Visual function correlates of self-reported vision-related nighttime driving difficulties / La función visual se correlaciona con las dificultades de conducción nocturna relacionadas con la visión autoinformadas

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. R2 = 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.(AU)

Circadian Regulation of the Rod Contribution to Mesopic Vision in Mice.

At intermediate (mesopic) light levels, rods and cones are both active and can contribute to vision. This presents a challenge to the retina because the visual responses originating with rods and cones are distinct, yet their visual responses must be seamlessly combined. The current study aimed to establish how the circadian clock regulates rod and/or cone vision in these conditions, given the strong time-of-day change in the reliance on each photoreceptor. Visual responses were recorded in the retina and visual thalamus of anaesthetized male mice at distinct circadian time points, and the method of receptor silent substitution was used to selectively stimulate different photoreceptor types. With stimuli designed to only activate rods, responses in the mesopic range were highly rhythmic and peaked in amplitude in the subjective night. This rhythm was abolished following intravitreal injection of the gap junction blocker meclofenamic acid, consistent with a circadian variation in the strength of electrical coupling of photoreceptors. In contrast, responses to stimuli designed to only activate cones were arrhythmic within the mesopic to photopic range when adapted to the background irradiance. The outcome was that combined rod-plus-cone responses showed a stable contrast-response relationship across mesopic-photopic backgrounds in the circadian day, whereas at night, responses were significantly amplified at lower light levels. These data support the idea that the circadian clock is a key regulator of vision, in this case defining the relative amplitude of rod/cone vision across the mesopic transition according to time of day.SIGNIFICANCE STATEMENT Although the importance of circadian clocks in regulating vision has been long recognized, less is known about how the clock shapes vision in conditions where both rods and cones are active (mesopic conditions). Here, the novel approach of receptor silent substitution has been applied to trace rod and cone visual responses in mice across the circadian cycle and has identified pronounced rhythms in rod, but not cone, vision. This has the effect of boosting responses in dimmer backgrounds at night at the cost of impaired contrast-response stability across the mesopic to photopic range. Thus, the circadian clock drives anticipatory changes in the relative contribution of rods versus cones to vision, which match the prevailing visual environment.

Mesopic conditions optimise the detection of visual function loss in drivers with simulated media opacity.

Drivers have different visual demands across varying contrast and luminance conditions. However, vision assessments for driving are typically conducted under photopic conditions. This study investigated the sensitivity of photopic and mesopic conditions to detect contrast sensitivity (CS) loss in drivers with simulated media opacities. CS was measured in forty-seven healthy drivers aged 18-50 years (mean ± SD: 25.5 ± 6.5) under photopic and mesopic-adapted luminance levels with the Pelli-Robson chart and the Mesotest II (without glare). Media opacities were simulated using white-opacity containing Lee Fog filters (1-5) and CS measured in a randomised order. A significant (p < 0.001) reduction in photopic CS (logCS) was measured with the Pelli-Robson chart only when media opacity was simulated with Fog filter 5 (1.53 ± 0.15, 2.8 triplets reduction) compared to baseline (1.95 ± 0.03). Mean mesopic CS demonstrated a significant (all p < 0.001) reduction from baseline (1.67 ± 0.14) for Fog filters 3 (1.4 triplets, 1.45 ± 0.16), 4 (2.4 triplets, 1.31 ± 0.14) and 5 (4.3 triplets, 1.02 ± 0.15). For Mesotest II, only Fog filter 5 produced a significant reduction (0.10 ± 0.09; p < 0.001) in mean mesopic CS from baseline (0.30 ± 0.01). Mesopic CS is more vulnerable to different levels of simulated media opacity, hence should be considered clinically when assessing visual function in older drivers at risk of media opacity.

Spatial Dissociation of Subretinal Drusenoid Deposits and Impaired Scotopic and Mesopic Sensitivity in AMD.

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.

Impact of symptomatic vitreous degeneration on photopic and mesopic contrast thresholds.

