Pupillary Response Patterns in Patients with Known Substance Use Based on Stimulus Chromaticity; A Pedagogically Based Assessment

Curr Eye Res. 2025 Oct 27:1-8. doi: 10.1080/02713683.2025.2577767. Online ahead of print.

ABSTRACT

PURPOSE: Use of illicit substances such as cocaine is associated with alteration in catecholamine-mediated neurotransmission throughout the CNS, including the eye. One of the most accessible physiologic parameters associated with neuromodulatory features of substance abuse is the pupillary light reflex (PLR). In this study, we examined a domain of the PLR characterized by melanopsin-driven intrinsically photosensitive retinal ganglion cells (ipRGCs) to assess the impact of substance abuse on ipRGC function.

METHODS: An exploratory PLR examination on ten subjects with a documented history of substance use (HSU) without preexisting ocular disease was conducted with a comparator control cohort. Cases included assessment of cognitive function, depression, insomnia, and retinal nerve fiber thickness. IpRGC functionality was demonstrated by the PLR using a pedagogical-based methodology centered on response parameters with the introduction of a complementary analysis employing pseudo-one-phase modeling. Discriminant analysis employing the area under the receiver operating characteristic curve (AUC of ROC) categorized normal vs. abnormal ipRGC response.

RESULTS: There was no statistical association between ipRGC function and insomnia; however, insomnia was more prevalent among those with ipRGC abnormality. Indication of clinical depression was seen in 70% of study participants and was unrelated to ipRGC function. Pseudo-one-phase modeling demonstrated a significantly higher plateau in the HSU group as well as a slower initial rate of pupil recovery consistent with abnormal PIPR dynamics and complementary to AUC metrics. Discriminant analysis identified that 60% of HSU demonstrated ipRGC abnormality.

CONCLUSION: Abnormal ipRGC functionality was demonstrated among those with HSU in this small exploratory study utilizing both AUC-ROC analysis as well as assessment of PLR waveform characteristics using features of a pseudo-first-order model.

PMID:41143850 | DOI:10.1080/02713683.2025.2577767