Refractive Error and Retinopathy Outcomes in Type 1 Diabetes: the DCCT/EDIC Study

Objective: Determine relationship between refractive error and diabetic retinopathy (DR).

Design: Clinical trial SUBJECTS: Myopia is a non-modifiable risk factor reportedly associated with less severe DR in small case series, but this association has not been confirmed in large prospective studies. With a large cohort of patients with type I diabetes followed over 30 years with serial refractive error and DR stage measurements, the Diabetes Control and Complications Trial and follow-up Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC) provide a unique opportunity to evaluate the association between refractive error and DR development and progression.

Methods: DR stage was measured every six months from standard fundus photographs and refractive error was measured annually during the 6.5 years of DCCT, then both were staggered every fourth year during EDIC with the full cohort measured at EDIC years 4 and 10. DR outcomes were 2- or 3-step progression, presence of proliferative DR (PDR), clinically significant macular edema (CSME), diabetic macular edema (DME) or ocular surgery. Myopia, emmetropia and hyperopia were defined as a spherical equivalent of ≤ -0.5, > -0.5 and < 0.5, and ≥0.5, respectively.

Main outcome measures: For each outcome separately, Cox proportional hazards models assessed the association between refractive error status and the subsequent risk of that outcome, both without and with adjustment for potential risk factors.

Results: Hyperopia was associated with higher risk of 2-step progression (hazard ratio (HR)=1.29, 95%CI 1.05-1.59), 3-step progression (HR=1.35, 95%CI 1.05-1.73) and PDR (HR=1.40, 95%CI 1.02-1.92) compared to emmetropia in unadjusted models. These associations remained significant after adjustment for DCCT treatment group, cohort, age, sex, smoking, duration of diabetes, systolic and diastolic blood pressure, pulse, LDL, HDL, triglycerides, albumin excretion rate, and DCCT/EDIC mean updated HbA1c (2-step progression: HR=1.28, 95%CI 1.03-1.58; 3-step progression: HR=1.30, 95%CI 1.00-1.68; PDR: HR=1.38, 95%CI 1.00-1.90). Myopia was not associated with any of the five DR outcomes in the unadjusted models, and only marginally associated with 2-step progression (HR=1.11, 95%CI 1.00-1.24) in the adjusted models.

Conclusions: Myopia is not associated with DR progression risk. Hyperopia is an independent risk factor for 2-step and 3-step DR progression and PDR.

Keywords: DCCT/EDIC; Diabetes mellitus; diabetic retinopathy; refractive error.