{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:58:39Z","timestamp":1791928719878,"version":"4.3.4"},"reference-count":46,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"2","license":[{"start":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T00:00:00Z","timestamp":1551139200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2019,2,26]]},"DOI":"10.1167\/iovs.18-26209","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T15:42:31Z","timestamp":1551195751000},"page":"787","source":"Crossref","is-referenced-by-count":6,"title":["Anti-Fumarase Antibody as a Predictor of Functional Efficacy of Anti-VEGF Therapy for Diabetic Macular Edema"],"prefix":"10.1167","volume":"60","author":[{"given":"Tatsuya","family":"Yoshitake","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomaoki","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Yoshitake","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Suzuma","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Dodo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitaka","family":"Tsujikawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"i1552-5783-60-2-787-b01","doi-asserted-by":"crossref","unstructured":"Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012; 35: 556\u2013564.","DOI":"10.2337\/dc11-1909"},{"key":"i1552-5783-60-2-787-b02","doi-asserted-by":"crossref","unstructured":"Elman MJ, Aiello LP, Beck RW, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010; 117: 1064\u20131077.e35.","DOI":"10.1016\/j.ophtha.2010.02.031"},{"key":"i1552-5783-60-2-787-b03","doi-asserted-by":"crossref","unstructured":"Mitchell P, Bandello F, Schmidt-Erfurth U, et al. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011; 118: 615\u2013625.","DOI":"10.1016\/j.ophtha.2011.01.031"},{"key":"i1552-5783-60-2-787-b04","doi-asserted-by":"crossref","unstructured":"Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012; 119: 789\u2013801.","DOI":"10.1016\/j.ophtha.2011.12.039"},{"key":"i1552-5783-60-2-787-b05","doi-asserted-by":"crossref","unstructured":"Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014; 121: 2247\u20132254.","DOI":"10.1016\/j.ophtha.2014.05.006"},{"key":"i1552-5783-60-2-787-b06","doi-asserted-by":"crossref","unstructured":"Ip MS, Domalpally A, Hopkins JJ, Wong P, Ehrlich JS. Long-term effects of ranibizumab on diabetic retinopathy severity and progression. Arch Ophthalmol. 2012; 130: 1145\u20131152.","DOI":"10.1001\/archophthalmol.2012.1043"},{"key":"i1552-5783-60-2-787-b07","doi-asserted-by":"crossref","unstructured":"Campochiaro PA, Wykoff CC, Shapiro H, Rubio RG, Ehrlich JS. Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema. Ophthalmology. 2014; 121: 1783\u20131789.","DOI":"10.1016\/j.ophtha.2014.03.021"},{"key":"i1552-5783-60-2-787-b08","doi-asserted-by":"crossref","unstructured":"Domalpally A, Ip MS, Ehrlich JS. Effects of intravitreal ranibizumab on retinal hard exudate in diabetic macular edema: findings from the RIDE and RISE phase III clinical trials. Ophthalmology. 2015; 122: 779\u2013786.","DOI":"10.1016\/j.ophtha.2014.10.028"},{"key":"i1552-5783-60-2-787-b09","doi-asserted-by":"crossref","unstructured":"Seo KH, Yu SY, Kim M, Kwak HW. Visual and morphologic outcomes of intravitreal ranibizumab for diabetic macular edema based on optical coherence tomography patterns. Retina. 2016; 36: 588\u2013595.","DOI":"10.1097\/IAE.0000000000000770"},{"key":"i1552-5783-60-2-787-b10","doi-asserted-by":"crossref","unstructured":"Mori Y, Suzuma K, Uji A, et al. Restoration of foveal photoreceptors after intravitreal ranibizumab injections for diabetic macular edema. Sci Rep. 2016; 6: 39161.","DOI":"10.1038\/srep39161"},{"key":"i1552-5783-60-2-787-b11","doi-asserted-by":"crossref","unstructured":"Smiddy WE. Clinical applications of cost analysis of diabetic macular edema treatments. Ophthalmology. 