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Introduction: One of the most important factors affecting visual performance during vision aided by night vision goggles (NVGs) is image quality, which depends mainly on the image-intensifier technology used. Although NVGs with green image color (P43 phosphor) are only accepted in military aviation, white image (P45 phosphor) seems to be equally well-regarded by aviators. The aim of our study was to determine if the experience of using NVGs with the green screen affects image preference for that color, and if the screen color preference is related to luminance level., Methods: Subjects (127 military pilots, 26-56 yr, M = 37.2; 62 pilots with flight experience with NVG use) were asked to observe a model terrain board at two different luminance levels (corresponding roughly to ambient conditions during starlight and one-half moonlight) while using two types of NVGs (green P43 and white P45 phosphor screens). The pilots were asked to answer a questionnaire about their preference for NVG display color., Results: The findings showed a significant difference between screen color preference and pilots' experience with the green-phosphor-based NVGs (43.5% vs. 23.1% for white screens). However, there was no relationship between screen color preference and luminance level., Discussion: Previous NVG experience seems to play an important role in shaping a user's individual preference for a certain phosphor screen color, although green and white phosphor screens both provide satisfactory visibility. Nevertheless, when deciding, it is advisable to experiment with both colors and select the one that suits the user's preferences and needs. Lewkowicz R, Dereń-Szumełda J. Phosphor screens color preferences depending on night vision experience and luminance level. Aerosp Med Hum Perform. 2024; 95(10):749-757.

Purpose: To compare early visual quality of small incision lenticule extraction (SMILE) versus laser in situ keratomileusis (LASIK) in terms of low contrast acuity., Methods: A secondary analysis was performed using a harmonized dataset derived from two completed prospective cohort studies on active-duty military service members undergoing either SMILE (n = 37), wavefront-guided (WFG) LASIK (n = 51), or wavefront-optimized (WFO) LASIK (n = 56). Night vision and photopic and mesopic low contrast visual acuity (LCVA) up to 3 months postoperatively were compared between groups., Results: Compared to SMILE-treated eyes, WFG LASIK-treated eyes had significantly better night vision and photopic LCVA at 1 month postoperatively (beta = -0.039, P = .016; beta = -0.043, P = .007, respectively). WFO LASIK-treated eyes had significantly better photopic LCVA at 1 month postoperatively (beta = -0.039, P = .012) but had worse mesopic LCVA at 3 months postoperatively (beta = 0.033, P = .015) versus SMILE-treated eyes., Conclusions: SMILE and LASIK, on either a WFG or WFO laser platform, yielded excellent outcomes, but LCVA seemed to recover quicker following LASIK compared to SMILE. [ J Refract Surg . 2024;40(9):e667-e671.] .

Clinical Relevance: Patients prescribed pilocarpine ophthalmic solution are advised to be cautious when driving at night, but studies evaluating the effects of pilocarpine hydrochloride ophthalmic solution 1.25% (pilo), approved to treat presbyopia, on driving at night are lacking., Background: This double-masked, crossover, phase 3b study evaluated night-driving performance with pilo or the placebo once daily., Methods: Forty-three adults (40-55 years) with presbyopia impacting daily activities and mesopic, high-contrast, binocular distance-corrected near vision 6/12-6/30 were randomised to bilateral treatment with pilo followed by placebo or placebo followed by pilo (with a ≥7-day washout between interventions). Night-driving performance was evaluated at twilight at a closed-circuit course. Primary efficacy endpoint: overall composite night-driving performance Z score at the end of the 7-14-day intervention period, 1 hour post-instillation. Pilo was considered non-inferior if the lower limit of the 95% confidence interval (CI) for the least squares mean difference (LSMD, pilo minus placebo) was >-0.25. Other efficacy endpoints: individual components of the night-driving performance test (hazard avoidance rate; road sign recognition rate and distance; pedestrians recognition distance; overall driving and lane-keeping times) and night-driving experience questionnaire. Safety included treatment-emergent adverse events (TEAEs)., Results: The mean overall composite Z scores were -0.121 (pilo) and 0.118 (placebo). The LSMD (pilo minus placebo) was -0.224 (95% CI, -0.346, -0.103), with 3 of the 7 individual tasks being significantly better with the placebo. The questionnaire did not reveal significant differences between pilo and the placebo. There were no serious or severe TEAEs and no TEAE-related discontinuations. The most common ocular TEAEs were headache and visual impairment with pilo (both 27.9%), and dry eye (7.0%) with the placebo., Conclusion: The overall performance of night driving was inferior with pilo, compared with placebo. The study findings are consistent with the current class labelling and provide evidence to inform regulators and assist clinicians considering prescribing pilo to adults who seek treatment of presbyopia symptoms and drive at night. ClinicalTrials.gov identifier: NCT04837482.

Purpose: To investigate the visual function correlates of self-reported vision-related night driving difficulties among drivers., Methods: One hundred and seven drivers (age: 46.06 ± 8.24, visual acuity [VA] of 0.2logMAR or better) were included in the study. A standard vision and night driving questionnaire (VND-Q) was administered. VA and contrast sensitivity were measured under photopic and mesopic conditions. Mesopic VA was remeasured after introducing a peripheral glare source into the participants' field of view to enable computation of disability glare index. Regression analyses were used to assess the associations between VND-Q scores, and visual function measures., Results: The mean VND-Q score was -3.96±1.95 logit (interval scale score: 2.46±1.28). Simple linear regression models for photopic contrast sensitivity, mesopic VA, mesopic contrast sensitivity, and disability index significantly predicted VND-Q score (P<0.05), with mesopic VA and disability glare index accounting for the greatest variation (21 %) in VND-Q scores followed by photopic contrast sensitivity (19 %), and mesopic contrast sensitivity (15 %). A multiple regression model to determine the association between the predictors (photopic contrast sensitivity, mesopic VA, mesopic contrast sensitivity, and disability index) and VND-Q score yielded significant results, F (4, 102) = 8.58, P < 0.001, adj. R 2 = 0.2224. Seeing dark-colored cars was the most challenging vision task., Conclusion: Changes in mesopic visual acuity, photopic and mesopic contrast sensitivity, as well as disability glare index are associated with and explain night driving-related visual difficulties. It is recommended to incorporate measurement of these visual functions into assessments related to driving performance., Competing Interests: Declarations of Competing Interest The authors declare there are no conflicts of interest., (Copyright © 2023 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To investigate the efficacy of our wearable night-vision aid in patients with concentric peripheral visual field loss., Study Design: Prospective, single blind, three-group, and three-period crossover clinical study., Methods: The study included patients with concentric peripheral visual field loss, a best-corrected visual acuity (decimal visual acuity) of 0.1 or higher in the better eye, and the presence of a central visual field. HOYA MW10 HiKARI® (HOYA Corporation), our original wearable night-vision aid, was used as the test device with three types of camera lenses (standard-, middle-, and wide-angle lenses). Under both bright and dark conditions, the angle of the horizontal visual field was measured using each of the three lens types for each group. The baseline angle was measured when each participant wore the night-vision aid (powered off)., Results: The study included 21 participants. Under bright condition, the perceived horizontal visual field was significantly wider than the baseline setup when using the standard-angle lens ("the standard lens"); the middle-angle lens ("the middle lens") was significantly wider than both the baseline setup and the standard lens; and the wide-angle lens ("the wide lens") was significantly wider than the other lenses. Under dark condition, the perceived horizontal visual field was again significantly wider when using the middle lens than the baseline setup and the standard lens, and when using the wide lens, the perceived horizontal visual field was again wider than when using the other lenses. The control in the bright condition was significantly wider (p < 0.001) than when used in the dark condition, while the standard-angle lens in the dark condition was significantly wider (p = 0.05) than when used in the bright condition. In regards to the middle and wide lenses, there was no statistically significant result emerging from either of the illumination conditions., Conclusion: Our wearable night-vision aid with a middle-angle or wide-angle lens appears to provide wider visual field images in patients with concentric peripheral visual field loss, regardless of whether the illumination conditions are bright or dark., (© 2024. Japanese Ophthalmological Society.)

