Assessing Pupil Light Reflex Metrics in Glaucoma: Insights from a Systematic Review and Meta-Analysis.

Topic: This systematic review and meta-analysis aimed to identify the most affected pupil light reflex (PLR) metrics and determine the optimal stimulus conditions for detecting glaucomatous deficits. Clinical Relevance: The PLR is altered in glaucoma and understanding the basis of this change may provide a useful method for disease detection and progression monitoring. Methods: A comprehensive literature search was conducted across PubMed, Embase, and Google Scholar databases from June 2023 to April 2025. Studies evaluating PLR in glaucoma patients and healthy controls were included. Data extraction focused on PLR metrics such as amplitude of constriction, velocity of constriction and dilation, latency of constriction and dilation, and postillumination pupil response (PIPR). A meta-analysis was performed (Hedges' g) to determine the impact of glaucoma on each PLR metric. Subgroup and moderator analyses were conducted to assess the influence of dark adaptation, stimulus duration, and stimulus color on PLR metrics and to examine the relationship between PLR metrics and age, retinal nerve fiber layer (RNFL) thickness, and mean deviation (MD). This systematic review is registered with PROSPERO (CRD420251079002). Results: A meta-analysis revealed that the amplitude of constriction (the most affected metric), latency of constriction, velocity of constriction, and PIPR were significantly affected in mild glaucoma. Subgroup analysis suggested that the testing conditions involving a stimulus lasting >1 second, after dark adaptation of <5 minutes, are most sensitive for detecting PLR deficits. Moderator analysis indicated that age, RNFL thickness, and MD were associated with variations in PLR metrics. In severe glaucoma, the amplitude of constriction, duration of dilation, velocity of constriction, and PIPR showed the largest effect sizes (ESs). Overall, severe glaucoma led to larger ESs, indicating greater change in PLR metrics was associated with disease severity. Conclusions: These findings suggest that the amplitude of constriction is the most affected PLR metric in both mild and severe glaucoma. Furthermore, our results indicate that a stimulus lasting >1 second, when presented after a dark adaptation of <5 minutes, may represent the most sensitive condition for detecting amplitude of constriction deficits in mild glaucoma. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.