Bayesian network analysis of drug treatment strategies for thyroid associated ophthalmopathy.

BACKGROUND: The first line treatment for moderate to severe active thyroid associated ophthalmopathy is glucocorticoid pulse therapy, but for patients with contraindications to hormone therapy or hormone resistance, it is urgent to find a suitable treatment plan. AIMS: To find a reliable alternative to hormone pulse therapy for thyroid associated ophthalmopathy by comparing the efficacy with first-line treatment regimens. METHODS: Search PubMed, Ovid, Web of science, Cochrane library, and Clinical Trials.gov for randomized controlled trials on the treatment of thyroid associated ophthalmopathy published as of July 7, 2024. Quality evaluation and Bayesian network analysis were conducted using RevMan 5.3 software, STATA15.0 software, and ADDIS 1.16.8 software. RESULTS: A total of 666 patients were included in 11 studies and 8 interventions. Network analysis showed that the three interventions of mycophenolate mofetil combined with glucocorticoids, Teprotumumab and 99Tc-MDP were superior to glucocorticoid pulse therapy in improving clinical activity scores and proptosis. The regimen of glucocorticoids combined with statins can improve the quality of life score and diplopia score of patients. Neither methotrexate combined with glucocorticoids nor rituximab alone showed additional advantages when compared with glucocorticoid pulse therapy. CONCLUSION: Mycophenolate mofetil combined with glucocorticoid therapy is very beneficial for moderate to severe active thyroid associated ophthalmopathy. Mycophenolate mofetil may be a good choice when patients have contraindications to hormone use or hormone resistance. Teprotumumab is very promising and may be able to avoid patients undergoing orbital decompression surgery. The durability and safety of its long-term efficacy need to be further observed.

Teprotumumab for Thyroid Eye Disease-related Strabismus.

PURPOSE: To assess and quantify teprotumumab's effect on thyroid eye disease-related strabismus by change in measured horizontal and vertical deviations and change in extraocular motility. METHODS: We reviewed a series of patients with thyroid eye disease-related strabismus treated with teprotumumab. Exclusion criteria included age under 18 years, strabismus of alternate etiology, or thyroid eye disease-related reconstructive surgery during the treatment course. Primary outcomes were absolute (prism diopters) and relative (%) differences in horizontal and vertical deviations in primary position at distance, as well as change in ductions of the more affected eye. Secondary outcomes included incidence and timing of strabismus surgery postteprotumumab. RESULTS: Thirty-one patients were included, with mean age 63 years and thyroid eye disease duration 10 months. After teprotumumab, there was 6 prism diopters (39%) mean reduction in vertical deviation ( p < 0.001), without significant change in mean horizontal deviation ( p = 0.75). Supraduction, abduction, adduction, and infraduction significantly improved in the more restricted eye ( p < 0.01, p < 0.01, p = 0.04, and p = 0.01, respectively). Thirty-five percent of patients underwent strabismus surgery posttreatment, at an average 10 months after last infusion. CONCLUSIONS: Teprotumumab produced a statistically significant reduction in vertical but not horizontal strabismus angles in primary position at distance. Extraocular motility in all 4 ductions also improved. A substantial minority of patients still required strabismus surgery following teprotumumab.

Determinants of clinical outcome in patients with moderate/severe Graves' orbitopathy undergoing treatment with parenteral glucocorticoids: a retrospective study.

