Retinal Photoreceptor Functions Are Compromised in Patients With Resistance to Thyroid Hormone Syndrome (RTHβ)

Context: In animal models, disruption of thyroid hormone (TH) receptor-beta (TR beta) reduces the long/medium wavelength (L/M) and increases the short-wavelength (S) cones. Retinal photoreceptor (RP) functions are unknown in patients with resistance to TH syndrome (RTH beta) with dominant-negative TR beta mutations. Objective: To investigate RP functions in RTH beta. Design, Setting, and Participants: Case-control study involving 27 RTH beta patients and 31 age/sex-matched controls, conducted in two tertiary referral centers in Italy. Main Outcome Measures: Color vision sensitivity assessed by Farnsworth; central macular thickness (CMT) of the outer retinal layer measured by spectral-domain optical coherence tomography; and retinal function tested by full-field electroretinogram (ERG) and S-cone ERG. Results: Color sensitivity was worse in RTH beta patients than controls (P = 0.002). CMT was overlapping between the study groups but directly correlated with sex hormone-binding globuline levels in RTH beta. We found a significant reduction in amplitude of the cone (P = 0.024) and of the rod response (P = 0.006) in the ERG of RTH beta patients compared with controls. The response of the L/M cones measured by a specialized ERG test was lower in RTH beta than controls (P = 0.027), whereas no differences were found in the S-cone response. No correlations were found between TH levels, total error score, or electrophysiological results. Furthermore, no differences were found between patients with maternal or de novo/paternal inheritance. Conclusions: We report, to our knowledge, the first in vivo evidence of functional defects of RP in RTH beta. These changes occur independently of endogenous TH levels or the prenatal exposure to high or normal maternal TH.