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Supervised deep learning (DL) algorithms are highly dependent on training data for which human graders are assigned, for example, for optical coherence tomography (OCT) image annotation. Despite the tremendous success of DL, due to human judgment, these ground truth labels can be inaccurate and/or ambiguous and cause a human selection bias. We therefore investigated the impact of the size of the ground truth and variable numbers of graders on the predictive performance of the same DL architecture and repeated each experiment three times. The largest training dataset delivered a prediction performance close to that of human experts. All DL systems utilized were highly consistent. Nevertheless, the DL under-performers could not achieve any further autonomous improvement even after repeated training. Furthermore, a quantifiable linear relationship between ground truth ambiguity and the beneficial effect of having a larger amount of ground truth data was detected and marked as the more-ground-truth effect.
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Aprendizado Profundo , Humanos , Tomografia de Coerência Óptica/métodos , Viés de Seleção , AlgoritmosRESUMO
BACKGROUND/AIMS: To investigate the progression of quantitative autofluorescence (qAF) measures and the potential as clinical trial endpoint in ABCA4-related retinopathy. METHODS: In this longitudinal monocentre study, 64 patients with ABCA4-related retinopathy (age (mean±SD), 34.84±16.36 years) underwent serial retinal imaging, including optical coherence tomography (OCT) and qAF (488 nm excitation) imaging using a modified confocal scanning laser ophthalmoscope with a mean (±SD) review period of 20.32±10.90 months. A group of 110 healthy subjects served as controls. Retest variability, changes of qAF measures over time and its association with genotype and phenotype were analysed. Furthermore, individual prognostic feature importance was assessed, and sample size calculations for future interventional trials were performed. RESULTS: Compared with controls, qAF levels of patients were significantly elevated. The test-retest reliability revealed a 95% coefficient of repeatability of 20.37. During the observation time, young patients, patients with a mild phenotype (morphological and functional) and patients with mild mutations showed an absolute and relative increase in qAF values, while patients with advanced disease manifestation (morphological and functional), and homozygous mutations at adulthood revealed a decrease in qAF. Considering these parameters, required sample size and study duration could significantly be reduced. CONCLUSION: Under standardised settings with elaborated conditions towards operators and analysis to counterbalance variability, qAF imaging might be reliable, suitable for quantifying disease progression and constitutes a potential clinical surrogate marker in ABCA4-related retinopathy. Trial design based on patients' baseline characteristics and genotype has the potential to provide benefits regarding required cohort size and absolute number of visits.
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Purpose: The purpose of this study was to develop and validate a deep learning (DL) framework for the detection and quantification of reticular pseudodrusen (RPD) and drusen on optical coherence tomography (OCT) scans. Methods: A DL framework was developed consisting of a classification model and an out-of-distribution (OOD) detection model for the identification of ungradable scans; a classification model to identify scans with drusen or RPD; and an image segmentation model to independently segment lesions as RPD or drusen. Data were obtained from 1284 participants in the UK Biobank (UKBB) with a self-reported diagnosis of age-related macular degeneration (AMD) and 250 UKBB controls. Drusen and RPD were manually delineated by five retina specialists. The main outcome measures were sensitivity, specificity, area under the receiver operating characteristic (ROC) curve (AUC), kappa, accuracy, intraclass correlation coefficient (ICC), and free-response receiver operating characteristic (FROC) curves. Results: The classification models performed strongly at their respective tasks (0.95, 0.93, and 0.99 AUC, respectively, for the ungradable scans classifier, the OOD model, and the drusen and RPD classification models). The mean ICC for the drusen and RPD area versus graders was 0.74 and 0.61, respectively, compared with 0.69 and 0.68 for intergrader agreement. FROC curves showed that the model's sensitivity was close to human performance. Conclusions: The models achieved high classification and segmentation performance, similar to human performance. Translational Relevance: Application of this robust framework will further our understanding of RPD as a separate entity from drusen in both research and clinical settings.
