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American Journal of Ophthalmology Dec 2019Improved understanding of thyroid eye disease (TED) pathogenesis has facilitated identification of a targeted molecular approach for TED treatment offering the potential... (Review)
Review
PURPOSE
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.
DESIGN
Perspective.
METHODS
Review of the literature and authors' experience.
RESULTS
Many publications demonstrate IGF-1R overexpression in TED, and its activation as an autoantigen as a critical factor in TED pathogenesis. Several in vitro 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.
CONCLUSIONS
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.
Topics: Antibodies, Monoclonal, Humanized; Exophthalmos; Graves Ophthalmopathy; Humans; Randomized Controlled Trials as Topic; Receptor, IGF Type 1
PubMed: 31377284
DOI: 10.1016/j.ajo.2019.07.021 -
Journal of Neuro-ophthalmology : the... Mar 2024Teprotumumab, an insulin-like growth factor I receptor inhibitory antibody, improved proptosis, diplopia, inflammatory signs/symptoms, and quality of life in patients... (Review)
Review
BACKGROUND
Teprotumumab, an insulin-like growth factor I receptor inhibitory antibody, improved proptosis, diplopia, inflammatory signs/symptoms, and quality of life in patients with active thyroid eye disease (TED) in clinical trials. The trials excluded patients with dysthyroid optic neuropathy (DON). Recently, many case reports and case series have reported the successful use of teprotumumab to treat DON. Here, we review the data from published cases and our clinical experience in treating patients having DON with teprotumumab.
METHODS
A literature search was conducted of patients with DON treated with teprotumumab from January 2020 through September 2022. Data from DON patients from the authors' (M.A.T. and C.A.B.) clinical practice were included. Primary outcome measure was mean (SD) improvements for visual acuity, color vision, and visual fields. Improvements in proptosis and clinical activity score (CAS) and diplopia were compared before and after teprotumumab administration.
RESULTS
Ten observational studies/case reports were identified along with 2 patients in our practice. In all, there were 24 active TED patients with DON (37 eyes) who were treated with teprotumumab. Mean (SD) age was 66.5 (13.6) years and 13 (54%) were females, disease duration ranged from 2 months to >15 years. 22/24 patients had none, minimal improvement or progression of visual loss with intravenous/oral corticosteroids, orbital decompression (n = 9), and orbital radiation (n = 2). There were 2 patients who received teprotumumab as the only therapy. Overall, 88% (21/24) reported improvement in visual acuity after teprotumumab and in 75% (18/24), improvement in vision was observed after just 2 infusions of teprotumumab. Three eyes had decompression surgery in close proximity to teprotumumab infusions and were excluded from analyses. Mean (SD) improvement in visual acuity was 3.73 lines (SD 3.74), range 2-15 lines in 33 eyes. The mean (SD) improvement in the mean deviation on visual field testing in 15 eyes was 5.6 db (3.0 db). Mean (SD) improvement in proptosis was 4.37 mm (SD: 2.11) (20 patients, 32 eyes); and clinical activity score: mean reduction of 5.1 (1.3) for 18 patients. Teprotumumab was well tolerated in all but one patient. Adverse events reported included fatigue, dysgeusia, hearing loss, nausea, hyperglycemia, and muscle spasms.
CONCLUSIONS
Teprotumumab is an effective treatment for DON in our experience and in published cases in whom treatment with steroids, surgery, or orbital radiation was unsuccessful.
Topics: Female; Humans; Infant; Male; Diplopia; Quality of Life; Optic Nerve Diseases; Graves Ophthalmopathy; Exophthalmos; Antibodies, Monoclonal, Humanized
PubMed: 37751310
DOI: 10.1097/WNO.0000000000001994 -
The British Journal of Ophthalmology Jun 2022Teprotumumab, a specific blocking antibody to the insulin like growth factor 1 receptor, significantly reduced proptosis in patients with thyroid eye disease (TED) in... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Teprotumumab, a specific blocking antibody to the insulin like growth factor 1 receptor, significantly reduced proptosis in patients with thyroid eye disease (TED) in recent clinical trials. Given its specificity, we expect it to demonstrate greater efficacy on the worse affected orbit, in patients with asymmetric TED. Herein, we investigate the differential impact of teprotumumab on the orbits of such patients.
METHODS
In this pooled analysis of patients who were enrolled in the recent phase 2 (NCT01868997) and phase 3 (NCT03298867) trials, all patients with asymmetric TED (difference in exophthalmometry of ≥3 mm) were screened for eligibility. The primary outcomes of the trials, proptosis, diplopia and Clinical Activity Score (CAS) response, were evaluated in both orbits of patients who had received treatment or placebo, to examine the differential response from baseline to week 24.
RESULTS
From a pooled group of 84 patients randomised to receive teprotumumab and 87 randomised to placebo, 10 (12%) and 12 (14%), respectively, met the inclusion criteria. The teprotumumab-treated patients demonstrated significant reductions in proptosis, CAS and diplopia in both orbits of each patient and this was not seen with placebo. The reduction in proptosis and CAS was significantly greater in the worse affected orbit, improving symmetry. In the placebo arm, while the mean CAS in the study eye reduced over time, proptosis and diplopia did not change in either orbit.