Objective: The objective of our work was to assess the impact of flight conditions by aircraft type on the workload estimated using NASA-Task Load Index (NASA-TLX)., Background: Learning about subjective workload is important for assessing the impact of a pilot's work environment on their performance in the cockpit. This is an important element of flight safety and includes the prevention of aviation accidents., Methods: The study included 146 military pilots that fly the following aircrafts: flying fast-jet (21), fixed-wing (24), and rotary-wing (101). The NASA-TLX questionnaire was used to assess workload and pilots were asked to determine the level of workload resulting from flying under the following conditions: daytime flight (VFR), night-vision flight performed under Night Visual Flight Rules (NVFR), and night-vision flight using night-vision goggles (NVGs)., Results: The highest level of workload was consistently attributed to flights performed under NVG conditions. NVFR conditions were rated as the most burdensome, while VFR conditions were rated as the least burdensome. Fast-jet pilots rated their mental performance and effort workload as significantly higher than pilots of other aircrafts., Conclusion: Pilots' perceived workload is influenced by both flight conditions and the type of aircraft they fly. Workload knowledge is important for flight safety and should be taken into account during training and flight-task planning., Application: The results of our study can be useful both in flight training and in work on the effectiveness of the human-machine interface. Awareness of one's own limitations due to the work environment can help improve flight safety., 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. We would like to thank pilot Major Marek Gąsik for consulting on aviation knowledge The authors also wish to extend thanks to the anonymous reviewers for their valuable comments and suggestions for improving the quality of this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Visual fields under mesopic and scotopic lighting are increasingly being used for macular functional assessment. This review evaluates its statistical significance and clinical relevance, and the optimal testing protocol for early/intermediate age-related macular degeneration (AMD). PubMed and Embase were searched from inception to 14/05/2022. All quality assessments were performed according to GRADE guidelines. The primary outcome was global mean sensitivity (MS), further meta-analysed by: AMD classification scheme, device, test pattern, mesopic/scotopic lighting, stimuli size/chromaticity, pupil dilation, testing radius (area), background luminance, adaptation time, AMD severity, reticular pseudodrusen presence, and follow-up visit. From 1489 studies screened, 42 observational study results contributed to the primary meta-analysis. Supported by moderate GRADE certainty of the evidence, global MS was significantly reduced across all devices under mesopic and scotopic lighting with large effect size (-0.9 [-1.04, -0.75] Hedge's g, P < 0.0001). The device (P < 0.01) and lighting (P < 0.05) used were the only modifiable factors affecting global MS, whereby the mesopic MP-1 and MAIA produced the largest effect sizes and exceeded test-retest variabilities. Global MS was significantly affected by AMD severity (intermediate versus early AMD; -0.58 [-0.88, -0.29] Hedge's g or -2.55 [3.62, -1.47] MAIA-dB) and at follow-up visit (versus baseline; -0.62 [-0.84, -0.41] Hedge's g or -1.61[-2.69, -0.54] MAIA-dB). Magnitudes of retinal sensitivity changes in early/intermediate AMD are clinically relevant for the MP-1 and MAIA devices under mesopic lighting within the central 10° radius. Other factors including pupil dilation and dark adaptation did not significantly affect global MS in early/intermediate AMD., (© 2024. The Author(s).)

The perception of halos and other night vision disturbances is a common complaint in clinical practice. Such visual disturbances must be assessed in order to fully characterize each patient's visual performance, which is particularly relevant when carrying out a range of daily tasks. Visual problems are usually assessed using achromatic stimuli, yet the stimuli encountered in daily life have very different chromaticities. Hence, it is important to assess the effect of the chromaticity of visual stimuli on night vision disturbances. The aim of this work is to study the influence of the chromaticity of different visual stimuli on night vision disturbances by analyzing straylight and visual discrimination under low-light conditions. For that, we assessed the monocular and binocular visual discrimination of 27 subjects under low illumination using the Halo test. The subjects' visual discrimination was assessed after exposure to different visual stimuli: achromatic, red, green, and blue, both at the monitor's maximum luminance and maintaining the same luminance value for the different visual stimuli. Monocular straylight was also measured for an achromatic, red, green, and blue stimuli. The blue stimulus had the greatest effect on halos in both monocular and binocular conditions. Visual discrimination was similar for the red, green, and achromatic stimuli, but worsened at lower luminance. The greatest influence of straylight was observed for the blue stimulus. In addition, visual discrimination correlated with straylight measurements for achromatic stimuli, wherein greater straylight values correlated with an increased perception of halos and other visual disturbances., (© 2024. The Author(s).)

Purpose: To longitudinally assess the impact of high-risk structural biomarkers for natural disease progression in non-exudative age-related macular degeneration (AMD) on spatially resolved mesopic and scotopic fundus-controlled perimetry testing., Methods: Multimodal retinal imaging data and fundus-controlled perimetry stimuli points were semiautomatically registered according to landmark correspondences at each annual visit over a period of up to 4 years. The presence of sub-RPE drusen, subretinal drusenoid deposits, pigment epithelium detachments (PEDs), hyper-reflective foci (HRF), vitelliform lesions, refractile deposits, and incomplete RPE and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) were graded at each stimulus position and visit. Localized retinal layer thicknesses were extracted. Mixed-effect models were used for structure-function correlation., Results: Fifty-four eyes of 49 patients with non-exudative AMD (mean age, 70.7 ± 9.1 years) and 27 eyes of 27 healthy controls (mean age, 63.4 ± 8.9 years) were included. During study course, presence of PED had the highest functional impact with a mean estimated loss of -1.30 dB (P < 0.001) for mesopic and -1.23 dB (P < 0.001) for scotopic testing, followed by HRF with -0.89 dB (mesopic, P = 0.001) and -0.87 dB (scotopic, P = 0.005). Subretinal drusenoid deposits were associated with a stronger visual impairment (mesopic, -0.38 dB; P = 0.128; scotopic, -0.37 dB; P = 0.172) compared with sub-RPE drusen (-0.22 dB, P = 0.0004; -0.18 dB, P = 0.006). With development of c-RORA, scotopic retinal sensitivity further significantly decreased (-2.15 dB; P = 0.02). Thickening of the RPE-drusen-complex and thinning of the outer nuclear layer negatively impacted spatially resolved retinal sensitivity., Conclusions: The presence of PED and HRF had the greatest prognostic impact on progressive point-wise sensitivity losses. Higher predominant rod than cone-mediated localized retinal sensitivity losses with early signs of retinal atrophy development indicate photoreceptor preservation as a potential therapeutic target for future interventional AMD trials.

High sensitivity of scotopic vision (vision in dim light conditions) is achieved by the rods' low background noise, which is attributed to a much lower thermal activation rate (k th ) of rhodopsin compared with cone pigments. Frogs and nocturnal geckos uniquely possess atypical rods containing noncanonical cone pigments that exhibit low k th , mimicking rhodopsin. Here, we investigated the convergent mechanism underlying the low k th of rhodopsins and noncanonical cone pigments. Our biochemical analysis revealed that the k th of canonical cone pigments depends on their absorption maximum (λ max ). However, rhodopsin and noncanonical cone pigments showed a substantially lower k th than predicted from the λ max dependency. Given that the λ max is inversely proportional to the activation energy of the pigments in the Hinshelwood distribution-based model, our findings suggest that rhodopsin and noncanonical cone pigments have convergently acquired low frequency of spontaneous-activation attempts, including thermal fluctuations of the protein moiety, in the molecular evolutionary processes from canonical cone pigments, which contributes to highly sensitive scotopic vision., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Interphotoreceptor retinoid-binding protein (IRBP) is an abundant glycoprotein in the subretinal space bound by the photoreceptor (PR) outer segments and the processes of the retinal pigmented epithelium (RPE). IRBP binds retinoids, including 11-cis-retinal and all-trans-retinol. In this study, visual function for demanding visual tasks was assessed in IRBP knock-out (KO) mice. Surprisingly, IRBP KO mice showed no differences in scotopic critical flicker frequency (CFF) compared to wildtype (WT). However, they did have lower photopic CFF than WT. IRBP KO mice had reduced scotopic and photopic acuity and contrast sensitivity compared to WT. IRBP KO mice had a significant reduction in outer nuclear layer (ONL) thickness, PR outer and inner segment, and full retinal thickness (FRT) compared to WT. There were fewer cones in IRBP KO mice. Overall, these results confirm substantial loss of rods and significant loss of cones within 30 days. Absence of IRBP resulted in cone circuit damage, reducing photopic flicker, contrast sensitivity, and spatial frequency sensitivity. The c-wave was reduced and accelerated in response to bright steps of light. This result also suggests altered retinal pigment epithelium activity. There appears to be a compensatory mechanism such as higher synaptic gain between PRs and bipolar cells since the loss of the b-wave did not linearly follow the loss of rods, or the a-wave. Scotopic CFF is normal despite thinning of ONL and reduced scotopic electroretinogram (ERG) in IRBP KO mice, suggesting either a redundancy or plasticity in circuits detecting (encoding) scotopic flicker at threshold even with substantial rod loss.

Purpose: Subretinal drusenoid deposits (SDD) first appear in the rod-rich perifovea and can extend to the cone-rich fovea. To refine the spatial relationship of visual dysfunction with SDD burden, we determined the topography of mesopic and scotopic light sensitivity in participants with non-neovascular AMD with and without SDD., Methods: Thirty-three subjects were classified into three groups: normal (n = 9), AMD-Drusen (with drusen and without SDD; n = 12), and AMD-SDD (predominantly SDD; n = 12). Mesopic and scotopic microperimetry were performed using 68 targets within the Early Treatment Diabetic Retinopathy Study grid, including points at 1.7° from the foveal center (rod:cone ratio, 0.35). Age-adjusted linear regression was used to compare mesopic and scotopic light sensitivities across groups., Results: Across the entire Early Treatment Diabetic Retinopathy Study grid and within individual subfields, the three groups differed significantly for mesopic and scotopic light sensitivities (all P < 0.05). The AMD-SDD group exhibited significantly decreased mesopic and scotopic sensitivity versus both the normal and the AMD-Drusen groups (all P < 0.05), while AMD-Drusen and normal eyes did not significantly differ (all P > 0.05). The lowest relative sensitivities were recorded for scotopic light levels, especially in the central subfield, in the AMD-SDD group., Conclusions: SDD-associated decrements in rod-mediated vision can be detected close to the foveola, and these deficits are proportionately worse than functional loss in the rod-rich perifovea. This finding suggests that factors other than the previously hypothesized direct cytotoxicity to photoreceptors and local transport barrier limitations may negatively impact vision. Larger prospective studies are required to confirm these observations.

