How Ambient Light Conditions Impact Infrared Pupillometry in ICU

Study Overview

Holmskär et al. published a prospective crossover study in the Journal of Clinical Monitoring and Computing (2025) investigating whether ambient light conditions affect hardware pupillometry parameters in critically ill patients. The research was conducted at Karolinska University Hospital, Stockholm, Sweden, examining 20 adult patients requiring invasive ventilation in neurointensive and general intensive care units.

The study built on previous work by Ong et al (2018), where statistically significant ambient light effects on pupil reactivity in critically ill have been shown.

Background and Clinical Context

Manual pupillary light reflex examination has significant limitations including substantial interrater variability and subjective interpretation. Hardware pupillometry addresses these issues by providing automated, reproducible measurements with excellent interrater reliability. The technology records pupil behavior during light stimulation and calculates a composite pupillary light reflex score called the "Neurological Pupil index (NPi)", which ranges from 0 to 5 with ≥3 indicating normal pupillary responses.

Despite widespread clinical use of hardware pupillometry for applications including neuro-monitoring, cardiac arrest prognostication, and stroke evaluation, among others, the effects of ambient light on measurements have remained largely unknown. Only one previous study had examined this question (Ong et al 2018), showing significant ambient light effects on pupillary light reflex values in critical care patients.

Study Design and Methods

The researchers conducted a prospective crossover study with 20 patients, doubling their initial sample size calculation to account for uncertainty from previous small studies. Inclusion criteria required patients ≥18 years old who were unconscious or sedated and receiving invasive ventilation. Exclusion criteria included ocular trauma affecting pupillary reaction and intracranial pressure fluctuations exceeding ±2 mmHg during measurements.

The crossover design tested three conditions in sequence: dark conditions (DC1), bright conditions (BC), and dark conditions again (DC2). Dark conditions were achieved with all lights off, shades closed, and doors closed, measured post-hoc at 1 lux. Bright conditions used overhead ceiling lights at full intensity, measured at 301 lux. Measurements were performed at two-minute intervals, with patients' eyelids closed between observations.

Patient characteristics reflected typical critical care populations: 60% female, median age 57 years, with diagnoses including traumatic brain injury (30%), subarachnoid hemorrhage (25%), cardiac arrest (15%), and ischemic stroke (15%). Most patients received standard intensive care treatments including propofol (85%), opioids (85%), and vasopressors (85%).

Primary Findings: Pupillary Light Reflex Changes with Ambient Light

The study demonstrated statistically significant effects of ambient light on pupillary light reflex measurements. Under dark conditions (DC1), median "NPi" values were 4.6 (right eye) and 4.7 (left eye). Under bright conditions, these decreased significantly to 4.2 (right eye) and 4.1 (left eye).

The median pupillary light reflex decrease from dark to bright conditions was 0.3 for the right eye (p=0.01) and 0.4 for the left eye (p<0.001). The score decreased in 75% of patients (right eye) and 85% of patients (left eye) when transitioning to bright conditions. "In 25% of participants the NPi decreased by 0.6 or more" (Holmskär et al. 2025) on the right side, with similar magnitudes on the left side.

When conditions returned from bright to dark (BC to DC2), pupillary light reflex values increased significantly with median increases of 0.3 (right eye) and 0.4 (left eye), both p<0.001. "No significant difference was found between the two dark condition measurements (DC1 and DC2)" (Holmskär et al. 2025), confirming that changes resulted from lighting rather than temporal factors.

Secondary Analysis: Affected Hardware Pupillometry Parameters

The secondary analysis revealed which specific parameters contributed to pupillary light reflex score changes. "The secondary analysis showed that the differences in NPi were driven by differences in most, but not all, QP parameters included in NPi" (Holmskär et al. 2025). Significant differences between dark and bright conditions were observed for maximum pupil size, relative change in pupil size, constriction velocity, and maximum constriction velocity. However, latency and minimum pupil size showed no significant differences bilaterally, and dilation velocity was unaffected on the right side.

Maximum pupil size decreased under bright conditions by median values of 0.17 mm (right, p<0.001) and 0.19 mm (left, p<0.001). Relative change in pupil size showed the largest differences, decreasing by median values of 7.0% (right, p<0.001) and 9.5% (left, p<0.001) under bright conditions. Constriction velocities decreased by mean values of 0.39 mm/s (right, p=0.001) and 0.42 mm/s (left, p<0.001).