CLINICAL RELEVANCE: Contrast thresholds under photopic and mesopic luminance conditions are compromised in subjects with vitreous degeneration. A plausible explanation is needed for the visual discomfort expressed by patients suffering from symptomatic vitreous degeneration. BACKGROUND: The current study investigates the effect of symptomatic vitreous degeneration on photopic and mesopic contrast at high spatial frequencies. METHODS: An age-matched sample of 115 subjects, comprising 30 subjects with symptomatic vitreous floaters (cases) and 85 healthy subjects (controls), was included in this study. Visual acuity and flicker thresholds were measured for all participants. Photopic and mesopic functional contrast thresholds at 10 cycles per degree were measured for all participants to assess the effect of floaters on contrast. Further, to determine the effect of posterior vitreous detachment on contrast, the sample was divided into three groups: cases with posterior vitreous detachment (n = 12); cases without posterior vitreous detachment (n = 18); and controls (n = 85), and their contrast thresholds were compared. RESULTS: Photopic and mesopic contrast thresholds were lower by 37.4% and 27.5%, respectively, when the cases were compared with the controls (p = 0.028 and p < 0.001 for photopic and mesopic contrast thresholds, respectively). Photopic contrast was lower by 64.0% in cases with posterior vitreous detachment compared with controls (p = 0.001). Compared with controls, mesopic contrast was lower in cases with posterior vitreous detachment and in cases without posterior vitreous detachment by 30.3% and 25.6%, respectively (p = 0.014 and p = 0.017 for cases with and without posterior vitreous detachment, respectively). CONCLUSION: : Subjects with vitreous degeneration have diminished photopic and mesopic contrast thresholds compared with controls. This finding highlights the negative impact of vitreous degeneration on the quality of vision.

Effects of D-serine treatment on outer retinal function.

The role of the N-Methyl-D-Aspartate Receptor (NMDAR) in the outer retina is unclear despite expression of the NMDAR-complex and its subunits in the outer retina. The flash-electroretinogram (fERG) offers a non-invasive measurement of the retinal field potentials of the outer retina that can serve to clarify NMDAR contribution to early retinal processing. The role of the NMDAR in retinal function was assessed using a genetic mouse model for NMDAR hypofunction (SR-/-), where the absence of the enzyme serine racemase (SR) results in an 85% reduction of retinal D-serine. NMDAR hypo- and hyperfunction in the retina results in alterations in the components of the fERG. The fERG was examined after application of exogenous D-serine to the eye in order to determine whether pre- and post-topical delivery of D-serine would alter the fERG in SR-/- mice and their littermate WT controls. Amplitude and implicit time of the low-frequency components, the a- and b-wave, were conducted. Reduced NMDAR function resulted in a statistically significantly delayed a-wave and reduced b-wave in SR-/- animals. The effect of NMDAR deprivation was more prominent in male SR-/- mice. A hyperfunction of the NMDAR, through exogenous topical delivery of 5 mM D-serine, in WT mice caused a significantly delayed a-wave implicit time and reduced b-wave amplitude. These changes were not observed in female WT mice. There were temporal delays in the a-wave and amplitude and a decrease in the b-wave amplitude and implicit time in both hypo- and NMDAR hyperfunctional male mice. These results suggest that NMDAR and D-serine are involved in the retinal field potentials of the outer retina that interact based on the animal's sex. This implicates the involvement of gonadal hormones and D-serine in retinal functional integrity.

Development of a Method to Potentially Substitute Direct Evaluation of Mesopic Visual Acuity in Drivers.

(1) Background: In mesopic lighting conditions, or under adverse environmental circumstances, visual information is reduced, which increases the risk of traffic accidents. This effect could be reduced with a precise evaluation of the visual function under mesopic conditions, but it is difficult to replicate in clinics. This study aims to develop an easy-to-adopt method to evaluate mesopic visual acuity (VA) in drivers. (2) Methods: Prospective and observational study in drivers. logMAR mesopic VA was compared with photopic VA measured under different combinations of contrast charts and filters to find the combination that responds best to mesopic conditions. (3) Results: Fifty-six drivers were examined. The best correlation was found with an 80% density filter and a Weber contrast chart of 20%. The logMAR VA for this combination was 0.01 ± 0.11, which was close to the mesopic VA values (0.01 ± 0.12). The difference between both logMAR VA was 0.00 ± 0.06 (R = 0.86; p ≤ 0.001; ICC = 0.86). (4) Conclusions: The use of 20% contrast optotypes and the interposition of an 80% filter under photopic conditions provide VA values similar to those measured under mesopic lighting conditions, making this simple system a good predictor of mesopic VA values.

