Active Thyroid Eye Disease Research Articles

Radiologic imaging shows variable accuracy in diagnosing orbital inflammatory disease and assessing its activity

Radiologic orbital imaging provides important information in the diagnosis and management of orbital inflammation. However, the diagnostic value of orbital imaging is not well elucidated. This study aimed to investigate the diagnostic accuracy of orbital imaging to diagnose orbital inflammatory diseases and its ability to detect active inflammation. We collected 75 scans of 52 patients (49 computed tomography (CT) scans; 26 magnetic resonance (MR) imaging scans). Clinical diagnoses included thyroid eye disease (TED) (41 scans, 31 patients), non-specific orbital inflammation (NSOI) (22 scans, 14 patients), sarcoidosis (4 scans, 3 patients), IgG4-related ophthalmic disease (IgG4-ROD) (5 scans, 3 patients), and granulomatosis with polyangiitis (GPA) (3 scans, 1 patient). Two experienced neuroradiologists interpreted the scans, offered a most likely diagnosis, and assessed the activity of inflammation, blinded to clinical findings. The accuracy rate of radiological diagnosis compared to each clinical diagnosis was evaluated. Sensitivity and specificity in detecting active inflammation were analyzed for TED and NSOI. The accuracy rate of radiologic diagnosis was 80.0% for IgG4-ROD, 77.3% for NSOI, and 73.2% for TED. Orbital imaging could not diagnose sarcoidosis. Orbital CT had a sensitivity of 50.0% and a specificity of 75.0% to predict active TED using clinical assessment as the gold standard. The sensitivity/specificity of orbital MR was 83.3/16.7% for the detection of active NSOI. In conclusion, orbital imaging is accurate for the diagnosis of IgG4, NSOI, and TED. Further studies with a large number of cases are needed to confirm this finding, especially with regard to uncommon diseases. Orbital CT showed moderate sensitivity and good specificity for identifying active TED.

Retinal vascularity, nerve fiber, and ganglion cell layer thickness in thyroid eye disease on optical coherence tomography angiography

ABSTRACT Purpose To compare the retinal vascularity, peripapillary vascularity, nerve fiber layer thickness and ganglion cell layer thickness between active, inactive thyroid eye disease (TED) and healthy eyes. Methods Retrospective comparative cross-sectional cohort study. Patients with TED, active and inactive on the VISA score, and healthy eyes were included. All patients underwent optical coherence tomography angiography with detailed demographic and clinical data capture. Using automated software, retinal and peripapillary vascularity index, nerve fiber layer thickness, and ganglion cell layer thickness were calculated and were compared between the groups. Results Twenty-four eyes with active TED, 102 eyes with inactive TED and 52 healthy eyes were included. Independent sample t test was used to compare parametric data and Mann-Whitney test to compare non-parametric data. The age and gender were comparable across groups. The peripapillary vascularity index (26.82 ± 4.13 versus 34.92 ± 5.08, p = .002) and the macular vascularity index (20.32 ± 2.5 versus 31.21 ± 3.89, p < .0001) were reduced in active TED eyes versus inactive eyes. Macular vascularity index was comparable in the inactive versus the healthy eyes. The RNFL thickness was increased in the active TED eyes versus the inactive eyes (45.11 ± 18.3 versus 35.55 ± 7, p = .03) and active versus healthy eyes (45.11 ± 18.3 versus 36.28 ± 7.89, p = .03). Ganglion cell layer thickness between all three groups was comparable. Conclusion Decrease in peripapillary and macular vascular density and increase in RNFL thickness are seen in active TED compared to inactive TED and healthy eyes. In disease inactivity, these parameters are comparable to healthy eyes.

Considerations for Use of Immune Checkpoint Inhibitors in Cancer Therapy for Patients with Co-Existing Thyroid Eye Disease.

Immune checkpoint inhibitors (ICIs) have revolutionised the field of oncology. While most ICIs are well-tolerated, severe and fatal immune-related adverse events (irAEs) have been documented, likely related to the strengthened immunity harnessed by ICIs against tumours. Endocrinopathies are some of the most common irAEs, with both hypothyroidism and hyperthyroidism encountered after ICI use. As such, patients with pre-existing autoimmune conditions, such as Graves’ disease (GD) with clinically active thyroid eye disease (TED), are excluded from most clinical trials studying ICIs due to concerns of exacerbating pre-existing autoimmune conditions or of increasing the potential for irAE development. The limited information currently available on the safety and efficacy of ICIs in this population poses a clinical challenge for oncologists. The objective of this commentary is to highlight these challenges and provide treatment recommendations pertaining to two specific cohorts of patients with GD, namely GD patients with minimal eye complications and GD patients with previous TED who underwent radiotherapy, surgery or pulse methylprednisolone and whose disease is now quiescent, and to patients with subclinical autoimmune thyroid disease.

Teprotumumab for the treatment of active thyroid eye disease

Teprotumumab, an IGF-1R monoclonal antibody, showed promising results for the treatment of Graves’ orbitopathy in a first phase 2 study reported in 2017 [1]. Here, this randomized double-masked, placebo controlled phase 3 multicenter study confirms those initial promising results in patients with moderate-to severe Graves’ eye disease: The primary outcome of proptosis reduction by ≥2 mm after 24 weeks was reached by 83% on teprotumumab vs. 10% of controls. Also, all secondary outcomes, including objective measures of thyroid eye disease activity and subjective quality of life, were better in the teprotumumab group with clinically relevant differences vs. placebo. Adverse events were mostly mild-to-moderate, however one patient had to stop treatment due to infusion-related reaction.

OR18-01 Effect of Teprotumumab on Proptosis Reduction Across Various Demographic Sub-Groups

Introduction: Teprotumumab, an insulin-like growth factor 1 receptor inhibitory monoclonal antibody, was recently shown to significantly reduce proptosis in patients with active, moderate-to-severe thyroid eye disease (TED) in phase 2 and phase 3 clinical trials.1,2 Prior analyses have demonstrated a combined trial proptosis response (≥2 mm reduction) rate of 77.4% in the teprotumumab group and 14.9% in the placebo group after 24 weeks of therapy (p < 0.001).3 The current analysis was performed to investigate whether or not patient demographic characteristics influence the teprotumumab proptosis response. Methods: Data from two 24-week randomized, double-masked, placebo-controlled, parallel-group, multicenter studies (Phase 2 [NCT01868997], Phase 3 [NCT03298867[) were combined. All patients had active TED associated with Graves’ disease. The study eye designated at baseline manifested more severe TED and a clinical activity score of > 4. Subjects were divided into subgroups based on gender, smoking status, and age at baseline (younger: <65, older: ≥65). The percentage of proptosis (≥2 mm) responders and proptosis change from baseline were examined in each of these subgroups. Because most of both teprotumumab (85%) and placebo (87%) subjects were white, there were insufficient numbers of subjects to examine the effect of race on the teprotumumab proptosis response. All analyses were performed on the intent-to-treat (ITT) population using data from the study eye. Results: A total of 171 patients comprised the population from the two studies. Eighty-four and 87 patients were randomized to the teprotumumab and placebo groups, respectively, and the treatment groups had balanced baseline characteristics. At week 24, significantly more teprotumumab than placebo patients were proptosis responders in all examined subgroups (male: 73.1% vs. 5.0%, female: 79.3% vs. 17.9%, smokers: 70.0% vs. 23.1%, non-smokers 79.7% vs. 11.5%, younger: 76.1% vs. 16.2%, older: 84.6% vs. 7.7%; all p < 0.001). In continuous variable analyses, the mean proptosis reduction from baseline was also significantly greater at week 24 in teprotumumab-treated patients than placebo patients (male: -3.34 vs. -0.07 mm, female: -3.10 vs. -0.42 mm, smokers: -2.99 vs. -0.72 mm, non-smokers: -3.20 vs. -0.31 mm, younger: -3.10 vs. -0.39 mm, older: -3.55 vs. -0.22 mm; all p < 0.001). Conclusion: Teprotumumab was effective across subgroups of age, gender, and smoking status in the pooled 24-week clinical trials. Reference: (1) Smith TJ, et al. N Engl J Med 2017;376:1748-1761. (2) Douglas RS, et al. AACE 2019 late-breaking abstract. (3) Kahaly GJ, et al. Thyroid 2019;29(Suppl1):A-1 [abstract].

