Effect of varying skin surface electrode position on electroretinogram responses recorded using a handheld stimulating and recording system.

PURPOSE: A handheld device (the RETeval system, LKC Technologies) aims to increase the ease of electroretinogram (ERG) recording by using specially designed skin electrodes, rather than corneal electrodes. We explored effects of electrode position on response parameters recorded using this device. METHODS: Healthy adult twins were recruited from the TwinsUK cohort and underwent recording of light-adapted flicker ERGs (corresponding to international standard stimuli). In Group 1, skin electrodes were placed in a "comfortable" position, which was up to 20 mm below the lid margin. For subsequent participants (Group 2), the electrode was positioned 2 mm from the lid margin as recommended by the manufacturer. Amplitudes and peak times (averaged from both eyes) were compared between groups after age-matching and inclusion of only one twin per pair. Light-adapted flicker and flash ERGs were recorded for an additional 10 healthy subjects in two consecutive recording sessions: in the test eye, electrode position was varied from 2 to 10-20 mm below the lid margin between sessions; in the fellow (control) eye, the electrode was 2 mm below the lid margin throughout. Amplitudes and peak times (test eye normalised to control eye) were compared for the two sessions. RESULTS: Including one twin per pair, and age-matching yielded 28 individuals per group. Flicker ERG amplitudes were significantly lower for Group 1 than Group 2 participants (p = 0.0024). However, mean peak times did not differ between groups (p = 0.54). For the subjects in whom electrode position was changed between recording sessions, flash and flicker amplitudes were significantly lower when positioned further from the lid margin (p < 0.005), but peak times were similar (p > 0.5). CONCLUSIONS: Moving the skin electrodes further from the lid margin significantly reduces response amplitudes, highlighting the importance of consistent electrode positioning. However, this does not significantly affect peak times. Thus, it may be feasible to adopt a more comfortable position in participants who cannot tolerate the recommended position if analysis is restricted to peak time parameters.

The effect of non-neovascular age-related macular degeneration on face recognition performance.

PURPOSE: There is a well-established research base surrounding face recognition in patients with age-related macular degeneration (AMD). However, much of this existing research does not differentiate between results obtained for 'wet' AMD and 'dry' AMD. Here, we test the hypothesis that face recognition performance is worse in patients with dry AMD compared with visually healthy peers. METHODS: Patients (>60 years of age, logMAR binocular visual acuity 0.7 or better) with dry AMD of varying severity and visually healthy age-related peers (controls) completed a modified version of the Cambridge Face Memory Test (CFMT). Percentage of correctly identified faces was used as an outcome measure for performance for each participant. A 90% normative reference limit was generated from the distribution of CFMT scores recorded in the visually healthy controls. Scores for AMD participants were then specifically compared to this limit, and comparisons between average scores in the AMD severity groups were investigated. RESULTS: Thirty patients (median [interquartile range] age of 76 [70, 79] years) and 34 controls (median age of 70 [64, 75] years) were examined. Four, seventeen and nine patients were classified as having early, intermediate and late AMD (geographic atrophy) respectively. Five (17%) patients recorded a face recognition performance worse than the 90% limit (Fisher's exact test, p = 0.46) set by controls; four of these had geographic atrophy. Patients with geographic atrophy identified fewer faces on average (±SD) (61% ± 22%) than those with early and intermediate AMD (75 ± 11%) and controls (74% ± 11%). CONCLUSIONS: People with dry AMD may not suffer from problems with face recognition until the disease is in its later stages; those with late AMD (geographic atrophy) are likely to have difficulty recognising faces. The results from this study should influence the management and expectations of patients with dry AMD in both community practice and hospital clinics.

Seeing it differently: self-reported description of vision loss in dry age-related macular degeneration.