2012; 119: 2558\u20132562.","DOI":"10.1016\/j.ophtha.2012.09.015"},{"key":"i1552-5783-60-2-787-b12","doi-asserted-by":"crossref","unstructured":"Avery RL, Gordon GM. Systemic safety of prolonged monthly anti-vascular endothelial growth factor therapy for diabetic macular edema: a systematic review and meta-analysis. JAMA Ophthalmol. 2016; 134: 21\u201329.","DOI":"10.1001\/jamaophthalmol.2015.4070"},{"key":"i1552-5783-60-2-787-b13","doi-asserted-by":"crossref","unstructured":"Do DV, Nguyen QD, Boyer D, et al. One-year outcomes of the da Vinci Study of VEGF trap-eye in eyes with diabetic macular edema. Ophthalmology. 2012; 119: 1658\u20131665.","DOI":"10.1016\/j.ophtha.2012.02.010"},{"key":"i1552-5783-60-2-787-b14","doi-asserted-by":"crossref","unstructured":"Prunte C, Fajnkuchen F, Mahmood S, et al. Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study. Br J Ophthalmol. 2016; 100: 787\u2013795.","DOI":"10.1136\/bjophthalmol-2015-307249"},{"key":"i1552-5783-60-2-787-b15","doi-asserted-by":"crossref","unstructured":"Bressler SB, Qin H, Beck RW, et al. Factors associated with changes in visual acuity and central subfield thickness at 1 year after treatment for diabetic macular edema with ranibizumab. Arch Ophthalmol. 2012; 130: 1153\u20131161.","DOI":"10.1001\/archophthalmol.2012.1107"},{"key":"i1552-5783-60-2-787-b16","doi-asserted-by":"crossref","unstructured":"Sophie R, Lu N, Campochiaro PA. Predictors of functional and anatomic outcomes in patients with diabetic macular edema treated with ranibizumab. Ophthalmology. 2015; 122: 1395\u20131401.","DOI":"10.1016\/j.ophtha.2015.02.036"},{"key":"i1552-5783-60-2-787-b17","doi-asserted-by":"crossref","unstructured":"Sadiq MA, Soliman MK, Sarwar S, et al. Effect of vitreomacular adhesion on treatment outcomes in the Ranibizumab for Edema of the Macula in Diabetes (READ-3) Study. Ophthalmology. 2016; 123: 324\u2013329.","DOI":"10.1016\/j.ophtha.2015.09.032"},{"key":"i1552-5783-60-2-787-b18","doi-asserted-by":"crossref","unstructured":"Wen J, Jiang Y, Zheng X, Zhou Y. Six-month changes in cytokine levels after intravitreal bevacizumab injection for diabetic macular oedema and macular oedema due to central retinal vein occlusion. Br J Ophthalmol. 2015; 99: 1334\u20131340.","DOI":"10.1136\/bjophthalmol-2014-306341"},{"key":"i1552-5783-60-2-787-b19","doi-asserted-by":"crossref","unstructured":"Sohn HJ, Han DH, Kim IT, et al. Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema. Am J Ophthalmol. 2011; 152: 686\u2013694.","DOI":"10.1016\/j.ajo.2011.03.033"},{"key":"i1552-5783-60-2-787-b20","doi-asserted-by":"crossref","unstructured":"Shimura M, Yasuda K, Motohashi R, Kotake O, Noma H. Aqueous cytokine and growth factor levels indicate response to ranibizumab for diabetic macular oedema. Br J Ophthalmol. 2017; 101: 1518\u20131523.","DOI":"10.1136\/bjophthalmol-2016-309953"},{"key":"i1552-5783-60-2-787-b21","doi-asserted-by":"crossref","unstructured":"Harhaj NS, Antonetti DA. Regulation of tight junctions and loss of barrier function in pathophysiology. Int J Biochem Cell Biol. 2004; 36: 1206\u20131237.","DOI":"10.1016\/j.biocel.2003.08.007"},{"key":"i1552-5783-60-2-787-b22","doi-asserted-by":"crossref","unstructured":"Gardner TW, Antonetti DA, Barber AJ, LaNoue KF, Levison SW. Diabetic retinopathy: more than meets the eye. Surv Ophthalmol. 