Effect of the EVO+ Visian Phakic Implantable Collamer Lens on Visual Performance and Quality of Vision and Life.

PURPOSE: To assess the effect of EVO+ (V5) Visian implantable collamer lens implantation on mesopic visual performance, quality of vision (QoV), and quality of life (QoL). DESIGN: Prospective interventional case series. METHODS: Thirty-six eyes of 36 participants who underwent EVO+ implantation for myopia were evaluated preoperatively and at postoperative visits at 1 week and 1, 3, and 6 months. Visual acuity (VA) and mesopic contrast sensitivity (CS) with and without halogen- and xenon-type glare sources were evaluated at each visit. Subjective QoV was assessed with the QoV questionnaire and QoL assessed with the Quality of Life Impact of Refractive Correction (QIRC) questionnaire at each visit. Ring-shaped dysphotopsia was also assessed at each postoperative visit. Linear, cumulative link and logit mixed models were fitted to analyze the effect of the EVO+. RESULTS: Following EVO+ implantation, VA significantly (P ≤ .012) improved at the 4 postoperative visits. Mesopic CS progressively improved at 1, 3, and 6 months postoperatively (P ≤ .012). Halogen glare CS decreased at 1 week and halogen and xenon glare CS improved at 6 months (P ≤ .016). Photostress recovery time after halogen glare improved at 3 and 6 months (P ≤ .004). QoV scores improved at 1 week and 3 and 6 months (P ≤ .001). QIRC scores improved postoperatively (P < .001). Ring-shaped dysphotopsia decreased at 3 and 6 months (P ≤ .007). CONCLUSIONS: EVO+ implantation provides good mesopic visual performance, QoV, and QoL during up to 6 months follow-up. Some activities performed under mesopic conditions with glare sources may be affected during the first postoperative week. Ring-shaped dysphotopsia is negligibly bothersome 6 months after surgery.

Recovery of Contrast Sensitivity After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To study the change in contrast sensitivities in eyes with Fuchs endothelial dystrophy and bullous keratopathy after Descemet membrane endothelial keratoplasty (DMEK). METHODS: In this prospective study, 50 pseudophakic eyes of 50 patients who received DMEK surgery at the Charité-Universitätsmedizin Berlin were included. Visual acuity; contrast sensitivity using OPTEC 6500 at spatial frequencies of 1.5, 3, 6, 12, and 18 cycles/degree in photopic and mesopic light with and without glare; central corneal thickness (CCT); and anterior and posterior corneal aberrations were measured preoperatively and at 3 and 12 months postoperatively. RESULTS: Best-corrected visual acuity (preoperative 0.67 ± 0.46 and after 12 months 0.19 ± 0.16 LogMAR, P < 0.001) and photopic and mesopic contrast sensitivities with and without glare improved significantly, whereas CCT decreased significantly (preoperative 677 ± 114 µm, after 12 months 527 ± 29 µm, P < 0.001). Preoperative CCT correlates significantly with preoperative photopic contrast sensitivity (correlation coefficient -0.462, P = 0.002), and postoperative total anterior aberrations correlates with postoperative photopic contrast sensitivity (correlation coefficient -0.361, P = 0.006). CONCLUSIONS: Photopic and mesopic contrast sensitivities, especially with glare, are impaired in patients with Fuchs endothelial dystrophy and bullous keratopathy. The extent of the corneal thickening seems to mainly influence the contrast sensitivity preoperatively. DMEK surgery improves the contrast sensitivity significantly. However, higher postoperative anterior corneal aberrations limit the postoperative contrast sensitivities.

Normal- and Low-Luminance Automated Quantitative Contrast Sensitivity Assessment in Eyes With Age-Related Macular Degeneration.

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.

Ambient Light Regulates Retinal Dopamine Signaling and Myopia Susceptibility.

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.

Motion perception at mesopic light levels: effects of physiological ageing and eccentricity.

