Systematic review of ocular surface treatments in the setting of thyroid eye disease.

Introduction: Approximately 85% of patients with thyroid eye disease experience ocular surface symptoms. Although corneal exposure plays a role in inducing inflammatory changes to the ocular surface, multiple studies reveal more complexity to the abnormal tear film composition and parameters in thyroid eye disease patients including those who do not have proptosis or increased corneal exposure. Currently, a majority of cases of thyroid associated dry eye symptoms are given treatments intended for ocular surface disease arising from different etiologies. Methods: Medline via Ovid, Cochrane CENTRAL, PubMed, and Google Scholar were systematically searched for articles evaluating the efficacy of treatments for dry eye symptoms in patients with thyroid eye disease. Articles were from all geographic regions and dates ranged from inception until October 2023. Results: Seven papers ultimately met inclusion criteria and were included in this review. These papers revealed that multiple topical and non-topical treatment modalities address dry eye symptoms in thyroid eye disease and improve subjective and objective ocular surface parameters. However, due to the few studies that exist and due to disparities in sample size and study design, no overwhelming best practices were identified that could influence clinical practice. Conclusion: This systematic review identifies the current treatments that exist and highlights the clear unmet need for a large population suffering with dry eye symptoms. Ideally, further well-designed investigations into this area would target topical, non-invasive modalities to develop first line options for thyroid eye disease patients.

Percutaneous triamcinolone injection for upper eyelid retraction in thyroid eye disease.

Purpose: To evaluate percutaneous triamcinolone (TA) injection efficacy in treating upper eyelid retraction (UER) for Australian thyroid eye disease (TED) patients. Methods: We conducted a retrospective analysis across 8 years and multiple diverse Australian centres identified UER patients who received TA injections. A single operator administered 40mg/1ml TA through upper eyelid skin. Assessments at 4-6 weeks and subsequent eyelid measurements gauged treatment response and complications. Results: 24 patients and 25 eyelids were included in the study. 91.6% were female, mean age 40.8 ± 10.3 years with mean follow-up of 17.5 months (± 18.5). Pre-treatment MRD1 was 6.2mm ± 1.4, and we observed a mean improvement of 2.2mm from pre-treatment to post-treatment (p<0.001). The mean UER measurement before treatment (defined as MRD1 - 4.0mm) was 3.0mm ± 1.3 (range, 0-6mm). After treatment, the mean UER measurement was -0.1mm. Quality of life (QOL) assessment improved significantly, from pre-treatment score of 4.13 ± 2.4 to post-treatment 8.0 ±1.7 (p<0.001). Conclusions: Percutaneous injection of TA is an effective and safe treatment option for UER in patients with TED. This technique can be performed without upper eyelid eversion, which makes it more tolerable for patients and less complex for the operator compared to the transconjunctival injection approach. Our results show a significant improvement in MRD1 and UER, as well as patient QOL. Moreover, we found a low rate of complications (4.2% induced ptosis) and no cases of raised intraocular pressure. Percutaneous TA injection can greatly reduce the need for eyelid lowering surgery in this patient population.

Refractory sphenoid wing osteomyelitis as a complication of orbital decompression.

Osteomyelitis of the sphenoid wing is a rare clinical entity that can result in significant morbidity due to cranio-orbital infection. This entity has never previously been described as a complication of orbital decompression. An elderly patient developed relapsing orbital cellulitis and cranio-orbital abscesses following orbital decompression. Multiple attempts at incision and drainage with extended antibiotic therapy failed to eliminate the infection. The patient's clinical course was indicative of sphenoid osteomyelitis at the prior decompression site. A combined craniotomy-orbitotomy with debridement of the involved portion of the sphenoid resulted in resolution of the patient's clinical symptoms. Surgeons should be aware of the possibility of this rare infection following any surgery in which bone is structurally modified or removed, including orbital decompression.

