Abstract
Purpose
To report two cases of thyroid eye disease (TED) associated compressive optic neuropathy (CON) that resolved after treatment with teprotumumab.
Observation
Two patients presented with active TED resulting in mild CON with the typical corresponding visual field (VF) defects. Both patients were initiated on intravenous (IV) corticosteroid therapy but despite treatment had persistent VF defects. Both patients were then treated with teprotumumab and demonstrated marked clinical improvement and complete resolution of TED-CON VF defects early in their infusion course.
Conclusions and importance
These cases suggest that teprotumumab can be a rapid and effective treatment for TED-CON, and raises the question of whether it may be superior to IV corticosteroid therapy.
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Introduction
Thyroid eye disease (TED) is an autoimmune disorder that causes inflammation, expansion, and fibrosis of the extraocular muscles and connective tissue of the orbit. The underlying pathogenic mechanism has not been fully elucidated but evidence suggests involvement of autoantibody-mediated upregulation of thyroid stimulating hormone receptor (TSHR) and insulin-like growth factor receptor 1 (IGF-1R) complex in orbital fibroblasts. This phenotypically heterogenous disease can lead to a range of disfiguring and debilitating ocular manifestations including proptosis, diplopia, and in its more severe form, compressive optic neuropathy (CON). Traditional treatment options for sight threatening TED-CON include intravenous (IV) or oral corticosteroid therapy or surgical orbital decompression, each of which has variable efficacy in treatment and the potential for significant adverse side effects and complications. ,
Teprotumumab, a fully human monoclonal antibody directed against IGF-1R, was recently approved by the United States Food and Drug Administration (FDA) to address the need for an effective and targeted medical therapy for patients with TED. The teprotumumab randomized clinical trials demonstrated promising results for the treatment of moderate and severe TED; however, patients with CON were excluded from the trials. , In this report, we describe two cases of TED with mild CON and typical visual field (VF) defects that persisted despite IV corticosteroid therapy, but resolved completely shortly after initiation of treatment with teprotumumab. The research in this manuscript is compliant with the Declaration of Helsinki and Health Insurance Portability and Accountability Act regulations.
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Case 1
A 68-year-old Caucasian female with Graves’ disease treated with radioactive iodine therapy eleven years prior was referred for evaluation of periorbital swelling, proptosis, pain with extraocular movements, and binocular diplopia for 3 months. The patient was taking levothyroxine with serum thyroid hormone levels in the normal range and was a never-smoker. On examination, visual acuity (VA) was 20/25 in both eyes (OU) with no relative afferent pupillary defect (rAPD). Ishihara color testing was 8 out of 8 plates OU, but the patient reported subjective red desaturation in the left eye (OS). Extraocular motility was moderately restricted in supraduction and abduction OS. The intraocular pressures (IOP) were 22 mm Hg right eye (OD) and 24 mm Hg OS. Hertel exophthalmometry measured 24 mm OD and 27 mm OS. She had severe bilateral eyelid edema and erythema, conjunctival injection and chemosis. The optic discs appeared normal OU. The Clinical Activity Score (CAS) was 6 out of 7. Computed tomography (CT) of the orbits revealed enlarged extraocular muscles, left greater than right, with apical crowding, raising concern for CON OS ( Fig. 1 ). Humphrey visual field (HVF) testing was full OD and showed a Stage 1a small inferior paracentral hemifield defect with a mean deviation (MD) of −0.83 dB OS ( Fig. 2 A). The patient was started on weekly 500 mg IV solumedrol, but following a discussion with her hepatologist the treatment was discontinued after four doses due to elevated liver enzymes. Alternative treatment options were discussed including orbital decompression and teprotumumab. The patient opted for teprotumumab; however, there was a predictable delay in initiating treatment due to insurance and infusion center logistical details.
Two months after discontinuation of IV solumedrol, just prior to receiving teprotumumab, she presented urgently with a subjective decrease in color vision OS, worsening pain with extraocular movement, and progressive diplopia. On examination, VA was 20/25 OU with no rAPD. Ishihara color testing was 8 out of 8 plates OU with persistent subjective red desaturation OS. Extraocular motility demonstrated interval worsening with severe restriction in supraduction and new restriction in infraduction and adduction OS. The IOP was 25 mm Hg OD and 26 mm Hg OS. Hertel exophthalmometry measured 24.5 mm OD and 26.5 mm OS. The eyelid and conjunctival inflammation persisted bilaterally. The CAS was 7 out of 10. Repeat HVF testing remained full OD and there was progression to a Stage 1b large inferior paracentral hemifield defect with the MD worsening to −3.70 dB OS ( Fig. 2 B). The patient opted for careful monitoring until initiation of teprotumumab and was started on timolol OU. She received her first infusion of teprotumumab two weeks later.
A few days after the first dose of teprotumumab, she reported complete resolution of retrobulbar pain, eyelid edema and erythema, and near complete resolution of diplopia. After her third infusion of teprotumumab, VA was 20/25 OU with no rAPD, Ishihara color testing was 8 out of 8 plates OU, and there was resolution of the subjective red desaturation OS. Extraocular motility improved in all directions of gaze. The IOP improved to 16 mm Hg OD and 17 mm Hg OS while remaining on timolol. Hertel exophthalmometry measured 20 mm OD and 23.5 mm OS (an improvement of 4.5 mm OD and 3 mm OS). There was resolution of eyelid inflammation and chemosis, and improvement in conjunctival injection bilaterally. The CAS was 1 out of 10. HVF testing revealed complete resolution of the previous defect with MD of +0.40 dB OS ( Fig. 2 C).
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Case 2
A 68-year-old Caucasian female with Graves’ disease diagnosed seven years prior presented with blurry vision OD and binocular diplopia for 6 months that had acutely worsened over the past weeks. The patient was taking methimazole with serum thyroid hormone levels in the normal range and was a never-smoker. On examination, VA was 20/30 OD and 20/25 OS with an rAPD OD. Ishihara color testing was 8 out of 8 plates OU, but with slower response OD. Extraocular motility was severely restricted in supraduction and moderately restricted in abduction and adduction OU. The IOP was 25 mm Hg OD and 21 mm Hg OS. Hertel exophthalmometry measured 20.5 mm OD and 21 mm OS. She had moderately severe eyelid edema and mild chemosis OU. The optic discs appeared normal OU. The CAS was 3 out of 7. CT of the orbits revealed enlarged extraocular muscles and apical crowding concerning for CON, right greater than left ( Fig. 3 ). HVF testing showed a Stage 2a pattern with advancement of the inferior altitudinal defect above the horizontal midline into the superior temporal field with MD of −3.61 dB OD ( Fig. 4 A) and full field OS. The patient was started on weekly 500 mg IV solumedrol until teprotumumab therapy could be initiated.
