|
|
Early Response after Initial Anti-VEGF Injection to Predict the Therapeutic Effect on Macular Edema Secondary to Branch Retinal Vein Occlusion |
Bo Jiang, Chang Liu, Zhongyu Zhang, Jia Shi, Jiaqi Xu, Minghao Sun, Dawei Sun |
Department of Ophthalmology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China |
|
|
Abstract Objective: To identify the relationship between the early changes in central macular thickness (CMT) 24 hours after initial anti-vascular endothelial growth factor (VEGF) injection and the long-term therapeutic effect; to determine the threshold of the long-term prognosis by measuring the receiver operating characteristic (ROC) curve in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Method: This was a retrospective series of consecutive cases conducted to recruit 276 BRVO patients from December 2014 to December 2016 in the ophthalmic outpatient department of the Second Affiliated Hospital of Harbin Medical University. CMT was measured by OCT before injection, 24 hours after injection, and every 4 weeks up to 48 weeks. The best corrected visual acuity (BCVA) was measured by the ETDRS visual acuity scale. The threshold of the treatment effect at 48 weeks was determined by an ROC curve. Pearson correlation analysis and logistic regression analysis were used to identify the factors that might affect the treatment outcome. Results: All 60 eligible BRVO patients (60 eyes) showed a significant decrease in CMT at each time point after injection and BCVA increased significantly. The decrease in CMT at 24 hours after the first injection was significantly correlated with both the decrease in CMT at 48 weeks (r=0.664, P<0.001), and the change in visual acuity at 48 weeks (r=0.642, P<0.001). ROC curve analysis showed that the 18% decrease in CMT at 24 hours was the most sensitive and specific. According to this threshold, the patients were divided into two groups: 24 cases in group A decreased less than 18% at 24 hours and 36 cases in group B decreased more than 18%. The logistic regression analysis group (<18%) was a positive predictor of cure (OR: 19.549, 95%CI: 4.324-88.378, P<0.01). The improvement in visual acuity was 13±11 and 19±14 letters, respectively, and the difference was statistically significant (t=-1.375, P<0.001). Conclusion: The long-term therapeutic effect of ME secondary to BRVO in patients is correlated with the decline in CMT 24 hours after the first anti-VEGF injection using OCT, the decrease more than 18% predicts a good the long-term therapeutic effect.
|
Received: 18 August 2018
|
Fund: Fundamental Research Funds for the Provincial Universities (2017LCZX42); Heilongjiang Postdoctoral Financial Assistant (LBH-Z18127) |
Corresponding Authors:
Dawei Sun, Department of Ophthalmology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China (Email: drsundw@126.com)
|
|
|
|
[1] |
Hayreh SS, Zimmerman B, McCarthy MJ, et al. Systemic diseases associated with various types of retinal vein occlusion. Am J Ophthalmol, 2001, 131(1): 61-77.
|
[2] |
Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med, 1994, 331(22): 1480- 1487. DOI: 10.1056/NEJM199412013312203.
|
[3] |
Campochiaro PA, Hafiz G, Shah SM, et al. Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator. Mol Ther, 2008, 16(4): 791-799. DOI: 10.1038/mt.2008.10.
|
[4] |
Noma H, Funatsu H, Yamasaki M, et al. Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6. Am J Ophthalmol, 2005, 140(2): 256-261. DOI: 10.1016/j.ajo.2005.03. 003.
|
[5] |
Ozaki H, Hayashi H, Vinores SA, et al. Intravitreal sustained release of VEGF causes retinal neovascularization in rabbits and breakdown of the blood-retinal barrier in rabbits and primates. Exp Eye Res, 1997, 64(4): 505-517. DOI: 10.1006/exer.1996. 0239.
|
[6] |
Coscas G, Loewenstein A, Augustin A, et al. Management of retinal vein occlusion-consensus document. Ophthalmologica, 2011, 226(1): 4-28. DOI: 10.1159/000327391.
|
[7] |
Campochiaro PA, Heier JS, Feiner L, et al. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study.
