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Purpose: Study the scotopic oscillatory potentials (OPs) in mice over a wide range of flash luminance levels using the Hilbert transform (HT) to extract new features of the high frequency components of the electroretinogram (ERG). Methods: Scotopic ERGs [Intensity: − 6.3 to 0.9 log cd∙s∙m−2; 12 h of dark-adaptation] were obtained from adult mice (C57BL/6; n = 7). The Hilbert transform (HT) was obtained within 3 consecutive frequency bands (65–90 Hz, 90–115 Hz and 115–140 Hz), with OPs being denoised, automatically identified and analyzed. Measurements included: number of OPs, duration of the OP response, surface-under-the-curve (SUC) of the HT envelopes, implicit times, and instantaneous frequency at the HT envelope peak, mean peak time differences (PTD) between the envelopes of each frequency band (measuring their synchrony), correlation coefficient and lag between consecutive HT envelopes, as well as the number of peaks on the HT envelopes. Results: The OP response duration, number of OPs and PTD all peaked for flashes between the level corresponding to the RodVmax (maximal b-wave amplitude of the rod ERG; i.e., the first asymptote of the scotopic luminance-response curve) and K (the flash luminance at which the amplitude of the b-wave is half of that of the RodVmax;), i.e., between -3.9 and -2.4 log cd∙s∙m−2. The correlation between consecutive envelopes is close to 1 at flashes > -1.2 log cd∙s∙m−2, with small lags (min. = 1.93 ± 0.45 ms at − 1.2 log cd∙s∙m−2), then gradually drops to 0.81 ± 0.02 at the dimmest flash intensity (with a max. lag = 14.76 ± 8.92 ms at − 5.1 log cd∙s∙m−2). Finally, we found that the single OP burst (i.e., a single HT envelope peak) seen at flash intensities > − 1.2 log cd∙s∙m−2 progressively divided in two (or more) OP bursts (i.e., multiple HT envelope peaks) with gradually dimmer flashes. Conclusions: Our HT method enabled the analysis of the OP response without the subjective interpretation of the experimenter. Analysis of the scotopic OPs at dim flashes with the HT revealed a novel feature of the OP response not yet reported elsewhere, namely: a split of the OP response into two (or more) distinct bursts. Furthermore, the synchrony peak (measured with the PTD) matched the peak in OP response duration between K and RodVmax, suggesting a disorganization (or dephasing) of the retinal signal in ERGs evoked for weaker flashes. The increased synchronization and correlation of the single burst observed for the strongest flashes could suggest an optimization or saturation of the retinal response. We believe that these novel features of the OP components of the ERG went unnoticed given that previous studies did not use weak enough flashes and failed to recognize the added value that time and frequency domain analysis of the ERG (such as what is achieved with the HT) brings to the interpretation (and our understanding) of the retinal response. [ABSTRACT FROM AUTHOR]

Introduction Foot-borne soldiers sometimes carry out nighttime operations. It has previously been reported an elevated metabolic demand and impaired walking economy during outdoor walking on a gravel road in darkness wearing night vision goggles (NVG), compared with wearing a headlamp. The aim of the present study was to evaluate the effect of wearing NVG while walking in a hilly forest terrain and compare the results between experienced and inexperienced NVG users. Materials and Methods At nighttime, two different groups, inexperienced (five men and six women) and experienced (nine men) NVG users, walked 1.1 km at a self-selected comfortable pace in a hilly forest. Part I was mainly uphill, and Part II was mainly downhill. Walks were performed wearing a headlamp (light), monocular NVG (mono), binocular NVG (bino), or mono with a 25 kg extra weight (backpack). Walking economy calculated from oxygen uptake in relation to body mass and covered distance (V̇O2 (mL/[kg · km])), heart rate, gait, and walking speed were measured. Results In both groups, walking economy was deteriorated in all three conditions with limited vision (mono, bino, and backpack) compared to the light condition, both during Part I (mono/bino, experienced: +26/+25%, inexperienced: +34/+28%) and Part II (mono/bino, experienced: +44/+46%, inexperienced: +63/+49%). In the backpack condition, the relative change of walking economy was greater for the inexperienced group than the experienced group: Part I (experienced: +46%, inexperienced: +70%), Part II (experienced: +71%, inexperienced: +111%). Concurrently, the step length was shorter in all three conditions with limited vision during Part I (mono/bino/backpack, experienced: −7/−7/−15%, inexperienced: −12/−12/−19%) and Part II (mono/bino/backpack; experienced: −8/−8/−14%, inexperienced: −17/−15/−24%) than in the light condition. The experienced NVG users walked faster during all conditions, but there was no difference in heart rate between groups. Conclusions Despite that foveal vision using NVG is adequate, it appears that the mechanical efficiency during nighttime walking in hilly terrain was markedly lower while wearing NVG than with full vision, regardless of whether the soldier was an experienced or inexperienced NVG user. Moreover, the walking economy was even more affected when adding the 25-kg extra weight. It is probable that the deteriorated mechanical efficiency was partly due to the shorter step length in all three conditions with limited vision. [ABSTRACT FROM AUTHOR]

Background: Urologists frequently activate foot pedals in a low-light operating room (OR). Pedal activation in low-light conditions poses the potential for incorrect pedal activation, potentially leading to increased radiation exposure, patient burns, or OR fires. This study compares speed, accuracy, dark adaptation, and surgeon preference for pedal activation in 4 lighting conditions. Materials and Methods: During a simulated percutaneous nephrolithotomy (PCNL), pedals for C-arm, laser, and ultrasonic lithotripter (USL) were randomized to 3 different positions. Urology attendings, residents, and medical students activated pedals in a randomized order in 4 settings: a dark OR with no illumination, an OR with overhead illumination, a dark OR with glowstick illumination, and a dark OR with blacklight illumination. Endpoints included pedal activation time; number of attempted, incomplete, and incorrect activations; dark adaptation; and subjective pedal preference. ANOVA was used for analysis with p < 0.05 considered significant. Results: In our study with 20 participants, the mean pedal activation times were significantly faster when using glowstick illumination (6.77 seconds) and blacklight illumination (5.34 seconds) compared with the no illumination arm (8.47 seconds, p < 0.001). Additionally, individual pedal activations for the C-arm, laser, and USL were significantly faster with glowstick and blacklight illumination compared with a dark OR (p < 0.001 for all). The blacklight illumination arm demonstrated decreased attempted (0.30 vs. 3.45, p < 0.001), incomplete (1.25 vs. 7.75, p < 0.001), and incorrect activations (0.35 vs. 1.25, p < 0.001) compared with the dark setting, while demonstrating no difference compared with having room lights on. Dark adaptation was significantly improved with blacklight illumination compared with having the room lights on (134.5 vs. 140.5 luminance, p < 0.001). All participants (100%) preferred illuminated pedals compared with the dark OR, with 90% favoring the blacklight illumination. Conclusions: During a simulated PCNL, blacklight illumination significantly improved accuracy and efficiency of pedal activation compared with the conventional dark OR, while maintaining the surgeon's dark adaptation. [ABSTRACT FROM AUTHOR]

The color contour detection model used for simulating the cone photoreceptor cell-lateral geniculate nucleus (LGN) - primary visual cortex (V1) visual pathway has achieved reliable results. In contrast, the rod photoreceptor cells employ a dark adaptive mechanism, which plays a key role in contour extraction in poorly lit environments. We employ this mechanism to propose a bionic model for contour detection. The proposed model divides the dark adaptation process into several stages and extracts the image information at each stage for subsequent integration. For evaluation, we applied the proposed dark adaptation model as the front-end processing method of the gray and color contour detection model, and performed experimental verification on the RuG, BSDS300/500, and NYUD databases. In comparison with a similar state-of-the-art model, the detection performance of the proposed model has several advantages; in particular, it extracts contour information more effectively in interior scenes lit with dim colors. [ABSTRACT FROM AUTHOR]

