The potential application of artificial intelligence for diagnosis and management of glaucoma in adults

BACKGROUND: Glaucoma is the most frequent cause of irreversible blindness worldwide. There is no cure, but early detection and treatment can slow the progression and prevent loss of vision. It has been suggested that artificial intelligence (AI) has potential application for detection and management of glaucoma. SOURCES OF DATA: This literature review is based on articles published in peer-reviewed journals. AREAS OF AGREEMENT: There have been significant advances in both AI and imaging techniques that are able to identify the early signs of glaucomatous damage. Machine and deep learning algorithms show capabilities equivalent to human experts, if not superior. AREAS OF CONTROVERSY: Concerns that the increased reliance on AI may lead to deskilling of clinicians. GROWING POINTS: AI has potential to be used in virtual review clinics, telemedicine and as a training tool for junior doctors. Unsupervised AI techniques offer the potential of uncovering currently unrecognized patterns of disease. If this promise is fulfilled, AI may then be of use in challenging cases or where a second opinion is desirable. AREAS TIMELY FOR DEVELOPING RESEARCH: There is a need to determine the external validity of deep learning algorithms and to better understand how the 'black box' paradigm reaches results

Optical Coherence Tomography in the UK Biobank Study - Rapid Automated Analysis of Retinal Thickness for Large Population-Based Studies

PURPOSE: To describe an approach to the use of optical coherence tomography (OCT) imaging in large, population-based studies, including methods for OCT image acquisition, storage, and the remote, rapid, automated analysis of retinal thickness. METHODS: In UK Biobank, OCT images were acquired between 2009 and 2010 using a commercially available “spectral domain” OCT device (3D OCT-1000, Topcon). Images were obtained using a raster scan protocol, 6 mm x 6 mm in area, and consisting of 128 B-scans. OCT image sets were stored on UK Biobank servers in a central repository, adjacent to high performance computers. Rapid, automated analysis of retinal thickness was performed using custom image segmentation software developed by the Topcon Advanced Biomedical Imaging Laboratory (TABIL). This software employs dual-scale gradient information to allow for automated segmentation of nine intraretinal boundaries in a rapid fashion. RESULTS: 67,321 participants (134,642 eyes) in UK Biobank underwent OCT imaging of both eyes as part of the ocular module. 134,611 images were successfully processed with 31 images failing segmentation analysis due to corrupted OCT files or withdrawal of subject consent for UKBB study participation. Average time taken to call up an image from the database and complete segmentation analysis was approximately 120 seconds per data set per login, and analysis of the entire dataset was completed in approximately 28 days. CONCLUSIONS: We report an approach to the rapid, automated measurement of retinal thickness from nearly 140,000 OCT image sets from the UK Biobank. In the near future, these measurements will be publically available for utilization by researchers around the world, and thus for correlation with the wealth of other data collected in UK Biobank. The automated analysis approaches we describe may be of utility for future large population-based epidemiological studies, clinical trials, and screening programs that employ OCT imaging

Agreement Between Spectral-Domain and Swept-Source Optical Coherence Tomography Retinal Thickness Measurements in Macular and Retinal Disease

INTRODUCTION: To assess inter-device agreement in optical coherence tomography-derived retinal thickness measurements in patients with known macular conditions between spectral-domain and swept-source optical coherence tomography (OCT). METHODS: Two hundred seventy-two subjects were included in the study. They consisted of 91 male (33.5%) and 181 female (66.5%) subjects, and 132 left (48.5%) and 140 right (51.5%) eyes. Each subject underwent spectral-domain OCT (SD-OCT, Spectralis, Heidelberg Engineering; RTVue XR Avanti XR HD, Optovue) and swept-source OCT (SS-OCT; DRI-OCT-1, Atlantis, Topcon) in a single imaging session performed by the same clinical trial-certified technician. The comparison of retinal thickness reproducibility between devices was performed using Bland-Altman analyses and across the entire data set using the intraclass correlation coefficient (ICC). RESULTS: The ICC of the retinal thickness measurements (95% confidence interval) made using all three OCT instruments was 0.81 (0.77-0.84). The mean difference in mean retinal thickness between Spectralis SD-OCT and Topcon SS-OCT was 59.1 μm (95% limit of agreement [LoA] -21.7 to 139.8 μm). The mean difference in mean retinal thickness between Optovue SD-OCT and Topcon SS-OCT was 21.8 μm (95% LoA -34.7  to 78.3 μm). CONCLUSIONS: Retinal layer thickness measurements vary between SS-OCT and SD-OCT devices. We describe inter-device agreement in retinal thickness between SS-OCT and SD-OCT in patients with macular conditions. Clinicians should be aware of the differences in retinal thickness values when imaging patients using different OCT devices and should consider using the same OCT device model in order to monitor clinical change. TRIAL REGISTRATION: ClinicalTrials.gov Identifier (NCT02828215)

