Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus.
Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.
Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242; michael-abramoff@uiowa.edu.
Elliott H
EH
Sohn
Department of Ophthalmology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; michael-abramoff@uiowa.edu.
Hille W
HW
van Dijk
Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242;
Chunhua
C
Jiao
Department of Ophthalmology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
Pauline H B
PH
Kok
Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242;
Woojin
W
Jeong
Department of Ophthalmology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
Nazli
N
Demirkaya
Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242;
Allison
A
Garmager
Department of Global Health, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
Ferdinand
F
Wit
Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242;
Murat
M
Kucukevcilioglu
Oogziekenhuis Rotterdam, 3011 BH Rotterdam, The Netherlands;
Mirjam E J
ME
van Velthoven
Department of Endocrinology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
J Hans
JH
DeVries
Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242;
Robert F
RF
Mullins
Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242;
Markus H
MH
Kuehn
Department of Ophthalmology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
Reinier Otto
RO
Schlingemann
Iowa Institute for Biomedical Imaging, University of Iowa, Iowa City, IA 52242; Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA 52242;
Milan
M
Sonka
Department of Ophthalmology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
Frank D
FD
Verbraak
Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa, Iowa City, IA 52242; Iowa Institute for Biomedical Imaging, University of Iowa, Iowa City, IA 52242; Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA 52242; Iowa City VA Health Care System, Iowa City, IA 52246; Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242 michael-abramoff@uiowa.edu.
Michael David
MD
Abràmoff
D000328:Adult; D000818:Animals; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000473:pathology* / Q000503:physiopathology*; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology; D012162:Retinal Degeneration / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology; D013045:Species Specificity
diabetes; diabetic retinopathy; neurodegeneration; optical coherence tomography; retina