Foveal light and dark adaptation in patients with glaucoma and healthy subjects: A case-control study.
ABSTRACT: To determine whether foveal light and dark adaptation are affected in glaucoma.Case-control study with 23 glaucoma patients and 51 controls. Light and dark adaptation were measured twice. After 10 minutes pre-adaptation to 0.0032 cd/m2, the background luminance increased stepwise to 320 (5 log unit step) or 10,000 cd/m2 (6.5 log unit step) for 10 minutes, then it decreased back to 0.0032 cd/m2 for 30 minutes. Foveal contrast sensitivity [CS]) as a function of time was determined using a 1.15 degree increment. Time resolution of the experiments was 30 seconds. Multiple linear regression was used to analyse the effect of glaucoma on the CS plateau and adaptation time (time to reach the plateau minus 3 dB); analyses were adjusted for age and gender.After light adaptation to 320 and 10,000 cd/m2, glaucoma patients had a 0.22 (P<0.001) and 0.13 (P = 0.010) log unit lower CS plateau than controls, respectively. After dark adaptation, this difference was 0.21 (P = 0.018) and 0.30 (P<0.001) log unit, respectively. Light adaptation occurred too fast to determine an accurate light adaptation time. Dark adaptation times of glaucoma patients and controls were similar, for both the 5 (7.2 versus 5.5 minutes; P = 0.10) and the 6.5 (18.2 versus 16.6 minutes; P = 0.14) log unit step.After a sudden increase or decrease in luminance, the logCS adaptation curves of glaucoma patients are shifted downwards compared to the curves of healthy subjects. Glaucoma patients have a lower CS plateau than healthy subjects, for both light and dark adaptation; dark adaptation times are similar.
Project description:Chromatic pupillometry is a technique that is increasingly used to assess retinal disorders. As age may be one of the various factors which can influence the pupillary light reaction, this study aimed to evaluate the pupil responses to colored light stimuli in the pediatric population. Fifty-three children with normal vision and without any history of ocular disorders were tested with a portable pupillometer. Four test sequences were used: five dim blue (470 nm) stimuli presented in half log steps ranging from -3.15 to -1.15 log cd/m2 after 3 min of dark adaptation, five red (622 nm) stimuli of -1.15, -0.7, -0.15, 0.3, and 0.85 log cd/m2 after 1 min light adaptation, one bright blue stimulus of 2.2 log cd/m2 and one bright red of 2 log cd/m2. The results were grouped by age: a younger group included 27 children aged from 3 to 10 years old and an older group included 26 from 10 and 1 month to 18 years old. The younger group had a smaller pupil diameter after dark adaptation compared with the older group. A linear regression defining the photopic threshold showed that younger subjects had a higher threshold, e.g., needed a brighter red stimulus to evoke a threshold pupil response comparable that of subjects. Age thus seems to influence outer retinal sensitivity at least as evaluated by the pupillary photopic threshold intensity. The post-illumination pupillary reaction was used as a marker of intrinsic melanopsin activity and did not show any difference between the two age groups.
Project description:To date, most studies involving in vivo electroretinography in mice are performed on steady state adapted animals. In this study, we focused on the dynamics of adaptation to high and low light levels in the mouse retina. Two flash electroretinogram (ERG) protocols and one flicker ERG protocol were employed. In the two flash ERG protocols, the animals were adapted to either 25 or 40 cd/m2 white light and ERGs were recorded for up to 15 min of adaptation. Afterwards, flash ERGs were recorded for up to 45 min of dark adaptation. Amplitudes of the flash ERG increased during light adaptation, while implicit times of the different wave components decreased. During subsequent dark adaptation, the amplitudes further increased. The increase in a-to-b-wave ratio indicated adaptational processes at the photoreceptor synapse. In the flicker ERG protocol, the responses to 12 Hz sinusoidal luminance modulation during the adaptation to 25 cd/m2 and a 1 cd/m2 mean luminances were recorded. The amplitudes of the first harmonic components in the flicker protocol decreased during light adaptation but increased during dark adaptation. This is at odds with the changes in the flash ERG, indicating that adaptation may be different in different retinal pathways.
