Pupillometric alterations in Graves' disease: Beyond thyroid functional status

To evaluate static and dynamic pupillometric parameters in patients with Graves' disease (GD) compared with healthy controls, and to examine their relationships with thyroid functional status, thyroid hormone levels, clinical activity, thyrotropin receptor antibody (TRAb) levels, and orbitopathy.

In this prospective cross-sectional study, 51 patients with GD and 45 healthy controls underwent automated pupillometry. Static pupil diameters were measured under scotopic, mesopic, and photopic conditions, and mean pupil dilation speed (MPDS) was assessed during redilation. Associations with clinical and biochemical variables were assessed using Spearman correlation with Benjamini-Hochberg correction and multiple linear regression. Significant group differences were further assessed using age- and sex-adjusted analysis of covariance, and thyroid hormone-pupillometry correlations were compared between groups using Fisher's r-to-z transformation.

Compared with controls, patients with GD exhibited larger mesopic (p = 0.032) and photopic (p = 0.021) pupil diameters and lower MPDS (p = 0.034), with differences remaining significant after age and sex adjustment. Among patients with GD, no statistically significant differences in pupillometric parameters were detected between euthyroid and hyperthyroid patients or according to orbitopathy status (all p > 0.05). Clinical Activity Score (CAS) correlated with scotopic (ρ = 0.498, p < 0.001) and mesopic pupil diameters (ρ = 0.442, p = 0.006) and inversely with MPDS (ρ=-0.561, p < 0.001); TRAb correlated with mesopic (ρ = 0.431, p = 0.006) and photopic pupil diameters (ρ = 0.502, p = 0.001) and inversely with MPDS (ρ=-0.538, p = 0.001). Continuous free triiodothyronine (fT3) correlated with all static pupil diameters and MPDS in GD, most strongly with mesopic pupil diameter (ρ = 0.598, p < 0.001). Between-group comparisons confirmed stronger fT3 correlations with scotopic (p = 0.047) and mesopic (p = 0.023) pupil diameters in GD than in controls. Multivariable analyses identified CAS as an independent predictor of scotopic pupil diameter (p = 0.006) and MPDS (p = 0.028), TRAb of photopic pupil diameter (p = 0.001), and fT3 of mesopic pupil diameter (p = 0.010). Age independently predicted scotopic (p < 0.001), photopic pupil diameter (p = 0.016), and MPDS (p = 0.003).

In this study of patients with GD, no statistically significant differences in pupillometric parameters were detected according to categorical thyroid functional status or orbitopathy status. However, fT3 independently predicted mesopic pupil diameter, while CAS and TRAb demonstrated independent, parameter-specific associations with static and dynamic pupillometric measures. As comparable hormone-pupillometry associations were not demonstrated in healthy controls, pupillometric alterations in GD may reflect disease-related clinical and biochemical influences beyond categorical thyroid status alone.