PURPOSE: To explore the differential effects of age and eccentricity on the perception of motion at photopic and mesopic light levels. METHODS: Thirty-six visually normal participants (18 younger; mean age 25 years, range: 20-31) and (18 older; mean age 70 years, range: 60-79) underwent two testing sessions, one at photopic and one at mesopic light levels. In each session, motion perception was tested binocularly at two eccentricities (centrally, and peripherally at 15° rightwards and 5° superior to the horizontal) for four motion tasks: minimum contrast of a drifting Gabor to identify motion direction (motion contrast); translational global motion coherence; biological motion embedded in noise and the minimum duration of a high-contrast Gabor to determine the direction of motion, using two Gabor sizes to measure spatial surround suppression of motion. RESULTS: There was a significant main effect of light condition (higher thresholds in mesopic) for motion contrast (p < 0.001), translational global motion (p = 0.001) and biological motion (p < 0.001); a significant main effect of age (higher thresholds in older adults) for motion contrast (p < 0.001) and biological motion (p = 0.04) and a significant main effect of eccentricity (higher thresholds peripherally) for motion contrast (p < 0.001) and biological motion (p < 0.001). Additionally, we found a significant three-way interaction between light levels, age and eccentricity for translational global motion (similar increase in mesopic thresholds centrally for both groups, but a much larger deterioration in older adult's peripheral mesopic thresholds, p = 0.02). Finally, we found a two-way interaction between light condition and eccentricity for translational global motion (higher values in central mesopic relative to peripheral photopic, p = 0.001) and for biological motion (higher values in peripheral mesopic relative to central photopic, p < 0.001). CONCLUSIONS: For the majority of tasks assessed, motion perception was reduced in mesopic relative to photopic conditions, to a similar extent in both age groups. However, because some older adults exhibited elevated thresholds even under photopic conditions, particularly in the periphery, the ability to detect mesopic moving stimuli even at high contrast was markedly impaired in some individuals. Our results imply age-related differences in the detection of peripheral moving stimuli at night that might impact hazard avoidance and night driving ability.

Retinal light sensitivity as outcome measure in recessive Stargardt disease.

BACKGROUND/AIMS: To evaluate the applicability of mesopic light sensitivity measurements obtained by fundus-controlled perimetry (FCP, also termed 'microperimetry') as clinical trial endpoint in Stargardt disease (STGD1). METHODS: In this retrospective, monocentre cohort study, 271 eyes of 136 patients (age, 37.1 years) with STGD1 and 87 eyes of 54 healthy controls (age, 41.0 years) underwent mesopic FCP, using a pattern of 50 stimuli (achromatic, 400-800 nm) centred on the fovea. The concurrent validity of mesopic FCP testing using the MAIA device (CenterVue, Italy), the retest variability and its determinants, and the progression of sensitivity loss over time were investigated using mixed-model analyses. The main outcomes were the average pointwise sensitivity loss in dependence of patients' demographic, functional and imaging characteristics, the intrasession 95% coefficient of repeatability, and the pointwise sensitivity loss over time. RESULTS: Pointwise sensitivity loss was on average (estimate (95% CI)) 13.88 dB (12.55 to 15.21) along the horizontal meridian and was significantly associated with the electrophysiological subgroup, presence/absence of foveal sparing, best-corrected visual acuity and disease duration. The 95% coefficient of repeatability was 12.15 dB (10.78 to 13.38) and varied in dependence of the underlying mean sensitivity and local sensitivity slope. The global progression rate for the sensitivity loss was 0.45 dB/year (0.13 to 0.78) and was higher for the central and inner ETDRS subfields compared with more peripheral regions. CONCLUSIONS: Mesopic light sensitivity measured by FCP is reliable and susceptible for functional changes. It constitutes a potential clinical outcome for both natural history studies as well as future interventional studies in patients with STGD1.

Influences of luminance contrast and ambient lighting on visual context learning and retrieval.

Invariant spatial context can guide attention and facilitate visual search, an effect referred to as "contextual cueing." Most previous studies on contextual cueing were conducted under conditions of photopic vision and high search item to background luminance contrast, leaving open the question whether the learning and/or retrieval of context cues depends on luminance contrast and ambient lighting. Given this, we conducted three experiments (each contains two subexperiments) to compare contextual cueing under different combinations of luminance contrast (high/low) and ambient lighting (photopic/mesopic). With high-contrast displays, we found robust contextual cueing in both photopic and mesopic environments, but the acquired contextual cueing could not be transferred when the display contrast changed from high to low in the photopic environment. By contrast, with low-contrast displays, contextual facilitation manifested only in mesopic vision, and the acquired cues remained effective following a switch to high-contrast displays. This pattern suggests that, with low display contrast, contextual cueing benefited from a more global search mode, aided by the activation of the peripheral rod system in mesopic vision, but was impeded by a more local, fovea-centered search mode in photopic vision.