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Aprendizado Profundo , Degeneração Macular , Drusas Retinianas , Humanos , Tomografia de Coerência Óptica , Drusas Retinianas/diagnóstico por imagem , Retina , Degeneração Macular/diagnóstico por imagemRESUMO
INTRODUCTION: The study aimed to explore the psychometric properties of the National Eye Institute Visual Function Questionnaire (NEI VFQ) and Impact of Vision Impairment (IVI) profile in recessive Stargardt disease (STGD1). METHODS: The NEI VFQ-25 and IVI-28 were administered to individuals with STGD1. Responses were analyzed following psychometrically established dimension structures of the NEI VFQ (visual function [VF] subscale; socioemotional [SE] subscale) and of the IVI (functional [F] subscale; emotional [E] subscale). We analyzed internal consistency, dimensionality, item fit, and differential item functioning (DIF), using latent trait models. Criterion validity was assessed using Pearson correlation coefficients. RESULTS: Seventy-one participants (42 females, 29 males; mean age, 44 ± 19 years) were included. Self-reported difficulty levels were lower than the mean difficulty of items in both instruments. Person reliability and person separation index of the instruments were 0.85 and 2.40 (NEI VFQ-VF), 0.69 and 1.49 (NEI-VFQ-SE), 0.88 and 2.77 (IVI-F), and 0.72 and 1.62 (IVI-E). No items showed misfit at a level distorting the measurement system. One IVI item showed DIF by gender but was retained as person measures were largely unaffected by its removal. NEI VFQ-VF and IVI-F as well as NEI VFQ-SE and IVI-E were positively correlated (r = 0.79 and 0.64, respectively). CONCLUSION: The NEI VFQ and IVI have acceptable psychometric properties in STGD1 with the IVI allowing more sensitive person stratification. Targeting of questionnaires to individuals with STGD1 might be improved by including additional content domains specific to the disease.
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Qualidade de Vida , Perfil de Impacto da Doença , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Acuidade Visual , Doença de Stargardt , Reprodutibilidade dos Testes , Inquéritos e Questionários , Medidas de Resultados Relatados pelo PacienteRESUMO
Purpose: To investigate macular curvature, including the evaluation of potential associations and the dome-shaped macular configuration, given the increasing myopia prevalence and expected associated macular malformations. Methods: The study included a total of 65,440 subjects with a mean age (± SD) of 57.3 ± 8.11 years with spectral-domain optical coherence tomography (OCT) data from a unique contemporary resource for the study of health and disease that recruited more than half a million people in the United Kingdom (UK Biobank). A deep learning model was used to segment the retinal pigment epithelium. The macular curvature of the OCT scans was calculated by polynomial fit and evaluated. Further, associations with demographic, functional, ocular, and infancy factors were examined. Results: The overall macular curvature values followed a Gaussian distribution with high inter-eye agreement. Although all of the investigated parameters, except maternal smoking, were associated with the curvature in a multilinear analysis, ethnicity and refractive error consistently revealed the most significant effect. The prevalence of a macular dome-shaped configuration was 4.8% overall, most commonly in Chinese subjects as well as hypermetropic eyes. An increasing frequency up to 22.0% was found toward high refractive error. Subretinal fluid was rarely found in these eyes. Conclusions: Macular curvature revealed associations with demographic, functional, ocular, and infancy factors, as well as increasing prevalence of a dome-shaped macular configuration in high refractive error including high myopia and hypermetropia. These findings imply different pathophysiologic processes that lead to macular development and might open new fields to future myopia and macula research.
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Macula Lutea , Miopia , Erros de Refração , Idoso , Bancos de Espécimes Biológicos , Humanos , Pessoa de Meia-Idade , Miopia/complicações , Miopia/diagnóstico , Miopia/epidemiologia , Erros de Refração/complicações , Tomografia de Coerência Óptica/métodos , Acuidade VisualRESUMO
Cynomolgus monkeys exhibit human-like features, such as a fovea, so they are often used in non-clinical research. Nevertheless, little is known about the natural variation of the choroidal thickness in relation to origin and sex. A combination of deep learning and a deterministic computer vision algorithm was applied for automatic segmentation of foveolar optical coherence tomography images in cynomolgus monkeys. The main evaluation parameters were choroidal thickness and surface area directed from the deepest point on OCT images within the fovea, marked as the nulla with regard to sex and origin. Reference choroid landmarks were set underneath the nulla and at 500 µm intervals laterally up to a distance of 2000 µm nasally and temporally, complemented by a sub-analysis of the central bouquet of cones. 203 animals contributed 374 eyes for a reference choroid database. The overall average central choroidal thickness was 193 µm with a coefficient of variation of 7.8%, and the overall mean surface area of the central bouquet temporally was 19,335 µm2 and nasally was 19,283 µm2. The choroidal thickness of the fovea appears relatively homogeneous between the sexes and the studied origins. However, considerable natural variation has been observed, which needs to be appreciated.
