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Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 8/2017

Open Access 01-08-2017 | Retinal Disorders

Effect of intravitreal ranibizumab on the ocular circulation of the untreated fellow eye

Authors: Masahiko Sugimoto, Takayasu Nunome, Rie Sakamoto, Maki Kobayashi, Mineo Kondo

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 8/2017

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Abstract

Purpose

To evaluate the effects of unilateral intravitreal ranibizumab (IVR) on the ocular circulation of the fellow eyes.

Methods

Fifteen eyes of 15 patients with macular edema (average age 69.6 ± 11.8 years) were studied. Eleven eyes had diabetic macular edema (DME) and four eyes had macular edema associated with a branch retinal vein occlusion. Each eye received 0.5 mg of IVR. The blood circulation on the optic nerve head of the treated and untreated eyes were determined by laser speckle flowgraphy (LSFG, Softcare Co., Ltd) before, 1 day, and 1 week after the IVR. The mean blur rate (MBR) and the relative changes of the MBRs determined as dMBR(%) = 100−(MBR before/MB after) × 100) were evaluated. The central macular thickness (CMT) and the rate of reduction in the thickness (dCMT = 100−(CMT before/CMT after) × 100) were also evaluated.

Results

The mean dMBR was significantly higher in the treated eyes than the untreated eyes at 1 day (−16.4 ± 17.0% vs 2.31 ± 19.3%) and at 1 week (−12.0 ± 14.6% vs 4.50 ± 25.9%) after the IVR (P = 0.02, paired t tests).

