Choroidal neovascularisation (CNV) is a common vision-threatening complication of myopia and pathological myopia. Despite significant advances in understanding the epidemiology, pathogenesis and ...natural history of myopic CNV, there is no standard definition of myopic CNV and its relationship to axial length and other myopic degenerative changes. Several treatments are available to ophthalmologists, but with the advent of new therapies there is a need for further consensus and clinical management recommendations. Verteporfin photodynamic therapy has been an established treatment for subfoveal myopic CNV for many years, but this treatment does not restore visual acuity and is associated with long-term chorioretinal atrophy. More recently, clinical trials investigating the efficacy and safety of anti-vascular endothelial growth factor agents in patients with myopic CNV have demonstrated substantial visual acuity gains and quality of life increases compared with photodynamic therapy. These enhanced outcomes provide updated evidence-based clinical management guidelines of myopic CNV, and increase the need for a generally accepted definition for myopic CNV. This review critically summarises the latest myopic CNV literature in the context of clinical experience and recommends a myopic CNV treatment algorithm.
The purpose of this study was to compare optical coherence tomography (OCT) angiography to standard fluorescein angiography (FA) in the grading of diabetic macular ischemia.
In our study, OCT ...angiography and traditional FA images were acquired from 24 diabetic patients. The level of diabetic macular ischemia in the superficial capillary plexus was graded with standard Early Treatment Diabetic Retinopathy Study (ETDRS) protocols and a comparison between conventional FA and OCT angiography was performed. The deep vascular plexus and choriocapillaris were also graded for macular ischemia. Additionally, flow indices were analyzed for all OCT angiography images.
We identified moderate agreement between diabetic macular ischemia grades for conventional FA and OCT angiography (weighted κ of 0.53 and 0.41). In addition, the intergrader agreement for the superficial, deep, and choriocapillaris scores was substantial (weighted κ of 0.65, 0.61, and 0.65, respectively). Finally, the parafoveal flow indices were shown to have a statistically significant relationship with diabetic macular ischemia grades for the superficial capillary plexus (P = 0.04) and choriocapillaris (P = 0.036), with a trend toward significance for the deep capillary plexus (P = 0.13).
We demonstrated moderate agreement between diabetic macular ischemia grading results for OCT angiography and conventional FA using standard ETDRS protocols. We also showed that OCT angiography images could be graded for diabetic macular ischemia with substantial intergrader agreement.
Purpose of Review
This paper systematically reviews the recent progress in diabetic retinopathy screening. It provides an integrated overview of the current state of knowledge of emerging techniques ...using artificial intelligence integration in national screening programs around the world. Existing methodological approaches and research insights are evaluated. An understanding of existing gaps and future directions is created.
Recent Findings
Over the past decades, artificial intelligence has emerged into the scientific consciousness with breakthroughs that are sparking increasing interest among computer science and medical communities. Specifically, machine learning and deep learning (a subtype of machine learning) applications of artificial intelligence are spreading into areas that previously were thought to be only the purview of humans, and a number of applications in ophthalmology field have been explored. Multiple studies all around the world have demonstrated that such systems can behave on par with clinical experts with robust diagnostic performance in diabetic retinopathy diagnosis. However, only few tools have been evaluated in clinical prospective studies.
Summary
Given the rapid and impressive progress of artificial intelligence technologies, the implementation of deep learning systems into routinely practiced diabetic retinopathy screening could represent a cost-effective alternative to help reduce the incidence of preventable blindness around the world.
Abstract Age-related macular degeneration (AMD) is the leading cause of severe visual loss in people aged 50 years or older in the developed world. In recent years, major advances have been made in ...the treatment of AMD, with the introduction of anti-angiogenic agents, offering the first hope of significant visual recovery for patients with neovascular AMD. In line with these advances, a new imaging modality—optical coherence tomography (OCT)—has emerged as an essential adjunct for the diagnosis and monitoring of patients with AMD. The ability to accurately interpret OCT images is thus a prerequisite for both retina specialists and comprehensive ophthalmologists. Despite this, the relatively recent introduction of OCT and the absence of formal training, coupled with rapid evolution of the technology, may make such interpretation difficult. These problems are compounded by the phenotypically heterogeneous nature of AMD and its complex morphology as visualized using OCT. We address these issues by summarizing the current understanding of OCT image interpretation in patients with AMD and describe how OCT can best be applied in clinical practice.
