Systematic review and meta-analysis of diagnostic accuracy of detection of any level of diabetic retinopathy using digital retinal imaging

Purpose
Visual impairment from diabetic retinopathy (DR) is a rising global public health concern, which can be prevented with screening and early treatment. Digital retinal imaging has become a preferred choice as it enables higher accuracy, acceptability, and coverage of screening. A DR screening (DRS) modality using digital retinal imaging which is suited to the health system and its context is a key factor in the success of a programme. However, often there are gaps in evidence base to choose a DRS strategy using digital retinal imaging that fits to a programme requirement. The available reviews and summary estimates provided diagnostic test accuracy (DTA) of detection of DR by combining both digital and non-digital modalities.
Setting/Venue
The aim of this review is to evaluate how different characteristics of the DRS using digital retinal imaging, such as number of fields, pupil status impacts on diagnostic test accuracy (DTA), and its relevance to a low-income setting. This will inform decision making for choosing strategy in those aspects of a DRS programme. This is an assessment of different imaging strategies for a systematic clinic-based screening rather than a population-based screening tool.
Methods
We conducted a search to identify studies on DRS using digital retinal imaging of diabetics at health-care facilities. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed in preparation of the protocol and reporting. We developed a comprehensive search strategy and searched MEDLINE (Ovid), Cochrane Database of Systematic reviews (CDSR) and CENTRAL from the date of inception to September 2016. We included studies that aimed to evaluate the accuracy of DRS using digital imaging as the index test. We used the Early Treatment Diabetic Retinopathy Study (ETDRS) 7-field image interpretation as the gold standard, and mydriatic bio-microscopy by an ophthalmologist as the clinical reference standard where the gold standard was not performed. We assessed the bias using the Quality Assessment of Diagnostic Accuracy |Studies (QUADAS-2) framework. The outcome examined was sensitivity and specificity of detection of ‘any level of DR’. Summary estimates of different sub-groups were calculated using DTA values weighted according to the sample size. The DTA of each screening method was derived after exclusion of ungradable images, considering eye as the unit of analysis. We examined the effect on detection from using different combinations of retinal fields, pupil status, index test graders and setting.
Results
6646 titles and abstracts were retrieved, and data extracted from 122 full reports. Twenty-six studies were included in the review. Of the 21 studies included in the meta-analysis 39 different modalities were identified in terms of pupil status, retinal field strategy and human resources involved in index test DR grading. The pooled sensitivity of detection of any level of DR using non-mydriatic digital imaging was 86% (95% CI 85-87%). The 2-field strategy gave the highest estimate of sensitivity of 91% (95% CI 90-93%). The 1 and >2-field strategies gave summary estimates of sensitivity of 78% (95% CI 76-80%) and 88% (95% CI 86-91%), respectively. The highest sensitivity was observed in mydriatic >2-field strategy (92%, 95% CI 90-94%). The sensitivity of the 1-field strategy was 80% (95% CI 77-82%) and 85% (95% CI 84-87%) for the 2-field strategy. Overall, there was no difference in sensitivity between non-mydriatic and mydriatic methods (86%, 95% CI 85-87) after exclusion of ungradable images. The highest specificity was observed in >2-field methods (94%, 95% CI 93-96%) where mydriasis did not affect specificity. The highest DTA (sensitivity 90%, 95% CI 88-91%; specificity 95%, 95% CI 94-96%) was observed when screening was delivered at secondary/tertiary level clinics.
Conlusions
Both non-mydriatic and mydriatic strategies showed very high discriminative power in ruling out presence or absence of any level of DR with the diagnostic odds ratio (DOR) of nonmydriatic strategies being 68.03 (95% CI 35.5-130.0) and positive likelihood ratio of 11.79 (SE 3.04, 95% CI 7.1-19.5). Diagnostic test accuracy for the detection of any level of DR showed that DRS using 2 fields delivered at non-primary care settings is a feasible approach. Dilatation of pupils did not improve the detection of any level of DR for those with gradable images, but such a wide range of ungradable were presented in these studies that this aspect must be taken into account when setting up DRSP. There wasn’t adequate evidence in primary studies to comment on DTA of non-ophthalmological human resources on DRS, so this aspect requires further research. Good quality digital imaging has the potential for real time interpretation of retinal images, which together with counselling for risk factors may improve the acceptability of DRS and uptake of referral for ophthalmic assessment if conducted in a culturally acceptable way.