2002; 47 (Suppl 2): S253\u2013S262.","DOI":"10.1016\/S0039-6257(02)00387-9"},{"key":"i1552-5783-60-2-787-b23","doi-asserted-by":"crossref","unstructured":"Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med. 2012; 366: 1227\u20131239.","DOI":"10.1056\/NEJMra1005073"},{"key":"i1552-5783-60-2-787-b24","doi-asserted-by":"crossref","unstructured":"Streilein JW. Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol. 2003; 3: 879\u2013889.","DOI":"10.1038\/nri1224"},{"key":"i1552-5783-60-2-787-b25","doi-asserted-by":"crossref","unstructured":"Shechter R, London A, Schwartz M. Orchestrated leukocyte recruitment to immune-privileged sites: absolute barriers versus educational gates. Nat Rev Immunol. 2013; 13: 206\u2013218.","DOI":"10.1038\/nri3391"},{"key":"i1552-5783-60-2-787-b26","doi-asserted-by":"crossref","unstructured":"Ambati J, Atkinson JP, Gelfand BD. Immunology of age-related macular degeneration. Nat Rev Immunol. 2013; 13: 438\u2013451.","DOI":"10.1038\/nri3459"},{"key":"i1552-5783-60-2-787-b27","doi-asserted-by":"crossref","unstructured":"Kleinman ME, Yamada K, Takeda A, et al. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature. 2008; 452: 591\u2013597.","DOI":"10.1038\/nature06765"},{"key":"i1552-5783-60-2-787-b28","doi-asserted-by":"crossref","unstructured":"Adamus G, Chew EY, Ferris FL, Klein ML. Prevalence of anti-retinal autoantibodies in different stages of Age-related macular degeneration. BMC Ophthalmol. 2014; 14: 154.","DOI":"10.1186\/1471-2415-14-154"},{"key":"i1552-5783-60-2-787-b29","doi-asserted-by":"crossref","unstructured":"Adamus G. Are anti-retinal autoantibodies a cause or a consequence of retinal degeneration in autoimmune retinopathies? Front Immunol. 2018; 9: 765.","DOI":"10.3389\/fimmu.2018.00765"},{"key":"i1552-5783-60-2-787-b30","doi-asserted-by":"crossref","unstructured":"Yoshitake S, Murakami T, Suzuma K, et al. Anti-fumarase antibody promotes the dropout of photoreceptor inner and outer segments in diabetic macular oedema. Diabetologia. 2019; 62: 504\u2013516.","DOI":"10.1007\/s00125-018-4773-1"},{"key":"i1552-5783-60-2-787-b31","doi-asserted-by":"crossref","unstructured":"Murakami T, Ueda-Arakawa N, Nishijima K, et al. Integrative understanding of macular morphologic patterns in diabetic retinopathy based on self-organizing map. Invest Ophthalmol Vis Sci. 2014; 55: 1994\u20132003.","DOI":"10.1167\/iovs.13-13417"},{"key":"i1552-5783-60-2-787-b32","doi-asserted-by":"crossref","unstructured":"Murakami T, Nishijima K, Akagi T, et al. Optical coherence tomographic reflectivity of photoreceptors beneath cystoid spaces in diabetic macular edema. Invest Ophthalmol Vis Sci. 2012; 53: 1506\u20131511.","DOI":"10.1167\/iovs.11-9231"},{"key":"i1552-5783-60-2-787-b33","doi-asserted-by":"crossref","unstructured":"Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985; 103: 1796\u20131806.","DOI":"10.1001\/archopht.1985.01050120030015"},{"key":"i1552-5783-60-2-787-b34","doi-asserted-by":"crossref","unstructured":"Jonas JB, Sofker A. Intraocular injection of crystalline cortisone as adjunctive treatment of diabetic macular edema. Am J Ophthalmol. 2001; 132: 425\u2013427.","DOI":"10.1016\/S0002-9394(01)01010-8"},{"key":"i1552-5783-60-2-787-b35","doi-asserted-by":"crossref","unstructured":"Lewis H, Abrams GW, Blumenkranz MS, Campo RV. Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology. 1992; 99: 753\u2013759.","DOI":"10.1016\/S0161-6420(92)31901-3"},{"key":"i1552-5783-60-2-787-b36","doi-asserted-by":"crossref","unstructured":"Abramoff MD, Fort PE, Han IC, Jayasundera KT, Sohn EH, Gardner TW. Approach for a clinically useful comprehensive classification of vascular and neural aspects of diabetic retinal disease. Invest Ophthalmol Vis Sci. 2018; 59: 519\u2013527.","DOI":"10.1167\/iovs.17-21873"},{"key":"i1552-5783-60-2-787-b37","doi-asserted-by":"crossref","unstructured":"Spaide RF, Koizumi H, Freund KB. Photoreceptor outer segment abnormalities as a cause of blind spot enlargement in acute zonal occult outer retinopathy-complex diseases. Am J Ophthalmol. 