Conclusion

These findings indicate that if ranibizumab enters the systemic circulation, the concentration is not high enough to affect the ocular circulation of the fellow eyes.
Literature
1.
go back to reference Rosenfeld PJ, Brown DM, Heier JS et al (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431CrossRefPubMed Rosenfeld PJ, Brown DM, Heier JS et al (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431CrossRefPubMed
2.
go back to reference Brown DM, Kaiser PK, Michels M et al (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444CrossRefPubMed Brown DM, Kaiser PK, Michels M et al (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444CrossRefPubMed
3.
go back to reference Heier JS, Campochiaro PA, Yau L et al (2012) Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophthalmology 119:802–809CrossRefPubMed Heier JS, Campochiaro PA, Yau L et al (2012) Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophthalmology 119:802–809CrossRefPubMed
4.
go back to reference Nguyen QD, Brown DM, Marcus DM et al (2012) Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 119:789–801CrossRefPubMed Nguyen QD, Brown DM, Marcus DM et al (2012) Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 119:789–801CrossRefPubMed
5.
go back to reference Ueta T, Yanagi Y, Tamaki Y et al (2009) Cerebrovascular accidents in ranibizumab. Ophthalmology 116:362CrossRefPubMed Ueta T, Yanagi Y, Tamaki Y et al (2009) Cerebrovascular accidents in ranibizumab. Ophthalmology 116:362CrossRefPubMed
6.
go back to reference Fung AE, Rosenfeld PJ, Reichel E (2006) The international intravitreal bevacizumab safety survey: using the internet to assess drug safety worldwide. Br J Ophthalmol 90:1344–1349CrossRefPubMedPubMedCentral Fung AE, Rosenfeld PJ, Reichel E (2006) The international intravitreal bevacizumab safety survey: using the internet to assess drug safety worldwide. Br J Ophthalmol 90:1344–1349CrossRefPubMedPubMedCentral
7.
go back to reference Curtis LH, Hammill BG, Schulman KA et al (2010) Risks of mortality, myocardial infarction, bleeding, and stroke associated with therapies for age-related macular degeneration. Arch Ophthalmol 128:1273CrossRefPubMed Curtis LH, Hammill BG, Schulman KA et al (2010) Risks of mortality, myocardial infarction, bleeding, and stroke associated with therapies for age-related macular degeneration. Arch Ophthalmol 128:1273CrossRefPubMed
8.
go back to reference Schlenker MB, Thiruchelvam D, Redelmeier DA (2015) Intravitreal anti-vascular endothelial growth factor treatment and the risk of thromboembolism. Am J Ophthalmol 160:569–580CrossRefPubMed Schlenker MB, Thiruchelvam D, Redelmeier DA (2015) Intravitreal anti-vascular endothelial growth factor treatment and the risk of thromboembolism. Am J Ophthalmol 160:569–580CrossRefPubMed
9.
go back to reference Thulliez M, Angoulvant D, Le Lez ML et al (2014) Cardiovascular events and bleeding risk associated with intravitreal antivascular endothelial growth factor monoclonal antibodies: systematic review and meta-analysis. JAMA Ophthalmol 132:1317–1326CrossRefPubMed Thulliez M, Angoulvant D, Le Lez ML et al (2014) Cardiovascular events and bleeding risk associated with intravitreal antivascular endothelial growth factor monoclonal antibodies: systematic review and meta-analysis. JAMA Ophthalmol 132:1317–1326CrossRefPubMed
10.
go back to reference Kitchens JW, Do DV, Boyer DS et al (2016) Comprehensive review of ocular and systemic safety events with intravitreal aflibercept injection in randomized controlled trials. Ophthalmology 123:1511–1520CrossRefPubMed Kitchens JW, Do DV, Boyer DS et al (2016) Comprehensive review of ocular and systemic safety events with intravitreal aflibercept injection in randomized controlled trials. Ophthalmology 123:1511–1520CrossRefPubMed
11.
go back to reference Tamaki Y, Araie M, Kawamoto E et al (1994) Noncontact, two-dimensional measurement of retinal microcirculation using laser speckle phenomenon. Invest Ophthalmol Vis Sci 35:3825–3834PubMed Tamaki Y, Araie M, Kawamoto E et al (1994) Noncontact, two-dimensional measurement of retinal microcirculation using laser speckle phenomenon. Invest Ophthalmol Vis Sci 35:3825–3834PubMed
12.
go back to reference Tamaki Y, Araie M, Tomita K et al (1997) Effect of topical timolol on tissue circulation in optic nerve head. Jpn J Ophthalmol 41:297–304CrossRefPubMed Tamaki Y, Araie M, Tomita K et al (1997) Effect of topical timolol on tissue circulation in optic nerve head. Jpn J Ophthalmol 41:297–304CrossRefPubMed
13.
go back to reference Nagahara M, Tamaki Y, Tomidokoro A et al (2011) In vivo measurement of blood velocity in human major retinal vessels using the laser speckle method. Invest Ophthalmol Vis Sci 52:87–92CrossRefPubMed Nagahara M, Tamaki Y, Tomidokoro A et al (2011) In vivo measurement of blood velocity in human major retinal vessels using the laser speckle method. Invest Ophthalmol Vis Sci 52:87–92CrossRefPubMed
