{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T14:47:17Z","timestamp":1782226037377,"version":"3.54.5"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,10]],"date-time":"2022-04-10T00:00:00Z","timestamp":1649548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["K23-EY022947-01A1"],"award-info":[{"award-number":["K23-EY022947-01A1"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>The objective of this study was to identify biomarkers that predict a future need for anti-VEGF therapy in diabetic retinopathy (DR). Eyes with DR that underwent ultra-widefield angiography (UWFA) and had at least a 1 year follow-up were grouped based on future anti-VEGF treatment requirements: (1) not requiring treatment, (2) immediate treatment (within 3 months of UWFA), and (3) delayed treatment (after 3 months of UWFA). Quantitative UWFA features and clinical factors were evaluated. Random forest models were built to differentiate eyes requiring immediate and delayed treatment from the eyes not requiring treatment. A total of 173 eyes were included. The mean follow-up was 22 (range: 11\u201343) months. The macular leakage index, panretinal leakage index, presence of DME, and visual acuity were significantly different in eyes requiring immediate (n = 38) and delayed (n = 34) treatment compared to eyes not requiring treatment (n = 101). Random forest model differentiating eyes requiring immediate treatment from eyes not requiring treatment demonstrated an AUC of 0.91 \u00b1 0.07. Quantitative angiographic features have potential as important predictive biomarkers of a future need for anti-VEGF therapy in DR and may serve to guide the frequency of a follow-up.<\/jats:p>","DOI":"10.3390\/jpm12040608","type":"journal-article","created":{"date-parts":[[2022,4,10]],"date-time":"2022-04-10T06:02:54Z","timestamp":1649570574000},"page":"608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Predictive Assessment of Quantitative Ultra-Widefield Angiographic Features for Future Need for Anti-VEGF Therapy in Diabetic Eye Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Alice C.","family":"Jiang","sequence":"first","affiliation":[{"name":"The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"School of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0395-8711","authenticated-orcid":false,"given":"Duriye Damla","family":"Sevgi","sequence":"additional","affiliation":[{"name":"The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Mugnaini","sequence":"additional","affiliation":[{"name":"The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Whitney","sequence":"additional","affiliation":[{"name":"The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil K.","family":"Srivastava","sequence":"additional","affiliation":[{"name":"The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E.","family":"Talcott","sequence":"additional","affiliation":[{"name":"The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0987-2916","authenticated-orcid":false,"given":"Ming","family":"Hu","sequence":"additional","affiliation":[{"name":"The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.","family":"Reese","sequence":"additional","affiliation":[{"name":"The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justis P.","family":"Ehlers","sequence":"additional","affiliation":[{"name":"The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/S0161-6420(86)33650-9","article-title":"Diabetic Macular Edema: A Review","volume":"93","author":"Bresnick","year":"1986","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"(1985). Photocoagulation For Diabetic Macular Edema: Early Treatment Diabetic Retinopathy Study Report Number 1 Early Treatment Diabetic Retinopathy Study Research Group. Arch. Ophthalmol., 103, 1796\u20131806.","DOI":"10.1001\/archopht.1985.01050120030015"},{"key":"ref_3","first-page":"735","article-title":"Treatment Patterns of Anti-Vascular Endothelial Growth Factor and Laser Therapy Among Patients with Diabetic Macular Edema","volume":"21","author":"Jiang","year":"2015","journal-title":"J. Manag. Care Spec. Pharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.ophtha.2011.01.031","article-title":"The RESTORE Study: Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy for Diabetic Macular Edema","volume":"118","author":"Mitchell","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.ophtha.2016.02.022","article-title":"Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial","volume":"123","author":"Wells","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.ophtha.2011.12.039","article-title":"Ranibizumab for Diabetic Macular Edema: Results from 2 Phase III Randomized Trials: RISE and RIDE","volume":"119","author":"Nguyen","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2147\/OPTH.S118807","article-title":"Retinal Reperfusion in Diabetic Retinopathy Following Treatment with Anti-VEGF Intravitreal Injections","volume":"11","author":"Levin","year":"2017","journal-title":"Clin. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1016\/j.ophtha.2015.07.034","article-title":"Diabetic Retinopathy Severity and Peripheral Lesions Are Associated with Nonperfusion on Ultrawide Field Angiography","volume":"122","author":"Silva","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1136\/bjophthalmol-2011-300774","article-title":"Peripheral Retinal Ischaemia, as Evaluated by Ultra-Widefield Fluorescein Angiography, Is Associated with Diabetic Macular Oedema","volume":"96","author":"Wessel","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.ophtha.2019.05.034","article-title":"Quantitative Ultra-Widefield Angiography and Diabetic Retinopathy Severity","volume":"126","author":"Ehlers","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3928\/23258160-20140709-07","article-title":"Precise Montaging and Metric Quantification of Retinal Surface Area from Ultra-Widefield Fundus Photography and Fluorescein Angiography","volume":"45","author":"Croft","year":"2014","journal-title":"Ophthalmic Surg. Lasers Imaging Retina"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.oret.2019.07.011","article-title":"Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy: Outcomes from the RECOVERY Randomized Trial","volume":"3","author":"Wykoff","year":"2019","journal-title":"Ophthalmol. Retin."