The role of dark adaptation in understanding early AMD.

The main aim of the paper is to discuss current knowledge on how Age Related Macular Degeneration (AMD) affects Dark Adaptation (DA). The paper is divided into three parts. Firstly, we outline some of the molecular mechanisms that control DA. Secondly, we review the psychophysical issues and the corresponding analytical techniques. Finally, we characterise the link between slowed DA and the morphological abnormalities in early AMD. Historically, DA has been regarded as too cumbersome for widespread clinical application. Yet the technique is extremely useful; it is widely accepted that the psychophysically obtained slope of the second rod-mediated phase of the dark adaptation function is an accurate assay of photoreceptor pigment regeneration kinetics. Technological developments have prompted new ways of generating the DA curve, but analytical problems remain. A simple potential solution to these, based on the application of a novel fast mathematical algorithm, is presented. This allows the calculation of the parameters of the DA curve in real time. Improving current management of AMD will depend on identifying a satisfactory endpoint for evaluating future therapeutic strategies. This must be implemented before the onset of severe disease. Morphological changes progress too slowly to act as a satisfactory endpoint for new therapies whereas functional changes, such as those seen in DA, may have more potential in this regard. It is important to recognise, however, that the functional changes are not confined to rods and that building a mathematical model of the DA curve enables the separation of rod and cone dysfunction and allows more versatility in terms of the range of disease severity that can be monitored. Examples are presented that show how analysing the DA curve into its constituent components can improve our understanding of the morphological changes in early AMD.

The Light and the Dark of Early and Intermediate AMD: Cone- and Rod-Mediated Changes Are Linked to Fundus Photograph and FAF Abnormalities.

Purpose: The purpose of this paper is to describe the extent to which scotopic and photopic measures of visual function predict color fundus photograph (CFP) and fundus autofluorescence (FAF) changes in early and intermediate nonexudative AMD. Methods: Sixty-nine observers were recruited: 56 AMD patients (mean age, 73 ± 12.98 years) and 13 controls (mean age, 67.77 ± 9.72 years). A nonmydriatic retinal camera was used to obtain stereo fundus photographs and FAF images were recorded with a cSLO Heidelberg Spectralis HRA+OCT. Visual acuity (VA) was measured using an Early Treatment of Diabetic Retinopathy Study chart. Contrast sensitivity (CS) was assessed with a Pelli-Robson chart. Dark adaptation (DA) curves were recorded at 3° eccentricity using a PC-based technique. Analysis of these curves yielded five parameters: cone threshold (CT), cone time constant (CC), cone-rod break (α), slope of the second rod component (S2), and rod-rod break (ß). Results: Both cone and rod sensitivity recovery were grossly abnormal in the patients. The rod recovery slope (S2) most accurately predicted the fundus photograph-based grade and the FAF classification (ρ = 0.61 and ρ = 0.60, respectively; both P < 0.0001). CS showed a strong association with FAF (ρ = 0.50, P < 0.0001) and with fundus photograph-based grade (ρ = 0.38, P < 0.002). There was no correlation between VA and either imaging method. Conclusions: Dynamic, rod-based measures most accurately reflect the severity of early AMD. Although less specific to AMD than DA changes, static photopic abnormalities such as CS also correspond with morphologic changes. Assessment of function in early AMD should include dynamic rod- and cone-mediated measurements of sensitivity recovery.

Slowed Dark Adaptation in Early AMD: Dual Stimulus Reveals Scotopic and Photopic Abnormalities.

