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It has been associated with risk factors such as poor blood\u2010glucose control and hypertension, and it manifests prior to the long\u2010term benefits of optimizing glycaemic control. The majority of evidence supports an association of large and rapid reductions in blood\u2010glucose levels with early worsening of DR. Despite a general awareness of early worsening within the diabetes community, mechanisms to explain the phenomenon remain speculative. We provide an overview of early worsening of DR and its pathophysiology based on current data. We describe the phenomenon in various settings, including in patients receiving insulin\u2010 or non\u2010insulin\u2010based treatments, in those undergoing bariatric surgery, and in pregnant women. We discuss various mechanisms and theories that have been suggested to explain this paradoxical phenomenon, and we summarize the implications of these in clinical practice.<\/jats:p>","DOI":"10.1111\/dom.13538","type":"journal-article","created":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T06:41:06Z","timestamp":1537252866000},"page":"454-466","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":270,"title":["Worsening of diabetic retinopathy with rapid improvement in systemic glucose control: A review"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8519-4964","authenticated-orcid":false,"given":"Stephen C.","family":"Bain","sequence":"first","affiliation":[{"name":"School of Medicine Swansea University  Swansea UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Klufas","sequence":"additional","affiliation":[{"name":"Wills Eye Hospital\/Mid Atlantic Retina  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Ho","sequence":"additional","affiliation":[{"name":"Wills Eye Hospital\/Mid Atlantic Retina  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology and Metabolism, and Harris Manchester College University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,15]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-S010"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1909"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.12"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)90464-0"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.34.3.S74"},{"key":"e_1_2_14_7_1","first-page":"1","article-title":"Near\u2010normoglycemia and late diabetic complications. 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