Blood-retinal barrier glycerol permeability in diabetic macular edema and healthy eyes: estimations from macular volume changes after peroral glycerol.
OBJECTIVE
To compare the changes in macular volume (MV) between healthy subjects and patients with diabetic macular edema (DME) after an osmotic load and to determine the glycerol permeability (P(gly)) of the blood-retinal barrier (BRB).


METHODS
In this unmasked study, 13 patients with DME and 5 healthy control subjects ingested a glycerol solution (0.57 g/mL) of 3 mL/kg body weight (maximum, 250 mL). Subsequently, the MV determined by the retinal maps provided by the optical coherence tomography (OCT) fast macular thickness protocol was monitored at 12 time points for 180 minutes. A mathematical model of glycerol and osmotic water movements across the BRB was constructed to estimate P(gly).


RESULTS
Median MV decreased from 7.30 mm(3) (range, 6.68-7.35) to the maximum median DeltaMV of -0.30 mm(3) (25%-75% quartile: -0.34 to -0.25) in the healthy volunteers and from 7.97 mm(3) (range, 6.85-9.89) to DeltaMV of -0.14 mm(3) (25%-75% quartile: -0.19 to -0.08) in the diabetic group (intergroup difference: P < 0.05). P(gly) was 6.1 x 10(-6) (SE 1.8 x 10(-6)) and 74 x 10(-6) (SE 42 x 10(-6)) cm/s in the healthy and diabetic participants, respectively (P < 0.0001). No rebound phenomenon was observed in either group.


CONCLUSIONS
The maximum reduction in MV was doubled in the healthy group compared with the diabetic group, whereas the glycerol permeability was 12 times higher in the diabetic participants. These findings confirm the paradigm of BRB breakdown in DME, but also suggest a novel procedure for the determination of retinal permeability to various agents, which is independent of the vitreous condition (ClinicalTrials.gov number, NCT00333671).
Thornit
Dorte Nellemann
DN
Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark. dornel@dadlnet.dk
Vinten
Carl Martin
CM
Sander
Birgit
B
Lund-Andersen
Henrik
H
la Cour
Morten
M
D000368:Aged; D001692:Biological Transport; D001794:Blood Pressure / Q000502:physiology; D001813:Blood-Retinal Barrier / Q000502:physiology*; D001834:Body Water / Q000378:metabolism; D002199:Capillary Permeability; D003404:Creatinine / Q000097:blood; D003930:Diabetic Retinopathy / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D005990:Glycerol / Q000378:metabolism*; D006801:Humans; D008269:Macular Edema / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009994:Osmolar Concentration; D011446:Prospective Studies; D012160:Retina / Q000378:metabolism*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
D003404:Creatinine; D006442:Glycated Hemoglobin; D005990:Glycerol; C517652:hemoglobin A1c protein, human