Purpose: To understand the spatial relationship between local rod-mediated visual function and reticular pseudodrusen (RPD) in eyes with large drusen. Design: Retrospective cross-sectional study. Participants: One eye with large drusen (>125 μm) each from 91 individuals with intermediate age-related macular degeneration, with and without RPD. Methods: All participants underwent dark adaptation testing using a dark-adapted chromatic perimeter, where visual sensitivities were measured over 30 minutes of dark adaptation after photobleach. The rod intercept time (RIT; a measure of dynamic rod function) and pointwise sensitivity difference (PWSD; a relative measure of rod- compared with cone-mediated function) was determined at multiple retinal locations, and their association with the overall (central 20° × 20° region) and local (2° diameter region centered on the location tested) extent of RPD and drusen (quantified using multimodal imaging) was examined. Main Outcome Measures: Association between overall and local extent of RPD and drusen with RIT and PWSD at each retinal location tested. Results: In a multivariable analysis, delayed RIT was associated with an increasing overall (P < 0.001), but not local (P = 0.884), extent of RPD. In contrast, the increasing local (P < 0.001), but not overall (P = 0.475), extent of drusen was associated with delayed RIT. Furthermore, only an increasing overall extent of RPD (P < 0.001) was associated with reduced PWSD (or worse rod compared with cone function), but not the local extent of RPD and drusen, or overall extent of drusen (P ≥ 0.344). Conclusions: Local rod-mediated function was associated with the overall, rather than local, extent of RPD in eyes with large drusen, suggesting that there may be widespread pathologic changes in eyes with RPD that account for this. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Antarctic algae are exposed to prolonged periods of extreme darkness due to polar night, and coverage by ice and snow can extend such dark conditions to up to 10 months. A major group of microalgae in benthic habitats of Antarctica are diatoms, which are key primary producers in these regions. However, the effects of extremely prolonged dark exposure on their photosynthesis, cellular ultrastructure, and cell integrity remain unknown. Here we show that five strains of Antarctic benthic diatoms exhibit an active photosynthetic apparatus despite 10 months of dark-exposure. This was shown by a steady effective quantum yield of photosystem II (Y[II]) upon light exposure for up to 2.5 months, suggesting that Antarctic diatoms do not rely on metabolically inactive resting cells to survive prolonged darkness. While limnic strains performed better than their marine counterparts, Y(II) recovery to values commonly observed in diatoms occurred after 4-5 months of light exposure in all strains, suggesting long recovering times. Dark exposure for 10 months dramatically reduced the chloroplast ultrastructure, thylakoid stacking, and led to a higher proportion of cells with compromised membranes than in lightadapted cells. However, photosynthetic oxygen production was readily measurable after darkness and strong photoinhibition only occurred at high light levels (>800 µmol photons m-2 s-1). Our data suggest that Antarctic benthic diatoms are well adapted to long dark periods. However, prolonged darkness for several months followed by only few months of light and another dark period may prevent them to regain their full photosynthetic potential due to long recovery times, which might compromise long-term population survival. [ABSTRACT FROM AUTHOR]

Nighttime object detection is challenging due to dim, uneven lighting. The IIHS research conducted in 2022 shows that pedestrian anti-collision systems are less effective at night. Common solutions utilize costly sensors, such as thermal imaging and LiDAR, aiming for highly accurate detection. Conversely, this study employs a low-cost 2D image approach to address the problem by drawing inspiration from biological dark adaptation mechanisms, simulating functions like pupils and photoreceptor cells. Instead of relying on extensive machine learning with day-to-night image conversions, it focuses on image fusion and gamma correction to train deep neural networks for dark adaptation. This research also involves creating a simulated environment ranging from 0 lux to high brightness, testing the limits of object detection, and offering a high dynamic range testing method. Results indicate that the dark adaptation model developed in this study improves the mean average precision (mAP) by 1.5−6% compared to traditional models. Our model is capable of functioning in both twilight and night, showcasing academic novelty. Future developments could include using virtual light in specific image areas or integrating with smart car lighting to enhance detection accuracy, thereby improving safety for pedestrians and drivers. [ABSTRACT FROM AUTHOR]

Antarctic algae are exposed to prolonged periods of extreme darkness due to polar night, and coverage by ice and snow can extend such dark conditions to up to 10 months. A major group of microalgae in benthic habitats of Antarctica are diatoms, which are key primary producers in these regions. However, the effects of extremely prolonged dark exposure on their photosynthesis, cellular ultrastructure, and cell integrity remain unknown. Here we show that five strains of Antarctic benthic diatoms exhibit an active photosynthetic apparatus despite 10 months of dark-exposure. This was shown by a steady effective quantum yield of photosystem II (Y[II]) upon light exposure for up to 2.5 months, suggesting that Antarctic diatoms do not rely on metabolically inactive resting cells to survive prolonged darkness. While limnic strains performed better than their marine counterparts, Y(II) recovery to values commonly observed in diatoms occurred after 4-5 months of light exposure in all strains, suggesting long recovering times. Dark exposure for 10 months dramatically reduced the chloroplast ultrastructure, thylakoid stacking, and led to a higher proportion of cells with compromised membranes than in light-adapted cells. However, photosynthetic oxygen production was readily measurable after darkness and strong photoinhibition only occurred at high light levels (>800 µmol photons m-2 s-1). Our data suggest that Antarctic benthic diatoms are well adapted to long dark periods. However, prolonged darkness for several months followed by only few months of light and another dark period may prevent them to regain their full photosynthetic potential due to long recovery times, which might compromise long-term population survival.

The photocycle of visual opsins is essential to maintain the light sensitivity of the retina. The early physical observations of the rhodopsin photocycle by Böll and Kühne in the 1870s inspired over a century's worth of investigations on rhodopsin biochemistry. A single photon isomerizes the Schiff‐base linked 11‐cis‐retinylidene chromophore of rhodopsin, converting it to the all‐trans agonist to elicit phototransduction through photoactivated rhodopsin (Rho*). Schiff base hydrolysis of the agonist is a key step in the photocycle, not only diminishing ongoing phototransduction but also allowing for entry and binding of fresh 11‐cis chromophore to regenerate the rhodopsin pigment and maintain light sensitivity. Many challenges have been encountered in measuring the rate of this hydrolysis, but recent advancements have facilitated studies of the hydrolysis within the native membrane environment of rhodopsin. These techniques can now be applied to study hydrolysis of agonist in other opsin proteins that mediate phototransduction or chromophore turnover. In this review, we discuss the progress that has been made in characterizing the rhodopsin photocycle and the journey to characterize the hydrolysis of its all‐trans‐retinylidene agonist. [ABSTRACT FROM AUTHOR]

During night driving, the light source in the cockpit comes from electronic screens, and the brightness has a direct impact on the driver's visual ergonomics. Based on the characteristics of the cargo ship cockpit light environment during night driving, the performance of participants under different screen brightness is analyzed through dark environment experiments. From the perspective of task effectiveness, the light environment of the cargo ship cockpit is evaluated based on three dimensions of cognitive efficiency, dark adaptability, and comfort. The experimental data is fitted to construct a light environment evaluation model of the cargo ship cockpit for night tasks. And it is concluded that the task performed well when the screen brightness value is controlled at 20cd/m². It plays a guiding role in the optimization of the light environment of the cockpit during cargo ship night driving. [ABSTRACT FROM AUTHOR]