Project description:In glaucoma, the density of retinal ganglion cells is reduced. It is largely unknown how this influences retinal information processing. An increase in spatial summation and a decrease in contrast gain control and contrast adaptation have been reported. A decrease in lateral inhibition might also arise. This could result in a larger than expected response to some stimuli, which could mask ganglion cell loss on functional testing (structure-function discrepancy). The aim of this study was to compare lateral inhibition between glaucoma patients and healthy subjects; we used a case-control design. Cases (n = 18) were selected to have advanced visual field loss in combination with a normal visual acuity. Controls (n = 50) were not allowed to have symptoms or signs of any eye disease. Lateral inhibition was measured psychophysically on a computer screen, with (1) a modified illusory movement experiment and (2) a contrast sensitivity (CS) test. Illusory movement was quantified by nulling it with a real movement; measure of lateral inhibition was the amount of illusory movement. CS was measured at 1 and 4 cycles per degree (cpd); measure of lateral inhibition was the difference between log CS at 4 and 1 cpd. Both measures were compared between cases and controls; analyses were adjusted for age and gender. There was no difference between cases and controls for these two measures of lateral inhibition (p = 0.58 for illusory movement; p = 0.20 for CS). The movement threshold was higher in cases than in controls (p = 0.008) and log CS was lower, at both 1 (-0.20; p = 0.008) and 4 (-0.28; p = 0.001) cpd. Our results indicate that spatially antagonistic mechanisms are not specifically affected in glaucoma, at least not in the intact center of a severely damaged visual field. This suggests that the structure-function discrepancy in glaucoma is not related to a decrease in lateral inhibition.
Project description:Purpose:To examine spatial changes in rod-mediated function in relationship to local structural changes across the central retina in eyes with a spectrum of age-related macular degeneration (AMD) disease severity. Methods:Participants were categorized into five AMD severity groups based on fundus features. Scotopic thresholds were measured at 14 loci spanning ±18° along the vertical meridian from one eye of each of 42 participants (mean = 71.7 ± 9.9 years). Following a 30% bleach, dark adaptation was measured at eight loci (±12°). Rod intercept time (RIT) was defined from the time to detect a -3.1 log cd/m2 stimulus. RITslope was defined from the linear fit of RIT with decreasing retinal eccentricity. The presence of subretinal drusenoid deposits (SDD), ellipsoid (EZ) band disruption, and drusen at the test loci was evaluated using optical coherence tomography. Results:Scotopic thresholds indicated greater rod function loss in the macula, which correlated with increasing AMD group severity. RITslope, which captures the spatial change in the rate of dark adaptation, increased with AMD severity (P < 0.0001). Three rod function phenotypes emerged: RF1, normal rod function; RF2, normal scotopic thresholds but slowed dark adaptation; and RF3, elevated scotopic thresholds with slowed dark adaptation. Dark adaptation was slowed at all loci with SDD or EZ band disruption, and at 32% of loci with no local structural changes. Conclusions:Three rod function phenotypes were defined from combined measurement of scotopic threshold and dark adaptation. Spatial changes in dark adaptation across the macula were captured with RITslope, which may be a useful outcome measure for functional studies of AMD.
Project description:Previous studies have demonstrated that a light-dark cycle has promoted better sleep development and weight gain in preterm infants than constant light or constant darkness. However, it was unknown whether brief light exposure at night for medical treatment and nursing care would compromise the benefits brought about by such a light-dark cycle. To examine such possibility, we developed a special red LED light with a wavelength of >675 nm which preterm infants cannot perceive. Preterm infants born at <36 weeks' gestational age were randomly assigned for periodic exposure to either white or red LED light at night in a light-dark cycle after transfer from the Neonatal Intensive Care Unit to the Growing Care Unit, used for supporting infants as they mature. Activity, nighttime crying and body weight were continuously monitored from enrolment until discharge. No significant difference in rest-activity patterns, nighttime crying, or weight gain was observed between control and experimental groups. The data indicate that nursing care conducted at 3 to 4-hour intervals exposing infants to light for <15 minutes does not prevent the infants from developing circadian rest-activity patterns, or proper body growth as long as the infants are exposed to regular light-dark cycles.