PURPOSE: A realistic description of visual symptoms associated with dry age-related macular degeneration (AMD) is important for raising awareness of the condition and educating patients. This study aimed to develop a set of descriptors for dry AMD and examine the realism of images currently and frequently used to show visual symptoms of the condition. METHODS: Volunteers with dry AMD with a range of disease severity were given an eye examination and were asked to describe visual symptoms of their condition in a conversational interview. Participants were also asked to comment on a photograph typically used to portray the visual symptoms of AMD. Interviews were audio recorded, transcribed and subjected to content analysis. RESULTS: Twenty-nine participants were interviewed. Median (interquartile range [IQR]) age was 75 (70, 79) years. Median (IQR) binocular visual acuity (VA) and Pelli-Robson contrast sensitivity (CS) was 0.2 (0.18, 0.36) logMAR and 1.65 (1.50, 1.95) log CS respectively. Three, 17 and nine patients had early, intermediate and late (geographic atrophy, GA) AMD, respectively. The most frequently reported descriptor group was blur (n = 13) followed by missing (n = 10) and distortion (n = 7). We chose the most popular image used to portray the visual symptoms of dry AMD based on an internet search and showed this to 21 participants. Sixteen participants (76% [95% confidence interval 53-92%]), including three out of the seven people with geographic atrophy, unequivocally rejected the realism of the image. CONCLUSIONS: People with dry AMD use a wide range of descriptors for their visual experience. Visual symptoms of dry AMD as portrayed by commonly shown images were not the experience of most people in this study.

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.

An evaluation of two candidate functional biomarkers for AMD.

PURPOSE: To evaluate the intersession repeatability of the Colour Assessment and Diagnosis (CAD) test and a novel 14-Hz flicker test in a population of healthy participants 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 [standard deviation] age 36.3 [14.1] years) on two separate days. Intersession 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. These data can help clinicians decide if the results from repeated measures are of clinical significance. Despite pretest training, there was some evidence of a learning effect. Therefore, clinical trials using these techniques should ensure training is sufficient to minimize these effects.

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.

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.

Test-Retest Variability and Discriminatory Power of Measurements From Microperimetry and Dark Adaptation Assessment in People With Intermediate Age-Related Macular Degeneration - A MACUSTAR Study Report.

Purpose: The purpose of this study was to assess test-retest variability and discriminatory power of measures from macular integrity assessment (S-MAIA) and AdaptDx. Methods: This is a cross-sectional study of 167 people with intermediate age-related macular degeneration (iAMD), no AMD (controls; n = 54), early AMD (n = 28), and late AMD (n = 41), recruited across 18 European ophthalmology centers. Repeat measures of mesopic and scotopic S-MAIA average (mean) threshold (MMAT decibels [dB] and SMAT [dB]) and rod intercept time (RIT [mins]) at 2 visits 14 (±7) days apart were recorded. Repeat measures were assessed by Bland-Altman analysis, intra-class correlation coefficients (ICCs) and variability ratios. Secondary analysis assessed the area under the receiver operating characteristic curves (AUC) to determine the ability to distinguish people as having no AMD, early AMD, or iAMD. Results: Data were available for 128, 131, and 103 iAMD participants for the mesopic and scotopic S-MAIA and AdaptDx, respectively. MMAT and SMAT demonstrate similar test-retest variability in iAMD (95% confidence interval [CI] ICC of 0.79-0.89 and 0.78-0.89, respectively). ICCs were worse in RIT (95% CI ICC = 0.55-0.77). All tests had equivalent AUCs (approximately 70%) distinguishing between subjects with iAMD and controls, whereas early AMD was indistinguishable from iAMD on all measures (AUC = <55%). A learning effect was not seen in these assessments under the operating procedures used. Conclusions: MMAT, SMAT, and RIT have adequate test-retest variability and are all moderately good at separating people with iAMD from controls. Translational Relevance: Expected levels of test-retest variability and discriminatory power of the AdaptDx and MAIA devices in a clinical study setting must be considered when designing future trials for people with 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.

Electrophysiological Assessment in Birdshot Chorioretinopathy: Flicker Electroretinograms Recorded With a Handheld Device.

Purpose: The flicker electroretinogram (ERG) is a sensitive indicator of retinal dysfunction in birdshot chorioretinopathy (BCR). We explored recordings from a handheld device in BCR, comparing these with conventional recordings in the same patients and with handheld ERGs from healthy individuals. Methods: Non-mydriatic flicker ERGs, using the handheld RETeval system (LKC Technologies), were recorded with skin electrodes at two centers. At one center (group 1), the stimuli (85 Td·s, 850 Td background) delivered retinal illuminance equivalent to international standards; at the other center (group 2), a different protocol was used (32 Td·s, no background). Patients also underwent international standard flicker ERG recordings with conventional electrodes following mydriasis. Portable ERGs from patients were also compared with those from healthy individuals. Results: Thirty-two patients with BCR (mean age ± SD, 56.4 ± 11.3 years) underwent recordings. Portable and standard ERG parameters correlated strongly (r > 0.75, P < 0.01) in both groups. Limits of agreement for peak times were tighter in group 1 (n = 21; -4.3 to +2.0 ms [right eyes], -3.9 to 1.5 ms [left eyes]) than in group 2 (n = 11; -3.4 to +6.9 ms [right eyes], -4.8 to +9.0 ms [left eyes]). Compared with healthy controls (n = 66 and n = 90 for groups 1 and 2, respectively), patients with BCR showed smaller mean amplitudes and longer peak times. Conclusions: Portable ERGs correlated strongly with conventional recordings, suggesting potential in rapid assessment of cone system function in office settings. Translational Relevance: Flicker ERGs, known to be useful in BCR, can be obtained rapidly with a portable device with skin electrodes and natural pupils.