Vertebrate rods and cones operate over a wide range of ambient illumination, which is provided by light adaptation mechanisms regulating the sensitivity and speed of the phototransduction cascade. Three calcium-sensitive feedback loops are well established in both rods and cones: acceleration of the quenching of a lightactivated visual pigment and cGMP synthesis by guanylate cyclase, and increased affinity of ion channels for cGMP. Accumulating evidence suggests that the molecular mechanisms of light adaptation are more complex. While investigating these putative mechanisms, we discovered a novel phenomenon, observing that the recovery of light sensitivity in rods after turning off non-saturating adaptive light can take tens of seconds. Moreover, after a formal return of the membrane current to the dark level, cell sensitivity to the stimuli remains decreased for a further 1–2 min. We termed this phenomenon of prolonged photoreceptor desensitization ‘adaptation memory’ (of previous illumination) and the current study is focused on its detailed investigation in rods and an attempt to find the same phenomenon in cones. In rods, we have explored the dependencies of this phenomenon on adapting conditions, specifically, the intensity and duration of adapting illumination. Additionally, we report that fish and frog red-sensitive cones possess similar features of adaptation memory, such as a drop in sensitivity just after the steps of bright light and slow sensitivity recovery. However, we have found that the rate of this process and its nature are not the same as in rods. Our results indicate that the nature of the temporary drop in the sensitivity in rods and cones after adapting steps of light is different. In the rods, adaptation memory could be attributed to the existence of long-lasting modifications of the components of the phototransduction cascade after adapting illumination. In cones, the observed form of the adaptation memory seems to be due to the sensitivity drop caused by a decrease in the availability of the visual pigment, that is, by bleaching. [ABSTRACT FROM AUTHOR]

To report a rare case of Birt-Hogg-Dubé Syndrome (BHD) with progressive chorioretinopathy. Case report. A 55-year-old woman presented with longstanding nyctalopia attributed to a congenital retinal dystrophy, but no prior genetic testing. Her posterior pole examination demonstrated retinal pigment epithelium (RPE) mottling with extensive macular drusen and paracentral chorioretinal atrophy, consistent with a fleck retinopathy. Her past medical history was remarkable for nephrectomy for unilateral renal malignancy, parotid tumors and thyroid nodules. Dark adaptation time was prolonged, and electroretinography (ERG) revealed abnormal waveforms with depressed amplitudes. Genetic testing confirmed a deletion mutation in the folliculin (FLCN) gene and was negative for other relevant mutations, including EFEMP1 responsible for autosomal dominant macular and peripapillary drusen in Doyne honeycomb retinal dystrophy and TIMP3 responsible for Sorsby Fundus Dystrophy. BHD is a rare autosomal-dominant disorder with multi-systemic clinical manifestations caused by a mutation in the FLCN gene. Affected individuals are prone to renal and pulmonary cysts, renal cancer, and fibrofolliculomas. Reports on ocular manifestations of BHD include eyelid fibrofolliculomas, flecked chorioretinopathy, choroidal melanoma, choroidal melanoma with sector melanocytosis, and retinal pigment epithelial micro-detachments. In this case of BHD, we note a fleck retinopathy with bilateral chorioretinal atrophy, displaying a phenotype of extensive chorioretinopathy associated with impaired dark adaptation and ERG abnormalities. BHD: Birt-Hogg-Dubé syndrome; FLCN: Folliculin. RPE: retinal pigment epithelium; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye). OU: Oculus uterque (both eyes); ERG: electroretinogram; mfERG: multifocal electroretinography. ffERG: full-field electroretinography; FAF: fundus autofluorescence; OCT: optical coherence tomography; FA: fluorescein angiography; DA: dark-adapted; LA: light-adapted; mTOR: mammalian target of rapamycin; EFEMP1: epithelial growth factor-containing fibulin-like extracellular matrix protein 1; VPS13B: Vacuolar Protein Sorting 13 Homolog B; AGBL5: AATP/GTP-Binding Protein Like 5; ALMS1: Alstrom Syndrome 1; COL1BA1: Collagen Type I Beta, Alpha Chain 1; PDE6A: Rod Phosphodiesterase 6-alpha; USH2A: Usherin 2a; VCAN: Versican; RP: Retinitis pigmentosa; AR: Autosomal recessive. [ABSTRACT FROM AUTHOR]

Vertebrate rods and cones operate over a wide range of ambient illumination, which is provided by light adaptation mechanisms regulating the sensitivity and speed of the phototransduction cascade. Three calcium-sensitive feedback loops are well established in both rods and cones: acceleration of the quenching of a light-activated visual pigment and cGMP synthesis by guanylate cyclase, and increased affinity of ion channels for cGMP. Accumulating evidence suggests that the molecular mechanisms of light adaptation are more complex. While investigating these putative mechanisms, we discovered a novel phenomenon, observing that the recovery of light sensitivity in rods after turning off non-saturating adaptive light can take tens of seconds. Moreover, after a formal return of the membrane current to the dark level, cell sensitivity to the stimuli remains decreased for a further 1–2 min. We termed this phenomenon of prolonged photoreceptor desensitization ‘adaptation memory’ (of previous illumination) and the current study is focused on its detailed investigation in rods and an attempt to find the same phenomenon in cones. In rods, we have explored the dependencies of this phenomenon on adapting conditions, specifically, the intensity and duration of adapting illumination. Additionally, we report that fish and frog red-sensitive cones possess similar features of adaptation memory, such as a drop in sensitivity just after the steps of bright light and slow sensitivity recovery. However, we have found that the rate of this process and its nature are not the same as in rods. Our results indicate that the nature of the temporary drop in the sensitivity in rods and cones after adapting steps of light is different. In the rods, adaptation memory could be attributed to the existence of long-lasting modifications of the components of the phototransduction cascade after adapting illumination. In cones, the observed form of the adaptation memory seems to be due to the sensitivity drop caused by a decrease in the availability of the visual pigment, that is, by bleaching.

The short and long isoforms of FAIM (FAIM-S and FAIM-L) hold important functions in the central nervous system, and their expression levels are specifically enriched in the retina. We previously described that Faim knockout (KO) mice present structural and molecular alterations in the retina compatible with a neurodegenerative phenotype. Here, we aimed to study Faim KO retinal functions and molecular mechanisms leading to its alterations. Electroretinographic recordings showed that aged Faim KO mice present functional loss of rod photoreceptor and ganglion cells. Additionally, we found a significant delay in dark adaptation from early adult ages. This functional deficit is exacerbated by luminic stress, which also caused histopathological alterations. Interestingly, Faim KO mice present abnormal Arrestin-1 redistribution upon light reception, and we show that Arrestin-1 is ubiquitinated, a process that is abrogated by either FAIM-S or FAIM-L in vitro. Our results suggest that FAIM assists Arrestin-1 light-dependent translocation by a process that likely involves ubiquitination. In the absence of FAIM, this impairment could be the cause of dark adaptation delay and increased light sensitivity. Multiple retinal diseases are linked to deficits in photoresponse termination, and hence, investigating the role of FAIM could shed light onto the underlying mechanisms of their pathophysiology. [ABSTRACT FROM AUTHOR]

The substantial time taken for regaining visual sensitivity (dark adaptation) following bleaching exposures has been investigated for over a century. Psychophysical studies yielded the classic biphasic curve representing recovery of cone‐driven and rod‐driven vision. The electroretinogram (ERG) permits direct assessment of recovery at the level of the retina (photoreceptors, bipolar cells), with the first report over 70 years ago. Over the last two decades, ERG studies of dark adaptation have generated insights into underlying physiological processes. After large bleaches, rod photoreceptor circulating current, estimated from the rod‐isolated bright‐flash ERG a‐wave, takes 30 min to recover, indicating that products of bleaching, thought to be free opsin (unbound to 11‐cis‐retinal), continue to activate phototransduction, shutting off rod circulating current. In contrast, cone current, assessed with cone‐driven bright‐flash ERG a‐waves, recovers within 100 ms following similar exposures, suggesting that free opsin is less able to shut off cone current. The cone‐driven dim‐flash a‐wave can be used to track recovery of cone photopigment, showing regeneration is 'rate‐limited' rather than first order. Recoveries of the dim‐flash ERG b‐wave are consistent also with rate‐limited rod photopigment regeneration (where free opsin, desensitising the visual system as an 'equivalent background', is removed by rate‐limited delivery of 11‐cis‐retinal). These findings agree with psychophysical and retinal densitometry studies, although there are unexplained points of divergence. Post‐bleach ERG recovery has been explored in age‐related macular degeneration and in trials of visual cycle inhibitors for retinal diseases. ERG tracking of dark adaptation may prove useful in future clinical contexts. [ABSTRACT FROM AUTHOR]

