Clinical Effectiveness of Intravitreal Therapy With Ranibizumab vs Aflibercept vs Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion A Randomized Clinical Trial

被引：94

作者：

Hykin, Philip ^{[1
]}

Prevost, A. Toby ^{[2
]}

Vasconcelos, Joana C. ^{[2
]}

Murphy, Caroline ^{[3
]}

Kelly, Joanna ^{[3
]}

Ramu, Jayashree ^{[1
]}

Hounsome, Barry ^{[3
]}

Yang, Yit ^{[4
]}

Harding, Simon P. ^{[5
,6
]}

Lotery, Andrew ^{[7
]}

Chakravarthy, Usha ^{[8
]}

Sivaprasad, Sobha ^{[1
]}

Eleftheriadis, Haralabos ^{[9
]}

Briggs, Michael ^{[10
]}

Williams, Michael ^{[11
]}

Abugreen, Salwa ^{[12
]}

Ghanchi, Faruque ^{[13
]}

Narendran, Nirodhini ^{[14
]}

Hughes, Edward ^{[15
]}

Ross, Adam ^{[16
]}

Gupta, Nitin ^{[17
]}

Turner, Stephen ^{[18
]}

Osoba, Yinka ^{[18
]}

Patel, Jignesh ^{[19
]}

Pagliarini, Sergio ^{[20
]}

Lip, Peck-Lin ^{[21
]}

Patel, Nishal ^{[22
]}

Jafree, Afsar ^{[22
]}

Menon, Geeta ^{[23
]}

Patra, Sudeshna ^{[24
]}

Burton, Ben ^{[25
]}

Taylor, Simon ^{[26
]}

Mackenzie, Sarah ^{[27
]}

Gale, Richard ^{[28
]}

Vadivelu, Komala ^{[29
]}

McKibbin, Martin ^{[30
]}

George, Sheena ^{[31
]}

Almeida, Goncalo ^{[32
]}

Sen, Piyali ^{[33
]}

Patrao, Namritha ^{[33
]}

Menon, Deepthy ^{[33
]}

Nicholson, Luke ^{[33
]}

D'Souza, Yvonne ^{[34
]}

Talks, James ^{[35
]}

Sundaram, Venki ^{[36
]}

Banerjee, Sanjiv ^{[37
]}

Habib, Maged ^{[38
]}

Ram, Raghu ^{[39
]}

Brand, Christopher ^{[40
]}

Newman, Douglas ^{[41
]}

机构：

[1] Moorfields Biomed Res Ctr, Natl Inst Hlth Res, 162 City Rd, London EC1V 2PD, England

[2] Imperial Coll London, Imperial Clin Trials Unit, Sch Publ Hlth, London, England

[3] Kings Coll London, Kings Hlth Partners, Kings Clin Trials Unit, London, England

[4] Wolverhampton Eye Infirm, Wolverhampton, W Midlands, England

[5] Univ Liverpool, Eye & Vis Sci, St Pauls Eye Unit, Royal Liverpool Univ Hosp, Liverpool, Merseyside, England

[6] Liverpool Hlth Partners, Liverpool, Merseyside, England

[7] Univ Southampton, Dept Med, Southampton, Hants, England

[8] Queens Univ Belfast, Biomed Sci, Belfast, Antrim, North Ireland

[9] Kings Coll Hosp NHS Fdn Trust, Dept Ophthalmol, London, England

[10] Royal Liverpool & Broadgreen Univ Hosp NHS Trust, St Pauls Eye Unit, Liverpool, Merseyside, England

[11] Queens Univ Belfast, Dept Ophthalmol, Royal Victoria, Belfast, Antrim, North Ireland

[12] Royal Blackburn Hosp, Dept Ophthalmol, Blackburn, Lancs, England

[13] Bradford Teaching Hosp NHS Fdn Trust, Bradford Ophthalmol Res Network, Bradford, W Yorkshire, England

[14] Wolverhampton & Midland Counties Eye Infirm, New Cross Hosp, Wolverhampton, W Midlands, England

[15] Sussex Eye Hosp, Brighton, E Sussex, England

[16] Bristol Eye Hosp, Bristol, Avon, England

[17] West Suffolk NHS Fdn Trust, Dept Ophthalmol, Bury St Edmunds, Suffolk, England

