Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration

a systematic review and economic evaluation

Graham Mowatt, Rodolfo Hernández, Mayret Castillo, Noemi Lois, Andrew Elders, Cynthia Fraser, Olatunde Aremu, Winfried Amoaku, Jennifer Burr, Andrew Lotery, Craig Ramsay, Augusto Azuara-Blanco

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

BACKGROUND: Age-related macular degeneration is the most common cause of sight impairment in the UK. In neovascular age-related macular degeneration (nAMD), vision worsens rapidly (over weeks) due to abnormal blood vessels developing that leak fluid and blood at the macula.

OBJECTIVES: To determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected nAMD and monitoring those previously diagnosed with the disease.

DATA SOURCES: Databases searched: MEDLINE (1946 to March 2013), MEDLINE In-Process & Other Non-Indexed Citations (March 2013), EMBASE (1988 to March 2013), Biosciences Information Service (1995 to March 2013), Science Citation Index (1995 to March 2013), The Cochrane Library (Issue 2 2013), Database of Abstracts of Reviews of Effects (inception to March 2013), Medion (inception to March 2013), Health Technology Assessment database (inception to March 2013).

REVIEW METHODS: Types of studies: direct/indirect studies reporting diagnostic outcomes.

INDEX TEST: time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT).

COMPARATORS: clinical evaluation, visual acuity, Amsler grid, colour fundus photographs, infrared reflectance, red-free images/blue reflectance, fundus autofluorescence imaging, indocyanine green angiography, preferential hyperacuity perimetry, microperimetry. Reference standard: fundus fluorescein angiography (FFA). Risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. A Markov model was developed (65-year-old cohort, nAMD prevalence 70%), with nine strategies for diagnosis and/or monitoring, and cost-utility analysis conducted. NHS and Personal Social Services perspective was adopted. Costs (2011/12 prices) and quality-adjusted life-years (QALYs) were discounted (3.5%). Deterministic and probabilistic sensitivity analyses were performed.

RESULTS: In pooled estimates of diagnostic studies (all TD-OCT), sensitivity and specificity [95% confidence interval (CI)] was 88% (46% to 98%) and 78% (64% to 88%) respectively. For monitoring, the pooled sensitivity and specificity (95% CI) was 85% (72% to 93%) and 48% (30% to 67%) respectively. The FFA for diagnosis and nurse-technician-led monitoring strategy had the lowest cost (£ 39,769; QALYs 10.473) and dominated all others except FFA for diagnosis and ophthalmologist-led monitoring (£ 44,649; QALYs 10.575; incremental cost-effectiveness ratio £ 47,768). The least costly strategy had a 46.4% probability of being cost-effective at £ 30,000 willingness-to-pay threshold.

LIMITATIONS: Very few studies provided sufficient information for inclusion in meta-analyses. Only a few studies reported other tests; for some tests no studies were identified. The modelling was hampered by a lack of data on the diagnostic accuracy of strategies involving several tests.

CONCLUSIONS: Based on a small body of evidence of variable quality, OCT had high sensitivity and moderate specificity for diagnosis, and relatively high sensitivity but low specificity for monitoring. Strategies involving OCT alone for diagnosis and/or monitoring were unlikely to be cost-effective. Further research is required on (i) the performance of SD-OCT compared with FFA, especially for monitoring but also for diagnosis; (ii) the performance of strategies involving combinations/sequences of tests, for diagnosis and monitoring; (iii) the likelihood of active and inactive nAMD becoming inactive or active respectively; and (iv) assessment of treatment-associated utility weights (e.g. decrements), through a preference-based study.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42012001930.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Original languageEnglish
Pages (from-to)1-254
Number of pages254
JournalHealth Technology Assessment
Volume18
Issue number69
DOIs
Publication statusPublished - Dec 2014

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Optical Coherence Tomography
Macular Degeneration
Cost-Benefit Analysis
Fluorescein Angiography
Quality-Adjusted Life Years
Costs and Cost Analysis
Sensitivity and Specificity
Biomedical Technology Assessment
Databases
MEDLINE
Therapeutics
Meta-Analysis
Confidence Intervals
Visual Field Tests
Indocyanine Green
Information Services
Optical Imaging
National Institutes of Health (U.S.)
Social Work
Research

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Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration : a systematic review and economic evaluation. / Mowatt, Graham; Hernández, Rodolfo; Castillo, Mayret; Lois, Noemi; Elders, Andrew; Fraser, Cynthia; Aremu, Olatunde; Amoaku, Winfried; Burr, Jennifer; Lotery, Andrew; Ramsay, Craig; Azuara-Blanco, Augusto.

In: Health Technology Assessment, Vol. 18, No. 69, 12.2014, p. 1-254.