Teprotumumab for the Treatment of Active Thyroid Eye Disease

BackgroundThyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration–approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease.MethodsIn a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves’ ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful).ResultsA total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (−2.82 mm vs. −0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation.ConclusionsAmong patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.)

Thyroid eye disease survey: An anonymous web-based survey in the Indian subcontinent.

Purpose:To evaluate the current practice patterns in the treatment of thyroid eye disease (TED) in Indian subcontinent through a web-based survey of members of Oculoplastics Association of India (OPAI).Methods:This was an online web-based questionnaire survey disseminated via monkeysurvey.com to all ratified active members of OPAI between May 1, 2016 and June 30, 2016. Questions encompassed the background, training, region, and experience of oculoplastic surgeons along with the management protocol of TED.Results:Of the 435 emails sent to OPAI members, 9 bounced and 180 (42.3%) responded within the study period. A large majority (96%) of respondents were oculoplastic surgeons practicing in India and the remaining practiced within South-East Asia. Two-thirds of respondents were oculoplastic surgeons with less than 10 years of clinical experience; 82% were fellowship trained in Oculoplasty. Almost all (99%) favored a multidisciplinary management of TED. A large majority routinely grade the severity (89%) and activity (87%) of disease before management. While corticosteroid remained the treatment of choice, 54% preferred immune-modulators as the second-line of therapy for recalcitrant TED. Three-quarters did not use orbital radiotherapy as a management modality in active TED owing to concerns over its efficacy and/or safety.Conclusion:The survey gives useful insights to the practice patterns of TED management in Indian subcontinent. Multidisciplinary approach and grading of disease severity and activity were the rule rather than exception among OPAI members. Immune modulation was the preferred steroid-sparing agent in recalcitrant disease. Orbital radiotherapy was an uncommon treatment choice.

Thyroid Eye Disease: How A Novel Therapy May Change The Treatment Paradigm.

Thyroid eye disease (TED) is a complex, debilitating autoimmune disease that causes orbital inflammation and tissue remodeling, resulting in proptosis, diplopia, and in severe cases, loss of vision. TED can lead to facial disfigurement and severely impact patients’ quality of life. Although the course of TED was identified over 60 years ago, effective treatment options have proved to be challenging. Current treatments such as glucocorticoid therapy and orbital radiation focus on reducing orbital inflammation. However, these therapies fail to modify the disease outcomes, including proptosis and diplopia. Recent advances in the understanding of the molecular basis of TED have facilitated the development of targeted molecular therapies such as teprotumumab, an insulin-like growth factor-1 receptor inhibiting monoclonal antibody. In recent phase 2 and phase 3 randomized placebo-controlled trials, teprotumumab rapidly achieved improvement in clinical endpoints defining TED, including improved proptosis and diplopia. Dramatic improvement in clinical outcomes achieved after teprotumumab therapy during active TED are heretofore singular and comparable only to surgical therapies achieved during the inactive phase of TED. The advent of effective medical therapy can lead to a paradigm shift in the clinical management of TED. This review will provide an overview of TED, its epidemiology, insight into the molecular biology of the disease, clinical characteristics and diagnosis, and current and emerging treatment modalities.

Microbial Keratitis in Thyroid Eye Disease: Clinical Features, Microbiological Profile, and Treatment Outcome.

