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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  Types of studies: direct/indirect studies reporting diagnostic outcomes.
  
  
  METHODS
  time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  This study is registered as PROSPERO CRD42012001930.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Mowatt
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Hernández
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Mayret
authors.initials: M
authors.lastname: Castillo
authors.affiliation: Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK.
authors.forename: Noemi
authors.initials: N
authors.lastname: Lois
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Elders
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Fraser
authors.affiliation: Health Economics Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Olatunde
authors.initials: O
authors.lastname: Aremu
authors.affiliation: Department of Ophthalmology, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Winfried
authors.initials: W
authors.lastname: Amoaku
authors.affiliation: Medical and Biosocial Sciences, School of Medicine, University of St Andrews, St Andrews, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Burr
authors.affiliation: Clinical Neurosciences Research Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lotery
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Ramsay
authors.affiliation: Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK.
authors.forename: Augusto
authors.initials: A
authors.lastname: Azuara-Blanco
mesh_terms: D003362:Cost-Benefit Analysis; D005451:Fluorescein Angiography; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis* / Q000503:physiopathology*; D017059:Models, Econometric; D019057:Quality-Adjusted Life Years; D041623:Tomography, Optical Coherence / Q000379:methods*; D014792:Visual Acuity