Pop-Busui R, 2012. What do we know and we do not know about cardiovascular autonomic neuropathy in diabetes. J Cardiovasc Transl Res 5: 463–478.
Rassi A Jr, Rassi SG, Rassi A, 2001. Sudden death in Chagas' disease. Arq Bras Cardiol 76: 75–96.
Malik M, 1998. Clinical Guide to Cardiac Autonomic Tests. Dordrecht, The Netherlands: Kluwer Academic Publishers.
Ewing DJ, Campbell IW, Clarke BF, 1980. The natural history of diabetic autonomic neuropathy. Q J Med 49: 95–108.
Kowalewski MA, Urban M, 2004. Short- and long-term reproducibility of autonomic measures in supine and standing positions. Clin Sci (Lond) 106: 61–66.
Chavan NR, Dhundasi SA, Das KK, 2009. Determination of sensitivity among various cardiovascular autonomic function tests in diabetic patients of Bijapur. J Basic Clin Physiol Pharmacol 20: 187–196.
Ribeiro AL, Moraes RS, Ribeiro JP, Ferlin EL, Torres RM, Oliveira E, Rocha MO, 2001. Parasympathetic dysautonomia precedes left ventricular systolic dysfunction in Chagas disease. Am Heart J 141: 260–265.
Bowman NM, Kawai V, Gilman RH, Bocangel C, Galdos-Cardenas G, Cabrera L, Levy MZ, Cornejo del Carpio JG, Delgado F, Rosenthal L, Pinedo-Cancino VV, Steurer F, Seitz AE, Maguire JH, Bern C, 2011. Autonomic dysfunction and risk factors associated with Trypanosoma cruzi infection among children in Arequipa, Peru. Am J Trop Med Hyg 84: 85–90.
Vinik AI, Maser RE, Mitchell BD, Freeman R, 2003. Diabetic autonomic neuropathy. Diabetes Care 26: 1553–1579.
Pop-Busui R, Evans GW, Gerstein HC, Fonseca V, Fleg JL, Hoogwerf BJ, Genuth S, Grimm RH, Corson MA, Prineas R, 2010. Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care 33: 1578–1584.
Dutsch M, Marthol H, Michelson G, Neundorfer B, Hilz MJ, 2004. Pupillography refines the diagnosis of diabetic autonomic neuropathy. J Neurol Sci 222: 75–81.
Wilhelm H, Wilhelm B, 2003. Clinical applications of pupillography. J Neuroophthalmol 23: 42–49.
Pilley SF, Thompson HS, 1975. Pupillary “dilatation lag” in Horner's syndrome. Br J Ophthalmol 59: 731–735.
Cahill M, Eustace P, de Jesus V, 2001. Pupillary autonomic denervation with increasing duration of diabetes mellitus. Br J Ophthalmol 85: 1225–1230.
Ferrari GL, Marques JL, Gandhi RA, Heller SR, Schneider FK, Tesfaye S, Gamba HR, 2010. Using dynamic pupillometry as a simple screening tool to detect autonomic neuropathy in patients with diabetes: a pilot study. Biomed Eng Online 9: 26.
American Diabetes Association, 2013. Executive summary: standards of medical care in diabetes–2013. Diabetes Care 36 (Suppl 1): S4–S10.
Villar JC, Leon H, Morillo CA, 2004. Cardiovascular autonomic function testing in asymptomatic T. cruzi carriers: a sensitive method to identify subclinical Chagas' disease. Int J Cardiol 93: 189–195.
Oliveira E, Ribeiro AL, Assis Silva F, Torres RM, Rocha MO, 2002. The Valsalva maneuver in Chagas disease patients without cardiopathy. Int J Cardiol 82: 49–54.
Aminoff M, 2008. Neurology and General Medicine. Philadelphia, PA: Churchill Livingstone.
Moore ST, Haslwanter T, Curthoys IS, Smith ST, 1996. A geometric basis for measurement of three-dimensional eye position using image processing. Vision Res 36: 445–459.
MacDougall HG, Moore ST, 2005. Functional assessment of head-eye coordination during vehicle operation. Optom Vis Sci 82: 706–715.
Zhu D, Moore ST, Raphan T, 1999. Robust pupil center detection using a curvature algorithm. Comput Methods Programs Biomed 59: 145–157.
Mukherjee S, Vernino S, 2007. Dysfunction of the pupillary light reflex in experimental autoimmune autonomic ganglionopathy. Auton Neurosci 137: 19–26.
Hayes AF, Cai L, 2007. Using heteroskedasticity-consistent standard error estimators in OLS regression: an introduction and software implementation. Behav Res Methods 39: 709–722.
Moons KG, Harrell FE, Steyerberg EW, 2002. Should scoring rules be based on odds ratios or regression coefficients? J Clin Epidemiol 55: 1054–1055.
Harrell FE Jr, Lee KL, Mark DB, 1996. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 15: 361–387.
Marin-Neto JA, Cunha-Neto E, Maciel BC, Simoes MV, 2007. Pathogenesis of chronic Chagas heart disease. Circulation 115: 1109–1123.
Koeberle F, 1959. Cardiopathia parasympathicopriva. Munch Med Wochenschr 101: 1308–1310.
