Electrophysiological investigation of age-related macular degeneration

Age-related macular degeneration (AMD) affects 12.7 million people in Europe and North America (Klein et al., 1995 Klein et al. 1999). As a combination of decreasing birth rate and increasing longevity alter the demographic of the population, the impact of this disease can only increase. This places an immense burden, not only on the individuals afflicted by the condition, but on the financial resources of society as a whole. Unfortunately, treatment for AMD is still very restricted, and even our understanding of the pathogenesis of the disease is far from complete One concern in tackling the growing problem of AMD is that methods used in the assessment of the condition are limited, usually based on fundus appearance and visual acuity. The aim of this study was to develop a battery of electrophysiological tests which would be sensitive to the most subtle changes in retinal function in AMD. Such tests may aid diagnosis, provide a more sensitive measure of disease progression, and allow an early identification of phenotypic subtypes. Protocols were included for the recording of the focal rod ERG, the focal cone ERG, the S-cone ERG and the dynamic focal cone ERG, along with psychophysical tests of colour vision and dark adaptation. These tests were then applied to 31 subjects with ARM (12 with bilateral ARM, 11 with unilateral wet AMD and 8 with unilateral dry AMD), and 28 controls. In the analysis of ERG amplitudes a ratio of focal to full-field amplitude was introduced as a novel means of reducing intersubject variability in response. This was found to increase the accuracy of all tests in distinguishing between subject groups. The greatest separation between ARM and control groups was provided by the dynamic tests of visual function i.e. rod-cone break time of the dark adaptation function, and time constant of recovery of the dynamic focal cone ERG. The time to rod-cone break also showed potential in identifying subjects at increased risk of exudative retinal changes. Subjects were assigned to groups in this study on the basis of fundus appearance. However, individuals within each subject group showed a range of retinal function which belied the homogeneity of retinal signs. This raises the question of whether 'form' or 'function' should form the basis of classification and assessment of individuals with ARM and AMD.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Electrophysiological investigation of age-related macular degeneration

Age-related macular degeneration (AMD) affects 12.7 million people in Europe and North America (Klein et al., 1995 Klein et al. 1999). As a combination of decreasing birth rate and increasing longevity alter the demographic of the population, the impact of this disease can only increase. This places an immense burden, not only on the individuals afflicted by the condition, but on the financial resources of society as a whole. Unfortunately, treatment for AMD is still very restricted, and even our understanding of the pathogenesis of the disease is far from complete One concern in tackling the growing problem of AMD is that methods used in the assessment of the condition are limited, usually based on fundus appearance and visual acuity. The aim of this study was to develop a battery of electrophysiological tests which would be sensitive to the most subtle changes in retinal function in AMD. Such tests may aid diagnosis, provide a more sensitive measure of disease progression, and allow an early identification of phenotypic subtypes. Protocols were included for the recording of the focal rod ERG, the focal cone ERG, the S-cone ERG and the dynamic focal cone ERG, along with psychophysical tests of colour vision and dark adaptation. These tests were then applied to 31 subjects with ARM (12 with bilateral ARM, 11 with unilateral wet AMD and 8 with unilateral dry AMD), and 28 controls. In the analysis of ERG amplitudes a ratio of focal to full-field amplitude was introduced as a novel means of reducing intersubject variability in response. This was found to increase the accuracy of all tests in distinguishing between subject groups. The greatest separation between ARM and control groups was provided by the dynamic tests of visual function i.e. rod-cone break time of the dark adaptation function, and time constant of recovery of the dynamic focal cone ERG. The time to rod-cone break also showed potential in identifying subjects at increased risk of exudative retinal changes. Subjects were assigned to groups in this study on the basis of fundus appearance. However, individuals within each subject group showed a range of retinal function which belied the homogeneity of retinal signs. This raises the question of whether 'form' or 'function' should form the basis of classification and assessment of individuals with ARM and AMD