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Aprendizado Profundo , Tomografia de Coerência Óptica , Animais , Corioide/diagnóstico por imagem , Fóvea Central/diagnóstico por imagem , Humanos , Macaca fascicularis , Tomografia de Coerência Óptica/métodosRESUMO
Purpose: To examine whether sociodemographic, and ocular factors relate to optical coherence tomography (OCT)-derived foveal curvature (FC) in healthy individuals. Methods: We developed a deep learning model to quantify OCT-derived FC from 63,939 participants (age range, 39-70 years). Associations of FC with sociodemographic, and ocular factors were obtained using multilevel regression analysis (to allow for right and left eyes) adjusting for age, sex, ethnicity, height (model 1), visual acuity, spherical equivalent, corneal astigmatism, center point retinal thickness (CPRT), intraocular pressure (model 2), deprivation (Townsend index), higher education, annual income, and birth order (model 3). Fovea curvature was modeled as a z-score. Results: Males had on average steeper FC (0.077; 95% confidence interval [CI] 0.077-0.078) than females (0.068; 95% CI 0.068-0.069). Compared with whites, non-white individuals showed flatter FC, particularly those of black ethnicity. In black males, -0.80 standard deviation (SD) change when compared with whites (95% CI -0.89, -0.71; P 5.2e10-68). In black females, -0.70 SD change when compared with whites (95% CI -0.77, -0.63; p 2.3e10-93). Ocular factors (visual acuity, refractive status, and CPRT) showed a graded inverse association with FC that persisted after adjustment. Macular curvature showed a positive association with FC. Income showed a linear trend increase in males (P for linear trend = 0.005). Conclusions: We demonstrate marked differences in FC with ethnicity on the largest cohort studied for this purpose to date. Ocular factors showed a graded association with FC. Implementation of FC quantification in research and on the clinical setting can enhance the understanding of clinical macular phenotypes in health and disease.
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Bancos de Espécimes Biológicos , Fóvea Central , Feminino , Humanos , Masculino , Tomografia de Coerência Óptica/métodos , Reino Unido/epidemiologia , Acuidade VisualRESUMO
OBJECTIVES: To report the reduction in new neovascular age-related macular degeneration (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at 1 year. DESIGN: Retrospective clinical audit and simulation model. SETTING: Multiple UK National Health Service (NHS) ophthalmology centres. PARTICIPANTS: Data on the reduction in new nAMD referrals were obtained from four NHS Trusts comparing April 2020 with April 2019. To estimate the potential impact on 1-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20 825 nAMD eyes from 27 NHS Trusts. MAIN OUTCOME MEASURES: Simulated mean visual acuity and proportions of eyes with vision ≤6/60, ≤6/24 and ≥6/12 at 1 year under four hypothetical scenarios: 0-month, 3-month, 6-month and 9-month treatment delays. Estimated additional number of eyes with vision ≤6/60 at 1 year nationally. RESULTS: The number of nAMD referrals dropped on average by 72% (range 65%-87%). Simulated 1-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision ≤6/60 from 15.5% (13.2%-17.9%) to 23.3% (20.7%-25.9%), and a decrease in the proportion of eyes with vision ≥6/12 (driving vision) from 35.1% (32.1%-38.1%) to 26.4% (23.8%-29.2%). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level for 1 month nationally, these simulated results suggest an additional 186-365 eyes with vision ≤6/60 at 1 year. CONCLUSIONS: We report a large decrease in nAMD referrals during the COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision ≤6/60 and 25% relative decrease in the number of eyes with driving vision at 1 year.
