Long term retinal morphology and functional associations in treated neovascular age-related macular degeneration: Findings from the Inhibition of VEGF in Age-Related Choroidal Neovascularisation Trial

Tunde Peto; Rebecca N Evans; Barnaby C Reeves; Simon Harding; Savita  Madhusudhan; Andrew Lotery; Susan Downes; Konstantinos  Balaskas; Clare C Bailey; Alexander  Foss; Faruque Ghanchi; Yit C Yang; Dawn Phillips; Chris A Rogers; Alyson Muldrew; Barbra Hamill; Usha Chakravarthy

doi:10.1016/j.oret.2022.03.010

Long term retinal morphology and functional associations in treated neovascular age-related macular degeneration: Findings from the Inhibition of VEGF in Age-Related Choroidal Neovascularisation Trial

Tunde Peto, Rebecca N Evans, Barnaby C Reeves, Simon Harding, Savita Madhusudhan, Andrew Lotery, Susan Downes, Konstantinos Balaskas, Clare C Bailey, Alexander Foss, Faruque Ghanchi, Yit C Yang, Dawn Phillips, Chris A Rogers, Alyson Muldrew, Barbra Hamill, Usha Chakravarthy^*

^*Corresponding author for this work

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Abstract

Objective/Purpose

To describe the frequency of long-term morphological features and their relationships with visual function in participants who exited the inhibition of VEGF in age-related choroidal neovascularization (IVAN: ISRCTN92166560) trial.

Design

Multicenter cohort study up to 7 years after enrolment.

Participants

Patients enrolled in IVAN excluding participants who died or withdrew during the trial.

Methods

Multimodal fundus images, best corrected (BCVA) and low luminance visual acuity (LLVA) were obtained in a subset of 199 participants who attended a research visit. Clinical sites (n=20) also provided all visual acuity and clinical information from usual care records for 532 participants and submitted most recent color, OCT and other fundus images for 468 participants to a reading center.

Main Outcome Measures

Assessed from most recent images: intralesional macular atrophy (ILMA) within the footprint of the neovascular lesion; hyperreflective material (HRM); intraretinal fluid (IRF); subretinal fluid (SRF); pigment epithelial detachment (PED); disorganization of outer retinal layers (DROL). Cross sectional relationships between morphological features and BCVA/LLVA were estimated.

Results

ILMA was present in 31.8% of study eyes at IVAN exit (mean follow-up 1.96 years) and 89.5% at the most recent imaging visit (6.18 years). HRM, IRF, SRF, PED and DROL were present in 78.8%, 47.7%, 7.6%, 94.5% and 55% respectively. In the subset with complete imaging data, in eyes without DROL, BCVA was worst in the thinnest outer fovea tertile (thinnest minus middle and thickest tertiles, -19.7 and -19.5 letters respectively) whereas in eyes with DROL, BCVA was worst in the thickest (thinnest and middle tertiles minus thickest, 12.5 and 12.2 respectively). Regression models showed that presence of ILMA and HRM were independently associated with BCVA (22 letters worse (95% CI 11.2, 32.8, p<0.001) and 9.8 letters worse (95% CI 0.1, 19.4, p=0.047), respectively). SRF and foveal PED were associated with better BCVA (5.9 letters, 95% CI -7.9, 19.7, p<0.399; and 6.4 letters, 95% CI -1.1, 14.0, p=0.094 respectively). The model with LLVA was similar. Sensitivity analysis including the entire eligible cohort yielded similar estimates.

Conclusions

Macular atrophy and HRM were common after 7 years of follow-up and strongly associated with visual outcomes.

