Efficacy of intravitreal AFlibercept injection For Improvement of retinal Nonperfusion In diabeTic retinopathY (AFFINITY study)

Yoon Jeon Kim, Joon Hyung Yeo, Gisung Son, Hyojoo Kang, Yu Sub Sung, Joo Yong Lee, June-Gone Kim, Young Hee Yoon, Yoon Jeon Kim, Joon Hyung Yeo, Gisung Son, Hyojoo Kang, Yu Sub Sung, Joo Yong Lee, June-Gone Kim, Young Hee Yoon

Abstract

Introduction: To evaluate the effects of intravitreal aflibercept injection on retinal nonperfusion in patients with diabetic retinopathy (DR) using ultrawide field (UWF) fluorescein angiography (FA).

Research design and methods: Thirty-eight eyes of 38 consecutive patients with DR and substantial retinal nonperfusion (nonperfusion index (NPI): nonperfused/total gradable area >0.2) without macular edema were included in this prospective case series. Monthly injections of 2 mg aflibercept were given for 6 months. UWF-fundus photography and UWF-FA images were acquired at baseline, 6 months, and 12 months and evaluated by 2 masked, independent graders for the extent of retinal nonperfusion and vascular leakage. Twenty untreated fellow eyes were analyzed as controls.

Results: Inter-grader agreement was strong (r=0.875) for NPI measurements. NPI was 0.46±0.10 at baseline; NPI was decreased to 0.43±0.08 (p=0.015) after 6 monthly injections of aflibercept and then slightly increased to 0.44±0.09 (p=0.123) after 6 months of observation. Vascular leakage also significantly decreased by 21.0% at 6 months (p=0.010). Untreated fellow eyes did not show significant changes in NPI and vascular leakage during follow-up. Reduction in retinal nonperfusion was associated with severe nonproliferative diabetic retinopathy (NPDR) (vs PDR, OR 19.119, p=0.025) and higher leakage index (per 0.1, OR 15.152, p=0.020).

Conclusions: Intensive aflibercept treatment was effective in reducing retinal capillary nonperfusion in patients with DR without macular edema. Severe NPDR and profound vascular leakage were significantly associated with retinal reperfusion after aflibercept treatment.

Trial registration number: NCT03006081.

Keywords: diabetes complications; diabetic retinopathy.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Representative ultrawide field fluorescein angiographic images from a patient with significant improvement in retinal perfusion after aflibercept therapy. (A) Nonperfusion index (NPI) at baseline: 0.21. (B) NPI at 6 months: 0.15. (C) NPI at 12-month visit: 0.17. The white rectangles show an area of interest enlarged in the lowest row.
Figure 2
Figure 2
Changes in nonperfusion index (NPI) after 6 monthly aflibercept treatments. (A) NPIs of study eyes and fellow eyes. Topographical analysis of (B) the four quadrants and (C) three concentric zones.
Figure 3
Figure 3
Changes in vascular leakage index after six monthly aflibercept treatments.