|
|
Ophthalmology, 2010, 117(6): 1102-1112.e1. DOI: 10.1016/j. ophtha.2010.02.021.
|
[8] |
Yang S, Zhao J, Sun X. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review. Drug Des Devel Ther, 2016, 10: 1857-1867. DOI: 10. 2147/DDDT.S97653.
|
[9] |
Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study.
|
|
Ophthalmology, 2010, 117(6): 1124-1133.e1. DOI: 10.1016/j. ophtha.2010.02.022.
|
[10] |
Sonoda Y, Arimura N, Shimura M, et al. Early change of central macular thickness after intravitreous triamcinolone or bevacizumab in diabetic macular edema or retinal vein
|
|
occlusion. Retina, 2011, 31(2): 290-297. DOI: 10.1097/IAE. 0b013e3181eef070.
|
[11] |
Fawcett T. An Introduction to ROC analysis. Pattern Recognition Letters, 2005, 27(8): 861-874.
|
[12] |
Jaulim A, Ahmed B, Khanam T, et al. Branch retinal vein occlusion: epidemiology, pathogenesis, risk factors, clinical features, diagnosis, and complications. An update of the
|
|
literature. Retina, 2013, 33(5): 901-910. DOI: 10.1097/IAE. 0b013e3182870c15.
|
[13] |
Rogers SL, McIntosh RL, Lim L, et al. Natural history of branch retinal vein occlusion: an evidence-based systematic review. Ophthalmology, 2010, 117(6): 1094-1101.e5. DOI: 10.1016/j. ophtha.2010.01.058.
|
[14] |
Brown DM, Campochiaro PA, Bhisitkul RB, et al. Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study.Ophthalmology, 2011, 118(8): 1594-1602. DOI: 10.1016/j. ophtha.2011.02.022.
|
[15] |
Campochiaro PA, Sophie R, Pearlman J, et al. Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: the RETAIN study. Ophthalmology, 2014, 121(1): 209-219. DOI: 10.1016/j.ophtha.2013.08.038.
|
[16] |
Ach T, Hoeh AE, Schaal KB, et al. Predictive factors for changes in macular edema in intravitreal bevacizumab therapy of retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol,
|
20 |
10, 248(2): 155-159. DOI: 10.1007/s00417-009-1167-6.
|
[17] |
Jaissle GB, Szurman P, Feltgen N, et al. Predictive factors for functional improvement after intravitreal bevacizumab therapy for macular edema due to branch retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol, 2011, 249(2): 183-192. DOI: 10. 1007/s00417-010-1470-2.
|
[18] |
Wolf-Schnurrbusch UE, Ghanem R, Rothenbuehler SP, et al. Predictors of short-term visual outcome after anti-VEGF therapy of macular edema due to central retinal vein occlusion. Invest Ophthalmol Vis Sci, 2011, 52(6): 3334-3337. DOI: 10.1167/ iovs.10-6097.
|
[19] |
Naoya Yoshihara, Hiroto Terasaki, Makoto Shirasawa, et al. Permeability and anti-vascular endothelial growth factor effects of bevacizumab, ranibizumab, and aflibercept in polarized retinal pigment epithelial layer in vitro. Retina, 2017, 37(1): 179-190.
|
[20] |
Krohne TU, Liu Z, Holz FG, et al. Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans. Am J Ophthalmol, 2012, 154(4): 682-686. DOI: 10.
|
10 |
16/j.ajo.2012.03.047.
|
[21] |
Scholl S, Augustin A, Loewenstein A, et al. General pathophysiology of macular edema. Eur J Ophthalmol, 2011, 21 Suppl 6: S10-19. DOI: 10.5301/EJO.2010.6050.
|
[22] |
Reichenbach A, Wurm A, Pannicke T, et al. Müller cells as players in retinal degeneration and edema. Graefes Arch Clin Exp Ophthalmol, 2007, 245(5): 627-636. DOI: 10.1007/s00417- 006-0516-y.
|
[23] |
Spaide RF. Retinal vascular cystoid macular edema: Review and New Theory. Retina, 2016, 36(10): 1823-1842.
|
|
|
|