Pupillary responses to single and sinusoidal light stimuli in diabetic patients

Abstract

We examined effects of diabetes mellitus (DM) on the pupillary light reflex (PLR). Phasic pupillary response to a single light stimulus (200 ms) (pPLR) and to continuous sinusoidal stimuli with four different frequencies (0.1, 0.3, 0.7, 1.3Hz) (cPLR) were examined in 52 DM patients and 21 control subjects. We asked: does recording and frequency analysis of cPLR together with short time fourier [STFT] analysis of pPLR differentiate better between DM patients and normal subjects than pPLR only?Initial pupil diameter was significantly decreased in the DM group. For pPLR. maximal contraction velocity (Vmax), Vmax of redilation 1, reflex-amplitude and pPLR latency were significantly reduced in those patients who also showed signs of diabetic autonomic neuropathy (DNP). Tests of dynamic pupillary light reflex (cPLR) revealed that all DM patients had a significantly reduced gain at lower frequencies. Pupil phase lag was greater at 0.1 and 0.3Hz and smaller at 0.7 and 1.3 Hz in the DNP group (p<0.001). Comparison of single pPLR recordings of 5 DNP patients with 5 subjects using short time fast fourier (STFT) analysis revealed a characteristic change from low frequency content in healthy subjects to high frequency content in DNP patients.Significant changes in the PLR in DM can be found only when symptoms of autonomic neuropathy have been shown. Both sympathetic and the parasympathetic nervous systems are affected by diabetic autonomic neuropathy. Only recording of cPLR, together with STFT of pPLR can identify significant pathological deficits of pupillary control in single cases.

Keywords: autonomic neuropathy; diabetes mellitus; infrared reflex pupillography; neuroophthalmology; pupil; short time FFT analysis.; sinusoidal light stimuli to the pupil.

Figure 1

Example printout of pPLR time and dynamic variables and pPLR original.

Figure 2

Pupil size as function of age in normal subjects and DM patients. Note the smaller size in DM patients in spite of large variance. Continuous line: linear fit to normal results; dashed line: linear fit to data of DM patients. The fraction of meiosis with the initial pupil diameter that was due to the age of the patient would be accounted for by the addition of 0.04 mm per year to the recorded initial pupil diameter. This reflects the average decrease of pupil diameter per year of life; so we used an age corrected initial pupil diameter (ACPD). It is important to note that because of the age factor leading to smaller pupils over 60 years of age the discrimination between diabetics and normal subjects by pupil size becomes less evident, but is still significant with p<0.02.

Figure 3

pPLR single response from the left eye of a diabetic patient with signs of DNP (left) compared to a normal subject (right), using short time fourier transformation (STFT) as function of time plot. A significantly larger amount of high frequency content during both pPLR phases, contraction and dilation, is shown.

Figure 4

Single case example of a 59-year old male diabetic patient with autonomous polyneuropathy, who had suffered from a left dorso-paramedian ponto-mesencephalic lacunar stroke. (A) cMRT. (B) Values of his most important pupil recording parameters.

Figure 5

Phase lag and equivalent latency of pupil responses to sinusoidal light stimuli are reduced by increased mean light level. Left: phase lag data. Middle: corresponding equivalent latencies computed from phase lag by subtracting the minimum phase component then dividing by angular frequency in °/sec; subj. JCA. Right: latency of pPLR as function of response size. Note that in the light-pupil responses the response size increases with increasing stimulus size. Results are for subject GM, 20 responses per class. (Modified from Myers et al.