Research output: Contribution to journalArticle

Mowatt, Graham ; Hernández, Rodolfo ; Castillo, Mayret ; Lois, Noemi ; Elders, Andrew ; Fraser, Cynthia ; Aremu, Olatunde ; Amoaku, Winfried ; Burr, Jennifer ; Lotery, Andrew ; Ramsay, Craig ; Azuara-Blanco, Augusto. / Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration : a systematic review and economic evaluation. In: Health Technology Assessment. 2014 ; Vol. 18, No. 69. pp. 1-254.
@article{5e4fc47ae1d24cada017296bf57a5077,
title = "Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration: a systematic review and economic evaluation",
abstract = "BACKGROUND: Age-related macular degeneration is the most common cause of sight impairment in the UK. In neovascular age-related macular degeneration (nAMD), vision worsens rapidly (over weeks) due to abnormal blood vessels developing that leak fluid and blood at the macula.OBJECTIVES: To determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected nAMD and monitoring those previously diagnosed with the disease.DATA SOURCES: Databases searched: MEDLINE (1946 to March 2013), MEDLINE In-Process & Other Non-Indexed Citations (March 2013), EMBASE (1988 to March 2013), Biosciences Information Service (1995 to March 2013), Science Citation Index (1995 to March 2013), The Cochrane Library (Issue 2 2013), Database of Abstracts of Reviews of Effects (inception to March 2013), Medion (inception to March 2013), Health Technology Assessment database (inception to March 2013).REVIEW METHODS: Types of studies: direct/indirect studies reporting diagnostic outcomes.INDEX TEST: time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT).COMPARATORS: clinical evaluation, visual acuity, Amsler grid, colour fundus photographs, infrared reflectance, red-free images/blue reflectance, fundus autofluorescence imaging, indocyanine green angiography, preferential hyperacuity perimetry, microperimetry. Reference standard: fundus fluorescein angiography (FFA). Risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. A Markov model was developed (65-year-old cohort, nAMD prevalence 70{\%}), with nine strategies for diagnosis and/or monitoring, and cost-utility analysis conducted. NHS and Personal Social Services perspective was adopted. Costs (2011/12 prices) and quality-adjusted life-years (QALYs) were discounted (3.5{\%}). Deterministic and probabilistic sensitivity analyses were performed.RESULTS: In pooled estimates of diagnostic studies (all TD-OCT), sensitivity and specificity [95{\%} confidence interval (CI)] was 88{\%} (46{\%} to 98{\%}) and 78{\%} (64{\%} to 88{\%}) respectively. For monitoring, the pooled sensitivity and specificity (95{\%} CI) was 85{\%} (72{\%} to 93{\%}) and 48{\%} (30{\%} to 67{\%}) respectively. The FFA for diagnosis and nurse-technician-led monitoring strategy had the lowest cost (£ 39,769; QALYs 10.473) and dominated all others except FFA for diagnosis and ophthalmologist-led monitoring (£ 44,649; QALYs 10.575; incremental cost-effectiveness ratio £ 47,768). The least costly strategy had a 46.4{\%} probability of being cost-effective at £ 30,000 willingness-to-pay threshold.LIMITATIONS: Very few studies provided sufficient information for inclusion in meta-analyses. Only a few studies reported other tests; for some tests no studies were identified. The modelling was hampered by a lack of data on the diagnostic accuracy of strategies involving several tests.CONCLUSIONS: Based on a small body of evidence of variable quality, OCT had high sensitivity and moderate specificity for diagnosis, and relatively high sensitivity but low specificity for monitoring. Strategies involving OCT alone for diagnosis and/or monitoring were unlikely to be cost-effective. Further research is required on (i) the performance of SD-OCT compared with FFA, especially for monitoring but also for diagnosis; (ii) the performance of strategies involving combinations/sequences of tests, for diagnosis and monitoring; (iii) the likelihood of active and inactive nAMD becoming inactive or active respectively; and (iv) assessment of treatment-associated utility weights (e.g. decrements), through a preference-based study.STUDY REGISTRATION: This study is registered as PROSPERO CRD42012001930.FUNDING: The National Institute for Health Research Health Technology Assessment programme.",
author = "Graham Mowatt and Rodolfo Hern{\'a}ndez and Mayret Castillo and Noemi Lois and Andrew Elders and Cynthia Fraser and Olatunde Aremu and Winfried Amoaku and Jennifer Burr and Andrew Lotery and Craig Ramsay and Augusto Azuara-Blanco",
note = "We thank David Findlay Clark (service user with the condition), Graham Findlay (Chief Executive, North East Sensory Services) and Helen Jackman (Chief Executive, Macular Society) for providing valuable consumer insight and advice, and for commenting on the Plain English summary, and Malcolm McPherson (Community Optometrist) for providing a community optometrist perspective, through their participation as members of the study’s project advisory group; Usha Chakravarthy, Chris Rogers and colleagues for providing data from the IVAN trial; Mari Imamura and Xueli Jia for translating non-English language papers; and Lara Kemp for secretarial support. The economic model developed for the analysis was informed by an existing economic model developed by the Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, UK. The intellectual property rights associated with the SHTAC economic model are owned by the University of Southampton (UK) – all rights reserved. We thank Andrew Clegg and Jeremy Jones for providing access to the SHTAC AMD economic evaluation model (see www.southampton.ac.uk/shtac/research/published/ eyediseases.page?). This report was commissioned by the National Institute for Health Research (NIHR) HTA Programme as project number 10/57/22. The Health Services Research Unit and Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, are core-funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The views and opinions expressed are those of the authors and do not necessarily reflect those of the funders.",
year = "2014",
month = "12",
doi = "10.3310/hta18690",
language = "English",
volume = "18",
pages = "1--254",
journal = "Health Technology Assessment",
issn = "1366-5278",
publisher = "National Co-ordinating Centre for HTA",
number = "69",

