Evaluation of contrast threshold measurements and simultaneous brightness ratios in the diagnosis of glaucoma

There is considerable dissatisfaction with the reliability and sensitivity of the methods used to assess the glaucomatous visual field. Two types of visual field test, which have been proposed as having potential in diagnosing glaucomatous visual field defects, have been modified and tested on a group of patients from a glaucoma clinic, a group of age-matched control subjects and a younger control group. 1. A grating pattern was generated using a laser interferometer which projected a large diameter image onto the retina independent of the subject's refractive error. The experimental set up which produced the most reliable and consistently low contrast threshold values in normal subjects was sought. The display characteristics which were examined included different orientations for the field quadrants as projected to the subject; stationary and flickering patterns using a variety of flicker generation methods; red and green light sources; and concentric or vertical sinusoidal grating patterns. Ultimately the optimal display was found to be a stationary image consisting of a green, vertical sinusoidal grating pattern. Arcuate regions of the visual field (at 10 to 20° from fixation) were stimulated in 4 distinct, obliquely oriented quadrants and a low spatial frequency (one cycle per degree) was chosen. 2. Normal limits were obtained from age-matched control subjects for comparison with the results for the patients from the glaucoma clinic. In the patient group, of the 13 who completed the test, 9 individuals were identified as abnormal with one or more of their contrast threshold scores exceeding that limit. The patients' Friedmann visual field plots were analysed and the amount of loss in each quadrant was quantified. There was a positive correlation between the quantified visual field loss and contrast threshold scores in 6 patients, a statistically borderline correlation in 2 patients and the absence of a correlation was found in 5 patient's results. The results for a subgroup of 6 visually abnormal eyes (not affected by glaucoma) excluded from the age-matched control group are also described. Their visual defects included mild cataract, amblyopia and retinal detachment. There were no clear abnormal results in 5 of the eyes in this group; however, in one subject with retinal scarring due to an infection, there was a distinct elevation of contrast threshold in the affected eye. Humphrey visual field plots were obtained for all but one of the age-matched control subjects. 3. Simultaneous brightness ratios (SBR) have previously been shown to provide an indication of'glaucomatous damage. The same subject groups as described above were tested. SBRs were obtained for central vision in both eyes of subjects (inter-ocular ratio). This technique was now extended for the first time to paired regions within each eye (intra-ocular ratios) producing 'nasal I temporal' and 'upper I lower' ratios. In each test the subject controlled the brightness ratio which was changed in a smoothly graduated and continuou8 way. The most effective procedure for recording repeatable SBRs was first explored, and it was determined that these could be best obtained by alternating the start point of the graduated filter position. For each subject, 5 ratios were obtained: inter-ocular SBR; upper I lower intra-ocular SBR for right eye and left eye; and nasal I temporal intra-ocular SBR for right eye and left eye. 4. Normal limits were obtained from age-matched control subjects for comparison with the results for the patients from the glaucoma clinic. In each of the 5 SBR tests carried out, these limits were wide, reflecting considerable variation in the normal results. Of the 14 patients who completed the tests, 5 were identified as abnormal by one or more of their SBRs being outside normal limits. Three of these were identified as abnormal by their inter-ocular SBRs alone, one was abnormal according to his upper I lower intra-ocular SBR alone and one patient had an abnormal inter-ocular SBR and an abnormal intra-ocular SBR. The corresponding regions of the patients' Friedmann visual fields were quantified, and these values were used to calculate visual field loss ratios. There was a positive correlation between the visual field loss ratios and SBRs in 3 patients, but no correlation in 11 patients. In the sub-group of 6 visually abnormal eyes without glaucoma, mild cataract appeared not to adversely affect SBR. Mean SBRs were normal in the subject with retinal detachment but there was evidence of an enhanced amount of variation in the readings. Two subjects with a damaged retina and one with an amblyopic eye did produce abnormal inter-ocular SBRs, with the normal eye being significantly more sensitive in both cases