Elevated levels of the excitatory amino acid homocysteine (Hcy) have been implicated in retinal diseases in humans including glaucoma and macular degeneration. It is not clear whether elevated Hcy levels are pathogenic. Models of hyperhomocysteinemia (Hhcy) have proven useful in addressing this including mice with deficiency in the enzyme cystathionine β-synthase (CBS). Cbs +/- mice have a ∼two-fold increase in plasma and retinal Hcy levels. Previous studies of visual function and structure in Cbs +/- mice during the first 10 months of life revealed mild ganglion cell loss, but minimal electrophysiological alterations. It is not clear whether extended, chronic exposure to moderate Hhcy elevation will lead to visual function loss and retinal pathology. The present study addressed this by performing comprehensive analyses of retinal function/structure in 20 month Cbs +/- and Cbs +/+ (WT) mice including IOP, SD-OCT, scotopic and photopic ERG, pattern ERG (pERG), and visual acuity. Eyes were harvested for histology and immunohistochemical analysis of Brn3a (ganglion cells), dihydroethidium (oxidative stress) and GFAP (gliosis). The analyses revealed no difference in IOP between groups for age/strain. Visual acuity measured ∼0.36c/d for mice at 20 months in Cbs +/- and WT mice; contrast sensitivity did not differ between groups at either age. Similarly SD-OCT, scotopic/photopic ERG and pERG revealed no differences between 20 month Cbs +/- and WT mice. There was minimal disruption in retinal structure when eyes were examined histologically. Morphometric analysis revealed no significant differences in retinal layers. Immunohistochemistry revealed ∼5 RGCs/100 μm retinal length in both Cbs +/- and WT mice at 20 months. While there was greater oxidative stress and gliosis in older (20 month) mice versus young (4 month) mice, there was no difference in these parameters between the 20 month Cbs +/- and WT mice. We conclude that chronic, moderate Hhcy (at least due to deficiency of Cbs) is not accompanied by retinal structural/functional changes that differ significantly from age-matched WT littermates. Despite considerable evidence that severe Hhcy is toxic to retina, moderate Hhcy appears tolerated by retina suggesting compensatory cellular survival mechanisms., (Copyright © 2021. Published by Elsevier Ltd.)

Green rods (GRs) represent a unique type of photoreceptor to be found in the retinas of anuran amphibians. These cells harbor a cone-specific blue-sensitive visual pigment but exhibit morphology of the outer segment typical for classic red rods (RRs), which makes them a perspective model object for studying cone-rod transmutation. In the present study, we performed detailed electrophysiological examination of the light sensitivity, response kinetics and parameters of discrete and continuous dark noise in GRs of the two anuran species: cane toad and marsh frog. Our results confirm that anuran GRs are highly specialized nocturnal vision receptors. Moreover, their rate of phototransduction quenching appeared to be about two-times slower than in RRs, which makes them even more efficient single photon detectors. The operating intensity ranges for two rod types widely overlap supposedly allowing amphibians to discriminate colors in the scotopic region. Unexpectedly for typical cone pigments but in line with some previous reports, the spontaneous isomerization rate of the GR visual pigment was found to be the same as for rhodopsin of RRs. Thus, our results expand the knowledge on anuran GRs and show that these are even more specialized single photon catchers than RRs, which allows us to assign them a status of "super-rods".

The retinal circadian system consists of a network of clocks located virtually in every retinal cell-type. Although it is established that the circadian clock regulates many rhythmic processes in the retina, the links between retinal cell-specific clocks and visual function remain to be elucidated. Bmal1 is a principal, non-redundant component of the circadian clock in mammals and is required to keep 24 h rhythms in the retinal transcriptome and in visual processing under photopic light condition. In the current study, we investigated the retinal function in mice with a rod-specific knockout of Bmal1. For this purpose, we measured whole retina PER2::Luciferase bioluminescence and the dark-adapted electroretinogram (ERG). We observed circadian day-night differences in ERG a- and b-waves in control mice carrying one allele of Bmal1 in rods, with higher amplitudes during the subjective night. These differences were abolished in rod-specific Bmal1 knockout mice, whose ERG light-responses remained constitutively low (day-like). Overall, PER2::Luciferase rhythmicity in whole retinas was not defective in these mice but was characterized by longer period and higher rhythmic power compared to retinas with wild type Bmal1 gene. Taken together, these data suggest that a circadian clock located in rods regulates visual processing in a cell autonomous manner., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study was to present our hypothesis that aging alters metabolic function in ocular tissues. We tested the hypothesis by measuring metabolism in aged murine tissues alongside retinal responses to light., Methods: Scotopic and photopic electroretinogram (ERG) responses in young (3-6 months) and aged (23-26 months) C57Bl/6J mice were recorded. Metabolic flux in retina and eyecup explants was quantified using U-13C-glucose or U-13C-glutamine with gas chromatography-mass spectrometry (GC-MS), O2 consumption rate (OCR) in a perifusion apparatus, and quantifying adenosine triphosphatase (ATP) with a bioluminescence assay., Results: Scotopic and photopic ERG responses were reduced in aged mice. Glucose metabolism, glutamine metabolism, OCR, and ATP pools in retinal explants were mostly unaffected in aged mice. In eyecups, glutamine usage in the Krebs Cycle decreased while glucose metabolism, OCR, and ATP pools remained stable., Conclusions: Our examination of metabolism showed negligible impact of age on retina and an impairment of glutamine anaplerosis in eyecups. The metabolic stability of these tissues ex vivo suggests age-related metabolic alterations may not be intrinsic. Future experiments should focus on determining whether external factors including nutrient supply, oxygen availability, or structural changes influence ocular metabolism in vivo.

Purpose: Cytoplasmic dynein-1 (henceforth dynein) moves cargo in conjunction with dynactin toward the minus end of microtubules. The dynein heavy chain, DYNC1H1, comprises the backbone of dynein, a retrograde motor. Deletion of Dync1h1 abrogates dynein function. The purpose of this communication is to demonstrate effects of photoreceptor dynein inactivation during late postnatal development and in adult retina., Methods: We mated Dync1h1F/F mice with iCre75 and Prom1-CreERT2 mice to generate conditional rod and tamoxifen-induced knockout in rods and cones, respectively. We documented retina degeneration with confocal microscopy at postnatal day (P) 10 to P30 for the iCre75 line and 1 to 4 weeks post tamoxifen induction (wPTI) for the Prom1-CreERT2 line. We performed scotopic and photopic electroretinography (ERG) at P16 to P30 in the iCre75 line and at 1-week increments in the Prom1-CreERT2 line. Results were evaluated statistically using Student's t-test, two-factor ANOVA, and Welch's ANOVA., Results: Cre-induced homologous recombination of Dync1h1F/F mice truncated DYNC1H1 after exon 23. rodDync1h1-/- photoreceptors degenerated after P14, reducing outer nuclear layer (ONL) thickness and combined inner segment/outer segment (IS/OS) length significantly by P18. Scotopic ERG a-wave amplitudes decreased by P16 and were extinguished at P30. Cones were stable under rod-knockout conditions until P21 but inactive at P30. In tamDync1h1-/- photoreceptors, the IS/OS began shortening by 3wPTI and were nearly eliminated by 4wPTI. The ONL shrank significantly over this interval, indicating rapid photoreceptor degeneration following the loss of dynein., Conclusions: Our results demonstrate dynein is essential for the secretory pathway, formation of outer segments, and photoreceptor maintenance.

Purpose: Retinal ischemia/reperfusion (I/R) injury is a common cause of visual impairment and blindness for which there remain limited treatment options. Nucleoside reverse transcriptase inhibitors (NRTIs), such as zidovudine (AZT), have been shown to block the NLRP3 inflammasome and prevent retinal degeneration in a mouse model of age-related macular degeneration. The NLRP3 inflammasome has also been shown to be triggered in I/R injury. Therefore, we studied the neuroprotective effects of AZT using a pressure-induced retinal ischemia mouse model. Methods: C57BL/6J mice were randomly assigned to 1 of 2 treatment groups: vehicle-treated retinal I/R injury ( n  = 6) or AZT-treated retinal I/R injury ( n  = 6). Vehicle (1% dimethyl sulfoxide [DMSO] in phosphate-buffered saline [PBS]) or AZT 50 mg/kg in 1% DMSO in PBS were injected intraperitoneally twice daily for 5 days. On day 2 of treatment, retinal ischemia was induced by transient elevation of intraocular pressure for 45 min. Scotopic electroretinography (ERG) was used to quantify retinal function before and 1 week after retinal ischemic insult. Retinal morphology was examined 1 week after ischemic insult. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays and caspase 1 immunostaining was performed 24 h after retinal I/R injury. Results: Following I/R injury, ERG a- and b-wave amplitudes were significantly reduced in the vehicle-treated mice. AZT treatment significantly attenuated I/R-induced loss of retinal function as compared with vehicle-treated mice. Additionally, AZT-treated mice experienced significantly less inner retinal thinning as compared with vehicle-treated mice. TUNEL-positive cells were prevalent in the vehicle-treated I/R injury mouse retinas compared with the AZT-treated I/R injury mouse retinas. More caspase-1 immunoreactivity was detected in ganglion cell layer and inner nuclear layer (INL) in vehicle-treated I/R injury group than in AZT-treated I/R injury group. Conclusion: AZT treatment resulted in relative preservation of retinal structure and function following ischemic insult as compared with controls. This suggests AZT may have therapeutic value in the management of retinal ischemic diseases.

Purpose: To evaluate off-label use of netarsudil 0.02% for treatment of corneal edema associated with Fuchs dystrophy., Design: Prospective, randomized clinical trial., Methods: Twenty-nine subjects with symptomatic Fuchs dystrophy were enrolled and randomized to use netarsudil or placebo eye drops once daily for 3 months. The primary outcomes were the change in central corneal thickness between baseline and 1 month and between baseline and 3 months. Secondary outcomes included change in scotopic corrected distance visual acuity (CDVA) at 3 months and change in scores on a visual disability questionnaire validated for use with Fuchs dystrophy., Results: Compared with use of placebo, use of netarsudil produced significant reduction in central corneal thickness at 1 month (mean difference, -20 µm; 95% confidence interval, -32 to -9 µm) and 3 months (mean difference, -26 µm; 95% confidence interval, -39 to -12 µm) and significant improvement in scotopic CDVA at 3 months (mean difference +1.6 lines; 95% confidence interval, 0.2-3.0 lines). Scores on the visual disability questionnaire did not change significantly in either arm or differ significantly between arms. One subject assigned to netarsudil had baseline epithelial bullae and withdrew from the study because of disabling glare., Conclusions: Use of netarsudil was associated with reduction of corneal edema and improvement in scotopic CDVA in Fuchs dystrophy patients. Further study is needed to more fully assess patient satisfaction and visual acuity under various lighting conditions and to compare use of netarsudil with other treatment options such as endothelial keratoplasty., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To assess the effectiveness of an active learning approach to measuring the contrast sensitivity function (CSF) in patients with various degrees of dry age-related macular degeneration (AMD) under multiple luminance conditions., Design: Cross-sectional study., Methods: Patients with AMD (26 intermediate AMD, 19 AMD with subretinal drusenoid deposits [SDD], 20 geographic atrophy [GA]) and 23 age-matched controls were tested with the Manifold Contrast Vision Meter (Adaptive Sensory Technology) and the qCSF algorithm, which applies active learning to estimate a model of the CSF's global shape. Testing was performed under conditions of standard and low luminance. For each AMD severity, the area under log CSF (AULCSF) and contrast sensitivities at individual spatial frequencies were calculated for analysis. Low-luminance deficits (LLDs) for visual acuity (VA) and AULCSF were calculated as the difference between standard and low luminance values., Results: Progressive decreases in AULCSF were observed as disease severity increased. For standard luminance, pairwise comparisons revealed significant differences between control/intermediate AMD (P < .0005), control/SDD (P < .0005), control/GA (P < .0005), and intermediate AMD/GA (P < .005). Similarly, for low luminance, pairwise comparisons revealed significant differences between the controls and each disease group (all P < .0005), in addition to significant differences between intermediate AMD/SDD (P < .005), and intermediate AMD/GA (P < .005). No correlations were found between LLD VA and LLD AULCSF in any AMD groups., Conclusions: Contrast sensitivity measured via qCSF under both standard- and low-luminance conditions correlates with advancing stages of dry AMD. The interaction between luminance and contrast sensitivity appears to reflect a different aspect of visual function than the interaction between luminance and VA., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Many individuals drive with uncorrected refractive errors, which has implications for night driving, where poor visibility contributes to the increased crash risk relative to daytime. This study explored how small amounts of refractive blur affects the judgment of the walking direction of night-time pedestrians and whether different types of retro-reflective clothing influence this effect., Methods: Judgement of the walking direction of night-time pedestrians was investigated for 20 young participants with normal vision (mean age, 21.8 ± 1.6 years) for two levels of binocular blur (+0.50DS, +1.00DS) compared to baseline (best-corrected refractive correction). Participants seated in a stationary car with low beam headlamps observed a pedestrian wearing three clothing conditions: retro-reflective vest (1) and retro-reflective biomotion clothing (incorporating thin (2) or thick (3) retro-reflective strips), who walked across the road in three directions (straight across, away or towards the car). The order of conditions was randomised among participants. Participants reported the perceived pedestrian walking direction and how confident they rated their response. Outcome measures included the proportion of correct responses (response accuracy) and confidence ratings., Results: Blur had a significant effect on accuracy in judging pedestrian walking direction; accuracy decreased significantly with increasing blur (p < 0.001), with all blur levels being significantly different from one another. The effect of pedestrian clothing was also significant (p < 0.001); direction judgements were least accurate for vest, followed by both thin and thick biomotion, where accuracy judgements were similar. There was also a significant interaction between blur and clothing (p < 0.05). Similar trends were found for confidence ratings across the blur and clothing conditions. Greater confidence was significantly associated with increased response accuracy for the biomotion clothing, but not the vest., Conclusion: Findings highlight that even small amounts of blur (+0.50DS), that do not reduce visual acuity below the legal driving limits, reduce the ability to accurately judge pedestrian walking direction at night. Retro-reflective clothing in a biomotion configuration facilitated the highest accuracy and confidence in judgment of pedestrian walking direction, for both thin and thick strips compared to vest, for all blur levels., (© 2021 The Authors Ophthalmic and Physiological Optics © 2021 The College of Optometrists.)

Purpose: The measurement of standard visual acuity (VA) is the most well-known part of any ophthalmic examination to indicate visual function. Despite this, it is insensitive in detecting early disease changes. Therefore, other visual function tests have been developed including low luminance VA (LLVA) and low luminance deficit (LLD). This scoping literature review aims to summarise the current published applications of LLVA and LLD assessments to evaluate their utility as clinical markers and research outcome measures in a variety of ophthalmic conditions., Recent Findings: Sixty-five peer-reviewed publications were included. LLVA was pioneered for use in geographic atrophy, a subtype of age-related macular degeneration, which remains the mainstay of its clinical application. However, other studies have reported additional useful applications in inherited retinal diseases including rare maculopathies and rod-cone dystrophies. Although there are some variations in testing methodology, use of the standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart with a 2.0 log unit neutral density filter is the most popular approach. The optimal testing luminance is still to be defined., Summary: Overall, LLVA is an earlier clinical marker of change in central retinal function than standard VA. It has been shown to be a risk factor for disease progression and a better indicator of a patient's level of everyday visual function. It is inexpensive and simple to implement using readily available standard ophthalmic equipment., (© 2021 The Authors Ophthalmic and Physiological Optics © 2021 The College of Optometrists.)

Objective: The objective of this study was to assess and compare drivers' and non-drivers' outcomes in the Adult Developmental Eye Movement test (ADEM), a visual-verbal test that measures the time needed to read series of numbers in both a vertical and horizontal reading pattern. A set of driving parameters (i.e., experience, risk exposure, and day and night perceived difficulty) and demographic variables (i.e., age, gender, and academic level) were considered as potential predictors of the test performance., Methods: For this cross-sectional study, 302 healthy subjects (age range 20 to 86 years old) completed a self-reported questionnaire aimed at retrieving data on the independent variables, and underwent the ADEM in order to obtain the dependent outcomes. 214 (70.9%) of the participants were drivers. Non-parametric analyses and multilevel linear regression were used to assess differences between the variables and a prediction model. Also, some correlations were evaluated through the Spearman test., Results: Drivers showed significantly better test performance than non-drivers. The age, driving experience, and perceived difficulty in driving at night were obtained as potential predictors of the test performance with the applied linear regression model., Conclusion: The ADEM may be a practical, non-expensive, easy-to-apply tool in the assessment of drivers, useful for obtaining or renewing the driving license. This test may help in the detection of impairments in the saccadic efficiency that could have a detrimental effect on the driving performance., Competing Interests: The authors have declared that no competing interests exist.