Post-marketing Safety Concerns of Teprotumumab: A Real-World Pharmacovigilance Assessment.

PURPOSE: Teprotumumab is the only drug approval by The US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED), which targets the insulin-like growth factor-1 receptor. This study aimed to identify potential safety signals of teprotumumab by analyzing post-marketing safety data from the FDA Adverse Event Reporting System (FAERS) database in 2023. METHODS: The case/non-case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered three or more. RESULTS: Total of 2158 cases were included in the analysis. Main safety signals identified were ear and labyrinth disorders, reproductive system and breast disorders, metabolism and nutrition disorders and gastrointestinal disorders. Specifically, autophony (ROR [95% CI] = 4188.34 [1403.29-12500.8]), eyelid retraction (ROR [95% CI] = 2094.17 [850.69-5155.29]), deafness permanent (ROR [95% CI] = 1552.35 [789.07-3053.98]), deafness bilateral (ROR [95% CI] = 73.12 [41.14-129.97]), inflammatory bowel disease (ROR [95% CI] = 23.26 [13.46-40.19]), hyperglycaemic hyperosmolar nonketotic syndrome (ROR [95% CI] = 17.75 [5.70-55.28]) and amenorrhoea (ROR [95% CI] = 47.98 [36.22-63.54]) showed significant safety signals of teprotumumab. CONCLUSIONS: This study identified ear and labyrinth disorders, reproductive system and breast disorders, as specific safety signals of teprotumumab. Clinicians and pharmacists should be vigilant regarding these AEs. However, available data are currently insufficient, and further pharmacovigilance and surveillance are needed to fully understand this issue.

Superficial ocular vascular changes after orbital decompression in patients with thyroid ophthalmopathy measured by anterior segment OCT angiography; an observational study.

Thyroid eye disease (TED) is a common ophthalmologic manifestation of thyroid dysfunction. Despite various imaging techniques available, there hasn't been a widely adopted method for assessing the anterior segment vasculature in TED patients. Our study aimed to evaluate alterations in ocular surface circulation following orbital decompression surgery in TED patients and investigate factors influencing these changes. Using anterior segment optical coherence tomography-angiography (AS-OCTA), we measured ocular surface vascularity features, including vessel density (VD), vessel diameter index (VDI), and vessel length density (VLD), both before and after decompression surgery, alongside standard ophthalmic examinations. Our AS-OCTA analysis revealed a significant decrease in most of the temporal vasculature measurements six weeks post-surgery (p < 0.05). However, differences in the nasal region were not statistically significant. These findings indicate notable changes in ocular surface circulation following orbital decompression in TED patients, which may have implications for intraocular pressure (IOP) control and ocular surface symptoms management. AS-OCTA holds promise as a tool for evaluating the effectiveness of decompression surgery and assessing the need for further interventions.

Therapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves' orbitopathy.

Interleukin-2-inducible tyrosine kinase (ITK) is a crucial cytoplasmic protein in the T-cell signaling pathway. Here, we aimed to demonstrate the anti-inflammatory effect of the selective IL-2-induced tyrosine kinase inhibitor BMS-509744 (BMS) on Graves' orbitopathy (GO) in an in vitro model. ITK mRNA expression in orbital tissues from GO and normal controls was compared using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Primary cultured orbital fibroblasts from each group were pretreated with BMS and stimulated with interleukin (IL)-1ß to induce inflammatory reaction. ITK mRNA expression was evaluated using western blotting, and inflammatory cytokine production and downstream transcription factor expression were analyzed after pretreatment with BMS. ITK mRNA expression in GO tissues was significantly higher than that in normal control tissues. After stimulation with IL-1ß, ITK phosphorylation significantly increased in both GO orbital and normal control tissues. BMS inhibited IL-1ß-induced IL-8 expression in the GO orbital fibroblasts. BMS pretreatment significantly suppressed NF-κB phosphorylation in both GO and normal controls. The selective ITK inhibitor attenuates proinflammatory cytokine production and proinflammatory transcription factor phosphorylation in in vitro model of GO.