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.
Purpose To investigate the association between peripheral and central ischemia in diabetic retinopathy. Design Retrospective, cross-sectional. Methods Consecutive ultra-widefield fluorescein ...angiography images were collected from patients with diabetes over a 12-month period. Parameters quantified include the foveal avascular zone (FAZ) area, peripheral ischemic index, peripheral leakage index, and central retinal thickness measurements, as well as visual acuity. The peripheral ischemia or leakage index was calculated as the area of capillary nonperfusion or leakage, expressed as a percentage of the total retinal area. Results Forty-seven eyes of 47 patients were included. A moderate correlation was observed between the peripheral ischemia index and FAZ area (r = 0.49, P = .0001). A moderate correlation was also observed between the peripheral leakage index and FAZ area, but only in eyes that were laser naïve (r = 0.44, P = .02). A thinner retina was observed in eyes with macular ischemia (217 ± 81.8 μm vs 272 ± 36.0 μm) ( P = .02), but not peripheral ischemia (258 ± 76.3 μm vs 276 ± 68.0 μm) ( P = .24). The relationships between different patterns of peripheral and central macular pathology and visual acuity were evaluated in a step-wise multivariable regression model, and the variables that remained independently associated were age (r = 0.33, P = .03), FAZ area (r = 0.45, P = .02), and central retinal thickness (r = 0.38, P = .01), (R2 -adjusted = 0.36). Conclusions Ultra-widefield fluorescein angiography provides an insight into the relationships between diabetic vascular complications in the retinal periphery and central macula. Although we observed relationships between ischemia and vascular leakage in the macula and periphery, it was only macular ischemia and retinal thinning that was independently associated with a reduced visual function.
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.
The fovea is a depression in the center of the macula and is the site of the highest visual acuity. Optical coherence tomography (OCT) has contributed considerably in elucidating the pathologic ...changes in the fovea and is now being considered as an accompanying imaging method in drug development, such as antivascular endothelial growth factor and its safety profiling. Because animal numbers are limited in preclinical studies and automatized image evaluation tools have not yet been routinely employed, essential reference data describing the morphologic variations in macular thickness in laboratory cynomolgus monkeys are sparse to nonexistent. A hybrid machine learning algorithm was applied for automated OCT image processing and measurements of central retina thickness and surface area values. Morphological variations and the effects of sex and geographical origin were determined. Based on our findings, the fovea parameters are specific to the geographic origin. Despite morphological similarities among cynomolgus monkeys, considerable variations in the foveolar contour, even within the same species but from different geographic origins, were found. The results of the reference database show that not only the entire retinal thickness, but also the macular subfields, should be considered when designing preclinical studies and in the interpretation of foveal data.
Purpose To evaluate the clinical utility of optical coherence tomography angiography (OCTA) in patients with retinal vein occlusion (RVO), and to systematically compare OCTA images with changes seen ...on color fundus photography and fluorescein angiography (FA). Design Reliability analysis. Methods Eighty-one eyes of 76 patients with a history of RVO (branch, central, or hemicentral), both acute and chronic, underwent OCTA and color fundus photography. In 29 eyes, data were compared to FA imaging. Comparative and multimodal analysis of the 3 imaging procedures were performed. Results We identified good agreement between FA and OCTA scans centered on the macula for capillary nonperfusion (intraclass correlation coefficient ICC 0.825 for the 3 × 3-mm scan and 0.891 for the 8 × 8-mm scan). Agreement for area of capillary changes (dilation, pruning, and telangiectasia) was also substantial (ICC 0.712 for the 3 × 3-mm scan and 0.787 for the 8 × 8-mm scan). For foveal avascular zone grading, agreement was good for the 3 × 3-mm scan (kappa = 1.000 for radius and kappa = 0.799 for outline) but poor for the 8 × 8-mm scan (kappa = 0.156 for radius and kappa = 0.600 for outline). The quality of the images obtained was an important issue for OCTA, as 15.1% of scans were nongradable, particularly in patients unable to maintain fixation. Conclusions OCTA is a quick, reliable, and noninvasive method to evaluate the area of capillary nonperfusion and foveal avascular zone morphology in patients with RVO. However, good fixation is a requirement for acquisition of good-quality images.
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