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

Age-Related Macular Degeneration and Diabetic Retinopathy

This reprint includes contributions from leaders in the field of personalized medicine in ophthalmology. The contributions are diverse and cover pre-clinical and clinical topics. We hope you enjoy reading the articles

Modern trends in diagnostics and prediction of results of anti-vascular endothelial growth factor therapy of pigment epithelial detachment in neovascular agerelated macular degeneration using deep machine learning method (literature review)

Detachment of the pigment epithelium is the separation of the basement membrane of the retinal pigment epithelium from the inner collagen layer of Bruch’s membrane, which occurs in 80 % of cases in patients with neovascular age-related macular degeneration. The outcome of anti-VEGF therapy for pigment epithelial detachment may be adherence of the pigment epithelium, the formation of pigment epithelium tear, or preservation of the detachment. The pigment epithelium tear of 3–4th degrees can lead to a sharp decrease in visual acuity.Most retrospective studies confi rm the absence of a proven correlation between anatomical and functional outcomes in the treatment of pigment epithelial detachment in cases of maintaining the integrity of the pigment epithelium monolayer, and therefore the main attention of researchers is focused on studying the morphological features of pigment epithelial detachment during therapy with angiogenesis inhibitors. Modern technologies of spectral optical coherence tomography make it possible to evaluate detailed quantitative parameters of pigment epithelium detachment, such as height, width, maximum linear diameter, area, volume and refl ectivity within the detachment.Groups of Russian and foreign authors identify various biomarkers recorded on optical coherence tomography images. Dynamic registration of such biomarkers expands the ability of clinicians to predict morphological changes in pigment epithelial detachment during anti-VEGF therapy, as well as to optimize treatment regimens to prevent complications in the form of pigment epithelium tear leading to a decrease in visual acuity.Modern methods of deep machine learning and the use of neural networks allow achieving higher accuracy in diff erentiating the types of retinal fluids and automating the quantitative determination of fl uid under the pigment epithelium. These technologies allow achieving a high level of compliance with manual expert assessment and increasing the accuracy and speed of predicting morphological results of treatment of pigment epithelium detachments

Detection of macular atrophy in age-related macular degeneration aided by artificial intelligence

INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment worldwide. The endpoint of AMD, both in its dry or wet form, is macular atrophy (MA) which is characterized by the permanent loss of the RPE and overlying photoreceptors either in dry AMD or in wet AMD. A recognized unmet need in AMD is the early detection of MA development. AREAS COVERED: Artificial Intelligence (AI) has demonstrated great impact in detection of retinal diseases, especially with its robust ability to analyze big data afforded by ophthalmic imaging modalities, such as color fundus photography (CFP), fundus autofluorescence (FAF), near-infrared reflectance (NIR), and optical coherence tomography (OCT). Among these, OCT has been shown to have great promise in identifying early MA using the new criteria in 2018. EXPERT OPINION: There are few studies in which AI-OCT methods have been used to identify MA; however, results are very promising when compared to other imaging modalities. In this paper, we review the development and advances of ophthalmic imaging modalities and their combination with AI technology to detect MA in AMD. In addition, we emphasize the application of AI-OCT as an objective, cost-effective tool for the early detection and monitoring of the progression of MA in AMD

Detection of macular atrophy in age-related macular degeneration aided by artificial intelligence

INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment worldwide. The endpoint of AMD, both in its dry or wet form, is macular atrophy (MA) which is characterized by the permanent loss of the RPE and overlying photoreceptors either in dry AMD or in wet AMD. A recognized unmet need in AMD is the early detection of MA development. AREAS COVERED: Artificial Intelligence (AI) has demonstrated great impact in detection of retinal diseases, especially with its robust ability to analyze big data afforded by ophthalmic imaging modalities, such as color fundus photography (CFP), fundus autofluorescence (FAF), near-infrared reflectance (NIR), and optical coherence tomography (OCT). Among these, OCT has been shown to have great promise in identifying early MA using the new criteria in 2018. EXPERT OPINION: There are few studies in which AI-OCT methods have been used to identify MA; however, results are very promising when compared to other imaging modalities. In this paper, we review the development and advances of ophthalmic imaging modalities and their combination with AI technology to detect MA in AMD. In addition, we emphasize the application of AI-OCT as an objective, cost-effective tool for the early detection and monitoring of the progression of MA in AMD

Learn Single-horizon Disease Evolution for Predictive Generation of Post-therapeutic Neovascular Age-related Macular Degeneration

