Comparison of retinal regions-of-interest imaged by OCT for the classification of intermediate AMD

To study whether it is possible to differentiate intermediate age-related macular degeneration (AMD) from healthy controls using partial optical coherence tomography (OCT) data, that is, restricting the input B-scans to certain pre-defined regions of interest (ROIs). A total of 15744 B-scans from 269 intermediate AMD patients and 115 normal subjects were used in this study (split on subject level in 80% train, 10% validation and 10% test). From each OCT B-scan, three ROIs were extracted: retina, complex between retinal pigment epithelium (RPE) and Bruch membrane (BM), and choroid (CHO). These ROIs were obtained using two different methods: masking and cropping. In addition to the six ROIs, the whole OCT B-scan and the binary mask corresponding to the segmentation of the RPE-BM complex were used. For each subset, a convolutional neural network (based on VGG16 architecture and pre-trained on ImageNet) was trained and tested. The performance of the models was evaluated using the area under the receiver operating characteristic (AUROC), accuracy, sensitivity, and specificity. All trained models presented an AUROC, accuracy, sensitivity, and specificity equal to or higher than 0.884, 0.816, 0.685, and 0.644, respectively. The model trained on the whole OCT B-scan presented the best performance (AUROC = 0.983, accuracy = 0.927, sensitivity = 0.862, specificity = 0.913). The models trained on the ROIs obtained with the cropping method led to significantly higher outcomes than those obtained with masking, with the exception of the retinal tissue, where no statistically significant difference was observed between cropping and masking (p = 0.47). This study demonstrated that while using the complete OCT B-scan provided the highest accuracy in classifying intermediate AMD, models trained on specific ROIs such as the RPE-BM complex or the choroid can still achieve high performance

Performance of classification systems for age-related macular degeneration in the rotterdam study

Purpose: To compare frequently used classification systems for age-related macular degeneration(AMD) in their abilty to predictlate AMD. Methods:Intotal,9066participantsfromthepopulation-basedRotterdamStudywere followedupforprogressionofAMDduringastudyperiodupto30years.AMDlesions weregradedoncolorfundusphotographsafterconfirmationonotherimagemodalities andgroupedatbaselineaccordingtosixclassificationsystems.LateAMDwasdefinedas geographicatrophyorchoroidalneovascularization.Incidencerate(IR)andcumulative incidence(CuI)oflateAMDwerecalculated,andKaplan-Meierplotsandareaunderthe operating characteristics curves(AUCs)wereconstructed. Results: A total of 186 persons developed incident late AMD during a mean follow-up timeof8.7years.TheAREDSsimplifiedscaleshowedthehighestIRforlateAMDat104 cases/1000 py for ages 75 years. The 3-Continent harmonization classification provided the most stable progression. Drusen area >10% ETDRS grid (hazard ratio 30.05, 95% confidence interval [CI] 19.25–46.91) was most prognostic of progression. The highest AUC of late AMD (0.8372, 95% CI: 0.8070-0.8673) was achieved when all AMD features present at base line were included. Conclusions: Highest turnover rates from intermediate to late AMD were provided by the AREDS simplified scale and the Rotterdam classification. The 3-Continent harmonization classification showed the most stable progression. All features, especially drusenarea,contribute to late AMD prediction. Translational Relevance: Findings will help stakeholders select appropriate classification systems for screening,deep learning algorithms, or trials

Cellular and molecular dynamics in the foreign body reaction

Intracorporally implanted materials, such as medical devices, will provoke the body to initiate an inflammatory reaction. This inflammatory reaction to implanted materials is known as the foreign body reaction (FBR) and is characterized by 3 distinct phases: onset, progression, and resolution. The FBR proceeds in the creation of a dynamic microenvironment that is spatially well organized. The progression of the FBR is regulated by soluble mediators, such as cytokines, chemokines, and matrix metalloproteinases ( MMPs), which are produced locally by tissue cells and infiltrated inflammatory cells. These soluble mediators orchestrate the cascade of cellular processes in the microenvironment that accompanies the FBR, consisting of cellular activation, angiogenesis, extravasation, migration, phagocytosis, and, finally, fibrosis. The nature of the FBR requires that the soluble mediators act in a spatial and temporally regulated manner as well. This regulation is well known for several inflammatory processes, but scarce knowledge exists about the intricate relationship between the FBR and the expression of soluble mediators. This review discusses the key processes during the initiation, progression, and resolution phase, with emphasis on the role of soluble mediators. Besides other sites of implantation, we focus on the subcutaneous implantation model

Cytokine and chemokine dynamics differ between rats and mice after collagen implantation

Implanted scaffold materials induce an inflammatory reaction known as the 'foreign body reaction' (FBR). We hypothesized that the observed difference in FBR between rats and mice correlate with different expression dynamics of cytokines and chemokines, which are key orchestrators of the FBR. After implantation of hexamethylene diisocyanate cross-linked dermal sheep collagen, the overall gene expression pattern of IL-1, IL-6, IL-10, TNF alpha, CXCL1/KC, CXCL2/MIP2 and CCL2/MCP1 was roughly similar for the two species. During the onset of the FBR these genes were maximally expressed in rats and mice, after which the expression decreased to basal levels. The expression of CCL3/MIP1 alpha had a similar course, yet it increased after the progression phase of the FBR in both species. The expression of cytokines and chemokines in sham-operated animals was low throughout, showing that the implanted material by itself exerted the changes in gene expression of the invading cells. During the progression, genes encoding the PMN attractants CXCL1/KC and CXCL2/MIP2 were more highly expressed in mice than in rats, which would explain the prolonged presence of PMNs in mice during the FBR. Additionally, the strong induction of IFN gamma in rats coincided with a higher phagocytotic activity by macrophages. Throughout the FBR, the expression of TGF beta was constitutive and high in both species, but increased in mice during the progression phase. This could explain the extensive stroma formation during the murine FBR. Unexpectedly, the stronger expression of TNFa and CCL3/MIP1 alpha in mice, did not result in high macrophage attraction or phagocytosis of the implanted collagen disks. Copyright (c) 2007 John Wiley & Sons, Ltd