Tolerating subretinal fluid in neovascular age-related macular degeneration treated with ranibizumab using a treat-and-extend regimen: FLUID study 24-month results

FLUID Investigators

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

PURPOSE: To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF.

DESIGN: Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial.

PARTICIPANTS: Participants with treatment-naïve active subfoveal choroidal neovascularization (CNV).

METHODS: Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF; intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 μm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome.

MAIN OUTCOME MEASURES: Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24.

RESULTS: Of the 349 participants randomized (intensive arm, n = 174; relaxed arm, n = 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P = 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively; P = 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively; P = 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5]; P = 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8%; P = 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0%; P = 0.005).

CONCLUSIONS: Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.

Original languageEnglish
Pages (from-to)723-734
JournalOphthalmology
Volume126
Issue number5
Early online date29 Nov 2018
DOIs
Publication statusPublished - May 2019

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Subretinal Fluid
Macular Degeneration
Visual Acuity
Injections
Therapeutics
Choroidal Neovascularization
Ranibizumab
Clinical Trials

Cite this

@article{e559e4a3217c45e7945873112e7eb123,
title = "Tolerating subretinal fluid in neovascular age-related macular degeneration treated with ranibizumab using a treat-and-extend regimen: FLUID study 24-month results",
abstract = "PURPOSE: To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF.DESIGN: Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial.PARTICIPANTS: Participants with treatment-na{\"i}ve active subfoveal choroidal neovascularization (CNV).METHODS: Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF; intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 μm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome.MAIN OUTCOME MEASURES: Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24.RESULTS: Of the 349 participants randomized (intensive arm, n = 174; relaxed arm, n = 175), 279 (79.9{\%}) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P = 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5{\%} and 56.6{\%}, respectively; P = 0.92) and 20/200 or worse VA (8.7{\%} and 8.1{\%}, respectively; P = 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5]; P = 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5{\%}) than in the relaxed group (2.8{\%}; P = 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6{\%}) than the intensive group (15.0{\%}; P = 0.005).CONCLUSIONS: Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.",
author = "{FLUID Investigators} and Guymer, {Robyn H.} and Markey, {Caroline M.} and McAllister, {Ian L.} and Gillies, {Mark C.} and Alex Hunyor and Jennifer Arnold and Andrew Chang and Adil Syed and Geoffrey Broadhead and Thomas Pham and Thomas Hong and Lily Wong and Meidong Zhu and Shelley Burnett and Nichole Joachim and Wijeyanthy Wijeyakumar and Gabriel Manalang and Cleopatra Mhlanga and Nicole Joachim and Kimperly Spooner and Paul Mitchell and Suriya Foran and Christabel Wilson and Victoria Cossatto and Laskshmi Waniganayke and Vivien Mai and Rabiya Atif and Lakshmi Wa and Sapna Maharaj and David Liong and Christine Matic and Katherine Tran and Sheenal Jas and Danielle Gibbs and Sanj Wickremasinghe and Robyn Guymer and Lyndell Lim and Sukhpal Sandhu and Thanh Nguyen and Dania Qatarneh and Hessom Razavi and Elaine Chong and Matthew Little and Gaurav Bhardwau and Michael Ayres and Michael Chen and Daini Ong and Katarina Creese and Tricia Drew and {D'Sylva Parfett}, Carly and Tanya Pejnovic and Thuy Chau and Sutha Sanmugasundram and Maria Kolic and Elizabeth Glatz and Tonder, {Tina Marie} and Alan Luckie and Stephen Heery and Timothy Steele and Jennifer Arnold and Bryan Matthews and Julie Croft and Alex Breen and Bronwyn Gabriel and Maegan Anderson and Michelle Dodds and Marcus Dwyer and Bev Brown and Jacinta Dwyer and Ivan Fu and Helen Macauley and James Wong and Rajeev Chalasani and Charmaine Lim and Son Huynh and Timothy Nolan and James Leong and Kit Lau and Swas Kumar and Trang Nguyen and Joseph Bitar and Hannah Ahern and Arooj Ali and Nuria Zamora and Angela Lai and Randa Moussa and Carmen Do and Nitin Verma and Guy Bylsma and Andrew Traill and Beverley Curry and Amy Paprotny and Alfonso Ayesa and Alyse Johns and Zanobia Ujjainwala and Andrew Maver and Derek Chan and John Chang and Kang, {Hyong Kwon} and Gavin Stringfellow and Terence Tan and Helen Cass and Trish Forsyth and Anh Nguyen and Angela Chung and Harriette Ayson and Catherine Severino and Caroline Chahine and Lara Collis and Anita Cristy and Mona Mohmodian and Selina Webb and Muradiya Payir and Mara Garibaldi and Trazia Mekhail and Brendan Vote and Tze'Yo Toh and Nima Pakrou and Jennie Rossetto and Shannon Harris and Rachael Adams and Rachael Groves and Maddie Johns and Kristie Richards and Eliza Jenkins and Natalie Daley and James Baker and Mark Gorbatov and Lavaniya Rajanayagam and Ludmila Jitskaia and Jenny Xie and Anthony Nguyen and Ian McAllister and Fred Chen and Tim Isaacs and Dickens, {Tracey Anne} and Rachel Matthews and Amelia Jason and Ivy Tang and Gareth Lingham and Holly Brown and Alla Soloshenko and Max Cuypers and Anne McSweeney and Jolly Gilhotra and Shane Durkin and James Muecke and Kerin Haywood and Cathy Brko and Rinty Vincent and Carolyn Luscombe and Alex Hunyor and Christine Younan and Robert Chong and Rohan Merani and Adrian Fung and Ho, {I. Van} and Gerald Liew and Vinnci Lee and Gerald Chan and Sarah Liu and Tharini Ganess and Susanthy Rajasundaran and Maryam Sadat and Godfrey Quin and Stephen Ong and Claire Hooper and Vivien Dihn and Ward Al-Ghurani and Sally Ngai and Maria Choi and Gordana Tisma and {Van Heerden}, Anton and Anthony Hall and Kira Michalova and Natalie Coleman and Allanah Price and Mercy Nguyen and Clodia Hanna and Camille Collins and Elaina Dickeson and Annie Lee and Mela Bilyk and Theresa Lee and John Downie and Naggi Assaad and Leanne Cooper and Catherine Le and Amanda Armanssen and Zena Khalil",
year = "2019",
month = "5",
doi = "10.1016/j.ophtha.2018.11.025",
language = "English",
volume = "126",
pages = "723--734",
journal = "Ophthalmology: journal of the American Academy of Ophthalmology",
issn = "0161-6420",
publisher = "Elsevier",
number = "5",