Gradual Increase in Environmental Light Intensity Induces Oxidative Stress and Inflammation and Accelerates Retinal Neurodegeneration.

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.

Longitudinal Analysis of Structural and Functional Changes in Presence of Reticular Pseudodrusen Associated With Age-Related Macular Degeneration.

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.

The "speed" of acuity in scotopic vs. photopic vision.

PURPOSE: The effect of duration of optotype presentation on visual acuity measures has been extensively studied under photopic conditions. However, systematic data on duration dependence of acuity values under mesopic and scotopic conditions is scarce, despite being highly relevant for many visual tasks including night driving, and for clinical diagnostic applications. The present study aims to address this void. METHODS: We measured Landolt C acuity under photopic (90 cd/m2), mesopic (0.7 cd/m2), and scotopic (0.009 cd/m2) conditions for several optotype presentation durations ranging from 0.1 to 10 s using the Freiburg Acuity and Contrast Test. Two age groups were tested (young, 18-29 years, and older, 61-74 years). RESULTS: As expected, under all luminance conditions, better acuity values were found for longer presentation durations. Photopic acuity in young participants decreased by about 0.25 log units from 0.1 to 10 s; mesopic vision mimicked the photopic visual behavior. Scotopic acuities depended more strongly on presentation duration (difference > 0.78 log units) than photopic values. There was no consistent pattern of correlation between luminance conditions across participants. We found a qualitative similarity between younger and older participants, despite higher variability among the latter and differences in absolute acuity: Photopic acuity difference (0.1 vs. 10 s) for the older participants was 0.19 log units, and scotopic difference was > 0.62 log units. CONCLUSION: Scotopic acuity is more susceptible to changes in stimulus duration than photopic vision, with considerable interindividual variability. The latter may reflect differences in aging and sub-clinical pathophysiological processes and might have consequences for visual performance during nocturnal activities such as driving at night. Acuity testing with briefly presented scotopic stimuli might increase the usefulness of acuity assessment for tracking of the health state of the visual system.

Spatio-chromatic contrast sensitivity under mesopic and photopic light levels.

Contrast sensitivity functions (CSFs) characterize the sensitivity of the human visual system at different spatial scales, but little is known as to how contrast sensitivity for achromatic and chromatic stimuli changes from a mesopic to a highly photopic range reflecting outdoor illumination levels. The purpose of our study was to further characterize the CSF by measuring both achromatic and chromatic sensitivities for background luminance levels from 0.02 cd/m2 to 7,000 cd/m2. Stimuli consisted of Gabor patches of different spatial frequencies and angular sizes, varying from 0.125 to 6 cpd, which were displayed on a custom high dynamic range (HDR) display with luminance levels up to 15,000 cd/m2. Contrast sensitivity was measured in three directions in color space, an achromatic direction, an isoluminant "red-green" direction, and an S-cone isolating "yellow-violet" direction, selected to isolate the luminance, L/M-cone opponent, and S-cone opponent pathways, respectively, of the early postreceptoral processing stages. Within each session, observers were fully adapted to the fixed background luminance (0.02, 2, 20, 200, 2,000, or 7,000 cd/m2). Our main finding is that the background luminance has a differential effect on achromatic contrast sensitivity compared to chromatic contrast sensitivity. The achromatic contrast sensitivity increases with higher background luminance up to 200 cd/m2 and then shows a sharp decline when background luminance is increased further. In contrast, the chromatic sensitivity curves do not show a significant sensitivity drop at higher luminance levels. We present a computational luminance-dependent model that predicts the CSF for achromatic and chromatic stimuli of arbitrary size.

Association of Visual Function Measures with Drusen Volume in Early Stages of Age-Related Macular Degeneration.

