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.

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.

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.

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.

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.

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.

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.

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.

'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.

Measuring dynamic levels of self-perceived anxiety and concern during simulated mobility tasks in people with non-neovascular age-related macular degeneration.

BACKGROUND/AIMS: To assess response to real-world mobility scenarios in people with dry age-related macular degeneration (AMD) using a computer-based test. METHODS: Participants were shown 18 point-of-view computer-based movies simulating walking through real-world scenarios, and pressed a button during scenes which would cause them self-perceived anxiety or concern in their day-to-day life. Button pressure was recorded throughout. Pressure traces were generated, which aligned with each movie time point. Group averages based on AMD severity were generated. Bootstrapped confidence intervals (CIs) for responses by group were generated around traces. Traces were examined to discover events causing the greatest differences between groups. RESULTS: Participants had early/no AMD (n=8), intermediate AMD (n=7) or geographic atrophy (n=15 (GA)). Median (IQR) logMAR visual acuity was 0.04 (-0.04, 0.18), 0.26 (0.10, 0.40) and 0.32 (0.20, 0.56), respectively. Participants with intermediate AMD or GA recorded greater pressure than those with early and no AMD (Kruskal-Wallis, p=0.04). Four events involving navigating stairs and three under low luminance elicited greatest differences between groups (p<0.001). CONCLUSION: People with intermediate AMD or GA likely experience higher levels of concern associated with mobility. The test highlights areas of specific concern. Results should be useful in patient management and educating the public about the everyday effects of AMD.

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

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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.

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.

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.

Determining Optimal Test Parameters for Assessing Dark Adaptation in People With Intermediate Age-Related Macular Degeneration.

Purpose: The primary aim was to determine optimal test conditions for evaluating dark adaptation in intermediate age-related macular degeneration (iAMD) in order to minimize test time while maintaining diagnostic sensitivity. Methods: People with AMD and age-similar controls were recruited (aged >55 years). Rod intercept time (RIT) was assessed after a 76%, 70%, and 65% rhodopsin bleach at 5° eccentricity and 76% and 70% bleach at 12°. Test order was randomized and a 30-minute washout period added between tests. Results were compared between control and iAMD groups and receiver operating characteristics (ROC) curves were constructed. Results: A total of 26 participants with variable grades of macular health attended for two visits. There was a statistically significant difference in average RIT between the control and iAMD groups at 5° (median, IQR controls = 5.8 minutes, 3.8-7.5; iAMD = 20.6 minutes, 11.1-30.0; Mann-Whitney, P = 0.01) and at 12° (mean, controls: 4.54 minutes ± 2.12 SD, iAMD = 7.72 minutes ± 3.37 SD; independent samples t-test, P = 0.03) following a 76% bleach. Area under the ROC curves was 0.83 (confidence interval [CI]: 0.64-1.0) and 0.79 (CI: 0.59-0.99) for these two test conditions, respectively. Five participants (45%) in the iAMD group had RITs >20 minutes for 76% bleach at 5°, but none for any other test condition. Conclusions: Nearly half of the participants with iAMD produced unacceptably long recovery times (>20 minutes) using a 76% bleach at 5° eccentricity. The 76% bleach at 12° provided almost equivalent separation between AMD and controls but recovery was achieved within 20 minutes.

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.