Quantitative pupillometry - the established clinical category.
The bedside pupillary examination is among the oldest and most clinically established neurologic measurements. The limits of the bedside examination are well-documented. Inter-examiner agreement on pupillary size and reactivity is modest even among trained examiners. Subtle changes - gradual increases in pupillary diameter, subtle reductions in reactivity - are difficult to detect by direct observation under standard bedside lighting conditions.
Quantitative pupillometry addresses these limits by providing automated infrared measurement of pupil diameter and dynamic light response with millimeter-scale precision and millisecond-scale temporal resolution. In intensive care unit neurologic monitoring, in anesthesia and perioperative practice, in trauma resuscitation, and in the assessment of cardiac arrest survivors, automated pupillometry has become an established clinical instrument across hospitals nationwide.
The Neurological Pupil index (NPi) - origin and validation.
Chen JW, Gombart ZJ, Rogers S, Gardiner SK, Cecil S, Bullock RM. Pupillary reactivity as an early indicator of increased intracranial pressure: The introduction of the Neurological Pupil index. Surg Neurol Int. 2011;2:82.
The 2011 paper that introduced the Neurological Pupil index - a numerical scale derived from automated pupillometric measurement of pupillary light reflex parameters. The NPi ranges from 0 (non-reactive) to 5 (normal reactivity). Clinical convention, supported by subsequent validation work, holds that NPi values ≥ 3 are within the normal range while values < 3 are abnormal and warrant clinical attention.
Olson DM, Stutzman S, Saju C, Wilson M, Zhao W, Aiyagari V. Interrater reliability of pupillary assessments. Neurocrit Care. 2016;24(2):251–257.
PMID 26381281Documentation of the inter-rater reliability advantage of automated pupillometry over manual bedside examination - substantially improved agreement when pupillary measurements are obtained by automated pupillometer compared with manual observation.
Oddo M, Taccone FS, Petrosino M, et al. The Neurological Pupil index for outcome prognostication in people with acute brain injury (ORANGE): a prospective, observational, multicentre cohort study. Lancet Neurol. 2023;22(10):925–933.
The ORANGE prospective multicentre cohort - Outcome PRognostication of Acute Brain INjury with the NeurOloGical Pupil indEx - establishes the NPi as a prognostic measure for neurological outcome and mortality after acute brain injury. The published evidence base supporting clinical use of quantitative pupillometry is substantial and continues to grow.
The clinical use cases - where automated pupillometry is in established practice.
- Detection of increased intracranial pressure in neurocritical care, where pupillary reactivity reduction (NPi decline) has been described as an early indicator of intracranial pressure elevation.
- Prognostication after acute brain injury - the ORANGE cohort and related published literature establish NPi values measured serially during ICU admission as carrying prognostic value for neurological outcome.
- Prognostication after cardiac arrest - pupillometric measurements obtained during the post-cardiac-arrest period contribute to multimodal neurological prognostication and inform decisions about withdrawal of life-sustaining treatment.
- Monitoring of analgesia and anesthesia depth - pupillary unrest and pupillary dilation reflex have been studied as indicators of nociceptive response under general anesthesia.
- Detection of cerebral herniation and other acute neurologic deterioration in patients with limited examination capability - sedated, intubated, mechanically ventilated patients in whom standard bedside examination is constrained.
The platform's architectural advance.
The NeurOptics pupillometer line is the dominant FDA-cleared device in this clinical category. It is a handheld, single-eye instrument: the operator places the pupillometer over one eye at a time, holds it in place for the measurement, obtains a serial reading. The device produces excellent pupillometric measurements within an established workflow.
The ClearGazeTest platform delivers binocular 200-220 Hz integrated pupillometry through a head-mounted display. The architectural advantages are specific and quantifiable:
| Capability | NeurOptics NPi-200/300 (handheld) | ClearGazeTest platform (HMD) |
|---|---|---|
| Eyes measured | One eye at a time; serial measurement | Both eyes simultaneously; continuous bilateral |
| Inter-eye RAPD | Computed across sequential single-eye readings | Computed in real time from simultaneous bilateral data at the Kawasaki-Kardon 0.3 log-unit clinical threshold |
| Measurement cadence | Operator-driven spot measurements at clinical intervals | Continuous measurement supporting pupillary unrest analysis and dynamic-response characterization |
| Workflow | Operator presence required at each measurement; manual documentation | Headset-delivered measurement; FHIR R4 EHR integration; automated longitudinal documentation and trend visualization |
| Adjunct neuro-ocular substrate | Pupillometry only | Pupillometry plus the full fifteen-biomarker substrate - saccadic, smooth pursuit, vergence, VOR - measured in the same session |
The regulatory pathway.
The NeurOptics NPi-200 and NPi-300 devices are FDA 510(k)-cleared. The most natural regulatory pathway for the platform's ICU pupillometry application is therefore predicate comparison against the NeurOptics NPi device family. The platform's clinical validation will frame substantial equivalence in measurement intent (quantitative pupillary light reflex assessment), measurement output (NPi-equivalent quantitative score), and intended use (adjunct neurologic monitoring in adult and pediatric critical care).
The comparative-validation question
The platform's positioning depends on demonstration that the platform's binocular HMD-delivered pupillometry reproduces or exceeds the NeurOptics NPi in clinical validation cohorts. The Stage 2 concurrent-validity validation framework documented in the platform's engineering plan provides the comparative-validation protocol: side-by-side NPi measurement by the NeurOptics handheld and the platform's HMD-delivered pupillometry in matched ICU patient populations, with inter-method agreement, intra-method reproducibility, and longitudinal-trend agreement as the principal outcome measures.
Honest limits.
The platform's ICU pupillometry application is currently positioned as a comparative-validation target. The comparative work that would establish equivalence or superiority against the established NeurOptics device family has not yet been performed. The platform's claim is that the architecture is positioned to deliver superior measurement on the specific dimensions documented above; the demonstration that it does so in clinical populations remains the substance of future Stage 2 validation work. Until that work is complete and published, the platform's positioning is research-grade in the academic literature and pre-clearance in the regulatory sense. The platform respects the substantial published evidence base supporting the established quantitative-pupillometry clinical category and does not represent that platform measurements have yet been demonstrated to outperform the established devices.
The funding and academic-partnership pathway.
The company is exploring a range of non-dilutive funding pathways to support prospective validation of the instrumented HINTS application - including federal research programs in cerebrovascular and emergency neurology, emergency-readiness diagnostic initiatives, foundation research grants, and small-business commercialization mechanisms. In parallel, the company is in early discussions with academic neuro-otology and emergency-neurology groups regarding prospective validation collaborations.
These conversations are exploratory and ongoing: no funding has been awarded, and no academic partnership has been executed. Detailed funding planning is maintained internally as part of the company's broader strategic portfolio.
For the ICU, the operating room, and the post-arrest team.
The platform's ICU pupillometry application is in active development. Academic partnership conversations and ICU clinical-research engagement are open now.
Contact the clinical team →