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COVID-19 , Degeneração Macular , Degeneração Macular Exsudativa , Inibidores da Angiogênese , COVID-19/epidemiologia , Auditoria Clínica , Controle de Doenças Transmissíveis , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Degeneração Macular/epidemiologia , Pandemias , Ranibizumab/uso terapêutico , Estudos Retrospectivos , Medicina Estatal , Resultado do Tratamento , Reino Unido/epidemiologia , Transtornos da Visão , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/epidemiologiaRESUMO
BACKGROUND/AIMS: The reason for visual impairment in patients with nanophthalmos and posterior microphthalmos is not completely understood. Therefore, this study aims to investigate foveal structure, and the impact of demographic, clinical and imaging parameters on best-corrected visual acuity (BCVA) in these conditions. METHODS: Sixty-two eyes of 33 patients with nanophthalmos (n=40) or posterior microphthalmos (n=22), and 114 eyes of healthy controls with high-resolution retinal imaging including spectral-domain or swept-source optical coherence tomography images were included in this cross-sectional case-control study. Foveal retinal layer thickness was determined by two independent readers. A mixed-effect model was used to perform structure-function correlations and predict the BCVA based on subject-specific variables. RESULTS: Most patients (28/33) had altered foveal structure associated with loss of foveal avascular zone and impaired BCVA. However, widening of outer nuclear layer, lengthening of photoreceptor outer segments, normal distribution of macular pigment and presence of Henle fibres were consistently found. Apart from the presence of choroidal effusion, which had significant impact on BCVA, the features age, refractive error, axial length and retinal layer thickness at the foveal centre explained 61.7% of the variability of BCVA. CONCLUSION: This study demonstrates that choroidal effusion, age, refractive error, axial length and retinal layer thickness are responsible for the majority of interindividual variability of BCVA as well as the morphological foveal heterogeneity in patients with nanophthalmos or posterior microphthalmos. This might give further insights into the physiology of foveal development and the process of emmetropisation, and support clinicians in the assessment of these disease entities.
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Efusões Coroides , Microftalmia , Erros de Refração , Estudos de Casos e Controles , Estudos Transversais , Fóvea Central/irrigação sanguínea , Humanos , Microftalmia/complicações , Microftalmia/diagnóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade VisualRESUMO
PURPOSE: Virtual reality (VR) can be useful in explaining diseases and complications that affect children in order to improve medical communications with this vulnerable patient group. So far, children and young people's responses to high-end medical VR environments have never been assessed. METHODS: An unprecedented number of 320 children and young people were given the opportunity to interact with a VR application displaying original ophthalmic volume data via a commercially available tethered head-mounted display (HMD). Participants completed three surveys: demographics and experience with VR, usability and perceived utility of this technology and the Simulator Sickness Questionnaire. The second survey also probed participants for suggestions on improvements and whether this system could be useful for increasing engagement in science. RESULTS: A total of 206 sets of surveys were received. 165 children and young people (84 female) aged 12-18 years (mean, 15 years) completed surveys that could be used for analysis. 69 participants (47.59%) were VR-naïve, and 76 (52.41%) reported that they had previous VR experience. Results show that VR facilitated understanding of ophthalmological complications and was reasonably tolerated. Lastly, exposure to VR raised children and young people's awareness and interest in science. CONCLUSIONS: The VR platform used was successfully utilized and was well accepted in children to display and interact with volume-rendered 3D ophthalmological data. Virtual reality (VR) is suitable as a novel image display platform in ophthalmology to engage children and young people.
