Incidence and Risk Factors for Developing Diabetic Retinopathy among Youths with Type 1 or Type 2 Diabetes throughout the United States.
Despite the increasing prevalence of type 2 diabetes mellitus (T2DM) among children and adolescents, little is known about their risk of developing diabetic retinopathy (DR). We sought to identify risk factors for DR in youths with diabetes mellitus, to compare DR rates for youths with type 1 diabetes mellitus (T1DM) and those with T2DM, and to assess whether adherence to DR screening guidelines promoted by the American Academy of Ophthalmology, American Academy of Pediatrics, and American Diabetes Association adequately capture youths with DR.
Retrospective observational longitudinal cohort study.
Youths aged ≤21 years with newly diagnosed T1DM or T2DM who were enrolled in a large US managed-care network.
In this study of youths aged ≤21 years with newly diagnosed T1DM or T2DM who were under ophthalmic surveillance, we identified the incidence and timing of DR onset. Kaplan-Meier survival curves assessed the timing of initial diagnosis of DR for participants. Multivariable Cox proportional hazard regression modeling identified factors associated with the hazard of developing DR. Model predictors were age and calendar year at initial diabetes mellitus diagnosis, sex, race/ethnicity, net worth, and glycated hemoglobin A1c fraction (HbA1c).
Hazard ratios (HRs) with 95% confidence intervals (CIs) for developing DR.
Among the 2240 youths with T1DM and 1768 youths with T2DM, 20.1% and 7.2% developed DR over a median follow-up time of 3.2 and 3.1 years, respectively. Survival curves demonstrated that youths with T1DM developed DR faster than youths with T2DM (P < 0.0001). For every 1-point increase in HbA1c, the hazard for DR increased by 20% (HR = 1.20; 95% CI 1.06-1.35) and 30% (HR = 1.30; 95% CI 1.08-1.56) among youths with T1DM and T2DM, respectively. Current guidelines suggest that ophthalmic screening begin 3 to 5 years after initial diabetes mellitus diagnosis, at which point in our study, >18% of youths with T1DM had already received ≥1 DR diagnosis.
Youths with T1DM or T2DM exhibit a considerable risk for DR and should undergo regular screenings by eye-care professionals to ensure timely DR diagnosis and limit progression to vision-threatening disease.
Wang SY
,Andrews CA
,Herman WH
,Gardner TW
,Stein JD
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Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy.
Diabetic retinopathy (DR) is characterised by neurovascular degeneration as a result of chronic hyperglycaemia. Proliferative diabetic retinopathy (PDR) is the most serious complication of DR and can lead to total (central and peripheral) visual loss. PDR is characterised by the presence of abnormal new blood vessels, so-called "new vessels," at the optic disc (NVD) or elsewhere in the retina (NVE). PDR can progress to high-risk characteristics (HRC) PDR (HRC-PDR), which is defined by the presence of NVD more than one-fourth to one-third disc area in size plus vitreous haemorrhage or pre-retinal haemorrhage, or vitreous haemorrhage or pre-retinal haemorrhage obscuring more than one disc area. In severe cases, fibrovascular membranes grow over the retinal surface and tractional retinal detachment with sight loss can occur, despite treatment. Although most, if not all, individuals with diabetes will develop DR if they live long enough, only some progress to the sight-threatening PDR stage. OBJECTIVES: To determine risk factors for the development of PDR and HRC-PDR in people with diabetes and DR.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5), Ovid MEDLINE, and Ovid Embase. The date of the search was 27 May 2022. Additionally, the search was supplemented by screening reference lists of eligible articles. There were no restrictions to language or year of publication. SELECTION CRITERIA: We included prospective or retrospective cohort studies and case-control longitudinal studies evaluating prognostic factors for the development and progression of PDR, in people who have not had previous treatment for DR. The target population consisted of adults (≥18 years of age) of any gender, sexual orientation, ethnicity, socioeconomic status, and geographical location, with non-proliferative diabetic retinopathy (NPDR) or PDR with less than HRC-PDR, diagnosed as per standard clinical practice. Two review authors independently screened titles and abstracts, and full-text articles, to determine eligibility; discrepancies were resolved through discussion. We considered prognostic factors measured at baseline and any other time points during the study and in any clinical setting. Outcomes were evaluated at three and eight years (± two years) or lifelong. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included studies using a data extraction form that we developed and piloted prior to the data collection stage. We resolved any discrepancies through discussion. We used the Quality in Prognosis Studies (QUIPS) tool to assess risk of bias. We conducted meta-analyses in clinically relevant groups using a random-effects approach. We reported hazard ratios (HR), odds ratios (OR), and risk ratios (RR) separately for each available prognostic factor and outcome, stratified by different time points. Where possible, we meta-analysed adjusted prognostic factors. We evaluated the certainty of the evidence with an adapted version of the GRADE framework. MAIN RESULTS: We screened 6391 records. From these, we identified 59 studies (87 articles) as eligible for inclusion. Thirty-five were prospective cohort studies, 22 were retrospective studies, 18 of which were cohort and six were based on data from electronic registers, and two were retrospective case-control studies. Twenty-three studies evaluated participants with type 1 diabetes (T1D), 19 with type 2 diabetes (T2D), and 17 included mixed populations (T1D and T2D). Studies on T1D included between 39 and 3250 participants at baseline, followed up for one to 45 years. Studies on T2D included between 100 and 71,817 participants at baseline, followed up for one to 20 years. The studies on mixed populations of T1D and T2D ranged from 76 to 32,553 participants at baseline, followed up for four to 25 years. We found evidence indicating that higher glycated haemoglobin (haemoglobin A1c (HbA1c)) levels (adjusted OR ranged from 1.11 (95% confidence interval (CI) 0.93 to 1.32) to 2.10 (95% CI 1.64 to 2.69) and more advanced stages of retinopathy (adjusted OR ranged from 1.38 (95% CI 1.29 to 1.48) to 12.40 (95% CI 5.31 to 28.98) are independent risk factors for the development of PDR in people with T1D and T2D. We rated the evidence for these factors as of moderate certainty because of moderate to high risk of bias in the studies. There was also some evidence suggesting several markers for renal disease (for example, nephropathy (adjusted OR ranged from 1.58 (95% CI not reported) to 2.68 (2.09 to 3.42), and creatinine (adjusted meta-analysis HR 1.61 (95% CI 0.77 to 3.36)), and, in people with T1D, age at diagnosis of diabetes (< 12 years of age) (standardised regression estimate 1.62, 95% CI 1.06 to 2.48), increased triglyceride levels (adjusted RR 1.55, 95% CI 1.06 to 1.95), and larger retinal venular diameters (RR 4.28, 95% CI 1.50 to 12.19) may increase the risk of progression to PDR. The certainty of evidence for these factors, however, was low to very low, due to risk of bias in the included studies, inconsistency (lack of studies preventing the grading of consistency or variable outcomes), and imprecision (wide CIs). There was no substantial and consistent evidence to support duration of diabetes, systolic or diastolic blood pressure, total cholesterol, low- (LDL) and high- (HDL) density lipoproteins, gender, ethnicity, body mass index (BMI), socioeconomic status, or tobacco and alcohol consumption as being associated with incidence of PDR. There was insufficient evidence to evaluate prognostic factors associated with progression of PDR to HRC-PDR. AUTHORS' CONCLUSIONS: Increased HbA1c is likely to be associated with progression to PDR; therefore, maintaining adequate glucose control throughout life, irrespective of stage of DR severity, may help to prevent progression to PDR and risk of its sight-threatening complications. Renal impairment in people with T1D or T2D, as well as younger age at diagnosis of diabetes mellitus (DM), increased triglyceride levels, and increased retinal venular diameters in people with T1D may also be associated with increased risk of progression to PDR. Given that more advanced DR severity is associated with higher risk of progression to PDR, the earlier the disease is identified, and the above systemic risk factors are controlled, the greater the chance of reducing the risk of PDR and saving sight.
Perais J
,Agarwal R
,Evans JR
,Loveman E
,Colquitt JL
,Owens D
,Hogg RE
,Lawrenson JG
,Takwoingi Y
,Lois N
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《Cochrane Database of Systematic Reviews》
Relationship between Diabetic Retinopathy and Primary Open-Angle Glaucoma: A Systematic Review and Meta-Analysis.
Pathophysiological overlaps exist between diabetes and primary open-angle glaucoma (POAG) and presence of diabetes increases the risk of POAG. Considering that diabetic retinopathy (DR) is an ocular complication of diabetes, one could speculate that DR as a severity measure may associate with or even predict POAG. Given that POAG is asymptomatic in early stages, an association to DR may prove clinically important and facilitate an earlier diagnosis of POAG.
The aim of the study was to investigate if DR is associated with and predictive of POAG.
We systematically searched 11 literature databases on May 12, 2021. We screened a total of 1,535 records and found six studies eligible for qualitative and quantitative analysis. Two independent authors reviewed the studies, extracted data, and evaluated risk of bias within individual studies. Studies were reviewed qualitatively, and meta-analyses were made based on the odds ratios (ORs) with 95% confidence intervals (CI) of the association between DR and POAG using the random-effects model. Subgroup analyses were made on the association between subtypes of DR and POAG.
Six studies (two longitudinal and four cross-sectional) were eligible for review with a total of 255,614 patients with diabetes, of which 20,483 patients had any degree of DR and 5,258 had POAG. All studies were based on patients with type 2 diabetes except one with both type 1 and type 2 patients. Any DR was not associated with POAG (OR 1.17; 95% CI: 0.58-2.35; p = 0.65). Further stratification revealed that neither cross-sectional (OR 1.00; 95% CI: 0.56-1.81, p = 0.99) nor longitudinal studies (OR 1.47; 95% CI: 0.57-3.78, p = 0.43) demonstrated an association between DR and POAG.
We did not find convincing evidence of an associations between DR and prevalent or incident POAG.
Kjærsgaard M
,Grauslund J
,Vestergaard AH
,Subhi Y
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