Repeatability and Discriminatory Power of Chart-Based Visual Function Tests in Individuals With Age-Related Macular Degeneration: A MACUSTAR Study Report.

Importance: There is a need for validated clinical end points that are reliably able to quantify potential therapeutic effects of future treatments targeting age-related macular degeneration (AMD) before the onset of serious visual impairment. Objective: To assess the reliability and discriminatory power of 5 simple chart-based visual function (VF) tests as potential measures for clinical trial end points with regulatory and patient-access intention in intermediate AMD (iAMD). Design, Setting, and Participants: This international noninterventional study took place at 18 tertiary ophthalmology departments across Europe. Participants were recruited between April 2018 and March 2020 and were identified during routine clinical review. Participants with no AMD and early AMD were recruited from hospital staff, friends, and family of participants with AMD and via referrals from community ophthalmologists and optometrists. The repeatability and discriminatory power of 5 simple chart-based assessments of VF (best-corrected visual acuity [BCVA], low-luminance visual acuity [LLVA], Moorfields Acuity Test [MAT], Pelli-Robson Contrast Sensitivity [CS], and International Reading Speed Test [IReST]) were assessed in a repeated-measures design. VF assessments were performed on day 0 and day 14. Participants with early AMD, iAMD, late AMD, and no AMD were recruited. Main Outcomes and Measures: Intraclass correlation coefficients (ICCs) and Bland-Altman 95% limits of agreement (LoA) were computed to assess repeatability. Area under the receiver operating characteristic curves (AUCs) determined the discriminatory ability of all measures to classify individuals as having no AMD or iAMD and to differentiate iAMD from its neighboring disease states. Results: A total of 301 participants (mean [SD] age, 71 [7] years; 187 female participants [62.1%]) were included in the study. Thirty-four participants (11.3%) had early AMD, 168 (55.8%) had iAMD, 43 (14.3%) had late AMD, and 56 (18.6%) had no AMD. ICCs for all VF measures ranged between 0.88 and 0.96 when all participants were considered, indicating good to excellent repeatability. All measures displayed excellent discrimination between iAMD and late AMD (AUC, 0.92-0.99). Early AMD was indistinguishable from iAMD on all measures (AUC, 0.54-0.64). CS afforded the best discrimination between no AMD and iAMD (AUC, 0.77). Under the same conditions, BCVA, LLVA, and MAT were fair discriminators (AUC, 0.69-0.71), and IReST had poor discrimination (AUC, 0.57-0.61). Conclusions and Relevance: BCVA, LLVA, MAT, CS, and IReST had adequate repeatability in this multicenter, multiexaminer setting but limited power to discriminate between no AMD and iAMD. The prognostic power of these variables to predict conversion from iAMD to late AMD is being examined in the ongoing longitudinal part of the MACUSTAR study.

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.

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.

How is the risk of being diagnosed with referable diabetic retinopathy affected by failure to attend diabetes eye screening appointments?

BACKGROUND/AIMS: This study examines the anecdotal impression that in diabetes eye screening there is a relationship between number of consecutive missed screening appointments and the incidence of referable retinopathy at the next screening appointment that is attended. METHODS: A retrospective observational audit was conducted of data from 62,067 people who were due for annual diabetes eye screening in the North East London Diabetes Eye Screening Programme between January 2010 and January 2017, and who had missed at least one screening appointment within that time. RESULTS: Missing 5 consecutive screening appointments increased the incidence of referable retinopathy from a programme average of 4% up to 15%. The incidence of referable retinopathy in people missing 10 or more consecutive appointments was ~20%. There was an association between younger age, male gender, type I disease, and being of African ethnicity with increasing number of missed appointments. CONCLUSIONS: There was a strong association between the number of missed appointments and the proportion of patients showing referable retinopathy at the next visit. Approaches to reduce the number of missed appointments may help to reduce the incidence of referable retinopathy. These may be targeted at those showing the greatest non-attendance behaviour in the current study.

Optimising assessment of dark adaptation data using time to event analysis.

In age-related macular degeneration (AMD) research, dark adaptation has been found to be a promising functional measurement. In more severe cases of AMD, dark adaptation cannot always be recorded within a maximum allowed time for the test (~ 20-30 min). These data are recorded either as censored data-points (data capped at the maximum test time) or as an estimated recovery time based on the trend observed from the data recorded within the maximum recording time. Therefore, dark adaptation data can have unusual attributes that may not be handled by standard statistical techniques. Here we show time-to-event analysis is a more powerful method for analysis of rod-intercept time data in measuring dark adaptation. For example, at 80% power (at α = 0.05) sample sizes were estimated to be 20 and 61 with uncapped (uncensored) and capped (censored) data using a standard t-test; these values improved to 12 and 38 when using the proposed time-to-event analysis. Our method can accommodate both skewed data and censored data points and offers the advantage of significantly reducing sample sizes when planning studies where this functional test is an outcome measure. The latter is important because designing trials and studies more efficiently equates to newer treatments likely being examined more efficiently.

Are Current Methods of Measuring Dark Adaptation Effective in Detecting the Onset and Progression of Age-Related Macular Degeneration? A Systematic Literature Review.

INTRODUCTION: Dark adaptation (DA) has been proposed as a possible functional biomarker for age-related macular degeneration (AMD). In this systematic review we aim to evaluate current methodology used to assess DA in people with AMD, the evidence of precision in detecting the onset and progression of AMD, and the relationship between DA and other functional and structural measures. METHODS: MEDLINE, EMBASE, CINAHL, AMED, PsycINFO, PsycARTICLES were searched for studies published between January 2006 and January 2020 that assessed DA in people with AMD. Details of eligible studies including study design, characteristics of study population and outcomes were recorded. All included studies underwent quality appraisal using approved critical appraisal tools. This systematic review follows PRISMA guidelines (PROSPERO registration number: CRD42019129486). RESULTS: Forty-eight studies were eligible for inclusion, reporting a variety of instruments and protocols to assess different DA parameters. Twenty of these studies used the AdaptDx (MacuLogix, Hummelstown, PA, USA) instrument and assessed rod-intercept time (RIT). Most of these reported that RIT was delayed in people with AMD and this delay worsened with AMD severity. Four studies, involving 533 participants, reported estimates of diagnostic performance of AdaptDx to separate people with AMD from visually healthy controls. DA has been compared to other measures of visual function, patient-reported outcome measures (PROMs) and structural measures. Ten studies specifically considered evidence that the presence of certain structural abnormalities was associated with impaired DA in AMD. CONCLUSIONS: This systematic review indicates overwhelming evidence of reasonable quality for an association between impaired DA and AMD. Data on the repeatability and reproducibility of DA measurement are sparse. There is evidence that structural abnormalities such as reticular drusen are associated with prolongation of DA time. Fewer studies have explored an association between DA and other measures of visual function or PROMs. We found no studies that had compared DA with performance-based measures.

Inter-subject, inter-ocular and inter-session repeatability of the photopic negative response of the electroretinogram recorded using DTL and skin electrodes.

The photopic negative response (PhNR) has attracted interest as a flash ERG component reflecting inner retinal activity, with investigators adopting various approaches to analysing the response. This study has two principal aims: first to determine the most reliable technique for assessing the PhNR amplitude; secondly to compare the repeatability characteristics of the PhNR recorded using DTL and skin active electrodes. Electroretinograms were recorded in 31 subjects, using both electrode types, in response to a Ganzfeld red stimulus (Lee filter "bright red"; 1.76 log phot td.s; 4 Hz) presented over a steady blue background (Schott glass filter BG28; 3.9 log scot td). Sixteen subjects returned to assess repeatability. PhNR amplitude was measured from b-wave peak-to-PhNR trough, pre-stimulus baseline to trough, and from peak and baseline to a fixed time-point; a ratio of b-wave/PhNR amplitude was also calculated. Coefficients of variation (CoV), and inter-ocular and inter-session limits of agreement (LoA) were calculated for all measures. The ratio of b-wave/PhNR amplitude showed the lowest CoV (14.3% DTL; 23.2% skin), inter-ocular LoA (22.2% DTL; 25.0% skin), and inter-session LoA (22.8% DTL; 20.3% skin). The peak-to-trough and peak-to-fixed-time measurements were also consistently reliable. Least reliable measures were those measured from baseline. While skin electrode responses were significantly smaller than DTL responses (P < 0.0001), the variability was only slightly increased. This study suggests that peak-to-trough measurements are the most reliable means of measuring the PhNR and ratio calculation further improves repeatability. Skin electrodes provided a viable alternative to DTL electrodes for recording the PhNR.

