Non-invasive testing for early detection of neovascular macular degeneration in unaffected second eyes of older adults : EDNA diagnostic accuracy study
BACKGROUND: Neovascular age-related macular degeneration is a leading cause of sight loss, and early detection and treatment is important. For patients with neovascular age-related macular degeneration in one eye, it is usual practice to monitor the unaffected eye. The test used to diagnose neovascular age-related macular degeneration, fundus fluorescein angiography, is an invasive test. Non-invasive tests are available, but their diagnostic accuracy is unclear.
OBJECTIVES: The primary objective was to determine the diagnostic monitoring performance of tests for neovascular age-related macular degeneration in the second eye of patients with unilateral neovascular age-related macular degeneration. The secondary objectives were the cost-effectiveness of tests and to identify predictive factors of developing neovascular age-related macular degeneration.
DESIGN: This was a multicentre, prospective, cohort, comparative diagnostic accuracy study in a monitoring setting for up to 3 years. A Cox regression risk prediction model and a Markov microsimulation model comparing cost-effectiveness of the index tests over 25 years were used.
SETTING: This took place in hospital eye services.
PARTICIPANTS: Participants were adults (aged 50-95 years) with newly diagnosed (within the previous 6 weeks) neovascular age-related macular degeneration in one eye and an unaffected second (study) eye who were attending for treatment injections in the first eye and who had a study eye baseline visual acuity of ≥ 68 Early Treatment Diabetic Retinopathy Study letters.
INTERVENTIONS: The index tests were Amsler chart (completed by participants), fundus clinical examination, optical coherence tomography, self-reported vision assessment (completed by participants) and visual acuity. The reference standard was fundus fluorescein angiography.
MAIN OUTCOME MEASURES: The main outcome measures were sensitivity and specificity; the performance of the risk predictor model; and costs and quality-adjusted life-years.
RESULTS: In total, 552 out of 578 patients who consented from 24 NHS hospitals (n = 16 ineligible; n = 10 withdrew consent) took part. The mean age of the patients was 77.4 years (standard deviation 7.7 years) and 57.2% were female. For the primary analysis, 464 patients underwent follow-up fundus fluorescein angiography and 120 developed neovascular age-related macular degeneration on fundus fluorescein angiography. The diagnostic accuracy [sensitivity (%) (95% confidence interval); specificity (%) (95% confidence interval)] was as follows: optical coherence tomography 91.7 (85.2 to 95.6); 87.8 (83.8 to 90.9)], fundus clinical examination [53.8 (44.8 to 62.5); 97.6 (95.3 to 98.9)], Amsler [33.7 (25.1 to 43.5); 81.4 (76.4 to 85.5)], visual acuity [30.0 (22.5 to 38.7); 66.3 (61.0 to 71.1)] and self-reported vision [4.2 (1.6 to 9.8); 97.0 (94.6 to 98.5)]. Optical coherence tomography had the highest sensitivity across all secondary analyses. The final prediction model for neovascular age-related macular degeneration in the non-affected eye included smoking status, family history of neovascular age-related macular degeneration, the presence of nodular drusen with or without reticular pseudodrusen, and the presence of pigmentary abnormalities [c-statistic 0.66 (95% confidence interval 0.62 to 0.71)]. Optical coherence tomography monitoring generated the greatest quality-adjusted life-years gained per patient (optical coherence tomography, 5.830; fundus clinical examination, 5.787; Amsler chart, 5.736, self-reported vision, 5.630; and visual acuity, 5.600) for the lowest health-care and social care costs (optical coherence tomography, £19,406; fundus clinical examination, £19,649; Amsler chart, £19,751; self-reported vision, £20,198; and visual acuity, £20,444) over the lifetime of the simulated cohort. Optical coherence tomography dominated the other tests or had an incremental cost-effectiveness ratio below the accepted cost-effectiveness thresholds (£20,000) across the scenarios explored.
LIMITATIONS: The diagnostic performance may be different in an unselected population without any history of neovascular age-related macular degeneration; the prediction model did not include genetic profile data, which might have improved the discriminatory performance.