Background: Graves' orbitopathy (GO) occurs in approximately 25-40% of patients with Graves' disease (GD). High levels of anti-thyrotropin receptor antibodies (TRAbs), smoking habit, sex, older age, longer duration and amount of hyperthyroidism or hypothyroidism are well-recognized risk factors for the occurrence, severity and clinical course of GO. Oxidative stress (OX) has recently been shown to play a role in the pathogenesis of GO, and several clinical conditions related to OX have been investigated regarding the presentation and severity of GO. Aim: We aimed to evaluate the impact of clinical conditions related to oxidative stress on the outcome of intravenous glucocorticoid (ivGCs) therapy in a cohort of patients with active moderate to severe GO (AMS-GOs) treated at a single institution. Methods: We retrospectively studied a series of patients with AMS-GOs who were treated with ivGCs from January 2013 to May 2022. GO clinical evaluation was performed at baseline and at 6 (W6), 12 (W12) and 24 (W24) weeks after starting ivGCs by the seven-point clinical activity score (CAS) alone and by overall clinical criteria (CI) according to the European Group of Graves' Ophthalmopathy (EUGOGO). Total cholesterol and calculated LDL cholesterol (LDLc), triglyceride, body mass index (BMI), diabetes status, history of hypertension (HoH), smoking status, age and sex were used as covariates for the clinical outcome of GO to ivGCs. Results and conclusions: LDLc and HoH negatively and independently modulated the response of AMS-GOs to ivGCs. Notably, slightly elevated LDLc levels (> 130 mg/dl) reduced the response of orbital soft tissue to ivGCs, whereas more elevated LDLc levels (from 175 mg/dl to 190 mg/dl) and HoH were associated with poorer clinical response of eye motility and proptosis.

Epidemiology of thyroid-stimulating immunoglobulin in recent-onset symptomatic thyroid eye disease.

Purpose: This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients. Methods: A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI. Results: A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60-0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP. Conclusion: TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.

A Review of Novel Medical Treatments for Thyroid Eye Disease.

Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves disease. There has been no effective medication to prevent proptosis in thyroid eye disease until 2020 when the anti-insulin-like growth factor 1 receptor (anti-IGF-1R) antibody, Teprotumumab, was approved by the US Food and Drug Administration, sparking increased interest in immune-based drug development. This study aims to review the newly developed drug therapy as well as conventional treatment for TED. Treatment of TED has traditionally been high-dose steroids and orbital radiotherapy, but recently there has been a paradigm shift in the treatment of TED in the United States with the introduction of the therapeutic agent teprotumumab, which dramatically reduces proptosis. However, concerns remain about the development of hearing impairment as a potentially fatal complication and long-term safety. Recently, several clinical trials are underway to assess the efficacy and safety of novel drugs targeting mammalian target of rapamycin complex 1, interleukin-6, fragment crystallizable receptor, and IGF-1R in treating TED. With the explosive increase in interest from academia and pharmaceutical companies in TED, there is anticipation for the development of drugs that are equivalent or superior to teprotumumab while being safer.

Cyclosporin A inhibits PDGF-BB induced hyaluronan synthesis in orbital fibroblasts.

Orbital connective tissue changes are contributors to the pathogenesis in thyroid eye disease (TED). Activated fibroblasts respond to immune stimuli with proliferation and increased hyaluronan (HA) production. Cyclosporin A (CsA) was reported to be beneficial in the treatment of TED. PDGF isoforms are increased in orbital tissue of TED patients and enhance HA production. We aimed to study the effect of CsA on HA production and hyaluronan synthase (HAS1, 2 and 3) and hyaluronidase (HYAL1 and 2) mRNA expressions in orbital fibroblasts (OFs). Measurements were performed in the presence or absence of CsA (10 µM) in unstimulated or PDGF-BB (10 ng/ml) stimulated OFs. The HA production of TED OFs (n = 7) and NON-TED OFs (n = 6) were measured by ELISA. The levels of mRNA expressions were examined using RT-PCR. The proliferation rate and metabolic activity were measured by BrdU incorporation and MTT assays, respectively. Treatment with CsA resulted in an average 42% decrease in HA production of OFs (p < 0.0001). CsA decreased the expression levels of HAS2, HAS3 and HYAL2 (p = 0.005, p = 0.005 and p = 0.002, respectively.) PDGF-BB increased HA production (p < 0.001) and HAS2 expression (p = 0.004). CsA could reduce the PDGF-BB-stimulated HA production (p < 0.001) and HAS2 expression (p = 0.005) below the untreated level. In addition, CsA treatment caused a decrease in proliferation potential (p = 0.002) and metabolic activity (p < 0.0001). These findings point to the fact that CsA affects HA metabolism via HAS2, HAS3 and HYAL2 inhibition in OFs. In addition to its well characterized immunosuppressant properties, CsA's beneficial effect in TED may be related to its direct inhibitory effect on basal and growth factor stimulated HA production.

