Telemedicine for Detecting Diabetic Retinopathy
Telemedicine for Detecting Diabetic Retinopathy
Telemedicine is the transfer of digital photographs of the retina to a reading centre where they can be evaluated by an ophthalmologist. It allows clinicians to detect DR in a non-ophthalmological setting and thus allows them to serve patients in rural, remote and hard-to-reach locations. Previous literature reviews and studies have indicated that telemedicine is a cost-effective means of screening patients for DR and can alleviate some of the burden of DR. Patients have expressed a high degree of satisfaction with the telemedicine examination.
All of the included studies except the study by Lin et al were based on the number of eyes rather than the number of patients. We believe that 'eye count' versus 'person count' had little relationship with the results, so we included both in the meta-analysis. The overall high accuracy of telemedicine in detecting DR suggests that it is valuable for this purpose. When telemedicine was used to detect the absence of DR and mild NPDR, the diagnostic accuracy was higher when the images were acquired through mydriasis than through non-mydriasis and a wide angle (100–200°) of observation rather than a narrower angle (45–60° or the more commonly used 30°or 35°).
Sensitivity varied widely among primary studies, falling as low as zero (see figure 3). A potential explanation for this variability might be the small sample size and ungradable digital images. A previous meta-analysis was limited to the detection of the presence or absence of DR. In this review we analysed the full range of severity of DR and DME. It would have been ideal to use the entire sample size. When the total population was assigned to different clinical levels of DR, however, the sample sizes became quite small. In the study by Hubbard et al, of the total of 628 eyes, the 7F-ETDRS detected severe NPDR in one eye that was not detected by telemedicine; this resulted in a sensitivity of zero. Compared with 7F-ETDRS, digital imaging was more likely to result in images that could not be graded. The ungradable slides were excluded, but the ungradable digital images were included in the analysis. This reduced the sensitivity of telemedicine.
When telemedicine was used to detect the absence of DR, a positive number represented the absence of DR and a negative number represented any clinical level of DR within a 2×2 (true positive vs false positive and false negative vs true negative) array. We were also able to calculate sensitivity and specificity based on the distribution of results within the same 2×2 array. The sensitivity was just the specificity of DR absence detection and the specificity was just the sensitivity of DR absence detection. Thus, when any DR was detected, the pooled sensitivity was 95% (95% CI 94% to 96%) and the pooled specificity was 86% (95% CI 84% to 88%). Sensitivity is the effectiveness of telemedicine in detecting DR in patients who have DR, and thus reduces the risk of missing DR. The analogous sensitivity and specificity were also displayed in the subgroup analysis using digital imaging. The high sensitivity in detecting any clinical level of DR suggests the good performance of telemedicine in ophthalmology and supports its common use in DR screening. The pooled sensitivity for detecting severe NPDR was lower than for other levels of DR; this was also shown by the two subgroup analyses (see online supplementary table S3 http://bjo.bmj.com/content/99/6/823/suppl/DC1).
One limitation of this review was the presence of heterogeneity. The results of meta-regression analysis using covariates such as subject characteristics, recruitment methods and digital imaging techniques did not provide valuable information. Even after the subgroup analyses based on the digital imaging technique, heterogeneity was only partially ameliorated. In a previous study, the authors reported that the prevalence of DR of any clinical level was higher in people with type 1 diabetes than in those with type 2 diabetes. Even when we excluded the study that recruited subjects with type 1 diabetes only, heterogeneity was not ameliorated (data not shown). In the 20 studies that were included, the percentage of subjects with no DR varied from 1.27% to 59.86%; this may also have been a source of heterogeneity. Another limitation of our findings was that the raw data provided by three studies were unavailable and the data used in the meta-analysis were only from published papers. This, in turn, introduces the possibility of study selection bias. Additionally, the quality of telemedicine largely depends on the experience of readers who grade the digital images and the technician who takes the images. Thus, the use of telemedicine is limited.
In summary, the diagnostic accuracy of telemedicine using digital imaging in DR is overall high. The high sensitivity of its detection of any clinical level of DR indicates that telemedicine can be used widely for DR screening. Telemedicine based on digital imaging techniques that incorporate mydriasis and a wide (100–200°) field is the best choice for detecting the absence of DR and mild NPDR. Further research should be carried out to evaluate the diagnostic accuracy of telemedicine based on each digital imaging technique using a study design that may prevent heterogeneity across studies.