Role of Inositol-Requiring Enzyme 1 and Autophagy in the Pro-Fibrotic Mechanism Underlying Graves' Orbitopathy.

PURPOSE: Orbital fibroblasts play key roles in the pathogenesis of Graves' orbitopathy (GO), and previous findings have shown that endoplasmic reticulum (ER) stress and autophagy also contribute to GO. In this study, we investigated the presently unclear roles of inositol-requiring enzyme 1 (IRE1) and related autophagy processes in the pro-fibrotic mechanism of GO. MATERIALS AND METHODS: Orbital adipose/connective tissues were obtained from eight GO patients and six normal individuals during surgery. GO fibroblasts were transfected with IRE1 small-interfering RNA and treated with bafilomycin A1 (Baf-A1) to evaluate the inhibitory effects of ER stress and autophagy, and protein-expression levels were analyzed through western blotting after stimulation with transforming growth factor (TGF)-ß. RESULTS: TGF-ß stimulation upregulated IRE1 in GO orbital fibroblasts, whereas silencing IRE1 suppressed fibrosis and autophagy responses. Similarly, Baf-A1, an inhibitor of late-phase autophagy, decreased the expression of pro-fibrotic proteins. CONCLUSION: IRE1 mediates autophagy and the pro-fibrotic mechanism of GO, which provides a more comprehensive interpretation of GO pathogenesis and suggests potential therapeutic targets.

Inflammatory Markers in Thyroid Eye Disease: A Meta-Analysis.

Thyroid Eye Disease (TED) is an inflammatory autoimmune condition affecting the eyes, often associated with Graves' disease. Inflammation is important in TED, involving immune cells and orbital tissues. While inflammatory markers have been studied in other diseases, their role in TED is unclear. We included 734 participants from 5 eligible studies investigated associations between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) and TED. Initial analysis found no significant differences in these markers between TED and control groups. However, sensitivity analysis excluding an outlier study revealed significant differences in NLR, PLR, and MLR between groups, suggesting the potential association between these inflammatory markers and TED. More research is needed, but these findings indicate complex TED pathogenesis and that inflammation may offer insights for TED diagnosis and management.

Effect of orbital decompression surgery on the choroidal profile in patients with thyroid eye disease.

This study aimed to investigate the effect of orbital wall decompression surgery and reduction of proptosis on the choroidal vascularity index (CVI) and subfoveal choroidal thickness (SFCT) in patients with thyroid eye disease (TED). Fifty-one eyes from 38 patients with controlled TED and proptosis were enrolled in this study. The majority of the patients (50.9%) had a clinical activity score (CAS) of zero, and none had a CAS greater than 2. The patients underwent a complete baseline ophthalmologic examination, and their choroidal profile alterations were monitored using enhanced depth imaging optical coherence tomography (EDI-OCT) before and during the three months after surgery. Changes in SFCT, luminance area (LA), total choroidal area (TCA), and the choroidal vascularity index (CVI) were measured as the ratio of LA to TCA in EDI-OCT images. The participants had an average age of 46.47 years, and 22 were female (57.9%). The SFCT of the patients exhibited a significant reduction over the follow-up period, decreasing from 388 ± 103 to 355 ± 95 µm in the first month (p < 0.001) and further decreasing to 342 ± 109 µm by the third month compared to baseline (p < 0.001). The CVI exhibited a drop from 0.685 ± 0.037 at baseline to 0.682 ± 0.035 and 0.675 ± 0.030 at 1 and 3 months post-surgery, respectively. However, these changes were not statistically significant, indicating comparable decreases in both LA and TCA. There was a significant correlation between improved proptosis and reduction in SFCT (p < 0.001) but not with CVI (p = 0.171). In conclusion, during the three months of follow-up following orbital wall decompression, CVI did not change, while SFCT reduced significantly. Additionally, SFCT was significantly correlated with proptosis reduction, whereas CVI was not.