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Educação de Pacientes como Assunto/métodos , Realidade Virtual , Adolescente , Criança , Estudos de Viabilidade , Feminino , Humanos , Masculino , Oftalmologia/instrumentação , Inquéritos e QuestionáriosRESUMO
Purpose: To investigate the interreader agreement for grading of retinal alterations in age-related macular degeneration (AMD) using a reading center setting. Methods: In this cross-sectional case series, spectral-domain optical coherence tomography (OCT; Topcon 3D OCT, Tokyo, Japan) scans of 112 eyes of 112 patients with neovascular AMD (56 treatment naive, 56 after three anti-vascular endothelial growth factor injections) were analyzed by four independent readers. Imaging features specific for AMD were annotated using a novel custom-built annotation platform. Dice score, Bland-Altman plots, coefficients of repeatability, coefficients of variation, and intraclass correlation coefficients were assessed. Results: Loss of ellipsoid zone, pigment epithelium detachment, subretinal fluid, and drusen were the most abundant features in our cohort. Subretinal fluid, intraretinal fluid, hypertransmission, descent of the outer plexiform layer, and pigment epithelium detachment showed highest interreader agreement, while detection and measures of loss of ellipsoid zone and retinal pigment epithelium were more variable. The agreement on the size and location of the respective annotation was more consistent throughout all features. Conclusions: The interreader agreement depended on the respective OCT-based feature. A selection of reliable features might provide suitable surrogate markers for disease progression and possible treatment effects focusing on different disease stages. Translational Relevance: This might give opportunities for a more time- and cost-effective patient assessment and improved decision making as well as have implications for clinical trials and training machine learning algorithms.
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Inibidores da Angiogênese , Degeneração Macular Exsudativa , Estudos Transversais , Humanos , Japão , Aprendizado de Máquina , Reprodutibilidade dos Testes , Tóquio , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular , Acuidade VisualRESUMO
Machine learning has greatly facilitated the analysis of medical data, while the internal operations usually remain intransparent. To better comprehend these opaque procedures, a convolutional neural network for optical coherence tomography image segmentation was enhanced with a Traceable Relevance Explainability (T-REX) technique. The proposed application was based on three components: ground truth generation by multiple graders, calculation of Hamming distances among graders and the machine learning algorithm, as well as a smart data visualization ('neural recording'). An overall average variability of 1.75% between the human graders and the algorithm was found, slightly minor to 2.02% among human graders. The ambiguity in ground truth had noteworthy impact on machine learning results, which could be visualized. The convolutional neural network balanced between graders and allowed for modifiable predictions dependent on the compartment. Using the proposed T-REX setup, machine learning processes could be rendered more transparent and understandable, possibly leading to optimized applications.
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Aprendizado Profundo , Aprendizado de Máquina , Tomografia de Coerência Óptica , Adulto , Algoritmos , Animais , Inteligência Artificial , Competência Clínica , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Interpretação de Imagem Assistida por Computador/normas , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Macaca fascicularis , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Imagem Multimodal/tendências , Redes Neurais de Computação , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Retina/diagnóstico por imagem , Retina/patologia , Doenças Retinianas/diagnóstico , Doenças Retinianas/epidemiologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Tomografia de Coerência Óptica/estatística & dados numéricosRESUMO
Spatially-resolved retinal function can be measured by psychophysical testing like fundus-controlled perimetry (FCP or 'microperimetry'). It may serve as a performance outcome measure in emerging interventional clinical trials for macular diseases as requested by regulatory agencies. As FCP constitute laborious examinations, we have evaluated a machine-learning-based approach to predict spatially-resolved retinal function ('inferred sensitivity') based on microstructural imaging (obtained by spectral domain optical coherence tomography) and patient data in recessive Stargardt disease. Using nested cross-validation, prediction accuracies of (mean absolute error, MAE [95% CI]) 4.74 dB [4.48-4.99] were achieved. After additional inclusion of limited FCP data, the latter reached 3.89 dB [3.67-4.10] comparable to the test-retest MAE estimate of 3.51 dB [3.11-3.91]. Analysis of the permutation importance revealed, that the IS&OS and RPE thickness were the most important features for the prediction of retinal sensitivity. 'Inferred sensitivity', herein, enables to accurately estimate differential effects of retinal microstructure on spatially-resolved function in Stargardt disease, and might be used as quasi-functional surrogate marker for a refined and time-efficient investigation of possible functionally relevant treatment effects or disease progression.