CONCLUSIONS: Optical coherence tomography was the most accurate in diagnosing conversion to neovascular age-related macular degeneration in the fellow eye of patients with unilateral neovascular age-related macular degeneration. Economic modelling suggests that optical coherence tomography monitoring is cost-effective and leads to earlier diagnosis of and treatment for neovascular age-related macular degeneration in the second eye of patients being treated for neovascular age-related macular degeneration in their first eye.
FUTURE WORK: Future works should investigate the role of home monitoring, improved risk prediction models and impact on long-term visual outcomes.
STUDY REGISTRATION: This study was registered as ISRCTN48855678.
FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 8. See the NIHR Journals Library website for further project information.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Health technology assessment (Winchester, England) - 26(2022), 8 vom: 04. Jan., Seite 1-142 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Banister, Katie [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.02.2022 Date Revised 22.02.2023 published: Print ISRCTN: ISRCTN48855678 Citation Status MEDLINE |
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| doi: |
10.3310/VLFL1739 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM336520077 |
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| 100 | 1 | |a Banister, Katie |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Non-invasive testing for early detection of neovascular macular degeneration in unaffected second eyes of older adults |b EDNA diagnostic accuracy study |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 25.02.2022 | ||
| 500 | |a Date Revised 22.02.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a ISRCTN: ISRCTN48855678 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Neovascular age-related macular degeneration is a leading cause of sight loss, and early detection and treatment is important. For patients with neovascular age-related macular degeneration in one eye, it is usual practice to monitor the unaffected eye. The test used to diagnose neovascular age-related macular degeneration, fundus fluorescein angiography, is an invasive test. Non-invasive tests are available, but their diagnostic accuracy is unclear | ||
| 520 | |a OBJECTIVES: The primary objective was to determine the diagnostic monitoring performance of tests for neovascular age-related macular degeneration in the second eye of patients with unilateral neovascular age-related macular degeneration. The secondary objectives were the cost-effectiveness of tests and to identify predictive factors of developing neovascular age-related macular degeneration | ||
| 520 | |a DESIGN: This was a multicentre, prospective, cohort, comparative diagnostic accuracy study in a monitoring setting for up to 3 years. A Cox regression risk prediction model and a Markov microsimulation model comparing cost-effectiveness of the index tests over 25 years were used | ||
| 520 | |a SETTING: This took place in hospital eye services | ||
| 520 | |a PARTICIPANTS: Participants were adults (aged 50-95 years) with newly diagnosed (within the previous 6 weeks) neovascular age-related macular degeneration in one eye and an unaffected second (study) eye who were attending for treatment injections in the first eye and who had a study eye baseline visual acuity of ≥ 68 Early Treatment Diabetic Retinopathy Study letters | ||
| 520 | |a INTERVENTIONS: The index tests were Amsler chart (completed by participants), fundus clinical examination, optical coherence tomography, self-reported vision assessment (completed by participants) and visual acuity. The reference standard was fundus fluorescein angiography | ||
| 520 | |a MAIN OUTCOME MEASURES: The main outcome measures were sensitivity and specificity; the performance of the risk predictor model; and costs and quality-adjusted life-years | ||
