Early neural and vascular changes in the adolescent type 1 and type 2 diabetic retina

Abstract

Purpose: This cross-sectional study examines the existence and frequency of functional and structural abnormalities in the adolescent Type 1 diabetic retina. We also compare the results with those of adolescents with Type 2 diabetes.

Methods: Thirty-two adolescents with Type 1 diabetes (5.7 ± 3.6 years; mean duration ± SD), 15 with Type 2 diabetes (2.1 ± 1.3 years), and 26 age-matched control subjects were examined. Multifocal electroretinogram responses from 103 retinal regions were recorded. Optical coherence tomography was used to measure retinal thickness. Vascular diameter around the optic nerve was also assessed.

Results: Nine of the 32 (28%) adolescents with Type 1 diabetes and 6 of the 15 (40%) with Type 2 diabetes had significant multifocal electroretinogram implicit time delays compared with 2 of the 26 controls (8%). Retinal thicknesses in both patient groups were significantly (P ≤ 0.01) thinner than controls. The Type 2 group also showed significant (P ≤ 0.03) retinal venular dilation (235.8 ± 5.9 μm) compared with controls (219.6 ± 4.0 μm).

Conclusion: The present study illustrates that subtle but significant functional and structural changes occur very early in Type 1 diabetes. Adolescents with Type 2 diabetes appear to be more affected than those with Type 1 diabetes. Further longitudinal examination of the etiology and progression of these abnormalities is warranted.

Figure 1

Retinal Vessel Analysis and Multifocal Electroretinogram (mfERG). (A) Retinal blood vessels within outer annulus (½ to 1 disc diameter around the optic nerve) were analyzed with IVAN (University of Wisconsin-Madison, WI), an automated but supervised program. (B) Five field fundus mosaic depicting the retinal regions measured with the 103 mfERG stimulus pattern (yellow). Black 12 radial scans underlying the retinal thickness map. Black dots indicate the 9 samples used for retinal nerve fiber analysis. (C) Amplitude is the voltage difference between the N1 trough and P1 peak; implicit time is measured from the onset of the local flash to the P1 peak. (D) Example waveforms obtained from a normal control subject (white trace) and a subject with diabetes (yellow trace).

Figure 2

Response Z-score Distributions for Average Eyes. Box plots represent the 5^th, 25^th, 50^th, 75^th and 95^th percentiles. Control distributions for each measure are centered on a Z-score of zero. (Implicit Time) The implicit time distributions of the type 1 and type 2 groups were all significantly delayed compared to the control distribution (Tukey WSD). (Amplitude) The amplitude distribution of the type 2 group differed significantly from both the type 1 and controls (Tukey WSD). (Retinal Thickness) The retinal thickness distributions of both the type 1 and type 2 groups were significantly thinner than the control group (Tukey WSD). The (*) indicates a significant difference from controls.

Figure 3

Retinal distributions of abnormalities. Percentages of subjects with a response or measurement equal to or beyond ±2.0 Z-scores at each retinal location are coded gray to black from <5% to >25%. A. Frequency of implicit time abnormalities at each retinal location. B. Frequency of amplitude abnormalities at each retinal location. C. Frequency of abnormal retinal thickness at each retinal location.

Figure 4

Frequency of Abnormality. (Implicit Time) Percentage of subjects with an eye with 6 or more abnormally delayed Implicit Time response Z-scores (p < 0.03). (Amplitude) Percentage of subjects with an eye with 6 or more abnormal smaller Amplitude response Z-scores. (Retinal Thickness) Percentage of subjects with an eye with 3 or more abnormal thin Retinal Thickness Z-scores. The (*) indicates a significant difference from controls.

Figure 5

Significant Associations in Adolescents with Diabetes. (A) An association between HbA1c and mean implicit time in the type 1 group suggesting that as HbA1c increased there was a significant increase in implicit time (y = 0.13x + 26.21, R² = 0.17, P < 0.01). To make the relationship between HbA1c and implicit time visible, the range of the Y-axis is limited to 25-30 ms. (B) Retinal Thickness and Amplitude (C) An association between type 2 diabetes duration and mfERG amplitude suggesting that as duration increases mfERG increases (y = 24.85x + 168.05, R² = 0.41, P = 0.01).