Central Retinal Artery Occlusion after Peribulbar Injection of Triamcinolone Acetonide in Thyroid-associated Ophthalmopathy.

Central retinal artery occlusion (CRAO) is a form of acute ocular ischemic syndrome that causes visual loss. Timely treatment is of great importance for visual recovery, but the prognosis is usually poor. By analyzing the pathogenesis, diagnosis, and treatment process of a CRAO case after peribulbar injection of triamcinolone acetonide in thyroid-associated ophthalmopathy (TAO), this study aims to investigate the association of CRAO with hemodynamics and orbital pressure, thereby providing references in safety improvement of diagnosis and treatment on TAO.

Tocilizumab use for optic nerve compression in thyroid eye disease: a prospective longitudinal cohort.

PURPOSE: To assess the effectiveness of tocilizumab in reverting the signs and symptoms of dysthyroid optic neuropathy (DON) in thyroid eye disease and the need for emergency orbital decompression. The secondary outcomes are to identify the optimal number of tocilizumab cycles to achieve the primary outcome, to analyze the association between thyroid stimulating immunoglobulin (TSI), clinical activity score (CAS) and proptosis in response to the treatment and the need for rehabilitative orbital decompression. METHODS: Prospective longitudinal cohort study that included 13 patients who had unilateral or bilateral dysthyroid optic neuropathy (DON) due to severe and progressive sight-threatening thyroid eye disease based on the CAS system. Patients were seen in this facility starting from July 2017, and all had received intravenous tocilizumab. RESULTS: Initial visual acuity mean was 0.52 ± 0.38 and the final were 0.93 ± 0.11 with a mean difference of 0.41 and P < 0.00245. The mean CAS prior to the initiation of the treatment was 7.92 ± 0.66 and the final was 2.85 ± 1.03 with mean difference of 5.07 and P < 0.00001. Initial mean proptosis was 24.85 ± 2.31 and the final was 21.78 ± 2.18 with a mean difference of 3.07 and P < 0.000497. No emergency orbital decompression was performed. TSI was high initially in all cases with a wide range of 2.4 to 40 IU/L and with a mean of 10.70 ± 13.40. The final TSI mean was 2.90 ± 3.90 with a mean difference of 7.81 and significant P value (P < 0.0272). CONCLUSION: Tocilizumab use in optic nerve compression showed promising results as it can be the primary or an alternative treatment option.

Comparison of macular and optic disc vessel density in thyroid orbitopathy: a comparative octa study.

PURPOSE: To determine the microvascular and structural changes in the peripapillary and macular areas observed in patients with active thyroid orbitopathy(TO) before and after steroid treatment and compare with inactive TO and the control group by optical coherence tomography angiography (OCTA). MATERIAL AND METHOD: This cross-sectional study included 34 eyes of 17 active TO patients, 108 eyes of 54 inactive TO patients, and 60 eyes of 30 healthy controls. Central macular thickness (CMT), ganglion cell layer-inner plexiform layer (GCL-IPL) thickness, central choroidal thickness (CCT), retinal nerve fiber layer (RNFL) thickness, choroidal thickness in the peripapillary region, superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris vessel densities were determined by OCTA in before and after 12-week steroid treatment of active TO cases, inactive TO and control groups. RESULTS: Between the three groups in macula OCTA, a statistically significant difference was observed in the inferior and nasal quadrants in SCP (all p = 0.01) and only in the temporal quadrant choriocapillaris (p = 0.005). In peripapillary OCTA, a statistically significant difference was found only in the central choriocapillaris (p = 0.03). In the comparison of the active group before and after treatment, there was a statistically significant decrease in CMT and CCT; a statistically significant increase was observed in GCL-IPL (all p < 0.01). There was a statistically significant decrease in SCP and DCP only in the central (all p < 0.01). There was a statistically significant increase was found in the lower quadrant macular SCP vessel density and mean macular DCP in post-treatment measurements (p = 0.01 and p = 0.03, respectively). Peripapillary SCP and DCP vessel density was increased after treatment (p < 0.01). CONCLUSION: Active TO group had lower vessel density than inactive group and after treatment, vessel density was increased. Non-invasive quantitative analysis of retinal and optic disc perfusion using OCTA could be useful in early treatment before complications occur and monitoring patients with TO.

