Despite the existence of evidence-based recommendations to decrease risk and progression of Age-Related Macular Degeneration (AMD) for some time, self-reported practices suggest that eyecare ...professionals' advice and people with AMD's adherence to these recommendations can be very poor. This study uses qualitative methods to explore Australian eyecare professionals' perspective on barriers to effective AMD care. Seven focus groups involving 65 optometrists were conducted by an experienced facilitator. A nominal group technique was used to identify, prioritize and semi-quantify barriers and enablers to AMD care. Participants individually ranked their perceived top five barriers and enablers with the most important granted a score of 5 and the least important a score of 1. For each barrier or enabler, the number of votes it received and its total score were recorded. Barriers and enablers selected by at least one participant in their top 5 were then qualitatively analysed, grouped using thematic analysis and total score calculated for each consolidated barrier or enabler. In-depth individual interviews were conducted with 10 ophthalmologists and 2 optometrists. Contributions were audio-recorded, transcribed verbatim and analysed with NVivo software. One hundred and sixty-nine barriers and 51 enablers to AMD care were identified in the focus groups. Of these, 102 barriers and 42 enablers were selected as one of their top 5 by at least one participant and further consolidated into 16 barriers and 10 enablers after thematic analysis. Factors impacting AMD care identified through analysis of the transcripts were coded to three categories of influence: patient-centered, practitioner-centered, and structural factors. Eyecare professionals considered poor care pathways, people with AMD's poor disease understanding / denial, and cost of care / lack of funding, as the most significant barriers to AMD care; they considered shared care model, access, and communication as the most significant enablers to good AMD care. These findings suggest that Australian eyecare professionals perceive that there is a need for improved patient support systems and appropriately funded, clearer care pathway to benefit people with AMD.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To provide a detailed phenotype/genotype characterization of Bietti crystalline dystrophy (BCD).
Observational case series.
Twenty patients from 17 families recruited from a multiethnic British ...population.
Patients underwent color fundus photography, near-infrared (NIR) imaging, fundus autofluorescence (FAF) imaging, spectral domain optical coherence tomography (SD-OCT), and electroretinogram (ERG) assessment. The gene CYP4V2 was sequenced.
Clinical, imaging, electrophysiologic, and molecular genetics findings.
Patients ranged in age from 19 to 72 years (median, 40 years), with a visual acuity of 6/5 to perception of light (median, 6/12). There was wide intrafamilial and interfamilial variability in clinical severity. The FAF imaging showed well-defined areas of retinal pigment epithelium (RPE) loss that corresponded on SD-OCT to well-demarcated areas of outer retinal atrophy. Retinal crystals were not evident on FAF imaging and were best visualized with NIR imaging. Spectral domain OCT showed them to be principally located on or in the RPE/Bruch's membrane complex. Disappearance of the crystals, revealed by serial recording, was associated with severe disruption and thinning of the RPE/Bruch's membrane complex. Cases with extensive RPE degeneration (N = 5) had ERGs consistent with generalized rod and cone dysfunction, but those with more focal RPE atrophy showed amplitude reduction without delay (N = 3), consistent with restricted loss of function, or that was normal (N = 2). Likely disease-causing variants were identified in 34 chromosomes from 17 families. Seven were novel, including p.Met66Arg, found in all 11 patients from 8 families of South Asian descent. This mutation appears to be associated with earlier onset (median age, 30 years) compared with other substitutions (median age, 41 years). Deletions of exon 7 were associated with more severe disease.
The phenotype is highly variable. Several novel variants are reported, including a highly prevalent substitution in patients of South Asian descent that is associated with earlier-onset disease. Autofluorescence showed sharply demarcated areas of RPE loss that coincided with abrupt edges of outer retinal atrophy on SD-OCT; crystals were generally situated on or in the RPE/Bruch's complex but could disappear over time with associated RPE disruption. These results support a role for the RPE in disease pathogenesis.
Diabetic retinopathy screening in England involves labour-intensive manual grading of retinal images. Automated retinal image analysis systems (ARIASs) may offer an alternative to manual grading.
To ...determine the screening performance and cost-effectiveness of ARIASs to replace level 1 human graders or pre-screen with ARIASs in the NHS diabetic eye screening programme (DESP). To examine technical issues associated with implementation.
Observational retrospective measurement comparison study with a real-time evaluation of technical issues and a decision-analytic model to evaluate cost-effectiveness.
A NHS DESP.
Consecutive diabetic patients who attended a routine annual NHS DESP visit.
