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Ophthalmology Apr 2022To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare.
DESIGN
The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial.
PARTICIPANTS
Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC.
METHODS
OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks.
MAIN OUTCOME MEASURES
Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life.
RESULTS
Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, -3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment.
CONCLUSIONS
Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.
Topics: Antibodies, Monoclonal, Humanized; Diplopia; Exophthalmos; Graves Ophthalmopathy; Humans
PubMed: 34688699
DOI: 10.1016/j.ophtha.2021.10.017 -
Deutsches Arzteblatt International Sep 2022
Topics: Humans; Exophthalmos
PubMed: 36507730
DOI: 10.3238/arztebl.m2022.0128 -
Journal of Pediatric Hematology/oncology Aug 2022
Topics: Exophthalmos; Humans; Iron; Sulfides
PubMed: 35797179
DOI: 10.1097/MPH.0000000000002491 -
Survey of Ophthalmology 2017A 73-year-old woman presented with vision loss and recurrent proptosis with conjunctival chemosis 4 weeks after an uncomplicated fat-only orbital decompression for... (Review)
Review
A 73-year-old woman presented with vision loss and recurrent proptosis with conjunctival chemosis 4 weeks after an uncomplicated fat-only orbital decompression for thyroid eye disease. Her Graves disease was biochemically "burnt out," and she had diabetes mellitus. Initial neuro-imaging showed a straightened optic nerve and orbital apex fat streaking so a bilateral bony decompression of the orbital apex was performed for presumed compressive optic neuropathy. Vision failed to improve, and she experienced cognitive decline. She described metamorphopsia and insomnia. Examination showed a hemifield loss of red sensitivity, difficulties with higher visual processing, and memory problems. Occipital cortical ribboning was seen on diffusion weighted magnetic resonance imaging, cerebrospinal fluid was positive for 14-3-3, and her electroencephalogram showed periodic complexes. A diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease was made. She became akinetic and mute, dying a few months later.
Topics: Aged; Decompression, Surgical; Diagnosis, Differential; Electroencephalography; Exophthalmos; Female; Graves Ophthalmopathy; Humans; Magnetic Resonance Imaging; Occipital Lobe; Optic Nerve; Orbit
PubMed: 26742784
DOI: 10.1016/j.survophthal.2015.12.009 -
Clinical Endocrinology Jun 2022In Graves' disease (GD), autoantibodies to the thyroid stimulating hormone receptor (TSHR) cause hyperthyroidism. The condition is often associated with eye signs...
TSH receptor specific monoclonal autoantibody K1-70 targeting of the TSH receptor in subjects with Graves' disease and Graves' orbitopathy-Results from a phase I clinical trial.
OBJECTIVES
In Graves' disease (GD), autoantibodies to the thyroid stimulating hormone receptor (TSHR) cause hyperthyroidism. The condition is often associated with eye signs including proptosis, oedema, and diplopia (collectively termed Graves' orbitopathy [GO]). The safety profile of K1-70 (a human monoclonal TSHR specific autoantibody, which blocks ligand binding and stimulation of the receptor) in patients with GD was evaluated in a phase I clinical trial.
PATIENTS AND STUDY DESIGN
Eighteen GD patients stable on antithyroid drug medication received a single intramuscular (IM) or intravenous (IV) dose of K1-70 during an open label phase I ascending dose, safety, tolerability, pharmacokinetic and pharmacodynamic (PD) study. Immunogenic effects of K1-70 were also determined.
RESULTS
K1-70 was well-tolerated in all subjects at all doses and no significant immunogenic response was observed. There were no deaths or serious adverse events. Increased systemic exposure to K1-70 was observed following a change to IV dosing, indicating this was the correct dosage route. Expected PD effects occurred after a single IM dose of 25 mg or single IV dose of 50 mg or 150 mg with fT3, fT4, and TSH levels progressing into hypothyroid ranges. There were also clinically significant improvements in symptoms of both GD (reduced tremor, improved sleep, improved mental focus, reduced toilet urgency) and GO (reduced exophthalmos measurements, reduced photosensitivity).
CONCLUSIONS
K1-70 was safe, well tolerated and produced the expected PD effects with no immunogenic responses. It shows considerable promise as a new drug to block the actions of thyroid stimulators on the TSHR.
Topics: Antithyroid Agents; Autoantibodies; Graves Disease; Graves Ophthalmopathy; Humans; Receptors, Thyrotropin
PubMed: 35088429
DOI: 10.1111/cen.14681 -
Current Opinion in Ophthalmology Nov 2023Teprotumumab, an inhibitor of the insulin-like growth factor 1 receptor (IGF-1R), was approved by the US Food and Drug Administration in January 2020 for the treatment... (Review)
Review
PURPOSE OF REVIEW
Teprotumumab, an inhibitor of the insulin-like growth factor 1 receptor (IGF-1R), was approved by the US Food and Drug Administration in January 2020 for the treatment of thyroid eye disease (TED). The clinical trials leading to its approval enrolled patients with recent disease onset and significant inflammatory symptoms and signs. Subsequent real-world teprotumumab use in patients with longer duration of disease also may be effective, and there have been several publications reporting on experience in these patient groups.