},{"key":"ref_13","unstructured":"(2021, May 20). Automated Quantitative Characterisation of Retinal Vascular Leakage and Microaneurysms in Ultra-Widefield Fluorescein Angiography|Enhanced Reader. Available online: Chrome-extension:\/\/dagcmkpagjlhakfdhnbomgmjdpkdklff\/enhanced-reader.html?openApp&pdf=https%3A%2F%2Fbjo.bmj.com%2Fcontent%2Fbjophthalmol%2F101%2F6%2F696.full.pdf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1136\/bjophthalmol-2020-317241","article-title":"Longitudinal Assessment of Quantitative Ultra-Widefield Ischaemic and Vascular Parameters in Sickle Cell Retinopathy","volume":"106","author":"Scott","year":"2022","journal-title":"Br. J. Ophthalmol."},{"key":"ref_15","unstructured":"(2021, May 20). Automated Quality Optimized Phase Selection in Ultra-Widefield Angiography Using Retinal Vessel Segmentation with Deep Neural Networks|IOVS|ARVO Journals. Available online: https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2770382."},{"key":"ref_16","unstructured":"(2021, May 20). Longitudinal Precision of Vasculature Parameter Assessment on Ultra-Widefield Fluorescein Angiography Using a Deep-Learning Model for Vascular Segmentation in Eyes without Vascular Pathology|IOVS|ARVO Journals. Available online: https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2769705."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1097\/IAE.0000000000002422","article-title":"Anti\u2013vascular endothelial growth factor therapy can improve diabetic retinopathy score without change in retinal perfusion","volume":"39","author":"Bonnin","year":"2019","journal-title":"Retina"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1016\/j.ophtha.2016.07.032","article-title":"Intravitreal Aflibercept for Diabetic Macular Edema: 148-Week Results from the VISTA and VIVID Studies","volume":"123","author":"Heier","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1159\/000213639","article-title":"Microaneurysm Turnover Is a Biomarker for Diabetic Retinopathy Progression to Clinically Significant Macular Edema: Findings for Type 2 Diabetics with Nonproliferative Retinopathy","volume":"223","author":"Nunes","year":"2009","journal-title":"Ophthalmologica"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3986","DOI":"10.1167\/iovs.17-21510","article-title":"The Distribution of Leakage on Fluorescein Angiography in Diabetic Macular Edema: A New Approach to Its Etiology","volume":"58","author":"Najeeb","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1167\/tvst.6.2.7","article-title":"A Quantitative Approach to Predict Differential Effects of Anti-VEGF Treatment on Diffuse and Focal Leakage in Patients with Diabetic Macular Edema: A Pilot Study","volume":"6","author":"Allingham","year":"2017","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/j.ophtha.2019.06.022","article-title":"Widefield OCT-Angiography and Fluorescein Angiography Assessments of Nonperfusion in Diabetic Retinopathy and Edema Treated with Anti\u2013Vascular Endothelial Growth Factor","volume":"126","author":"Couturier","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100049","DOI":"10.1016\/j.xops.2021.100049","article-title":"Characterization of Ultra-Widefield Angiographic Vascular Features in Diabetic Retinopathy with Automated Severity Classification","volume":"1","author":"Sevgi","year":"2021","journal-title":"Ophthalmol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.2147\/OPTH.S275968","article-title":"Five-Year Patterns of Diabetic Retinopathy Progression in Us Clinical Practice","volume":"14","author":"Moshfeghi","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ajo.2014.03.009","article-title":"Patterns of Peripheral Retinal and Central Macula Ischemia in Diabetic Retinopathy as Evaluated by Ultra-Widefield Fluorescein Angiography","volume":"158","author":"Sim","year":"2014","journal-title":"Am. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.ajo.2013.01.007","article-title":"Characterization of Ischemic Index Using Ultra-Widefield Fluorescein Angiography in Patients with Focal and Diffuse Recalcitrant Diabetic Macular Edema","volume":"155","author":"Patel","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Figueiredo, N., Srivastava, S.K., Singh, R.P., Babiuch, A., Sharma, S., Rachitskaya, A., Talcott, K., Reese, J., Hu, M., and Ehlers, J.P. (2019). Longitudinal Panretinal Leakage and Ischemic Indices in Retinal Vascular Disease Following Aflibercept Therapy: The PERMEATE Study, Elsevier.","DOI":"10.1016\/j.oret.2019.09.001"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"474","DOI":"10.3928\/23258160-20160419-12","article-title":"Reduction of Diabetic Macular Edema in the Untreated Fellow Eye Following Intravitreal Injection of Aflibercept","volume":"47","author":"Calvo","year":"2016","journal-title":"Ophthalmic Surg. Lasers Imaging Retin."},{"key":"ref_29","first-page":"1","article-title":"Therapeutic Effect of Anti-VEGF for Age-Related Macular Degeneration in the Untreated Fellow Eye","volume":"2018","author":"Isildak","year":"2018","journal-title":"Case Rep. Ophthalmol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/eye.2014.265","article-title":"Re: \u201cFellow Eye Effect of Unilateral Intravitreal Bevacizumab Injection in Eyes with Diabetic Macular Edema\u201d","volume":"29","author":"Sharma","year":"2015","journal-title":"Eye"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/4\/608\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:51:16Z","timestamp":1760136676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/4\/608"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,10]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["jpm12040608"],"URL":"https:\/\/doi.org\/10.3390\/jpm12040608","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,10]]}}}