Discussion
Telemedicine is the transfer of digital photographs of the retina to a reading centre where they can be evaluated by an ophthalmologist. It allows clinicians to detect DR in a non-ophthalmological setting and thus allows them to serve patients in rural, remote and hard-to-reach locations. Previous literature reviews and studies have indicated that telemedicine is a cost-effective means of screening patients for DR and can alleviate some of the burden of DR. Patients have expressed a high degree of satisfaction with the telemedicine examination.
All of the included studies except the study by Lin et al were based on the number of eyes rather than the number of patients. We believe that 'eye count' versus 'person count' had little relationship with the results, so we included both in the meta-analysis. The overall high accuracy of telemedicine in detecting DR suggests that it is valuable for this purpose. When telemedicine was used to detect the absence of DR and mild NPDR, the diagnostic accuracy was higher when the images were acquired through mydriasis than through non-mydriasis and a wide angle (100–200°) of observation rather than a narrower angle (45–60° or the more commonly used 30°or 35°).
Sensitivity varied widely among primary studies, falling as low as zero (see figure 3). A potential explanation for this variability might be the small sample size and ungradable digital images. A previous meta-analysis was limited to the detection of the presence or absence of DR. In this review we analysed the full range of severity of DR and DME. It would have been ideal to use the entire sample size. When the total population was assigned to different clinical levels of DR, however, the sample sizes became quite small. In the study by Hubbard et al, of the total of 628 eyes, the 7F-ETDRS detected severe NPDR in one eye that was not detected by telemedicine; this resulted in a sensitivity of zero. Compared with 7F-ETDRS, digital imaging was more likely to result in images that could not be graded. The ungradable slides were excluded, but the ungradable digital images were included in the analysis. This reduced the sensitivity of telemedicine.
When telemedicine was used to detect the absence of DR, a positive number represented the absence of DR and a negative number represented any clinical level of DR within a 2×2 (true positive vs false positive and false negative vs true negative) array. We were also able to calculate sensitivity and specificity based on the distribution of results within the same 2×2 array. The sensitivity was just the specificity of DR absence detection and the specificity was just the sensitivity of DR absence detection. Thus, when any DR was detected, the pooled sensitivity was 95% (95% CI 94% to 96%) and the pooled specificity was 86% (95% CI 84% to 88%). Sensitivity is the effectiveness of telemedicine in detecting DR in patients who have DR, and thus reduces the risk of missing DR. The analogous sensitivity and specificity were also displayed in the subgroup analysis using digital imaging. The high sensitivity in detecting any clinical level of DR suggests the good performance of telemedicine in ophthalmology and supports its common use in DR screening. The pooled sensitivity for detecting severe NPDR was lower than for other levels of DR; this was also shown by the two subgroup analyses (see online supplementary table S3 http://bjo.bmj.com/content/99/6/823/suppl/DC1).
One limitation of this review was the presence of heterogeneity. The results of meta-regression analysis using covariates such as subject characteristics, recruitment methods and digital imaging techniques did not provide valuable information. Even after the subgroup analyses based on the digital imaging technique, heterogeneity was only partially ameliorated. In a previous study, the authors reported that the prevalence of DR of any clinical level was higher in people with type 1 diabetes than in those with type 2 diabetes. Even when we excluded the study that recruited subjects with type 1 diabetes only, heterogeneity was not ameliorated (data not shown). In the 20 studies that were included, the percentage of subjects with no DR varied from 1.27% to 59.86%; this may also have been a source of heterogeneity. Another limitation of our findings was that the raw data provided by three studies were unavailable and the data used in the meta-analysis were only from published papers. This, in turn, introduces the possibility of study selection bias. Additionally, the quality of telemedicine largely depends on the experience of readers who grade the digital images and the technician who takes the images. Thus, the use of telemedicine is limited.
In summary, the diagnostic accuracy of telemedicine using digital imaging in DR is overall high. The high sensitivity of its detection of any clinical level of DR indicates that telemedicine can be used widely for DR screening. Telemedicine based on digital imaging techniques that incorporate mydriasis and a wide (100–200°) field is the best choice for detecting the absence of DR and mild NPDR. Further research should be carried out to evaluate the diagnostic accuracy of telemedicine based on each digital imaging technique using a study design that may prevent heterogeneity across studies.
