Functional biomarkers of hypoxia in age-related macular degeneration

Age-related macular degeneration (AMD) is predicted to affect 196 million people by 2020 (Wong et al. 2014). To date there is no clear pathogenesis for the condition however, hypoxia has been implicated (Stefánsson et al. 2011). Currently, treatment is only available for neovascular AMD. To develop treatments targeted for early AMD a better understanding of the pathogenesis is required. There is also a need for sensitive functional biomarkers to improve diagnosis and monitoring and to expedite the evaluation of therauptics in clinical trials. The aim of this research was to investigate the hypothesis that hypoxia is involved in the pathogenesis of early AMD. Studies were carried out exploring the effect of transient systemic hypoxia (14% oxygen) and hyperoxia (60% oxygen) on scotopic thresholds and electroretinograms (ERGs) of participants with early AMD. It was hypothesised that the visual function of participants with AMD, but not age-matched controls, would improve during the hyperoxic episode and that hypoxia would have a greater detrimental effect on visual function in people with early AMD. There were no significant differences in scotopic thresholds within each group when breathing 60% or 14% oxygen compared to medical air (21% oxygen). There were also no significant differences in full-field ERG parameters between gas conditions or groups, apart from the amplitude of the b-wave which was significantly reduced under hypoxia in the control group. The amplitude of the focal flicker ERG was significantly higher in the control group than the AMD group when breathing both 14% and 21% oxygen. However, there were no significant differences in the parameters of the focal ERG within each group. These findings suggest that hypoxia is not responsible for the elevation of scotopic thresholds reported in AMD. There is also no evidence that ERG changes are attributable to hypoxia. This thesis provides no evidence to support the role of hypoxia in the pathogenesis of early 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

Glaucoma Home Monitoring Using a Tablet- Based Visual Field Test (Eyecatcher): An Assessment of Accuracy and Adherence Over 6 Months

PURPOSE: To assess accuracy and adherence of visual field (VF) home monitoring in a pilot sample of patients with glaucoma. DESIGN: Prospective longitudinal feasibility and reliability study. METHODS: Twenty adults (median 71 years) with an established diagnosis of glaucoma were issued a tablet perimeter (Eyecatcher) and were asked to perform 1 VF home assessment per eye, per month, for 6 months (12 tests total). Before and after home monitoring, 2 VF assessments were performed in clinic using standard automated perimetry (4 tests total, per eye). RESULTS: All 20 participants could perform monthly home monitoring, though 1 participant stopped after 4 months (adherence: 98% of tests). There was good concordance between VFs measured at home and in the clinic (r = 0.94, P < .001). In 21 of 236 tests (9%), mean deviation deviated by more than ±3 dB from the median. Many of these anomalous tests could be identified by applying machine learning techniques to recordings from the tablets' front-facing camera (area under the receiver operating characteristic curve = 0.78). Adding home-monitoring data to 2 standard automated perimetry tests made 6 months apart reduced measurement error (between-test measurement variability) in 97% of eyes, with mean absolute error more than halving in 90% of eyes. Median test duration was 4.5 minutes (quartiles: 3.9-5.2 minutes). Substantial variations in ambient illumination had no observable effect on VF measurements (r = 0.07, P = .320). CONCLUSIONS: Home monitoring of VFs is viable for some patients and may provide clinically useful data

The Human Touch:Using a Webcam to Autonomously Monitor Compliance During Visual Field Assessments