Objective Evaluation of Proliferative Diabetic Retinopathy Using OCT

PURPOSE: To present the routine use of OCT and OCT angiography (OCTA) for the objective diagnosis and monitoring of proliferative diabetic retinopathy (PDR). DESIGN: Retrospective, observational case series. PARTICIPANTS: Patients with diabetic retinopathy imaged using a standardized PDR protocol. METHODS: Patients routinely imaged with a standardized PDR protocol between March 2017 and January 2019 were included. This included a 12×9-mm structural OCT volume centered on the macula and a 6×6-mm OCTA scan centered on the optic nerve head obtained using a Topcon swept-source system (DRI OCT-1 Triton, Topcon, Tokyo, Japan). Ultra-widefield fluorescein angiography (FA) was also performed when clinically indicated. The ground truth for each case was determined by merging the findings from biomicroscopy and imaging modalities to generate the maximum level of detection for each finding. MAIN OUTCOME MEASURES: Detection rates of new-onset, regression, and reactivation of neovascularization of the disc (NVD) and neovascularization elsewhere (NVE) using different modalities (biomicroscopy/color photography, structural OCT, B-scan OCTA, en face OCTA). Detection of progression of tractional retinal detachment (TRD). RESULTS: A total of 383 eyes of 204 patients were evaluated. After excluding patients without PDR or with insufficient image quality, 47 eyes of 35 patients were included. For the detection of new-onset NVD and NVE, structural OCT had the highest detection rate (100%) of all modalities. However, for the detection of regression or reactivation of neovascularization (NV), B-scan OCTA had the highest detection rate (100%). Structural OCT detected regression only in 45.5% of cases, resulting in a low detection rate of reactivation (12.5%). Among 10 eyes with TRD, OCT detected fovea-threatening TRD during follow-up in 7 eyes, resulting in vitrectomy. CONCLUSIONS: This study demonstrates the utility of novel multimodal imaging in the daily management of patients with PDR. Posterior pole structural OCT had the best detection rate for NV, and B-scan OCTA showed the most potential for objective monitoring of disease after treatment

Predicting Incremental and Future Visual Change in Neovascular Age-Related Macular Degeneration Using Deep Learning

PURPOSE: To evaluate the predictive utility of quantitative imaging biomarkers, acquired automatically from optical coherence tomography (OCT) scans, of cross-sectional and future visual outcomes of patients with neovascular age-related macular degeneration (AMD) starting anti-vascular endothelial growth factor (VEGF) therapy. DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naïve, first-treated eyes of patients with neovascular AMD between 2007 and 2017 at Moorfields Eye Hospital (a large, UK single-centre) undergoing anti-VEGF therapy METHODS: Automatic segmentation was carried out by applying a deep learning segmentation algorithm to 137,379 OCT scans from 6467 eyes of 3261 patients with neovascular AMD. After applying selection criteria 926 eyes of 926 patients were taken forward for analysis. MAIN OUTCOME MEASURES: Correlation coefficients (R2) and mean absolute error (MAE) between quantitative OCT (qOCT) parameters and cross-sectional visual-function. The predictive value of these parameters for short-term visual change i.e. incremental visual acuity [VA] resulting from an individual injection, as well as, VA at distant timepoints (up to 12 months post-baseline). RESULTS: VA at distant timepoints could be predicted: R2 0.80 (MAE 5.0 ETDRS letters) and R2 0.7 (MAE 7.2) post-injection 3 and at 12 months post-baseline (both p < 0.001), respectively. Best performing models included both baseline qOCT parameters and treatment-response. Furthermore, we present proof-of-principle evidence that the incremental change in VA from an injection can be predicted: R2 0.14 (MAE 5.6) for injection 2 and R2 0.11 (MAE 5.0) for injection 3 (both p < 0.001). CONCLUSIONS: Automatic segmentation enables rapid acquisition of quantitative and reproducible OCT biomarkers with potential to inform treatment decisions in the care of neovascular AMD. This furthers development of point-of-care decision-aid systems for personalized medicine