14.
go back to reference Nagasato D, Mitamura Y, Semba K, Akaiwa K, Nagasawa T, Yoshizumi Y, Tabuchi H, Kiuchi Y (2016) Correlation between optic nerve head circulation and visual function before and after anti-VEGF therapy for central retinal vein occlusion: prospective, interventional case series. BMC Ophthalmol 16:36CrossRefPubMedPubMedCentral Nagasato D, Mitamura Y, Semba K, Akaiwa K, Nagasawa T, Yoshizumi Y, Tabuchi H, Kiuchi Y (2016) Correlation between optic nerve head circulation and visual function before and after anti-VEGF therapy for central retinal vein occlusion: prospective, interventional case series. BMC Ophthalmol 16:36CrossRefPubMedPubMedCentral
15.
go back to reference Sugiyama T, Araie M, Riva CE et al (2010) Use of laser speckle flowgraphy in ocular blood flow research. Acta Ophthalmol 8:723–729CrossRef Sugiyama T, Araie M, Riva CE et al (2010) Use of laser speckle flowgraphy in ocular blood flow research. Acta Ophthalmol 8:723–729CrossRef
16.
go back to reference Liang Y, Downs JC, Fortune B et al (2009) Impact of systemic blood pressure on the relationship between intraocular pressure and blood flow in the optic nerve head of nonhuman primates. Invest Ophthalmol Vis Sci 50:2154–2160CrossRefPubMed Liang Y, Downs JC, Fortune B et al (2009) Impact of systemic blood pressure on the relationship between intraocular pressure and blood flow in the optic nerve head of nonhuman primates. Invest Ophthalmol Vis Sci 50:2154–2160CrossRefPubMed
17.
go back to reference Wang L, Cull GA, Piper C et al (2012) Anterior and posterior optic nerve head blood flow in nonhuman primate experimental glaucoma model measured by laser speckle imaging technique and microsphere method. Invest Ophthalmol Vis Sci 53:8303–8309CrossRefPubMedPubMedCentral Wang L, Cull GA, Piper C et al (2012) Anterior and posterior optic nerve head blood flow in nonhuman primate experimental glaucoma model measured by laser speckle imaging technique and microsphere method. Invest Ophthalmol Vis Sci 53:8303–8309CrossRefPubMedPubMedCentral
18.
go back to reference Hirooka K, Saito W, Hashimoto Y et al (2014) Increased macular choroidal blood flow velocity and decreased choroidal thickness with regression of punctate inner choroidopathy. BMC Ophthalmol 14:73CrossRefPubMedPubMedCentral Hirooka K, Saito W, Hashimoto Y et al (2014) Increased macular choroidal blood flow velocity and decreased choroidal thickness with regression of punctate inner choroidopathy. BMC Ophthalmol 14:73CrossRefPubMedPubMedCentral
19.
go back to reference Takahashi H, Sugiyama T, Tokushige H, Maeno T, Nakazawa T, Ikeda T, Araie M (2013) Comparison of CCD-equipped laser speckle flowgraphy with hydrogen gas clearance method in the measurement of optic nerve head microcirculation in rabbits. Exp Eye Res 108:10–15CrossRefPubMed Takahashi H, Sugiyama T, Tokushige H, Maeno T, Nakazawa T, Ikeda T, Araie M (2013) Comparison of CCD-equipped laser speckle flowgraphy with hydrogen gas clearance method in the measurement of optic nerve head microcirculation in rabbits. Exp Eye Res 108:10–15CrossRefPubMed
20.
go back to reference Wang L, Cull GA, Piper C, Burgoyne CF, Fortune B (2012) Anterior and posterior optic nerve head blood flow in nonhuman primate experimental glaucoma model measured by laser speckle imaging technique and microsphere method. Invest Ophthalmol Vis Sci 53:8303–8309CrossRefPubMedPubMedCentral Wang L, Cull GA, Piper C, Burgoyne CF, Fortune B (2012) Anterior and posterior optic nerve head blood flow in nonhuman primate experimental glaucoma model measured by laser speckle imaging technique and microsphere method. Invest Ophthalmol Vis Sci 53:8303–8309CrossRefPubMedPubMedCentral
21.
go back to reference Nitta F, Kunikata H, Aizawa N et al (2014) The effect of intravitreal bevacizumab on ocular blood flow in diabetic retinopathy and branch retinal vein occlusion as measured by laser speckle flowgraphy. Clin Ophthalmol 8:1119–1127PubMedPubMedCentral Nitta F, Kunikata H, Aizawa N et al (2014) The effect of intravitreal bevacizumab on ocular blood flow in diabetic retinopathy and branch retinal vein occlusion as measured by laser speckle flowgraphy. Clin Ophthalmol 8:1119–1127PubMedPubMedCentral
22.
go back to reference Haritoglou C, Kook D, Neubauer A et al (2006) Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina 26:999–1005CrossRefPubMed Haritoglou C, Kook D, Neubauer A et al (2006) Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina 26:999–1005CrossRefPubMed
23.
go back to reference Friedlander SM, Welch RM (2006) Vanishing disc neovascularization folowing intravitreal bevacizumab (Avastin) injection. Arch Ophthalmol 124:1365CrossRefPubMed Friedlander SM, Welch RM (2006) Vanishing disc neovascularization folowing intravitreal bevacizumab (Avastin) injection. Arch Ophthalmol 124:1365CrossRefPubMed