Purpose: To assess which visual function measures are most strongly associated with overall retinal drusen volume in age-related macular degeneration (AMD). Methods: A total of 100 eyes (16 eyes with early AMD, 62 eyes with intermediate AMD, and 22 eyes from healthy controls) were recruited in this cross-sectional study. All subjects underwent several functional assessments: best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), visual acuity (VA) measured with the Moorfields Acuity Chart (MAC-VA), contrast sensitivity with the Pelli-Robson test, reading speed using the International Reading Speed texts, and mesopic and dark-adapted microperimetry. Drusen volume was automatically determined based on optical coherence tomography using an approach based on convolutional neural networks. The relationship between drusen volume and visual function was assessed with linear regressions controlling for confounders. Results: Mean drusen volume and MAC-VA differed significantly among all AMD stages and controls (P < 0.001). In univariate linear regression, LLVA, MAC-VA, contrast sensitivity, and mesopic and dark-adapted microperimetry were significantly negatively associated with the overall drusen volume (all P < 0.006). After controlling for AMD stage, age, and the presence of subretinal drusenoid deposits, MAC-VA and mesopic and dark-adapted microperimetry were still significantly associated with drusen volume (P = 0.008, P = 0.023, and P = 0.022, respectively). Conclusions: Our results suggest that MAC-VA, as well as mesopic and dark-adapted microperimetry, might indicate structural changes related to drusen volume in early stages of AMD.

Reflejo pupilar mesópico en pacientes tratados con fluoxetina / Mesopic pupillary reflex in patients treated with fluoxetine

INTRODUCCIÓN: Actualmente el tratamiento de enfermedades mentales mediante antidepresivos es muy frecuente. Los inhibidores selectivos de la recaptación de serotonina son los antidepresivos más prescritos a nivel mundial y han sido asociados con alteraciones en la acomodación o la pupila. El objetivo de este estudio es evaluar los efectos de la fluoxetina sobre el reflejo pupilar y la acomodación en población joven. METODOLOGÍA: El grupo de estudio contó con siete pacientes diagnosticados de depresión y tratados con fluoxetina; como grupo control se incluyeron 22 sujetos. Se evaluaron los reflejos pupilares y el estado acomodativo mediante el pupilómetro Power Refractor II. Se midieron 5 fases de 3 segundos cada una. En la fase 2 se produjo un deslumbramiento con una luz blanca. RESULTADOS: Para el diámetro pupilar se han obtenido valores máximos y mínimos mayores en el grupo de pacientes tratados con fluoxetina que en el control en todas las fases de medida. Para el grupo control se observa una contracción pupilar máxima en la fase de deslumbramiento, sin embargo, en el grupo de estudio se observa en la fase tras el deslumbramiento. En cuanto a la acomodación no se obtuvieron diferencias significativas entre ambos grupos. CONCLUSIONES: En pacientes tratados con fluoxetina existen alteraciones pupilares observándose diámetros pupilares mayores y menor velocidad de contracción pupilar. La falta de resultados concluyentes en cuanto a la acomodación no significa que no existan cambios relacionados con esta, cuya detección requerirá de futuros estudios utilizando diferentes metodologías y con un tamaño muestral mayor

INTRODUCTION: currently the treatment of mental illness by antidepressants is very frequent. Selective serotonin re-uptake inhibitors are the most prescribed antidepressants worldwide and have been associated with alterations in accommodation or pupil. The objective of this study is to evaluate the effects of fluoxetine on the pupillary reflex and the accommodation in young population. METHODOLOGY: The study group included seven patients diagnosed with depression and treated with fluoxetine; 22 subjects were included as a control group. The pupillary reflexes and the accommodative state were evaluated using the Power Refractor II pupilometer. Five phases of 3 seconds each were measured. In phase 2 there was a glare with a white light. RESULTS: For the pupil diameter, maximum and minimum values were obtained in the group of patients treated with fluoxetine than in the control in all the measurement phases. For the control group, a maximum pupillary contraction is observed in the glare phase, however, in the study group it is observed in the phase after glare. As for the accommodation, there are no significant differences between the two groups. CONCLUSIONS: In patients treated with fluoxetine there are pupillary alterations like a bigger pupillary diameters and slower pupillary contraction. The lack of conclusive results in terms of accommodation does not mean that there are no changes related to it, whose detection requires future studies with different methodologies and with a larger sample size