Recovery in pupillometric non-visual functions following chiasmal decompression in pituitary adenoma

Abstract

Pituitary adenomas frequently compress visual and non-visual pathways, resulting in visual field deficits and sleep disturbances. While transsphenoidal surgery is often anatomically effective, functional visual and non-visual outcomes remain variable and often unpredictable. This study investigates visual and non-visual (i.e., pupillometric) changes associated with optic nerve compression and decompression, and the potential role of chromatic pupillometry as an objective evaluation tool for visual dysfunction in pituitary adenoma. This longitudinal study included 27 patients with pituitary adenoma (median age = 55.4 years [IQR=23.4]) and 41 age-matched controls (53.6 [13.7] years), evaluated pre-operatively (mean duration ± SD: 7.0 ± 5.4 weeks prior to surgery) and post-operatively (12.0 ± 1.5 weeks post-surgery) with handheld chromatic pupillometry, in addition to comprehensive neuro-ophthalmological and neuroimaging examinations. Pupillometric features were analyzed for associations with structural changes and visual outcomes. There was a significant reduction in the upward displacement and increase in the thickness of the optic chiasm measured on MRI (p<0.001) following transsphenoidal surgery. Pupillary responses improved post-operatively, including increased maximum constriction to both red and blue light, but remained below control levels (p<0.05). In patients with full visual field index recovery (n=5), pupillometric responses were comparable to controls (p>0.05) while patients without recovery exhibited persistent deficits in these metrics. Remarkably, melanopsin-driven post-illumination pupil responses improved significantly, reaching control values post-operatively (p>0.05), regardless of visual field index recovery. Structural recovery correlated with improved visual field index (ρ= -0.62, p<0.001) and with maximum constriction to red light (ρ= -0.47, p=0.004). Following transsphenoidal surgery, there was a consistent recovery in pupillary light responses that correlated with clinical structural and functional changes observed in pituitary adenoma patients. Notably, melanopsin-mediated responses normalized post-operatively even in patients without visual field recovery, suggesting that non-visual pathways can recover independently of vision. Handheld chromatic pupillometry is a promising, non-invasive biomarker to track both visual and non-visual outcomes. Future studies integrating circadian and sleep markers are warranted to establish its role as a proxy for systemic non-visual functions in this population.