References

    1. Singer M, Tan CS, Bell D, et al. . Area of peripheral retinal nonperfusion and treatment response in branch and central retinal vein occlusion. Retina 2014;34:1736–42. 10.1097/IAE.0000000000000148
    1. 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. Am J Ophthalmol 2013;155:1038–44. 10.1016/j.ajo.2013.01.007
    1. Tsui I, Williams BK, Kok YO, et al. . Reliability of ischemic index grading in common retinal vascular diseases. Ophthalmic Surg Lasers Imaging Retina 2015;46:618–25. 10.3928/23258160-20150610-04
    1. Hofman P, van Blijswijk BC, Gaillard PJ, et al. . Endothelial cell hypertrophy induced by vascular endothelial growth factor in the retina: new insights into the pathogenesis of capillary nonperfusion. Arch Ophthalmol 2001;119:861–6.
    1. Campochiaro PA, Wykoff CC, Shapiro H, et al. . Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema. Ophthalmology 2014;121:1783–9. 10.1016/j.ophtha.2014.03.021
    1. Liu Y, Shen J, Fortmann SD, et al. . Reversible retinal vessel closure from VEGF-induced leukocyte plugging. JCI Insight 2017;2:e95530. 10.1172/jci.insight.95530
    1. Tolentino MJ, Miller JW, Gragoudas ES, et al. . Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. Ophthalmology 1996;103:1820–8. 10.1016/S0161-6420(96)30420-X
    1. Fan W, Wang K, Ghasemi Falavarjani K, et al. . Distribution of nonperfusion area on ultra-widefield fluorescein angiography in eyes with diabetic macular edema: DAVE study. Am J Ophthalmol 2017;180:110–6. 10.1016/j.ajo.2017.05.024
    1. Silva PS, Dela Cruz AJ, Ledesma MG, et al. . Diabetic retinopathy severity and peripheral lesions are associated with nonperfusion on ultrawide field angiography. Ophthalmology 2015;122:2465–72. 10.1016/j.ophtha.2015.07.034
    1. Campochiaro PA, Bhisitkul RB, Shapiro H, et al. . Vascular endothelial growth factor promotes progressive retinal nonperfusion in patients with retinal vein occlusion. Ophthalmology 2013;120:795–802. 10.1016/j.ophtha.2012.09.032
    1. Wykoff CC, Shah C, Dhoot D, et al. . Longitudinal retinal perfusion status in eyes with diabetic macular edema receiving intravitreal aflibercept or laser in VISTA study. Ophthalmology 2019;126:1171–80. 10.1016/j.ophtha.2019.03.040
    1. Nicholson L, Crosby-Nwaobi R, Vasconcelos JC, et al. . Mechanistic evaluation of panretinal photocoagulation versus aflibercept in proliferative diabetic retinopathy: CLARITY substudy. Invest Ophthalmol Vis Sci 2018;59:4277–84. 10.1167/iovs.17-23509
    1. Sivaprasad S, Prevost AT, Vasconcelos JC, et al. . 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. Lancet 2017;389:2193–203. 10.1016/S0140-6736(17)31193-5
    1. Wykoff CC, Nittala MG, Zhou B, et al. . Intravitreal aflibercept for retinal nonperfusion in proliferative diabetic retinopathy: outcomes from the randomized recovery trial. Ophthalmol Retina 2019;3:1076-1086. 10.1016/j.oret.2019.07.011
    1. Son G, Kim YJ, Sung YS, et al. . Analysis of quantitative correlations between microaneurysm, ischaemic index and new vessels in ultrawide-field fluorescein angiography images using automated software. Br J Ophthalmol 2019;103:bjophthalmol-2018-313596. 10.1136/bjophthalmol-2018-313596
    1. Wessel MM, Aaker GD, Parlitsis G, et al. . Ultra-wide-field angiography improves the detection and classification of diabetic retinopathy. Retina 2012;32:785–91. 10.1097/IAE.0b013e3182278b64
    1. Silva PS, Cavallerano JD, Haddad NMN, et al. . Peripheral lesions identified on ultrawide field imaging predict increased risk of diabetic retinopathy progression over 4 years. Ophthalmology 2015;122:949–56. 10.1016/j.ophtha.2015.01.008
    1. Silva PS, Cavallerano JD, Sun JK, et al. . Nonmydriatic ultrawide field retinal imaging compared with dilated standard 7-field 35-mm photography and retinal specialist examination for evaluation of diabetic retinopathy. Am J Ophthalmol 2012;154:549–59. 10.1016/j.ajo.2012.03.019
    1. Bates DO. Vascular endothelial growth factors and vascular permeability. Cardiovasc Res 2010;87:262–71. 10.1093/cvr/cvq105
    1. Fang M, Fan W, Shi Y, et al. . Classification of regions of nonperfusion on ultra-widefield fluorescein angiography in patients with diabetic macular edema. Am J Ophthalmol 2019;206:74–81. 10.1016/j.ajo.2019.03.030
    1. Bressler SB, Liu D, Glassman AR, et al. . Change in diabetic retinopathy through 2 years: secondary analysis of a randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab. JAMA Ophthalmol 2017;135:558–68. 10.1001/jamaophthalmol.2017.0821
    1. Dhoot DS, Baker K, Saroj N, et al. . Baseline factors affecting changes in diabetic retinopathy severity scale score after intravitreal aflibercept or laser for diabetic macular edema. Ophthalmology 2018;125:51–6. 10.1016/j.ophtha.2017.06.029
    1. Couturier A, Rey P-A, Erginay A, et al. . Widefield OCT-angiography and fluorescein angiography assessments of nonperfusion in diabetic retinopathy and edema treated with anti-vascular endothelial growth factor. Ophthalmology 2019;126:1685–94. 10.1016/j.ophtha.2019.06.022

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner