Myopia and diabetic retinopathy: A systematic review and meta-analysis

Methodological quality of the review: Medium confidence

Author: Xiang Wanga, Luosheng Tang, Ling Gao, Yujia Yang, Dan Cao, Yunping Li

Region: China, South-Korea, Singapore, Australia, Taiwan, USA, India

Sector: Myopia

Subsector: Myopia treatment

Equity focus: No

Study population: Adults

Type of programme: Community and hospital based

Review type: Other review

Quantitative synthesis method: Systematic review and meta-analysis

Qualitative synthesis method: Not applicable

Background: Diabetic retinopathy (DR), a common and specific microvascular complication of diabetes, remains the leading cause of preventable blindness in working-aged people. Previous studies have demonstrated that myopia protects against DR. However, population-based studies have revealed inconsistent and conflicting results. A better understanding of the relationship between myopia and DR may provide insight into the pathophysiology of DR. However, a meta-analysis of the results of all available studies that have evaluated the association of myopia with DR has not been performed to date.

Objectives: The aim of this study was to examine the association between myopia and DR, based on data from available population-based and clinic-based studies.

Main findings: A total of nine studies were included in the systematic review, including six population-based studies (four cross-sectional studies and two cohort studies) and three clinic-based cross-sectional studies. The studies were published between 1985 and 2015. Among the seven cross-sectional studies, five were conducted in Asia, one was conducted in Australia and one was conducted in the USA. Among the two cohort studies, one was conducted in the USA, and one was conducted in China. The seven cross-sectional studies comprised a total of 24,751 individuals aged >18 years, and the two cohort studies comprised a total of 4,480 individuals. The association of myopic SE with DR was reported in four population-based cross-sectional studies, one cohort study and two clinic-based cross-sectional studies. When combining the estimated effects based on these studies, myopic SE was significantly associated with a decreased risk for DR (pooled OR, 0.80; 95% CI, 0.67-0.95; P=0.011; I²=36.7%). Data on the association of each millimeter increase in AL and DR was available in three population-based cross-sectional studies, one cohort study and two clinic-based studies. When combining the estimated effects based on these studies, each millimeter increase in AL was significantly associated with a decreased risk of DR (pooled OR, 0.79; 95% CI, 0.73-0.86; P=0.000). Significant heterogeneity was observed among these six studies (I²=57.6%, P=0.038). The pooled OR was 0.79 (95% CI, 0.72-0.87; P=0.000), and significant heterogeneity was observed (I²=70.5%; P=0.017). Data regarding the association of each millimeter increase in AL and VTDR were available for five cross-sectional studies. When combining the estimated effects based on these studies, each millimeter increase in AL was significantly associated with a decreased risk of VTDR (pooled OR, 0.70; 95% CI, 0.60-0.82; P=0.000), with no evidence of heterogeneity (I²=0.0%; P=0.826). In all of the analyses, no evidence of publication bias, as indicated by the non-significant results of the Egger tests (all P>0.05) and Begg’s tests (all P>0.05), was observed.

Overall, authors concluded that individuals with myopia exhibit a decreased risk of developing DR or VTDR. An increased AL plays a critical role in this protective effect.

Methodology:

Inclusion criteria for this review included studies that: i) explored the associations among myopia, AL and DR; ii) used DR as an outcome measure, which was assessed based on fundus photographs according to standardised protocols, such as the Early Treatment Diabetic Retinopathy Study (ETDRS) or the Airlie House classification system; and iii) reported a measure of the association either as an odds ratio (OR) or a hazard ratio (HR) with a 95% confidence interval (CI), or allowed for the calculation of such metrics from the raw data presented in the article.

Authors performed a systematic search of PubMed and Embase to identify all relevant population-based and clinic-based studies published up to March 2015. The full texts of the remaining articles were reviewed to ensure that the studies met the inclusion and exclusion criteria. In addition, the reference lists of all of the identified studies were examined. Two authors independently conducted the search; any disagreements were resolved by adjudication with two additional reviewers. Using a standardised data extraction sheet, the following information (if available) was extracted from the studies and recorded: i) last name of the first author; ii) year of publication; iii) study name; iv) study design; v) race/ethnicity of the study population; vi) number of subjects included in the analysis; vii) age range of the study participants; viii) case definition of DR and myopia; ix) effect estimate(s); and x) the confounding factors for which adjustment was performed. We assessed the study quality using the tool described by Sanderson and colleagues. Authors performed the meta-analysis using STATA version 13.0 (StataCorp LP, College Station, TX, USA). The fully adjusted study specific ORs were combined to estimate the pooled OR and 95% CI. Statistical heterogeneity among studies was evaluated using the I² statistic. Myopic SE was defined as SE < -0.5 D compared with emmetropic eyes. We evaluated publication bias using the Egger regression asymmetry test and Begg’s test. A two-sided P-value less than 0.05 was regarded as significant for all analyses.

Applicability/external validity: Regarding external validity, the authors reported some limitations which need to be taken into consideration: first, according to the inclusion and exclusion criteria, few population-based studies were included. Only English language articles were included. Potential biases resulting from study differences in methodologies and strategies for adjusting for confounders may have affected the results. Most of the included studies in our meta-analysis were cross-sectional, and the number of available cohort studies was small. We also have some selection bias. The different studies used different thresholds for myopia, potentially affecting the estimates of the prevalence of myopia.

Geographic focus: Not discussed.

Summary of quality assessment:

There is medium confidence in the conclusions about the effects of this study. Literature searches were not comprehensive enough that we can be confident that relevant studies were not omitted in the review. In addition, it is not clear from the review if authors avoided bias when extracting data of included studies, and did not provide a summary quality assessment of each included study.