Background: Natural fluorescence in the eye may be increased or decreased by diseases that affect the retina. Imaging methods based on confocal scanning laser ophthalmoscopy (cSLO) can detect this 'fundus autofluorescence' (FAF) by illuminating the retina using a specific light 'excitation wavelength'. FAF imaging could assist the diagnosis or monitoring of retinal conditions. However, the accuracy of the method for diagnosis or monitoring is unclear.
Objective: To conduct a systematic review to determine the accuracy of FAF imaging using cSLO for the diagnosis or monitoring of retinal conditions, including monitoring of response to therapy.
Data sources: Electronic bibliographic databases; scrutiny of reference lists of included studies and relevant systematic reviews; and searches of internet pages of relevant organisations, meetings and trial registries. Databases included MEDLINE, EMBASE, The Cochrane Library, Web of Science and the Medion database of diagnostic accuracy studies. Searches covered 1990 to November 2014 and were limited to the English language.
Review methods: References were screened for relevance using prespecified inclusion criteria to capture a broad range of retinal conditions. Two reviewers assessed titles and abstracts independently. Full-text versions of relevant records were retrieved and screened by one reviewer and checked by a second. Data were extracted and critically appraised using the Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS) for assessing risk of bias in test accuracy studies by one reviewer and checked by a second. At all stages any reviewer disagreement was resolved through discussion or arbitration by a third reviewer.
Results: Eight primary research studies have investigated the diagnostic accuracy of FAF imaging in retinal conditions: choroidal neovascularisation (one study), reticular pseudodrusen (three studies), cystoid macular oedema (two studies) and diabetic macular oedema (two studies). Sensitivity of FAF imaging using an excitation wavelength of 488 nm was generally high (range 81-100%), but was lower (55% and 32%) in two studies using longer excitation wavelengths (514 nm and 790 nm, respectively). Specificity ranged from 34% to 100%. However, owing to limitations of the data, none of the studies provide conclusive evidence of the diagnostic accuracy of FAF imaging.
Limitations: No studies on the accuracy of FAF imaging for monitoring the progression of retinal conditions or response to therapy were identified. Owing to study heterogeneity, pooling of diagnostic outcomes in meta-analysis was not conducted. All included studies had high risk of bias. In most studies the patient spectrum was not reflective of those who would present in clinical practice and no studies adequately reported how FAF images were interpreted.
Conclusions: Although already in use in clinical practice, it is unclear whether or not FAF imaging is accurate, and whether or not it is applied and interpreted consistently for the diagnosis and/or monitoring of retinal conditions. Well-designed prospective primary research studies, which conform to the paradigm of diagnostic test accuracy assessment, are required to investigate the accuracy of FAF imaging in diagnosis and monitoring of inherited retinal dystrophies, early age-related macular degeneration, geographic atrophy and central serous chorioretinopathy.
Study registration: This study is registered as PROSPERO CRD42014014997.
Funding: The National Institute for Health Research Health Technology Assessment programme.