title: Three-year follow-up study of blood-retinal barrier and retinal thickness alterations in patients with type 2 diabetes mellitus and mild nonproliferative diabetic retinopathy.
abstract: OBJECTIVE
  To examine the 3-year alterations of the blood-retinal barrier and changes in retinal thickness occurring in the macular region in 14 eyes of 14 patients with type 2 diabetes mellitus (DM) and mild nonproliferative diabetic retinopathy.
  
  
  METHODS
  We classified 14 eyes of 14 patients with type 2 DM and mild nonproliferative diabetic retinopathy, as having disease levels 20 (microaneurysms only) or 35 (microaneurysm plus retinal hemorrhage[s] and/or hard exudates) of Wisconsin Card-Sorting Test grading, by using 7-field stereoscopic fundus photographs. We examined them 7 times at 6-month intervals, using fundus photography, fluorescein sodium angiography, the retinal leakage analyzer (RLA)-modified confocal scanning laser ophthalmoscope, and the retinal thickness analyzer. The retinal leakage and retinal thickness maps were aligned and integrated into 1 image. Data from the group of individuals with type 2 DM were compared with those of a healthy control population (n = 14; mean age, 48 years; age range, 42-55 years) to establish reference maps for the RLA and retinal thickness analyzers.
  
  
  RESULTS
  Areas of abnormally increased fluorescein leakage were detected in all eyes examined at baseline. The sites of increased fluorescein leakage reached values as high as 483% above normal levels, but in 20 of the total 95 examinations performed, fluorescein leakage returned to normal levels. Every eye that showed reversal to normal levels of fluorescein leakage showed stabilization or a decrease in glycosylated hemoglobin A(1c) values at the same visit. When comparing the RLA-leaking sites among the 7 examinations, they remained, in general, in the same locations, but there was a clear fluctuation in the percentage of increases. No clear correlation was observed among the location of areas of increased retinal thickness and RLA-leaking sites, the number of microaneurysms, or the glycosylated hemoglobin A(1c) values. Microaneurysms on fundus photographs showed different cumulative incidences throughout the follow-up period in the different eyes. Associations between these different abnormalities suggest specific patterns of evolution of type 2 DM-related retinal disease.
  
  
  CONCLUSIONS
  The dominant alteration in the retina of patients with type 2 DM and mild nonproliferative retinopathy is the presence of RLA-leaking sites. This damage seems to be reversible and directly associated with variations in glycemic metabolic control. Together with the intensity and persistence of RLA-leaking sites, the rates of microaneurysm accumulation and alterations of the foveal avascular zone may characterize different genetically based phenotypes of diabetic retinopathy.
authors.affiliation: Centre of Ophthalmology, University Hospital and Institute of Biomedical Research on Light and Image, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. clobo@aibili.pt
authors.forename: Conceição L
authors.initials: CL
authors.lastname: Lobo
authors.forename: Rui C
authors.initials: RC
authors.lastname: Bernardes
authors.forename: João P
authors.initials: JP
authors.lastname: Figueira
authors.forename: José R Faria
authors.initials: JR
authors.lastname: de Abreu
authors.forename: José G
authors.initials: JG
authors.lastname: Cunha-Vaz
mesh_terms: D000328:Adult; D000368:Aged; D001813:Blood-Retinal Barrier; D002199:Capillary Permeability; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005451:Fluorescein Angiography; D015590:Fluorophotometry; D005500:Follow-Up Studies; D006801:Humans; D007834:Lasers; D008297:Male; D008875:Middle Aged; D009887:Ophthalmoscopy / Q000379:methods; D010781:Photography; D012160:Retina / Q000473:pathology*; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology