{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:56:16Z","timestamp":1777521376025,"version":"3.51.4"},"reference-count":115,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000589","name":"Chief Scientist Office","doi-asserted-by":"publisher","award":["PCL\/20\/10"],"award-info":[{"award-number":["PCL\/20\/10"]}],"id":[{"id":"10.13039\/501100000589","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RE\/18\/6\/34217"],"award-info":[{"award-number":["RE\/18\/6\/34217"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Vascular endothelial growth factor inhibitors (VEGFis) have transformed the treatment of many retinal diseases, including diabetic maculopathy. Increasing evidence supports systemic absorption of intravitreal VEGFi and development of significant cardiorenal side effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a systematic review and meta-analysis (PROSPERO: CRD42020189037) of randomised controlled trials of intravitreal VEGFi treatments (bevacizumab, ranibizumab and aflibercept) for any eye disease. Outcomes of interest were cardiorenal side effects (hypertension, proteinuria, kidney function decline and heart failure). Fixed effects meta-analyses were conducted where possible.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>There were 78 trials (81 comparisons; 13\u2009175 participants) that met the criteria for inclusion: 47% were trials in diabetic eye disease. Hypertension (29 trials; 8570 participants) was equally common in VEGFi and control groups {7.3 versus 5.4%; relative risk [RR] 1.08 [95% confidence interval (CI) 0.91\u20131.28]}. New or worsening heart failure (10 trials; 3384 participants) had a similar incidence in VEGFi and control groups [RR 1.03 (95% CI 0.70\u20131.51)]. Proteinuria (5 trials; 1902 participants) was detectable in some VEGFi-treated participants (0.2%) but not controls [0.0%; RR 4.43 (95% CI 0.49\u201340.0)]. Kidney function decline (9 trials; 3471 participants) was similar in VEGFi and control groups. In participants with diabetic eye disease, the risk of all-cause mortality was higher in VEGFi-treated participants [RR 1.62 (95% CI 1.04\u20132.46)].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In trials of intravitreal VEGFi, we did not identify an increased risk of cardiorenal outcomes, although these outcomes were reported in only a minority of cases. There was an increased risk of death in VEGFi-treated participants with diabetic eye disease. Additional scrutiny of post-licensing observational data may improve the recognition of safety concerns in VEGFi-treated patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfac305","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T16:19:06Z","timestamp":1667319546000},"page":"1666-1681","source":"Crossref","is-referenced-by-count":13,"title":["A systematic review and meta-analysis of the effect of intravitreal VEGF inhibitors on cardiorenal outcomes"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6331-0178","authenticated-orcid":false,"given":"Jennifer S","family":"Lees","sequence":"first","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, College of Medical and Veterinary Sciences, University of Glasgow , Glasgow , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J H","family":"Dobbin","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, College of Medical and Veterinary Sciences, University of Glasgow , Glasgow , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin M P","family":"Elyan","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, College of Medical and Veterinary Sciences, University of Glasgow , Glasgow , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David F","family":"Gilmour","sequence":"additional","affiliation":[{"name":"Glasgow Centre for Ophthalmic Research, NHS Greater Glasgow and Clyde , Glasgow , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8848-9493","authenticated-orcid":false,"given":"Laurie P","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Faculty of Epidemiology and Population Health , London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ninian N","family":"Lang","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, College of Medical and Veterinary Sciences, University of Glasgow , Glasgow , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3387-2123","authenticated-orcid":false,"given":"Patrick B","family":"Mark","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, College of Medical and Veterinary Sciences, University of Glasgow , Glasgow , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"2023063001064509300_bib1","first-page":"561","article-title":"Anti-macular degeneration agents","volume":"18","author":"Rothen","year":"2005","journal-title":"Ophthalmol Clin North 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