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TY - JOUR

T1 - Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration

T2 - a systematic review and economic evaluation

AU - Mowatt, Graham

AU - Hernández, Rodolfo

AU - Castillo, Mayret

AU - Lois, Noemi

AU - Elders, Andrew

AU - Fraser, Cynthia

AU - Aremu, Olatunde

AU - Amoaku, Winfried

AU - Burr, Jennifer

AU - Lotery, Andrew

AU - Ramsay, Craig

AU - Azuara-Blanco, Augusto

N1 - We thank David Findlay Clark (service user with the condition), Graham Findlay (Chief Executive, North East Sensory Services) and Helen Jackman (Chief Executive, Macular Society) for providing valuable consumer insight and advice, and for commenting on the Plain English summary, and Malcolm McPherson (Community Optometrist) for providing a community optometrist perspective, through their participation as members of the study’s project advisory group; Usha Chakravarthy, Chris Rogers and colleagues for providing data from the IVAN trial; Mari Imamura and Xueli Jia for translating non-English language papers; and Lara Kemp for secretarial support. The economic model developed for the analysis was informed by an existing economic model developed by the Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, UK. The intellectual property rights associated with the SHTAC economic model are owned by the University of Southampton (UK) – all rights reserved. We thank Andrew Clegg and Jeremy Jones for providing access to the SHTAC AMD economic evaluation model (see www.southampton.ac.uk/shtac/research/published/ eyediseases.page?). This report was commissioned by the National Institute for Health Research (NIHR) HTA Programme as project number 10/57/22. The Health Services Research Unit and Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, are core-funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The views and opinions expressed are those of the authors and do not necessarily reflect those of the funders.

PY - 2014/12

Y1 - 2014/12

N2 - BACKGROUND: Age-related macular degeneration is the most common cause of sight impairment in the UK. In neovascular age-related macular degeneration (nAMD), vision worsens rapidly (over weeks) due to abnormal blood vessels developing that leak fluid and blood at the macula.OBJECTIVES: To determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected nAMD and monitoring those previously diagnosed with the disease.DATA SOURCES: Databases searched: MEDLINE (1946 to March 2013), MEDLINE In-Process & Other Non-Indexed Citations (March 2013), EMBASE (1988 to March 2013), Biosciences Information Service (1995 to March 2013), Science Citation Index (1995 to March 2013), The Cochrane Library (Issue 2 2013), Database of Abstracts of Reviews of Effects (inception to March 2013), Medion (inception to March 2013), Health Technology Assessment database (inception to March 2013).REVIEW METHODS: Types of studies: direct/indirect studies reporting diagnostic outcomes.INDEX TEST: time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT).COMPARATORS: clinical evaluation, visual acuity, Amsler grid, colour fundus photographs, infrared reflectance, red-free images/blue reflectance, fundus autofluorescence imaging, indocyanine green angiography, preferential hyperacuity perimetry, microperimetry. Reference standard: fundus fluorescein angiography (FFA). Risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. A Markov model was developed (65-year-old cohort, nAMD prevalence 70%), with nine strategies for diagnosis and/or monitoring, and cost-utility analysis conducted. NHS and Personal Social Services perspective was adopted. Costs (2011/12 prices) and quality-adjusted life-years (QALYs) were discounted (3.5%). Deterministic and probabilistic sensitivity analyses were performed.RESULTS: In pooled estimates of diagnostic studies (all TD-OCT), sensitivity and specificity [95% confidence interval (CI)] was 88% (46% to 98%) and 78% (64% to 88%) respectively. For monitoring, the pooled sensitivity and specificity (95% CI) was 85% (72% to 93%) and 48% (30% to 67%) respectively. The FFA for diagnosis and nurse-technician-led monitoring strategy had the lowest cost (£ 39,769; QALYs 10.473) and dominated all others except FFA for diagnosis and ophthalmologist-led monitoring (£ 44,649; QALYs 10.575; incremental cost-effectiveness ratio £ 47,768). The least costly strategy had a 46.4% probability of being cost-effective at £ 30,000 willingness-to-pay threshold.LIMITATIONS: Very few studies provided sufficient information for inclusion in meta-analyses. Only a few studies reported other tests; for some tests no studies were identified. The modelling was hampered by a lack of data on the diagnostic accuracy of strategies involving several tests.CONCLUSIONS: Based on a small body of evidence of variable quality, OCT had high sensitivity and moderate specificity for diagnosis, and relatively high sensitivity but low specificity for monitoring. Strategies involving OCT alone for diagnosis and/or monitoring were unlikely to be cost-effective. Further research is required on (i) the performance of SD-OCT compared with FFA, especially for monitoring but also for diagnosis; (ii) the performance of strategies involving combinations/sequences of tests, for diagnosis and monitoring; (iii) the likelihood of active and inactive nAMD becoming inactive or active respectively; and (iv) assessment of treatment-associated utility weights (e.g. decrements), through a preference-based study.STUDY REGISTRATION: This study is registered as PROSPERO CRD42012001930.FUNDING: The National Institute for Health Research Health Technology Assessment programme.

