Research progress of evaluating the prognosis of anti-vascular endothelial growth factor drug treatment for diabetic macular edema with clinical markers_Chinese Journal of Ocular Fundus Diseases

Authors：

Chen Qinyun ,  Zhang Xuedong

Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, China;

Corresponding author：

Zhang Xuedong, Email: zxued@sina.com

Keywords：

Diabetic retinopathy; Macular edema; Angiogenesis inhibitors; Biomarkers, pharmacological; Review

DOI：

10.3760/cma.j.cn511434-20200703-00318

Video：

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Abstract Full text Figures/Tables Video References Cited by

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs is the main treatment for diabetic macular edema (DME), however, 30% of patients still respond poorly to its treatment. At present, imaging markers that can indicate the prognosis of anti-VEGF drug treatment include ischemic index, deep retinal capillary plexus foveal avascular zone area, number of microaneurysms, blood flow density, disorder of the inner retinal layer, outer membrane and/or the degree of damage to the ellipsoid zone, strong reflex foci, intraretinal cysts, subretinal fluid. Biomarkers include high-sensitivity C-reactive protein, neutrophil to lymphocyte ratio, anti-fumarase antibody, intraocular aqueous humor cell adhesion molecule-1, interleukin (IL)-6, IL-8, etc. Understanding these clinical markers that may predict and evaluate the prognosis of anti-VEGF drug therapy can be beneficial to adjust the treatment plan, and more effectively monitor, treat, and manage DME patients.

Citation： Chen Qinyun, Zhang Xuedong. Research progress of evaluating the prognosis of anti-vascular endothelial growth factor drug treatment for diabetic macular edema with clinical markers. Chinese Journal of Ocular Fundus Diseases, 2021, 37(4): 321-326. doi: 10.3760/cma.j.cn511434-20200703-00318 Copy

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2. Wykoff CC, Elman MJ, Regillo CD, et al. Predictors of diabetic macular edema treatment frequency with ranibizumab during the open-label extension of the RIDE and RISE trials[J]. Ophthalmology, 2016, 123(8): 1716-1721. DOI: 10.1016/j.ophtha.2016.04.004.
3. Chatziralli I, Theodossiadis P, Parikakis E, et al. Dexamethasone intravitreal implant in diabetic macular edema: real-life data from a prospective study and predictive factors for visual outcome[J]. Diabetes Ther, 2017, 8(6): 1393-1404. DOI: 10.1007/s13300-017-0332-x.
4. Gonzalez VH, Campbell J, Holekamp NM, et al. Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol I data[J]. Am J Ophthalmol, 2016, 172(11): 72-79. DOI: 10.1016/j.ajo.2016.09.012.
5. Fan W, Uji A, Wang K, et al. Severity of diabetic macular edema correlates with retinal vascular bed area on ultra-wide field fluorescein andiography[J]. Retina, 2020, 40(6): 1029-1037. DOI: 10.1097/IAE.0000000000002579.
6. Bobak B, Thomas H, Tunde P, et al. Ultra-widefield fluorescein angiography as a biomarker for response to switch in therapy[J]. Ophthalmic Surg Lasers Imaging Retina, 2019, 50(12): 771-778. DOI: 10.3928/23258160-20191119-04.
7. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial[J]. Ophthalmology, 2016, 123(6): 1351-1359. DOI: 10.1016/j.ophtha.2016.02.022.
8. Singer MA, Kermany DS, Waters J, et al. Diabetic macular edema: it is more than just VEGF [J/OL]. F1000Res, 2016, 5: 1000-1019[2016-05-27]. https://pubmed.ncbi.nlm.nih.gov/27303642/. DOI: 10.12688/f1000research.8265.1.
9. Patel RD, Messner LV, Teitelbaum B, et al. Characterization of ischemic index using ultra-widefield fluorescein angiography in patients with focal and diffuse recalcitrant diabetic macular edema[J]. Am J Ophthalmol, 2013, 155(6): 1038-1044. DOI: 10.1016/j.ajo.2013.01.007.
10. Tan CS, Chew MC, van Hemert J, et al. Measuring the precise area of peripheral retinal non-perfusion using ultra-widefield imaging and its correlation with the ischaemic index[J]. Br J Ophthalmol, 2016, 100(2): 235-239. DOI: 10.1136/bjophthalmol-2015-306652.
11. Silva PS, Dela Cruz AJ, Ledesma MG, et al. Diabetic retinopathy severity and peripheral lesions are associated with nonperfusion on ultrawide field angiography[J]. Ophthalmology, 2015, 122(12): 2465-2472. DOI: 10.1016/j.ophtha.2015.07.034.
12. Ishibazawa A, Nagaoka T, Yokota H, et al. Characteristics of retinal neovascularization in proliferative diabetic retinopathy imaged by optical coherence tomography angiography[J]. Invest Ophthalmol Vis Sci, 2016, 57(14): 6247-6255. DOI: 10.1167/iovs.16-20210.
13. Muqit MM, Stanga PE. Fourier-domain optical coherence tomography evaluation of retinal and optic nerve head neovascularisation in proliferative diabetic retinopathy[J]. Br J Ophthalmol, 2014, 98(1): 65-72. DOI: 10.1136/bjophthalmol-2013-303941.
14. Lee J, Moon BG, Cho AR, et al. Optical coherence tomography angiography of dme and its association with anti-VEGF treatment response[J]. Ophthalmology, 2016, 123(11): 2368-2375. DOI: 10.1016/j.ophtha.2016.07.010.
15. Moon BG, Um T, Lee J, et al. Correlation between deep capillary plexus perfusion and long-term photoreceptor recovery after diabetic macular edema treatment[J]. Ophthalmol Retina, 2018, 2(3): 235-243. DOI: 10.1016/j.oret.2017.07.003.
16. Busch C, Wakabayashi T, Sato T, et al. Retinal microvasculature and visual acuity after intravitreal aflibercept in diabetic macular edema: an optical coherence tomography angiography study[J/OL]. Sci Rep, 2019, 9(1): 1561[2019-02-07]. https://pubmed.ncbi.nlm.nih.gov/30733512/. DOI: 10.1038/s41598-018-38248-1.
17. Enders C, Lang GE, Dreyhaupt J, et al. Quantity and quality of image artifacts in optical coherence tomography angiography[J/OL]. PLoS One, 2019, 14(1): e0210505[2019-01-25]. https://pubmed.ncbi.nlm.nih.gov/30682050/. DOI: 10.1371/journal.pone.0210505.
18. Deák GG, Schmidt-Erfurth UM, Jampol LM. Correlation of central retinal thickness and visual acuity in diabetic macular edema[J]. JAMA Ophthalmol, 2018, 136(11): 1215-1216. DOI: 10.1001/jamaophthalmol.2018.3848.
19. Zur D, Iglicki M, Sala-Puigdollers A, et al. Disorganization of retinal inner layers as a biomarker in patients with diabetic macular oedema treated with dexamethasone implant[J/OL]. Acta Ophthalmol, 2020, 98(2): e217-e223[2019-08-18]. https://pubmed.ncbi.nlm.nih.gov/31421028/. DOI: 10.1111/aos.14230.
20. Sun JK, Radwan SH, Soliman AZ, et al. Neural retinal disorganization as a robust marker of visual acuity in current and resolved diabetic macular edema[J]. Diabetes, 2015, 64(7): 2560-2570. DOI: 10.2337/db14-0782.
21. Das R, Spence G, Hogg RE, et al. Disorganization of inner retina and outer retinal morphology in diabetic macular edema[J]. JAMA Ophthalmol, 2018, 136(2): 202-208. DOI: 10.1001/jamaophthalmol.2017.6256.
22. Sun JK, Lin MM, Lammer J, et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema[J]. JAMA Ophthalmol, 2014, 132(11): 1309-1316. DOI: 10.1001/jamaophthalmol.2014.2350.
23. Blindbæk SL, Torp TL, Lundberg K, et al. Noninvasive retinal markers in diabetic retinopathy: advancing from bench towards bedside[J/OL]. J Diabetes Res, 2017, 17(4): 2562759[2017-04-13]. https://pubmed.ncbi.nlm.nih.gov/28491870/. DOI: 10.1155/2017/2562759.
24. Chhablani JK, Kim JS, Cheng L, et al. External limiting membrane as a predictor of visual improvement in diabetic macular edema after pars plana vitrectomy[J]. Graefe's Arch Clin Exp Ophthalmol, 2012, 250(10): 1415-1420. DOI: 10.1007/s00417-012-1968-x.
25. Maheshwary AS, Oster SF, Yuson RM, et al. The association between percent disruption of the photoreceptor inner segment-outer segment junction and visual acuity in diabetic macular edema[J]. Am J Ophthalmol, 2010, 150(1): 63-67. DOI: 10.1016/j.ajo.2010.01.039.
26. Forooghian F, Stetson PF, Meyer SA, et al. Relationship between photoreceptor outer segment length and visual acuity in diabetic macular edema[J]. Retina, 2010, 30(1): 63-70. DOI: 10.1097/IAE.0b013e3181bd2c5a.
27. Lee H, Jang H, Choi YA, et al. Association between soluble CD14 in the aqueous humor and hyperreflective foci on optical coherence tomography in patients with diabetic macular edema[J]. Invest Ophthalmol Vis Sci, 2018, 59(2): 715-721. DOI: 10.1167/iovs.17-23042.
28. Gross JG, Glassman AR, Liu D, et al. Five-year outcomes of panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial[J]. JAMA Ophthalmol, 2018, 136(10): 1138-1148. DOI: 10.1001/jamaophthalmol.2018.3255.
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