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.

Long-Term Efficacy of Teprotumumab in Thyroid Eye Disease: Follow-Up Outcomes in Three Clinical Trials.

Introduction: Thyroid eye disease (TED) is an autoimmune process characterized by extraocular muscle and orbital fat remodeling/expansion resulting in swelling, pain, redness, proptosis, and diplopia. Teprotumumab, an insulin-like growth factor-I receptor inhibitor, demonstrated improvements in TED signs and symptoms in three adequately powered clinical trials of 24 weeks duration. Here we analyze the long-term maintenance of responses with teprotumumab from these trials. Methods: A total of 112 patients who received 7 or 8 infusions of teprotumumab in the Phase 2, Phase 3 (OPTIC study), and OPTIC Extension (OPTIC-X) studies were included in this analysis. Responses, including clinical activity score (CAS ≥2-point improvement), the European Group of Graves' Orbitopathy ophthalmic composite outcome, diplopia (≥1 Gorman grade improvement), proptosis (≥2 mm improvement), Overall (improvement in proptosis + CAS), and disease inactivation (CAS ≤1), were assessed and pooled from study baseline to week 24 (formal study) and up to week 72 (formal follow-up). Graves' Ophthalmopathy quality-of-life (GO-QoL) scores were also assessed. Outcomes included the percentages of observed patient responses from the study baseline. Additional alternative treatments for TED were assessed as a surrogate of persistent benefit from week 24 through week 120 (extended follow-up). Studies differed in the timing of follow-up visits, and data from some visits were unavailable. Results: At week 72, 52/57 (91.2%), 51/57 (89.5%), 35/48 (72.9%), 38/56 (67.9%), and 37/56 (66.1%) of patients were responders for CAS, composite outcome, diplopia, proptosis, and Overall response, respectively. The mean reduction in proptosis was 2.68 mm (SD 1.92, n = 56), mean GO-QoL improvement was 15.22 (SE 2.82, n = 56), and disease inactivation (CAS ≤1) was detected in 40/57 (70.2%). Over 99 weeks following teprotumumab therapy, 19/106 (17.9%) patients reported additional TED therapy during formal and extended follow-up. Conclusion: The long-term response to teprotumumab as observed 51 weeks after therapy was similar to week 24 results in the controlled clinical trials. Inflammatory and ophthalmic composite outcome improvements were seen in 90% of patients with nearly 70% reporting improvement in diplopia and proptosis. Further, 82% of patients in this analysis did not report additional TED treatment (including surgery) over 99 weeks following the final teprotumumab dose.

Immune checkpoints: new insights into the pathogenesis of thyroid eye disease.

Thyroid eye disease (TED) is a disfiguring autoimmune disease characterized by changes in the orbital tissues and is caused by abnormal thyroid function or thyroid-related antibodies. It is the ocular manifestation of Graves' disease. The expression of thyroid-stimulating hormone receptor (TSHR) and the insulin-like growth factor-1 receptor (IGF-1 R) on the cell membrane of orbital fibroblasts (OFs) is responsible for TED pathology. Excessive inflammation is caused when these receptors in the orbit are stimulated by autoantibodies. CD34+ fibrocytes, found in the peripheral blood and orbital tissues of patients with TED, express immune checkpoints (ICs) like MHC II, B7, and PD-L1, indicating their potential role in presenting antigens and regulating the immune response in TED pathogenesis. Immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, it can also lead to the occurrence of TED in some instances, suggesting the abnormality of ICs in TED. This review will examine the overall pathogenic mechanism linked to the immune cells of TED and then discuss the latest research findings on the immunomodulatory role of ICs in the development and pathogenesis of TED. This will offer fresh perspectives on the study of pathogenesis and the identification of potential therapeutic targets.

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.

