The reactome pathway knowledgebase.

The Reactome Knowledgebase (https://reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations in a single consistent data model, an extended version of a classic metabolic map. Reactome functions both as an archive of biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. To extend our ability to annotate human disease processes, we have implemented a new drug class and have used it initially to annotate drugs relevant to cardiovascular disease. Our annotation model depends on external domain experts to identify new areas for annotation and to review new content. New web pages facilitate recruitment of community experts and allow those who have contributed to Reactome to identify their contributions and link them to their ORCID records. To improve visualization of our content, we have implemented a new tool to automatically lay out the components of individual reactions with multiple options for downloading the reaction diagrams and associated data, and a new display of our event hierarchy that will facilitate visual interpretation of pathway analysis results.

Early versus late switch: How long should we extend the anti-vascular endothelial growth factor therapy in unresponsive diabetic macular edema patients?

PURPOSE: To compare the results of early versus late switch to the dexamethasone intravitreal implant Ozurdex® in patients with diabetic macular edema who had a poor response to vascular endothelial growth factor inhibitors. METHODS: Retrospective and single-center study conducted, in a real setting, on consecutive diabetic macular edema patients who were switch to an intravitreal dexamethasone implant after a poor response to anti-vascular endothelial growth factor treatment. Study sample was divided into two groups: (1) early-switch group, included those eyes who received three anti-vascular endothelial growth factor injections before switch and (2) late-switch group, included those eyes that received six or more anti-vascular endothelial growth factor injections before switch. The primary end-point was the difference in mean change in best-corrected visual acuity and in central subfoveal thickness. RESULTS: A total of 69 (31 early-switch group and 38 late-switch group) eyes were included. In the early-switch group, median (25-75 quartile range) best-corrected visual acuity significantly increase from 0.2 (0.2-0.5) at baseline to 0.4 (0.3 -0.7) at month 24 (p = 0.0043). Whereas, in the late-switch group, best-corrected visual acuity did not increase (p = 0.8602). Central subfoveal thickness was significantly reduced in both early- and late-switch groups, p = 0.0002 and 0.0038, respectively. The proportion of eyes obtaining a central subfoveal thickness reduction ⩾ 10% was significantly greater in the early-switch group than in the late-switch group (71.0% vs 47.4%, respectively, p = 0.0498). Three (9.7%) and 10 (26.3%) eyes have developed ocular hypertension during the study in the early- and late-switch groups, respectively, p = 0.0816. CONCLUSION: Early switch to Ozurdex in patients who did not adequately respond to anti-vascular endothelial growth factor therapy provided better functional and anatomical outcomes.