Efficacy of tocilizumab in patients with moderate-to-severe corticosteroid-resistant thyroid eye disease: a prospective study.

PURPOSE: To evaluate the clinical outcomes of intravenous tocilizumab (TCZ) injection in patients with moderate-to-severe active thyroid eye disease (TED). METHODS: Patients with active and moderate-to-severe TED who did not respond to conventional therapies were treated with TCZ from June 2019 to January 2021. The medical records of the patients were evaluated before the treatment. We analyzed patient demographics, including the duration of Graves' disease and TED, and assessed subjective symptoms, such as diplopia and ocular movement, clinical activity score (CAS), modified NOSPECS score, and exophthalmos before treatment and at 4, 8, 12, and 16 weeks after the first drug injection. Blood tests, including TSH Rc Ab and TS Ab, were performed before treatment and 24 weeks after the first injection. And orbital computed tomography (CT) was performed and Barrett's Index was calculated at baseline and after completion of all injections. RESULTS: Nineteen completed the scheduled treatment. There were no significant side effects, other than herpes zoster in one case and headache and dermatitis in another. Clinical symptoms before and 16 weeks after the treatment showed mean CAS decreased by 2.4 points, mean modified NOSPECS score decreased by 3.7 points, and mean exophthalmos decreased by 0.4 mm. Diplopia and extraocular muscle limitation improved in ten and remained stationary in five of the 15 patients, who presented with extraocular motility abnormalities. Six of 11 patients who underwent orbit CT showed improvement in muscle size. The mean TSH Rc Ab decreased by 7.5 IU/L and TS-Ab decreased by 162.9%. CONCLUSION: TCZ can treat active moderate-to-severe TED, showing high drug compliance and reasonable response to inflammation and extraocular motility abnormality.

Thyroid stimulating immunoglobulin concentration is associated with disease activity and predicts response to treatment with intravenous methylprednisolone in patients with Graves' orbitopathy.