}

Tolerating subretinal fluid in neovascular age-related macular degeneration treated with ranibizumab using a treat-and-extend regimen : FLUID study 24-month results. / FLUID Investigators.

In: Ophthalmology, Vol. 126, No. 5, 05.2019, p. 723-734.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tolerating subretinal fluid in neovascular age-related macular degeneration treated with ranibizumab using a treat-and-extend regimen

T2 - FLUID study 24-month results

AU - FLUID Investigators

AU - Guymer, Robyn H.

AU - Markey, Caroline M.

AU - McAllister, Ian L.

AU - Gillies, Mark C.

AU - Hunyor, Alex

AU - Arnold, Jennifer

AU - Chang, Andrew

AU - Syed, Adil

AU - Broadhead, Geoffrey

AU - Pham, Thomas

AU - Hong, Thomas

AU - Wong, Lily

AU - Zhu, Meidong

AU - Burnett, Shelley

AU - Joachim, Nichole

AU - Wijeyakumar, Wijeyanthy

AU - Manalang, Gabriel

AU - Mhlanga, Cleopatra

AU - Joachim, Nicole

AU - Spooner, Kimperly

AU - Mitchell, Paul

AU - Foran, Suriya

AU - Wilson, Christabel

AU - Cossatto, Victoria

AU - Waniganayke, Laskshmi

AU - Mai, Vivien

AU - Atif, Rabiya

AU - Wa, Lakshmi

AU - Maharaj, Sapna

AU - Liong, David

AU - Matic, Christine

AU - Tran, Katherine

AU - Jas, Sheenal

AU - Gibbs, Danielle

AU - Wickremasinghe, Sanj

AU - Guymer, Robyn

AU - Lim, Lyndell

AU - Sandhu, Sukhpal

AU - Nguyen, Thanh

AU - Qatarneh, Dania

AU - Razavi, Hessom

AU - Chong, Elaine

AU - Little, Matthew

AU - Bhardwau, Gaurav

AU - Ayres, Michael

AU - Chen, Michael

AU - Ong, Daini

AU - Creese, Katarina

AU - Drew, Tricia

AU - D'Sylva Parfett, Carly

AU - Pejnovic, Tanya

AU - Chau, Thuy

AU - Sanmugasundram, Sutha

AU - Kolic, Maria

AU - Glatz, Elizabeth

AU - Tonder, Tina Marie

AU - Luckie, Alan

AU - Heery, Stephen

AU - Steele, Timothy

AU - Arnold, Jennifer

AU - Matthews, Bryan

AU - Croft, Julie

AU - Breen, Alex

AU - Gabriel, Bronwyn

AU - Anderson, Maegan

AU - Dodds, Michelle

AU - Dwyer, Marcus

AU - Brown, Bev

AU - Dwyer, Jacinta

AU - Fu, Ivan

AU - Macauley, Helen

AU - Wong, James

AU - Chalasani, Rajeev

AU - Lim, Charmaine

AU - Huynh, Son

AU - Nolan, Timothy

AU - Leong, James

AU - Lau, Kit

AU - Kumar, Swas

AU - Nguyen, Trang

AU - Bitar, Joseph

AU - Ahern, Hannah

AU - Ali, Arooj

AU - Zamora, Nuria

AU - Lai, Angela

AU - Moussa, Randa

AU - Do, Carmen

AU - Verma, Nitin

AU - Bylsma, Guy

AU - Traill, Andrew

AU - Curry, Beverley

AU - Paprotny, Amy

AU - Ayesa, Alfonso

AU - Johns, Alyse

AU - Ujjainwala, Zanobia

AU - Maver, Andrew

AU - Chan, Derek

AU - Chang, John

AU - Kang, Hyong Kwon

AU - Stringfellow, Gavin

AU - Tan, Terence

AU - Cass, Helen

AU - Forsyth, Trish

AU - Nguyen, Anh

AU - Chung, Angela

AU - Ayson, Harriette

AU - Severino, Catherine

AU - Chahine, Caroline

AU - Collis, Lara

AU - Cristy, Anita

AU - Mohmodian, Mona

AU - Webb, Selina

AU - Payir, Muradiya

AU - Garibaldi, Mara

AU - Mekhail, Trazia

AU - Vote, Brendan

AU - Toh, Tze'Yo

AU - Pakrou, Nima

AU - Rossetto, Jennie

AU - Harris, Shannon

AU - Adams, Rachael

AU - Groves, Rachael

AU - Johns, Maddie

AU - Richards, Kristie

AU - Jenkins, Eliza

AU - Daley, Natalie

AU - Baker, James

AU - Gorbatov, Mark

AU - Rajanayagam, Lavaniya

AU - Jitskaia, Ludmila

AU - Xie, Jenny

AU - Nguyen, Anthony

AU - McAllister, Ian

AU - Chen, Fred

AU - Isaacs, Tim

AU - Dickens, Tracey Anne

AU - Matthews, Rachel

AU - Jason, Amelia

AU - Tang, Ivy

AU - Lingham, Gareth

