Pupillary Hippus as a Biomarker: Spectral Signatures and Complexity Approaches in Autonomic and Clinical Contexts

Pupillary hippus, i.e., the spontaneous bilateral oscillation of pupil diameter under constant illumination, provides a non-invasive window into autonomic and central nervous system dynamics. Despite decades of research, a unified framework linking its spectral features, physiological underpinnings, and analytical complexity is still missing. In this narrative review, we synthesize spectral and nonlinear pupillometry studies to propose a paradigm- aware taxonomy of hippus frequency bands that integrates evidence from autonomic tests and cognitive-arousal paradigms. Across the literature, low-frequency components tend to covary with respiratory/vasomotor autonomic rhythms, while higher-frequency fluctuations and complexity indices are more sensitive to cognitive load, visual fatigue, and pathological states but remain methodologically heterogeneous. Finally, we explore contexts in which hippus-based biomarkers show clinical potential, with a main focus on glaucoma as an emerging translational model, while underscoring the methodological and translational gaps that currently hinder their validation and routine clinical adoption. Physiology, spectral metrics, and complexity-based analyses are integrated to lay the foundations of a coherent framework.