AB - BACKGROUND: Age-related macular degeneration is the most common cause of sight impairment in the UK. In neovascular age-related macular degeneration (nAMD), vision worsens rapidly (over weeks) due to abnormal blood vessels developing that leak fluid and blood at the macula.OBJECTIVES: To determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected nAMD and monitoring those previously diagnosed with the disease.DATA SOURCES: Databases searched: MEDLINE (1946 to March 2013), MEDLINE In-Process & Other Non-Indexed Citations (March 2013), EMBASE (1988 to March 2013), Biosciences Information Service (1995 to March 2013), Science Citation Index (1995 to March 2013), The Cochrane Library (Issue 2 2013), Database of Abstracts of Reviews of Effects (inception to March 2013), Medion (inception to March 2013), Health Technology Assessment database (inception to March 2013).REVIEW METHODS: Types of studies: direct/indirect studies reporting diagnostic outcomes.INDEX TEST: time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT).COMPARATORS: clinical evaluation, visual acuity, Amsler grid, colour fundus photographs, infrared reflectance, red-free images/blue reflectance, fundus autofluorescence imaging, indocyanine green angiography, preferential hyperacuity perimetry, microperimetry. Reference standard: fundus fluorescein angiography (FFA). Risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. A Markov model was developed (65-year-old cohort, nAMD prevalence 70%), with nine strategies for diagnosis and/or monitoring, and cost-utility analysis conducted. NHS and Personal Social Services perspective was adopted. Costs (2011/12 prices) and quality-adjusted life-years (QALYs) were discounted (3.5%). Deterministic and probabilistic sensitivity analyses were performed.RESULTS: In pooled estimates of diagnostic studies (all TD-OCT), sensitivity and specificity [95% confidence interval (CI)] was 88% (46% to 98%) and 78% (64% to 88%) respectively. For monitoring, the pooled sensitivity and specificity (95% CI) was 85% (72% to 93%) and 48% (30% to 67%) respectively. The FFA for diagnosis and nurse-technician-led monitoring strategy had the lowest cost (£ 39,769; QALYs 10.473) and dominated all others except FFA for diagnosis and ophthalmologist-led monitoring (£ 44,649; QALYs 10.575; incremental cost-effectiveness ratio £ 47,768). The least costly strategy had a 46.4% probability of being cost-effective at £ 30,000 willingness-to-pay threshold.LIMITATIONS: Very few studies provided sufficient information for inclusion in meta-analyses. Only a few studies reported other tests; for some tests no studies were identified. The modelling was hampered by a lack of data on the diagnostic accuracy of strategies involving several tests.CONCLUSIONS: Based on a small body of evidence of variable quality, OCT had high sensitivity and moderate specificity for diagnosis, and relatively high sensitivity but low specificity for monitoring. Strategies involving OCT alone for diagnosis and/or monitoring were unlikely to be cost-effective. Further research is required on (i) the performance of SD-OCT compared with FFA, especially for monitoring but also for diagnosis; (ii) the performance of strategies involving combinations/sequences of tests, for diagnosis and monitoring; (iii) the likelihood of active and inactive nAMD becoming inactive or active respectively; and (iv) assessment of treatment-associated utility weights (e.g. decrements), through a preference-based study.STUDY REGISTRATION: This study is registered as PROSPERO CRD42012001930.FUNDING: The National Institute for Health Research Health Technology Assessment programme.

U2 - 10.3310/hta18690

DO - 10.3310/hta18690

M3 - Article

VL - 18

SP - 1

EP - 254

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

IS - 69

ER -