The Relationship between Quantitative Pupillometry and Estimated Ganglion Cell Counts in Patients with Glaucoma

Purpose: To assess the relationship between pupillary light reflex and estimated retinal ganglion cell (RGC) counts in patients with glaucoma. Methods: We recorded and analyzed pupil responses using an automated binocular pupillometer in 148 patients with glaucoma (mean age 67±11, 49% female) and 71 controls (age 60±9.6, 69% female) as part of a prospective clinical study. The amplitude of pupil constriction was calculated as the percentage change in pupil diameter between constriction onset and peak constriction in response to controlled stimuli. The magnitude of a relative afferent pupillary defect (RAPD) was defined as the log of the ratio of the amplitude between two eyes multiplied by 10. RGC counts were estimated using empirical formulas that combine estimates from both functional (eccentricity and sensitivity measured by standard automated perimetry) and structural (retinal nerve fiber layer thickness-RNFL) tests. For analyses performed at the level of individual eyes, we used multi-level modeling to account for between-eye correlations within individuals. Results: Eyes with higher estimated RGC counts had a larger pupil response amplitude (Z score=8.24, P<0.001), shorter latency (Z=-3.17, P=0.002), faster constriction velocity (Z=6.64, P<0.001), shorter time to maximum constriction (Z=-1.96, P=0.049), and longer time to maximum dilation (Z=6.66, P<0.001). For every 0.3 log unit difference in RAPD score, there was an average decrease in estimated RGC count of 37,817 (P<0.001). Conclusion: There is a statistically significant association between estimated RGC count and pupillary response to stimuli. Quantitative pupillography may be useful in diagnosis and monitoring of optic neuropathies.