Project description:Dark adaptation can induce a rapid functional shift in the retina, and after that, the retinal function is believed to remain stable during the continuous dark exposure. However, we found that electroretinograms (ERG) b-waves gradually shifted during 24 hours' dark exposure in rodents. Detailed experiments were designed to explore this non-classical dark adaptation.In vivo ERG recording in adult and developing rodents after light manipulations.We revealed a five-fold decrease in ERG b-waves in adult rats that were dark exposed for 24 hours. The ERG b-waves significantly increased within the first hour's dark exposure, but after that decreased continuously and finally attained steady state after 1 day's dark exposure. After 3 repetitive, 10 minutes' light exposure, the dark exposed rats fully recovered. This recovery effect was eye-specific, and light exposure to one eye could not restore the ERGs in the non-exposed eye. The prolonged dark exposure-induced functional shift was also reflected in the down-regulation on the amplitude of intensity-ERG response curve, but the dynamic range of the responsive light intensity remained largely stable. Furthermore, the ERG b-wave shifts occurred in and beyond classical critical period, and in both rats and mice. Importantly, when ERG b-wave greatly shifted, the amplitude of ERG a-wave did not change significantly after the prolonged dark exposure.This rapid age-independent ERG change demonstrates a generally existing functional shift in the retina, which is at the entry level of visual system.
Project description:PURPOSE:To evaluate and quantify visual function metrics to be used as endpoints of age-related macular degeneration (AMD) stages and visual acuity (VA) loss in patients with early and intermediate AMD. DESIGN:Cross-sectional analysis of baseline data from a prospective study. METHODS:One hundred and one patients were enrolled at Duke Eye Center: 80 patients with early AMD (Age-Related Eye Disease Study [AREDS] stage 2 [n = 33] and intermediate stage 3 [n = 47]) and 21 age-matched, normal controls. A dilated retinal examination, macular pigment optical density measurements, and several functional assessments (best-corrected visual acuity, macular integrity assessment mesopic microperimety, dark adaptometry, low-luminance visual acuity [LLVA] [standard using a log 2.0 neutral density filter and computerized method], and cone contrast test [CCT]) were performed. Low-luminance deficit (LLD) was defined as the difference in numbers of letters read at standard vs low luminance. Group comparisons were performed to evaluate differences between the control and the early and intermediate AMD groups using 2-sided significance tests. RESULTS:Functional measures that significantly distinguished between normal and intermediate AMD were standard and computerized (0.5 cd/m2) LLVA, percent reduced threshold and average threshold on microperimetry, CCTs, and rod intercept on dark adaptation (P < .05). The intermediate group demonstrated deficits in microperimetry reduced threshhold, computerized LLD2, and dark adaptation (P < .05) relative to early AMD. CONCLUSIONS:Our study suggests that LLVA, microperimetry, CCT, and dark adaptation may serve as functional measures differentiating early-to-intermediate stages of dry AMD.
Project description:PURPOSE:To compare a new method for steady-state pattern electroretinogram (PERGx) with a validated method (PERGLA) in normal controls and in patients with optic neuropathy. METHODS:PERGx and PERGLA were recorded in a mixed population (n = 33, 66 eyes) of younger controls (C1; n = 10, age 38 ± 8.3 years), older controls (C2; n = 11, 57.9 ± 8.09 years), patients with early manifest glaucoma (G; n = 7, 65.7 ±11.6 years), and patients with nonarteritic ischemic optic neuropathy (N; n = 5, mean age 59.4 ± 8.6 years). The PERGx stimulus was a black-white horizontal grating generated on a 14 × 14 cm LED display (1.6 cycles/deg, 15.63 reversals/s, 98% contrast, 800 cd/m2 mean luminance, 25° field). PERGx signal and noise were averaged over 1024 epochs (?2 minutes) and Fourier analyzed to retrieve amplitude and phase. Partial averages (16 successive samples of 64 epochs each) were also analyzed to quantify progressive changes over recording time (adaptation). RESULTS:PERGLA and PERGx amplitudes and latencies were correlated (Amplitude R2 = 0.59, Latency R2 = 0.39, both P < 0.0001) and were similarly altered in disease. Compared to PERGLA, however, PERGx had shorter (16 ms) latency, higher (1.39×) amplitude, lower (0.37×) noise, and higher (4.2×) signal-to-noise ratio. PERGx displayed marked amplitude adaptation in C1 and C2 groups and no significant adaptation in G and N groups. CONCLUSIONS:The PERGx high signal-to-noise ratio may allow meaningful recording in advanced stages of optic nerve disorders. In addition, it quantifies response adaptation, which may be selectively altered in glaucoma and optic neuropathy. TRANSLATIONAL RELEVANCE:A new PERG method with increased dynamic range allows recording of retinal ganglion cell function in advanced stages of optic nerve disorders. It also quantifies the response decline during the test, an autoregulatory adaptation to metabolic challenge that decreases with age and presence of disease.
