Validation of Monocular Pupillometry in Healthy Controls and Patients With Autonomic Dysfunction: Pupillary Biomarkers for Autonomic Failure

Background Pupillary function is frequently impaired in autonomic disorders, and biomarkers for early diagnosis and disease progression are urgently needed. Pupillometry allows for noninvasive ocular autonomic evaluation. This prospective study technically and clinically validates a handheld monocular pupillometer available for broad application as an autonomic screening tool in autonomic disorders. Methods A total of 40 controls and 100 patients with autonomic disorders underwent pupillometry using the PLR‐4000(NeurOptics). Pupillary parasympathetic and sympathetic function were assessed by responses to a light stimulus and to 0.5% apraclonidine eye drops, respectively. Test–retest assessments and validations against a binocular device were performed. Results In healthy controls, the mean light reflex ratio was 42% ± 5.7% and the median response to apraclonidine was −5.0% (−8.8%–2.8%). Monocular and binocular pupillometers presented similar results. Test–retest experiments showed: median light response difference 3.0% (1.0%–4.8%), median % difference in response to apraclonidine 5.2% (2.2%–10.6%). In patients with neurodegenerative disorders ( n = 24), autonomic neuropathies ( n = 39), and autonomic ganglionopathies ( n = 9), pupillary abnormalities were very prevalent (52%, 45%, and 100%, respectively). All patients with intermittent autonomic disorders had normal pupillomotor function. Conclusions The presented device provides accurate, reproducible assessments of pupillary autonomic function in healthy controls and patients with autonomic disorders. With normative data provided, it is an easily accessible, well‐tolerated tool to quantitatively assess pupillomotor innervation in a broad clinical setting. Further studies are warranted to explore its potential as a noninvasive biomarker, complementing standard autonomic function tests for early detection, monitoring disease progression, and evaluating treatment response in disorders with autonomic failure.