RECENT FINDINGS
TED results in disfiguring changes such as ocular proptosis and affects visual function by altering extraocular muscle function, leading to diplopia. Compressive optic neuropathy also may occur, and disease manifestations may persist for years. Teprotumumab treatment in cases of TED in which prior interventions (medical or surgical) had failed, or in treatment-naïve patients whose disease had been stable for years, has been reported to improve both clinical signs and symptoms (proptosis, diplopia) and to reduce the pathologic orbital changes as assessed by orbital imaging.
SUMMARY
Teprotumumab may be an appropriate treatment for TED regardless of disease duration and irrespective of the presence or absence of markers of active inflammation within the orbit.
Topics: Humans; Graves Ophthalmopathy; Diplopia; Orbit; Exophthalmos
PubMed: 37610428
DOI: 10.1097/ICU.0000000000000997 -
Frontiers in Endocrinology 2020Graves' Orbitopathy (GO) is an autoimmune orbital disorder usually presenting as a sequala of autoimmune thyroid disease. The presence of GO is associated with increased... (Review)
Review
Graves' Orbitopathy (GO) is an autoimmune orbital disorder usually presenting as a sequala of autoimmune thyroid disease. The presence of GO is associated with increased psychological burden and, in severe cases may cause blindness. While most patients with GO present with bilateral disease, asymmetric or unilateral GO may affect a significant proportion of patients diagnosed with GO. Older age, male sex, active and severe disease correlate with asymmetric disease. However, the exact mechanisms causing asymmetry remain elusive. Herein, we review the literature on asymmetric GO and highlight its differences compared with bilateral GO.
Topics: Age Factors; Animals; Graves Disease; Graves Ophthalmopathy; Humans; Sex Factors
PubMed: 33391188
DOI: 10.3389/fendo.2020.611845 -
The Journal of Craniofacial Surgery May 2022To describe the clinical features and outcomes of patients who underwent transorbital debulking of sphenoid wing meningioma.
OBJECTIVE
To describe the clinical features and outcomes of patients who underwent transorbital debulking of sphenoid wing meningioma.
METHODS
Patients with a diagnosis of sphenoid wing meningioma who underwent transorbital debulking were included in this series. Preoperative and postoperative symptoms and examination findings, including best corrected visual acuity (BCVA) and proptosis were extracted from patient charts. All imaging studies, records of additional surgical and medical management, and complications of surgery were collated.
RESULTS
Eight patients were included. The most common symptoms at presentation were blurred vision (6/8) and proptosis (6/8). The most common clinical findings at presentation were decreased visual acuity and proptosis. Mean BCVA preoperatively was 0.93 in logMARunits andmeanrelative proptosis preoperatively was 4.88 mm. All patients underwent orbitotomy with or without bone flap with decompression of hyperostotic bone and subtotal resection of soft tissue mass. Mean follow-up time was 14months. Five of eight patients experienced postoperative improvement in BCVA, for mean change of 0.32. All patients demonstrated reduction in proptosis postoperatively with a mean reduction of 3.63 mm.
CONCLUSIONS
Sphenoid wing meningioma can present with decreased visual acuity and/or proptosis. It is possible to address both of these problems in selected patients with transorbital debulking, an approach that avoids the aesthetic and functional consequences of craniotomy. The aim of this technique is not surgical cure, but rather improvement in vision and disfigurement.
Topics: Cytoreduction Surgical Procedures; Esthetics, Dental; Exophthalmos; Humans; Meningeal Neoplasms; Meningioma; Retrospective Studies; Sphenoid Bone; Treatment Outcome
PubMed: 34608004
DOI: 10.1097/SCS.0000000000008148 -
Journal of Neuro-ophthalmology : the... Sep 2016We describe 2 unique cases of visual symptoms occurring during mastication in patients with lateral orbital wall defects. A 57-year-old man reported intermittent double...
We describe 2 unique cases of visual symptoms occurring during mastication in patients with lateral orbital wall defects. A 57-year-old man reported intermittent double vision and oscillopsia after a right fronto-temporal-orbito-zygomatic craniotomy with osteotomy of the lesser wing of the sphenoid for a complex invasive pituitary adenoma. Proptosis of the right globe was present only during mastication. Computed tomography (CT) revealed a bony defect in the right lateral orbital wall. A 48-year-old man presented with transient diplopia and scotoma in the right eye elicited by chewing. CT and magnetic resonance imaging demonstrated a bilobed lesion connecting the temporal fossa to the orbit through a defect in the right lateral orbital wall. The regional neuroanatomy and pathophysiology as pertaining to these cases are discussed.
Topics: Craniotomy; Diplopia; Exophthalmos; Humans; Magnetic Resonance Imaging; Male; Mastication; Middle Aged; Orbit; Postoperative Complications; Sphenoid Bone; Tomography, X-Ray Computed
PubMed: 26919071
DOI: 10.1097/WNO.0000000000000354 -
BMJ Case Reports Dec 2019
Topics: Adult; Conservative Treatment; Exophthalmos; Humans; Magnetic Resonance Imaging; Male; Orbital Diseases; Varicose Veins
PubMed: 31818898
DOI: 10.1136/bcr-2019-232887