Project description:PURPOSE:The intrinsically photosensitive retinal ganglion cells (ipRGCs) signal environmental light, control pupil size and entrain circadian rhythm. There is speculation that ipRGCs may be involved in the protective effects of light exposure in myopia. Here, the ipRGC-driven pupil response was evaluated in children and examined with light exposure and refractive error. METHODS:Children ages 5-15 years participated. Subjects wore an actigraph device prior to the lab visit for objective measures of light exposure and sleep. For pupillometry, the left eye was dilated and presented with stimuli, and the consensual pupil response was measured in the right eye. Pupil measurements were preceded by 5 min dark adaptation. In Experiment 1 (n = 14), 1 s long wavelength light ('red,' 651 nm, 167 cd m-2 ) and 10 increasing intensities of 1 s short wavelength light ('blue,' 456 nm, 0.167-167 cd m-2 ) were presented with a 60 s interstimulus interval. A piecewise two-segment regression was fit to the stimulus response function to determine the functional melanopsin threshold. Pupil responses were analysed with light exposure over the previous 24 h. For Experiment 2 (n = 42), three 1 s red and three 1 s blue alternating stimuli were presented with a 60 s interstimulus interval. Following an additional 5-min dark adaption, the experiment was repeated. Pupil metrics included peak constriction, the 6 s and 30 s post-illumination response (PIPR), early and late area under the curve (AUC). Following pupil measurements, cycloplegic refractive error and axial length were measured. RESULTS:For Experiment 1, PIPR metrics demonstrated a graded response to increasing intensity blue stimuli, with a mean functional melanopsin threshold of 6.2 ± 4.5 cd m-2 (range: 0.84-16.7 cd m-2 ). The 6 s PIPR and early AUC were associated with 24-h light exposure for high intensity stimuli (33.3 and 83.3 cd m-2 , p < 0.005 for both). For Experiment 2, there were no associations between pupil metrics and refractive error. The 6 s PIPR and early AUC to blue stimuli were significantly increased for Trial 2 compared to Trial 1. CONCLUSIONS:The ipRGC-driven pupil responses in children were robust and similar to responses previously measured in an adult population. The 6 s PIPR and early AUC to high intensity blue stimuli were associated with previous light exposure. There were no associations between the ipRGC-driven pupil response and refractive status in this cohort.
Project description:This study aimed to determine if rebamipide eyedrops can improve ocular surface damage caused by the use of glaucoma eyedrops.Female Kbl:Dutch rabbits were used to evaluate glaucoma eyedrop-induced ocular surface damage; one eye of each rabbit was untreated and the other was administered glaucoma eyedrops for 30 days. To evaluate the effects of rebamipide on ocular surface damage, one eye of each rabbit was administered vehicle-treated glaucoma eyedrops and the other was administered rebamipide-treated glaucoma eyedrops for 30 days. Corneal and conjunctival epithelial damage was evaluated using fluorescein and rose bengal staining, respectively. Conjunctival inflammation was observed by light microscopy with hematoxylin-eosin staining. Dark cells (in which the corneal microvilli were damaged) were analyzed by scanning electron microscopy.There were no significant differences in fluorescein staining between the untreated and glaucoma eyedrop-treated groups; however, rose bengal staining and the number of inflammatory cells in the conjunctiva significantly increased after glaucoma eyedrop treatment. There was a four-fold increase in the number of dark cells in the glaucoma eyedrop-treated group compared to untreated. In contrast, in the conjunctiva of the rebamipide-treated glaucoma eyedrop group, rose bengal staining scores, the number of inflammatory cells, and the number of dark cells were decreased compared to the vehicle-treated glaucoma eyedrop group.Results from our in vivo rabbit study demonstrated that short-term use of glaucoma eyedrops induces corneal epithelium disorders at the cellular level, but that simultaneous use of rebamipide has the potential to protect and repair the ocular surface.