Bonney KM, Engman DM, 2015. Autoimmune pathogenesis of Chagas heart disease: looking back, looking ahead. Am J Pathol 185: 1537–1547.
Machado FS, Tyler KM, Brant F, Esper L, Teixeira MM, Tanowitz HB, 2012. Pathogenesis of Chagas disease: time to move on. Front Biosci (Elite Ed) 4: 1743–1758.
Talvani A, Rocha MO, Ribeiro AL, Borda E, Sterin-Borda L, Teixeira MM, 2006. Levels of anti-M2 and anti-beta1 autoantibodies do not correlate with the degree of heart dysfunction in Chagas' heart disease. Microbes Infect 8: 2459–2464.
Morillo CA, Marin-Neto JA, Avezum A, Sosa-Estani S, Rassi A Jr, Rosas F, Villena E, Quiroz R, Bonilla R, Britto C, Guhl F, Velazquez E, Bonilla L, Meeks B, Rao-Melacini P, Pogue J, Mattos A, Lazdins J, Rassi A, Connolly SJ, Yusuf S, 2015. Randomized trial of benznidazole for chronic Chagas' cardiomyopathy. N Engl J Med 373: 1295–1306.
Ribeiro AL, Campos MS, Baptista LM, de Sousa MR, 2010. The Valsalva maneuver in Chagas disease patients without cardiopathy. Clin Auton Res 20: 79–83.
Bremner FD, Smith SE, 2006. Pupil abnormalities in selected autonomic neuropathies. J Neuroophthalmol 26: 209–219.
Pittasch D, Lobmann R, Behrens-Baumann W, Lehnert H, 2002. Pupil signs of sympathetic autonomic neuropathy in patients with type 1 diabetes. Diabetes Care 25: 1545–1550.
Smith SA, Smith SE, 1983. Reduced pupillary light reflexes in diabetic autonomic neuropathy. Diabetologia 24: 330–332.
Maguire AM, Craig ME, Craighead A, Chan AK, Cusumano JM, Hing SJ, Silink M, Howard NJ, Donaghue KC, 2007. Autonomic nerve testing predicts the development of complications: a 12-year follow-up study. Diabetes Care 30: 77–82.
Aschner P, 2002. Diabetes trends in Latin America. Diabetes Metab Res Rev 18 (Suppl 3): S27–S31.
International Diabetes Federation, 2014. Global Diabetes Scorecard—Tracking Progress for Action. Brussels, Belgium: International Diabetes Federation, 150.
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Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients.
Financial support: This work was supported by the National Institutes of Health Fogarty International Clinical Scholars Program. Additional funding for pupillometer development and salary support for Drs. Moore and Morris was provided by National Aeronautics and Space Administration grant NNX12AM25G.
Authors' addresses: Anthony Halperin, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Monica Pajuelo, Laboratory of Infectious Diseases Research, Universidad Peruana Cayetano Heredia, Lima, Peru, E-mail: email@example.com. Jeffrey A. Tornheim, Division of Infectious Diseases, The Johns Hopkins University School of Medicine, Baltimore, MD, E-mail: firstname.lastname@example.org. Nancy Vu, Internal Medicine Residency Program, Cleveland Clinic, Cleveland, OH, E-mail: email@example.com. Andrés M. Carnero, Laboratory of Infectious Diseases Research, Universidad Peruana Cayetano Heredia, Lima, Peru, E-mail: firstname.lastname@example.org. Gerson Galdos-Cardenas, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, and Universidad Católica Boliviana “San Pablo,” Santa Cruz de la Sierra, Bolivia, E-mail: email@example.com. Lisbeth Ferrufino, Clinical Laboratory, Hospital Universitario Japonés, Santa Cruz de la Sierra, Bolivia, E-mail: firstname.lastname@example.org. Marilyn Camacho, Department of Internal Medicine, Hospital Universitario Japonés, Santa Cruz de la Sierra, Bolivia, E-mail: email@example.com. Juan Justiniano, Department of Cardiology, Hospital Universitario Japonés, Santa Cruz de la Sierra, Bolivia, E-mail: firstname.lastname@example.org. Rony Colanzi, Department of Pathology, Hospital Universitario Japonés, Santa Cruz de la Sierra, Bolivia, and Universidad Católica Boliviana “San Pablo,” Santa Cruz de la Sierra, Bolivia, E-mail: email@example.com. Natalie M. Bowman, Division of Infectious Disease, Department of Medicine, University of North Carolina, Chapel Hill, NC, E-mail: firstname.lastname@example.org. Tiffany Morris, Department of Neurology, Icahn School of Medicine at Mount Sinai, New York City, NY, E-mail: email@example.com. Hamish MacDougall, School of Psychology, University of Sydney, Australia, E-mail: firstname.lastname@example.org. Caryn Bern, Division of Epidemiology and Biostatistics, University of California San Francisco School of Medicine, San Francisco, CA, E-mail: Caryn.Bern2@ucsf.edu. Steven T. Moore, Department of Neurology, Icahn School of Medicine at Mount Sinai, New York City, NY, E-mail: email@example.com. Robert H. Gilman, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, and Laboratory of Infectious Diseases Research, Universidad Peruana Cayetano Heredia, Lima, Peru, and Universidad Católica Boliviana “San Pablo,” Santa Cruz de la Sierra, Bolivia, E-mail: firstname.lastname@example.org.