Pupillography refines the diagnosis of diabetic autonomic neuropathy

https://doi.org/10.1016/j.jns.2004.04.008Get rights and content

Abstract

Although diabetic autonomic neuropathy involves most organs, diagnosis is largely based on cardiovascular tests. Light reflex pupillography (LRP) non-invasively evaluates pupillary autonomic function.

We tested whether LRP demonstrates autonomic pupillary dysfunction in diabetics independently from cardiac autonomic neuropathy (CAN) or peripheral neuropathy (PN).

In 36 type-II diabetics (39–84 years) and 36 controls (35–78 years), we performed LRP. We determined diameter (PD), early and late re-dilation velocities (DV) as sympathetic parameters and reflex amplitude (RA) and constriction velocity (CV) as parasympathetic pupillary indices. We assessed the frequency of CAN using heart rate variability tests and evaluated the frequency of PN using neurological examination, nerve conduction studies, thermal and vibratory threshold determination.

Twenty-eight (77.8%) patients had abnormal pupillography results, but only 20 patients (56%) had signs of PN or CAN. In nine patients with PN, only pupillography identified autonomic neuropathy. Four patients had pupillary dysfunction but no CAN or PN.

In comparison to controls, patients had reduced PD, late DV, RA and CV indicating sympathetic and parasympathetic dysfunction. The incidence and severity of pupillary abnormalities did not differ between patients with and without CAN or PN.

LRP demonstrates sympathetic and parasympathetic pupillary dysfunction independently from PN or CAN and thus refines the diagnosis of autonomic neuropathy in type-II diabetics.

Introduction

Autonomic neuropathy is one of the most disabling complications of diabetes mellitus with symptoms such as diarrhea or constipation, hypohidrosis or excessive gustatory sweating, erectile dysfunction or orthostatic hypotension [1], [2]. Several epidemologic studies demonstrate increased mortality rates in diabetic patients with autonomic neuropathy even if patients are still clinically asymptomatic [3], [4], [5], [6]. Early diagnosis of autonomic dysfunction in still asymptomatic patients and initiation of a more intense treatment might thus contribute to preventing a progression towards overt autonomic failure [1], [2], [7], [8]. Clinical diagnosis of autonomic dysfunction is largely based on the assessment of cardiac autonomic neuropathy by means of evaluation of heart rate variability (HRV) in response to challenge maneuvers such as metronomic breathing, Valsalva maneuver or active standing up [1], [2], [7], [8]. These tests primarily evaluate parasympathetic autonomic function [1], [9], [10], [11], [12], [13]. The additional evaluation of autonomic function of other organs might be relevant to identify autonomic dysfunction already in early stages of the disease.

The modulation of the pupillary diameter is known to be reduced in advanced stages of diabetes mellitus [14], [15]. Changes of the pupillary diameter, e.g. in response to light stimulation, are controlled by the sympathetic as well as the parasympathetic nervous system [14], [16], [17], [18], [19], [20], [21], [22], [23]. Several studies showed associations between abnormal autonomic control of the pupils and the prevalence of peripheral [14], [24] or cardiac autonomic neuropathy [15] in advanced stages of diabetes mellitus. However, the prevalence and severity of sympathetic versus parasympathetic dysfunction might be different at the eye and the heart. Diabetic neuropathy is a length-dependent dying-back neuropathy. The longer parasympathetic fibers innervating the heart are affected at earlier stages than the cardiac sympathetic fibers [1], [9], [10], [11], [12], [13] while sympathetic pupillary dysfunction might be more pronounced than parasympathetic pupillary dysfunction due to greater length of sympathetic than parasympathetic fibers innervating the eye [25]. Moreover, the vulnerability of the cardiac and pupillary autonomic nerve fibers might be different in diabetes mellitus.

So far, it has not been studied whether the prevalence of pupillary autonomic dysfunction differs from that of cardiac autonomic neuropathy or peripheral somatic neuropathy.

To evaluate whether the assessment of pupillary function refines the early diagnosis of diabetic autonomic neuropathy, we studied pupillary light reflex responses in diabetic patients and compared results to the evaluation of cardiac autonomic and peripheral somatic neuropathy.

Section snippets

Patients

Thirty-six type-II diabetic patients (16 female, 20 male, 39–84 years old [mean age: 57.3±23.5] with mean HbA1c values of 7.45±2.01 mg% and a disease duration ranging between 0.5 and 30 years [mean duration: 18.5±15.8]) and 36 healthy controls (16 female, 20 male, 34–78 years old [mean age: 55.1±19.7]) participated in the study. Informed consent was obtained according to the declaration of Helsinki. Patients with evidence of renal insufficiency, as defined by a serum creatinine of more than 2.2

Results

Fig. 2 demonstrates the number of patients with abnormal results of pupillary light reflexes alone and in combination with test results of cardiovascular autonomic function and/or peripheral nerve function. Overall, light reflex pupillography showed abnormal results in 28 of our 36 patients (77.8%). Seven of the 36 patients (19.4%) showed abnormal results with the tests of cardiac autonomic and/or peripheral neuropathy. Only 1 of the 36 patients (2.8%) had normal results with all of the three

Discussion

Our results demonstrate that impairment of light reflex responses occurs independently from peripheral diabetic neuropathy or from cardiovascular autonomic neuropathy. The prevalence of pupillary autonomic dysfunction was similar in patients with and those without signs of cardiac autonomic or peripheral neuropathy. Moreover, there is no correlation between parameters of cardiovascular and pupillary testing. More than 11% of our patients (4/36) had abnormal pupillary autonomic function but no

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