2008; 146: 111\u2013120.","DOI":"10.1016\/j.ajo.2008.02.027"},{"key":"i1552-5783-60-2-787-b38","doi-asserted-by":"crossref","unstructured":"Ojima Y, Tsujikawa A, Yamashiro K, Ooto S, Tamura H, Yoshimura N. Restoration of outer segments of foveal photoreceptors after resolution of central serous chorioretinopathy. Jpn J Ophthalmol. 2010; 54: 55\u201360.","DOI":"10.1007\/s10384-009-0766-4"},{"key":"i1552-5783-60-2-787-b39","doi-asserted-by":"crossref","unstructured":"Oishi A, Shimozono M, Mandai M, Hata M, Nishida A, Kurimoto Y. Recovery of photoreceptor outer segments after anti-VEGF therapy for age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2013; 251: 435\u2013440.","DOI":"10.1007\/s00417-012-2034-4"},{"key":"i1552-5783-60-2-787-b40","doi-asserted-by":"crossref","unstructured":"Murakami T, Tsujikawa A, Ohta M, et al. Photoreceptor status after resolved macular edema in branch retinal vein occlusion treated with tissue plasminogen activator. Am J Ophthalmol. 2007; 143: 171\u2013173.","DOI":"10.1016\/j.ajo.2006.08.030"},{"key":"i1552-5783-60-2-787-b41","doi-asserted-by":"crossref","unstructured":"Lee J, Moon BG, Cho AR, Yoon YH. Optical coherence tomography angiography of dme and its association with anti-VEGF treatment response. Ophthalmology. 2016; 123: 2368\u20132375.","DOI":"10.1016\/j.ophtha.2016.07.010"},{"key":"i1552-5783-60-2-787-b42","doi-asserted-by":"crossref","unstructured":"Flaxel CJ, Edwards AR, Aiello LP, et al. Factors associated with visual acuity outcomes after vitrectomy for diabetic macular edema: diabetic retinopathy clinical research network. Retina. 2010; 30: 1488\u20131495.","DOI":"10.1097\/IAE.0b013e3181e7974f"},{"key":"i1552-5783-60-2-787-b43","doi-asserted-by":"crossref","unstructured":"Nishijima K, Murakami T, Hirashima T, et al. Hyperreflective foci in outer retina predictive of photoreceptor damage and poor vision after vitrectomy for diabetic macular edema. Retina. 2014; 34: 732\u2013740.","DOI":"10.1097\/IAE.0000000000000005"},{"key":"i1552-5783-60-2-787-b44","doi-asserted-by":"crossref","unstructured":"Ting DS, Tan KA, Phua V, Tan GS, Wong CW, Wong TY. Biomarkers of diabetic retinopathy. Curr Diab Rep. 2016; 16: 125.","DOI":"10.1007\/s11892-016-0812-9"},{"key":"i1552-5783-60-2-787-b45","doi-asserted-by":"crossref","unstructured":"Brito P, Costa J, Gomes N, Costa S, Correia-Pinto J, Silva R. Serological inflammatory factors as biomarkers for anatomic response in diabetic macular edema treated with anti-VEGF. J Diabetes Complications. 2018; 32: 643\u2013649.","DOI":"10.1016\/j.jdiacomp.2018.05.006"},{"key":"i1552-5783-60-2-787-b46","doi-asserted-by":"crossref","unstructured":"Vujosevic S, Torresin T, Bini S, et al. Imaging retinal inflammatory biomarkers after intravitreal steroid and anti-VEGF treatment in diabetic macular oedema. Acta Ophthalmol. 2017; 95: 464\u2013471.","DOI":"10.1111\/aos.13294"}],"container-title":["Investigative Opthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?articleid=2726811","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:12Z","timestamp":1791927072000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.18-26209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,26]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.18-26209","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2019,2,26]]}}}