Associations with Retinal Pigment Epithelium Thickness Measures in a Large Cohort: Results from the UK Biobank

PURPOSE: To describe associations of ocular and systemic factors with retinal pigment epithelium (RPE)-Bruch's membrane (BM) complex thickness as measured by spectral-domain (SD) optical coherence tomography (OCT). DESIGN: Multisite community-based study. This research has been conducted using the UK Biobank Resource. PARTICIPANTS: Sixty-seven thousand three hundred eighteen people 40 to 69 years old received questionnaires, physical examination, and eye examination, including macular SD OCT. Systematic selection process identified 34 652 eyes with high-quality SD OCT images from normal individuals for analysis. METHODS: We included people with no self-reported ocular disease, diabetes, or neurologic disorders; visual acuity of ≥20/25; refraction between -6 diopters (D) to 6 D, and IOP of 6 to 21 mmHg. Only high-quality, well-centered SD OCT images with central, stable fixation were included. Descriptive statistics, t tests, and regression analyses were performed. Multivariate regression modeling was used to adjust for covariates and to identify relationships between RPE-BM thickness and ocular and systemic features. MAIN OUTCOME MEASURES: Retinal pigment epithelium-BM thickness, as measured by SD OCT segmentation using Topcon Advanced Boundary Segmentation at 9 Early Treatment of Diabetic Retinopathy Study subfields. RESULTS: Mean RPE-BM thickness was 26.3 μm (standard deviation, 4.8 μm) at central subfield. Multivariate regression with age stratification showed that RPE thinning became apparent after age 45. Among those aged ≤45, RPE-BM was significantly thicker among those of black or mixed/other race (+3.61 and +1.77 μm vs. white, respectively; P 45, RPE-BM was significantly thinner with older age (-0.10 μm/year; P < 0.001), Asian ethnicity (-0.45 μm vs. white; P = 0.02), taller height (-0.02 μm/cm; P < 0.001), higher IOP (-0.03 μm/mmHg; P < 0.001), and regular smoking (-0.27 μm vs. nonsmokers; P = 0.02). In contrast, RPE-BM was significantly thicker among black or mixed/other race (+3.29 μm and +0.81 μm vs. white, respectively; P < 0.001) and higher hyperopia (+0.28 μm/D; P < 0.001). There was no significant association with sex or Chinese ethnicity. CONCLUSIONS: We describe novel findings of RPE-BM thickness in normal individuals, a structure that varies with age, ethnicity, refraction, IOP, and smoking. The significant association with IOP is especially interesting and may have relevance for the etiology of glaucoma, while the association between age and smoking may have relevance for the etiology of age-related macular degeneration

Quantitative analysis of optical coherence tomography for neovascular age-related macular degeneration using deep learning

PURPOSE: To apply a deep learning algorithm for automated, objective, and comprehensive quantification of optical coherence tomography (OCT) scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD), and make the raw segmentation output data openly available for further research. DESIGN: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database. PARTICIPANTS: 2473 first-treated eyes and another 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June 2017. METHODS: A deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first and second eyes, by visual acuity (VA) and by race/ethnicity, and correlations between volumes. MAIN OUTCOME MEASURES: Volumes of segmented features (mm3), central subfield thickness (CST) (μm). RESULTS: In first-treated eyes, the majority had both IRF and SRF (54.7%). First-treated eyes had greater volumes for all segmented tissues, with the exception of drusen, which was greater in second-treated eyes. In first-treated eyes, older age was associated with lower volumes for RPE, SRF, NSR and sPED; in second-treated eyes, older age was associated with lower volumes of NSR, RPE, sPED, fvPED and SRF. Eyes from black individuals had higher SRF, RPE and serous PED volumes, compared with other ethnic groups. Greater volumes of the vast majority of features were associated with worse VA. CONCLUSION: We report the results of large scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care, and the detection of novel structure-function correlations. These data will be made publicly available for replication and future investigation by the AMD research community

Moorfields AMD database report 2: fellow eye involvement with neovascular age-related macular degeneration.