Orbital decompression surgery among Medicare beneficiaries in the post-teprotumumab era.

KEY POINTS: Utilization of orbital decompressions (ODS) increased (CAGR: +3.2%) from 2000 to 2019. FDA approved teprotumumab in January 2020; ODS utilization decreased (CAGR: -14.9%) from 2019 to 2022. In 2022, total spending was substantially higher for teprotumumab ($325 million) than surgery ($580,000).

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.

Whole-orbit-based multiparametric assessment of disease activity of thyroid eye disease on Dixon MRI.

PURPOSE: This study aimed to explore the diagnostic value of whole-orbit-based multiparametric assessment on Dixon MRI for the evaluation of the thyroid eye disease (TED) activity. METHODS: The retrospective study enrolled patients diagnosed as TED and obtained their axial and coronal Dixon MRI scans. Multiparameters were assessed, including water fraction (WF), fat fraction (FF) of extraocular muscles (EOMs), orbital fat (OF), and lacrimal gland (LG). The thickness of OF and herniation of LG were also measured. Univariable and multivariable logistic regression was applied to construct prediction models based on single or multiple structures. Receiver operating characteristic (ROC) curve analysis was also implemented. RESULTS: Univariable logistic analysis revealed significant differences in water fraction (WF) of the superior rectus (P = 0.018), fat fraction (FF) of the medial rectus (P = 0.029), WF of OF (P = 0.004), and herniation of LG (P = 0.012) between the active and inactive TED phases. Multivariable logistic analysis and corresponding receiver operating characteristic curve (ROC) analysis of each structure attained the area under the curve (AUC) values of 0.774, 0.771, and 0.729 for EOMs, OF, and LG, respectively, while the combination of the four imaging parameters generated a final AUC of 0.909. CONCLUSIONS: Dixon MRI may be used for fine multiparametric assessment of multiple orbital structures. The whole-orbit-based model improves the diagnostic performance of TED activity evaluation.

PAPP-A as a Potential Target in Thyroid Eye Disease.

CONTEXT: Proptosis in Thyroid Eye Disease (TED) can result in facial disfigurement and visual dysfunction. Treatment with Insulin-like growth factor I receptor (IGF-IR) inhibitors has been shown to be effective in reducing proptosis but with side effects. OBJECTIVE: To test the hypothesis that inhibition of IGF-IR indirectly and more selectively with PAPP-A inhibitors attenuates IGF-IR signaling in TED. DESIGN: Informed consent was obtained from TED patients undergoing surgery, and retro-orbital tissue collected for fibroblast isolation and culture. SETTING: Surgeries were performed in Mayo Clinic operating suites. Cell culture was performed in a sterile tissue culture facility. PATIENT SAMPLES: Retro-orbital tissue was collected from 19 TED patients. INTERVENTIONS: Treatment of TED fibroblasts with pro-inflammatory cytokines. Flow separation of CD34- and CD34+ orbital fibroblasts, the latter representing infiltrating fibrocytes into the orbit in TED. MAIN OUTCOME MEASURES: PAPP-A expression and proteolytic activity, IGF-I stimulation of phosphatidylinositol 3 kinase/Akt pathway and inhibition by immuno-neutralizing antibodies against PAPP-A, CD34+ status and associated PAPP-A and IGF-IR expression. RESULTS: Pro-inflammatory cytokines markedly increased PAPP-A expression in TED fibroblasts. IGF-IR expression was not affected by cytokine treatment. Inhibition of PAPP-A's proteolytic activity suppressed IGF-IR activation in orbital fibroblasts from TED patients. TED fibroblasts that were CD34+ represented ∼80% of the cells in culture and accounted for ∼70% of PAPP-A and IGF-IR expressing cells. CONCLUSIONS: These results support a role for PAPP-A in TED pathogenesis and indicate the potential for novel therapeutic targeting of the IGF axis.