What advice is currently given to patients with Age-Related Macular Degeneration (AMD) by eyecare practitioners, and how effective is it at bringing about a change in lifestyle? A systematic review

There is currently no treatment for early/intermediate Age-related Macular Degeneration (AMD) but Eye Care Professionals (ECPs) are recommended to advise patients about modifiable lifestyle factors, including dietary changes, that can slow disease progression. The aim of this review was to understand advice currently given to patients with AMD by ECPs and to evaluate evidence regarding patient compliance. A systematic review was conducted of literature published in electronic databases: CINAHL, MEDLINE, PsycINFO, PyscARTICLES, EMBASE, AMED. Methods followed PRISMA guidelines (PROSPERO registration number: CRD42020223724). Twenty-four reports were eligible for inclusion, 12 focused on ECP experience, 7 on patient experience, and 6 on impact of advice (one paper reported on the ECP and patient experience). Studies reported that a substantial proportion of patients did not recall receiving lifestyle modification advice from their ECP (57.95%, range 2–95% across patient based studies). Practitioners were most likely to provide advice about nutritional supplements (80%, range 67–93% across ECP studies), and least likely about smoking (44%, range 28–71% across ECP studies), however supplements advised did not always comply with evidence-based guidelines. The main reason for patients not following lifestyle advice was lack of provision by the ECP (54.5%, range 21–94% across studies on the impact of advice). The review highlighted a need for more studies to understand patient preferences for receiving advice and research on ECP perceived barriers to advice provision.S.D. is funded by The Macular SocietyPeer ReviewedPostprint (author's final draft

Evaluating Retinal Function in Age-Related Maculopathy with the ERG Photostress Test

PURPOSE. To evaluate the diagnostic potential of the electroretinogram (ERG) photostress test and the focal cone ERG in age-related maculopathy (ARM). METHODS. The cohort comprised 31 patients with ARM and 27 age-matched control subjects. The ERG photostress test was used to monitor cone adaptation after intense light adaptation. Focal 41- and 5-Hz cone ERGs were recorded monocularly (central 20°) to assess steady state retinal function. Univariate analysis identified electrophysiological parameters that differed between groups, and receiver operating characteristic (ROC) curves were constructed to assess their diagnostic potential. Logistic regression analysis determined the diagnostic potential of a model incorporating several independent predictors of ARM. RESULTS. The rate of recovery of the ERG photostress test was reduced (recovery was slower) in subjects with ARM. The parameter exhibited good diagnostic potential (P = 0.002, area under ROC curve = 0.74). The implicit times of the 5-Hz (a-wave, P = 0.002; b-wave, P < 0.001) and the 41-Hz (P < 0.001) focal cone ERGs were increased, and the 41-Hz focal cone ERG amplitude (P = 0.003) and focal to full-field amplitude ratio (P = 0.001) were reduced in the ARM group. Logistic regression analysis identified three independent predictors of ARM, including the rate of recovery of the ERG photostress test. CONCLUSIONS. Early ARM has a marked effect on the kinetics of cone adaptation. The clinical application of the ERG photostress test increases the sensitivity and specificity of a model for the diagnosis of ARM. Improved assessment of the functional integrity of the central retina will facilitate early diagnosis and evaluation of therapeutic interventions

Using short dietary questions to develop indicators of dietary behaviour for use in surveys exploring attitudinal and/or behavioural aspects of dietary choices

For countries where nutrition surveys are infrequent, there is a need to have some measure of healthful eating to plan and evaluate interventions. This study shows how it is possible to develop healthful eating indicators based on dietary guidelines from a cross sectional population survey. Adults 18 to 64 years answered questions about the type and amount of foods eaten the previous day, including fruit, vegetables, cereals, dairy, fish or meat and fluids. Scores were based on serves and types of food according to an established method. Factor analysis indicated two factors, confirmed by structural equation modeling: a recommended food healthful eating indicator (RF_HEI) and a discretionary food healthful eating indicator (DF_HEI). Both yield mean scores similar to an established dietary index validated against nutrient intake. Significant associations for the RF_HEI were education, income, ability to save, and attitude toward diet; and for the DF_HEI, gender, not living alone, living in a socially disadvantaged area, and attitude toward diet. The results confirm that short dietary questions can be used to develop healthful eating indicators against dietary recommendations. This will enable the exploration of dietary behaviours for “at risk” groups, such as those with excess weight, leading to more relevant interventions for populations