AU - Brown, Holly

AU - Soloshenko, Alla

AU - Cuypers, Max

AU - McSweeney, Anne

AU - Gilhotra, Jolly

AU - Durkin, Shane

AU - Muecke, James

AU - Haywood, Kerin

AU - Brko, Cathy

AU - Vincent, Rinty

AU - Luscombe, Carolyn

AU - Hunyor, Alex

AU - Younan, Christine

AU - Chong, Robert

AU - Merani, Rohan

AU - Fung, Adrian

AU - Ho, I. Van

AU - Liew, Gerald

AU - Lee, Vinnci

AU - Chan, Gerald

AU - Liu, Sarah

AU - Ganess, Tharini

AU - Rajasundaran, Susanthy

AU - Sadat, Maryam

AU - Quin, Godfrey

AU - Ong, Stephen

AU - Hooper, Claire

AU - Dihn, Vivien

AU - Al-Ghurani, Ward

AU - Ngai, Sally

AU - Choi, Maria

AU - Tisma, Gordana

AU - Van Heerden, Anton

AU - Hall, Anthony

AU - Michalova, Kira

AU - Coleman, Natalie

AU - Price, Allanah

AU - Nguyen, Mercy

AU - Hanna, Clodia

AU - Collins, Camille

AU - Dickeson, Elaina

AU - Lee, Annie

AU - Bilyk, Mela

AU - Lee, Theresa

AU - Downie, John

AU - Assaad, Naggi

AU - Cooper, Leanne

AU - Le, Catherine

AU - Armanssen, Amanda

AU - Khalil, Zena

PY - 2019/5

Y1 - 2019/5

N2 - PURPOSE: To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF.DESIGN: Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial.PARTICIPANTS: Participants with treatment-naïve active subfoveal choroidal neovascularization (CNV).METHODS: Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF; intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 μm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome.MAIN OUTCOME MEASURES: Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24.RESULTS: Of the 349 participants randomized (intensive arm, n = 174; relaxed arm, n = 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P = 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively; P = 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively; P = 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5]; P = 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8%; P = 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0%; P = 0.005).CONCLUSIONS: Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.

AB - PURPOSE: To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF.DESIGN: Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial.PARTICIPANTS: Participants with treatment-naïve active subfoveal choroidal neovascularization (CNV).METHODS: Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF; intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 μm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome.MAIN OUTCOME MEASURES: Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24.RESULTS: Of the 349 participants randomized (intensive arm, n = 174; relaxed arm, n = 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P = 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively; P = 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively; P = 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5]; P = 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8%; P = 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0%; P = 0.005).CONCLUSIONS: Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.

UR - http://www.scopus.com/inward/record.url?scp=85059860252&partnerID=8YFLogxK

U2 - 10.1016/j.ophtha.2018.11.025

DO - 10.1016/j.ophtha.2018.11.025

M3 - Article

VL - 126

SP - 723

EP - 734

JO - Ophthalmology: journal of the American Academy of Ophthalmology

JF - Ophthalmology: journal of the American Academy of Ophthalmology

SN - 0161-6420

IS - 5

ER -