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M. A. Bearse, Jr., W. W. Harrison, S. Barez, M. E. Schneck, A. J. Adams; The Nature of Local Retinal Response Delays in Diabetes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5017.
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The P1 implicit time (IT) of the multifocal electroretinogram (mfERG) is increased in diabetes and predictive of local nonproliferative diabetic retinopathy (NPDR) development (e.g. Han et al., 2004). This study examines the nature of these delays and whether they are fixed in duration or can be modified by the local adaptive state of the retina.
MfERGs were recorded from the central 45 deg of the retina using 103, 200 cd/sq.m stimulus elements. We tested 17 diabetic patients without retinopathy (NoR group), 15 patients with mild/moderate NPDR (NPDR group), and 25 healthy control subjects. Nine retinal regions were examined: the central 7.5 deg; 4 areas between 3.25-10.5 deg eccentricity; and 4 areas between 10.5-22.5 deg. Within each region, the mfERG kernel series was used to synthesize isolated flash responses evoked under 4 adaptation conditions: (1) no flashes in the 40 ms preceding the stimulus; (2) a flash 40 ms before the stimulus; (3) a flash 26.7 ms before; and (4) a flash 13.3 ms before. The response evoked by the preceding (adapting) flash was removed. To characterize these isolated adapted responses, P1 IT and N1-P1 amplitude (AMP) were measured. P1 IT and AMP changes relative to the "no preceding flash" condition (condition 1) were also calculated. Measurements were converted to Z-scores based on the control data to allow comparisons among retinal regions. Z-scores >= +/- 2 were considered abnormal.
The main effect of light adaptation (proximity of a preceding flash) on the isolated responses was a decrease in P1 IT, with very little effect on AMP. The P1 ITs were longer in both the NoR and NPDR groups under all 4 adaptation conditions compared to controls (P<0.006), with the greatest frequencies of abnormality (29-33%) occurring at higher light adaptation levels (conditions 3 and 4). Comparing the NoR and NPDR groups, mean P1 IT differed under condition 3 (P<0.004), indicating a shorter duration of the adaptation effect in the NPDR group. Compared to controls, decrease in P1 IT relative to condition 1 was less in the NPDR group for conditions 3 and 4 (P<0.006) and less in the NoR group for condition 4 (P=0.006). P1 IT decrease was less in the NPDR group compared to the NoR group in condition 3 (P<0.004).
The mfERG implicit time delays observed in diabetes do not decrease normally with light adaptation, and this abnormality is worsened when NPDR is present. This suggests that the response delays represent a form of retinal neuropathy that occurs before, and increases in severity with the appearance of, early clinical signs of NPDR.
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