24.
go back to reference Toklu Y, Cakmak HB, Raza S et al (2011) Short-term effects of intravitreal bevacizumab (Avastin®) on retrobulbar hemodynamics in patients with neovascular age-related macular degeneration. Acta Ophthalmol 89:e41–e45CrossRefPubMed Toklu Y, Cakmak HB, Raza S et al (2011) Short-term effects of intravitreal bevacizumab (Avastin®) on retrobulbar hemodynamics in patients with neovascular age-related macular degeneration. Acta Ophthalmol 89:e41–e45CrossRefPubMed
25.
go back to reference Shahin M, Gad MA, Hamza W (2014) Impact of intravitreal triamcinolone acetonide versus intravitreal bevacizumab on retrobulbar hemodynamic in patients with diabetic macular edema. Cutan Ocul Toxicol 33:49–53CrossRefPubMed Shahin M, Gad MA, Hamza W (2014) Impact of intravitreal triamcinolone acetonide versus intravitreal bevacizumab on retrobulbar hemodynamic in patients with diabetic macular edema. Cutan Ocul Toxicol 33:49–53CrossRefPubMed
26.
go back to reference Enaida H, Okamoto K, Fujii H et al (2010) LSFG findings of proliferative diabetic retinopathy after intravitreal injection of bevacizumab. Ophthalmic Surg Lasers Imaging 41:e1–e3 Enaida H, Okamoto K, Fujii H et al (2010) LSFG findings of proliferative diabetic retinopathy after intravitreal injection of bevacizumab. Ophthalmic Surg Lasers Imaging 41:e1–e3
27.
go back to reference Nalluri SR, Chu D, Keresztes R et al (2008) Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 300:2277–2285CrossRefPubMed Nalluri SR, Chu D, Keresztes R et al (2008) Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 300:2277–2285CrossRefPubMed
28.
go back to reference Zangari M, Fink LM, Elice F et al (2009) Thrombotic events in patients with cancer receiving antiangiogenesis agents. J Clin Oncol 27:4865–4873CrossRefPubMed Zangari M, Fink LM, Elice F et al (2009) Thrombotic events in patients with cancer receiving antiangiogenesis agents. J Clin Oncol 27:4865–4873CrossRefPubMed
29.
go back to reference Degenring RF, Jonas JB (2004) Serum levels of triamcinolone acetonide after intravitreal injection. Am J Ophthalmol 137:1142–1143CrossRefPubMed Degenring RF, Jonas JB (2004) Serum levels of triamcinolone acetonide after intravitreal injection. Am J Ophthalmol 137:1142–1143CrossRefPubMed
30.
go back to reference Chiariello M, Indolfi C, Cotecchia MR et al (1985) Asymptomatic transient ST changes during ambulatory ECG monitoring in diabetic patients. Am Heart J 110:529–534CrossRefPubMed Chiariello M, Indolfi C, Cotecchia MR et al (1985) Asymptomatic transient ST changes during ambulatory ECG monitoring in diabetic patients. Am Heart J 110:529–534CrossRefPubMed
31.
go back to reference Bouchi R, Babazono T, Yoshida N et al (2010) Silent cerebral infarction is associated with the development and progression of nephropathy in patients with type 2 diabetes. Hypertens Res 33:1000–1003CrossRefPubMed Bouchi R, Babazono T, Yoshida N et al (2010) Silent cerebral infarction is associated with the development and progression of nephropathy in patients with type 2 diabetes. Hypertens Res 33:1000–1003CrossRefPubMed
32.
go back to reference Bressler NM, Boyer DS, Williams DF et al (2012) Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials. Retina 32:1821–1828CrossRefPubMed Bressler NM, Boyer DS, Williams DF et al (2012) Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials. Retina 32:1821–1828CrossRefPubMed
33.
go back to reference Avery RL, Gordon GM (2016) Systemic safety of prolonged monthly anti-vascular endothelial growth factor therapy for diabetic macular edema: a systematic review and meta-analysis. JAMA Ophthalmol 134:21–29CrossRefPubMed Avery RL, Gordon GM (2016) Systemic safety of prolonged monthly anti-vascular endothelial growth factor therapy for diabetic macular edema: a systematic review and meta-analysis. JAMA Ophthalmol 134:21–29CrossRefPubMed
34.
go back to reference Julien S, Biesemeier A, Taubitz T et al (2014) Different effects of intravitreally injected ranibizumab and aflibercept on retinal and choroidal tissues of monkey eyes. Br J Ophthalmol 98:813–825CrossRefPubMed Julien S, Biesemeier A, Taubitz T et al (2014) Different effects of intravitreally injected ranibizumab and aflibercept on retinal and choroidal tissues of monkey eyes. Br J Ophthalmol 98:813–825CrossRefPubMed
35.
go back to reference Terasaki H, Sakamoto T, Shirasawa M et al (2015) Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro. Retina 35:1007–1015CrossRefPubMed Terasaki H, Sakamoto T, Shirasawa M et al (2015) Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro. Retina 35:1007–1015CrossRefPubMed
36.
go back to reference CATT Research Group, Martin DF, Maguire MG et al (2011) Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 364:1897–1908CrossRef CATT Research Group, Martin DF, Maguire MG et al (2011) Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 364:1897–1908CrossRef