Retinal images were manually graded and processed by three ARIASs: iGradingM (version 1.1; originally Medalytix Group Ltd, Manchester, UK, but purchased by Digital Healthcare, Cambridge, UK, at the initiation of the study, purchased in turn by EMIS Health, Leeds, UK, after conclusion of the study), Retmarker (version 0.8.2, Retmarker Ltd, Coimbra, Portugal) and EyeArt (Eyenuk Inc., Woodland Hills, CA, USA). The final manual grade was used as the reference standard. Arbitration on a subset of discrepancies between manual grading and the use of an ARIAS by a reading centre masked to all grading was used to create a reference standard manual grade modified by arbitration.
Screening performance (sensitivity, specificity, false-positive rate and likelihood ratios) and diagnostic accuracy 95% confidence intervals (CIs) of ARIASs. A secondary analysis explored the influence of camera type and patients' ethnicity, age and sex on screening performance. Economic analysis estimated the cost per appropriate screening outcome identified.
A total of 20,258 patients with 102,856 images were entered into the study. The sensitivity point estimates of the ARIASs were as follows: EyeArt 94.7% (95% CI 94.2% to 95.2%) for any retinopathy, 93.8% (95% CI 92.9% to 94.6%) for referable retinopathy and 99.6% (95% CI 97.0% to 99.9%) for proliferative retinopathy; and Retmarker 73.0% (95% CI 72.0% to 74.0%) for any retinopathy, 85.0% (95% CI 83.6% to 86.2%) for referable retinopathy and 97.9% (95% CI 94.9 to 99.1%) for proliferative retinopathy. iGradingM classified all images as either 'disease' or 'ungradable', limiting further iGradingM analysis. The sensitivity and false-positive rates for EyeArt were not affected by ethnicity, sex or camera type but sensitivity declined marginally with increasing patient age. The screening performance of Retmarker appeared to vary with patient's age, ethnicity and camera type. Both EyeArt and Retmarker were cost saving relative to manual grading either as a replacement for level 1 human grading or used prior to level 1 human grading, although the latter was less cost-effective. A threshold analysis testing the highest ARIAS cost per patient before which ARIASs became more expensive per appropriate outcome than human grading, when used to replace level 1 grader, was Retmarker £3.82 and EyeArt £2.71 per patient.
The non-randomised study design limited the health economic analysis but the same retinal images were processed by all ARIASs in this measurement comparison study.
Retmarker and EyeArt achieved acceptable sensitivity for referable retinopathy and false-positive rates (compared with human graders as reference standard) and appear to be cost-effective alternatives to a purely manual grading approach. Future work is required to develop technical specifications to optimise deployment and address potential governance issues.
The National Institute for Health Research (NIHR) Health Technology Assessment programme, a Fight for Sight Grant (Hirsch grant award) and the Department of Health's NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and the University College London Institute of Ophthalmology.
•A single sensory impairment was associated with a lower odds of successful aging.•Hearing-related measures had a greater influence on aging status than vision-related measures.•Concurrent vision and ...hearing loss was not associated with aging status.
We aimed to prospectively examine the relationship between vision and hearing loss and successful aging in a cohort of older adults.
We analyzed 5-year data (1997-9 to 2002-4) from 1,085 adults aged 55+ years, who were free of cancer, coronary artery disease and stroke at baseline and who had complete data on sensory loss.
Visual impairment was defined as visual acuity <20/40 (better eye), and hearing impairment as average pure-tone air conduction threshold >25 dBHL (500-4000 Hz, better ear). Successful aging was defined as the absence of: disability, depressive symptoms, cognitive impairment, respiratory symptoms and chronic diseases (cancer, coronary artery disease and stroke) at 5-year follow-up.
At 5-year follow-up, 243 (22.4%) participants had died and 248 (22.9%) had aged successfully. After multivariable adjustment, participants who had either best-corrected visual impairment or bilateral hearing impairment, versus those who did not have sensory impairment at baseline, had 37% reduced odds of successful aging after 5 years: OR 0.63 (95% CI 0.43-0.94). Concurrent vision and hearing loss at baseline was not associated with 5-year aging status. Participants with moderate and severe hearing handicap at baseline had 50% and 61% reduced odds of aging successfully after 5 years, respectively.
The presence of a single sensory impairment in older adults was associated with reduced odds of being disease-free and fully functional or having aged successfully, 5 years later. Objectively measured hearing loss and self-perceived hearing handicap, rather than vision loss, was more likely to negatively influence 5-year aging status.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Neovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. Anti-vascular endothelial growth factor (VEGF) agents, such as ranibizumab, bevacizumab, ...aflibercept, brolucizumab and faricimab have revolutionized the clinical management of nAMD. However, there remains an unmet clinical need for new and improved therapies for nAMD, since many patients do not respond optimally, may lose response over time or exhibit sub-optimal durability, impacting on real world effectiveness. Evidence is emerging that targeting VEGF-A alone, as most agents have done until recently, may be insufficient and agents that target multiple pathways (e.g., aflibercept, faricimab and others in development) may be more efficacious. This article reviews issues and limitations that have arisen from the use of existing anti-VEGF agents, and argues that the future may lie in multi-targeted therapies including alternative agents and modalities that target both the VEGF ligand/receptor system as well as other pathways.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Vision and hearing impairments are highly prevalent and have a significant impact on physical, psychological and social wellbeing. There is a need for accurate, contemporary national data on the ...prevalence, risk factors and impacts of vision and hearing loss in Australian adults.
The Australian Eye and Ear Health Survey (AEEHS) aims to determine the prevalence, risk factors and impacts of vision and hearing loss in both Aboriginal and Torres Strait Islander and non-Indigenous older adults.
The AEEHS is a population-based cross-sectional survey which will include 5,000 participants (3250 non-Indigenous aged 50 years or older and 1750 Aboriginal and Torres Strait Islander people aged 40 years or older) from 30 sites covering urban and rural/regional geographic areas, selected using a multi-stage, random cluster sampling strategy. Questionnaires will be administered to collect data on socio-demographic, medical, ocular and ontological history. The testing battery includes assessment of blood pressure, blood sugar, anthropometry, visual acuity (presenting, unaided, pinhole and best-corrected), refraction, tonometry, slit lamp and dilated eye examination, ocular imaging including optical coherence tomography (OCT), OCT-angiography and retinal photography, and automated visual fields. Audiometry, tympanometry and video otoscopy will also be performed. The primary outcomes are age-standardised prevalence of cause-specific vision and hearing impairment. Secondary outcomes are prevalence of non-blinding eye diseases (including dry eye disease), patterns in health service utilisation, universal health coverage metrics, risk factors for vision and hearing impairment, and impact on quality of life.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background The WHO and American Diabetes Association criteria for diagnosing diabetes mellitus assume the presence of a glycaemic threshold with high sensitivity for identifying retinopathy. ...However, this assumption is based on data from three previous studies that had important limitations in detecting retinopathy. We aimed to provide updated data for the relation between fasting plasma glucose (FPG) and retinopathy, and to assess the diagnostic accuracy of current FPG thresholds in identifying both prevalent and incident retinopathy. Methods We examined the data from three cross-sectional adult populations: those in the Blue Mountains Eye Study (BMES, Australia, n=3162), the Australian Diabetes, Obesity and Lifestyle Study (AusDiab, Australia, n=2182), and the Multi-Ethnic Study of Atherosclerosis (MESA, USA, n=6079). Retinopathy was diagnosed from multiple retinal photographs of each eye, and graded according to the modified Airlie House Classification system. Plasma glucose concentrations were measured from fasting venous blood samples. Findings The overall prevalence of retinopathy was 11·5% in BMES (95% CI 10·4–12·6%), 9·6% in AusDiab (8·4–10·9), and 15·8% in MESA (14·9–16·7). However, we found inconsistent evidence of a uniform glycaemic threshold for prevalent and incident retinopathy, with analyses suggesting a continuous relation. The widely used diabetes FPG cutoff of 7·0 mmol/L or higher had sensitivity less than 40% (range 14·8–39·1) for detecting retinopathy, with specificity between 80·8% and 95·8%. The area under receiver operating characteristic curves for FPG and retinopathy was low and ranged from 0·56 to 0·61. Interpretation We saw no evidence of a clear and consistent glycaemic threshold for the presence or incidence of retinopathy across different populations. The current FPG cutoff of 7·0 mmol/L used to diagnose diabetes did not accurately identify people with and without retinopathy. These findings suggest that the criteria for diagnosing diabetes could need reassessment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Fractals represent a type of derived geometric pattern that permits the characterization of the branching pattern of retinal vessels. We examined a new semiautomated method to measure retinal vessel ...fractals.
Methodology study.
Three hundred randomly selected participants from the population-based Blue Mountains Eye Study.
We developed a semiautomated computer program to measure the fractal dimension (D(f)) of the retinal vessels from digitized images of disk-centered retinal photographs. Two trained graders masked to participant characteristics measured D(f) of right eye images of participants. Reliability was determined by repeat grading of the images from 60 participants, and association with systolic and diastolic blood pressure was examined in all 300 participants.
D(f) of the retinal vessels.
Mean D(f) was 1.437 with a standard deviation of 0.025. Intragrader and intergrader reliability estimates were high with intraclass correlation ranging from 0.93 to 0.95. D(f) was inversely correlated with age (r = -0.42, P = 0.001) and systolic blood pressure (r = -0.29, P<0.0001). After adjustment for age and sex, mean D(f) was significantly lower in participants with than without hypertension (D(f) difference 0.01, P = 0.02).
The D(f) of the retinal vessels can be reliably measured from photographs and shows a strong inverse correlation with blood pressure. These data suggest that the D(f) may be a measure of early microvascular alterations from elevated blood pressure. Further studies to examine the systemic and ocular correlates of the D(f) of the retinal vessels are needed.
ObjectivesTo appraise the existing literature reporting an association between retinal markers and cognitive impairment in adults aged 65 years and over and to provide directions for future use of ...retinal scanning as a potential tool for dementia diagnosis.DesignSystematic review of peer-reviewed empirical articles investigating the association of retinal markers in assessing cognitive impairment.Data sourcesThree electronic databases, Medline, PsycINFO and EMBASE were searched from inception until March 2022.Eligibility criteriaAll empirical articles in English investigating the association between retinal markers and cognition in humans aged ≥65 years using various retinal scanning methodologies were included. Studies with no explicit evaluation of retinal scanning and cognitive outcomes were excluded. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool.Data extraction and synthesisData extraction was conducted by two authors (VJ, RS) and reviewed by another author (JS). Results were synthesised and described narratively.ResultsSixty-seven eligible studies examining 6815 older adults were included. Majority of studies were cross-sectional (n=60; 89.6%). Optical coherence tomography (OCT) was the most commonly used retinal scanning methodology to measure the thickness of retinal nerve fibre layer, the ganglion cell complex, choroid and macula. 51.1% of cross-sectional studies using OCT reported an association between the thinning of at least one retinal parameter and poor cognition. Longitudinal studies (n=6) using OCT also mostly identified significant reductions in retinal nerve fibre layer thickness with cognitive decline. Study quality was overall moderate.ConclusionRetinal nerve fibre layer thickness is linked with cognitive performance and therefore may have the potential to detect cognitive impairment in older adults. Further longitudinal studies are required to validate our synthesis and understand underlying mechanisms before recommending implementation of OCT as a dementia screening tool in clinical practice.PROSPERO registration numberCRD42020176757.
Most classification systems for age-related macular degeneration (AMD) were developed from patients in clinical trials. We aimed to validate the Age-Related Eye Diseases Study (AREDS) simplified ...severity scale of AMD classification using 5- and 10-year incident late AMD data from the population-based Blue Mountains Eye Study (BMES) cohort.
Comparative study of population-based cohort and clinical trial.
Blue Mountains Eye Study participants 40 to 97 years of age at baseline (n = 2134) and AREDS participants 55 to 80 years of age (n = 3640).
In the BMES, AMD lesions were graded from stereoscopic color photographs and were classified according to the AREDS simplified severity scale. The AREDS simplified scale calculates a risk score based on the number of early AMD risk factors (large drusen and pigment abnormalities) in both eyes that can range from 0 to 4.
Five- and 10-year incident late AMD (presence of geographic atrophy or choroidal neovascularization).
The AREDS simplified scale performed similarly when applied to both the BMES population-based participants and the AREDS clinical trial-based participants in predicting 5- and 10-year incidence of late AMD. For scores 0 to 4, the 5-year incidence rates for the BMES compared with the AREDS were 0.2% versus 0.4%, 3.1% versus 3.1%, 12.1% versus 11.8%, 13.5% versus 25.9%, and 47.1% versus 47.3%, respectively. The corresponding 10-year incidence rates for the BMES compared with the AREDS were 0.7% versus 1.5%, 7.3% versus 8.4%, 36.6% versus 27.6%, 20.0% versus 52.7%, and 75.0% versus 71.4%, respectively.
The AREDS simplified severity scale classified late AMD risk levels similarly when applied to population-based and clinical trial samples. These results support the robustness of the AREDS simplified severity scale.