Purpose: The recovery of visual sensitivity after a photobleach in early AMD is slowed in rods but cones also may be abnormal. The purpose of this article was to test different stimulus locations to investigate cone function and its relation to rod abnormalities. Methods: Stimuli were presented at two locations, 3.0° and 5.5°, in the inferior visual field. Post photobleach dark adaptation (DA) curves from 50 early-AMD patients were compared with those from 15 healthy controls of similar age. Curves were characterized in terms of four parameters: ct, cone threshold; α, the transition point from cone to rod function; S2, the slope of the second rod-mediated component; and ß, the transition from the second to the third rod-mediated component. Results: There were strong location effects for the healthy group and the AMD group. Cone threshold was higher for the outer compared with the inner stimulus (P = 0.001), S2 was steeper for outer compared with inner (P < 0.001), α was shorter for outer (P = 0.004), and ß was shorter for outer than inner (P = 0.002). The high variance in the patient data, particularly for α and ß, explained the absence of a group*location interaction in the statistics. Conclusions: The data provide a novel perspective on abnormal cone- and rod-sensitivity recovery in early dry AMD. The comparison of pairs of DA curves from different locations highlights the involvement of cones in the underlying pathology of AMD. Dynamic measures of visual function are particularly sensitive to early AMD.

Chips in the sunshine: color constancy with real versus simulated Munsell chips under illuminants adjacent to the daylight locus.

Accurate color judgments rely on a powerful cognitive component. Here we compare the performance of color constancy under real and simulated conditions. Shifts in the u'v' color plane induced by illuminant A (2750 K) and illuminant S (>20,000 K) were measured using asymmetric color matching. A general linear model was used to predict performance from the following dependent variables: chroma ("4" and "6"), illuminant ("A" and "S"), presentation mode ("Real" and "Monitor"), and hue zone ("blue," "green," "yellow," "red," and "purple"). There was a strong overall effect [F(7,264)=78.65, p<0.001]. Post hoc analysis showed that performance was substantially superior under real [chromatic constancy index (cCI)=0.76] compared with simulated cCI=0.55) conditions.

Slowed dark adaptation in older eyes; effect of location.

PURPOSE: The rate of rod sensitivity recovery following a photobleach is a basic measure of the integrity of the outer retina. Rods are selectively impaired in aging and many disorders of the retina, notably Age-Related Macular Degeneration (AMD). It is not known for certain whether the age-related deficit is a pan-retinal effect or if there are localised regions of impaired rod function. To address this important issue a dual arc stimulus was developed that samples sensitivity recovery in two retinal locations. METHODS: Arc-shaped stimuli were presented on a black CRT screen at two locations, in the inferior visual field. Following a bleach, which was localised to the stimuli, recovery of sensitivity was measured using a modified method of adjustment technique. Neutral density filters were used to extend the luminance range of the CRT. Sensitivity recovery functions were fitted by non-linear regression to a seven-parameter model. RESULTS: Pairs of sensitivity recovery functions were generated from the stimuli. The cone phases of these functions were identical. The slopes of the S2 sections of the curves were steeper for the outer stimuli for both young (p < 0.001) and older (p = 0.003) observers. The difference between the two was the same for the two groups. The α point was reached slightly earlier for the young observers and with the outer stimulus but neither of these effects reached statistical significance. The ß point occurred earlier for the outer stimuli and this effect was statistically significant only for the older group. CONCLUSIONS: The method places minimal demands on observers. The fact that rod sensitivity recovery is slowed in the older normal eye to the same extent in the two locations suggests that this deficit may be uniform across the retina. As there are localised losses in scotopic function in AMD, the technique is ideally suited to distinguishing impaired recovery dynamics due to normal ageing from those caused by disease.

Rapid method for assessing rod function using recovery of spatial contrast thresholds following a bleach.

Poor vision in low light is a common complaint of elderly people. This poorly understood phenomenon is likely to involve both receptoral and post receptoral mechanisms. We investigated the recovery of contrast thresholds for sine-wave gratings of low spatial frequencies and low mean luminance as a function of time in darkness after photo pigment bleaching. Thirteen subjects aged 30.4 (±10.7) years took part in the study. Contrast thresholds were measured for 15 min following almost complete photo pigment bleaching. The stimuli were achromatic sinusoidal gratings of 0.5, 1 and 2 cycle per degree (cpd) generated on a CRT monitor. They had mean luminance 0.01 cd m(-2) and subtended 10° in diameter. The dynamics of the recovery at each spatial frequency were modelled using monophasic and biphasic exponential decay functions. The data were best modelled by a bi-phasic decay with a distinct transition point around 7 min after the bleach. Both phases followed an exponential decay. The time constant (mean, standard error) for the first phase was 0.35 (0.04) min while for the second phase it was 5.15 (0.27) min. This difference was statistically significant (p < 0.001). A control experiment revealed the second, slower phase was mediated by rod photoreceptors. Maximum contrast sensitivity was reached 15 min after a photic bleach. The dynamics of contrast sensitivity recovery follow two phases and these may be attributed to the cone and rod systems.

