33 research outputs found
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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 Ï„) and yellow-blue (YB) chromatic sensitivity were independent predictors for AMD progression risk (cone Ï„, 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 Ï„, YB chromatic threshold and foveal thickness are independent predictors of likely risk of AMD progression
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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 Ï„) 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
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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
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The Effect of Systemic Hyperoxia and Hypoxia on Scotopic Thresholds in People with Early and Intermediate Age-related Macular Degeneration
Purpose: Morphological retinal changes combined with functional evidence implicate hypoxia in the pathogenesis of age-related macular degeneration (AMD). However, the role of hypoxia in the scotopic threshold deficit reported in AMD has not been investigated. This study compared scotopic thresholds in participants with early and intermediate AMD recorded under conditions of systemic hypoxia, hyperoxia and normoxia.
Materials and Methods: Over two sessions scotopic thresholds were measured with participants breathing 21% and 60% oxygen (n = 12 early AMD, n = 11 age-similar controls) or 21% and 14% oxygen (n = 16 early AMD, n = 20 age-similar controls). Thresholds were measured using a 'white', annular 12 degrees stimulus, using a QUEST procedure.
Results: There was no statistically significant change in scotopic thresholds within the AMD or control group when breathing the hyperoxic gas mixture (60% oxygen) or the hypoxic gas mixture (14% oxygen) when compared to the normoxic condition (21% oxygen). There was also no statistically significant difference in scotopic thresholds between groups under the hyperoxic or hypoxic gas conditions. The difference between groups under the normoxic condition was not statistically significant for the hyperoxia study (p =Â .70), but did reach significance in the hypoxia study (p =Â .05).
Conclusion: This study provided no evidence that breathing that breathing 14% or 60% oxygen altered scotopic thresholds in those with early AMD when compared to controls. However, the lack of elevated scotopic thresholds in the AMD group of the hyperoxia study is of note, as it is unlikely that hyperoxia would reduce thresholds which were not significantly raised at baseline, regardless of whether hypoxia was a factor in the disease pathogenesis. The findings of this study do not rule out a role for hypoxia in early AMD, but this needs to be assessed in future experiments using measures that differ significantly between people with AMD and controls
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The Relationship Between the Photopic Negative Response and Retinal Ganglion Cell Topography
Purpose: To assess the topographic relationship between the photopic negative response (PhNR) and retinal ganglion cell distribution in healthy individuals.
Method: Data was recorded from 16 healthy participants. The amplitude of PhNRs obtained in response to focal long duration (250 ms) and brief flash (5 ms), red (660 nm) on blue (469 nm) stimuli of increasing size (5° - full field) were measured. The number of retinal ganglion cell receptive fields (RGCf) in each stimulus area was established from the literature and regression analysis used to determine the relationships between: PhNR amplitude and number of RGCfs stimulated, PhNR density and the RGCf density and response per RGCf as a function of eccentricity.
Results: The overall amplitude of the PhNR increased with stimulus size and the response density declined from ∼0.1 μV/deg in the macular region to ∼0.003 μV/deg approximately 45° from the fovea. Contrary to expectations, the relationship between the PhNR and number of RGCf was nonlinear, the response from more eccentric neurons being about three times greater than those in the macular region.
Conclusions: Although the amplitude of the PhNR broadly maps on to the topographic distribution of RGCf the increase in PhNR amplitude with increasing eccentricity is only partly explained by RGCf numbers. Increases in the PhNR amplitude may be due to topographic variations in the contributions from other non-RGC neurons, as well as eccentricity-related morphologic and physiologic differences in RGCs
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Low-Level Nighttime Light Therapy for Age-Related Macular Degeneration: A Randomized Clinical Trial
Purpose: To investigate the safety, acceptability, and effectiveness of light therapy on the progression of AMD over 12 months.
