Predicting Drusen Regression from OCT in Patients with Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries. The presence of drusen is the hallmark of early/intermediate AMD, and their sudden regression is strongly associated with the onset of late AMD. In this work we propose a predictive model of drusen regression using optical coherence tomography (OCT) based features. First, a series of automated image analysis steps are applied to segment and characterize individual drusen and their development. Second, from a set of quantitative features, a random forest classifiser is employed to predict the occurrence of individual drusen regression within the following 12 months. The predictive model is trained and evaluated on a longitudinal OCT dataset of 44 eyes from 26 patients using leave-one-patient-out cross-validation. The model achieved an area under the ROC curve of 0.81, with a sensitivity of 0.74 and a specificity of 0.73. The presence of hyperreflective foci and mean drusen signal intensity were found to be the two most important features for the prediction. This preliminary study shows that predicting drusen regression is feasible and is a promising step toward identification of imaging biomarkers of incoming regression

Stable registration of pathological 3D-OCT scans using retinal vessels

We propose a multiple scanner vendor registration method for pathological retinal 3D spectral domain optical coherence tomography volumes based on Myronenko’s Coherent Point Drift and our automated vessel shadow segmentation. Coherent point drift is applied to the segmented retinal vessel point sets used as landmarks to generate the registration parameters required. In contrast to other registration methods, our solution incorporates a landmark detection and extraction method that specifically limits the extraction of false positives and a registration method capable of handling any such noise in the landmark point sets. Our experiments show modified Hausdorff distance is reduced by a minimum of 91% between target and registered vessel point sets with at least 94% of bifurcations correctly overlapping based on ground truth, a significant improvement over current methods

Modeling Disease Progression In Retinal OCTs With Longitudinal Self-Supervised Learning

Longitudinal imaging is capable of capturing the static ana\-to\-mi\-cal structures and the dynamic changes of the morphology resulting from aging or disease progression. Self-supervised learning allows to learn new representation from available large unlabelled data without any expert knowledge. We propose a deep learning self-supervised approach to model disease progression from longitudinal retinal optical coherence tomography (OCT). Our self-supervised model takes benefit from a generic time-related task, by learning to estimate the time interval between pairs of scans acquired from the same patient. This task is (i) easy to implement, (ii) allows to use irregularly sampled data, (iii) is tolerant to poor registration, and (iv) does not rely on additional annotations. This novel method learns a representation that focuses on progression specific information only, which can be transferred to other types of longitudinal problems. We transfer the learnt representation to a clinically highly relevant task of predicting the onset of an advanced stage of age-related macular degeneration within a given time interval based on a single OCT scan. The boost in prediction accuracy, in comparison to a network learned from scratch or transferred from traditional tasks, demonstrates that our pretrained self-supervised representation learns a clinically meaningful information.Comment: Accepted for publication in the MICCAI 2019 PRIME worksho

Sustained Benefits of Ranibizumab with or without Laser in Branch Retinal Vein Occlusion: 24-Month Results of the BRIGHTER Study

Purpose To evaluate the long-term (24-month) efficacy and safety of ranibizumab 0.5 mg administered pro re nata (PRN) with or without laser using an individualized visual acuity (VA) stabilization criteria in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). Design Phase IIIb, open-label, randomized, active-controlled, 3-arm, multicenter study. Participants A total of 455 patients. Methods Patients were randomized (2:2:1) to ranibizumab 0.5 mg (n = 183), ranibizumab 0.5 mg with laser (n = 180), or laser (with optional ranibizumab 0.5 mg after month 6; n = 92). After initial 3 monthly injections, patients in the ranibizumab with or without laser arms received VA stabilization criteria-driven PRN treatment. Patients assigned to the laser arm received laser at the investigator's discretion. Main Outcome Measures Mean (and mean average) change in best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) from baseline to month 24, and safety over 24 months. Results A total of 380 patients (83.5%) completed the study. Ranibizumab with or without laser led to superior BCVA outcomes versus laser (monotherapy and combined with ranibizumab from month 6; 17.3/15.5 vs. 11.6 letters; P P P = 0.4259). A greater reduction in CSFT was seen with ranibizumab with or without laser versus laser monotherapy over 24 months from baseline (ranibizumab monotherapy −224.7 μm, ranibizumab with laser −248.9 μm, laser [monotherapy and combined with ranibizumab from month 6] −197.5 μm). Presence of macular ischemia did not affect BCVA outcome or treatment frequency. There were no reports of neovascular glaucoma or iris neovascularization. No new safety signals were identified. Conclusions The BRIGHTER study results confirmed the long-term efficacy and safety profile of PRN dosing driven by individualized VA stabilization criteria using ranibizumab 0.5 mg in patients with BRVO. Addition of laser did not lead to better functional outcomes or lower treatment need. The safety results were consistent with the well-established safety profile of ranibizumab

Individualized Stabilization Criteria-Driven Ranibizumab versus Laser in Branch Retinal Vein Occlusion

Purpose To compare the 6-month efficacy and safety profile of an individualized stabilization criteria-driven pro re nata (PRN) regimen of ranibizumab 0.5 mg with or without laser versus laser alone in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). Design A 24-month, prospective, open-label, randomized, active-controlled, multicenter, phase IIIb study. Participants A total of 455 patients. Methods Eligible patients were randomized 2:2:1 to receive ranibizumab (n = 183), ranibizumab with laser (n = 180), or laser only (n = 92). Patients treated with ranibizumab with or without laser received a minimum of 3 initial monthly ranibizumab injections until visual acuity (VA) stabilization, and VA-based PRN dosing thereafter. In the ranibizumab with laser and laser-only groups, laser was given at the investigator's discretion at a minimum interval of 4 months and if VA was <79 letters. Main Outcome Measures Mean change from baseline at month 6 in best-corrected visual acuity (BCVA) (primary end point) and central subfield thickness, and safety over 6 months. Exploratory objectives were to evaluate the influence of baseline BCVA, disease duration, and ischemia on BCVA outcomes at month 6. Results Baseline mean BCVA was 57.7 letters, and mean BRVO duration was 9.9 months. Ranibizumab with or without laser was superior to laser only in improving mean BCVA from baseline at month 6 (14.8 and 14.8 vs. 6.0 letters; both P < 0.0001; primary end point met). Patients with a shorter BRVO duration at baseline had a higher mean BCVA gain than those with a longer BRVO duration. Patients with a poor baseline VA had a better BCVA gain than those with a higher baseline VA, although final BCVA was lower in those with poor baseline VA. In the ranibizumab with or without laser groups, the presence of some macular ischemia at baseline did not influence mean BCVA gains. There were no new ocular or nonocular safety events. Conclusions Ranibizumab with an individualized VA-based regimen, with or without laser, showed statistically significant superior improvement in BCVA compared with laser alone in patients with BRVO. Overall, there were no new safety events other than those reported in previous studies

Automated Fovea Detection in Spectral Domain Optical Coherence Tomography Scans of Exudative Macular Disease

In macular spectral domain optical coherence tomography (SD-OCT) volumes, detection of the foveal center is required for accurate and reproducible follow-up studies, structure function correlation, and measurement grid positioning. However, disease can cause severe obscuring or deformation of the fovea, thus presenting a major challenge in automated detection. We propose a fully automated fovea detection algorithm to extract the fovea position in SD-OCT volumes of eyes with exudative maculopathy. The fovea is classified into 3 main appearances to both specify the detection algorithm used and reduce computational complexity. Based on foveal type classification, the fovea position is computed based on retinal nerve fiber layer thickness. Mean absolute distance between system and clinical expert annotated fovea positions from a dataset comprised of 240 SD-OCT volumes was 162.3 µm in cystoid macular edema and 262 µm in nAMD. The presented method has cross-vendor functionality, while demonstrating accurate and reliable performance close to typical expert interobserver agreement. The automatically detected fovea positions may be used as landmarks for intra- and cross-patient registration and to create a joint reference frame for extraction of spatiotemporal features in “big data.” Furthermore, reliable analyses of retinal thickness, as well as retinal structure function correlation, may be facilitated

Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion: Twelve-Month Results of the CRYSTAL Study

Purpose To assess the 12-month efficacy and safety profile of an individualized regimen of ranibizumab 0.5 mg driven by stabilization criteria in patients with macular edema secondary to central retinal vein occlusion (CRVO). Design A 24-month, prospective, open-label, single-arm, multicenter study. Participants Three hundred fifty-seven patients. Methods Patients were treated with monthly ranibizumab 0.5-mg injections (minimum of 3 injections) until stable visual acuity (VA) was maintained for 3 consecutive months. Thereafter, ranibizumab 0.5 mg was dosed as needed if monthly monitoring indicated a loss of VA resulting from disease activity. Main Outcome Measures Mean change from baseline at month 12 in best-corrected VA (BCVA; primary end point) and safety over 12 months. The efficacy of this regimen in subgroups categorized by baseline BCVA score, CRVO duration, or presence of macular ischemia (exploratory analysis). Results At baseline, the mean BCVA was 53.0 letters and mean CRVO duration was 8.9 months (median, 2.4 months). Ranibizumab 0.5-mg treatment resulted in a statistically significant mean gain in BCVA from baseline at month 12 of 12.3 letters (standard deviation [SD], 16.72 letters; P < 0.0001). The mean number of ranibizumab injections up to month 12 was 8.1 (SD, 2.77). At month 12, mean BCVA gains were similar with or without macular ischemia at baseline (11.6 vs. 12.1 letters); the mean BCVA gain was higher with baseline CRVO duration of less than 3 months (13.4 letters) than with a longer duration (≥3-<9 months, 11.1 letters; ≥9 months, 10.9 letters). Patients with lower baseline BCVA had larger mean BCVA gains at month 12 than those with higher baseline BCVA (≤39/40-59/≥60 and 18.0/12.7/8.9 letters, respectively), although the absolute BCVA at month 12 was higher with higher baseline BCVA. No new ocular or nonocular safety events were observed. Conclusions An individualized dosing regimen of ranibizumab 0.5 mg driven by stabilization criteria for up to 12 months resulted in significant BCVA gain in a broad population of patients with macular edema secondary to CRVO, including those with macular ischemia at baseline. The safety findings were consistent with those reported in previous ranibizumab studies in patients with CRVO

Curr Opin Ophthalmol

The application of artificial intelligence (AI) technologies in screening and diagnosing retinal diseases may play an important role in telemedicine and has potential to shape modern healthcare ecosystems, including within ophthalmology. In this article, we examine the latest publications relevant to AI in retinal disease and discuss the currently available algorithms. We summarize four key requirements underlining the successful application of AI algorithms in real-world practice: processing massive data; practicability of an AI model in ophthalmology; policy compliance and the regulatory environment; and balancing profit and cost when developing and maintaining AI models. The Vision Academy recognizes the advantages and disadvantages of AI-based technologies and gives insightful recommendations for future directions