{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:38:44Z","timestamp":1792471124360,"version":"4.5.0"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000329","name":"Novo Nordisk UK Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hybrid closed\u2010loop (HCL) systems achieve rapid, algorithm\u2010driven improvements in glycaemia in type 1 diabetes (T1D). Paradoxically, rapid improvement in glycaemic control is associated with early worsening of diabetic retinopathy (EWDR), a phenomenon established in the intensive insulin therapy era. Whether HCL initiation carries a clinically meaningful EWDR risk is unknown. No systematic review has previously addressed this question.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review and structured quantitative synthesis was performed using study\u2010level estimates only (PROSPERO CRD:420261391951). MEDLINE, SCOPUS and Web of Science were searched to 14th May 2026. Studies reporting retinal outcomes in people with T1D initiating any HCL system were eligible. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using ROBINS\u2010I and certainty of evidence using the GRADE framework. EWDR incidence was summarised using study\u2010level proportions, and comparative studies were summarised using study\u2010specific risk ratios for HCL versus control therapy. Given substantial heterogeneity in EWDR definitions, retinal assessment timing, follow\u2010up duration, and comparator groups, no pooled or meta\u2010analytic estimates were derived.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight studies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091487 participants; 860 HCL users) were included; all were observational and six were retrospective. EWDR varied markedly with the timing of retinal assessment. In studies assessing the retina within \u2264\u200912\u2009months of HCL initiation, EWDR rates ranged from 8.9% to 26.5%. Studies with longer follow\u2010up reported lower rates of retinal worsening or incident DR, 6.7% at 24\u2009months and 6.1% over a mean follow\u2010up of 4.9\u2009years, suggesting that these studies may capture background DR progression rather than true early worsening. Three comparative studies included 177 HCL users and 315 controls; EWDR study\u2010specific risk ratios were directionally inconsistent, ranging from 0.32 to 1.51, and were therefore not pooled. The most consistently identified risk factors were higher baseline HbA1c and older age. The magnitude of HbA1c reduction was not a consistent predictor of EWDR in the HCL context, in contrast to pre\u2010HCL era evidence. Risk of bias ranged from moderate to critical and certainty of evidence was very low for all outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Study\u2010defined retinal worsening was reported in a minority of participants. The current evidence base is dominated by retrospective studies, variable retinal assessment timing, and inconsistent EWDR definitions. Well\u2010designed prospective studies with protocol\u2010specified retinal surveillance anchored to HCL initiation are required to generate reliable incidence estimates, identify risk factors, determine visual consequences, and inform standardised screening guidance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71084","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:38:56Z","timestamp":1783568336000},"page":"8878-8894","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Early Worsening of Diabetic Retinopathy Following Initiation of Hybrid Closed\u2010Loop\/Automated Insulin Delivery Systems in Type 1 Diabetes: A Systematic Review and Structured Study\u2010Level Synthesis"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9991-7369","authenticated-orcid":false,"given":"Matthew","family":"Anson","sequence":"first","affiliation":[{"name":"Diabetes &amp; Endocrinology Research, Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"},{"name":"Department of Diabetes &amp; Endocrinology University Hospitals of Liverpool Group  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Iqbal","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health The University of Sheffield  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shazli","family":"Azmi","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Weston","sequence":"additional","affiliation":[{"name":"Department of Diabetes &amp; Endocrinology University Hospitals of Liverpool Group  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Diabetes &amp; Endocrinology University Hospitals of Liverpool Group  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahreen","family":"Choudhury","sequence":"additional","affiliation":[{"name":"Sheffield Medical School The University of Sheffield  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Health Data Science, Institute of Population Health University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Sciences, Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip I.","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Sciences, Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"},{"name":"St Pauls Eye Unit University Hospitals of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uazman","family":"Alam","sequence":"additional","affiliation":[{"name":"Diabetes &amp; 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