In humans, visual stimuli can be perceived across an enormous range of light levels. Evidence suggests that different neural mechanisms process different subdivisions of this range. For instance, in the retina, stimuli presented at very low (scotopic) light levels activate rod photoreceptors, whereas cone photoreceptors are activated relatively more at higher (photopic) light levels. Similarly, different retinal ganglion cells are activated by scotopic versus photopic stimuli. However, in the brain, it remains unknown whether scotopic versus photopic information is: 1) processed in distinct channels, or 2) neurally merged. Using high-resolution functional magnetic resonance imaging at 7 T, we confirmed the first hypothesis. We first localized thick versus thin-type columns within areas V2, V3, and V4, based on photopic selectivity to motion versus color, respectively. Next, we found that scotopic stimuli selectively activated thick- (compared to thin-) type columns in V2 and V3 (in measurements of both overlap and amplitude) and V4 (based on overlap). Finally, we found stronger resting-state functional connections between scotopically dominated area MT with thick- (compared to thin-) type columns in areas V2, V3, and V4. We conclude that scotopic stimuli are processed in partially segregated parallel streams, emphasizing magnocellular influence, from retina through middle stages of visual cortex., (© The Author(s) 2020. Published by Oxford University Press.)

Purpose: Exposure to high-intensity or outdoor lighting has been shown to decrease the severity of myopia in both human epidemiological studies and animal models. Currently, it is not fully understood how light interacts with visual signaling to impact myopia. Previous work performed in the mouse retina has demonstrated that functional rod photoreceptors are needed to develop experimentally-induced myopia, alluding to an essential role for rod signaling in refractive development., Methods: To determine whether dim rod-dominated illuminance levels influence myopia susceptibility, we housed male C57BL/6J mice under 12:12 light/dark cycles with scotopic (1.6 × 10-3 candela/m2), mesopic (1.6 × 101 cd/m2), or photopic (4.7 × 103 cd/m2) lighting from post-natal day 23 (P23) to P38. Half the mice received monocular exposure to -10 diopter (D) lens defocus from P28-38. Molecular assays to measure expression and content of DA-related genes and protein were conducted to determine how illuminance and lens defocus alter dopamine (DA) synthesis, storage, uptake, and degradation and affect myopia susceptibility in mice., Results: We found that mice exposed to either scotopic or photopic lighting developed significantly less severe myopic refractive shifts (lens treated eye minus contralateral eye; -1.62 ± 0.37D and -1.74 ± 0.44D, respectively) than mice exposed to mesopic lighting (-3.61 ± 0.50D; P < 0.005). The 3,4-dihydroxyphenylacetic acid /DA ratio, indicating DA activity, was highest under photopic light regardless of lens defocus treatment (controls: 0.09 ± 0.011 pg/mg, lens defocus: 0.08 ± 0.008 pg/mg)., Conclusions: Lens defocus interacted with ambient conditions to differentially alter myopia susceptibility and DA-related genes and proteins. Collectively, these results show that scotopic and photopic lighting protect against lens-induced myopia, potentially indicating that a broad range of light levels are important in refractive development.

Purpose: Müller's muscle is a sympathetically innervated smooth muscle which serves as an accessory upper eyelid retractor. Its physiologic function and purpose have not yet been clearly defined. We hypothesize that sympathetic innervation to Müller's muscle serves to adjust the upper eyelid's position to variations in pupil size in response to changes in light intensity., Methods: This is a single center cross-sectional study. Healthy volunteers were asked to fixate on a distant non-accommodative target, and a video scan of the anterior segment was performed for each subject's right eye using the Heidelberg Spectralis® optical coherence tomography scanner in infrared mode. The video was taken both in photopic and scotopic conditions, recording the resultant transition of the pupil and eyelids. The pupil diameter (PD), upper eyelid margin-to-reflex distance (MRD1), lower eyelid margin-to-reflex distance (MRD2), and vertical palpebral fissure height (PFH) were measured., Results: Thirty-three healthy volunteers (19 women, 57.6%) with a median age of 40 years (range 30-58) were included. The mean PD under photopic conditions increased significantly under scotopic conditions, from 3483 ± 521 μm to 6135 ± 703 μm, respectively (P < 0.0001). An increase in MRD1 was observed following transition from light to dark, with a mean change of 348 ± 311 μm (P < 0.0001). There was no significant change in MRD2., Conclusions: Upper eyelid retraction occurs after transition from photopic to scotopic conditions. This movement suggests the existence of an "eyelid-light reflex" involving Müller's muscle that adjusts the position of the eyelids as the pupil dilates under scotopic conditions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose : To evaluate the optical quality of highly myopic eyes under light and dark conditions and correlate it with other relevant parameters. Materials and Methods : A cross-sectional, observational study was performed on 180 eyes of 90 highly myopic patients (29 males and 61 females; mean age: 27.833 ± 0.364 years [range: 18-45 years]). The modulation transfer function (MTF) cutoff frequency, Strehl ratio, objective scattering index (OSI), and predicted visual acuity (PVA; 100%, 20%, and 9%) under different lighting conditions were measured to evaluate the optical quality, which was correlated with probable relevant factors, including, axis length, spherical equivalent (SE), uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (BDVA), astigmatism, and corneal curvature. The relationship between these visual parameters and optical quality was analyzed using a generalized linear model. Results : The OSIs were 1.241 ± 0.068 and 1.515 ± 0.076; the MTF cutoff frequencies were 37.725 ± 0.559 and 30.238 ± 0.550 cpd; the Strehl ratios were 0.219 ± 0.004 and 0.175 ± 0.003; and the PVAs at 100%, 20%, and 9% were 1.257 ± 0.019 and 1.001 ± 0.018, 0.949 ± 0.017 and 0.719 ± 0.015, and 0.579 ± 0.011 and 0.439 ± 0.010, under bright and dark conditions respectively. The optical quality parameters were correlated with age, SE, BDVA, corneal astigmatism, and curvature to different degrees under different lighting conditions. Conclusions : The optical quality declined in highly myopic eyes under both bright and dark lighting conditions. SE, BDVA, corneal astigmatism, and curvature were correlated with optical quality to different degrees under different lighting conditions.

Night-vision handheld scopes are of wide use in military operations at dark conditions. In some cases in the battlefield, as in our case report, if there is no light coming from any source (neither from Moon nor from Stars), infrared light-emitting diode illumination can be coupled with night-vision goggles. Reflected illumination from the target is mostly blue filtered through the night-vision goggles objective lens. Retinal damage induced by unfiltered blue light and visible light has been previously reported. We described a phototoxic maculopathy induced by night-vision handheld scope assembled with infrared light-emitting diode illuminator in two soldiers who are on duty at nights for nearly two-thirds of the last year. The phototoxic maculopathy can represent with typical optical coherence tomography findings such as intraretinal hyperreflective accumulation particularly located on the surface of outer retinal segments defect or presumably in the vicinity of the light passageway. Here, we presented a unique factor causing phototoxic maculopathy.

Purpose: Functional adaptation to ambient light is a key characteristic of retinal ganglion cells (RGCs), but little is known about how adaptation is affected by factors that are harmful to RGC health. We explored adaptation-induced changes to RGC physiology when exposed to increased intraocular pressure (IOP), a major risk factor for glaucoma., Methods: Wild-type mice of both sexes were subjected to 2 weeks of IOP elevation using the bead model. Retinas were assessed using a multielectrode array to record RGC responses to checkerboard white noise stimulation under both scotopic and photopic light levels. This information was used to calculate a spike-triggered average (STA) for each RGC with which to compare between lighting levels., Results: Low but not high IOP elevation resulted in several distinct RGC functional changes: (1) diminished adaptation-dependent receptive field (RF) center-surround interactions; (2) increased likelihood of a scotopic STA; and (3) increased spontaneous firing rate. Center RF size change with lighting level varied among RGCs, and both the center and surround STA peak times were consistently increased under scotopic illumination, although none of these properties were impacted by IOP level., Conclusions: These findings provide novel evidence that RGCs exhibit reduced light-dependent adaptation and increased excitability when IOP is elevated to low but not high levels. These results may reveal functional changes that occur early in glaucoma, which can potentially be used to identify patients with glaucoma at earlier stages when intervention is most beneficial.

Purpose : Morphological retinal changes combined with functional evidence implicate hypoxia in the pathogenesis of age-related macular degeneration (AMD). However, the role of hypoxia in the scotopic threshold deficit reported in AMD has not been investigated. This study compared scotopic thresholds in participants with early and intermediate AMD recorded under conditions of systemic hypoxia, hyperoxia and normoxia. Materials and Methods : Over two sessions scotopic thresholds were measured with participants breathing 21% and 60% oxygen (n = 12 early AMD, n = 11 age-similar controls) or 21% and 14% oxygen (n = 16 early AMD, n = 20 age-similar controls). Thresholds were measured using a 'white', annular 12 degrees stimulus, using a QUEST procedure. Results : There was no statistically significant change in scotopic thresholds within the AMD or control group when breathing the hyperoxic gas mixture (60% oxygen) or the hypoxic gas mixture (14% oxygen) when compared to the normoxic condition (21% oxygen). There was also no statistically significant difference in scotopic thresholds between groups under the hyperoxic or hypoxic gas conditions. The difference between groups under the normoxic condition was not statistically significant for the hyperoxia study ( p = .70), but did reach significance in the hypoxia study ( p = .05). Conclusion : This study provided no evidence that breathing that breathing 14% or 60% oxygen altered scotopic thresholds in those with early AMD when compared to controls. However, the lack of elevated scotopic thresholds in the AMD group of the hyperoxia study is of note, as it is unlikely that hyperoxia would reduce thresholds which were not significantly raised at baseline, regardless of whether hypoxia was a factor in the disease pathogenesis. The findings of this study do not rule out a role for hypoxia in early AMD, but this needs to be assessed in future experiments using measures that differ significantly between people with AMD and controls.