Assessment of age changes and repeatability for computer-based rod dark adaptation.

PURPOSE: To characterize the rate of rod-mediated sensitivity decline with age using a PC-driven cathode ray tube (CRT) monitor. To provide data regarding the repeatability of the technique. METHODS: Dark adaptation was monitored for 30 min following a minimum 30 % pigment bleach, using a white 1° stimulus (modulated at 1 Hz), presented 11° below fixation on a CRT monitor. Thirty-three subjects with no ocular pathology and normal fundus photographs were divided into two groups: older (≥45, n = 16) and younger (<45, n = 17). RESULTS: Rod recovery was assessed using component S2 of dark adaptation. S2 was significantly slower in the older (0.19 ± 0.03 log cd.m(-2).min(-1)) compared with the younger group (0.23 ± 0.03 log cd.m(-2).min(-1), t = -4.05, p < 0.0003), despite no difference in visual acuity and fundus appearance. Faster rates of S2 recovery were correlated with lower threshold at 30 min (T30) (r = -0.49). Correlation coefficients between first and second measurements for S2 and T30 were 0.49 (p < 0.009) and 0.84 (p < 0.0001) respectively. The coefficient of repeatability was 0.07 log cd.m(-2).min(-1) for S2 and 0.35 log cd.m(-2) for T30. The coefficients of variation for S2 and T30 were 15 % and 10 % respectively. CONCLUSIONS: Dark adaptation is slowed in normal ageing. CRT-based dark adaptometry is easily implemented and highly repeatable. The technique described in this article would be useful for documenting visual changes in future clinical trials assessing retinal health in the older eye with and without ocular pathology.

A novel on-eye wettability analyzer for soft contact lenses.

PURPOSE: To develop novel methodology to assess two in vivo wettability parameters, contact angle and index of liquid spreading (ILS), for hydrogel contact lenses and to provide a comprehensive investigation of the measurement errors (repeatability) associated with these two parameters. METHODS: A Novel On-eye Wettability Analyzer (NOWA) was constructed which delivered a drop of 0.4% sodium hyaluronate mixed with sodium fluorescein directly on to a lens surface in vivo while a two-camera digital system recorded both the resultant contact angle and liquid spreading. Ten subjects each wore a different etafilcon A lens (-0.50 DS) in the right eye for 30 min before measurement on three separate occasions. For contact angles, the coefficient of repeatability (COR) associated with three measurement conditions (image analysis COR, intrasubject COR, and intersubject COR) was determined. For ILS, the COR associated with two measurement conditions (intrasubject COR and intersubject COR) was also determined. RESULTS: The in vivo contact angle for the etafilcon A lens was 19.8° ± 2.9° (mean ± standard deviation). COR values for contact angle were 3.2°, 5.2°, and 8.0° for image analysis, intrasubject measures, and intersubject measures, respectively. The mean ± standard deviation ILS was 2.0 ± 0.3 mm, and COR values were 0.4 and 0.8 mm for intrasubject and intersubject measures, respectively. CONCLUSIONS: This research demonstrates that it is possible to obtain hydrogel lens contact angles in vivo and to provide a new wettability parameter (ILS) with the NOWA instrumentation. The COR values obtained were considered to be acceptable. Intersubject COR values were greater than intrasubject COR values for both contact angle and ILS; this is likely to be due to greater variability of tear film characteristics between subjects than within an individual. The use of this novel methodology and its associated clinical parameters across a wider range of lens types in various clinical situations warrants further investigation.