Alterations of the blood-retinal barrier and retinal thickness in preclinical retinopathy in subjects with type 2 diabetes

Arch Ophthalmol. 2000 Oct;118(10):1364-9. doi: 10.1001/archopht.118.10.1364.


Objective: To identify alterations of the blood-retinal barrier by mapping retinal fluorescein leakage into the vitreous and changes in retinal thickness occurring in the macular region in preclinical diabetic retinopathy.

Methods: Ten eyes from 10 patients with type 2 diabetes and no lesions visible on fundus photography (level 10 of Wisconsin grading) were examined with the retinal leakage analyzer (RLA) (Confocal Scanning Laser Ophthalmoscope [modified]; Carl Zeiss Inc, Thornwood, NY) and the retinal thickness analyzer (RTA) (Talia Technology, Mevaseret Zion, Israel). The maps of retinal leakage and retinal thickness were aligned and integrated in the same image to correlate leakage with thickness. Data from the group of individuals with diabetes were compared with those of a healthy control population (N = 14; mean age, 48 years; range, 42-55 years) and used to establish reference maps for the RLA and RTA.

Results: Areas of abnormally increased fluorescein leakage were detected in 9 of 10 eyes examined. The increased leakage in 6 (67%) of 9 eyes reached values higher than 40% more than the mean +2 SD RLA control value. Areas of abnormally increased thickness were found in 7 of 10 eyes examined. For the most part, the increases in retinal thickness were not severe (ie, <15% increase in 5 eyes and an 18% increase in 1 eye). The eyes with the most extensive leakage (cases 1, 3, and 9) showed relatively good coincidence between the location of the areas of increased leakage and the location of the areas of increased thickness. In 4 eyes (cases 2, 5, 7, and 8), no such correlation was apparent. The 3 remaining eyes showed little coincidence between these locations. Characteristically, the latter 3 eyes had areas of abnormally increased thickness that were much larger than the areas of increased fluorescein leakage, which were relatively moderate or absent of any leakage.

Conclusions: Localized sites of increased fluorescein leakage and zones of increased retinal thickness were found in most eyes in a series of 10 eyes in the preretinopathy stage from 10 patients with type 2 diabetes. Increases in retinal thickness may be observed that do not coincide with sites of retinal leakage. Two types of increased retinal thickness may, therefore, be present in the preretinopathy stage of diabetic retinopathy, one directly associated with an alteration of the blood-retinal barrier, and another occurring without apparent breakdown of blood-retinal barrier.

MeSH terms

  • Adult
  • Blood-Retinal Barrier*
  • Capillary Leak Syndrome / diagnosis*
  • Capillary Leak Syndrome / metabolism
  • Capillary Permeability
  • Diabetes Mellitus, Type 2 / pathology*
  • Diabetic Retinopathy / diagnosis*
  • Diabetic Retinopathy / metabolism
  • Female
  • Fluorescein / metabolism
  • Fluorescein Angiography
  • Fundus Oculi
  • Humans
  • Male
  • Middle Aged
  • Ophthalmoscopy
  • Retina / metabolism
  • Retina / pathology*
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology*


  • Fluorescein