Validation of a Smartphone Pupillometry Application in Diagnosing Severe Traumatic Brain Injury.

The pupillary light reflex (PLR) is an important biomarker for the detection and management of traumatic brain injury (TBI). We investigated the performance of PupilScreen, a smartphone-based pupillometry app, in classifying healthy control subjects and subjects with severe TBI in comparison to the current gold standard NeurOptics pupillometer (NPi-200 model with proprietary Neurological Pupil Index [NPi] TBI severity score). A total of 230 PLR video recordings taken using both the PupilScreen smartphone pupillometer and NeurOptics handheld device (NPi-200) pupillometer were collected from 33 subjects with severe TBI (sTBI) and 132 subjects who were healthy without self-reported neurological disease. Severe TBI status was determined by Glasgow Coma Scale (GCS) at the time of recording. The proprietary NPi score was collected from the NPi-200 pupillometer for each subject. Seven PLR curve morphological parameters were collected from the PupilScreen app for each subject. A comparison via t-test and via binary classification algorithm performance using NPi scores from the NPi-200 and PLR parameter data from the PupilScreen app was completed. This was used to determine how the frequently used NPi-200 proprietary NPi TBI severity score compares to the PupilScreen app in ability to distinguish between healthy and sTBI subjects. Binary classification models for this task were trained for the diagnosis of healthy or severe TBI using logistic regression, k-nearest neighbors, support vector machine, and random forest machine learning classification models. Overall classification accuracy, sensitivity, specificity, area under the curve, and F1 score values were calculated. Median GCS was 15 for the healthy cohort and 6 (interquartile range 2) for the severe TBI cohort. Smartphone app PLR parameters as well as NPi from the digital infrared pupillometer were significantly different between healthy and severe TBI cohorts; 33% of the study cohort had dark eye colors defined as brown eyes of varying shades. Across all classification models, the top performing PLR parameter combination for classifying subjects as healthy or sTBI for PupilScreen was maximum diameter, constriction velocity, maximum constriction velocity, and dilation velocity with accuracy, sensitivity, specificity, area under the curve (AUC), and F1 score of 87%, 85.9%, 88%, 0.869, and 0.85, respectively, in a random forest model. The proprietary NPi TBI severity score demonstrated greatest AUC value, F1 score, and sensitivity of 0.648, 0.567, and 50.9% respectively using a random forest classifier and greatest overall accuracy and specificity of 67.4% and 92.4% using a logistic regression model in the same classification task on the same dataset. The PupilScreen smartphone pupillometry app demonstrated binary healthy versus severe TBI classification ability greater than that of the NPi-200 proprietary NPi TBI severity score. These results may indicate the potential benefit of future study of this PupilScreen smartphone pupillometry application in comparison to the NPi-200 digital infrared pupillometer across the broader TBI spectrum, as well as in other neurological diseases.