[18] Torbay Hosp, Dept Ophthalmol, Torquay, Devon, England

[19] Essex Cty Hosp, Dept Ophthalmol, Colchester, Essex, England

[20] Hosp St Cross, Macular Unit, Rugby, England

[21] Birmingham & Midlands Eye Clin, Birmingham, W Midlands, England

[22] Kent & Canterbury Hosp, Canterbury, Kent, England

[23] Frimley Pk Hosp NHS Fdn Trust, Dept Ophthalmol, Surrey, England

[24] Barts Hlth NHS Trust, Whipps Cross Hosp, London, England

[25] James Paget Univ Hosp, Great Yarmouth, Norfolk, England

[26] Royal Surrey Cty Hosp, Dept Ophthalmol, Guildford, Surrey, England

[27] Harrogate & Dist NHS Fdn Trust, Harrogate, N Yorkshire, England

[28] York Teaching Hosp NHS Fdn Trust, York, N Yorkshire, England

[29] Cty Durham & Darlington NHS Fdn Trust, Darlington Mem Hosp, Darlington, Durham, England

[30] Leeds Teaching Hosp NHS Trust, St Jamess Univ Hosp, Dept Ophthalmol, Leeds, W Yorkshire, England

[31] Hillingdon Hosp NHS Fdn Trust, Dept Ophthalmol, London, England

[32] Maidstone & Tunbridge Wells NHS Trust, Dept Ophthalmol, Tunbridge Wells, Kent, England

[33] Moorfields Eye Hosp, London, England

[34] Manchester Univ NHS Fdn Trust, Cent Manchester Hosp, Manchester, Lancs, England

[35] Royal Victoria Infirm, Newcastle Upon Tyne, Tyne & Wear, England

[36] Luton & Dunstable NHS Univ Hosp, Luton, Herts, England

[37] Univ Hosp Wales, Cardiff, S Glam, Wales

[38] Sunderland Eye Infirm, Sunderland, Tyne & Wear, England

[39] North Glamorgan NHS Trust, Royal Glamorgan Hosp, Llantrisant, Wales

[40] Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England

[41] Addenbrookes Hosp, Cambridge, England

[42] Gartnavel Royal Hosp, Dept Ophthalmol, Glasgow, Lanark, Scotland

[43] Bolton NHS Fdn Trust, Dept Ophthalmol, Bolton, England

[44] Calderdale Royal Hosp, Halifax, England

[45] Univ Hosp Leicester NHS Trust, Leicester, Leics, England

[46] Norfolk & Norwich Univ Hosp, Dept Ophthalmol, Norwich, Norfolk, England

[47] Cheltenham Gen Hosp, Cheltenham, Glos, England

[48] Hull & East Yorkshire Hosp NHS Trust, Dept Ophthalmol, Kingston Upon Hull, N Humberside, England

[49] Western Eye Hosp, London, England

[50] Princess Alexandra Hosp, Harlow, Essex, England

来源：

JAMA OPHTHALMOLOGY | 2019年 / 137卷 / 11期

关键词：

SUSTAINED BENEFITS; VISUAL-ACUITY; PREVALENCE; INJECTION;

D O I：

10.1001/jamaophthalmol.2019.3305

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

IMPORTANCE The comparative clinical effectiveness of ranibizumab, aflibercept, and bevacizumab for the management of macular edema due to central retinal vein occlusion (CRVO) is unclear. OBJECTIVE To determine whether intravitreal aflibercept or bevacizumab compared with ranibizumab results in a noninferior mean change in vision at 100 weeks for eyes with CRVO-related macular edema. DESIGN, SETTING, AND PARTICIPANTS This prospective, 3-arm, double-masked, randomized noninferiority trial (Lucentis, Eylea, Avastin in Vein Occlusion [LEAVO] Study) took place from December 12, 2014, through December 16, 2016, at 44 UK National Health Service ophthalmology departments. Inclusion criteria included age 18 years or older, visual impairment due to CRVO-related macular edema of less than 12 months with best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score (approximate Snellen equivalent) in the study eye between 19 (20/400) and 78 (20/32), and spectral domain optical coherence tomography imaging central subfield thickness of 320 mu m or greater. Data were analyzed from March 4, 2019, to April 26, 2019. INTERVENTIONS Participants were randomized (1:1:1) to receive repeated intravitreal injections of ranibizumab (0.5 mg/0.05 mL) (n=155), aflibercept (2.0 mg/0.05 mL) (n=154), or bevacizumab (1.25 mg/0.05 mL) (n=154) for 100 weeks. MAIN OUTCOMES AND MEASURES Adjusted mean change in BCVA in the study eye at 100 weeks wherein noninferiority was concluded if the lower bounds of the 95% CI of both the intention-to-treat and the per protocol analyses were above -5 letters. RESULTS Of 463 participants, 265 (57.2%) were male, with a mean (SD) age of 69.1 (13.0) years. The mean (SD) gain in BCVA letter score was 12.5 (21.1) for ranibizumab, 15.1 (18.7) for aflibercept, and 9.8 (21.4) for bevacizumab at 100 weeks. Aflibercept was noninferior to ranibizumab (intention-to-treat-adjusted mean BCVA difference, 2.23 letters; 95% CI, -2.17 to 6.63 letters; P<.001). Bevacizumab was not noninferior to ranibizumab (intention-to-treat-adjusted mean BCVA difference, -1.73 letters; 95% CI, -6.12 to 2.67 letters; P=.07). The per protocol analysis conclusions were similar. Fewer mean injections were given in the aflibercept group (10.0) than in the ranibizumab (11.8) group (mean difference at 100 weeks, -1.9; 95% CI, -2.9 to -0.8). CONCLUSIONS AND RELEVANCE Mean changes in vision after treatment of macular edema due to CRVO were no worse using aflibercept compared with ranibizumab. Mean changes in vision using bevacizumab compared with ranibizumab were inconclusive regarding vision outcomes (ie, the change in visual acuity from baseline, on average, may be worse or may not be worse when using bevacizumab compared with ranibizumab).