Background: Thyroid stimulating immunoglobulins (TSI) play a central role in the pathogenesis of Graves' orbitopathy (GO), while soluble interleukin-2 receptor (sIL-2R) is a marker for T-cell activity. We investigated TSI and sIL-2R levels in relation to thyroid function, disease activity and severity and response to treatment with intravenous methylprednisolone (IVMP) in patients with GO. Methods: TSI (bridge-based TSI binding assay), sIL-2R, TSH and fT4 levels were measured in biobank serum samples from 111 GO patients (37 male, 74 female; mean age 49.2 years old) and 25 healthy controls (5 male, 20 female; mean age 39.8 years old). Clinical characteristics and response to treatment were retrospectively retrieved from patient files. Results: Higher sIL-2R levels were observed in GO patients compared to controls (p < 0.001). sIL-2R correlated with fT4 (r = 0.26), TSH (r = -0.40) and TSI (r = 0.21). TSI and sIL-2R concentrations were higher in patients with active compared to inactive GO (p < 0.001 and p < 0.05, respectively). Both TSI and sIL-2R correlated with total clinical activity score (CAS; r = 0.33 and r = 0.28, respectively) and with several individual CAS items. Cut-off levels for predicting active GO were 2.62 IU/L for TSI (AUC = 0.71, sensitivity 69%, specificity 69%) and 428 IU/mL for sIL-2R (AUC = 0.64, sensitivity 62%, specificity 62%). In multivariate testing higher TSI (p < 0.01), higher age (p < 0.001) and longer disease duration (p < 0.01) were associated with disease activity. TSI levels were higher in patients with a poor IVMP response (p = 0.048), while sIL-2R levels did not differ between responders and non-responders. TSI cut-off for predicting IVMP response was 19.4 IU/L (AUC = 0.69, sensitivity 50%, specificity 91%). In multivariate analysis TSI was the only independent predictor of response to IVMP (p < 0.05). Conclusions: High TSI levels are associated with active disease (cut-off 2.62 IU/L) and predict poor response to IVMP treatment (cut-off 19.4 IU/L) in GO. While sIL-2R correlates with disease activity, it is also related to thyroid function, making it less useful as an additional biomarker in GO.

Change in upper eyelid position after teprotumumab treatment for thyroid eye disease.

PURPOSE: Despite the high prevalence, treatment challenges, and significant impact of eyelid retraction on vision and quality of life among patients with thyroid eye disease, the effects of teprotumumab on eyelid retraction are not fully understood. This study evaluated change in upper eyelid position after teprotumumab. METHODS: A retrospective study of all patients who completed eight teprotumumab infusions at one institution from January 1 2020 to December 31 2022. Primary outcome was change in upper eyelid position immediately after treatment and at most recent follow-up compared to pre-treatment. RESULTS: Among 234 eyes of 118 patients, average margin reflex distance-1 (MRD1) pre-treatment was 5.25 mm (range 0-10.0, SD 1.75), 4.66 mm (1.0-9.0, SD 1.32) immediately post-treatment (p < 0.001), and 4.50 mm (0-10.0, SD 1.52) at most recent follow-up (mean follow-up duration 10.60 months). In total, 136 (58.12%) eyes of 88 patients had MRD1 reduction immediately post-treatment, averaging 1.49 mm (0.5-5.0 mm, SD 0.97). Every 1-mm increase in pre-treatment MRD1 increased the odds of MRD1 reduction by 15.03% (CI 10.52-19.72, p < 0.001) and increased the reduction amount by 0.48 mm (CI 0.39-0.57, p < 0.001). Of 154 eyes of 78 patients with most recent follow-up, 107 (69.48%) eyes had stable or further improved retraction at most recent follow-up compared to immediately post-treatment. CONCLUSIONS: This study found a modest but significant reduction in MRD1 in approximately 60% of eyes, independent of proptosis change, which was sustained by most patients over longer-term follow-up. Higher pre-treatment MRD1 corresponded with greater improvement. These results suggest an overall mild benefit of teprotumumab for upper eyelid retraction.

Differential diagnosis of thyroid orbitopathy - diseases mimicking the presentation or activity of thyroid orbitopathy.

Thyroid orbitopathy (TO) is the most common cause of orbital tissue inflammation, accounting for about 60% of all orbital inflammations. The inflammatory activity and severity of TO should be diagnosed based on personal experience and according to standard diagnostic criteria. Magnetic resonance imaging (MRI) of the orbit is used not only to identify swelling and to differentiate inflammatory active from non-active TO, but also to exclude other pathologies, such as orbital tumours or vascular lesions. However, a group of diseases can mimic the clinical manifestations of TO, leading to serious diagnostic difficulties, especially when the patient has previously been diagnosed with a thyroid disorder. Diagnostic problems can be presented by cases of unilateral TO, unilateral or bilateral TO in patients with no previous or concomitant symptoms of thyroid disorders, lack of symptoms of eyelid retraction, divergent strabismus, diplopia as the only symptom of the disease, and history of increasing diplopia at the end of the day. The lack of visible efficacy of ongoing immunosuppressive treatment should also raise caution and lead to a differential diagnosis of TO. Differential diagnosis of TO and evaluation of its activity includes conditions leading to redness and/or swelling of the conjunctiva and/or eyelids, and other causes of ocular motility disorders and eye-setting disorders. In this paper, the authors review the most common diseases that can mimic TO or falsify the assessment of inflammatory activity of TO.