CONCLUSION
The findings in this study suggest the differential impact of teprotumumab on orbits that are clinically more affected by TED, suggesting that teprotumumab reduces asymmetry.
Topics: Antibodies, Monoclonal, Humanized; Diplopia; Exophthalmos; Graves Ophthalmopathy; Humans
PubMed: 33579690
DOI: 10.1136/bjophthalmol-2020-318314 -
British Medical Journal Feb 1972
Review
Topics: Cushing Syndrome; Diagnosis, Differential; Exophthalmos; Graves Disease; Humans; Hyperthyroidism; Immunoglobulins; Iodine Radioisotopes; Long-Acting Thyroid Stimulator; Orbit; Pituitary Gland; Thyroid Diseases; Thyrotropin
PubMed: 4550413
DOI: 10.1136/bmj.1.5796.360 -
Postgraduate Medical Journal Aug 1990A male aged 19 presented with a protruding left eye increasing slowly for 3 years. On examination there was proptosis and downward displacement of the eye globe.
A male aged 19 presented with a protruding left eye increasing slowly for 3 years. On examination there was proptosis and downward displacement of the eye globe.
Topics: Adult; Exophthalmos; Histiocytoma, Benign Fibrous; Humans; Male; Orbital Neoplasms; Tomography, X-Ray Computed
PubMed: 2170964
DOI: 10.1136/pgmj.66.778.662 -
Frontiers in Endocrinology 2023The effects of various treatments on Graves' ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
The effects of various treatments on Graves' ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to severe GO, direct comparisons between different mAbs are lacking.We therefore conducted this meta-analysis to objectively compare the efficacy and safety of intravenous mAbs.
METHODS
To identify eligible trials, references published before September 2022 were electronically searched in PubMed, Web of Science, Pubmed, Embase,Cochrane Library, CBM, CNKI,Wan-Fang and ICTRP databases.The Newcastle-Ottawa scale (NOS) and the Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias of the original studies.The primary and secondary outcomes were the response and inactivation rates, with the secondary outcomes being the clinical activity score (CAS),the improvement of proptosis and diplopia improvement,and the adverse event rate. Publication bias was evaluated, along with subgroup and sensitivity analyses.
RESULTS
A total of 12 trials with 448 patients were included. The meta-analysis showed that TCZ (tocilizumab) was most likely to be the best treatment in terms of response according to indirect contrast, followed by TMB (teprotumumab) and RTX (rituximab).TCZ, followed by TMB and RTX, was also most likely to be the best treatment in terms of reducing proptosis. In terms of improving diplopia, TMB was most likely to be the best treatment, followed by TCZ and RTX.TCZ was the highest probability of safety, followed by RTX and TMB.
CONCLUSIONS
Based on the best available evidence,TCZ should be the preferred treatment for moderate to severe GO.In the absence of head-to-head trials,indirect comparisons of treatments are routinely used to estimate the effectiveness of the treatments of interest. In addition,the optimal dose and potential mechanism of action of monoclonal antibodies remain to be established,and it is encouraging that the treatment paradigm for GO may change in the future.This study was designed in accordance with the Preferred Reporting Items for conducting Systematic Reviews and Meta-Analyses (PRISMA)(27).
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/prospero, identifier CRD42023398170.
Topics: Humans; Antibodies, Monoclonal; Immunoglobulins, Intravenous; Diplopia; Rituximab; Graves Ophthalmopathy; Exophthalmos
PubMed: 37288301
DOI: 10.3389/fendo.2023.1160936 -
Journal of General Internal Medicine Apr 2017
Topics: Carotid-Cavernous Sinus Fistula; Exophthalmos; Humans; Male; Middle Aged; Tomography, X-Ray Computed
PubMed: 27612485
DOI: 10.1007/s11606-016-3860-6 -
BMC Ophthalmology May 2023To present the clinical features of thyroid-associated ophthalmopathy (TAO) with different CT types, and to report the outcomes of endoscopic orbital decompression...
PURPOSE
To present the clinical features of thyroid-associated ophthalmopathy (TAO) with different CT types, and to report the outcomes of endoscopic orbital decompression combined with fat decompression (EOD-FD).
PATIENTS AND METHODS
Thirty-four patients with TAO who underwent EOD-FD between December 2020 and March 2022 in the Ophthalmology Department of Li Huili Hospital Affiliated with Ningbo University, were included in this retrospective interventional case series. Patients were categorized into two groups based on the results of computerized tomography (CT) scans: muscle expansion type and fat hyperplasia type.