The daylight and color vision of diurnal vertebrates depends on cone photoreceptors. The capability of cones to operate and respond to changes in light brightness even under high illumination is attributed to their fast rate of recovery to the ground photosensitive state. This process requires the rapid replenishing of photoisomerized visual chromophore (11‐cis‐retinal) to regenerate cone visual pigments. Recently, several gene candidates have been proposed to contribute to the cone‐specific retinoid metabolism, including acyl‐CoA wax alcohol acyltransferase 2 (AWAT2, aka MFAT). Here, we evaluated the role of AWAT2 in the regeneration of visual chromophore by the phenotypic characterization of Awat2−/− mice. The global absence of AWAT2 enzymatic activity did not affect gross retinal morphology or the rate of visual chromophore regeneration by the canonical RPE65‐dependent visual cycle. Analysis of Awat2 expression indicated the presence of the enzyme throughout the murine retina, including the retinal pigment epithelium (RPE) and Müller cells. Electrophysiological recordings revealed reduced maximal rod and cone dark‐adapted responses in AWAT2‐deficient mice compared to control mice. While rod dark adaptation was not affected by the lack of AWAT2, M‐cone dark adaptation both in isolated retina and in vivo was significantly suppressed. Altogether, these results indicate that while AWAT2 is not required for the normal operation of the canonical visual cycle, it is a functional component of the cone‐specific visual chromophore regenerative pathway. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and effectiveness of photobiomodulation (PBM) in the treatment of diabetic macular edema (DME). Methods: It was a single-center, self-controlled prospective study. The clinical records of 12 diabetic retinopathy patients (5 males and 7 females, 20 eyes in total) who were treated with PBM for DME at the Second Affiliated Hospital, Zhejiang University School of Medicine, were analyzed. The mean age was 56 (26–68) years. All the participants received PBM treatment during darkness at night in no less than 5 days per week and no less than 8 ​h per day. In the baseline check and follow-up checks (1, 2, 6, 10, and 12 months after the start of treatment), the best-corrected visual acuity, the thickness of the retina in the macula, and the changes of the fundus lesions were observed. Wilcoxon signed rank test was used to compare the results before and after treatment. P ​ ​0.05) from the baseline result, except that in the 6th month (P ​= ​0.049). Obvious improvement could be observed in retinal fundus fluorescein angiography images. Conclusions: PBM is a safe and effective treatment of DME, which deserves further investigation.

Abstract Background Age-related macular degeneration (AMD), a leading cause of irreversible vision impairment in the United States and globally, is a disease of the photoreceptor support system involving the retinal pigment epithelium (RPE), Bruch’s membrane, and the choriocapillaris in the setting of characteristic extracellular deposits between outer retinal cells and their blood supply. Research has clearly documented the selective vulnerability of rod photoreceptors and rod-mediated (scotopic) vision in early AMD, including delayed rod-mediated dark adaptation (RMDA) and impaired rod-mediated light and pattern sensitivity. The unifying hypothesis of the Alabama Study on Early Macular Degeneration (ALSTAR2) is that early AMD is a disease of micronutrient deficiency and vascular insufficiency, due to detectable structural changes in the retinoid re-supply route from the choriocapillaris to the photoreceptors. Functionally this is manifest as delayed rod-mediated dark adaptation and eventually as rod-mediated visual dysfunction in general. Methods A cohort of 480 older adults either in normal macular health or with early AMD will be enrolled and followed for 3 years to examine cross-sectional and longitudinal associations between structural and functional characteristics of AMD. Using spectral domain optical coherence tomography, the association between (1) subretinal drusenoid deposits and drusen, (2) RPE cell bodies, and (3) the choriocapillaris’ vascular density and rod- and cone-mediated vision will be examined. An accurate map and timeline of structure-function relationships in aging and early AMD gained from ALSTAR2, especially the critical transition from aging to disease, will identify major characteristics relevant to future treatments and preventative measures. Discussion A major barrier to developing treatments and prevention strategies for early AMD is a limited understanding of the temporal interrelationships among structural and functional characteristics while transitioning from aging to early AMD. ALSTAR2 will enable the development of functionally valid, structural biomarkers for early AMD, suitable for use in forthcoming clinical trials as endpoint/outcome measures. The comprehensive dataset will also allow hypothesis-testing for mechanisms that underlie the transition from aging to AMD, one of which is a newly developed Center-Surround model of cone resilience and rod vulnerability. Trial registration ClinicalTrials.gov Identifier NCT04112667 , October 7, 2019.

Following photopigment bleaching, the rhodopsin and cone-opsins show a characteristic exponential regeneration in the dark with a photocycle dependent on the retinal pigment epithelium. Melanopsin pigment regeneration in animal models requires different pathways to rods and cones. To quantify melanopsin-mediated light adaptation in humans, we first estimated its photopigment regeneration kinetics through the photo-bleach recovery of the intrinsic melanopsin pupil light response (PLR). An intense broadband light (~120,000 Td) bleached 43% of melanopsin compared to 86% of the cone-opsins. Recovery from a 43% bleach was 3.4X slower for the melanopsin than cone-opsin. Post-bleach melanopsin regeneration followed an exponential growth with a 2.5 min time-constant (τ) that required 11.2 min for complete recovery; the half-bleaching level (Ip) was ~ 4.47 log melanopic Td (16.10 log melanopsin effective photons.cm-2.s-1; 8.25 log photoisomerisations.photoreceptor-1.s-1). The effect on the cone-directed PLR of the level of the melanopsin excitation during continuous light adaptation was then determined. We observed that cone-directed pupil constriction amplitudes increased by ~ 10% when adapting lights had a higher melanopic excitation but the same mean photometric luminance. Our findings suggest that melanopsin light adaptation enhances cone signalling along the non-visual retina-brain axis. Parameters τ and Ip will allow estimation of the level of melanopsin bleaching in any light units; the data have implications for quantifying the relative contributions of putative melanopsin pathways to regulate the post-bleach photopigment regeneration and adaptation. [ABSTRACT FROM AUTHOR]

For millennia, people have used "averted vision" to improve their detection of faint celestial objects, a technique first documented around 325 BCE. Yet, no studies have assessed gaze location during averted vision to determine what pattern best facilitates perception. Here, we characterized averted vision while recording eye‐positions of dark‐adapted human participants, for the first time. We simulated stars of apparent magnitudes 3.3 and 3.5, matching their brightness to Megrez (the dimmest star in the Big Dipper) and Tau Ceti. Participants indicated whether each star was visible from a series of fixation locations, providing a comprehensive map of detection performance in all directions. Contrary to prior predictions, maximum detection was first achieved at ~8° from the star, much closer to the fovea than expected from rod‐cone distributions alone. These findings challenge the assumption of optimal detection at the rod density peak and provide the first systematic assessment of an age‐old facet of human vision. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of central serous chorioretinopathy (CSCR) on retinal function using dark adaptation in a human subject, and to follow it through resolution of the disease. Patients: Single patient, 50 years old male patient, with acute CSCR in one eye and resolved old CSCR in the other eye. Observations: Observational study in patient with CSCR followed through resolution of the subretinal fluid (52 days). Dark adaptation was assessed using the AdaptDx® (Maculogix Inc.) measured by Rod Intercept time (RIT) in minutes. A normal retinal locus of the same eye on the opposite side of the fovea was used as control. Retinal separation (microns) was measured using Spectralis Optical Coherence Tomography (Spectralis®, HRA + OCT, Heidelberg engineering). Change in time to dark adapt, were correlated with retinal separation measured in microns, during the course of CSCR.The Rod Intercept time was delayed in the area of detached retina compared to the normal region (control) on presentation with retinal separation (RS) of 104 μm. The Rod Intercept time returned to normal as the retinal separation from retinal pigment epithelium decreased and eventually resolved. Conclusions: This case shows that delay in dark adaptation is proportional to the amount of separation of neurosensory retina from retinal pigment epithelium in CSCR, this may offer a potential of using DA to characterize visual function in CSCR. The association of dark adaptation response with the state of retinal pigment epithelial function and its ability to predict the recurrence of CSCR needs further evaluation.

Introduction: Dark adaptation (DA) has been proposed as a possible functional biomarker for age-related macular degeneration (AMD). In this systematic review we aim to evaluate current methodology used to assess DA in people with AMD, the evidence of precision in detecting the onset and progression of AMD, and the relationship between DA and other functional and structural measures. Methods: MEDLINE, EMBASE, CINAHL, AMED, PsycINFO, PsycARTICLES were searched for studies published between January 2006 and January 2020 that assessed DA in people with AMD. Details of eligible studies including study design, characteristics of study population and outcomes were recorded. All included studies underwent quality appraisal using approved critical appraisal tools. This systematic review follows PRISMA guidelines (PROSPERO registration number: CRD42019129486). Results: Forty-eight studies were eligible for inclusion, reporting a variety of instruments and protocols to assess different DA parameters. Twenty of these studies used the AdaptDx (MacuLogix, Hummelstown, PA, USA) instrument and assessed rod-intercept time (RIT). Most of these reported that RIT was delayed in people with AMD and this delay worsened with AMD severity. Four studies, involving 533 participants, reported estimates of diagnostic performance of AdaptDx to separate people with AMD from visually healthy controls. DA has been compared to other measures of visual function, patient-reported outcome measures (PROMs) and structural measures. Ten studies specifically considered evidence that the presence of certain structural abnormalities was associated with impaired DA in AMD. Conclusions: This systematic review indicates overwhelming evidence of reasonable quality for an association between impaired DA and AMD. Data on the repeatability and reproducibility of DA measurement are sparse. There is evidence that structural abnormalities such as reticular drusen are associated with prolongation of DA time. Fewer studies have explored an association between DA and other measures of visual function or PROMs. We found no studies that had compared DA with performance-based measures. [ABSTRACT FROM AUTHOR]

A great diversity of adaptations is found among animals with compound eyes and even closely related taxa can show variation in their light‐adaptation strategies. A prime example of a visual system evolved to function in specific light environments is the fiddler crab, used widely as a model to research aspects of crustacean vision and neural pathways. However, questions remain regarding how their eyes respond to the changes in brightness spanning many orders of magnitude, associated with their habitat and ecology. The fiddler crab Afruca tangeri forages at low tide on tropical and semi‐tropical mudflats, under bright sunlight and on moonless nights, suggesting that their eyes undergo effective light adaptation. Using synchrotron X‐ray tomography, light and transmission electron microscopy and in vivo ophthalmoscopy, we describe the ultrastructural changes in the eye between day and night. Dark adaptation at dusk triggered extensive widening of the rhabdoms and crystalline cone tips. This doubled the ommatidial acceptance angles and increased microvillar surface area for light capture in the rhabdom, theoretically boosting optical sensitivity 7.4 times. During daytime, only partial dark‐adaptation was achieved and rhabdoms remained narrow, indicating strong circadian control on the process. Bright light did not evoke changes in screening pigment distributions, suggesting a structural inability to adapt rapidly to the light level fluctuations frequently experienced when entering their burrow to escape predators. This should enable fiddler crabs to shelter for several minutes without undergoing significant dark‐adaptation, their vision remaining effectively adapted for predator detection when surfacing again in bright light. [ABSTRACT FROM AUTHOR]

The nuclei of cone photoreceptors are located on the apical side of the outer nuclear layer (ONL) in vertebrate retinas. However, the functional role of this evolutionarily conserved localization of cone nuclei is unknown. We previously showed that Linkers of the Nucleoskeleton to the Cytoskeleton (LINC complexes) are essential for the apical migration of cone nuclei during development. Here, we developed an efficient genetic strategy to disrupt cone LINC complexes in mice. Experiments with animals from both sexes revealed that disrupting cone LINC complexes resulted in mislocalization of cone nuclei to the basal side of ONL in mouse retina. This, in turn, disrupted cone pedicle morphology, and appeared to reduce the efficiency of synaptic transmission from cones to bipolar cells. Although we did not observe other developmental or phototransduction defects in cones with mislocalized nuclei, their dark adaptation was impaired, consistent with a deficiency in chromophore recycling. These findings demonstrate that the apical localization of cone nuclei in the ONL is required for the timely dark adaptation and efficient synaptic transmission in cone photoreceptors. [ABSTRACT FROM AUTHOR]

Purpose: To compare dark-adapted (DA) ERG between 10, 15 and 20 min of dark adaptation (DA). Methods: In a counterbalanced random block design, 40 healthy adult subjects were dark-adapted for 10, 15 or 20 min before we recorded ERGs to nine flash strengths from 0.001 to 10.0 cd s/m2 (dilated pupils) with a DTL-like electrode. Before and between sessions, the room was lit. Apart from choosing a wider range of stimulus strengths, and adding shorter DA times, the recordings fully complied with the ISCEV ERG Standard, namely using corneal electrodes, mydriasis and a standard DA sequence. Results: The a-wave amplitude was not affected by any adaptation condition. For the b-wave amplitude, effects of reduced DA time are stronger for weaker flashes: Reducing DA from 20 to 10 min had no measurable effect on the DA 3 ERG, but reduced the DA 0.01 b-wave significantly (p < 0.0001) to 87 ± 2% (mean ± SEM). The DA 0.001 b-wave (not part of the ISCEV ERG Standard) was more affected (down to 72 ± 4%). There was a small, but significant, increase, only for weak flashes, in a- and b-wave peak times for 20 compared to 10-min dark adaptation time. Conclusion: Reducing dark adaptation time from 20 to 10 min in normal participants has no effect on the ISCEV DA 3 and DA 10 ERG. The reduction in DA 0.01 ERGs to 87 ± 2% agrees with Hamilton and Graham (Doc Ophthalmol 133:11–19, 2016. 10.1007/s10633-016-9554-x) who found 90 ± 2% and with Asakawa et al. (Doc Ophthalmol 139:33–44, 2019. 10.1007/s10633-019-09693-8) who found 83%. Pending verification in pathophysiological states, the current results suggest that one might be able to correct for the 10% amplitude loss when gaining 10 min through shortened DA. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD), a leading cause of irreversible vision impairment in the United States and globally, is a disease of the photoreceptor support system involving the retinal pigment epithelium (RPE), Bruch's membrane, and the choriocapillaris in the setting of characteristic extracellular deposits between outer retinal cells and their blood supply. Research has clearly documented the selective vulnerability of rod photoreceptors and rod-mediated (scotopic) vision in early AMD, including delayed rod-mediated dark adaptation (RMDA) and impaired rod-mediated light and pattern sensitivity. The unifying hypothesis of the Alabama Study on Early Macular Degeneration (ALSTAR2) is that early AMD is a disease of micronutrient deficiency and vascular insufficiency, due to detectable structural changes in the retinoid re-supply route from the choriocapillaris to the photoreceptors. Functionally this is manifest as delayed rod-mediated dark adaptation and eventually as rod-mediated visual dysfunction in general.Methods: A cohort of 480 older adults either in normal macular health or with early AMD will be enrolled and followed for 3 years to examine cross-sectional and longitudinal associations between structural and functional characteristics of AMD. Using spectral domain optical coherence tomography, the association between (1) subretinal drusenoid deposits and drusen, (2) RPE cell bodies, and (3) the choriocapillaris' vascular density and rod- and cone-mediated vision will be examined. An accurate map and timeline of structure-function relationships in aging and early AMD gained from ALSTAR2, especially the critical transition from aging to disease, will identify major characteristics relevant to future treatments and preventative measures.Discussion: A major barrier to developing treatments and prevention strategies for early AMD is a limited understanding of the temporal interrelationships among structural and functional characteristics while transitioning from aging to early AMD. ALSTAR2 will enable the development of functionally valid, structural biomarkers for early AMD, suitable for use in forthcoming clinical trials as endpoint/outcome measures. The comprehensive dataset will also allow hypothesis-testing for mechanisms that underlie the transition from aging to AMD, one of which is a newly developed Center-Surround model of cone resilience and rod vulnerability.Trial Registration: ClinicalTrials.gov Identifier NCT04112667, October 7, 2019. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Plasma metabolomic profiles have been shown to be associated with age-related macular degeneration (AMD) and its severity stages. However, all studies performed to date have been cross-sectional and have not assessed progression of AMD. This prospective, longitudinal, pilot study analyzes, for the first time, the association between plasma metabolomic profiles and progression of AMD over a 3-year period. At baseline and 3 years later, subjects with AMD (n = 108 eyes) and controls (n = 45 eyes) were imaged with color fundus photos for AMD staging and tested for retinal function with dark adaptation (DA). Fasting plasma samples were also collected for metabolomic profiling. AMD progression was considered present if AMD stage at 3 years was more advanced than at baseline (n = 26 eyes, 17%). Results showed that, of the metabolites measured at baseline, eight were associated with 3-year AMD progression (p < 0.01) and 19 (p < 0.01) with changes in DA. Additionally, changes in the levels (i.e., between 3 years and baseline) of 6 and 17 metabolites demonstrated significant associations (p < 0.01) with AMD progression and DA, respectively. In conclusion, plasma metabolomic profiles are associated with clinical and functional progression of AMD at 3 years. These findings contribute to our understanding of mechanisms of AMD progression and the identification of potential therapeutics for this blinding disease.

Existing literature on sensory deprivation suggests that short-lasting periods of dark adaptation (DA) can cause changes in visual cortex excitability. DA cortical effects have previously been assessed through phosphene perception, i.e., the ability to report visual sensations when a transcranial magnetic stimulation (TMS) pulse is delivered over the visual cortex. However, phosphenes represent an indirect measure of visual cortical excitability which relies on a subjective report. Here, we aimed at overcoming this limitation by assessing visual cortical excitability by combining subjective (i.e., TMS-induced phosphenes) and objective (i.e., TMS-evoked potentials - TEPs) measurements in a TMS-EEG protocol after 30 min of DA. DA effects were compared to a control condition, entailing 30 min of controlled light exposure. TMS was applied at 11 intensities in order to estimate the psychometric function of phosphene report and explore the relationship between TEPs and TMS intensity. Compared to light adaptation, after DA the slope of the psychometric function was significantly steeper, and the amplitude of a TEP component (P60) was lower, only for high TMS intensities. The perceptual threshold was not affected by DA. These results support the idea that DA leads to a change in the excitability of the visual cortex, accompanied by a behavioral modification of visual perception. Furthermore, this study provides a first valuable description of the relationship between TMS intensity and visual TEPs. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between adaptation time and the parameters of electroretinography (ERG) and pupillography in healthy subjects. Methods: Forty-six eyes of 23 healthy women (mean age 21.7 years) were enrolled. ERG and pupillography were tested in each of the right and left 23 eyes, respectively. ERG with a skin electrode was used to determine amplitude and implicit time by the records of rod-, flash-, cone-, and flicker-responses with white light (0.01–30 cd s/m2). Infrared pupillography was used to record the pupillary light reflex to 1-s stimulation of red light (100 cd/m2). Cone- and flicker- (rod-, flash- and pupil) responses were recorded after light (dark) adaptation at 1, 5, 10, 15, and 20 min. Results: Amplitude (µV) was significantly different between 1 min and ≥ 5 or ≥ 10 min after adaptation in b-wave of cone- or rod-response, respectively. Implicit time (ms) differed significantly between 1 min and ≥ 5 min after adaptation with b-wave of cone- and rod-response. There were significant differences between 1 min and ≥ 10 or ≥ 5 min after dark adaptation in parameter of minimum pupil diameter (mm) or constriction rate (%), respectively. Conclusions: Cone-driven ERG can be recorded, even in 5 min of light adaptation time without any special light condition, whereas rod-driven ERG and pupillary response results can be obtained in 10 min or longer of dark adaptation time in complete darkness. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the anatomic versus functional changes in diabetic retinopathy (DR) by studying the correlation of retinal vascular perfusion density and dark adaptation (DA). Methods: Optical coherence tomography angiography (OCTA) and DA tests were performed in diabetic patients and nondiabetic controls. DA was measured using AdaptDx dark adaptometer and the rod intercept was recorded. Macular OCTA images were acquired using the RTVue XR Avanti with AngioVue. Results: Eighty-six eyes from 57 patients with diabetes (19 with no DR, 19 with non-proliferative DR [NPDR], and 19 with proliferative DR [PDR] who had undergone photocoagulation) and 10 eyes from 10 patients without diabetes were recruited. A significant decrease in vascular density and a prolonged rod intercept were found as DR progressed (P <.01). A negative trend was found between vascular density and the rod intercept. The negative trend in the deep layer (R2 = 0.28) was more substantial than that in the superficial layer (R2 = 0.14). A prolonged rod intercept was associated with elevated HbA1c (R2 = 0.08). Conclusions: The vascular density of the macula could be assessed by OCTA and the functional change in the outer retina could be measured non-invasively by DA. The severity of decreasing vascular density and prolongation of DA are proportional to progression of DR. Decreased deep retinal vascular perfusion density and impaired DA response are correlated and show a negative trend according to the severity of DR. [ABSTRACT FROM AUTHOR]

