Use of Smartphones to Detect Diabetic Retinopathy: Scoping Review and Meta-Analysis of Diagnostic Test Accuracy Studies

Background Diabetic retinopathy (DR), a common complication of diabetes mellitus, is the leading cause of impaired vision in adults worldwide. Smartphone ophthalmoscopy involves using a smartphone camera for digital retinal imaging. Utilizing smartphones to detect DR is potentially more affordable, accessible, and easier to use than conventional methods. Objective This study aimed to determine the diagnostic accuracy of various smartphone ophthalmoscopy approaches for detecting DR in diabetic patients. Methods We performed an electronic search on the Medical Literature Analysis and Retrieval System Online (MEDLINE), EMBASE, and Cochrane Library for literature published from January 2000 to November 2018. We included studies involving diabetic patients, which compared the diagnostic accuracy of smartphone ophthalmoscopy for detecting DR to an accurate or commonly employed reference standard, such as indirect ophthalmoscopy, slit-lamp biomicroscopy, and tabletop fundus photography. Two reviewers independently screened studies against the inclusion criteria, extracted data, and assessed the quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies–2 tool, with disagreements resolved via consensus. Sensitivity and specificity were pooled using the random effects model. A summary receiver operating characteristic (SROC) curve was constructed. This review is reported in line with the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies guidelines. Results In all, nine studies involving 1430 participants were included. Most studies were of high quality, except one study with limited applicability because of its reference standard. The pooled sensitivity and specificity for detecting any DR was 87% (95% CI 74%-94%) and 94% (95% CI 81%-98%); mild nonproliferative DR (NPDR) was 39% (95% CI 10%-79%) and 95% (95% CI 91%-98%); moderate NPDR was 71% (95% CI 57%-81%) and 95% (95% CI 88%-98%); severe NPDR was 80% (95% CI 49%-94%) and 97% (95% CI 88%-99%); proliferative DR (PDR) was 92% (95% CI 79%-97%) and 99% (95% CI 96%-99%); diabetic macular edema was 79% (95% CI 63%-89%) and 93% (95% CI 82%-97%); and referral-warranted DR was 91% (95% CI 86%-94%) and 89% (95% CI 56%-98%). The area under SROC curve ranged from 0.879 to 0.979. The diagnostic odds ratio ranged from 11.3 to 1225. Conclusions We found heterogeneous evidence showing that smartphone ophthalmoscopy performs well in detecting DR. The diagnostic accuracy for PDR was highest. Future studies should standardize reference criteria and classification criteria and evaluate other available forms of smartphone ophthalmoscopy in primary care settings.

Of the 80 patients, 32 patients had signs of referable DR (moderate NPDR or higher on ICDR scale and/or presence of CSME) as per the ground truth.

Kim 2017
Manuscript for this abstract was at that point in publication.

Kim 2018
No reply from corresponding author after two weeks.
NB: This study employed a different methodology to calculate the sensitivity and specificity of smartphone ophthalmoscopy compared to other studies. To ensure consistency, we used data from this table instead:

Ryan, 2015
No reply from corresponding author after two weeks. Sengupta, 2018

Reference standard:
Patients underwent a comprehensive dilated retinal examination which included indirect ophthalmoscopy and evaluation of the retina using a +90D lens on the slit lamp.

Sensitivity and specificity values for detection of Macula Edema (M1):
Since very few eyes had macular edema (DME) alone and not R2 or R3 disease, this was not evaluated separately. Irrespective of the DR status, for both graders, and for both imaging modalities, the sensitivity of detecting DME ranged between 82.5-91.5% and specificity was 78-80%.
Other clues such as presence of hard exudates and microaneurysms near the fovea are used by graders to comment on presence of DME, while clinical examination allows depth perception.

As 4 eyes were excluded from the Remidio FOP analysis, what were the gold standard diabetic retinopathy diagnoses for those 4 eyes?
Answer: 2 out of 4 were R1 and another 2 were R2 disease.

2⨉2 table for vision-threatening diabetic retinopathy (VTDR) and diabetic macular edema (DME):
The actual data numbers (exact numbers of VTDR and DME) cannot be shared with any external sources as it is prohibited by the Ethics committee.

Toy 2016
In the Results section, smartphone-acquired fundus images were compared to the "clinical grade as a reference (standard)". What specific tests were performed to determine the clinical grades?
Clinical grade was determined by two masked graders based on the International Clinical Classification for Diabetic Retinopathy (ICDR) disease severity scale.
Was there any unpublished data related to sensitivity and specificity values of smartphone-acquired fundus photographs for any of the following conditions: • Any form of diabetic retinopathy?
• Any specific grade/type of diabetic retinopathy (mild/moderate/severe non-proliferative or proliferative)?
Using clinical grade as the reference to detect referral-warranted retinopathy, photograph grade was found to be 91% sensitive and 99% specific, with a 95% positive predictive value and a 98% negative predictive value. The requested sensitivity and specificity values for the various grades can be calculated from our Table 3 and Table 4. Please note that the number of patients in some of the categories were small, so caution is advised in drawing definitive conclusions from the subgroups.