{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:15:39Z","timestamp":1792462539788,"version":"4.5.0"},"reference-count":37,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["NIHR132948"],"award-info":[{"award-number":["NIHR132948"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"Background<\/jats:title>\nDiabetic retinopathy is a major cause of sight loss in people with diabetes. The most severe form, proliferative diabetic retinopathy, carries a high risk of vision loss, vitreous haemorrhage, macular oedema and other harms. Panretinal photocoagulation is the primary treatment for proliferative diabetic retinopathy. Anti-vascular endothelial growth factor drugs are used to treat various eye conditions and may be beneficial for people with diabetic retinopathy.<\/jats:p>\n<\/jats:sec>\nObjective<\/jats:title>\nTo investigate the efficacy and safety of anti-vascular endothelial growth factor therapy for the treatment of diabetic retinopathy when compared to panretinal photocoagulation.<\/jats:p>\n<\/jats:sec>\nMethods<\/jats:title>\nA systematic review and network meta-analysis of all published randomised controlled trials comparing anti-vascular endothelial growth factor (alone or in combination with panretinal photocoagulation) to panretinal photocoagulation in people with diabetic retinopathy. The database searches were updated in May 2023. Trials where the primary focus was treatment of macular oedema or vitreous haemorrhage were excluded.<\/jats:p>\n<\/jats:sec>\nResults<\/jats:title>\nA total of 14 trials were included: 3 of aflibercept, 5 of bevacizumab and 6 of ranibizumab. Two trials were of patients with non-proliferative diabetic retinopathy; all others were in proliferative diabetic retinopathy. Overall, anti-vascular endothelial growth factor was slightly better than panretinal photocoagulation at preventing vision loss, measured as best corrected visual acuity, at up to 2 years follow-up [mean difference in the logarithm of the minimum angle of resolution \u22120.089 (or 3.6 Early Treatment Diabetic Retinopathy Study letters), 95% confidence interval \u22120.180 to \u22120.019]. There was no clear evidence of any difference between the anti-vascular endothelial growth factors, but the potential for bias complicated the comparison. One trial found no benefit of anti-vascular endothelial growth factor over panretinal photocoagulation after 5 years. Anti-vascular endothelial growth factor was superior to panretinal photocoagulation at preventing macular oedema (relative risk 0.29, 95% confidence interval 0.18 to 0.49) and vitreous haemorrhage (relative risk 0.77, 95% confidence interval 0.61 to 0.99). There was no clear evidence that the effectiveness of anti-vascular endothelial growth factor varied over time.<\/jats:p>\n<\/jats:sec>\nConclusions<\/jats:title>\nAnti-vascular endothelial growth factor injections reduce vision loss when compared to panretinal photocoagulation, but the benefit is small and unlikely to be clinically meaningful. Anti-vascular endothelial growth factor may have greater benefits for preventing complications such as macular oedema. Observational studies extending follow-up beyond the 1-year duration of most trials are needed to investigate the longer-term effects of repeated anti-vascular endothelial growth factor injections.<\/jats:p>\n<\/jats:sec>\nFunding<\/jats:title>\nThis article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR132948.<\/jats:p>\n<\/jats:sec>","DOI":"10.3310\/pcgv5709","type":"journal-article","created":{"date-parts":[[2024,12,14]],"date-time":"2024-12-14T09:45:26Z","timestamp":1734169526000},"page":"1-71","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Anti-VEGF drugs compared with laser photocoagulation for the treatment of diabetic retinopathy: a systematic review and meta-analysis"],"prefix":"10.3310","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1999-8515","authenticated-orcid":true,"given":"Mark","family":"Simmonds","sequence":"first","affiliation":[{"name":"Centre for Reviews and Dissemination, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4569-5136","authenticated-orcid":true,"given":"Alexis","family":"Llewellyn","sequence":"additional","affiliation":[{"name":"Centre for Reviews and Dissemination, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2765-7363","authenticated-orcid":true,"given":"Ruth","family":"Walker","sequence":"additional","affiliation":[{"name":"Centre for Reviews and Dissemination, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1073-1099","authenticated-orcid":true,"given":"Helen","family":"Fulbright","sequence":"additional","affiliation":[{"name":"Centre for Reviews and Dissemination, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1932-3689","authenticated-orcid":true,"given":"Matthew","family":"Walton","sequence":"additional","affiliation":[{"name":"Centre