BACKGROUND/AIMS: Neovascular age-related macular degeneration (nAMD) is frequently bilateral, and previous reports on 'fellow eyes' have assumed sequential treatment after a period of treatment of the first eye only. The aim of our study was to analyse baseline characteristics and visual acuity (VA) outcomes of fellow eye involvement with nAMD, specifically differentiating between sequential and non-sequential (due to macular scarring in the first eye) antivascular endothelial growth factor treatment and timelines for fellow eye involvement. METHODS: Retrospective, electronic medical record database study of the Moorfields AMD database of 6265 patients/120 286 single entries with data extracted between 21 October 2008 and 9 August 2018. The data set for analysis consisted of 1180 sequential, 807 non-sequential and 3410 unilateral eyes. RESULTS: Mean VA (ETDRS letters±SD) of sequentially treated fellow eyes at baseline was significantly higher (63±13), VA gain over 2 years lower (0.37±14) and proportion of eyes with good VA (≥70 letters) higher (46%) than the respective first eyes (baseline VA 54±16, VA gain at 2 years 5.6±15, percentage of eyes with good VA 39%). Non-sequential fellow eyes showed baseline characteristics and VA outcomes similar to first eyes. Fellow eye involvement rate was 32% at 2 years, and median time interval to fellow eye involvement was 71 (IQR: 27-147) weeks. CONCLUSION: This report shows that sequentially treated nAMD fellow eyes have better baseline and final VA than non-sequentially treated eyes after 2 years of treatment. Sequentially treated eyes also had a greater proportion with good VA after 2 years

A broad distribution of the alternative oxidase in microsporidian parasites

Microsporidia are a group of obligate intracellular parasitic eukaryotes that were considered to be amitochondriate until the recent discovery of highly reduced mitochondrial organelles called mitosomes. Analysis of the complete genome of Encephalitozoon cuniculi revealed a highly reduced set of proteins in the organelle, mostly related to the assembly of ironsulphur clusters. Oxidative phosphorylation and the Krebs cycle proteins were absent, in keeping with the notion that the microsporidia and their mitosomes are anaerobic, as is the case for other mitosome bearing eukaryotes, such as Giardia. Here we provide evidence opening the possibility that mitosomes in a number of microsporidian lineages are not completely anaerobic. Specifically, we have identified and characterized a gene encoding the alternative oxidase (AOX), a typically mitochondrial terminal oxidase in eukaryotes, in the genomes of several distantly related microsporidian species, even though this gene is absent from the complete genome of E. cuniculi. In order to confirm that these genes encode functional proteins, AOX genes from both A. locustae and T. hominis were over-expressed in E. coli and AOX activity measured spectrophotometrically using ubiquinol-1 (UQ-1) as substrate. Both A. locustae and T. hominis AOX proteins reduced UQ-1 in a cyanide and antimycin-resistant manner that was sensitive to ascofuranone, a potent inhibitor of the trypanosomal AOX. The physiological role of AOX microsporidia may be to reoxidise reducing equivalents produced by glycolysis, in a manner comparable to that observed in trypanosome

Non-operative treatment for perforated gastro-duodenal peptic ulcer in Duchenne Muscular Dystrophy: a case report

BACKGROUND: Clinical characteristics and complications of Duchenne muscular dystrophy caused by skeletal and cardiac muscle degeneration are well known. Gastro-intestinal involvement has also been recognised in these patients. However an acute perforated gastro-duodenal peptic ulcer has not been documented up to now. CASE PRESENTATION: A 26-year-old male with Duchenne muscular dystrophy with a clinical and radiographic diagnosis of acute perforated gastro-duodenal peptic ulcer is treated non-operatively with naso-gastric suction and intravenous medication. Gastrointestinal involvement in Duchenne muscular dystrophy and therapeutic considerations in a high risk patient are discussed. CONCLUSION: Non-surgical treatment for perforated gastro-duodenal peptic ulcer should be considered in high risk patients, as is the case in patients with Duchenne muscular dystrophy. Patients must be carefully observed and operated on if non-operative treatment is unsuccessful