To report the incidence, clinical features, microbiologic profile, and risk indicators in the development of microbial keratitis in Thyroid Eye Disease (TED). All patients who were diagnosed to have TED and developed microbial keratitis between the years 2009 to 2017 at the Ophthalmic Plastic Surgery service, LV Prasad Eye Institute were included in this retrospective interventional study. The clinical features, microbiological profile, and treatment outcome of the infection were studied. Possible risk factors leading to the development of microbial keratitis were studied. A total of 1,000 patients of TED were evaluated in the 10-year period. Of the 1,000, 13 patients (14 eyes, 1.4%) were diagnosed with microbial keratitis. The average age at presentation was 44 years (range 1969 years). Of the 13 patients, 10 (77%) were men, 12 (92%) were hyperthyroid, and 12 (92%) were active (average clinical activity score 3) at presentation. Average exophthalmometry value in the involved eye was 24.75mm, and severe eyelid retraction (>2mm scleral show) was noted in 13 of 14 eyes. None of the patients had optic nerve compression. Moderate motility restriction (2 in all gazes) was noted in 6 eyes, and severe motility restriction (4 in all gazes) in 8 eyes. At presentation, 11 (85%) had visual acuity of counting fingers at 1 meter or less, The mean follow up from the time of presentation was 18.3 months (range 566 months). Majority of the eyes (8/14) presented with severe infection (panophthalmitis with microbial keratits = 1, total corneal infiltrate with/without melt = 4, severe thinning/perforation = 4). Microbiological work up of 14 eyes revealed presence of gram-negative bacteria in 5 eyes which included Escherichia coli, Pseudomonas sp., and Acinetobacter sp., and gram-positive bacteria in 4 eyes including Streptococcus pneumoniae, Corynebacterium sp., and Staphylococcus sp. Three eyes revealed a mixed infection of E. coli with Alternaria sp, and E. coli with Corynebacterioum amycolatum while 1 had Corynebacterium pseudodiptheriticum, and S. pneumoniae. Two eyes of the bilateral case showed no growth. Antibiotic susceptibility revealed 6 of the 7 gram-negative isolates were multidrug resistant, whereas the gram-positive isolates were susceptible to most drugs tested. Surgical procedures required were tarsorrhaphy in 7 eyes, tissue adhesive with bandage contact lens in 4, evisceration in 4, levator recession in 2, 3-wall orbital decompression in 2, and penetrating keratoplasty in 1 eye. The visual acuity at presentation was counting fingers or worse in 10/14 eyes. Posttreatment, 10 eyes achieved resolution of infiltrate (with visual improvement in 2), and 4 required evisceration. In the authors large series of TED, microbial keratitis was noted in 1.3% of patients presenting to a tertiary eye center. Majority presented with advanced diseases and ended with a poor outcome. Gram-negative isolates showed multidrug resistance. An association with early phase of active TED (CAS 3 or more), severe eyelid retraction, and moderate-severe motility restriction is suggested.Microbial Keratitis occurs in 1.3% cases of Thyroid Eye Disease. It is more common in men, and in active disease. The microbiological spectrum and possible clinical risk factors are presented.

A New Era in the Treatment of Thyroid Eye Disease

Improved understanding of thyroid eye disease (TED) pathogenesis has facilitated identification of a targeted molecular approach for TED treatment offering the potential to halt or slow disease progression in a nonsurgical manner. Herein, we provide a summary of the current knowledge of TED management, followed by discussion of a novel insulin-like growth factor-1 receptor (IGF-1R) antagonist antibody and its potential to change the course of the disease. Perspective. Review of the literature and authors' experience. Many publications demonstrate IGF-1R overexpression in TED, and its activation as an autoantigen as a critical factor in TED pathogenesis. Several invitro studies demonstrate that IGF-1R inhibition attenuates downstream molecular events including cytokine and hyaluronan production, and cellular differentiation. These observations led to the hypothesis that blocking IGF-1R may abrogate the clinical progression of TED. The recent completion of phase 2 and 3 randomized, placebo-controlled trials demonstrate the efficacy and safety of teprotumumab, a fully human monoclonal IGF-1R antagonist antibody, in patients with moderate-to-severe, active TED. Both the phase 2 and the recent phase 3 study results demonstrate that more patients with active TED receiving teprotumumab experienced a meaningful improvement in proptosis. Current TED treatment strategies target inflammation and symptoms, but do not modify the disease course. Therefore, proptosis as well as strabismus and its resulting diplopia often remain, impacting patient well-being and quality of life over the long term. Targeted molecular therapy using teprotumumab demonstrates disease-modifying benefits with the potential to shift the paradigm for TED treatment.

Early low-dose rituximab for active thyroid eye disease: An effective and well-tolerated treatment.

Thyroid eye disease (TED) is an autoimmune inflammatory disease that can be disfiguring and potentially sight threatening. Suppression of inflammation in active disease can reduce the risk of visual loss and limit long-term sequelae. Current management involves inflammation suppression using glucocorticoids. The aim of this study was to evaluate the efficacy of early disease intervention with targeted immunomodulatory therapy to alter disease course. This paper reports the efficacy of low-dose rituximab in reducing clinical activity in TED in a small population. A retrospective audit of consecutive patients with active TED managed primarily with a 100mg rituximab infusion. Further glucocorticoid or steroid-sparing agents were prescribed if clinically indicated. Clinical activity score, VISA overall severity score and Oxford Quality of Life score were recorded at each visit as well as TSH receptor antibody levels (TRAb), B cell subsets and adverse reactions. Twelve patients had mean follow-up of 6.3months. Clinical activity scores significantly decreased (mean score 5.08 to 1.58; P<0.001), VISA overall severity scores reduced by 50% from 12 to 6, P<0.001 and the mean cumulative dose of IV methylprednisolone was 2.3g. 100mg rituximab induced significant CD19+ B cell depletion (n=8, P<0.001). There was no significant reduction in serum TRAb (n=8, P=0.06). A transient infusion-related rash was the only adverse effect, n=4. QoL scores did not differ markedly before and after treatment. Low-dose rituximab is an efficacious, well-tolerated and safe treatment for active TED; reducing disease activity and allowing reduced administration of systemic steroid.

Dry eye syndrome in thyroid eye disease patients: The role of increased incomplete blinking and Meibomian gland loss.

To compare the structure and function of the Meibomian gland and eyelid blinking patterns between thyroid eye disease (TED) patients with dry eye and nonthyroidal dry eye (DE) patients. This was a prospective, cross-sectional and observational study. Clinical measurements were performed as follows: (1) external examination, (2) Lipiview® Interferometer (lipid layer thickness, incomplete blinking rate and meibography) and (3) slit-lamp biomicroscopy (corneal staining, tear break-up time (TBUT), meibum expression). The TED and DE groups included 98 and 62 patients, respectively. The meiboscores of the upper eyelid in TED and DE groups were significantly different (1.21±0.76 and 0.94±0.71, respectively, p=0.046). The rate of incomplete blinking was 53.3±34.5 and 34.6±36.3%, respectively, and was significantly higher in the TED group (p=0.006). In the TED group, CAS was the only variable affecting the meiboscore of the upper and lower eyelids (p=0.031, 0.039, respectively). Significantly, active TED patients had more decreased basal tear secretion than inactive TED patients (7.4±2.1mm versus 8.5±1.5mm, p=0.024). Moreover, active TED patients had decreased meibum expression in both upper and lower eyelids compared with inactive TED patients (2.20±0.88 versus 1.08±0.84, p=0.002 in upper eyelid, 2.10±0.88 versus 1.18±0.88, p=0.007 in lower eyelid, respectively). In TED patients, incomplete blinking and loss of Meibomian gland structure in the upper eyelid were more prominent than in DE patients. CAS was a factor affecting the structural loss of Meibomian glands in TED individuals.

Teprotumumab, an insulin-like growth factor-1 receptor antagonist antibody, in the treatment of active thyroid eye disease: a focus on proptosis

Thyroid eye disease is a disabling autoimmune disease associated with orbital inflammation and tissue remodeling which can result in significant proptosis, leading to visual alterations and is potentially sight threatening. Current evidence indicates that autoantibodies to the insulin-like growth factor 1 receptor (IGF-1R), along with the thyroid-stimulating hormone receptor (TSHR), mediate the pathogenesis in susceptible individuals. Teprotumumab, a monoclonal IGF-1R antagonist, has demonstrated previously in a 24 week, randomized, controlled trial to produce significant changes in composite outcomes of proptosis and clinical activity score as compared with placebo. Further examination of the proptosis results reported here, indicate that the proptosis outcome (≥ 2 mm reduction) was met in 71.4% of the teprotumumab-treated patients as compared with 20% of the placebo-treated patients (p < 0.001). Additionally, the proptosis benefit was observed early in the trial (study week 6), and all individual patients demonstrated some benefit at week 24. Improvement was noted among smokers, non-smokers, men and women, and particularly those with higher levels of proptosis at baseline. The level of proptosis reduction with teprotumumab reported here is similar to that seen with decompression surgery. If these results are confirmed in the ongoing Phase 3 trial, teprotumumab will offer an alternative to surgery and its associated complications.

Comparative Efficacy of Medical Treatments for Thyroid Eye Disease: A Network Meta-Analysis.

Purpose Numerous medical strategies have been proposed for the treatment of thyroid eye disease (TED); however, the best methods for standard treatment are still a matter of controversy. The purpose of this network meta-analysis was to integrate previous evidence to create hierarchies of comparative efficacy of eleven commonly used medical treatments for TED. Methods A comprehensive search of electronic scientific literature databases was performed and the data from randomized controlled trials (RCTs) comparing treatment outcomes for patients with active TED were selected. Treatment strategies included in this network meta-analysis were intravenous glucocorticoids (IVGC), oral glucocorticoids (OGC), orbital injection of glucocorticoids (OIGC), orbital radiotherapy (OR), intravenous glucocorticoids combined with orbital radiotherapy (IVGC + OR), oral glucocorticoids combined with orbital radiotherapy (OGC + OR), rituximab (RTX), somatostatin analogs, intravenous immunoglobulin (IVIG), teprotumumab, and cyclosporine. The outcomes were response rate, mean difference in proptosis reduction, and reduction in disease activity. A random-effects network meta-analysis using a frequent method was conducted in STATA. Results Twenty-three studies comprising a total of 1047 patients were included in the analysis. Inconsistency plots showed heterogeneity in the IVGC-Placebo-RTX loop to some extent (RoR = 8.029, P=0.075). Rankings of response rates were as follows: IVGC + OR, teprotumumab, IVGC, OGC + OR, RTX, OIGC, OR, IVIG, OGC, somatostatin, placebo, and cyclosporine. The rank probability analysis of proptosis reduction showed that teprotumumab was the most effective, followed by IVGC, IVGC + OR, OIGC, OGC, OGC + OR, OR, somatostatin, cyclosporine, and placebo. Conclusions IVGC, alone or combination with OR, and teprotumumab should be preferred as the most effective strategies for active moderate to severe TED. Teprotumumab showed profound effect on proptosis reduction. OIGC, OR, and somatostatin analogs showed some statistical benefit and can be employed as second-line treatment strategies. RTX is a promising biologic agent, but more RCTs are required to define its appropriate role in treating TED.

Efficacy and safety of pulsed intravenous methylprednisolone in early active thyroid eye disease

ABSTRACTIntroduction: The mainstay of therapy for active inflammatory phase of thyroid eye disease (TED) is immunosuppression. Patients in our centre with early active TED are treated with pulsed intravenous methylprednisolone (IVMP). Two different protocols are offered in our centre: High dose (1g/day for 3 days, monthly for 6 months), or EUGOGO protocol (500 mg weekly for six weeks, followed by 250 mg weekly for the next 6 weeks).Methods: A prospective cohort study of patients undergoing the two IVMP protocols was performed from January 2009 to May 2015. Main outcome measures were improvement of Clinical Activity Score (CAS) and International Thyroid Eye Disease (ITEDS) – VISA Inflammatory Index.Results: We had a total of 63 patients. Mean age was 43.1 ± 13.1years, females comprised 49.2% (n = 31), and 31 (49.2%) had a positive smoking history. Following IVMP, 65.0% (n = 41) had good response, 31.7% (n = 20) partial, and 3.3% (n = 2) poor. There were significant differences (p < 0.001) in CAS and ITEDS scores between pre-IVMP and post-IVMP visits, for both protocols. A higher proportion of patients receiving the modified EUGOGO protocol (58.3%) had persistent activity and required additional immunosuppression compared to those who underwent the high dose protocol (33.3%). Mild side effects were experienced by 5 (7.9%) and 3 (4.8%) patients at 3 and 6 months, respectively. There were no severe side effects, cardiovascular events or liver failure.Conclusion: With adequate screening and follow-up, six repeated cycles of high dose pulsed IVMP is an effective treatment for TED and can significantly reduce the morbidity associated with this debilitating condition. None of the 51 patients from the high dose protocol met with any serious side effects.

Transconjunctival Triamcinolone Injection for Upper Lid Retraction in Thyroid Eye Disease-A New Injection Method.

