Superior reproducibility and repeatability in automated quantitative pupillometry compared to standard manual assessment, and quantitative pupillary response parameters present high reliability in critically ill cardiac patients

Abstract

Background: Quantitative pupillometry is part of multimodal neuroprognostication of comatose patients after out-of-hospital cardiac arrest (OHCA). However, the reproducibility, repeatability, and reliability of quantitative pupillometry in this setting have not been investigated.

Methods: In a prospective blinded validation study, we compared manual and quantitative measurements of pupil size. Observer and device variability for all available parameters are expressed as mean difference (bias), limits of agreement (LoA), and reliability expressed as intraclass correlation coefficients (ICC) with a 95% confidence interval.

Results: Fifty-six unique quadrupled sets of measurement derived from 14 sedated and comatose patients (mean age 70±12 years) were included. For manually measured pupil size, inter-observer bias was -0.14±0.44 mm, LoA of -1.00 to 0.71 mm, and ICC at 0.92 (0.86-0.95). For quantitative pupillometry, we found bias at 0.03±0.17 mm, LoA of -0.31 to 0.36 mm and ICCs at 0.99. Quantitative pupillometry also yielded lower bias and LoA and higher ICC for intra-observer and inter-device measurements. Correlation between manual and automated pupillometry was better in larger pupils, and quantitative pupillometry had less variability and higher ICC, when assessing small pupils. Further, observers failed to detect 26% of the quantitatively estimated abnormal reactivity with manual assessment. We found ICC >0.91 for all quantitative pupillary response parameters (except for latency with ICC 0.81-0.91).

Conclusion: Automated quantitative pupillometry has excellent reliability and twice the reproducibility and repeatability than manual pupillometry. This study further presents novel estimates of variability for all quantitative pupillary response parameters with excellent reliability.

Fig 1. Patient assessment procedure.

Flowchart of “Patient assessment procedure” depicting a complete set of quadruple measurement-pairs to the same patient within 5 minutes, with every measurement-pair comprising one manual, and one quantitative measurement, to both left and right eye, subsequently, blinded to the other observer.

Fig 2. Standard manual versus quantitative pupillometry—Pupil size.

Bland Altman plots depicting intra-, and inter-observer variability of pupil size measured with manual and quantitative pupillometry.

Fig 3. Additional quantitative pupillary response parameters.

Bland Altman plots depicting intra-, and inter-observer variability of quantitative pupillary response parameter. %CH = percental change, CV = average constriction velocity, MCV = maximum constriction velocity, DV = dilation velocity, LAT = latency of constriction, NPi = Neurological Pupil index, LoA = limit of agreement.

Fig 4. Device reproducibility and repeatability.

Bland Altman plots depicting intra-, and inter-device variability of quantitative pupillometry. MAX size = maximum pupillary diameter, MIN size = minimum pupillary diameter, %CH = percental change, CV = average constriction velocity, MCV = maximum constriction velocity, DV = dilation velocity, LAT = latency of constriction, NPi = Neurological Pupil index, LoA = limit of agreement.