Long-term remission of corticosteroid-resistant Graves' orbitopathy after therapy with tocilizumab.

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[Research status of potential therapeutic targets for thyroid-associated ophthalmopathy].

Thyroid-associated ophthalmopathy (TAO) is an autoimmune eye disease that affects visual function and appearance, involving pathological remodeling processes of orbital tissue such as inflammatory reaction, oxidative stress, lipogenesis, and fibrosis. Current clinical first-line treatment options cannot be effective for all patients. This article summarizes the research on potential therapeutic targets of TAO at home and abroad in recent years, including receptor protein targets, immune cell targets, fat suppression targets, anti-fibrosis targets, transcription factor targets, and metabolic regulatory enzyme targets. Both non-natural compounds and natural compounds are introduced, with a view to providing clinical researchers with reference and ideas in the treatment of TAO and promoting the clinical application of new therapeutic drugs.

Late orbital radiotherapy combined with intravenous methylprednisolone in the management of long-lasting active graves' orbitopathy: a case report and literature review.

PURPOSE: To present a case and review the literature on Orbital Radiotherapy (OR) combined with intravenous methylprednisolone, focusing on its late application in patients with long-lasting active Graves' Orbitopathy (GO). Additionally, we suggest emerging perspective for future research in this context. METHOD: Relevant literature (randomized controlled studies, retrospective studies and reviews) was explored on PubMed from January 1973 to January 2024, searching "orbital radiotherapy" & "Graves disease". RESULTS: OR is a well-established second-line treatment for moderate-to-severe active GO, providing response rates comparable to glucocorticoids. Its anti-inflammatory effect makes OR particularly suitable for early active GO, and when combined with glucocorticoids, outcomes are synergistically improved. The emergence of the new Volumetric Modulated Arc Image-Guided Radiation Therapy (VMAT-IGRT) technique enables precise radiation delivery to the target, significantly reducing associated toxicity. This technological advancement enhances the feasibility of radiotherapy in benign diseases like GO. A retrospective study indicated that late OR in patients with long-lasting active GO may improve diplopia and visual acuity, decreasing disease activity. Our case report supports this conclusion. CONCLUSIONS: This report and literature review underscores the importance of considering late OR combined with intravenous methylprednisolone as a viable treatment option for GO patients with prolonged disease activity, emphasizing the crucial role of personalized therapy in managing GO. However, further investigations are warranted to validate this approach in cases of long-lasting active GO.

Bridging and Validation of the Specific Graves Ophthalmopathy Quality of Life Questionnaire With Health State Utility Values.

OBJECTIVE: In thyroid eye disease (TED), inflammation and expansion of orbital muscle and periorbital fat result in diplopia and proptosis, severely impacting patient quality of life (QOL). The reported health state utility (HSU) scores, which are QOL measures, allow quantification of TED impact and improvement with therapies; however, no current QOL instrument has been validated with HSU scores for TED. Here, we used the disease-specific Graves Ophthalmopathy Quality of Life (GO-QOL) questionnaire and HSU scores to validate QOL impact. METHODS: The GO-QOL scores from patients in 2 randomized, masked, placebo-controlled teprotumumab trials (N=171) were compared with 6 HSU values based on severity of proptosis/diplopia in those studies. Patient GO-QOL and HSU scores were compared at baseline and after 6-month treatment via regression analyses. GO-QOL and HSU scores were correlated for validation and quantification of QOL impact by severity state and to estimate quality-adjusted life year improvement. RESULTS: GO-QOL scores were correlated with TED severity, indicating that worse severity was associated with lower (worse) GO-QOL scores. Less severe health states were represented by higher (better) GO-QOL scores. Importantly, GO-QOL scores were positively correlated with utility scores of the 6 health states, allowing for conversion of the GO-QOL scores to utility scores. A positive (improved) 0.013 utility change was found for each 1-point (positive) improvement in GO-QOL score produced by teprotumumab versus placebo. CONCLUSION: Patients with moderate-to-severe active TED health states demonstrate increasing TED severity associated with declining utility values and worsening GO-QOL scores. These results indicate that the GO-QOL scores can be used to bridge to the HSU scores for benefit quantification.

