{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:10:35Z","timestamp":1784005835589,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of the study was to determine the efficacy and safety of combined anti\u2010VEGF and steroid therapy in treatment refractory DME patients. We conducted a systematic review and meta\u2010analysis of peer\u2010reviewed articles reporting on visual, anatomical and adverse outcomes to compare the efficacy and safety of combined intravitreal anti\u2010VEGF\/steroids versus anti\u2010VEGF monotherapy for refractory DME. Seven studies (4 RCTs and 3 observational studies) reporting on 452 eyes were included. Our systematic review showed that combination therapy is significantly more effective for anatomical outcomes in the treatment of resistant DME compared to anti\u2010VEGF monotherapy in six studies. Two studies found that addition of intravitreal steroids promoted faster visual improvement, but not significantly better final visual outcomes compared to anti\u2010VEGF monotherapy. Combination therapy was associated with a higher incidence of IOP\u2010related adverse events (RR\u2009=\u20090.10, 95% CI\u2009=\u2009[0.02, 0.42], <jats:italic>p<\/jats:italic>\u2009=\u20090.002) and cataract\u2010related adverse events (RR\u2009=\u20090.10, 95% CI\u2009=\u2009[0.01, 0.71], <jats:italic>p<\/jats:italic>\u2009=\u20090.02). Our systematic review and meta\u2010analysis of seven studies and 452 eyes revealed that combination therapy of anti\u2010VEGF and steroid intravitreal drugs in the management of treatment refractory DME resulted in superior anatomical outcomes in all but one study. Combination therapy led to superior short\u2010term visual outcomes in two studies, while others reported no difference between treatment groups. Meta\u2010analysis revealed that combination therapy was associated with more adverse events. Future research should provide guidance on the standard definitions for treatment resistance and therapeutic alternatives for DME patients with sub\u2010optimal response to anti\u2010VEGF treatment.<\/jats:p>","DOI":"10.1111\/aos.15724","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T04:10:44Z","timestamp":1687839044000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Anti\u2010VEGF and steroid combination therapy relative to anti\u2010VEGF mono therapy for the treatment of refractory DME: A systematic review of efficacy and meta\u2010analysis of safety"],"prefix":"10.1111","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4714-738X","authenticated-orcid":false,"given":"Amin","family":"Hatamnejad","sequence":"first","affiliation":[{"name":"Michael DeGroote School of Medicine McMaster University  Hamilton Ontario Canada"},{"name":"Octane Imaging Lab  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Orr","sequence":"additional","affiliation":[{"name":"Octane Imaging Lab  Toronto Ontario Canada"},{"name":"Vitreous Retina Macula Specialists of Toronto  Etobicoke Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"Dadak","sequence":"additional","affiliation":[{"name":"Michael DeGroote School of Medicine McMaster University  Hamilton Ontario Canada"},{"name":"Octane Imaging Lab  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8928-5599","authenticated-orcid":false,"given":"Arshad","family":"Khanani","sequence":"additional","affiliation":[{"name":"Sierra Eye Associates  Reno Nevada USA"},{"name":"The University of Nevada, Reno School of Medicine  Reno Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5859-8162","authenticated-orcid":false,"given":"Rishi","family":"Singh","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Martin Health System, Cleveland Clinic  Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Netan","family":"Choudhry","sequence":"additional","affiliation":[{"name":"Octane Imaging Lab  Toronto Ontario Canada"},{"name":"Vitreous Retina Macula Specialists of Toronto  Etobicoke Ontario Canada"},{"name":"Department of Ophthalmology and Vision Sciences University of Toronto  Toronto Ontario Canada"},{"name":"Cleveland Clinic Canada  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,26]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"483","article-title":"Intravitreal bevacizumab with or without triamcinolone for refractory diabetic macular edema; 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