Purpose: Although zebrafish rods begin to develop as early as 2 days postfertilization (dpf), they are not deemed anatomically mature and functional until 15 to 21 dpf. A recent study detected a small electroretinogram (ERG) from rods in a cone mutant called no optokinetic response f (nof) at 5 dpf, suggesting that young rods are functional. Whether they can mediate behavioral responses in larvae is unknown., Methods: We first confirmed rod function by measuring nof ERGs under photopic and scotopic illumination at 6 dpf. We evaluated the role of rods in visual behaviors using two different assays: the visual-motor response (VMR) and optokinetic response (OKR). We measured responses from wild-type (WT) larvae and nof mutants under photopic and scotopic illuminations at 6 dpf., Results: Nof mutants lacked a photopic ERG. However, after prolonged dark adaptation, they displayed scotopic ERGs. Compared with WT larvae, the nof mutants displayed reduced VMRs. The VMR difference during light onset gradually diminished with decreased illumination and became nearly identical at lower light intensities. Additionally, light-adapted nof mutants did not display an OKR, whereas dark-adapted nof mutants displayed scotopic OKRs., Conclusions: Because the nof mutants lacked a photopic ERG but displayed scotopic ERGs after dark adaptation, the mutants clearly had functional rods. WT larvae and the nof mutants displayed comparable scotopic light-On VMRs and scotopic OKRs after dark adaptation, suggesting that these responses were driven primarily by rods. Together, these observations indicate that rods contribute to zebrafish visual behaviors as early as 6 dpf.

Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon has been considered maladaptive and may preclude vision restoration in the blind. However, several recent studies utilizing triggered photoreceptor ablation have shown adaptive responses in bipolar cells expected to support normal vision. Whether such homeostatic plasticity occurs during progressive photoreceptor degenerative disease to help maintain normal visual behavior is unknown. We addressed this issue in an established mouse model of Retinitis Pigmentosa caused by the P23H mutation in rhodopsin. We show robust modulation of the retinal transcriptomic network, reminiscent of the neurodevelopmental state, and potentiation of rod - rod bipolar cell signaling following rod photoreceptor degeneration. Additionally, we found highly sensitive night vision in P23H mice even when more than half of the rod photoreceptors were lost. These results suggest retinal adaptation leading to persistent visual function during photoreceptor degenerative disease., Competing Interests: HL, NP, TB, JS, KP, FV No competing interests declared, (© 2020, Leinonen et al.)

From starlight to sunlight, adaptation alters retinal output, changing both the signal and noise among populations of retinal ganglion cells (RGCs). Here we determine how these light level-dependent changes impact decoding of retinal output, testing the importance of accounting for RGC noise correlations to optimally read out retinal activity. We find that at moonlight conditions, correlated noise is greater and assuming independent noise severely diminishes decoding performance. In fact, assuming independence among a local population of RGCs produces worse decoding than using a single RGC, demonstrating a failure of population codes when correlated noise is substantial and ignored. We generalize these results with a simple model to determine what conditions dictate this failure of population processing. This work elucidates the circumstances in which accounting for noise correlations is necessary to take advantage of population-level codes and shows that sensory adaptation can strongly impact decoding requirements on downstream brain areas.

Purpose: To examine longitudinal changes of retinal thickness and retinal sensitivity in patients with intermediate age-related macular degeneration (iAMD) and predominantly reticular pseudodrusen (RPD)., Methods: At baseline 30 eyes of 25 iAMD patients underwent optical coherence tomography imaging, mesopic and scotopic fundus-controlled perimetry (FCP) with follow-up examinations at month 12 (20 eyes), 24 (12 eyes), and 36 (11 eyes). Thicknesses of different retinal layers and results of FCP testing (n = 56 stimuli) were spatially and longitudinally analyzed using linear mixed-effects models., Results: At baseline, the thickness of the partial outer retinal layer (pORL, 70.21 vs. 77.47 µm) and both mesopic (16.60 vs. 18.72 dB) and scotopic (12.14 vs. 18.67 dB) retinal sensitivity were decreased in areas with RPD compared with unremarkable areas (P < 0.001). Over three years, mean change of pORL was -0.66 normative standard deviation (SD; i.e., z-score, P < 0.001) for regions with existing RPD, -0.40 SD (P < 0.001) for regions with new occurring RPD, and -0.17 SD (P = 0.041) in unremarkable regions. Decrease of scotopic and mesopic sensitivity over three years was more pronounced in areas with existing (-3.51 and -7.76 dB) and new occurring RPD (-2.06 and -5.97 dB). Structure-function analysis revealed that 1 SD decrease of pORL thickness was associated with a sensitivity reduction of 3.47 dB in scotopic and 0.79 dB in mesopic testing., Conclusions: This study demonstrates progressive outer retinal degeneration and impairment of photoreceptor function in eyes with iAMD and RPD over three years. Preservation of outer retinal thickness and reduction of RPD formation may constitute meaningful surrogate endpoints in interventional trials on eyes with AMD and RPD aiming to slow outer retinal degeneration.

Purpose: Retinitis pigmentosa (RP) is a blinding neurodegenerative disease of the retina that can be affected by many factors. The present study aimed to analyze the effect of different environmental light intensities in rd10 mice retina., Methods: C57BL/6J and rd10 mice were bred and housed under three different environmental light intensities: scotopic (5 lux), mesopic (50 lux), and photopic (300 lux). Visual function was studied using electroretinography and optomotor testing. The structural and morphological integrity of the retinas was evaluated by optical coherence tomography imaging and immunohistochemistry. Additionally, inflammatory processes and oxidative stress markers were analyzed by flow cytometry and western blotting., Results: When the environmental light intensity was higher, retinal function decreased in rd10 mice and was accompanied by light-dependent photoreceptor loss, followed by morphological alterations, and synaptic connectivity loss. Moreover, light-dependent retinal degeneration was accompanied by an increased number of inflammatory cells, which became more activated and phagocytic, and by an exacerbated reactive gliosis. Furthermore, light-dependent increment in oxidative stress markers in rd10 mice retina pointed to a possible mechanism for light-induced photoreceptor degeneration., Conclusions: An increase in rd10 mice housing light intensity accelerates retinal degeneration, activating cell death, oxidative stress pathways, and inflammatory cells. Lighting intensity is a key factor in the progression of retinal degeneration, and standardized lighting conditions are advisable for proper analysis and interpretation of experimental results from RP animal models, and specifically from rd10 mice. Also, it can be hypothesized that light protection could be an option to slow down retinal degeneration in some cases of RP.

Introduction: The use of night vision goggles (NVGs) by medical staff operating in active combat areas may present a tactical advantage in maintaining unit concealment. This study seeks to assess the degree to which NVG use improves speed and ease of intravenous access in comparison to no NVG use, and which NVG system (monocular, binocular or panoramic) provides the best conditions for the clinician., Methods: Cannulation was carried out using both eyes open (BEO) and one eye open (OEO) in well-lit conditions to establish a baseline measurement. The same procedure was then performed with a variety of NVGs, with and without infrared (IR) light sources in a dark room, and the degree of difficulty, time to procedural completion and success rate were compared., Results: NVG use improved procedure speed in comparison to the BEO method in the dark. Among the NVG methods trialled, binocular NVG (BNVG) methods outperformed panoramic NVG (PNVG) and monocular NVG in terms of success rate., Conclusions: Use of BNVG resulted with a better success rate in our study. We would like to emphasise that although combatant units prefer PNVGs for the wider temporal vision they provide, it must be kept in mind that this may pose a disadvantage in peripheral vascular access procedures while providing first aid to the casualty at close distances., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To determine the characteristics of the full-field electroretinograms (ERGs) of eyes with Stickler syndrome., Methods: Twenty-two eyes of 14 Japanese patients from nine families with Stickler syndrome were studied. All of the patients were found to have mutations in the COL2A1 gene and had undergone ERG recordings. The ERGs from one of the two eyes were compared to 11 eyes of 11 normal control subjects who were matched by age, sex, and refractive error., Results: One patient had non-recordable ERGs under both scotopic and photopic conditions. For the remaining 13 patients, the amplitudes of the b-waves of the scotopic combined, rod, and cone responses were significantly smaller than those of the control subjects (P = 0.0001, P = 0.015, P = 0.0006, respectively). The implicit times of the b-wave of the scotopic combined and photopic responses were significantly prolonged (P = 0.0037 and P = 0.0126). The age was inversely and significantly correlated with the amplitudes of the scotopic combined a-wave (P = 0.0184) and b-wave (P = 0.0076) in 13 eyes. The amplitudes of the scotopic combined b-wave amplitudes were not significantly correlated with the refractive error., Conclusions: The reduced or absent full-field ERGs in eyes with Stickler syndrome indicate that the physiology of the entire retina was negatively altered. The greater reduction in the ERGs with increasing age suggests that the physiological alterations of the retina are progressive.