Abstract Obesity has been associated with abnormal lipid metabolism and with tissue hypoxia. Human Bruch's membrane (BrM) lipid deposits have been proposed to create a diffusion barrier to metabolic exchange between the choroid and photoreceptors, delaying the regeneration of photopigments. The speed of retinal dark adaptation (DA) is dependent on the regeneration of these photopigments. While the retina is extremely sensitive to hypoxia, the inner retina, which encodes visual contrast, is more affected by hypoxia than the outer retina. This study examines the association between adiposity measures and the time course of DA measured psychophysically through contrast detection to test the functionality of both the outer and inner retina. Cone-mediated DA recovery of contrast threshold (CT) was measured following near-total photopigment bleach for 6 min in 52 healthy eyes of 52 individuals (42.6 ± 18.3 years). Stimuli were sine-wave gratings of low-spatial frequency (1 cycle-per-degree (cpd)) and low luminance (1 cd/m2) generated at the centre of a CRT monitor. CT recovery functions were fitted to an exponential decay model to determine the time constant (τ, seconds) of cone sensitivity recovery, final cone CT (CT f) and CT elevation (CT 0). Weight, height and waist circumference (WC) were measured and body mass index (BMI) and waist-to-height ratio (WHtR) calculated. Relationships were examined through Spearman correlation and through multiple linear regression using age, optical and adiposity measures as independent variables. The repeatability of cone time constant measurements was estimated by the Bland-Altman method and reported as the coefficient of repeatability (CoR). Mean ± SD of time constant and CT f were 57.3 ± 27.7 s and −1.78 ± 0.20 log 10 units respectively. Cone time constant showed positive Spearman correlation with WC (p = 0.008) and WHtR (p = 0.023) but not with BMI (p = 0.058). Only WHtR emerged as an independent predictor of time constant (p = 0.001). CT f was not correlated with any adiposity measures. Mean cone time constant was 41 s slower in subjects (25%, n = 13) with abdominal obesity (WHtR≥0.5). Mean CT f was not significantly different in subjects with or without abdominal obesity. CoR for cone time constant was ±16 s. In adult subjects, greater abdominal obesity (WHtR) was related to a longer contrast recovery time for cone-mediated DA (time to dark-adapt) suggesting outer retinal dysfunction. Final contrast threshold, preferentially processed by inner retinal cells, was unaffected by abdominal obesity. Highlights • Cone-mediated dark adaptation slowed down as abdominal obesity increased. • Final contrast threshold was unaffected by abdominal obesity in healthy eyes. • Intersession repeatability of contrast sensitivity recovery time constant was good. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) and senile cataract are associated with the age. The basic method of surgery in all types of cataracts is phacoemulsification. The damaging effect of ultrasound is connected with the violation of morpho-functional relationships of photoreceptors in the central area of retina. The main role in antioxidant protection from photo-damage and oxidative stress belongs to lutein and zeaxantine. The regular use of Retinorm in the preand post-operative period can prevent a AMD development and progression. Evaluation of the efficiency in treatment with Retinorm can be performed using the contrast sensitivity and the dark adaptation.

The purpose of this study was to analyze the association between plasma metabolite levels and dark adaptation (DA) in age-related macular degeneration (AMD). This was a cross-sectional study including patients with AMD (early, intermediate, and late) and control subjects older than 50 years without any vitreoretinal disease. Fasting blood samples were collected and used for metabolomic profiling with ultra-performance liquid chromatography–mass spectrometry (LC-MS). Patients were also tested with the AdaptDx (MacuLogix, Middletown, PA, USA) DA extended protocol (20 min). Two measures of dark adaptation were calculated and used: rod-intercept time (RIT) and area under the dark adaptation curve (AUDAC). Associations between dark adaption and metabolite levels were tested using multilevel mixed-effects linear modelling, adjusting for age, gender, body mass index (BMI), smoking, race, AMD stage, and Age-Related Eye Disease Study (AREDS) formulation supplementation. We included a total of 71 subjects: 53 with AMD (13 early AMD, 31 intermediate AMD, and 9 late AMD) and 18 controls. Our results revealed that fatty acid-related lipids and amino acids related to glutamate and leucine, isoleucine and valine metabolism were associated with RIT (p < 0.01). Similar results were found when AUDAC was used as the outcome. Fatty acid-related lipids and amino acids are associated with DA, thus suggesting that oxidative stress and mitochondrial dysfunction likely play a role in AMD and visual impairment in this condition.

Background: Hypoxia may contribute to the development and progression of diabetic macular oedema (DMO) and diabetic retinopathy. The photoreceptors are the most metabolically active cells in the retina and the rod photoreceptors consume the maximal amount of oxygen for dark adaptation. Therefore, a lightmask emitting 500- to 505-nm light and worn at night during sleep may prevent rod-related dark adaptation and, thereby, reduce the retinal oxygen consumption and improve or prevent progression of DMO and diabetic retinopathy as evidenced in small short-term studies. Objectives: The clinical effectiveness and safety of using a lightmask to prevent dark adaptation as a treatment and preventative option was evaluated for DMO over 24 months. Design: A Phase III, multicentre, prospective, single-masked, randomised controlled clinical trial that evaluated the clinical effectiveness and safety of a lightmask that prevents dark adaptation to treat and prevent non-central DMO versus standard care (i.e. non-lightmask arm) at 24 months. A subset of participants also enrolled for a mechanistic substudy that evaluated the role of hypoxia in DMO. Setting: Fifteen NHS clinical sites in the UK. Participants: Adults with non-centre-involving DMO. Intervention: The participants were randomly assigned (1 : 1) to being offered a lightmask (Noctura 400 Sleep Masks, Polyphotonix Medical Ltd, Durham, UK) to wear at night during sleep to prevent dark adaptation or to the non-lightmask arm (standard care) for 24 months. The participants were evaluated every 4 months. Main outcome measure: The primary outcome was defined as a change in retinal thickness at the zone of maximum thickness measured by spectral domain optical coherence tomography at 24 months in the study eye, analysed using a linear mixed-effects model that estimated adjusted treatment effects at both 12 and 24 months. Results: A total of 308 participants were recruited between April 2014 and May 2015. A total of 155 participants in the lightmask arm and 153 in the control arm contributed to the intention-to-treat strategy. The lightmask arm did not show any difference in effect compared with the non-lightmask arm [adjusted mean difference between arms –0.65 µm, 95% confidence interval –6.90 to 5.59 µm; p = 0.84). The compliance of wearing the lightmask was suboptimal, as recorded electronically, from the returned lightmasks. There were no lightmask-related severe adverse events. The mechanistic study aimed at studying the effect of improving hypoxia by inhaling 100% oxygen or by offering lightmasks to wear during sleep at night over 12 months did not demonstrate any clinically beneficial effect on DMO. Conclusion: The lightmask, as offered in this trial to prevent dark adaptation, did not show any treatment or preventative effect in participants with non-central oedema or diabetic retinopathy at 24 months. No effect was seen as early as 4 months when compliance was higher. Future work: Future research is needed to evaluate the role of rod-induced hypoxia in the pathogenesis of DMO and diabetic retinopathy. Trial registration: Current Controlled Trials ISRCTN85596558. Funding: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership. The report will be published in full in Efficacy and Mechanism Evaluation; Vol. 6, No. 2. See the NIHR Journals Library website for further project information. The lightmasks were purchased at a discounted rate from Polyphotonix Medical Ltd.

Dark adaptation is a highly sensitive neural function and may be the first symptom of many status including the physiologic and pathologic entity, suggesting that it could be instrumental for diagnose. However, shortcomings such as the lack of standardized parameters, the long duration of examination, and subjective randomness would substantially impede the use of dark adaptation in clinical work. In this review we summarize the recent research about the dark adaptation, including two visual cycles-canonical and cone-specific visual cycle, affecting factors and the methods for measuring dark adaptation. In the opinions of authors, intensive investigations are needed to be done for the widely use of this significant visual function in clinic.

Abstract Forensic practitioners are recommended to dark adapt their eyes prior to conducting evidential searches in the dark. The dark adaptation process remains poorly standardised across the discipline, with little quantified regarding the benefits of such preparative steps. Herein, we report the findings of a study that recruited 50 participants to assess the effectiveness of the Crime-lite Eye™, a darkness adaptation device developed to assist forensic practitioners both in the laboratory and in field. Participants were tasked with searching for the fluorescent signatures left by reaction of 1,8-diazafluoren-9-one (DFO) with amino acids, in a manner akin to the fluorogenic fingerprint treatment of porous evidence. Using an Epson Stylus Photo R265 inkjet printer, ink cartridges were filled with alanine solutions of various concentrations, allowing different motifs to be printed onto copy paper and subsequently developed using DFO. Participants searched for this 'evidence' both with and without dark adapted vision. On average, participants were able to locate and correctly recognise 16% more evidence once dark adapted using the Crime-lite Eye™. The increase in evidence located by participants once dark adapted suggests that crime scene officers should be dark adapting in order to visualise as much as possible. The time taken to dark adapt, 10 min on average during this study, is not excessively long, and should not significantly slow the investigation. Highlights • Inkjet printed alanine shapes were produced using a standard inkjet printer. • These alanine shapes produced consistent fluorescent marks when treated with DFO. • Dark adapting the eyes can increase the amount of fluorescent evidence found. • Dark adaptation allows fluorescent evidence to be more accurately observed. • The Crime-lite Eye™ is a viable method to obtain a known level of dark adaptation. [ABSTRACT FROM AUTHOR]

Inkjet-printing amino acids has been suggested as a method to obtain pseudo latent fingermarks which are identical to each other and can therefore be used to compare different fingermark development techniques. This article outlines how this method of printing amino acids was utilized to obtain standardized fluorescent patterns that could be used to assess individual's dark adaptation. Shapes, letters and patterns were printed in alanine using a standard inkjet printer, then developed using DFO to provide fluorescent images when viewed under green light and through a red filter. Images were also printed and developed using ninhydrin to obtain the resultant developed image in Ruhemann's purple. The use of the fluorescent patterns to assess dark adaptation led to the confirmation that forensic examiners should dark adapt their eyes prior to looking for fluorescent evidence in the dark, as 16% more evidence was discoverable after waiting an average of 10 minutes in the dark prior to examination. [ABSTRACT FROM AUTHOR]

Perceptual sensitivity is usually estimated over trials and time intervals, which results in imprecise and biased estimates when it changes rapidly over time. We develop a novel procedure, the quick Change-Detection (qCD) method, to accurately, precisely, and efficiently assess the trial-by-trial time course of perceptual sensitivity change. Based on Bayesian adaptive testing, qCD selects the optimal stimulus, and updates, trial by trial, a joint probability distribution of the parameters that quantify perceptual sensitivity change over time. We demonstrate the utility of the method in measuring the time course of dark adaptation. Simulations showed that the accuracy and precision of the estimated dark adaptation curve after one qCD run (root mean squared error (RMSE): 0.002; the half width of the 68.2% credible interval (HWCI): 0.016; standard deviation (SD): 0.020; all in log10 units) was higher than those obtained by ten runs of the quick Forced-Choice (qFC) procedure (RMSE: 0.020; HWCI: 0.032; SD: 0.031) and ten runs of a weighted up-down staircase procedure (RMSE: 0.026; SD: 0.031). Further, the dark adaptation curve obtained from one qCD run in a psychophysics experiment was highly consistent with the average of four qFC runs (RMSE = 0.076 log10 units). Overall, qCD provides a procedure to characterize the detailed time course of perceptual sensitivity change in both basic research and clinical applications. [ABSTRACT FROM AUTHOR]

Background: Impairments in visual function have been well characterized in vitamin A deficiency. However, eye function may also be sensitive to other nutrient deficiencies.Objective: We examined associations between visual function-characterized by pupillary threshold or pupillary responsiveness-and nutritional status in Zambian children.Methods: We used digital pupillometry to measure visual responses to calibrated light stimuli (-2.9 to 0.1 log cd/m2) among dark-adapted children aged 4-8 y (n = 542). We defined pupillary threshold as the first light stimulus at which pupil diameter decreased by ≥10% and considered a pupillary threshold ≥-0.9 log cd/m2 as impaired. Pupillary responsiveness was defined by absolute percentage of change in pupil diameter from pre- to poststimulus. We tested associations between these measures and serum concentrations of retinol, β-carotene, ferritin, soluble transferrin receptor, and hemoglobin (Hb <11.0 or 11.5 g/dL were used to define anemia, depending on age), as well as anthropometric indexes, with the use multilevel mixed-effects models.Results: Pupillary threshold was correlated only with serum retinol (r = 0.12, P < 0.05). The strongest correlates of pupillary responsiveness were Hb (r = -0.16, P < 0.01), height-for-age z score (r = 0.14, P < 0.05), weight-for-age z score (r = 0.14, P < 0.05), and soluble transferrin receptor (r = 0.12, P < 0.05). In multivariate models, anemia was positively associated with pupillary responsiveness (β = 2.99; 95% CI: 1.26, 4.72).Conclusions: In this marginally nourished population, we found positive correlations between vitamin A status, iron status, or anthropometric indexes and visual function. Hb was negatively associated with visual function, with greater pupillary responsiveness among anemic children. We posit that this may signal altered parasympathetic activity, possibly driven by infection. Future studies should consider a broader range of indicators to better characterize the relation between nutrition and visual function. This trial was registered at clinicaltrials.gov as NCT01695148. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association between macular pigment optical density (MPOD) and rod-mediated dark adaptation (RMDA) in persons ≥60 years old with normal maculas as determined by an accepted color fundus photography grading system. Methods: This cross-sectional analysis used baseline data from eyes in the Alabama Study on Early Age-Related Macular Degeneration. Eyes at step 1 in the AREDS 9-step grading system were considered normal. Eyes were additionally assessed by spectral domain optical coherence tomography (SD-OCT). Foveal MPOD was estimated via heterochromatic flicker photometry, and RMDA was assessed with a computerized dark adaptometer. The association between RMDA and MPOD was examined via Spearman correlation coefficients adjusted for age. Results: In 306 eyes from 306 persons (mean age 68.2 years) in normal macular health, MPOD was not associated with RMDA (age-adjusted rank correlation = 0.043, p = 0.45). After 81 eyes with incidental macular findings by SD-OCT evaluation were excluded, the association between MPOD and RMDA remained null (N = 225, age-adjusted r = 0.015, p = 0.82). Conclusion: In a large sample of normal aged eyes, RMDA, a visual function that is rate limited by retinoid availability to photoreceptors across the complex of retinal pigment epithelium, Bruch’s membrane, and choriocapillaris, is not related to MPOD in the neurosensory retina. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To determine (i) whether, compared to controls, visual complaints of glaucoma patients are more pronounced under extreme luminance conditions than in the optimal luminance condition and (ii) whether complaints belonging to different extreme luminance conditions are associated. Methods: We developed a luminance‐specific questionnaire and sent it to 221 glaucoma patients (response rate 81%); controls (182) were primarily their spouses. Median (interquartile range) mean deviation of the visual field of the patients’ better eye was −4.5 (−10.7 to −1.9) dB. Questions were addressing visual performance under five luminance conditions: presumed optimal (outdoor on a cloudy day), low, high, sudden decrease and sudden increase. We compared percentages of patients and controls who reported visual complaints while performing activities under different luminance conditions. Results: Percentages of patients and controls with visual complaints were 4 versus 0% (p = 0.02) for optimal luminance and 48 versus 6% (p < 0.001), 22 versus 1% (p < 0.001), 32 versus 1% (p < 0.001) and 25 versus 3% (p < 0.001) for low, high, sudden decrease and sudden increase in luminance. Within the group of glaucoma patients, the frequency of complaints increased significantly with increasing disease severity at a Bonferroni‐corrected p value of 0.003 for all but one (p = 0.005) luminance‐specific questions that addressed extreme luminance conditions. Conclusion: The concept of (early stage) glaucoma as an asymptomatic disease is only valid with optimal luminance. Differences in visual complaints between glaucoma patients and controls are greater under extreme luminance conditions, especially in the dark. The fact that the cases were aware of their diagnosis could have induced bias. [ABSTRACT FROM AUTHOR]

Cone photoreceptors, dark adaptation, electroretinography, optogenetics, retina, rod photoreceptors Keywords: cone photoreceptors; dark adaptation; electroretinography; optogenetics; retina; rod photoreceptors EN cone photoreceptors dark adaptation electroretinography optogenetics retina rod photoreceptors 4583 4584 2 11/03/22 20221101 NES 221101 Rod and cone photoreceptors are highly specialised cells, with unique structural modifications to subserve their function as adaptive light detectors and the first neurons in the visual pathway. Molecular basis of phototransduction Phototransduction, the process by which the detection of light by the photoreceptor brings about an electrical response, has been elucidated at the molecular level in rods and cones, with important differences between the two classes of photoreceptor characterised. [Extracted from the article]