RESULTS
Thirty-four TAO patients (55 eyes) were included in this study, and the mean age was 38.62 years (range 22-60 years). The average eye protrusion (EP) reduced from preoperative 23.20 mm to postoperative 19.66 mm (p < 0.0001). Mean intraocular pressure (IOP) decreased from 20.11 mmHg at baseline to 17.29 mmHg postoperatively (p < 0.0001), with a reduction of 2.84 mmHg (14.12%). Twenty cases of muscle expansion and fourteen cases of fat hyperplasia were definite by CT imaging. The mean IOP in the muscle expansion group was higher than that in the fat hyperplasia group (p < 0.05). Elevated intraocular pressure (IOP) occurred in 23 eyes (36.11%), and it was associated with extraocular muscle involvement, gender, and EP. In 3 cases of impaired vision, the mean best corrected visual acuity (VA) improved from 0.4 preoperatively to 0.84 postoperatively (p < 0.01). There were 8 cases with visual field (VF) damage and/or corneal epithelium damage, and all these damages were reversible.
CONCLUSION
In this study, we describe the clinical features and experience of EOD-FD in patients with TAO. EOD-FD is an effective technique in reducing IOP and proptosis, with a low incidence of postoperative diplopia.
Topics: Adult; Humans; Middle Aged; Young Adult; Decompression; Exophthalmos; Graves Ophthalmopathy; Hyperplasia; Orbit; Retrospective Studies; Treatment Outcome; Endoscopy
PubMed: 37193956
DOI: 10.1186/s12886-023-02957-7 -
Turkish Journal of Ophthalmology Aug 2020To evaluate the effect of proptosis on choroidal thickness in patients with Graves' ophthalmopathy.
OBJECTIVES
To evaluate the effect of proptosis on choroidal thickness in patients with Graves' ophthalmopathy.
MATERIALS AND METHODS
Twenty-five eyes of 25 Graves' patients with proptosis, 25 eyes of 25 Graves' patients without proptosis, and 25 eyes of 25 healthy individuals were included in this prospective study. The subfoveal choroidal thickness and choroidal thicknesses at 6 points from the fovea at 500 μm intervals were measured by Cirrus HD-OCT. All measurements were compared among the proptosis, non-proptosis, and control groups and the active, inactive, and control groups.
RESULTS
The mean subfoveal choroidal thickness in the proptosis group was 289.7±68.5 μm, 322.5±55.8 μm in the non-proptosis group, and 316.1±63.0 μm in the control group. The mean nasal choroidal thickness was 260.5±63.5 μm in the proptosis group, 293.9±57.9 μm in the non-proptosis group, and 279.5±63.1 μm in the control group. The mean temporal choroidal thickness was 261.8±60.9 μm in the proptosis group, 289.0±51.8 μm in the non-proptosis group, and 287.8±56.2 μm in the control group. Mean choroidal thickness was 264.7±58.5 μm in the proptosis group, 296.2±47.5 μm in the non-proptosis group, and 288.3±55.1 μm in the control group. There were no statistically significant differences among the groups with respect to choroidal thickness measurements (p>0.05).
CONCLUSION
No significant difference in choroidal thickness was detected between Graves' patients with and without proptosis and the controls. There was no effect of clinical activation on choroidal thickness.
Topics: Adult; Choroid; Disease Progression; Exophthalmos; Female; Follow-Up Studies; Graves Ophthalmopathy; Humans; Male; Prospective Studies; Tomography, Optical Coherence
PubMed: 32854466
DOI: 10.4274/tjo.galenos.2020.97415 -
PloS One 2020We propose a new method to calculate proptosis by using the simple Heron's formula and analyze its feasibility. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
We propose a new method to calculate proptosis by using the simple Heron's formula and analyze its feasibility.
METHOD
It was a none-inferiority trial. The registration number was ChiCTR1900026490. The absolute value of proptosis in 120 eyes, 60 patients without eye injury or diseases, was measured by computed tomography (CT) and simple Heron's formula. We did regression analysis and analyzed the differences between the two methods with Medcalc software version 19.0.4. The result was showed by Passing-Bablok regression analysis diagram and Bland and Altman plot.
RESULTS
The Passing-Bablok showed that the result of proptosis measured by CT and simple Heron's formula showed good positive correlation. A 95% limit of agreement in proptosis between CT and Heron's formula method was -0.46 to 0.54 mm in right eye and -0.45 to 0.46 mm in left eye. 1.66% (1/60) point was outside 95% LoA in both eyes. Moreover, a 95% limit of agreement between CT and Heron's formula method was -0.42 to 0.56 mm in difference of both eyes. 3.33% (2/60) points were outside 95% LoA. The points in all Bland and Altman plots were lower than 5%. It means that the results of comparison between the two methods had a good consistency in the measurement of proptosis.
CONCLUSIONS
Heron's formula could be applied to calculate proptosis and has a good consistency compared with computed tomography (CT). This method is practical in proptosis assessment because of its accuracy, reliability and simplicity.
Topics: Adult; Anthropometry; Exophthalmos; Eye; Feasibility Studies; Female; Humans; Male; Middle Aged; Reproducibility of Results; Tomography, X-Ray Computed; Young Adult
PubMed: 32480401
DOI: 10.1371/journal.pone.0234016