Purpose: To determine the influence of RIBEYE deletion and the resulting absence of synaptic ribbons on retinal light signaling by electroretinography., Methods: Full-field flash electroretinograms (ERGs) were recorded in RIBEYE knock-out (KO) and wild-type (WT) littermate mice under photopic and scotopic conditions, with oscillatory potentials (OPs) extracted by digital filtering. Flicker ERGs and ERGs following intravitreal injection of pharmacological agents were also obtained under scotopic conditions., Results: The a-wave amplitudes were unchanged between RIBEYE KO and WT mice; however, the b-wave amplitudes were reduced in KOs under scotopic, but not photopic, conditions. Increasing stimulation frequency led to a greater reduction in RIBEYE KO b-wave amplitudes compared with WTs. Furthermore, we observed prominent, supernormal OPs in RIBEYE KO mice in comparison with WT mice. Following intravitreal injections with l-2 amino-4-phosphonobutyric acid and cis-2,3 piperidine dicarboxylic acid to block ON and OFF responses at photoreceptor synapses, OPs were completely abolished in both mice types, indicating a synaptic origin of the prominent OPs in the KOs. Conversely, tetrodotoxin treatment to block voltage-gated Na+ channels/spiking neurons did not differentially affect OPs in WT and KO mice., Conclusions: The decreased scotopic b-wave and decreased responses to increased stimulation frequencies are consistent with signaling malfunctions at photoreceptor and inner retinal ribbon synapses. Because phototransduction in the photoreceptor outer segments is unaffected in the KOs, their supernormal OPs presumably result from a dysfunction in retinal synapses. The relatively mild ERG phenotype in KO mice, particularly in the photopic range, is probably caused by compensatory mechanisms in retinal signaling pathways.

Some flying animals use active sensing to perceive and avoid obstacles. Nocturnal mosquitoes exhibit a behavioral response to divert away from surfaces when vision is unavailable, indicating a short-range, mechanosensory collision-avoidance mechanism. We suggest that this behavior is mediated by perceiving modulations of their self-induced airflow patterns as they enter a ground or wall effect. We used computational fluid dynamics simulations of low-altitude and near-wall flights based on in vivo high-speed kinematic measurements to quantify changes in the self-generated pressure and velocity cues at the sensitive mechanosensory antennae. We validated the principle that encoding aerodynamic information can enable collision avoidance by developing a quadcopter with a sensory system inspired by the mosquito. Such low-power sensing systems have major potential for future use in safer rotorcraft control systems., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Blue-blocking lenses (BBLs) are marketed as providing retinal protection from acute and cumulative exposure to blue light over time. The selective reduction in visible wavelengths transmitted through BBLs is known to influence the photosensitivity of retinal photoreceptors, which affects both visual and non-visual functions. This study measured the spectral transmittance of BBLs and evaluated their effect on blue perception, scotopic vision, circadian rhythm, and protection from photochemical retinal damage., Methods: Seven different types of BBLs from six manufacturers and untinted control lenses with three different powers (+2.00 D, -2.00 D and Plano) were evaluated. The whiteness index of BBLs used in this study was calculated using Commission International de l'Eclairage (CIE) Standard Illuminates D65, and CIE 1964 Standard with a 2° Observer. The protective qualities of BBLs and their effect on blue perception, scotopic vision, and circadian rhythm were evaluated based on their spectral transmittance, which was measured with a Cary 5,000 UV-Vis-NIR spectrophotometer., Results: BBLs were found to reduce blue light (400-500 nm) by 6-43 per cent, providing significant protection from photochemical retinal damage compared to control lenses (p ≤ 0.05). All BBLs were capable of reducing the perception of blue colours, scotopic sensitivities and circadian sensitivities by 5-36 per cent, 5-24 per cent, and 4-27 per cent, respectively depending on the brand and power of the lens., Conclusion: BBLs can provide some protection to the human eye from photochemical retinal damage by reducing a portion of blue light that may affect visual and non-visual performances, such as those critical to scotopic vision, blue perception, and circadian rhythm., (© 2019 Optometry Australia.)

Purpose: To determine the electroretinographical and psychophysical parameters that can help to verify patients' complaints of reduced night vision., Methods: We tested 275 consecutive patients with normal appearing fundi, complaining of visual difficulties at night, using flash electroretinography (ERG) and dark adaptation (DA) test. Two ERG parameters were used to assess a scotopic retinal function: the amplitude of the response to dim blue flash (the rod response) and the b-wave ratio (measured/expected). Dark adaptation was measured with green- and red-light stimuli after exposure to a bright, bleaching light. The psychophysical parameter of night vision was defined as the threshold for detection of the blue-green stimulus that was measured after 40-45 min in complete darkness., Results: Fifty-five patients were excluded from the analysis because of a discrepancy between the two ERG parameters in assessment of scotopic retinal function. The remaining 220 patients were divided into 4 groups: (1) normal ERG and normal DA, (2) subnormal ERG and subnormal DA, (3) normal ERG and subnormal DA and (4) subnormal ERG and normal DA. The ERG and DA tests supported the complaint of visual difficulties at night in 67 patients (group 2), while 34 patients were characterized as having normal scotopic visual function (group 1). The other 119 patients (groups 3 and 4) presented a diagnostic dilemma because one test (ERG or dark adaptation) showed normal scotopic function, while the other indicated subnormal scotopic function., Conclusion: Our findings indicate that ERG is an essential, but not sufficient test for verifying patient's complaint on visual difficulties in the dark. We suggest using both electroretinography and psychophysical dark adaptation to test patients complaining of reduced night vision.

Complex visual signaling through various combinations of colors and patterns has been well documented in a number of diurnal reptiles. However, there are many nocturnal species with highly sensitive vision, being able to discriminate colors in night conditions, as was shown in geckos. Because of their sensitivity to chromatic signals, including UV (ultraviolet), they may have potential hidden features in their coloration, which may play role in intraspecific communication (e.g. mate choice) or interspecific signals (e.g. antipredatory function). We explored this hypothesis in nocturnal Leopard geckos (Eublepharis macularius), a species using visual signals in both antipredation defense and courtship, having ontogenetic color change accompanied by a shift in behavior. We used UV photography and visual modeling in order to compare various aspects of their coloration (luminance, contrast, color proportions) between sexes, age groups and populations. We found that Leopard geckos have considerable UV reflectance in white patches on their tails (and on the head in juveniles). Though, no prominent differences were detected in their coloration between various groups. We hypothesize that the limitation of UV reflectance to the head and tail, which are both actively displayed during defense, especially in juveniles, might potentially boost the effect of antipredation signaling., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Pupillary evaluation is a crucial element of physical exams. Noting size, reactivity, and consensual response is critical in assessing for optic nerve dysfunction. We aim to establish normative data for scotopic pupillary size and function in the pediatric population in a clinical setting., Methods: Pupillometry was obtained prospectively for consecutive, normal patients < 18 years old being evaluated by Lurie Children's Ophthalmology. Quantitative data included maximum (MAX) and minimum (MIN) diameters, constriction percentage (CON), latency (LAT), average (ACV) and maximum (MCV) constriction velocities, average dilation velocity (ADV), and 75% recovery time (T75). Iris color was noted as light, intermediate, or dark., Results: 196 eyes of 101 participants (42.6% male, ages 1-17 years, average age 10.3 years) were analyzed. Mean MAX was 6.6 mm (5.1-8.1 mm 95% CI); MIN was 4.7 mm (3.1-6.1 mm 95% CI); CON was 30% (17-42 95% CI); LAT was 230 milliseconds (160-300 ms 95% CI); ACV was 3.70 mm/sec (2.21-5.18 mm/sec 95% CI); and ADV was 0.88 mm/sec (0.38-1.38 mm/sec 95% CI). Age had a positive correlation with MAX, MIN, and CON. 84.2 and 95.8% of participants showed resting pupil asymmetry of ≤0.5 mm and ≤ 1.0 mm, respectively., Conclusions: Quantitative pupillometry can be a useful tool for screening pediatric patients. We sought to establish normative data in this group. We found males to have significantly greater MCV and CON than females (p < 0.05). Also, age had a positive correlation with MAX, MIN, and CON.

