title: Retinal microaneurysm count predicts progression and regression of diabetic retinopathy. Post-hoc results from the DIRECT Programme.
abstract: OBJECTIVE
  To study the association between baseline retinal microaneurysm score and progression and regression of diabetic retinopathy, and response to treatment with candesartan in people with diabetes.
  
  
  METHODS
  This was a multicenter randomized clinical trial. The progression analysis included 893 patients with Type 1 diabetes and 526 patients with Type 2 diabetes with retinal microaneurysms only at baseline. For regression, 438 with Type 1 and 216 with Type 2 diabetes qualified. Microaneurysms were scored from yearly retinal photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Retinopathy progression and regression was defined as two or more step change on the ETDRS scale from baseline. Patients were normoalbuminuric, and normotensive with Type 1 and Type 2 diabetes or treated hypertensive with Type 2 diabetes. They were randomized to treatment with candesartan 32 mg daily or placebo and followed for 4.6 years.
  
  
  RESULTS
  A higher microaneurysm score at baseline predicted an increased risk of retinopathy progression (HR per microaneurysm score 1.08, P < 0.0001 in Type 1 diabetes; HR 1.07, P = 0.0174 in Type 2 diabetes) and reduced the likelihood of regression (HR 0.79, P < 0.0001 in Type 1 diabetes; HR 0.85, P = 0.0009 in Type 2 diabetes), all adjusted for baseline variables and treatment. Candesartan reduced the risk of microaneurysm score progression.
  
  
  CONCLUSIONS
  Microaneurysm counts are important prognostic indicators for worsening of retinopathy, thus microaneurysms are not benign. Treatment with renin-angiotensin system inhibitors is effective in the early stages and may improve mild diabetic retinopathy. Microaneurysm scores may be useful surrogate endpoints in clinical trials.
authors.affiliation: Department of Ophthalmology, Odense University Hospital, Odense, Denmark. a.k.sjoelie@ouh.regionsyddanmark.dk
authors.forename: A K
authors.initials: AK
authors.lastname: Sjølie
authors.forename: R
authors.initials: R
authors.lastname: Klein
authors.forename: M
authors.initials: M
authors.lastname: Porta
authors.forename: T
authors.initials: T
authors.lastname: Orchard
authors.forename: J
authors.initials: J
authors.lastname: Fuller
authors.forename: H H
authors.initials: HH
authors.lastname: Parving
authors.forename: R
authors.initials: R
authors.lastname: Bilous
authors.forename: S
authors.initials: S
authors.lastname: Aldington
authors.forename: N
authors.initials: N
authors.lastname: Chaturvedi
mesh_terms: D000328:Adult; D000783:Aneurysm / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012043:Regression, Psychology; D012074:Remission Induction; D012164:Retinal Diseases / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D013777:Tetrazoles / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007004:Hypoglycemic Agents; D013777:Tetrazoles; C081643:candesartan