Purpose: To explore the feasibility of using various easy-to-obtain biomarkers to monitor non-compliance (measurement error) during visual field assessments. Methods: Forty-two healthy adults (42 eyes) and seven glaucoma patients (14 eyes) underwent two same-day visual field assessments. An ordinary webcam was used to compute seven potential biomarkers of task compliance, based primarily on eye gaze, head pose, and facial expression. We quantified the association between each biomarker and measurement error, as defined by (1) test-retest differences in overall test scores (mean sensitivity), and (2) failures to respond to visible stimuli on individual trials (stimuli -3 dB or more brighter than threshold). Results: In healthy eyes, three of the seven biomarkers were significantly associated with overall (test-retest) measurement error (P = 0.003-0.007), and at least two others exhibited possible trends (P = 0.052-0.060). The weighted linear sum of all seven biomarkers was associated with overall measurement error, in both healthy eyes (r = 0.51, P <0.001) and patients (r = 0.65, P <0.001). Five biomarkers were each associated with failures to respond to visible stimuli on individual trials (all P <0.001). Conclusions: Inexpensive, autonomous measures of task compliance are associated with measurement error in visual field assessments, in terms of both the overall reliability of a test and failures to respond on particular trials ("lapses"). This could be helpful for identifying low-quality assessments and for improving assessment techniques (e.g., by discounting suspect responses or by automatically triggering comfort breaks or encouragement). Translational Relevance: This study explores a potential way of improving the reliability of visual field assessments, a crucial but notoriously unreliable clinical measure

Acceptability of a home-based visual field test (Eyecatcher) for glaucoma home monitoring: a qualitative study of patients' views and experiences

Objectives To explore the acceptability of home visual field (VF) testing using Eyecatcher among people with glaucoma participating in a 6-month home monitoring pilot study. Design Qualitative study using face-to-face semistructured interviews. Transcripts were analysed using thematic analysis. Setting Participants were recruited in the UK through an advertisement in the International Glaucoma Association (now Glaucoma UK) newsletter. Participants Twenty adults (10 women; median age: 71 years) with a diagnosis of glaucoma were recruited (including open angle and normal tension glaucoma; mean deviation=2.5 to -29.9 dB). Results All participants could successfully perform VF testing at home. Interview data were coded into four overarching themes regarding experiences of undertaking VF home monitoring and attitudes towards its wider implementation in healthcare: (1) comparisons between Eyecatcher and Humphrey Field Analyser (HFA); (2) capability using Eyecatcher; (3) practicalities for effective wider scale implementation; (4) motivations for home monitoring. Conclusions Participants identified a broad range of benefits to VF home monitoring and discussed areas for service improvement. Eyecatcher was compared positively with conventional VF testing using HFA. Home monitoring may be acceptable to at least a subset of people with glaucoma

The Human Touch: Using a Webcam to Autonomously Monitor Compliance During Visual Field Assessments

Purpose: To explore the feasibility of using various easy-to-obtain biomarkers to monitor non-compliance (measurement error) during visual field assessments.Methods: Forty-two healthy adults (42 eyes) and seven glaucoma patients (14 eyes) underwent two same-day visual field assessments. An ordinary webcam was used to compute seven potential biomarkers of task compliance, based primarily on eye gaze, head pose, and facial expression. We quantified the association between each biomarker and measurement error, as defined by (1) test-retest differences in overall test scores (mean sensitivity), and (2) failures to respond to visible stimuli on individual trials (stimuli -3 dB or more brighter than threshold).Results: In healthy eyes, three of the seven biomarkers were significantly associated with overall (test-retest) measurement error (P = 0.003-0.007), and at least two others exhibited possible trends (P = 0.052-0.060). The weighted linear sum of all seven biomarkers was associated with overall measurement error, in both healthy eyes (r = 0.51, P < 0.001) and patients (r = 0.65, P < 0.001). Five biomarkers were each associated with failures to respond to visible stimuli on individual trials (all P < 0.001).Conclusions: Inexpensive, autonomous measures of task compliance are associated with measurement error in visual field assessments, in terms of both the overall reliability of a test and failures to respond on particular trials ("lapses"). This could be helpful for identifying low-quality assessments and for improving assessment techniques (e.g., by discounting suspect responses or by automatically triggering comfort breaks or encouragement).Translational Relevance: This study explores a potential way of improving the reliability of visual field assessments, a crucial but notoriously unreliable clinical measure

Characteristics of 698 patients with dissociative seizures: a UK multicenter study

Objective We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology. Methods We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non‐Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations. Results In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self‐reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two‐thirds were unemployed. Significance Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment