Automated Detection of Leakage in Fluorescein Angiography Images with Application to Malarial Retinopathy

The detection and assessment of leakage in retinal fluorescein angiogram images is important for the management of a wide range of retinal diseases. We have developed a framework that can automatically detect three types of leakage (large focal, punctate focal, and vessel segment leakage) and validated it on images from patients with malarial retinopathy. This framework comprises three steps: vessel segmentation, saliency feature generation and leakage detection. We tested the effectiveness of this framework by applying it to images from 20 patients with large focal leak, 10 patients with punctate focal leak, and 5,846 vessel segments from 10 patients with vessel leakage. The sensitivity in detecting large focal, punctate focal and vessel segment leakage are 95%, 82% and 81%, respectively, when compared to manual annotation by expert human observers. Our framework has the potential to become a powerful new tool for studying malarial retinopathy, and other conditions involving retinal leakage

A method for quantifying sectoral optic disc pallor in fundus photographs and its association with peripapillary RNFL thickness

Purpose: To develop an automatic method of quantifying optic disc pallor in fundus photographs and determine associations with peripapillary retinal nerve fibre layer (pRNFL) thickness. Methods: We used deep learning to segment the optic disc, fovea, and vessels in fundus photographs, and measured pallor. We assessed the relationship between pallor and pRNFL thickness derived from optical coherence tomography scans in 118 participants. Separately, we used images diagnosed by clinical inspection as pale (N=45) and assessed how measurements compared to healthy controls (N=46). We also developed automatic rejection thresholds, and tested the software for robustness to camera type, image format, and resolution. Results: We developed software that automatically quantified disc pallor across several zones in fundus photographs. Pallor was associated with pRNFL thickness globally (\b{eta} = -9.81 (SE = 3.16), p < 0.05), in the temporal inferior zone (\b{eta} = -29.78 (SE = 8.32), p < 0.01), with the nasal/temporal ratio (\b{eta} = 0.88 (SE = 0.34), p < 0.05), and in the whole disc (\b{eta} = -8.22 (SE = 2.92), p < 0.05). Furthermore, pallor was significantly higher in the patient group. Lastly, we demonstrate the analysis to be robust to camera type, image format, and resolution. Conclusions: We developed software that automatically locates and quantifies disc pallor in fundus photographs and found associations between pallor measurements and pRNFL thickness. Translational relevance: We think our method will be useful for the identification, monitoring and progression of diseases characterized by disc pallor/optic atrophy, including glaucoma, compression, and potentially in neurodegenerative disorders.Comment: 44 pages, 20 figures, 7 tables, submitte

How Does Blood-Retinal Barrier Breakdown Relate to Death and Disability in Pediatric Cerebral Malaria?

Background In cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling. Methods We used retinal angiography to study blood-retinal barrier integrity. We analyzed retinal leakage, histopathology, brain MRI, and associations with death and neurological disability in prospective cohorts of Malawian children with cerebral malaria. Results Three types of retinal leakage were seen: Large focal leak (LFL), punctate leak (PL) and vessel leak. LFL and PL were associated with death (OR 13.20, 95%CI 5.21-33.78 and 8.58, 2.56-29.08 respectively), and brain swelling (p<0.05). Vessel leak and macular non-perfusion were associated with neurological disability (3.71, 1.26-11.02 and 9.06, 1.79-45.90). LFL was observed as an evolving retinal hemorrhage. A core of fibrinogen and monocytes was found in 39 (93%) white-centered hemorrhages. Conclusions Blood-retina barrier breakdown occurs in three patterns in cerebral malaria. Associations between LFL, brain swelling, and death suggest that the rapid accumulation of cerebral hemorrhages, with accompanying fluid egress, may cause fatal brain swelling. Vessel leak from barrier dysfunction, and non-perfusion were not associated with severe brain swelling, but with neurological deficits, suggesting hypoxic injury in survivors