Within-Individual Variability Analysis

To distinguish lighting effects from measurement noise, researchers analyzed within-individual variability at each lighting condition. Median intra-individual differences in pupillary light reflex scores were minimal: 0 (both eyes) under DC1, 0.1 (right) and -0.1 (left) under BC, and 0.1 (right) and 0 (left) under DC2.

"All within-individual differences in NPi at DC1, BC and DC2 were significantly smaller than the differences DC1-BC and BC-DC2" (Holmskär et al. 2025). This confirms that lighting-related changes represent true physiological responses rather than random measurement variability.

Sensitivity Analysis

A sensitivity analysis excluding two patients with abnormal baseline pupillary light reflex scores (< 3 in at least one eye) did not change the overall results. The median score changes remained consistent: decreases of 0.3 (right) and 0.4 (left) from DC1 to BC, increases of 0.3 (right) and 0.4 (left) from BC to DC2, and no significant difference between DC1 and DC2.

Clinical Implications

The study findings have several important clinical implications. Pupillary light reflex score decreases of 0.3-0.4 units could affect clinical interpretation, particularly in patients with values near the normal threshold of 3.0. In 25% of patients, decreases exceeded 0.6-0.7 units, representing potentially clinically significant changes.

For cardiac arrest prognostication, where lower pupillary light reflex scores predict poor outcomes, ambient light-induced decreases could bias assessments. In brain death determination, where pupillary light reflex absence is a neurological criterion, standardized lighting becomes crucial for distinguishing between scores of 0.0 (absent) and >0.0 (present).

The findings can also impact intracranial pressure monitoring applications. Inconsistent ambient lighting could introduce variability that masks true neurological changes or creates false trends.

Study Limitations

The study had several limitations. The sample size of 20 patients was relatively small. The single-center design and convenience sampling may limit generalizability. Short two-minute intervals between observations may not allow complete retinal adaptation, potentially underestimating the full magnitude of ambient light effects.

Not all patients had invasive intracranial pressure monitoring, and data on pain levels or fever were not collected. The heterogeneous patient population, while strengthening generalizability, may have introduced variability. Post-hoc ambient light measurements may not precisely reflect conditions during data collection.

Comparison with Previous Research

The findings corroborate the only previous study examining ambient light effects on pupillary light reflex scores, which included seven healthy volunteers and seven critical care patients (Ong et al 2018). That study also showed significant ambient light effects on hardware pupillometry values, though with longer washout periods between measurements. The current study's larger size and exclusive focus on critical care patients strengthens the evidence base.

Future Directions

The authors suggest several areas for future investigation. Automated light correction methods could potentially eliminate ambient light effects, making pupillometry more robust across clinical environments. Some smartphone applications already show promise with automatic ambient light correction (Bogucki et al.). These systems demonstrate the potential to maintain measurement accuracy across varying environmental conditions while preserving sensitivity to detect neurological changes, potentially eliminating the need for strict lighting standardization protocols.

In addition, studies examining whether measurements under both bright and dark conditions provide additional diagnostic information could expand clinical applications. The development of correction algorithms based on ambient light intensity represents another promising research direction.

Conclusions

"We corroborate previous findings that the level of ambient light affects QP parameters in critically ill patients" (Holmskär et al. 2025). This study provides compelling evidence that ambient light significantly affects hardware pupillometry parameters in critical care patients. The median pupillary light reflex score decrease of 0.3-0.4 units from dark to bright conditions, with 25% of patients experiencing larger decreases, represents clinically relevant changes that could influence important medical decisions.

The crossover design and careful control of confounding factors strengthen confidence in these conclusions. The reversibility of lighting effects and absence of differences between repeated dark measurements confirm that observed changes result from ambient lighting rather than other factors.

"This needs to be considered for accurate interpretation of QP parameters" (Holmskär et al. 2025). These findings necessitate consideration of ambient light standardization in clinical practice and research protocols. Wider adoption of automated lighting correction methods could improve the accuracy of neurological assessment.

For the full study and complete methodology details, you can read more in the original publication.

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