Teprotumumab for Thyroid Eye Disease-related Strabismus.

PURPOSE: To assess and quantify teprotumumab's effect on thyroid eye disease-related strabismus by change in measured horizontal and vertical deviations and change in extraocular motility. METHODS: We reviewed a series of patients with thyroid eye disease-related strabismus treated with teprotumumab. Exclusion criteria included age under 18 years, strabismus of alternate etiology, or thyroid eye disease-related reconstructive surgery during the treatment course. Primary outcomes were absolute (prism diopters) and relative (%) differences in horizontal and vertical deviations in primary position at distance, as well as change in ductions of the more affected eye. Secondary outcomes included incidence and timing of strabismus surgery postteprotumumab. RESULTS: Thirty-one patients were included, with mean age 63 years and thyroid eye disease duration 10 months. After teprotumumab, there was 6 prism diopters (39%) mean reduction in vertical deviation ( p < 0.001), without significant change in mean horizontal deviation ( p = 0.75). Supraduction, abduction, adduction, and infraduction significantly improved in the more restricted eye ( p < 0.01, p < 0.01, p = 0.04, and p = 0.01, respectively). Thirty-five percent of patients underwent strabismus surgery posttreatment, at an average 10 months after last infusion. CONCLUSIONS: Teprotumumab produced a statistically significant reduction in vertical but not horizontal strabismus angles in primary position at distance. Extraocular motility in all 4 ductions also improved. A substantial minority of patients still required strabismus surgery following teprotumumab.

Selenium supplementation in inactive moderate to severe Graves' orbitopathy patients: a randomized controlled trial.

PURPOSE: This study was designed to evaluate the effect of selenium supplementation in inactive moderate-severe Graves' orbitopathy (GO) patients. METHODS: This study was a single-center, placebo-controlled, double-masked, randomized trial. Inactive moderate-severe GO participants were randomized to receive six months of 200 micrograms/day of selenium supplementation or placebo. Thorough eye exams, clinical activity score (CAS), Graves' Ophthalmopathy quality of life questionnaire (GO-QOL), and serum selenium level were evaluated at baseline and 6 months after the interventions. The chi-squared or Fisher's exact test was used to compare categorical variables. The t-test and the paired t-test were used to compare continuous variables between two independent samples and two dependent samples, respectively. RESULTS: A total of 25 participants were enrolled, 13 in the selenium group and 12 in the placebo group. Both groups had adequate baseline serum selenium levels at 98.96 ± 15.63 mcg/L and 102.55 ± 17.71 mcg/L, respectively. After 6 months of intervention, the selenium group showed a greater improvement in palpebral aperture (mean difference: -1.4 ± 1.7 mm, p = .04) compared to the placebo group (-0.3 ± 2.7 mm). Notably, 5(41.67%) people in the placebo group developed larger palpebral apertures. Proptosis, ocular motility, and soft tissue signs did not change significantly. GO-QOL and CAS score improvement showed no statistically significant difference between both groups. Minor adverse effects were observed. CONCLUSIONS: Selenium supplementation has a positive effect on eyelid aperture even in inactive moderate-to-severe GO patients with a sufficient baseline selenium level.