37.
go back to reference Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman AR et al (2015) Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 372:1193–1203CrossRef Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman AR et al (2015) Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 372:1193–1203CrossRef
38.
go back to reference Avery RL, Castellarin AA, Steinle NC et al (2014) Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD. Br J Ophthalmol 98:1636–1641CrossRefPubMedPubMedCentral Avery RL, Castellarin AA, Steinle NC et al (2014) Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD. Br J Ophthalmol 98:1636–1641CrossRefPubMedPubMedCentral
39.
go back to reference Yoshida I, Shiba T, Taniguchi H et al (2014) Evaluation of plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab and aflibercept for exudative age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 252:1483–1489CrossRefPubMed Yoshida I, Shiba T, Taniguchi H et al (2014) Evaluation of plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab and aflibercept for exudative age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 252:1483–1489CrossRefPubMed
40.
go back to reference Wang X, Sawada T, Sawada O et al (2014) Serum and plasma vascular endothelial growth factor concentrations before and after intravitreal injection of aflibercept or ranibizumab for age-related macular degeneration. Am J Ophthalmol 158:738–744CrossRefPubMed Wang X, Sawada T, Sawada O et al (2014) Serum and plasma vascular endothelial growth factor concentrations before and after intravitreal injection of aflibercept or ranibizumab for age-related macular degeneration. Am J Ophthalmol 158:738–744CrossRefPubMed
41.
go back to reference Zhang Y, Yao Z, Kaila N et al (2014) Pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion or diabetic macular edema. Ophthalmology 121:2237–2246CrossRefPubMed Zhang Y, Yao Z, Kaila N et al (2014) Pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion or diabetic macular edema. Ophthalmology 121:2237–2246CrossRefPubMed
42.
go back to reference Christoforidis JB, Carlton MM, Knopp MV, Hinkle GH (2011) PET/CT imaging of I-124-radiolabeled bevacizumab and ranibizumab after intravitreal injection in a rabbit model. Invest Ophthalmol Vis Sci 52:5899–5903CrossRefPubMed Christoforidis JB, Carlton MM, Knopp MV, Hinkle GH (2011) PET/CT imaging of I-124-radiolabeled bevacizumab and ranibizumab after intravitreal injection in a rabbit model. Invest Ophthalmol Vis Sci 52:5899–5903CrossRefPubMed
43.
go back to reference Xu L, Lu T, Tuomi L et al (2013) Pharmacokinetics of ranibizumab in patients with neovascular age-related macular degeneration: a population approach. Invest Ophthalmol Vis Sci 54:1616–1624CrossRefPubMed Xu L, Lu T, Tuomi L et al (2013) Pharmacokinetics of ranibizumab in patients with neovascular age-related macular degeneration: a population approach. Invest Ophthalmol Vis Sci 54:1616–1624CrossRefPubMed
44.
go back to reference Calvo CM, Sridhar J, Shahlaee A et al (2016) Reduction of diabetic macular edema in the untreated fellow eye following intravitreal injection of aflibercept. Ophthalmic Surg Lasers Imaging Retina 47:474–476CrossRefPubMed Calvo CM, Sridhar J, Shahlaee A et al (2016) Reduction of diabetic macular edema in the untreated fellow eye following intravitreal injection of aflibercept. Ophthalmic Surg Lasers Imaging Retina 47:474–476CrossRefPubMed
45.
go back to reference Hanhart J, Tiosano L, Averbukh E, Banin E, Hemo I, Chowers I (2014) Fellow eye effect of unilateral intravitreal bevacizumab injection in eyes with diabetic macular edema. Eye (Lond) 28:646–653CrossRef Hanhart J, Tiosano L, Averbukh E, Banin E, Hemo I, Chowers I (2014) Fellow eye effect of unilateral intravitreal bevacizumab injection in eyes with diabetic macular edema. Eye (Lond) 28:646–653CrossRef
46.
go back to reference Bakbak B, Ozturk BT, Gonul S, Yilmaz M, Gedik S (2013) Comparison of the effect of unilateral intravitreal bevacizumab and ranibizumab injection on diabetic macular edema of the fellow eye. J Ocul Pharmacol Ther 29:728–732CrossRefPubMed Bakbak B, Ozturk BT, Gonul S, Yilmaz M, Gedik S (2013) Comparison of the effect of unilateral intravitreal bevacizumab and ranibizumab injection on diabetic macular edema of the fellow eye. J Ocul Pharmacol Ther 29:728–732CrossRefPubMed
Metadata
Title
Effect of intravitreal ranibizumab on the ocular circulation of the untreated fellow eye
Authors
Masahiko Sugimoto
Takayasu Nunome
Rie Sakamoto
Maki Kobayashi
Mineo Kondo
Publication date
01-08-2017
Publisher
Springer Berlin Heidelberg
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 8/2017
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-017-3692-z

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