participants' thoughts and feelings around the study and different study tests. DISCUSSION: The study highlights a need for reliable and sensitive validated visual function measures that can be used in future clinical trials. This work will build on work from other studies and be used to inform an outcome measure framework for rod-cone degenerations. The study is in keeping with the United Kingdom Department of Health and Social Care research initiatives and strategies for increasing research opportunities for NHS patients as part of their NHS care. TRIAL REGISTRATION: ISRCTN registry, ISRCTN24016133, Visual Function in Retinal Degeneration, registered on 18th August 2022.

Effect of low luminance on face recognition in adults with central and peripheral vision loss.

PURPOSE: To investigate the effect of low luminance on face recognition, specifically facial identity discrimination (FID) and facial expression recognition (FER), in adults with central vision loss (CVL) and peripheral vision loss (PVL) and to explore the association between clinical vision measures and low luminance FID and FER. METHODS: Participants included 33 adults with CVL, 17 with PVL and 20 controls. FID and FER were assessed under photopic and low luminance conditions. For the FID task, 12 sets of three faces with neutral expressions were presented and participants asked to indicate the odd-face-out. For FER, 12 single faces were presented and participants asked to name the expression (neutral, happy or angry). Photopic and low luminance visual acuity (VA) and contrast sensitivity (CS) were recorded for all participants and for the PVL group, Humphrey Field Analyzer (HFA) 24-2 mean deviation (MD). RESULTS: FID accuracy in CVL, and to a lesser extent PVL, was reduced under low compared with photopic luminance (mean reduction 20% and 8% respectively; p < 0.001). FER accuracy was reduced only in CVL (mean reduction 25%; p < 0.001). For both CVL and PVL, low luminance and photopic VA and CS were moderately to strongly correlated with low luminance FID (ρ = 0.61-0.77, p < 0.05). For PVL, better eye HFA 24-2 MD was moderately correlated with low luminance FID (ρ = 0.54, p = 0.02). Results were similar for low luminance FER. Together, photopic VA and CS explained 75% of the variance in low luminance FID, and photopic VA explained 61% of the variance in low luminance FER. Low luminance vision measures explained little additional variance. CONCLUSION: Low luminance significantly reduced face recognition, particularly for adults with CVL. Worse VA and CS were associated with reduced face recognition. Clinically, photopic VA is a good predictor of face recognition under low luminance conditions.

Environmental Light Has an Essential Effect on the Disease Expression in a Dominant RPE65 Mutation.

The retina pigmented epithelium 65 kDa protein (RPE65) is an essential enzyme in the visual cycle that regenerates the 11-cis-retinal chromophore obligatory for vision. Mutations in RPE65 are associated with blinding diseases. D477G (C.1430G > A) is the only known RPE65 variant to cause autosomal dominant retinitis pigmentosa (adRP). Previously, we reported that the heterozygous D477G knock-in (WT/KI) mice exposed to dim light intensity demonstrated delayed chromophore regeneration rates and slowed recovery of photoreceptor sensitivity following photobleaching. However, visual function and retinal architecture were indistinguishable from the wild-type (WT) mice. In this study, when maintained under the physiological day-light intensity (2 K lux), the WT/KI heterozygous mice displayed retina degeneration and reduced electroretinography (ERG) amplitude, recapitulating that observed in human patients. Our findings indicated the importance of the light environment in the mechanism of RPE65 D477G pathogenicity.