Xuxi Zhang

Data extraction and quality assessment Data from the 22 studies were extracted by two reviewers (Yusufu and Zhang) with a standardized data extraction form. The extraction form included: the name of the study (most studies had an official name; if not, the study was named after the first author), the year of publication, number of participants, follow ‐ up interval, the characteristics of participants (including data of IG and CG respectively, e.g. types of patients, gender ratio, mean age, duration of diabetes, glycated hemoglobin, blood pressure, total cholesterol, body mass index and percentage of patients without DR at baseline), study design and location, intervention methods, the number of participants who developed or did not develop DR in both IG and CG, and/or the number of DR patients whose condition worsened or did not worsen in both groups, and/ or the number of participants with DR progression (For studies failing to provide distinctive data on new onset and worsening DR, the term “progression” was adopted to cover both new onset and worsening DR). The details of each study can be found in Supplementary Table S1 and S2. In all 22 studies, ophthalmologists diagnosed and/or evaluated DR based on on ‐ site ophthalmoscopy or report from the primary care physicians. Most studies 5 ‐ 8, 10, 14, 18, 19, 21 adopted the protocol of the Early Treatment Diabetic Retinopathy Study (ETDRS) to define the grade of DR and make diagnosis of DR. Some studies adopted the Wisconsin Epidemiologic Study of Diabetic Retinopathy 15, 17 , the EURODIAB six ‐ level grading 11, 12, 16 , and other grading scales 13, 20 to define the grade of DR and make diagnosis of DR. DR worsening was defined as a change of at least two steps from baseline measurement in any eye. 5, 7, 8, 10, 14 One study 11 defined DR worsening based on an increase of at least one level in any eye. DR progression was defined as a change of at least two or three steps from baseline measurement in any eye. 6, 18, 19, 21 Two studies 12, 16 defined DR progression as an increase of at least one level in any eye. The detailed criteria used for the diagnosis, worsening and progression of DR in each study can be found in Supplementary Table S3. Some studies did not provide the needed data, in which case, the data needed for the evaluation of the effect of interventions were obtained through calculation. One study 8 only provided the percentage of patients who developed DR at follow ‐ up in the IG and CG respectively. We calculated the number of patients with newly developed DR based on the percentage and the number of patients. One study 15 provided the number of patients without DR at baseline and follow ‐ up respectively in both IG and CG . We subtracted the number of patients without DR at follow ‐ up from the number of patients without DR at baseline to obtain the number of patients with newly developed DR. One study 13 provided the number of patients with DR at baseline and follow ‐ up in both IG and CG . We subtracted the number of patients with DR at baseline from the number of patients with DR at follow ‐ up to get the number of patients with newly developed DR. The interventions were classified into five categories based on modifiable risk factors:1) Blood ‐ pressure ‐ control intervention, 2) Glycemic ‐ control intervention, 3) Lipid ‐ control 166 Chapter 7