The effect of bleach duration and age on the ERG photostress test

Background: The ERG photostress test assesses the recovery of the focal 41 Hz ERG following exposure to a bright light that bleaches a significant proportion of photopigment. The aims of this study were: 1) to compare the repeatability of the ERG photostress test recovery time constant following long and short duration light exposure, and 2) to determine the effect of age on the ERG photostress test recovery time constant. Methods: Focal 41 Hz ERGs were recorded from 23 participants (age range 20–71 years) at 20-second intervals for 5 minutes following either a short-duration (photoflash) or long-duration (equilibrium) light exposure. After a 5-minute wash-out period, the procedure was repeated using the second bleach modality. The time constant of cone recovery was determined by fitting an exponential model to the amplitude recovery data. The whole procedure was repeated on a second occasion. The co-efficient of repeatability (CoR) was calculated for each bleaching technique. The relationship between the time constant of recovery and age was investigated (Pearson’s correlation coefficient). Results: The time constant of recovery following an equilibrium bleach was more repeatable than recovery following a photoflash (CoR = 85s and 184s respectively). Eight trials (from seven participants) failed to show a reduction in amplitude following the photoflash, suggesting that a blink or fixation loss had occurred. All participants were reliably light-adapted by the equilibrium bleach. For the equilibrium bleach data, the time constant of recovery increased with age at a rate of 27 seconds per decade. Conclusions: The equilibrium bleach was more reliable and repeatable than the photoflash. Increasing participant age was shown to result in a lengthening of the recovery time constant, of a magnitude comparable to previously published psychophysical data

Electrophysiological ON and OFF responses in autosomal dominant optic atrophy

Purpose To assess the effect of ADOA on the ON and OFF components of the photopic negative response (PhNR). Methods Twelve participants from 6 families with OPA1 ADOA and 16 age matched controls were recruited. Electrophysiological assessment involved long flash focal (20o) and full field ERGs using red flash (664 nm, 250 msec, 55 cd/m2, 2 Hz) on a rod saturating blue background (454 nm, 100 scot cd/m2); and brief xenon flash ERGs using red filter (Lee Filter “Terry Red”, max 300 µs flash duration, 1.69 cd.s.m-2, 4 Hz) over a continuous rod saturating blue background (Schott Glass Filter BG28, 206 scot cd/m2). Amplitudes (from peak and baseline to fixed time point) and implicit times of the ERG components were analysed. Results Mean amplitude (peak to fixed time) of the focal PhNR-ON were significantly (p < 0.05) reduced by 40% while the focal PhNR-OFF was completely eliminated. In the long duration full field ERG, the PhNR-ON and –OFF were reduced by 21% and 57% respectively. Subtraction of the grand averaged ERG of ADOA participants from that of the controls produced a difference plot with a nearly symmetrical loss in the PhNR-ON and OFF components of the focal ERG. ROC curve analysis showed focal PhNR-ON and OFF amplitudes performed better than their full field counterparts. Conclusions We show that OFF components of the photopic ERG were more severely affected in ADOA than ON components. Additionally, the focal PhNR-ON and –OFF components were more effective in assessing ADOA than their full field components

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

We describe a new technique, high fdelity 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 refectance 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 diferences between those with and without AMD. Rod and cone visual pigment synthesis rates in those with AMD (v=0.043SD 0.019min−1 and v=0.119SD 0.046min−1, respectively) were approximately half those observed in healthy controls (v=0.079SD 0.024min−1 for rods and v=0.206SD 0.069min−1 for cones). By mapping visual pigment kinetics across the central retina, high fdelity 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

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