Factors Associated with Fluctuations in Central Subfield Thickness in Patients with Diabetic Macular Edema Using Diabetic Retinopathy Clinical Research Protocols T and V

PURPOSE: To identify baseline ocular and systemic factors associated with central subfield thickness (CST) fluctuations in patients with diabetic macular edema (DME) using data from Diabetic Retinopathy Clinical Research Protocols T and V. DESIGN: Post hoc analysis of clinical trial databases. SUBJECTS: Patients in Protocols T and V. METHODS: The standard deviation (SD) of all recorded CSTs for each patient during each Protocol’s study period was calculated. The CST SD (corresponding to CST fluctuations) for each patient was analyzed against baseline ocular and systemic factors using linear regression analyses. Each Protocol was analyzed separately. MAIN OUTCOME MEASURES: Factors associated with CST fluctuations. RESULTS: A total of 1197 eyes of 1197 subjects were included. In Protocol T (559 eyes, mean CST SD was 56.4 ± 35.1 microns), using multivariate linear regression analysis, baseline urine albumin/creatine ratio (for every 1000 mg/g, CST point estimate 3.50, 95% confidence interval [CI] 0.58 to 6.43, P = 0.0190), and baseline CST (for every 10 microns, 0.87, 95% CI 0.58 to 1.16, P < 0.0001) were positively associated with CST fluctuations. Baseline visual acuity (for every 10 ETDRS letters, −9.52, 95% CI −11.89 to −7.15, P < 0.0001) was negatively associated with CST fluctuations. In Protocol V (638 eyes, mean CST SD 36.6 ± 28.4 microns), gender (female, 2.18, 95% CI 0.30 to 4.06, P = 0.0227), baseline CST (for every 10 microns, 2.51, 95% CI 2.21 to 2.82, P < 0.0001), systolic blood pressure (for every 1 mm of mercury, 0.11, 95% CI 0.01 to 0.21, P = 0.0261), and observation with deferred anti-VEGF injections (5.04, 95% CI 2.51 to 7.58, P < 0.0001) were positively associated with CST fluctuations. Type 2 diabetes (−7.37, 95% CI −13.64 to −1.11, P = 0.0209) and prompt anti-VEGF injections (−6.51, 95% CI −9.07 to −3.96, P < 0.0001) were negatively associated with CST fluctuations. CONCLUSIONS: Worse visual acuity at baseline, baseline renal disease, hypertension, female gender, type 1 diabetes, and delayed anti-VEGF treatment may be associated with increased CST fluctuations in patients with DME. Addressing these parameters may limit CST fluctuations and help identify patients requiring more frequent monitoring or treatment.