Original language	English
Pages (from-to)	664-675
Number of pages	12
Journal	Opthalmology Retina
Volume	6
Issue number	8
Early online date	18 Mar 2022
DOIs	https://doi.org/10.1016/j.oret.2022.03.010
Publication status	Published - 3 Aug 2022

Bibliographical note

Funding Information:
T.P.: Advisory board/honoraria – Bayer, Novartis, Roche, Heidelberg, Optos, Pharma as Alimera; Grants – National Institute for Health Research United Kingdom Health Technology Assessment Programme.K.B.: Grants and personal fees – Bayer, Novartis, Roche, Apellis; Personal fees – Heidelberg Engineering.S.D.: Grants – National Institute for Health Research United Kingdom Health Technology Assessment Programme, Pharma for studies in AMD; Personal fees, Consultant – Boehringer Ingelheim, Circadian Therapeutics, Allergan regarding AMD, and sleep disorders in ocular disease, inherited retinal diseases; Medical Advisory Board chair – RETINA United Kingdom (charitable organization, unremunerated work).B.C.R.: Grants – National Institute of Health Research.Supported by the National Institute for Health Research United Kingdom Health Technology Assessment Programme that funded both the IVAN trial (reference: 07/36/01) and this long-term follow-up of IVAN participants (reference: 07/36/501). The views and opinions expressed are those of the authors and do not necessarily reflect those of the National Institute for Health Research Health Technology Assessment programme, the National Institute for Health Research, the United Kingdom National Health Service, or the Department of Health. This study was designed and delivered in collaboration with the Bristol Trials Centre, a United Kingdom Clinical Research Collaboration–registered clinical trials unit that is in receipt of National Institute for Health Research clinical trials unit funding.

Publisher Copyright:
© 2022

Keywords

IVAN trial
long-term follow-up
macular atrophy
disorganization of outer retina
spectral domain OCT

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Peto, T., Evans, R. N., Reeves, B. C., Harding, S., Madhusudhan, S., Lotery, A., Downes, S., Balaskas, K., Bailey, C. C., Foss, A., Ghanchi, F., Yang, Y. C., Phillips, D., Rogers, C. A., Muldrew, A., Hamill, B., & Chakravarthy, U. (2022). Long term retinal morphology and functional associations in treated neovascular age-related macular degeneration: Findings from the Inhibition of VEGF in Age-Related Choroidal Neovascularisation Trial. Opthalmology Retina, 6(8), 664-675. https://doi.org/10.1016/j.oret.2022.03.010

@article{9787052edc8f490aab34fb4902835dcb,

title = "Long term retinal morphology and functional associations in treated neovascular age-related macular degeneration: Findings from the Inhibition of VEGF in Age-Related Choroidal Neovascularisation Trial",

abstract = "Objective/PurposeTo describe the frequency of long-term morphological features and their relationships with visual function in participants who exited the inhibition of VEGF in age-related choroidal neovascularization (IVAN: ISRCTN92166560) trial.DesignMulticenter cohort study up to 7 years after enrolment.ParticipantsPatients enrolled in IVAN excluding participants who died or withdrew during the trial.MethodsMultimodal fundus images, best corrected (BCVA) and low luminance visual acuity (LLVA) were obtained in a subset of 199 participants who attended a research visit. Clinical sites (n=20) also provided all visual acuity and clinical information from usual care records for 532 participants and submitted most recent color, OCT and other fundus images for 468 participants to a reading center.Main Outcome MeasuresAssessed from most recent images: intralesional macular atrophy (ILMA) within the footprint of the neovascular lesion; hyperreflective material (HRM); intraretinal fluid (IRF); subretinal fluid (SRF); pigment epithelial detachment (PED); disorganization of outer retinal layers (DROL). Cross sectional relationships between morphological features and BCVA/LLVA were estimated.ResultsILMA was present in 31.8% of study eyes at IVAN exit (mean follow-up 1.96 years) and 89.5% at the most recent imaging visit (6.18 years). HRM, IRF, SRF, PED and DROL were present in 78.8%, 47.7%, 7.6%, 94.5% and 55% respectively. In the subset with complete imaging data, in eyes without DROL, BCVA was worst in the thinnest outer fovea tertile (thinnest minus middle and thickest tertiles, -19.7 and -19.5 letters respectively) whereas in eyes with DROL, BCVA was worst in the thickest (thinnest and middle tertiles minus thickest, 12.5 and 12.2 respectively). Regression models showed that presence of ILMA and HRM were independently associated with BCVA (22 letters worse (95% CI 11.2, 32.8, p<0.001) and 9.8 letters worse (95% CI 0.1, 19.4, p=0.047), respectively). SRF and foveal PED were associated with better BCVA (5.9 letters, 95% CI -7.9, 19.7, p<0.399; and 6.4 letters, 95% CI -1.1, 14.0, p=0.094 respectively). The model with LLVA was similar. Sensitivity analysis including the entire eligible cohort yielded similar estimates.ConclusionsMacular atrophy and HRM were common after 7 years of follow-up and strongly associated with visual outcomes.",

keywords = "IVAN trial, long-term follow-up, macular atrophy, disorganization of outer retina, spectral domain OCT",

author = "Tunde Peto and Evans, {Rebecca N} and Reeves, {Barnaby C} and Simon Harding and Savita Madhusudhan and Andrew Lotery and Susan Downes and Konstantinos Balaskas and Bailey, {Clare C} and Alexander Foss and Faruque Ghanchi and Yang, {Yit C} and Dawn Phillips and Rogers, {Chris A} and Alyson Muldrew and Barbra Hamill and Usha Chakravarthy",

note = "Funding Information: T.P.: Advisory board/honoraria – Bayer, Novartis, Roche, Heidelberg, Optos, Pharma as Alimera; Grants – National Institute for Health Research United Kingdom Health Technology Assessment Programme.K.B.: Grants and personal fees – Bayer, Novartis, Roche, Apellis; Personal fees – Heidelberg Engineering.S.D.: Grants – National Institute for Health Research United Kingdom Health Technology Assessment Programme, Pharma for studies in AMD; Personal fees, Consultant – Boehringer Ingelheim, Circadian Therapeutics, Allergan regarding AMD, and sleep disorders in ocular disease, inherited retinal diseases; Medical Advisory Board chair – RETINA United Kingdom (charitable organization, unremunerated work).B.C.R.: Grants – National Institute of Health Research.Supported by the National Institute for Health Research United Kingdom Health Technology Assessment Programme that funded both the IVAN trial (reference: 07/36/01) and this long-term follow-up of IVAN participants (reference: 07/36/501). The views and opinions expressed are those of the authors and do not necessarily reflect those of the National Institute for Health Research Health Technology Assessment programme, the National Institute for Health Research, the United Kingdom National Health Service, or the Department of Health. This study was designed and delivered in collaboration with the Bristol Trials Centre, a United Kingdom Clinical Research Collaboration–registered clinical trials unit that is in receipt of National Institute for Health Research clinical trials unit funding. Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = aug,

day = "3",

doi = "10.1016/j.oret.2022.03.010",

language = "English",

volume = "6",

pages = "664--675",

journal = "Opthalmology Retina",

issn = "2468-7219",

publisher = "Elsevier Inc.",

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Peto, T, Evans, RN , Reeves, BC, Harding, S, Madhusudhan, S, Lotery, A, Downes, S, Balaskas, K, Bailey, CC, Foss, A, Ghanchi, F, Yang, YC, Phillips, D, Rogers, CA, Muldrew, A, Hamill, B & Chakravarthy, U 2022, 'Long term retinal morphology and functional associations in treated neovascular age-related macular degeneration: Findings from the Inhibition of VEGF in Age-Related Choroidal Neovascularisation Trial', Opthalmology Retina, vol. 6, no. 8, pp. 664-675. https://doi.org/10.1016/j.oret.2022.03.010

