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.

How effective is eccentric viewing training? A systematic literature review.

PURPOSE: The global prevalence of age-related macular degeneration and associated central vision loss is rising. Central vision loss hinders the performance of many activities of daily living. Adaptive strategies such as eccentric viewing and steady eye strategy may be used to compensate for central vision loss. In order to establish the potential of these rehabilitation strategies, this systematic review evaluates current literature regarding the effectiveness of eccentric viewing and steady eye strategy training in people with central vision loss. RESULTS: 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 eccentric viewing and steady eye strategy training can improve near visual acuity, reading speed, and performance of activities of daily living in people with central vision loss. 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 eccentric viewing 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. CONCLUSION: This report highlights the need for further robust research to establish the true potential and cost effectiveness of eccentric viewing and steady eye strategy training as a rehabilitation strategy for individuals with central vision loss.

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. 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 coefficient of repeatability (CoR) was calculated to assess the repeatability of the methods, and a repeated-measures analysis of variance was used to compare mean recovery parameters. RESULTS: All four methods demonstrated a similar level of intersession repeatability for measurement of cone recovery, yielding CoRs between 1.18 and 1.56 min. 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 between 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.

Aging and cone dark adaptation.

PURPOSE: Following exposure to a bright light that bleaches a significant portion of photopigment, the eyes take several minutes to regain sensitivity. This slow process, known as dark adaptation, is impaired in patients with age-related macular degeneration and is an important candidate biomarker for this disease. The aim of this study was to evaluate the effect of age on cone dark adaptation. METHODS: Data were obtained from 41 healthy adults aged between 20 and 83 years. Pupils were dilated and 96% of cone photopigment was "bleached," before threshold was monitored continuously for 5 min in the dark, using a 4° diameter achromatic spot centered on the fovea. Threshold recovery data were modeled, and the time constant of cone recovery (τ), initial cone thresholds, and final cone thresholds were determined. Regression analysis was used to determine the relationship between age and cone dark adaptation parameters. RESULTS: Cone τ increased by 16.4 s/decade of life, indicating a progressive slowing of dark adaptation with increasing age. This change in cone τ throughout adulthood was significant (p < 0.0005). There was no significant relationship between increasing age and initial cone threshold (p = 0.84) or final cone threshold (p = 0.82). CONCLUSIONS: Our results provide evidence for age-related slowing of cone dark adaptation after a full bleach in healthy adults, which is likely to contribute to visual difficulties when moving from bright to dim photopic light levels. We propose that the sensitivity and specificity of cone τ as a biomarker for early age-related macular disease could be improved by taking into account the significant age-related decline in this parameter.

Topography of cone dark adaptation deficits in age-related maculopathy.

PURPOSE: Despite widespread agreement that dark adaptation is abnormal in age-related maculopathy (ARM), the optimal retinal location for detection of this deficit is unclear. We quantified the diagnostic potential of cone dark adaptation as a function of retinal eccentricity and compared this with the diagnostic potential of the time to the rod-cone-break (RCB). METHODS: Cone dark adaptation was monitored after an 80% cone photopigment bleach in 10 subjects with ARM and 10 age-matched controls, using four achromatic annuli (0.5, 2, 7, and 12° radius) centered on the fovea. Threshold recovery data were modeled and the time constant of cone recovery (τ), final cone threshold, and time to RCB were determined. Diagnostic potential was evaluated by constructing receiver operating characteristic curves for these parameters. RESULTS: Cone τ was significantly longer for the ARM group at 2, 7, and 12°. The greatest difference between groups was observed at 12° from fixation. At this location, the mean τ was 3.49 (±2.02) min and 0.64 (±0.38) min for ARM and control subjects, respectively (p = 0.002), and time to RCB was 17.68 (±5.37) min and 9.05 (±2.11) min for ARM and control subjects, respectively (p = 0.001). Correspondingly, receiver operating characteristic curves showed that the diagnostic potential of dark adaptometry is greatest for stimuli presented 12° from fixation; for cone τ, the area under the curve = 0.99 ± 0.02 and for time to RCB, area under the curve = 0.96 ± 0.04. CONCLUSIONS: This study has shown cone-mediated dark adaptation to be significantly impaired in ARM. Our results provide compelling evidence in support of the diagnostic potential of cone dark adaptation and the use of annular stimuli at 12°. The observation that cone τ is highly diagnostic at this eccentricity is significant clinically because this parameter may be quantified within a few minutes.

The repeatability of the Goldmann-Weekers adaptometer for measuring cone adaptation.

To assess the inter-session repeatability of the Goldmann-Weekers adaptometer for the measurement of cone dark adaptation in a population of healthy subjects. Data were obtained from 31 healthy adults (mean age 21.5 ± 2.5) on 2 days. At each visit, pupils were dilated and a 96% bleach of cone photopigment was administered to the test eye before threshold was monitored continuously for 5 min in the dark using the Goldmann-Weekers adaptometer. A single exponential function was fitted to the threshold recovery data on a least squares basis. The coefficient of repeatability (CoR) was calculated to assess the repeatability of the time constant of recovery (τ), initial threshold and final threshold. Cone dark adaptation functions were successfully recorded from all subjects on both visits. The CoR was 79.48 s for τ, 0.71 log cdm(-2) for the initial threshold, and 0.58 log cdm(-2) for the final threshold. Paired samples t-tests showed that there were no significant differences between visits for any of the parameters assesed. Although the Goldmann-Weekers adaptometer was capable of monitoring the rapid changes in threshold that occur during cone dark adaptation, the CoR for τ was relatively large compared to the mean recovery time constants (126.48 ± 40.33 and 119.94 ± 33.25 s at the first and second visits, respectively). This indicates that the Goldmann-Weekers adaptometer is unlikely to be a useful instrument to chart changes in an individual's vision over time.