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Retina/fisiopatologia , Doença de Stargardt/fisiopatologia , Testes de Campo Visual/métodos , Adulto , Feminino , Fundo de Olho , Humanos , Processamento de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Degeneração Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/fisiopatologia , Doença de Stargardt/metabolismo , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Campos VisuaisRESUMO
One-in-four ophthalmology trials are single-armed, which poses challenges to their interpretation. We demonstrate how real-world cohorts used as external/synthetic control arms can contextualize such trials. We herein emulated a target trial on the intention-to-treat efficacy of off-label bevacizumab (q6w) pro re nata relative to fixed-interval aflibercept (q8w) for improving week 54 visual acuity of eyes affected by neovascular age-related macular degeneration. The bevacizumab arm (n = 65) was taken from the ABC randomized controlled trial. A total of 4,471 aflibercept-treated eyes aligning with the ABC trial eligibility were identified from electronic health records and synthetic control arms were created by emulating randomization conditional on age, sex, and baseline visual read via exact matching and propensity score methods. We undertook an inferiority analysis on mean difference at 54 weeks; outcomes regression on achieving a change in visual acuity of greater than or equal to 15, greater than or equal to 10, and less than or equal to -15 Early Treatment Diabetic Retinopathy (ETDRS) letters at week 54; and a time-to-event analysis on achieving a change in visual acuity of greater than or equal to 15, greater than or equal to 10, and less than or equal to -15 ETDRS letters by week 54. The findings suggest off-label bevacizumab to be neither inferior nor superior to licensed aflibercept. Our study highlights how real-world cohorts representing the counterfactual intervention could aid the interpretation of single-armed trials when analyzed in accord to the target trial framework. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? One-in-four randomized controlled trials in ophthalmology are single-armed, which poses challenges for interpreting their efficacy relative to standard of care. Recent conceptual advances in the methods of causal inference and in the emulation of target trials suggests that the standard-of-care arms representing the counterfactual intervention can be approximated with observational data. WHAT QUESTION DID THIS STUDY ADDRESS? How real-world cohorts representing the counterfactual intervention can aid the interpretation of single-armed ophthalmological trials. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Our study highlights how real-world cohorts representing the counterfactual intervention could aid the interpretation of single-armed ophthalmological trials when undertaken in accord with the target trial framework. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? External counterfactual arms could reduce the time and cost to reach potential regulatory approval.
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Bevacizumab/farmacologia , Degeneração Macular/tratamento farmacológico , Proteínas Recombinantes de Fusão/farmacologia , Acuidade Visual/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/uso terapêutico , Estudos de Coortes , Simulação por Computador , Interpretação Estatística de Dados , Estudos de Equivalência como Asunto , Feminino , Humanos , Degeneração Macular/diagnóstico , Masculino , Estudos Multicêntricos como Assunto , Uso Off-Label , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Resultado do TratamentoRESUMO
PURPOSE: We sought to develop and validate a deep learning model for segmentation of 13 features associated with neovascular and atrophic age-related macular degeneration (AMD). DESIGN: Development and validation of a deep-learning model for feature segmentation. METHODS: Data for model development were obtained from 307 optical coherence tomography volumes. Eight experienced graders manually delineated all abnormalities in 2712 B-scans. A deep neural network was trained with these data to perform voxel-level segmentation of the 13 most common abnormalities (features). For evaluation, 112 B-scans from 112 patients with a diagnosis of neovascular AMD were annotated by 4 independent observers. The main outcome measures were Dice score, intraclass correlation coefficient, and free-response receiver operating characteristic curve. RESULTS: On 11 of 13 features, the model obtained a mean Dice score of 0.63 ± 0.15, compared with 0.61 ± 0.17 for the observers. The mean intraclass correlation coefficient for the model was 0.66 ± 0.22, compared with 0.62 ± 0.21 for the observers. Two features were not evaluated quantitatively because of a lack of data. Free-response receiver operating characteristic analysis demonstrated that the model scored similar or higher sensitivity per false positives compared with the observers. CONCLUSIONS: The quality of the automatic segmentation matches that of experienced graders for most features, exceeding human performance for some features. The quantified parameters provided by the model can be used in the current clinical routine and open possibilities for further research into treatment response outside clinical trials.