To evaluate the role of transconjunctival triamcinolone acetonide (TA) injection in the management of upper eyelid retraction in thyroid eye disease. Retrospective interventional review of all patients who underwent transconjunctival TA injection (40 mg/mL) for thyroid eye disease-related upper eyelid retraction from January 2010 to December 2016 in a single tertiary institution. The present study comprised 2 groups: Patients receiving only TA injection (group 1), and patients receiving both TA injection and other immunosuppressive therapy (group 2). There were a total of 99 patients and 135 eyes. Group 1 comprised of 36 eyes (26.7%), while group 2 comprised 99 (73.3%). Normalization or improvement of margin reflex distance 1 was seen in 77.4% and 97.2% of group 1 patients at early and late review, respectively, and 77.6% and 87.8% of group 2, respectively. Absence or improvement in International Thyroid Eye Disease Society inflammatory index was seen in 83.9% and 86.1% of group 1 at early and late review, respectively, and 71.9% and 76.8% of group 2, respectively. Both active (73.7%) and inactive (79.3%) groups showed good early success for improvement in margin reflex distance 1, with increased late success and no significant difference between the groups. For International Thyroid Eye Disease Society inflammatory index, the active group had better early and late success than the inactive group, with the difference being significant (P = 0.002) for late success. Transconjunctival TA injection is an effective treatment option for thyroid eye disease-related upper eyelid retraction, as a primary and adjunctive treatment, in both active and inactive thyroid eye disease patients.

Central Retinal Vein Occlusion with Chorioretinal Folds Secondary to Active Thyroid Eye Disease

Central Retinal Vein Occlusion with Chorioretinal Folds Secondary to Active Thyroid Eye Disease

Early use of steroid-sparing agents in the inactivation of moderate-to-severe active thyroid eye disease: a step-down approach.

The current first-line treatment for management of active thyroid eye disease (TED) is high-dose intravenous corticosteroids, which have the potential for serious adverse effects. Our aim was to evaluate the effect of steroid-sparing agents (SSAs) in patients with moderate-to-severe active TED, using methotrexate as first-line. Presented is a retrospective, four-year, single-centre, consecutive case series of patients with moderate-to-severe TED treated using the Oxford protocol. Treatment modality, disease activity, and adverse effects are reported at presentation, 6- and 12-month follow-up. 104 consecutive TED patients treated by the Oxford TED team were reviewed. 24 patients with moderate-to-severe active disease were identified (mean age 46.8years;12 female) with a mean pretreatment VISA inflammatory index score of 5.5/10 (SD=1.98; range 1-9). Intravenous methyl-prednisolone (IVMP) and an SSA was commenced in all patients. Mean total steroid dose was 2.72g (SD=1.4;1.0-6.9). 38% of patients (n=9) received ≤1.5g of IVMP. Only two patients required >4.5g of IVMP equating to the EUGOGO treatment protocol dose for this patient group. There was significant improvement in inflammatory index score both at the intermediate review (mean score 2.7; SD=2.8; P<0.001; mean follow up 25.2weeks) and at one year or last follow-up (mean score 1.4; SD=1.5; P<0.001; mean follow up 48.0weeks). No serious or long-term adverse effects were reported. This study suggests that the initiation of an SSA, using methotrexate as first-line, with limited adjuvant IVMP is an effective and safe treatment for moderate-to-severely active TED, resulting in a significant reduction in both disease activity and total steroid load.

Radiotherapy for Active Thyroid Eye Disease.

To critically review the published literature on orbital radiotherapy as a treatment modality for thyroid eye disease (TED). A systematic review and analysis of the relevant published literature was performed. Thyroid eye disease is an autoimmune condition that is amenable to treatments that modulate the immune response, including orbital radiotherapy (ORT). Ideal candidates for ORT are patients in the early, active phase of TED with moderate to severe, or rapidly progressive, disease, including patients with significant motility deficits and compressive optic neuropathy. Patients with progressive strabismus may also benefit. Patients with mild or inactive disease will not benefit from ORT when compared with the natural history of the disease. Orbital radiotherapy should generally be used in conjunction with corticosteroid therapy, with response to corticosteroids demonstrating the immunomodulatory therapeutic potential of ORT. When treating TED-compressive optic neuropathy, ORT may help obviate the need for urgent surgical decompression, or postpone it until the stable, inactive phase of the disease. Orbital radiotherapy treatment doses should approach 20 Gy in most cases, but lower doses may be considered in younger patients without significant dysmotility. The safety profile of ORT is well established, and side effects are minimal in appropriately selected patients. Radiotherapy is a safe and effective treatment for active TED in appropriately selected patients.

Early low dose rituximab for active thyroid eye disease: an effective and well tolerated treatment

Early low dose rituximab for active thyroid eye disease: an effective and well tolerated treatment