An Evaluation of a Battery of Functional and Structural Tests as Predictors of Likely Risk of Progression of Age-Related Macular Degeneration.

Purpose: To evaluate the ability of visual function and structural tests to identify the likely risk of progression from early/intermediate to advanced AMD, using the Age-Related Eye Disease Study (AREDS) simplified scale as a surrogate for risk of progression. The secondary aim was to determine the relationship between disease severity grade and the observed functional and structural deficits. Methods: A total of 100 participants whose AMD status varied from early to advanced were recruited. Visual function was assessed using cone dark adaptation, 14 Hz flicker and chromatic threshold tests and retinal structure was assessed by measuring drusen volume and macular thickness. The predictive value of the tests was estimated using ordinal regression analysis. Group comparisons were assessed using analysis of covariance. Results: Change in cone dark adaptation (cone τ) and yellow-blue (YB) chromatic sensitivity were independent predictors for AMD progression risk (cone τ, pseudo R2 = 0.35, P < 0.001; YB chromatic threshold, pseudo R2 = 0.16, P < 0.001). The only structural predictor was foveal thickness (R2 = 0.05, P = 0.047). Chromatic sensitivity and cone dark adaptation were also the best functional tests at distinguishing between severity groups. Drusen characteristics clearly differentiated between participants with early and advanced disease, but were not able to differentiate between those with early AMD and controls. Mean differences in retinal thickness existed between severity groups at the foveal (P = 0.040) and inner (P = 0.001) subfields. Conclusions: This study indicates that cone τ, YB chromatic threshold and foveal thickness are independent predictors of likely risk of AMD progression

Effects of focal frontal lesions on response inhibition

This study examined the performance of 38 normal subjects and 43 patients with focal lesions of the frontal lobes on a simple go-nogo task where the probability of the nogo stimulus was either 75% or 25%. Patients with lesions to the superior medial parts of the frontal lobes, in particular to the left superior portion of Brodmann area 6 (which includes the supplementary motor areas and the premotor areas for the right hand) had an increased number of false alarms (incorrect responses to the nogo stimulus). These results indicate that area 6 is specifically involved in the inhibition of response. Patients with lesions to the right anterior cingulate (areas 24 and 32) were slower and more variable in their reaction time. These findings could be explained by an inability to sustain stimulus-response contingencies. Lesions to the right ventrolateral prefrontal cortex (Brodmann areas 44, 45, 47) also increased the variability of response, perhaps by disrupting monitoring performance

An Evaluation of Two Candidate Functional Biomarkers for Age-Related Macular Degeneration

PURPOSE: To evaluate the inter-session repeatability of the Colour Assessment and Diagnosis (CAD) test and a novel 14-Hz flicker test in a population of healthy participants in order to provide benchmark data for their use as functional biomarkers for age-related macular degeneration (AMD). METHODS: Visual function was assessed using both techniques in 30 healthy adults (mean age 36.3 ± 14.1 years) on 2 separate days. Inter-session repeatability of RG and YB CAD thresholds and 14-Hz flicker thresholds was assessed by determining their coefficient of repeatability (CoR). RESULTS: The CoR was calculated to be 0.39 CAD units (17.0%) for RG thresholds, 0.43 CAD units (31.1%) for YB thresholds and 0.015 (53.4%) for 14-Hz flicker contrast thresholds. On average, thresholds improved by 4.72% (RG), 6.33% (YB) and 13.3% (14-Hz flicker) between visits 1 and 2, suggesting a small but consistent learning effect. The CoR for all parameters was relatively small compared to the mean thresholds obtained (RG: mean 2.27 ± 4.58, CoR 0.39; YB: mean 1.37 ± 0.55, CoR 0.43; 14-Hz flicker: mean 0.028 ± 0.01, CoR 0.015). CONCLUSIONS: This study has described the repeatability of the CAD and 14-Hz flicker tests. The data can help clinicians decide if the results from repeated measures are of clinical significance. Despite pre-test training, there was some evidence of a learning effect. Therefore, clinical trials using these techniques should ensure training is sufficient to minimize these effects

Community-based screening for infantile anemia in an Okinawan village, Japan

Infancy is a vulnerable age group for anemia throughout the world. However, community-based screening for infantile anemia is seldom reported. This study determined the prevalence of anemia among infants in an Okinawan village from 2003 to 2008, in relation to secondary prevention of the condition. The prevalence among infants aged 3–5, 6–12 and 16–23 months was 12.3%, 15.8%, and 4.2%, respectively, based on cross-sectional surveys (n = 3070 ), and was 11.0%, 17.2%, and 3.9% according to another retrospective cohort study (n = 511 ). The relatively low prevalence of anemia at early childhood suggested that previous detection and treatment through early and late infantile screening had been successful

Low-level night-time light therapy for age-related macular degeneration (ALight): study protocol for a randomized controlled trial

Background: Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. The only treatments currently available, such as ranibizumab injections, are for neovascular AMD, which accounts for only 10 to 15% of people with the condition. Hypoxia has been implicated as one of the primary causes of AMD, and is most acute at night when the retina is most metabolically active. By increasing light levels at night, the metabolic requirements of the retina and hence the hypoxia will be considerably reduced. This trial seeks to determine whether wearing a light mask that emits a dim, green light during the night can prevent the progression of early AMD. Methods: ALight is a Phase I/IIa, multicentre, randomized controlled trial. Sixty participants (55 to 88 years old) with early AMD in one eye and neovascular AMD (nAMD) in the fellow eye will be recruited from nAMD clinics. They will be randomized (in the ratio 1:1), either to receive the intervention or to be in the untreated control group, stratified according to risk of disease progression. An additional 40 participants with healthy retinal appearance, or early AMD only, will be recruited for a baseline cross-sectional analysis. The intervention is an eye mask that emits a dim green light to illuminate the retina through closed eyelids at night. This is designed to reduce the metabolic activity of the retina, thereby reducing the potential risk of hypoxia. Participants will wear the mask every night for 12 months. Ophthalmologists carrying out monthly assessments will be masked to the treatment group, but participants will be aware of their treatment group. The primary outcome measure is the proportion of people who show disease progression during the trial period in the eye with early AMD. A co-primary outcome measure is the rate of retinal adaptation. As this is a trial of a CE-marked device for an off-label indication, a further main aim of this trial is to assess safety of the mask in the cohort of participants with AMD

Measurement of cone dark adaptation: a comparison of four psychophysical methods

Purpose: Dark adaptometry is an important clinical tool for the diagnosis of a range of conditions, including age-related macular degeneration (AMD). In order to identify the most robust, clinically applicable technique for the measurement of cone dark adaptation, the repeatability and agreement of four psychophysical methods were assessed. Methods: Data were obtained from 31 healthy adults on two occasions, using four psychophysical methods. Participants’ pupils were dilated and 96% of cone photopigment was bleached before threshold was monitored in the dark using one of the techniques, selected at random. This procedure was repeated for each of the remaining methods. An exponential recovery function was fitted to all threshold recovery data. The co-efficient of repeatability (CoR) was calculated to assess the repeatability of the methods and a repeated measures analysis of variance (ANOVA) was used to compare mean recovery parameters. Results: All four methods demonstrated a similar level of inter-session repeatability for measurement of cone recovery, yielding CoRs between 1.18 and 1.56 minutes. There were no statistically significant differences in estimates of mean time constant of cone recovery (cone τ) between the four methods (p = 0.488), however significant differences initial and final cone thresholds were reported (p < 0.005). Conclusions: All of the techniques were capable of monitoring the rapid changes in visual threshold that occur during cone dark adaptation and the repeatability of the techniques was similar. This indicates that, despite the respective advantages and disadvantages of these psychophysical techniques, all four methods would be suitable for measuring cone dark adaptation in clinical practice

The effect of pre-adapting light intensity on dark adaptation in early age-related macular degeneration

Background This study aimed to identify the pre-adapting light intensity that generated the maximum separation in the parameters of dark adaptation between participants with early age-related macular degeneration (AMD) and healthy control participants in the minimum recording time. Methods Cone dark adaptation was monitored in 10 participants with early AMD and 10 age-matched controls after exposure to three pre-adapting light intensities, using an achromatic annulus (12° radius) centred on the fovea. Threshold recovery data were modelled, and the time constant of cone recovery (τ), final cone threshold, and time to rod-cone-break (RCB) were determined. The diagnostic potential of these parameters at all pre-adapting intensities was evaluated by constructing receiver operating characteristic (ROC) curves. Results There were significant differences between those with early AMD and healthy controls in cone τ and time to RCB (p < 0.05) at all pre-adapting ‘bleaching’ intensities. ROC curves showed that the diagnostic potential of dark adaptometry was high following exposure to all three pre-adapting intensities, generating an area under the curve in excess of 0.87 ± 0.08 for cone τ and time to RCB for all conditions. Conclusions Dark adaptation was shown to be highly diagnostic for early AMD across a range of pre-adapting light intensities, and therefore, the lower pre-adapting intensities evaluated in this study may be used to expedite dark adaptation measurement in the clinic without compromising the integrity of the data obtained. This study reinforces the suggestion that cone and rod dark adaptation are good candidate biomarkers for early AMD

Functional Imaging of the Outer Retinal Complex using High Fidelity Imaging Retinal Densitometry

We describe a new technique, high fidelity Imaging Retinal Densitometry (IRD), which probes the functional integrity of the outer retinal complex. We demonstrate the ability of the technique to map visual pigment optical density and synthesis rates in eyes with and without macular disease. A multispectral retinal imaging device obtained precise measurements of retinal reflectance over space and time. Data obtained from healthy controls and 5 patients with intermediate AMD, before and after photopigment bleaching, were used to quantify visual pigment metrics. Heat maps were plotted to summarise the topography of rod and cone pigment kinetics and descriptive statistics conducted to highlight differences between those with and without AMD. Rod and cone visual pigment synthesis rates in those with AMD (v = 0.043 SD 0.019 min-1 and v = 0.119 SD 0.046 min-1, respectively) were approximately half those observed in healthy controls (v = 0.079 SD 0.024 min-1 for rods and v = 0.206 SD 0.069 min-1 for cones). By mapping visual pigment kinetics across the central retina, high fidelity IRD provides a unique insight into outer retinal complex function. This new technique will improve the phenotypic characterisation, diagnosis and treatment monitoring of various ocular pathologies, including AMD

Energy spectra of elements with 18 or = Z or = 28 between 10 and 300 GeV/amu

The HEAO-3 Heavy Nuclei Experiment is composed of ionization chambers above and below a plastic Cerenkov counter. The energy dependence of the abundances of elements with atomic number, Z, between 18 and 28 at very high energies where they are rare and thus need the large area x time are measured. The measurements of the Danish-French HEAO-3 experiment (Englemann,, et al., 1983) are extended to higher energies, using the relativistic rise of ionization signal as a measure of energy. Source abundances for Ar and Ca were determined