Date Published: March 23, 2017
Publisher: Public Library of Science
Author(s): Jin A. Choi, Hyo Won Kim, Jin-Woo Kwon, Yun-sub Shim, Dong Hyun Jee, Jae-Seung Yun, Yu-Bae Ahn, Chan Kee Park, Seung-Hyun Ko, Patrice E. Fort.
To investigate changes in the neural retina according to the presence of retinal nerve fiber layer (RNFL) defects in type 2 diabetes, and to determine the association between inner retina thickness and the severity of diabetic complications.
We studied non-glaucomatous patients with type 2 diabetes and control subjects Circumpapillary RNFL and macula ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured by spectral-domain optical coherence tomography. In patients with type 2 diabetes, a cardiovascular autonomic function test (AFT) was performed, which included the heart rate parameter of beat-beat variation—with deep breathing, in response to the Valsalva maneuver, and on postural change from lying to standing. The results of each test were scored as 0 for normal and 1 for abnormal. A total AFT score of 1 was defined as early cardiovascular autonomic neuropathy (CAN), and an AFT score≥ 2 as definite CAN.
We compared control eyes (n = 70), diabetic eyes with RNFL defects (n = 47), and eyes without RNFL defects (n = 30). The average RNFL and GCIPL thicknesses were significantly different among groups (all, P<0.05). On post-hoc testing, diabetic eyes with RNFL defects had a significantly thinner average GCIPL thickness than those without RNFL defects. On multivariate analyses, significantly thinner average GCIPL was seen in early CAN staging (B = -4.32, P = 0.016) and in definite CAN staging (B = -10.33, P<0.001), compared with no CAN involvement, after adjusting for confounding parameters. Cardiovascular autonomic dysfunction was associated with early neurodegenerative changes in type 2 diabetes.
It is widely recognized that the early neurodegenerative changes that characterize diabetes involve dysfunction and degeneration of retinal neurons even before the manifestation of vascular symptoms.[1, 2] High blood glucose induces apoptosis in retinal neural cells. Increased neurofilament phosphorylation, glial cell reactivity during metabolic stress,[5, 6] microglial activation, and altered glutamate regulation  are also involved in neurodegeneration in the diabetic retina. These early changes especially involve the inner retina, as shown by the reduction in thickness of the retinal nerve fiber layer (RNFL) and loss of ganglion cell bodies.
A total of 333 patients with diabetes underwent ophthalmic examinations between July 2014 and July 2015. Of these, 199 with glaucomatous optic discs or glaucomatous VF losses were excluded, and 14 were excluded because of ambiguous RNFL defects. Six eyes about which the two observers were in disagreement in terms of RNFL defect measurements were also excluded. Also, 37 eyes were excluded because AFT results were lacking. Finally, 77 patients with type 2 diabetes and 70 control subjects were included. The interobserver ICC (95% confidence interval) for the detection of photographic RNFL defects was 0.918 (0.874–0.947).
In the present study, diabetic patients with RNFL defects showed a lower macular GCIPL thickness compared with those without RNFL defects. The average macular GCIPL thickness was significantly decreased with the severity of CAN after adjusting for potential confounding factors. Collectively, our results suggest that diabetic cardiovascular autonomic neuropathy is associated with the early neurodegenerative changes of type 2 diabetes, as shown in representative case (Table 5; Fig 2).