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Neovascularização de Coroide/diagnóstico por imagem , Aprendizado Profundo , Atrofia Geográfica/diagnóstico por imagem , Drusas Retinianas/diagnóstico por imagem , Degeneração Macular Exsudativa/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/fisiopatologia , Feminino , Atrofia Geográfica/tratamento farmacológico , Atrofia Geográfica/fisiopatologia , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Redes Neurais de Computação , Curva ROC , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Drusas Retinianas/tratamento farmacológico , Drusas Retinianas/fisiopatologia , Sensibilidade e Especificidade , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/fisiopatologiaRESUMO
Geographic atrophy (GA) represents the non-exudative late stage of age-related macular degeneration and constitutes a leading cause of legal blindness in the developed world. It is characterized by areas of loss of outer retinal layers including photoreceptors, degeneration of the retinal pigment epithelium, and rarefication of the choriocapillaris. As all three layers are functionally connected, the precise temporal sequence and relative contribution of these layers towards the development and progression of GA is unclear. The advent of optical coherence tomography angiography (OCT-A) has allowed for three-dimensional visualization of retinal blood flow. Using OCT-A, recent studies have demonstrated that choriocapillaris flow alterations are particularly associated with the development of GA, exceed atrophy boundaries spatially, and are a prognostic factor for future GA progression. Furthermore, OCT-A may be helpful to differentiate GA from mimicking diseases. Evidence for a potential protective effect of specific forms of choroidal neovascularization in the context of GA has been reported. This article aims to give a comprehensive review of the current literature concerning the application of OCT-A in GA, and summarizes the opportunities and limitations with regard to pathophysiologic considerations, differential diagnosis, study design, and patient assessment.
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Atrofia Geográfica , Degeneração Macular , Corioide , Angiofluoresceinografia , Atrofia Geográfica/diagnóstico , Humanos , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: To evaluate the feasibility and safety of a coaxial dual-wavelength optical coherence tomography (OCT) device (marked as Hydra-OCT). METHODS: Healthy participants without ocular pathology underwent retinal imaging using the Hydra-OCT allowing for simultaneous measurement of retinal scanning of 840 and 1,072 nm wavelength. Before and after measurement, best-corrected visual acuity and patients' comfort were assessed. Representative OCT images from both wavelengths were compared by 5 independent graders using a subjective grading scheme. RESULTS: A total of 30 eyes of 30 participants (8 females and 22 males) with a mean age of 26.5 years (range from 19 to 55 years) were included. Dual-wavelength image acquisition was made possible in each subject. The participant's effort and comfort assessment using the Hydra-OCT imaging revealed an equivalent value as compared to the commercially available OCT machine. No adverse events were reported, and visual acuity was not altered by the Hydra-OCT. Imaging between the systems was comparable. CONCLUSIONS: This study provides evidence for the feasibility and safety of a coaxial dual-wavelength OCT imaging method under real-life conditions. The novel Hydra-OCT imaging device may offer additional insights into the pathology of retinal and choroidal diseases.
Assuntos
Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/instrumentação , Adulto , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND/AIMS: To evaluate the applicability of mesopic light sensitivity measurements obtained by fundus-controlled perimetry (FCP, also termed 'microperimetry') as clinical trial endpoint in Stargardt disease (STGD1). METHODS: In this retrospective, monocentre cohort study, 271 eyes of 136 patients (age, 37.1 years) with STGD1 and 87 eyes of 54 healthy controls (age, 41.0 years) underwent mesopic FCP, using a pattern of 50 stimuli (achromatic, 400-800 nm) centred on the fovea. The concurrent validity of mesopic FCP testing using the MAIA device (CenterVue, Italy), the retest variability and its determinants, and the progression of sensitivity loss over time were investigated using mixed-model analyses. The main outcomes were the average pointwise sensitivity loss in dependence of patients' demographic, functional and imaging characteristics, the intrasession 95% coefficient of repeatability, and the pointwise sensitivity loss over time. RESULTS: Pointwise sensitivity loss was on average (estimate (95% CI)) 13.88 dB (12.55 to 15.21) along the horizontal meridian and was significantly associated with the electrophysiological subgroup, presence/absence of foveal sparing, best-corrected visual acuity and disease duration. The 95% coefficient of repeatability was 12.15 dB (10.78 to 13.38) and varied in dependence of the underlying mean sensitivity and local sensitivity slope. The global progression rate for the sensitivity loss was 0.45 dB/year (0.13 to 0.78) and was higher for the central and inner ETDRS subfields compared with more peripheral regions. CONCLUSIONS: Mesopic light sensitivity measured by FCP is reliable and susceptible for functional changes. It constitutes a potential clinical outcome for both natural history studies as well as future interventional studies in patients with STGD1.