Novel linkage approach to join community-acquired and national data

BackgroundCommunity optometrists in Scotland have performed regular free-at-point-of-care eye examinations for all, for over 15 years. Eye examinations include retinal imaging but image storage is fragmented and they are not used for research. The Scottish Collaborative Optometry-Ophthalmology Network e-research project aimed to collect these images and create a repository linked to routinely collected healthcare data, supporting the development of pre-symptomatic diagnostic tools.MethodsAs the image record was usually separate from the patient record and contained minimal patient information, we developed an efficient matching algorithm using a combination of deterministic and probabilistic steps which minimised the risk of false positives, to facilitate national health record linkage. We visited two practices and assessed the data contained in their image device and Practice Management Systems. Practice activities were explored to understand the context of data collection processes. Iteratively, we tested a series of matching rules which captured a high proportion of true positive records compared to manual matches. The approach was validated by testing manual matching against automated steps in three further practices.ResultsA sequence of deterministic rules successfully matched 95% of records in the three test practices compared to manual matching. Adding two probabilistic rules to the algorithm successfully matched 99% of records.ConclusionsThe potential value of community-acquired retinal images can be harnessed only if they are linked to centrally-held healthcare care data. Despite the lack of interoperability between systems within optometry practices and inconsistent use of unique identifiers, data linkage is possible using robust, almost entirely automated processes

Valuing Alzheimer's Disease drugs:A health technology assessment perspective on outcomes

ObjectivesDue to the nature of Alzheimer's disease (AD), health technology assessment (HTA) agencies might face considerable challenges in choosing appropriate outcomes and outcome measures for drugs that treat the condition. This study sought to understand which outcomes informed previous HTAs, to explore possible reasons for prioritizations, and derive potential implications for future assessments of AD drugs.MethodWe conducted a literature review of studies that analyzed decisions made in HTAs (across disease areas) in three European countries: England, Germany, and The Netherlands. We then conducted case studies of technology assessments conducted for AD drugs in these countries.ResultsOverall, outcomes measured using clinical scales dominated decisions or recommendations about whether to fund AD drugs, or price negotiations. HTA processes did not always allow the inclusion of outcomes relevant to people with AD, their carers, and families. Processes did not include early discussion and agreement on what would constitute appropriate outcome measures and cut-off points for effects.ConclusionsWe conclude that in order to ensure that future AD drugs are valued appropriately and timely, early agreement with various stakeholders about outcomes, outcome measures, and cut-offs is important

Conducting public involvement in dementia research:The contribution of the European Working Group of People with Dementia to the ROADMAP project

Background Dementia outcomes include memory loss, language impairment, reduced quality of life and personality changes. Research suggests that outcomes selected for dementia clinical trials might not be the most important to people affected. Objective One of the goals of the ‘Real world Outcomes across the Alzheimer's Disease spectrum for better care: Multi‐modal data Access Platform’ (ROADMAP) project was to identify important outcomes from the perspective of people with dementia and their caregivers. We review how ROADMAP's Public Involvement shaped the programme, impacted the research process and gave voice to people affected by dementia. Design The European Working Group of People with Dementia (EWGPWD) were invited to participate. In‐person consultations were held with people with dementia and caregivers, with advance information provided on ROADMAP activities. Constructive criticism of survey content, layout and accessibility was sought, as were views and perspectives on terminology and key concepts around disease progression. Results The working group provided significant improvements to survey accessibility and acceptability. They promoted better understanding of concepts around disease progression and how researchers might approach measuring and interpreting findings. They effectively expressed difficult concepts through real‐world examples. Conclusions The role of the EWGPWD in ROADMAP was crucial, and its impact was highly influential. Involvement from the design stage helped shape the ethos of the programme and ultimately its meaningfulness. Public contribution People with dementia and their carers were involved through structured consultations and invited to provide feedback on project materials, methods and insight into terminology and relevant concepts

What outcomes are important to patients with mild cognitive impairment or Alzheimer's disease, their caregivers, and health-care professionals? A systematic review

Introduction: Clinical trials involving patients with Alzheimer’s disease (AD) continue to try to identify disease-modifying treatments. Although trials are designed to meet regulatory and registration requirements, many do not measure outcomes of the disease most relevant to key stakeholders. Methods: A systematic review sought research that elicited information from people with AD, their caregivers, and health-care professionals on which outcomes of the disease were important. Studies published in any language between 2008 and 2017 were included. Results: Participants in 34 studies described 32 outcomes of AD. These included clinical (memory, mental health), practical (ability to undertake activities of daily living, access to health information), and personal (desire for patient autonomy, maintenance of identity) outcomes of the disease. Discussion: Evidence elicited directly from the people most affected by AD reveals a range of disease outcomes that are relevant to them but are not commonly captured in clinical trials of new treatments.</br

