Pupil Signs of Sympathetic Autonomic Neuropathy in Patients With Type 1 Diabetes
- 1Department of Endocrinology and Metabolism, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany
- 2Department of Ophthalmology, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany
OBJECTIVE—Pupillary autonomic neuropathy is considered an early sign of the development of systemic autonomic neuropathy. Sympathetic denervation is related to the duration of diabetes and the development of systemic autonomic dysfunction. We investigated pupil responsiveness to directly and indirectly acting sympathomimetics in type 1 diabetic patients with and without long-term complications, defined as cardiac autonomic neuropathy (CAN), peripheral sensomotor neuropathy, retinopathy, and nephropathy, and in healthy subjects.
RESEARCH DESIGN AND METHODS—A total of 47 randomly chosen type 1 diabetic patients and 20 healthy subjects were selected for this study. Patients were divided into groups determined by whether they had long-term diabetic complications. Pharmacological tests were performed with cocaine 4%, epinephrine 1%, and pholedrine 5% eye drops. Horizontal pupil diameter (HPD) was measured at the beginning of the pharmacological tests and at defined time points after instillation of the eye drops.
RESULTS—Statistical analysis showed a significantly smaller HPD in the patients before instillating eye drops (P = 0.011). In particular, the HPD was significantly smaller in the patient group without CAN when compared with healthy subjects (P = 0.004). Maximal cocaine reaction was diminished in the complication group (P < 0.001). Epinephrine test, visual acuity, ocular pressure, and HbA1c did not differ in patients with or without long-term complications. The noncomplication group showed no significant differences in pupillary responses as compared with healthy subjects. The complication group showed a smaller HPD (P = 0.022), reduced pupillary responses in the cocaine (P = 0.037) and pholedrine tests (P < 0.001), and anisocor pupil sizes after instillation of the eye drops (P = 0.034).
CONCLUSIONS—Our results clearly show that sympathetic denervation does exist in the pupil of diabetic patients and that it can be rapidly assessed using the cocaine test. These data and the results of the epinephrine test suggest a mixed pre- and postganglionic dysfunction of the sympathetic plexus. The significant smaller HPD in patients without CAN compared with that of healthy subjects could be a sign for early involvement of the pupil function before cardiac manifestation of systemic autonomic diabetic neuropathy.
- CAN, cardiac autonomic neuropathy
- DCCT, Diabetes Control and Complications Trial
- HPD, horizontal pupil diameter
- MCR, maximum cocaine reaction
- MPR, maximum pholedrine reaction
- ROC, receiver-operating characteristic
- rHPD, reduced horizontal pupil diameter
- rMCR, reduced maximum cocaine reaction
- rMPR, reduced maximum pholedrine reaction
Address correspondence and reprint requests to Hendrik Lehnert, Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Zentrum für Innere Medizin, Klinik für Endokrinologie und Stoffwechselkrankheiten, Leipziger Str. 44, 39120 Magdeburg, Germany. E-mail:.
Received for publication 25 July 2001 and accepted in revised form 31 May 2002.
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