引用

页码：1256 / 1264

页数：9

共 22 条

[1]

[Anonymous], RET VEIN OCCL RVO

[2]

[Anonymous], LANCET

[3] Early Response to Anti-Vascular Endothelial Growth Factor and Two-Year Outcomes Among Eyes With Diabetic Macular Edema in Protocol T [J].

Bressler, Neil M. ;

Beaulieu, Wesley T. ;

Maguire, Maureen G. ;

Glassman, Adam R. ;

Blinder, Kevin J. ;

Bressler, Susan B. ;

Gonzalez, Victor H. ;

Jampol, Lee M. ;

Melia, Michele ;

Sun, Jennifer K. ;

Wells, John A., III .

AMERICAN JOURNAL OF OPHTHALMOLOGY, 2018, 195 :93-100

[4] Intravitreal Aflibercept Injection for Macular Edema Secondary to Central Retinal Vein Occlusion: 1-Year Results From the Phase 3 COPERNICUS Study [J].

Brown, David M. ;

Heier, Jeffrey S. ;

Clark, W. Lloyd ;

Boyer, David S. ;

Vitti, Robert ;

Berliner, Alyson J. ;

Zeitz, Oliver ;

Sandbrink, Rupert ;

Zhu, Xiaoping ;

Haller, Julia A. .

AMERICAN JOURNAL OF OPHTHALMOLOGY, 2013, 155 (03) :429-437

[5] Sustained Benefits from Ranibizumab for Macular Edema following Central Retinal Vein Occlusion: Twelve-Month Outcomes of a Phase III Study [J].

Campochiaro, Peter A. ;

Brown, David M. ;

Awh, Carl C. ;

Lee, S. Young ;

Gray, Sarah ;

Saroj, Namrata ;

Murahashi, Wendy Yee ;

Rubio, Roman G. .

OPHTHALMOLOGY, 2011, 118 (10) :2041-2049

[6] Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial [J].

Chakravarthy, Usha ;

Harding, Simon P. ;

Rogers, Chris A. ;

Downes, Susan M. ;

Lotery, Andrew J. ;

Culliford, Lucy A. ;

Reeves, Barnaby C. .

LANCET, 2013, 382 (9900) :1258-1267

[7] Visual acuity outcome and predictive factors after bevacizumab for central retinal vein occlusion [J].

Daien, Vincent ;

Navarre, Sophie ;

Fesler, Pierre ;

Vergely, Laurence ;

Villain, Max ;

Schneider, Christelle .

EUROPEAN JOURNAL OF OPHTHALMOLOGY, 2012, 22 (06) :1013-1018

[8] PROSPECTIVE STUDY OF INTRAVITREAL TRIAMCINOLONE ACETONIDE VERSUS BEVACIZUMAB FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION [J].

Ding, Xiaoyan ;

Li, Jiaqing ;

Hu, Xuting ;

Yu, Shanshan ;

Pan, Jianying ;

Tang, Shibo .

RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES, 2011, 31 (05) :838-845

[9] Benefit from Bevacizumab for Macular Edema in Central Retinal Vein Occlusion: Twelve-Month Results of a Prospective, Randomized Study [J].

Epstein, David L. ;

Algvere, Peep V. ;

von Wendt, Gunvor ;

Seregard, Stefan ;

Kvanta, Anders .

OPHTHALMOLOGY, 2012, 119 (12) :2587-2591

[10] Intravitreal Aflibercept Injection for Macular Edema Due to Central Retinal Vein Occlusion [J].

Heier, Jeffrey S. ;

Clark, W. Lloyd ;

Boyer, David S. ;

Brown, David M. ;

Vitti, Robert ;

Berliner, Alyson J. ;

Kazmi, Husain ;

Ma, Yu ;

Stemper, Brigitte ;

Zeitz, Oliver ;

Sandbrink, Rupert ;

Haller, Julia A. .

OPHTHALMOLOGY, 2014, 121 (07) :1414-U143

← 1 2 3 →