Refractive Error and Retinopathy Outcomes in Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Ophthalmology. 2021 Apr;128(4):554-560. doi: 10.1016/j.ophtha.2020.09.014. Epub 2020 Sep 14.

Abstract

Purpose: To determine the relationship between refractive error and diabetic retinopathy (DR).

Design: Clinical trial.

Participants: Type I diabetes individuals with serial refractive error and DR stage measurements over 30 years in the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study.

Methods: Stage of DR was measured every 6 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. Outcomes of DR 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 hazard (PH) models assessed the association between the refractive error status and the subsequent risk of that outcome, both without and with adjustment for potential risk factors.

Results: Hyperopia was associated with a higher risk of 2-step progression (hazard ratio [HR], 1.29; 95% confidence interval [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 with 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 pressures, pulse, low-density lipoprotein, high-density lipoprotein, triglycerides, albumin excretion rate, and DCCT/EDIC mean updated hemoglobin A1c (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 5 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.

Trial registration: ClinicalTrials.gov NCT00360815 NCT00360893.

Keywords: DCCT/EDIC; Diabetes mellitus; Diabetic retinopathy; Refractive error.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Blood Pressure
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetic Retinopathy / diagnosis
  • Diabetic Retinopathy / etiology
  • Diabetic Retinopathy / physiopathology*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hyperopia / physiopathology*
  • Macular Edema / diagnosis
  • Macular Edema / etiology
  • Macular Edema / physiopathology
  • Male
  • Middle Aged
  • Myopia / physiopathology*
  • Proportional Hazards Models
  • Risk Factors

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human

Associated data

  • ClinicalTrials.gov/NCT00360815
  • ClinicalTrials.gov/NCT00360893