| 520 | |a RESULTS: In total, 552 out of 578 patients who consented from 24 NHS hospitals (n = 16 ineligible; n = 10 withdrew consent) took part. The mean age of the patients was 77.4 years (standard deviation 7.7 years) and 57.2% were female. For the primary analysis, 464 patients underwent follow-up fundus fluorescein angiography and 120 developed neovascular age-related macular degeneration on fundus fluorescein angiography. The diagnostic accuracy [sensitivity (%) (95% confidence interval); specificity (%) (95% confidence interval)] was as follows: optical coherence tomography 91.7 (85.2 to 95.6); 87.8 (83.8 to 90.9)], fundus clinical examination [53.8 (44.8 to 62.5); 97.6 (95.3 to 98.9)], Amsler [33.7 (25.1 to 43.5); 81.4 (76.4 to 85.5)], visual acuity [30.0 (22.5 to 38.7); 66.3 (61.0 to 71.1)] and self-reported vision [4.2 (1.6 to 9.8); 97.0 (94.6 to 98.5)]. Optical coherence tomography had the highest sensitivity across all secondary analyses. The final prediction model for neovascular age-related macular degeneration in the non-affected eye included smoking status, family history of neovascular age-related macular degeneration, the presence of nodular drusen with or without reticular pseudodrusen, and the presence of pigmentary abnormalities [c-statistic 0.66 (95% confidence interval 0.62 to 0.71)]. Optical coherence tomography monitoring generated the greatest quality-adjusted life-years gained per patient (optical coherence tomography, 5.830; fundus clinical examination, 5.787; Amsler chart, 5.736, self-reported vision, 5.630; and visual acuity, 5.600) for the lowest health-care and social care costs (optical coherence tomography, £19,406; fundus clinical examination, £19,649; Amsler chart, £19,751; self-reported vision, £20,198; and visual acuity, £20,444) over the lifetime of the simulated cohort. Optical coherence tomography dominated the other tests or had an incremental cost-effectiveness ratio below the accepted cost-effectiveness thresholds (£20,000) across the scenarios explored | ||
| 520 | |a LIMITATIONS: The diagnostic performance may be different in an unselected population without any history of neovascular age-related macular degeneration; the prediction model did not include genetic profile data, which might have improved the discriminatory performance | ||
| 520 | |a CONCLUSIONS: Optical coherence tomography was the most accurate in diagnosing conversion to neovascular age-related macular degeneration in the fellow eye of patients with unilateral neovascular age-related macular degeneration. Economic modelling suggests that optical coherence tomography monitoring is cost-effective and leads to earlier diagnosis of and treatment for neovascular age-related macular degeneration in the second eye of patients being treated for neovascular age-related macular degeneration in their first eye | ||
| 520 | |a FUTURE WORK: Future works should investigate the role of home monitoring, improved risk prediction models and impact on long-term visual outcomes | ||
| 520 | |a STUDY REGISTRATION: This study was registered as ISRCTN48855678 | ||
| 520 | |a FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 8. See the NIHR Journals Library website for further project information | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ADULT | |
| 650 | 4 | |a AMSLER | |
| 650 | 4 | |a CHOROID | |
| 650 | 4 | |a COST-BENEFIT ANALYSIS | |
| 650 | 4 | |a DIAGNOSTIC TESTS, ROUTINE | |
| 650 | 4 | |a FLUORESCEIN ANGIOGRAPHY | |
| 650 | 4 | |a HUMANS | |
| 650 | 4 | |a QUALITY-ADJUSTED LIFE-YEARS | |
| 650 | 4 | |a RETINA | |
| 650 | 4 | |a RISK FACTORS | |
| 650 | 4 | |a SELF-REPORT VISUAL FUNCTION | |
| 650 | 4 | |a SENSITIVITY AND SPECIFICITY | |
| 650 | 4 | |a TOMOGRAPHY, OPTICAL COHERENCE | |
| 650 | 4 | |a VISUAL ACUITY | |
| 650 | 4 | |a WET MACULAR DEGENERATION | |
| 700 | 1 | |a Cook, Jonathan A |e verfasserin |4 aut | |
| 700 | 1 | |a Scotland, Graham |e verfasserin |4 aut | |
| 700 | 1 | |a Azuara-Blanco, Augusto |e verfasserin |4 aut | |
| 700 | 1 | |a Goulão, Beatriz |e verfasserin |4 aut | |
| 700 | 1 | |a Heimann, Heinrich |e verfasserin |4 aut | |
| 700 | 1 | |a Hernández, Rodolfo |e verfasserin |4 aut | |
| 700 | 1 | |a Hogg, Ruth |e verfasserin |4 aut | |
| 700 | 1 | |a Kennedy, Charlotte |e verfasserin |4 aut | |
| 700 | 1 | |a Sivaprasad, Sobha |e verfasserin |4 aut | |
| 700 | 1 | |a Ramsay, Craig |e verfasserin |4 aut | |
| 700 | 1 | |a Chakravarthy, Usha |e verfasserin |4 aut | |
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