Diabetic macular edema (DME), which causes retinal thickening, is a main cause of visual impairment in patients with diabetes (1,2). The important pathophysiology of DME is the loss of retinal capillary pericytes, resulting in increased vascular permeability of the blood-retinal barrier (BRB) (3). However, there is only one report about the active transport of the BRB in patients with DME (4). The aim of this study was to evaluate the active transport of the BRB in patients with clinically significant diabetic macular edema (CSME) (5) in type 2 diabetes using differential vitreous fluorophotometry (DVF).

We studied six eyes of six patients with type 2 diabetes with CSME (age range 53–70 years, mean 63 years), five eyes of five patients with type 2 diabetes without CSME (age range 64–73 years, mean 69 years), and seven eyes of seven normal subjects (age range 58–66 years, mean 62 years). Informed consent was obtained from all subjects. All procedures adhered to the tenets of the Declaration of Helsinki. The eyes were diagnosed based on the findings of a best-corrected visual acuity, slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, and fluorescein angiography (5).

Fluorescein (F) and fluorescein monoglucuronide (FG) concentrations in the vitreous were determined using DVF modified Fluorotron Master (OcuMetrics, Mountain View, CA). The fluorescence readings were converted to F and FG concentrations using the methods of McLaren et al. (6). DVF was performed 120 min after intravenous injection of 14 mg/kg sodium fluorescein. The F/FG ratio, a good indicator of the estimated active transport of the BRB, was calculated based on the concentration of F and FG in the vitreous obtained by DVF (7). If the active transport of the BRB is low, the F/FG ratio increases. We compared the F/FG ratio in the three groups using one-way ANOVA and Scheffe’s test.

The F/FG ratio in the control subjects, the patients without CSME, and the patients with CSME were 0.42 ± 0.32 (0.13–0.95), 0.50 ± 0.34 (0.10–0.80), and 2.84 ± 1.20 (1.13–4.12), respectively. The F/FG ratio was markedly higher in the patients with CSME than in the control subjects (P = 0.0001) and in the patients without CSME (P = 0.0004).

This result indicates directly and clinically the active transport dysfunction of the BRB in the patients with CSME. We reported the abnormal inward permeability of the retina caused by BRB breakdown in patients without CSME with diabetes using vitreous fluorophotometry (8). However, in the present study, the active transport of the BRB was normal in the patients without CSME. Dysfunctional active transport of the BRB may not be found until DME develops. The abnormality of the active transport of the BRB may be a pathogenic mechanism of DME. The pharmacologic normalization of the active transport of the BRB may be the future treatment of DME.

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Address correspondence to Fumihiko Mori, MD, PhD, Department of Ophthalmology, Asahikawa Medical College, Midorigaoka Higashi 2-1-1-1, Asahikawa 078-8510, Japan. E-mail: [email protected].

This study was supported by Grant-in-Aid for Encouragement of Young Scientists 13771007 (to F.M) and Scientific Research (C) 14571652 (to A.Y.).

The authors thank Dr. Bruce Ishimoto for assistance on the Fluorotron Master.

DIABETES CARE
2002