for Reviews and Dissemination, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6962-2893","authenticated-orcid":true,"given":"Rob","family":"Hodgson","sequence":"additional","affiliation":[{"name":"Centre for Reviews and Dissemination, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7921-9109","authenticated-orcid":true,"given":"Laura","family":"Bojke","sequence":"additional","affiliation":[{"name":"Centre for Health Economics, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0287-4724","authenticated-orcid":true,"given":"Lesley","family":"Stewart","sequence":"additional","affiliation":[{"name":"Centre for Reviews and Dissemination, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-0221","authenticated-orcid":true,"given":"Sofia","family":"Dias","sequence":"additional","affiliation":[{"name":"Centre for Reviews and Dissemination, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Rush","sequence":"additional","affiliation":[{"name":"Patient Representative, Belfast, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G","family":"Lawrenson","sequence":"additional","affiliation":[{"name":"Department of Optometry and Visual Sciences, City University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6265-0381","authenticated-orcid":true,"given":"Tunde","family":"Peto","sequence":"additional","affiliation":[{"name":"Centre for Public Health, Queen\u2019s University Belfast, Belfast, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8734-3089","authenticated-orcid":true,"given":"David","family":"Steel","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6221","published-online":{"date-parts":[[2024,12]]},"reference":[{"key":"key2025061713160600_ref1-bib1","doi-asserted-by":"crossref","first-page":"e014444","DOI":"10.1136\/bmjopen-2016-014444","article-title":"Population trends in the 10-year incidence and prevalence of diabetic retinopathy in the UK: a cohort study in the Clinical Practice Research Datalink 2004\u20132014","volume":"7","author":"Mathur","year":"2017","journal-title":"BMJ Open"},{"key":"key2025061713160600_ref2-bib2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/eye.2012.287","article-title":"The Royal College of Ophthalmologists\u2019 clinical guidelines for diabetic retinopathy: a summary","volume":"27","author":"Ghanchi","year":"2013","journal-title":"Eye (Lond)"},{"key":"key2025061713160600_ref3-bib3","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1016\/j.ophtha.2008.08.023","article-title":"The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XXII the twenty-five-year progression of retinopathy in persons with type 1 diabetes","volume":"115","author":"Klein","year":"2008","journal-title":"Ophthalmology"},{"key":"key2025061713160600_ref4-bib4","doi-asserted-by":"crossref","first-page":"e1221","DOI":"10.1016\/S2214-109X(17)30393-5","article-title":"Global causes of blindness and distance vision impairment 1990\u20132020: a systematic review and meta-analysis","volume":"5","author":"Flaxman","year":"2017","journal-title":"Lancet Glob Health"},{"key":"key2025061713160600_ref5-bib5","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1001\/archopht.1979.01020010310003","article-title":"Four risk factors for severe visual loss in diabetic retinopathy. The third report from the Diabetic Retinopathy Study","volume":"97","author":"The Diabetic Retinopathy Study Research Group","year":"1979","journal-title":"Arch Ophthalmol"},{"key":"key2025061713160600_ref6-bib6","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1097\/IAE.0000000000000192","article-title":"Ocular findings at initial pan retinal photocoagulation for proliferative diabetic retinopathy predict the need for future pars plana vitrectomy","volume":"34","author":"Parikh","year":"2014","journal-title":"Retina"},{"key":"key2025061713160600_ref7-bib7","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S0161-6420(13)38014-2","article-title":"Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12","volume":"98","author":"Early Treatment Diabetic Retinopathy Study Research Group","year":"1991","journal-title":"Ophthalmology"},{"key":"key2025061713160600_ref8-bib8","doi-asserted-by":"crossref","first-page":"v","DOI":"10.3310\/hta19510","article-title":"Pan-retinal photocoagulation and other forms of laser treatment and drug therapies for non-proliferative diabetic retinopathy: systematic review and economic evaluation","volume":"19","author":"Royle","year":"2015","journal-title":"Health Technol Assess"},{"key":"key2025061713160600_ref9-bib9","volume-title":"Aflibercept for Treating Diabetic Macular Oedema","author":"National Institute for Health and Care Excellence","year":"2015"},{"key":"key2025061713160600_ref10-bib10","volume-title":"Ranibizumab for Treating Diabetic Macular Oedema","author":"National Institute for Health and Care Excellence","year":"2013"},{"key":"key2025061713160600_ref11-bib11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ajo.2019.03.005","article-title":"Anti-vascular endothelial growth factor therapy for diabetic retinopathy: consequences of inadvertent treatment interruptions","volume":"204","author":"Wubben","year":"2019","journal-title":"Am J Ophthalmol"},{"key":"key2025061713160600_ref12-bib12","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ophtha.2018.07.027","article-title":"Outcomes of eyes lost to follow-up with proliferative diabetic retinopathy that received panretinal photocoagulation versus intravitreal anti-vascular endothelial growth factor","volume":"126","author":"Obeid","year":"2019","journal-title":"Ophthalmology"},{"key":"key2025061713160600_ref13-bib13","volume-title":"Anti-VEGF Treatment","author":"Royal National Institute of Blind People (RNIB)"},{"key":"key2025061713160600_ref14-bib14","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1016\/j.ophtha.2018.04.007","article-title":"Guidelines on diabetic eye care: the International Council of Ophthalmology recommendations for screening, follow-up, referral, and treatment based on resource settings","volume":"125","author":"Wong","year":"2018","journal-title":"Ophthalmology"},{"key":"key2025061713160600_ref15-bib15","volume-title":"Diabetic Retinopathy (Guidance in Development)","author":"National Institute for Health and Care Excellence","year":"2023"},{"key":"key2025061713160600_ref16-bib16","volume-title":"Systematic Reviews: CRD\u2019s Guidance for Undertaking Reviews in Health Care","author":"Centre for Reviews and Dissemination"},{"key":"key2025061713160600_ref17-bib17","doi-asserted-by":"crossref","first-page":"264","DOI":"10.7326\/0003-4819-151-4-200908180-00135","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"151","author":"Moher","year":"2009","journal-title":"Ann Intern Med"},{"key":"key2025061713160600_ref18-bib18","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"Rob 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"key2025061713160600_ref19-bib19","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"key":"key2025061713160600_ref20-bib20","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1111\/rssa.12579","article-title":"Multilevel network meta-regression for population-adjusted treatment comparisons","volume":"183","author":"Phillippo","year":"2020","journal-title":"J R Stat Soc Ser A Stat Soc"},{"key":"key2025061713160600_ref21-bib21","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1177\/0272989X12455847","article-title":"Evidence synthesis for decision making 4: inconsistency in networks of evidence based on randomized controlled trials","volume":"33","author":"Dias","year":"2013","journal-title":"Med Decis Making"},{"key":"key2025061713160600_ref22-bib22","doi-asserted-by":"crossref","first-page":"538","DOI":"10.7326\/M18-3542","article-title":"Threshold analysis as an alternative to GRADE for assessing confidence in guideline recommendations based on network meta-analyses","volume":"170","author":"Phillippo","year":"2019","journal-title":"Ann Intern Med"},{"key":"key2025061713160600_ref23-bib23","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1016\/S0140-6736(17)31193-5","article-title":"Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial","volume":"389","author":"Sivaprasad","year":"2017","journal-title":"Lancet"},{"key":"key2025061713160600_ref24-bib24","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1001\/jamaophthalmol.2021.0606","article-title":"Effect of intravitreous anti-vascular endothelial growth factor vs sham treatment for prevention of vision-threatening complications of diabetic retinopathy: the Protocol W randomized clinical trial","volume":"139","author":"Maturi","year":"2021","journal-title":"JAMA Ophthalmol"},{"key":"key2025061713160600_ref25-bib25","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1001\/jamaophthalmol.2021.2809","article-title":"Evaluation of intravitreal aflibercept for the treatment of severe nonproliferative diabetic retinopathy: results from the PANORAMA randomized clinical trial","volume":"139","author":"Brown","year":"2021","journal-title":"JAMA Ophthalmol"},{"key":"key2025061713160600_ref26-bib26","first-page":"00211","article-title":"Panretinal photocoagulation versus intravitreal bevacizumab for proliferative diabetic retinopathy treatment","volume":"7","author":"Marashi","year":"2017","journal-title":"Adv Ophthalmol Vis Syst"},{"key":"key2025061713160600_ref27-bib27","first-page":"10","article-title":"Comparison between panretinal photocoagulation and panretinal photocoagulation plus intravitreal bevacizumab in proliferative diabetic retinopathy","volume":"24","author":"Ahmad","year":"2012","journal-title":"J Ayub Med Coll