Retinal photoreceptor functions are compromised in patients with resistance to thyroid hormone syndrome (RTHβ)

CONTEXT: In animal models, disruption of thyroid hormone receptor-beta (TRβ) reduces the medium-wavelength (L/M) and increases the short-wavelength (S)-cones. The retinal photoreceptors (RPs) functions are unknown in patients with resistance to thyroid hormone syndrome with dominant-negative TRβ mutations (RTHβ). OBJECTIVE: to investigate RPs function in RTHβ. DESIGN, SETTING AND PARTICIPANTS: case-control study involving 27 RTHβ patients and 31 age-gender-matched controls, conducted in two tertiary referral centers in Italy. MAIN OUTCOME MEASURES: colour vision sensitivity assessed by Farnsworth with calculation of Total Score Error (TES); central macular thickness (CMT) of the outer retinal layer measured by Spectral Domain-Optical Coherence Tomography (SD-OCT); retinal function tested by full-field electroretinogram (ERG) and S-cone ERG. RESULTS: mean TES was worse in RTHβ than controls (p 0.002). CMT was overlapping between the study groups, but directly correlated with SHBG levels in RTHβ. We found a statistically significant reduction in amplitude of the cone (P=0.024) and also of the rod response (p=0.006) in the ERG of RTHβ compared to controls. The response of the L/M-cones measured by a specialized ERG test was lower in RTHβ than controls (P=0.027), while no differences were found in the S-cone response. No correlations were found between serum thyroid hormones (TH) levels, TES or electrophysiological results. Furthermore, no differences were found between patients with maternal or de-novo/paternal inheritance. CONCLUSIONS: We report the first in vivo evidence of functional defects of RPs in RTHβ. These changes occur independently of endogenous TH levels or the prenatal exposure to high or normal maternal TH.