Successful Treatment of Bilateral Compressive Optic Neuropathy With Teprotumumab

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Successful Treatment of Bilateral Compressive Optic Neuropathy With Teprotumumab Gillian R. Paton, MD, Brady Kwong, BA, Madhura A. Tamhankar, MD A 78-year-old man presented with bilateral decreased vision along with an inferior scotoma in his left eye and double vision after cataract surgery. His medical history was significant for hypothyroidism treated with levothyroxine, and multiple myeloma diagnosed 12 years ago, currently in remission after stem cell transplant. Best-corrected vision was 20/30 in the right (right eye) and 20/60 in the left eye (left eye) with dyschromatopsia and a left afferent pupillary defect. Inferior visual field defect was noted by confrontation technique from the left eye. Hertel exophthalmometry measurements revealed proptosis of 22 mm right eye and 24 mm left eye with bilateral eyelid retraction and limitation of ocular ductions in all directions in the left eye. Ocular alignment revealed a left hypertropia of 4 prism diopters (PDs) and exotropia of 2 PD. He had bilateral conjunctival injection and chemosis. Hypertrophy of plica semilunaris was seen in the left eye. There was nuclear sclerosis right eye, pseudophakia left eye with a pale appearing left optic nerve. His presentation raised the concern for active thyroid eye disease and compressive optic neuropathy (CON). MRI of the orbits revealed bilateral proptosis, diffuse enlargement of the extraocular muscles with relative sparing of the tendons and compression of the left optic nerve at the orbital apex (Fig. 1A). He was initially treated with intravenous methylprednisolone 500 mg weekly for 4 weeks and then 250 mg weekly for additional 4 weeks and reported some improvement in vision. However, after steroids were discontinued, his vision deteriorated to 20/70 right eye and 20/250 left eye with worsening proptosis, severe conjunctival chemosis, hypertrophy of caruncle and plica semilunaris in the left eye and ocular dysmotility (Fig. 2A). Because of his worsening clinical status teprotumumab was requested for emergency use. One week after teprotumumab was administered; there was significant improvement in vision, conjunctival chemosis, and proptosis (Fig. 2B-D). After the second teprotumumab infusion, vision improved to 20/30 right eye, 20/40 left eye with improvement in color vision and complete recovery of visual fields. After 4 teprotumumab infusions, his vision was 20/30 right eye, 20/25 left eye, clinical activity score was zero, and proptosis reduced to 16 mm of Hg in both eyes. Repeat MRI showed marked improvement in the enlargement of the extraocular muscles (Fig. 1B). Thyroid-associated orbitopathy (TAO) is an autoimmune condition that affects the retrobulbar tissues causing hypertrophy of retrobulbar fat and extraocular muscles. It is typically associated with Graves hyperthyroidism and can vary in severity ranging from mild to vision-threatening complications (1). CON from TAO causes visual deterioration that requires emergent treatment with steroids and/or orbital decompression. Teprotumumab is a monoclonal antibody that inhibits insulin-like growth factor I receptor (IGF-IR). Multiple proinflammatory factors are known to be expressed by IGF-1R in relation to extraocular muscles and orbital fibroblast, including IL-1b, 26, 28, 210, 212, and 216 as well as tumor Division of Neuro-ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania. The authors report no conflicts of interest. Address correspondence to Madhura A. Tamhankar MD, Scheie Eye Institute, University of Pennsylvania, Division of Neuroophthalmology, 51 North 39th Street, Philadelphia, PA 19107; E-mail: [e-mail] Paton et al: J Neuro-Ophthalmol 2023; 43: e209-e210 FIG. 1. A. T1 axial MRI of the orbits showing enlargement of the extraocular muscles in both eyes causing compressive optic neuropathy. B. T1 axial MRI of the orbits showing improvement in the extraocular muscle enlargement after 5 infusions of teprotumumab. e209 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. A. External photograph showing bilateral proptosis and severe left eye conjunctival chemosis and proptosis before teprotumumab infusion. B–D. External photograph showing marked improvement in the conjunctival chemosis and proptosis after first (Fig. 1B), second (Fig. 1C), and fourth (Fig. 1D) teprotumumab infusions. necrosis factor alpha. Blocking of IGF-1R promotes downregulation of the pro-inflammatory mediators thereby reducing orbital inflammation (2). Teprotumumab first received Food and Drug Administration approval for the management of active TAO in January 2020. Its efficacy was studied in 2 clinical trials that showed the drug to be an effective treatment for patients with active forms of TAO with a reduction of 2 points in the clinical activity score and an average reduction in proptosis of 2 mm compared with placebo (2,3). The efficacy of teprotumumab for TAO-related CON has not been previously studied as patients with CON were excluded from the 2 clinical trials. However, 3 recent reports of efficacy of Teprotumumab in the treatment of CON have emerged (4–6). Sears reported a 45-year-old man with left CON of several months duration who had visual acuity of 20/160 before the initiation of therapy and improving to 20/ 30 after 2 teprotumumab infusions (4). Slentz reported a 62year-old man presenting with early CON in the right eye with visual acuity of 20/25 right eye and 20/20 left eye, bilateral proptosis, severe right eye conjunctival chemosis, optic nerve hemorrhages, and inferonasal field defect. Significant improvement was documented in this patient after a full course of teprotumumab (5). Hwang reported a case of an 81-year-old woman with bilateral CON with vision of 20/100 right eye and counting fingers at 3 feet left eye who failed oral steroid treatment. Vision improved to 20/40 right eye and 20/30 left eye with 8 infusions of teprotumumab (6). In our patient, because his vision loss was gradually progressive and bilateral, we decided to try intravenous steroids initially and although he did notice improvement with weekly intravenous steroids, his vision started to deteriorate after steroids were stopped. Orbital decompression was also considered, but held off because of availability of teprotumumab and initial encouraging reports of efficacy seen with this medication. Given the dramatic resolution of proptosis, chemosis, and recovery of normal vision, we were able to avoid the morbidity associated with orbital decompression in this older patient. Moreover, a follow-up MRI of the orbits showed radiographic improvement with decrease in the thicke210 ness of the extraocular muscles after 5 infusions of teprotumumab. Although the efficacy of teprotumumab in those with CON was not studied in the 2 placebo-controlled trials (2,3), there is emerging evidence that teprotumumab may be a very effective medication in those with sight-threatening CON and should be considered as first line therapy ahead of steroids and/ or orbital decompression in such patients. STATEMENT OF AUTHORSHIP Conception and design: G. R. Paton, B. Kwong, M. A. Tamhankar; Acquisition of data: G. R. Paton, B. Kwong, M. A. Tamhankar; Analysis and interpretation of data: G. R. Paton, B. Kwong, M. A. Tamhankar. Drafting the manuscript: G. R. Paton, B. Kwong, M. A. Tamhankar; Revising it for intellectual content: G. R. Paton, B. Kwong, M. A. Tamhankar. Final approval of the completed manuscript: G. R. Paton, B. Kwong, M. A. Tamhankar. REFERENCES 1. Weiler DL. Thyroid eye disease: a review. Clin Exp Optom. 2017;100:20–25. 2. Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376:1748–1761. 3. Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EHZ, Perdok R, Fleming JC, Fowler BT, Marcocci C, Marinò M, Antonelli A, Dailey R, Harris GJ, Eckstein A, Schiffman J, Tang R, Nelson C, Salvi M, Wester S, Sherman JW, Vescio T, Holt RJ, Smith TJ. 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