Abbottabad"},{"key":"key2025061713160600_ref28-bib28","doi-asserted-by":"crossref","first-page":"923","DOI":"10.29271\/jcpsp.2018.12.923","article-title":"Panretinal photocoagulation plus intravitreal bevacizumab versus panretinal photocoagulation alone for proliferative diabetic retinopathy","volume":"28","author":"Ali","year":"2018","journal-title":"J Coll Physicians Surg Pak"},{"key":"key2025061713160600_ref29-bib29","first-page":"157","article-title":"Comparison of efficacy of combination therapy of an intravitreal injection of bevacizumab and photocoagulation versus pan retinal photocoagulation alone in high risk proliferative diabetic retinopathy","volume":"37","author":"Rebecca","year":"2021","journal-title":"Pak J Med Sci"},{"key":"key2025061713160600_ref30-bib30","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1097\/IAE.0000000000001027","article-title":"Choroidal thickness changes in proliferative diabetic retinopathy treated with panretinal photocoagulation versus panretinal photocoagulation with intravitreal bevacizumab","volume":"36","author":"Roohipoor","year":"2016","journal-title":"Retina"},{"key":"key2025061713160600_ref31-bib31","first-page":"1008","article-title":"Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial (vol,314 pg 2137, 2015)","volume":"321","author":"Gross","year":"2019","journal-title":"JAMA"},{"key":"key2025061713160600_ref32-bib32","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1097\/IAE.0000000000000363","article-title":"A randomized controlled trial of panretinal photocoagulation with and without intravitreal ranibizumab in treatment-naive eyes with non-high-risk proliferative diabetic retinopathy","volume":"35","author":"Ferraz","year":"2015","journal-title":"Retina"},{"key":"key2025061713160600_ref33-bib33","doi-asserted-by":"crossref","first-page":"e530","DOI":"10.1111\/aos.14312","article-title":"Efficacy and safety of ranibizumab with or without panretinal laser photocoagulation versus laser photocoagulation alone in proliferative diabetic retinopathy \u2013 the PRIDE study","volume":"98","author":"Lang","year":"2020","journal-title":"Acta Ophthalmol"},{"key":"key2025061713160600_ref34-bib34","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.ophtha.2017.12.008","article-title":"Ranibizumab plus panretinal photocoagulation versus panretinal photocoagulation alone for high-risk proliferative diabetic retinopathy (PROTEUS study)","volume":"125","author":"Figueira","year":"2018","journal-title":"Ophthalmology"},{"key":"key2025061713160600_ref35-bib35","doi-asserted-by":"crossref","first-page":"e567","DOI":"10.1111\/j.1755-3768.2011.02184.x","article-title":"Panretinal photocoagulation (PRP) versus PRP plus intravitreal ranibizumab for high-risk proliferative diabetic retinopathy","volume":"89","author":"Filho","year":"2011","journal-title":"Acta Ophthalmol"},{"key":"key2025061713160600_ref36-bib36","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10633-018-9655-9","article-title":"Retinal function in eyes with proliferative diabetic retinopathy treated with intravitreal ranibizumab and multispot laser panretinal photocoagulation","volume":"137","author":"Messias","year":"2018","journal-title":"Doc Ophthalmol"},{"key":"key2025061713160600_ref37-bib37","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1167\/iovs.02-1100","article-title":"How sensitive to clinical change are ETDRS logMAR visual acuity measurements?","volume":"44","author":"Rosser","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"}],"container-title":["Health Technology Assessment"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2046765","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/sites\/journalslibrary\/files\/journal_data\/PCGV5709\/PCGV5709.xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/njl-admin.nihr.ac.uk\/document\/download\/2046765","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T07:52:10Z","timestamp":1750146730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/hta\/published-articles\/PCGV5709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":37,"alternative-id":["10.3310\/PCGV5709"],"URL":"https:\/\/doi.org\/10.3310\/pcgv5709","relation":{},"ISSN":["2046-4924"],"issn-type":[{"value":"2046-4924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"This content has been made freely available to all.","name":"free","label":"Free to read"},{"value":"08-2021","name":"contractual_start_date","label":"contractual_start_date","group":{"name":"article_history","label":"Article History"}},{"value":"11-2023","name":"editorial_review_begun","label":"editorial review begun","group":{"name":"article_history","label":"Article History"}},{"value":"08-2024","name":"accepted_for_publication","label":"Accepted for publication","group":{"name":"article_history","label":"Article History"}}]}}