Most of the existing disease prediction methods in the field of medical image processing fall into two classes, namely image-to-category predictions and image-to-parameter predictions. Few works have focused on image-to-image predictions. Different from multi-horizon predictions in other fields, ophthalmologists prefer to show more confidence in single-horizon predictions due to the low tolerance of predictive risk. We propose a single-horizon disease evolution network (SHENet) to predictively generate post-therapeutic SD-OCT images by inputting pre-therapeutic SD-OCT images with neovascular age-related macular degeneration (nAMD). In SHENet, a feature encoder converts the input SD-OCT images to deep features, then a graph evolution module predicts the process of disease evolution in high-dimensional latent space and outputs the predicted deep features, and lastly, feature decoder recovers the predicted deep features to SD-OCT images. We further propose an evolution reinforcement module to ensure the effectiveness of disease evolution learning and obtain realistic SD-OCT images by adversarial training. SHENet is validated on 383 SD-OCT cubes of 22 nAMD patients based on three well-designed schemes based on the quantitative and qualitative evaluations. Compared with other generative methods, the generative SD-OCT images of SHENet have the highest image quality. Besides, SHENet achieves the best structure protection and content prediction. Qualitative evaluations also demonstrate that SHENet has a better visual effect than other methods. SHENet can generate post-therapeutic SD-OCT images with both high prediction performance and good image quality, which has great potential to help ophthalmologists forecast the therapeutic effect of nAMD

The Genotype-Phenotype Correlation of the key features of Non-Proliferative Diabetic Retinopathy

Diabetic Retinopathy (DR) is a leading cause of visual impairment but its pathophysiology is not well understood. Moderate/severe non-proliferative DR (NPDR) is characterised by the presence of three features: deep haemorrhages (DH), venous beading (VB) and intraretinal microvascular abnormalities (IRMA). They are grouped together as risk factors for progression to sight threatening DR. It remains unclear whether these individual features have similar pathophysiologies, and whether they respond equally to anti-VEGF, a new therapy for NPDR. Optomap images of 504 NPDR eyes were examined to evaluate the distribution and prevalence of these three features. DNA samples from 199 patients with NPDR and 397 diabetic patients with no DR were collected. The genotype of specific candidate genes were evaluated in patients with DR, VB or IRMA vs no DR. Optical coherence tomography angiography (OCTA) images of 30 patients were examined for focal ischemia adjacent to VB and IRMA. The responses of these three features to anti-VEGF treatment were also re-examined in the images from the CLARITY trial. DH were present in most cases of NPDR. VB and IRMA did not always co-exist in the same eye and when they do, were often in different locations. VEGF, TGFb-1 and ARHGAP22 polymorphisms (ischaemia-related genes) were more common in patients with DR and IRMA, but not VB. Areas of focal ischaemia were more frequently adjacent to IRMA than to VB. DH and IRMA responded to anti-VEGF therapy but VB did not. These findings suggest that VB and IRMA do not share the same pathophysiology, and that IRMA are more likely to be ischaemic driven. Nonetheless, some IRMA may not be driven by ischaemia as they have no adjacent ischaemia on OCTA, do not carry the specific genotype, and do not respond to anti-VEGF. Furthermore, patients with VB may not benefit from anti-VEGF therapy

Automating the eye examination using optical coherence tomography

Optical coherence tomography (OCT) devices are becoming ubiquitous in eye clinics worldwide to aid the diagnosis and monitoring of eye disease. Much of this uptake relates to the ability to non-invasively capture micron-resolution images, enabling objective and quantitative data to be obtained from ocular structures. Although safe and reasonably quick to perform, the costs involved with operating OCT devices are not trivial, and the requirement for OCT and other imaging in addition to other clinical measures is placing increasing demand on ophthalmology clinics, contributing to fragmented patient pathways and often extended waiting times. In this thesis, a novel “binocular optical coherence tomography” system that seeks to overcome some of the limitations of current commercial OCT systems, is clinically evaluated. This device incorporates many aspects of the eye examination into a single patient-operated instrument, and aims to improve the efficiency and quality of eye care while reducing the overall labour and equipment costs. A progressive framework of testing is followed that includes human factors and usability testing, followed by early stage diagnostic studies to assess the agreement, repeatability, and reproducibility of individual diagnostic features. Health economics analysis of the retinal therapy clinic is used to model cost effectiveness of current practice and with binocular OCT implementation. The binocular OCT and development of other low-cost OCT systems may improve accessibility, however there remains a relative shortage of experts to interpret the images. Artificial intelligence (AI) is likely to play a role in rapid and automated image classification. This thesis explores the application of AI within retinal therapy clinics to predict the onset of exudative age-related macular degeneration in fellow eyes of patients undergoing treatment in their first eye. Together with automated and simultaneous imaging of both eyes with binocular OCT and the potential for low-cost patient-facing systems, AI is likely to have a role in personalising management plans, especially in a future where preventive treatments are available