Side Effects and Adverse Events After Treatment With Teprotumumab for Thyroid Eye Disease: A Retrospective Observational Case Series.

As the use of teprotumumab for thyroid eye disease (TED) becomes more prolific, there remains a scarcity of literature regarding the associated side effects and adverse events of teprotumumab use. The authors present a single-center retrospective, observational case review of TED patients who received at least a single dose of teprotumumab infusion at the oculofacial plastic surgery service between February 2020 and July 2023. The most predominant recollected side effects were fatigue, brittle nails, dry eye symptoms, hair loss, muscle spasms, and dry mouth. Significant adverse events were limited to two cases of a blood clot and a single case of pulmonary embolism. This is the first retrospective study of patient-reported side effects and adverse events experienced by a cohort of teprotumumab users.

A Chinese survey of clinical practice on the management of thyroid eye disease.

Objective: The management of thyroid eye disease (TED) has undergone significant changes for decades. The study sought to investigate current clinical practice on the management of TED in China. Methods: An online questionnaire survey was conducted from April to May 2023. The questionnaire involved diagnostic criteria for TED, multidisciplinary treatment (MDT) collaboration, and treatment preference for mild, moderate, and severe TED. Results: A total of 289 questionnaires were collected, with 165 from endocrinologists and 124 from ophthalmologists. Only 36.7% of participants claimed there was an MDT clinical pattern for TED in their institutions. The coverage of biological agents was around 10% or lower. These were distinctly lower than in Western countries. About 62.6% of participants believed the incidence of TED has increased in recent years. Imaging techniques were used widely to assist in the diagnosis of TED. However, there was still controversy regarding the definition of proptosis in the Chinese population. Most doctors managed risk factors and provided orbital supportive treatments of artificial tears and glasses. For mild active TED, endocrinologists (39.4%) were inclined to recommend therapy for hyperthyroidism alone, while ophthalmologists (43.6%) preferred orbital corticosteroid injections. Currently, the most widely used treatment for moderate to severe active TED was high-dose intravenous corticosteroid (94.8%), while orbital radiotherapy combined with immunosuppressive agents was the most recognized second-line therapy (43.6%). Conclusion: The study documented the consistency and differences between current clinical practices in the management of TED in China and the recently updated guidelines. There was a remarkable difference between ophthalmology and endocrinology departments, warranting management optimization.

Teprotumumab improves light sensitivity in patients with thyroid eye disease.

BACKGROUND: Teprotumumab, a novel IGF-1R antibody, has been shown to significantly reduce the signs of acute and chronic Thyroid Eye Disease (TED). Light sensitivity is a reported symptom in patients with TED. There is a lack of a prospective study that has explored the effects on light sensitivity in a large cohort of patients with acute and chronic TED following treatment with teprotumumab. METHODS: Consecutive patients who were diagnosed with TED and reported light sensitivity at baseline were considered for study eligibility. All patients had measurements of Visual Light Sensitivity Questionnaire-8 (VLSQ-8), proptosis, clinical activity score (CAS), and MRD1 (distance between the upper eyelid margin and corneal reflex, mm) and MRD2 (distance between the lower eyelid margin and corneal reflex, mm) before and after treatment. RESULTS: Ninety patients (41 acute, 49 chronic) met the inclusion criteria. The mean (SD) age was 47.3 (14.3). Eighty-six (95.6%) patients completed all 8 infusions. There was a significant reduction in the total score and across all categories of the VLSQ-8 (p <  0.01 for all). Seventy-two (80%) patients had a clinically significant improvement (≥2 reduction) in at least one category. There was no significant difference in the total VLSQ-8 score between the acute and chronic group (p = 0.8). CONCLUSION: Teprotumumab improves light sensitivity in patients with acute and chronic TED. The results of this study highlight that the improvements in light sensitivity following treatment are not directly related to the mechanical changes in TED, suggesting another underlying mechanism is potentially involved.