Retinal ganglion cells (GCs) are important visual neurons which carry complex spatiotemporal information from the retina to higher visual centers in the brain. By taking advantage of pathway-specific knockout/mutant mice and multi-electrode array (MEA) recording techniques, we analyze contributions of rod and cone pathways to responsiveness, kinetics and receptive field profiles of GCs under scotopic and photopic conditions. Our data suggest: (1) Scotopic responses of some GCs require all three rod pathways, some require only the secondary and tertiary rod pathways, and others require only the tertiary rod pathway. (2) There are more responsive GCs in photopic conditions than responsive GCs in scotopic conditions. (3) Gap junctions slow down GCs' scotopic light responses and increase GCs' ratio of antagonistic to center inputs. (4) Cone pathways do not affect the kinetics but alter the ratio of antagonistic to center inputs of scotopic GC responses, and they speed up GCs photopic responses and alter the ratio of GCs' antagonistic to center synaptic inputs and receptive field profiles. (5) Rod bipolar cells shorten response latency of ON GCs and increase the ratio of GCs' antagonistic to center synaptic inputs. (6) Light adaptation speeds up GCs' temporal processing and tunes GC photopic responses to higher frequencies, and the tertiary rod pathway plays a significant role in adaptation-induced TTP changes in some GCs. (7) GC RF center sizes are partially mediated by AIIACs and GC-GC coupling. (8) Connexin36 gap junctions and cone pathways alter synaptic circuits underlying antagonistic surround inputs to GCs in photopic conditions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A correlation is known to exist between visual sensitivity and oscillations in red opsinand rhodopsin gene expression in zebrafish, both regulated by the clock gene. This indicates that an endogenous circadian clock regulates behavioural visual sensitivity, apart from the regulation exerted by the pineal organ. However, the specific mechanisms for cones (photopic vision) and rods (scotopic vision) are poorly understood. In this work, we performed gene expression, cosinor and immunohistochemical analyses to investigate other key genes involved in light perception, encoding the different subunits of phosphodiesterase pde6 and transducin Gα T , in constant lighting conditions and compared to normal light-dark conditions. We found that cones display prominent circadian oscillations in mRNA levels for the inhibitory subunit gene pde6ha that could contribute to the regulation of photopic sensitivity by preventing overstimulation in photopic conditions. In rods, the mRNA levels of the inhibitory subunit gene pde6ga oscillate under normal conditions and dampen down in constant light but continue oscillating in constant darkness. There is an increase in total relative expression for pde6gb in constant conditions. These observations, together with previous data, suggest a complex regulation of the scotopic sensitivity involving endogenous and non-endogenous components, possibly present also in other teleost species. The Gα T genes do not display mRNA oscillations and therefore may not be essential for the circadian regulation of photosensitivity. In summary, our results support different regulation for the zebrafish photopic and scotopic sensitivities and suggest circadian regulation of pde6ha as a key factor regulating photopic sensitivity, while the regulatory mechanisms in rods appear to be more complex., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To report the clinical and genetic characteristics of 6 cases with late-onset night blindness with peripheral flecks accompanied by progressive trickle-like macular degeneration., Methods: Clinical and genetic data were collected from 6 independent patients who complained of night blindness in their fifth to eighth decade of life. The ophthalmological examinations included ophthalmoscopy, fundus autofluorescence (FAF), and full-field electroretinography (ERG). Whole exome sequencing with target gene analysis was performed to determine the causative genes and variants., Results: All of the patients first complained of night blindness at the ages of 40-71 years. Funduscopic examinations demonstrated white or atrophic flecks scattered in the posterior pole and peripheral retina bilaterally. FAF showed patchy hypo-autofluorescence spots in the posterior pole similar to that of the trickling type of age-related macular degeneration (AMD). The region of abnormal FAF rapidly expanded with age, and one eye developed a choroidal neovascularization. The full-field scotopic ERGs with 20 min of dark adaptation were severely reduced or extinguished in all cases. There was partial recovery of the ERGs after 180 min of dark adaptation. The cone ERGs were reduced in all cases. Whole exome sequencing revealed no pathogenic variants of 301 retinal disease-associated genes., Conclusions: The six cases had some common features with the flecked retina syndrome, familial drusen, and late-onset retinal degeneration although none had pathogenic variants causative for these disorders. These cases may represent a subset of severe trickling AMD or a new clinical entity of acquired pan-retinal visual cycle deficiency of unknown etiology.

Purpose: To evaluate the feasibility in the clinical practice of a fast and simple mesopic microperimetry examination comparing the retinal sensitivity in eyes with drusen and reticular pseudodrusen by scotopic and mesopic testing., Methods: In eyes with only drusen and only reticular pseudodrusen, retinal sensitivity was assessed by mesopic testing and after 35 minutes of dark adaptation by scotopic testing using 2 grids of 6 and 10 stimulus points., Results: Fifteen eyes with drusen and 14 eyes with reticular pseudodrusen were enrolled with mean best-corrected visual acuity of 20/20. In mesopic and scotopic examination, we found significant higher retinal sensitivity of eyes with drusen compared with reticular pseudodrusen (P < 0.001). The mean duration of the examination of mesopic testing was less than 2 minutes, significantly reduced compared with scotopic testing (P < 0.01)., Conclusion: Eyes with reticular pseudodrusen presented a significantly reduced retinal sensitivity than eyes with drusen with scotopic and mesopic testing. The different retinal sensitivity between patients was found despite both group presenting good visual acuity. The retinal sensitivity evaluated by mesopic testing may replace the use of scotopic testing and best-corrected visual acuity examination, saving time and providing useful information in the assessment of macular function to identify patients with risk of disease progression.

Background: Defects in retinol dehydrogenase 12 ( RDH12 ) account for 3.4%-10.5 % of Leber congenital amaurosis and early-onset severe retinal dystrophy (EOSRD) and are a potential target for gene therapy. Clinical trials in inherited retinal diseases have unique challenges, and natural history studies are critical to successful trial design. The purpose of this study was to characterise the natural history of RDH12 -associated retinal degeneration., Methods: A retrospective chart review was performed in individuals with retinal degeneration and two likely disease-causing variants in RDH12 ., Results: 57 subjects were enrolled from nine countries. 33 subjects had clinical records available from childhood. The data revealed an EOSRD, with average age of onset of 4.1 years. Macular atrophy was a universal clinical finding in all subjects, as young as 2 years of age. Scotopic and photopic electroretinography (ERG) responses were markedly reduced in all subjects, and a non-recordable ERG was documented as young as 1 year of age. Assessment of visual acuity, visual field and optical coherence tomography revealed severe loss of function and structure in the majority of subjects after the age of 10 years. Widefield imaging in 23 subjects revealed a unique, variegated watercolour-like pattern of atrophy in 13 subjects and sparing of the peripapillary area in 18 subjects., Conclusions: This study includes the largest collection of phenotypic data from children with RDH12 -associated EOSRD and provides a comprehensive description of the timeline of vision loss in this severe, early-onset condition. These findings will help identify patients with RDH12 -associated retinal degeneration and will inform future design of therapeutic trials., Competing Interests: Competing interests: ATF reports a grant from the Vitreoretinal Surgery Foundation and a K12 grant from the National Institute of Health, during the conduct of the study; other from Ionis Pharamceuticals, outside the submitted work. RRA reports a patent on RDH12 gene therapy. DAT reports a grant from the Foundation Fighting Blindness, during the conduct of the study; In addition, DAT has a patent for viral vectors comprising RDH12 coding regions and methods of treating retinal dystrophies pending., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Glaucoma patients commonly report increasing visual problems under low luminance or glare conditions, yet there is limited understanding of the structural basis of visual functional losses. This report examines the relationship between glaucomatous macular damage, assessed using structure-function correlation, and visual difficulty under low luminance conditions, as measured by Low Luminance Questionnaire (LLQ)., Design: Observational cohort study., Methods: Setting: Tertiary care referral center., Participants: A total of 252 eyes of 126 participants with mild or moderate open-angle glaucoma (24-2 mean deviation [MD] better than -12 dB) selected from a consecutive sample., Predictor: Focal and diffuse macular defects were identified based on corresponding abnormal regions on probability maps from spectral-domain optical coherence tomography (SDOCT) optic disc and macular cube scans, and 10-2 and 24-2 visual fields (VF)., Main Outcome Measure: LLQ scores., Results: Eighty-two of the 126 (65%) better eyes (defined by 24-2 VF MD) had evidence of macular damage, while the remaining 44 did not have macular damage. Of the 82 with damage, 33 (40%) had diffuse damage and 49 (60%) had focal damage. After adjusting for 24-2 MD and age in the multivariable regression, diffuse macular damage remained a significant predictor of the LLQ subscales "difficulty with extreme lighting" (P = .0024), ''difficulty with low lighting" (P = .037), and "diminished mobility"; (P = .042). In contrast, there was no significant difference in LLQ scores in any subscale between participants with focal macular damage and those without macular damage., Conclusion: Mild diffuse glaucomatous macular damage, as detected by abnormal topographic regions on measures of structure and function, is associated with decreased LLQ scores., (Copyright © 2019 Elsevier Inc. All rights reserved.)