Long term retinal morphology and functional associations in treated neovascular age-related macular degeneration: Findings from the Inhibition of VEGF in Age-Related Choroidal Neovascularisation Trial. / Peto, Tunde; Evans, Rebecca N ; Reeves, Barnaby C et al.
In: Opthalmology Retina, Vol. 6, No. 8, 03.08.2022, p. 664-675.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Long term retinal morphology and functional associations in treated neovascular age-related macular degeneration

T2 - Findings from the Inhibition of VEGF in Age-Related Choroidal Neovascularisation Trial

AU - Peto, Tunde

AU - Evans, Rebecca N

AU - Reeves, Barnaby C

AU - Harding, Simon

AU - Madhusudhan, Savita

AU - Lotery, Andrew

AU - Downes, Susan

AU - Balaskas, Konstantinos

AU - Bailey, Clare C

AU - Foss, Alexander

AU - Ghanchi, Faruque

AU - Yang, Yit C

AU - Phillips, Dawn

AU - Rogers, Chris A

AU - Muldrew, Alyson

AU - Hamill, Barbra

AU - Chakravarthy, Usha

N1 - Funding Information: T.P.: Advisory board/honoraria – Bayer, Novartis, Roche, Heidelberg, Optos, Pharma as Alimera; Grants – National Institute for Health Research United Kingdom Health Technology Assessment Programme.K.B.: Grants and personal fees – Bayer, Novartis, Roche, Apellis; Personal fees – Heidelberg Engineering.S.D.: Grants – National Institute for Health Research United Kingdom Health Technology Assessment Programme, Pharma for studies in AMD; Personal fees, Consultant – Boehringer Ingelheim, Circadian Therapeutics, Allergan regarding AMD, and sleep disorders in ocular disease, inherited retinal diseases; Medical Advisory Board chair – RETINA United Kingdom (charitable organization, unremunerated work).B.C.R.: Grants – National Institute of Health Research.Supported by the National Institute for Health Research United Kingdom Health Technology Assessment Programme that funded both the IVAN trial (reference: 07/36/01) and this long-term follow-up of IVAN participants (reference: 07/36/501). The views and opinions expressed are those of the authors and do not necessarily reflect those of the National Institute for Health Research Health Technology Assessment programme, the National Institute for Health Research, the United Kingdom National Health Service, or the Department of Health. This study was designed and delivered in collaboration with the Bristol Trials Centre, a United Kingdom Clinical Research Collaboration–registered clinical trials unit that is in receipt of National Institute for Health Research clinical trials unit funding. Publisher Copyright: © 2022

PY - 2022/8/3

Y1 - 2022/8/3

N2 - Objective/PurposeTo describe the frequency of long-term morphological features and their relationships with visual function in participants who exited the inhibition of VEGF in age-related choroidal neovascularization (IVAN: ISRCTN92166560) trial.DesignMulticenter cohort study up to 7 years after enrolment.ParticipantsPatients enrolled in IVAN excluding participants who died or withdrew during the trial.MethodsMultimodal fundus images, best corrected (BCVA) and low luminance visual acuity (LLVA) were obtained in a subset of 199 participants who attended a research visit. Clinical sites (n=20) also provided all visual acuity and clinical information from usual care records for 532 participants and submitted most recent color, OCT and other fundus images for 468 participants to a reading center.Main Outcome MeasuresAssessed from most recent images: intralesional macular atrophy (ILMA) within the footprint of the neovascular lesion; hyperreflective material (HRM); intraretinal fluid (IRF); subretinal fluid (SRF); pigment epithelial detachment (PED); disorganization of outer retinal layers (DROL). Cross sectional relationships between morphological features and BCVA/LLVA were estimated.ResultsILMA was present in 31.8% of study eyes at IVAN exit (mean follow-up 1.96 years) and 89.5% at the most recent imaging visit (6.18 years). HRM, IRF, SRF, PED and DROL were present in 78.8%, 47.7%, 7.6%, 94.5% and 55% respectively. In the subset with complete imaging data, in eyes without DROL, BCVA was worst in the thinnest outer fovea tertile (thinnest minus middle and thickest tertiles, -19.7 and -19.5 letters respectively) whereas in eyes with DROL, BCVA was worst in the thickest (thinnest and middle tertiles minus thickest, 12.5 and 12.2 respectively). Regression models showed that presence of ILMA and HRM were independently associated with BCVA (22 letters worse (95% CI 11.2, 32.8, p<0.001) and 9.8 letters worse (95% CI 0.1, 19.4, p=0.047), respectively). SRF and foveal PED were associated with better BCVA (5.9 letters, 95% CI -7.9, 19.7, p<0.399; and 6.4 letters, 95% CI -1.1, 14.0, p=0.094 respectively). The model with LLVA was similar. Sensitivity analysis including the entire eligible cohort yielded similar estimates.ConclusionsMacular atrophy and HRM were common after 7 years of follow-up and strongly associated with visual outcomes.