Relationship between visual field loss and contrast threshold elevation in glaucoma

BACKGROUND: There is a considerable body of literature which indicates that contrast thresholds for the detection of sinusoidal grating patterns are abnormally high in glaucoma, though just how these elevations are related to the location of visual field loss remains unknown. Our aim, therefore, has been to determine the relationship between contrast threshold elevation and visual field loss in corresponding regions of the peripheral visual field in glaucoma patients. METHODS: Contrast thresholds were measured in arcuate regions of the superior, inferior, nasal and temporal visual field in response to laser interference fringes presented in the Maxwellian view. The display consisted of vertical green stationary laser interference fringes of spatial frequency 1.0 c deg(-1 )which appeared in a rotatable viewing area in the form of a truncated quadrant extending from 10 to 20° from fixation which was marked with a central fixation light. Results were obtained from 36 normal control subjects in order to provide a normal reference for 21 glaucoma patients and 5 OHT (ocular hypertensive) patients for whom full clinical data, including Friedmann visual fields, had been obtained. RESULTS: Abnormally high contrast thresholds were identified in 20 out of 21 glaucoma patients and in 2 out of 5 OHT patients when compared with the 95% upper prediction limit for normal values from one eye of the 36 normal age-matched control subjects. Additionally, inter-ocular differences in contrast threshold were also abnormally high in 18 out of 20 glaucoma patients who had vision in both eyes compared with the 95% upper prediction limit. Correspondence between abnormally high contrast thresholds and visual field loss in the truncated quadrants was significant in 5 patients, borderline in 4 patients and absent in 9 patients. CONCLUSION: While the glaucoma patients tested in our study invariably had abnormally high contrast thresholds in one or more of the truncated quadrants in at least one eye, reasonable correspondence with the location of the visual field loss only occurred in half the patients studied. Hence, while contrast threshold elevations are indicative of glaucomatous damage to vision, they are providing a different assessment of visual function from conventional visual field tests

Real-world evidence in Alzheimer’s disease: the ROADMAP Data Cube

INTRODUCTION:The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum. METHODS:Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys. RESULTS:Information about 66 data sources and 13 outcome domains were integrated into a Data Cube. Gap analysis identified cognitive ability, functional ability/independence, behavioral/neuropsychiatric symptoms, treatment, comorbidities, and mortality as the outcomes collected most. Data were most lacking in caregiver-related outcomes. In general, electronic health records covered a broader, less detailed data spectrum than research cohorts. DISCUSSION:This integrated real-world AD data overview provides an intuitive visual model that facilitates initial assessment and identification of gaps in relevant outcomes data to inform future prospective data collection and matching of data sources and outcomes against research protocols

STORIES Statement: publication standards for healthcare education evidence synthesis

Fully copy of the STORIES statement - a checklist of reporting guidance for health education evidence synthesis Structured approach for Reporting In health education of Evidence Synthesis Background Evidence synthesis techniques in healthcare education have been enhanced through the activities of experts in the field and the Best Evidence Medical Education (BEME) collaborative. Despite this, significant heterogeneity in techniques and reporting of healthcare education systematic review still exist and limit the usefulness of such reports. The aim of this project was to produce the STORIES (STructured apprOach to the Reporting In healthcare education of Evidence Synthesis) statement to offer a guide for reporting evidence synthesis in health education for use by authors and journal editors. Methods A review of existing published evidence synthesis consensus statements was undertaken. A modified Delphi process was used. In stage one, expert participants were asked to state whether common existing items identified were relevant, to suggest relevant texts and specify any items they feel should be included. The results were analysed and a second stage commenced where all synthesised items were presented and participants asked to state whether they should be included or amend as needed. After further analysis, the full statement was sent for final review and comment. Results Nineteen experts participated in the panel from 35 invitations. Thirteen text sources were proposed, six existing items amended and twelve new items synthesised. After stage two, 25 amended consensus items were proposed for inclusion. The final statement contains several items unique to this context, including description of relevant conceptual frameworks or theoretical constructs, description of qualitative methodologies with rationale for their choice and presenting the implications for educators in practice of the results obtained. Conclusions An international expert panel has agreed upon a consensus statement of 25 items for the reporting of evidence synthesis within healthcare education. This unique set of items is focused on context, rather than a specific methodology. This statement can be used for those writing for publication and reviewing such manuscripts to ensure reporting supports and best informs the wider healthcare education community