Methods: This was a phase I/IIa, prospective, proof-of-concept, single-center, unmasked randomized controlled trial. Sixty participants (55 to 88 years) with early AMD in the study eye and neovascular AMD (nAMD) in the fellow eye were recruited from a hospital nAMD clinic. Eligible participants were randomized (ratio 1:1) to receive light therapy or to an untreated control group. Light therapy was delivered via a light-emitting mask (peak 505 nm, 23 scotopic Td), which was worn each night for 12 months. Co-primary outcome measures were disease progression (onset of nAMD or increased drusen volume beyond test-retest limits) and change in time constant of cone dark adaptation. Other main outcomes included adverse events, compliance, and subjective sleep quality data.
Results: Disease progression over 12 months was seen in 38.1% (18.1%-61.6% confidence interval [CI]) of intervention participants and 48.3% (29.4%-67.5% CI) of controls (Mantel-Haenszel test, common odds ratio = 0.763, P = 0.495). A significantly larger delay in cone adaptation was observed in the intervention group (1.66 ± 0.61 minutes) than in the control group (0.66 ± 0.49 minutes) over the follow-up period. No reported adverse events were deemed to be associated with the intervention.
Conclusions: Although acceptable to the patients, light therapy did not have a substantial effect on the progression of early AMD over 12 months. Further investigation is necessary to discover the permanency and cause of the adverse effect of light therapy on dark adaptation
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How effective is eccentric viewing training? A systematic literature review
Purpose: The global prevalence of age-related macular degeneration (AMD) and associated central vision loss (CVL) is rising. CVL hinders the performance of many activities of daily living (ADLs). Adaptive strategies such as eccentric viewing (EV) and steady eye strategy (SES) may be used to compensate for CVL. In order to establish the potential of these rehabilitation strategies, this systematic review evaluates current literature regarding the effectiveness of EV and SES training in people with CVL.
Recent Findings: The search strategies identified 2605 publications, 36 of which met the inclusion criteria for the review, but only three of which were randomised controlled trials. This literature shows that EV and SES training can improve near visual acuity, reading speed, and performance of ADLs in people with CVL. However, there was insufficient literature to establish a relationship between training and distance visual acuity or quality-of-life. There is no conclusive evidence to show that a particular model of EV training is superior to another, little clear evidence of a relationship between participant characteristics and training outcomes and no data regarding the cost effectiveness of training.
Summary: This report highlights the need for further robust research to establish the true potential and cost effectiveness of EV and SES training as a rehabilitation strategy for individuals with CVL
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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
The depression in visual impairment trial (DEPVIT): trial design and protocol
<b>Background</b>
The prevalence of depression in people with a visual disability is high but screening for depression and referral for treatment is not yet an integral part of visual rehabilitation service provision. One reason for this may be that there is no good evidence about the effectiveness of treatments in this patient group. This study is the first to evaluate the effect of depression treatments on people with a visual impairment and co morbid depression.<p></p>
<b>Methods/design</b>
The study is an exploratory, multicentre, individually randomised waiting list controlled trial. Participants will be randomised to receive Problem Solving Therapy (PST), a ‘referral to the GP’ requesting treatment according to the NICE’s ‘stepped care’ recommendations or the waiting list arm of the trial. The primary outcome measure is change (from randomisation) in depressive symptoms as measured by the Beck’s Depression Inventory (BDI-II) at 6 months. Secondary outcomes include change in depressive symptoms at 3 months, change in visual function as measured with the near vision subscale of the VFQ-48 and 7 item NEI-VFQ at 3 and 6 months, change in generic health related quality of life (EQ5D), the costs associated with PST, estimates of incremental cost effectiveness, and recruitment rate estimation.<p></p>
<b>Discussion</b>
Depression is prevalent in people with disabling visual impairment. This exploratory study will establish depression screening and referral for treatment in visual rehabilitation clinics in the UK. It will be the first to explore the efficacy of PST and the effectiveness of NICE’s ‘stepped care’ approach to the treatment of depression in people with a visual impairment.<p></p>