Abstract Disclosure: A. Malik: Amgen Inc. S. Bray: Amgen Inc. M. Ochoa-Maya: Amgen Inc. C. Giannopoulou: Amgen Inc. S. Kim: Amgen Inc. H. Patel: Amgen Inc. G.J. Kahaly: Amgen Inc. Introduction: Thyroid Eye Disease (TED) is a debilitating autoimmune disorder which can result in significant changes to vision and physical appearance, negatively affecting patients’ quality of life (QOL). We examined data from the Graves Ophthalmopathy Quality of Life Questionnaire (GO-QOL) in patients with active TED to assess impact on daily activities by age, sex, and history of anxiety and/or depression (Anx-Dep). Method: This post hoc analysis included GO-QOL data at baseline from 3 teprotumumab clinical trials (Phase 2 [NCT01868997], OPTIC [NCT03298867] and OPTIC-J [RCT2031210453]) of moderate-to-severe, active TED patients. GO-QOL scores (visual function [VF] and appearance [AP]) were assessed with higher scores indicating better QOL. Frequency of responses on individual questions were examined for extent of limitation (1=seriously limited, 2=a little limited, 3=not at all limited) in daily activities, appearance, and social interactions. Mean response was calculated for each question with lower scores indicating greater impairment (range 1-3). Responses were assessed by sex and age from all 3 studies, and by Anx-Dep history from Phase 2 and OPTIC; OPTIC-J did not capture Anx-Dep history. Results: Among 225 patients from all 3 studies, 163 (72%) were female, mean (SD) age was 50.7 (12.7) years. At baseline, AP and VF scores were 59.7 and 67.0, respectively. Most common limitations reported in VF were reading (68%) and watching TV (62%). The most commonly reported AP limitations were appearance (96%), self-confidence (67%), and avoidance of photos (64%). Females reported higher impairment than males in both AP scores (55.4 vs 70.9) and VF scores (66.0 vs 69.8). Females had lower mean scores and more impact/concern specifically for masking changes in appearance (1.9 vs 2.5), avoiding photos (1.8 vs 2.4), and effect on self-confidence (1.9 vs 2.3). Younger (<50 yrs) patients had lower AP scores vs older (>65 yrs) patients (56.8 vs 70.3) and lower mean scores for appearing less in photos (1.8 vs 2.4), masking changes in appearance (1.9 vs 2.4) and influence on self-confidence (2.0 vs 2.3); VF scores were 69.6 and 64.4, respectively. Among 171 patients from Ph 2 and OPTIC, 30 (17.5%) reported having Anx-Dep. Patients with Anx-Dep had lower VF scores (57.7 vs 65.8), AP scores (45.3 vs 59.5), and lower mean scores for feeling hindered (1.7 vs 2.2), effect on self-confidence (1.5 vs 2.0), and feeling socially isolated (2.2 vs 2.5) compared to those without Anx-Dep. Conclusion: Female patients, younger individuals, and those with Anx-Dep reported greater QOL impairment. These findings underscore the substantial burden of TED on patients and highlight the importance of recognizing and addressing the psychosocial impact in clinical care. Presentation: Saturday, July 12, 2025