Early worsening of diabetic retinopathy after rapid improvement of blood glucose control in patients with diabetes

Diabetes Metab. 2018 Feb;44(1):4-14. doi: 10.1016/j.diabet.2017.10.014. Epub 2017 Nov 11.


Aim: To review the frequency, importance of and risk factors for "early worsening of diabetic retinopathy" (EWDR) after rapid improvement of blood glucose in patients with diabetes.

Methods: This was a systematic review of key references (PubMed 1980-2016) and the current international recommendations for the above-mentioned topics.

Results: EWDR has been described during intensive treatment (IT) in patients with uncontrolled type 1 or 2 diabetes, and after pancreas transplantation or bariatric surgery. EWDR arises in 10-20% of patients within 3-6 months after abrupt improvement of glucose control, and in nearly two times that proportion in patients with advanced baseline diabetic retinopathy (DR). While EWDR is often transient and predominantly driven by the development of cotton-wool spots and intraretinal microvascular abnormalities in patients with no or minimal DR, it can lead to irreversible retinal damage in patients with advanced DR before IT. Its identified risk factors include higher baseline levels and larger magnitudes of reduction of HbA1c, longer diabetes durations and previous severity of DR.

Conclusion: Intensive diabetes treatment inducing a rapid fall in glucose should prompt vigilance and caution, particularly in patients with long-term and uncontrolled diabetes and DR prior to IT. Careful retinal examination should be performed in all patients before initiating IT; however, in patients with severe non-proliferative or proliferative DR, panretinal photocoagulation therapy should be performed promptly. During the year following IT, quarterly eye monitoring is required in patients at high risk of EWDR (long-term uncontrolled diabetes, previous advanced DR), whereas follow-up every 6 months can be applied in patients with short-term diabetes and no/minimal DR before IT. To date, there is no evidence that controlling the speed or magnitude of HbA1c decreases will reduce the risk of EWDR in patients with diabetes.

Keywords: Bariatric surgery; Early worsening of diabetes retinopathy; Insulin intensive treatment; Pancreas transplantation.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Angiogenesis Inducing Agents / metabolism
  • Bariatric Surgery
  • Blood Glucose / physiology*
  • Diabetic Retinopathy* / drug therapy
  • Diabetic Retinopathy* / epidemiology
  • Diabetic Retinopathy* / physiopathology
  • Disease Progression
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage
  • Insulin / therapeutic use
  • Male
  • Pancreas Transplantation
  • Risk Factors
  • Vascular Endothelial Growth Factor A / metabolism


  • Angiogenesis Inducing Agents
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A