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 = .70), but did reach significance in the hypoxia study (p = .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.

Novel computer-based assessments of everyday visual function in people with age-related macular degeneration.

PURPOSE: To test the hypothesis that the performance in novel computer-based tasks of everyday visual function worsens with disease severity in people with non-neovascular age-related macular degeneration. METHODS: Participants with and without non-neovascular age-related macular degeneration (≥60 years, minimum logMAR binocular visual acuity 0.7) performed a series of standard visual function tests and two novel computer-based tasks. In a visual search task, participants had to locate an image of a single real-world object within an array of 49 distractor images. Next, in a series of simulated dynamic driving scenes, participants were asked to identify one or two approaching real-world road signs and then select these road signs from four options. Outcome measures were median response times and total correct responses. RESULTS: Forty-nine participants had no macular disease (n = 11), early/intermediate age-related macular degeneration (n = 16) or geographic atrophy (n = 22). Groups were age-similar with median (interquartile range) logMAR visual acuity of 0.00 (-0.08,0.12), 0.13 (-0.08,0.70) and 0.32 (0.12,0.70) respectively. Median (interquartile range) visual search response times were 1.9 (1.0,2.4), 1.8 (1.1,3.7) and 2.4 (1.2,6.0) seconds respectively. Median (interquartile range) road sign response times (single road signs) were 1.2 (0.4,1.7), 1.5 (0.9,2.8) and 1.8 (1.0,5.5) seconds respectively. Median (interquartile range) road sign response times (double road signs) were 1.7 (0.7,2.4), 2.3 (1.2,3.1) and 2.5 (1.7,6) seconds respectively. Participants with geographic atrophy recorded slower response times in all tasks and over 50% performed outside the normative limit for task performance. There were no significant differences between groups in total correct responses across all tasks. CONCLUSIONS: In a novel computer-based assessment, people with increasing severity of age-related macular degeneration take longer to perform visual search of everyday objects and take longer to identify road signs than those with no age-related macular degeneration. These novel assessments could be useful as patient-relevant, secondary outcomes for clinical trials.

'You've got dry macular degeneration, end of story': a qualitative study into the experience of living with non-neovascular age-related macular degeneration.

BACKGROUND/OBJECTIVES: To investigate the impact of non-neovascular (dry) age-related macular degeneration (AMD) on the person with respect to diagnosis, vision loss and coping strategies. SUBJECTS/METHODS: Volunteers with dry AMD with a range of disease severity were given an eye examination and asked to describe aspects of their experience with dry AMD in a semi-structured interview. Interviews were audio-recorded, transcribed, and subjected to Framework analysis. Overarching themes were pre-defined, whilst subthemes were derived from the data. RESULTS: Twenty-seven participants (81% female), with early (n = 3), intermediate (n = 16) and advanced dry AMD (GA; n = 8) were interviewed. Median (interquartile range) age (years), logMAR binocular visual acuity and Pelli-Robson contrast sensitivity were 76 (71, 80), 0.2 (0.18, 0.40) and 1.65 (1.35, 1.93), respectively. Overarching themes (and subthemes) were: diagnosis (relationship with healthcare professional, psychological impact of diagnosis, and knowledge of AMD, both pre- and post-diagnosis), impact of visual loss (functional and psychological) and coping strategies (help from others and personal strategies). Many participants reported feelings of distress at the time of diagnosis and, particularly noteworthy, several reported a constant fear of their condition worsening. CONCLUSIONS: Dry AMD, for which there is currently no treatment, can have a significant impact on individuals, even in its early stages, before significant functional vision loss is manifest, as well as in its intermediate and advanced stages. Results from this study offer important insight into the experience of living with dry AMD not previously explored. Moreover, the results have the potential to serve as an educational resource for eyecare professionals.