Assuntos
Luz , Visão Mesópica/fisiologia , Retina/efeitos da radiação , Doença de Stargardt/fisiopatologia , Campos Visuais/fisiologia , Adulto , Feminino , Genes Recessivos , Humanos , Masculino , Pessoa de Meia-Idade , Retina/fisiopatologia , Estudos Retrospectivos , Doença de Stargardt/genética , Acuidade Visual/fisiologia , Testes de Campo Visual , Adulto JovemRESUMO
PURPOSE: To investigate lipofuscin-related quantitative autofluorescence measures and their association with demographic characteristics, retinal structure, retinal function and genotype in ABCA4-related retinopathy (Stargardt disease 1). DESIGN: Cross-sectional study with age-matched healthy control subjects. METHODS: A total of 77 patients with ABCA4-related retinopathy and 110 control subjects underwent quantitative fundus autofluorescence (qAF) imaging using a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to measure qAF as surrogate for lipofuscin accumulation. Measures of qAF were correlated with demographic characteristics, structural alterations on optical coherence tomography and fundus autofluorescence imaging, retinal function assessed by full-field electroretinography (ERG) and fundus-controlled perimetry, and genotype. RESULTS: Most patients (76.6%) had qAF levels >95% prediction interval of the age-related control group, with best discrimination between cases and control subjects in younger patients. Reduced discrimination based on qAF measures was associated with mild disease, more advanced disease with dark flecks, or older age because of the physiological age-related increase in qAF and a ceiling effect in patients. Nullizygous patients presented with high qAF levels earlier in life compared with those with at least 1 milder ABCA4 variant. Within the sectors of qAF measurements, at approximately 7-9° eccentricity, increased qAF without flecks or with only bright flecks was associated with topographically related preserved retinal thickness and fundus-controlled perimetry results, and with normal full-field ERG recordings. All 3 parameters were increasingly abnormal with the development of dark flecks and decreasing qAF. CONCLUSIONS: The accumulation of lipofuscin depends on the severity of ABCA4 variants, precedes other structural changes, and may remain without clinically relevant effect on retinal function.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Angiofluoresceinografia/métodos , Mutação , Doenças Retinianas/diagnóstico , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica/métodos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Adolescente , Adulto , Criança , Estudos Transversais , DNA/genética , Análise Mutacional de DNA , Eletrorretinografia , Feminino , Fundo de Olho , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/genética , Doenças Retinianas/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: To investigate the prognostic value of demographic, functional, genetic, and imaging parameters on retinal pigment epithelium atrophy progression secondary to ABCA4-related retinopathy. METHODS: Patients with retinal pigment epithelium atrophy secondary to ABCA4-related retinopathy were examined longitudinally with fundus autofluorescence imaging. Lesion area, perimeter, circularity, caliper diameters, and focality of areas with definitely decreased autofluorescence were determined. A model was used to predict the lesion enlargement rate based on baseline variables. Sample size calculations were performed to model the power in a simulated interventional study. RESULTS: Sixty-eight eyes of 37 patients (age range, 14-78 years) with a follow-up time of 10 to 100 months were included. The mean annual progression of retinal pigment epithelium atrophy was 0.89 mm. The number of atrophic areas, the retina-wide functional impairment, and the age-of-onset category constituted significant predictors for future retinal pigment epithelium atrophy growth, explaining 25.7% of the variability. By extension of a simulated study length and/or specific patient preselection based on these baseline characteristics, the required sample size could significantly be reduced. CONCLUSION: Trial design based on specific shape-descriptive factors and patients' baseline characteristics and the adaption of the trial duration may provide potential benefits in required cohort size and absolute number of visits.