AB - Objective/PurposeTo describe the frequency of long-term morphological features and their relationships with visual function in participants who exited the inhibition of VEGF in age-related choroidal neovascularization (IVAN: ISRCTN92166560) trial.DesignMulticenter cohort study up to 7 years after enrolment.ParticipantsPatients enrolled in IVAN excluding participants who died or withdrew during the trial.MethodsMultimodal fundus images, best corrected (BCVA) and low luminance visual acuity (LLVA) were obtained in a subset of 199 participants who attended a research visit. Clinical sites (n=20) also provided all visual acuity and clinical information from usual care records for 532 participants and submitted most recent color, OCT and other fundus images for 468 participants to a reading center.Main Outcome MeasuresAssessed from most recent images: intralesional macular atrophy (ILMA) within the footprint of the neovascular lesion; hyperreflective material (HRM); intraretinal fluid (IRF); subretinal fluid (SRF); pigment epithelial detachment (PED); disorganization of outer retinal layers (DROL). Cross sectional relationships between morphological features and BCVA/LLVA were estimated.ResultsILMA was present in 31.8% of study eyes at IVAN exit (mean follow-up 1.96 years) and 89.5% at the most recent imaging visit (6.18 years). HRM, IRF, SRF, PED and DROL were present in 78.8%, 47.7%, 7.6%, 94.5% and 55% respectively. In the subset with complete imaging data, in eyes without DROL, BCVA was worst in the thinnest outer fovea tertile (thinnest minus middle and thickest tertiles, -19.7 and -19.5 letters respectively) whereas in eyes with DROL, BCVA was worst in the thickest (thinnest and middle tertiles minus thickest, 12.5 and 12.2 respectively). Regression models showed that presence of ILMA and HRM were independently associated with BCVA (22 letters worse (95% CI 11.2, 32.8, p<0.001) and 9.8 letters worse (95% CI 0.1, 19.4, p=0.047), respectively). SRF and foveal PED were associated with better BCVA (5.9 letters, 95% CI -7.9, 19.7, p<0.399; and 6.4 letters, 95% CI -1.1, 14.0, p=0.094 respectively). The model with LLVA was similar. Sensitivity analysis including the entire eligible cohort yielded similar estimates.ConclusionsMacular atrophy and HRM were common after 7 years of follow-up and strongly associated with visual outcomes.

KW - IVAN trial

KW - long-term follow-up

KW - macular atrophy

KW - disorganization of outer retina

KW - spectral domain OCT

U2 - 10.1016/j.oret.2022.03.010

DO - 10.1016/j.oret.2022.03.010

M3 - Article (Academic Journal)

C2 - 35314388

SN - 2468-7219

VL - 6

SP - 664

EP - 675

JO - Opthalmology Retina

JF - Opthalmology Retina

IS - 8

ER -

Long term retinal morphology and functional associations in treated neovascular age-related macular degeneration: Findings from the Inhibition of VEGF in Age-Related Choroidal Neovascularisation Trial

Abstract

Bibliographical note

Keywords

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