Optic Disc Edema Associated With Ustekinumab Therapy

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Optic Disc Edema Associated With Ustekinumab Therapy Dustin J. Randall, MD, Natalie K. Modersitzki, BS, Sravanthi Vegunta, MD, Meagan D. Seay, DO A 54-year-old man with a medical history of psoriasis and pericarditis presented to the neuro-ophthalmology clinic with a chief complaint of “seeing clouds” in the periphery of his right eye over the past 3 weeks. These symptoms were episodic, lasting 15 seconds each and occurring several times a day. He had pain in his right eye which resolved spontaneously after 2 days. The patient reported a history of chronic headache, though denied any recent changes in severity. Approximately 9 months before the onset of visual disturbances, he was prescribed ustekinumab, a monoclonal antibody for psoriasis, and had received 3 doses (once every 3 months), most recently 2 months before symptom onset. Visual acuities, color vision, and intraocular pressure were normal at the time of presentation. Pupillary testing revealed a 0.9 log unit right afferent pupillary defect. His efferent visual and slitlamp examinations were normal, without evidence of intraocular inflammation. The right optic nerve was elevated with anomalous vasculature and with blurred margins 360° around the nerve. The left optic nerve was elevated with blurred margins 270° around the nerve (Fig. 1). Optical coherence tomography of the peripapillary retinal nerve fiber layer revealed diffuse elevation of both optic nerves (Fig. 2). Automated visual field (AVF) 24-2 showed an enlarged blind spot with inferior arcuate defect of the right eye and an enlarged blind spot of the left eye. Orbital ultrasound showed large calcified drusen in the right optic nerve and a normal left optic nerve with a negative 30-degree test bilaterally. Owing to suspicion that the optic disc edema was caused by ustekinumab, he received no further infusions of ustekinumab and initiated treatment with cyclosporine. MRI of the brain and orbits with and without contrast was normal, including no features of elevated intracranial pressure and no optic nerve enhancement. A lumbar puncture was performed 2 weeks after initial presentation, revealing an opening pressure of 15 cm H2O and values of 3/uL white blood cells (reference 0–5/uL), 29 red blood cells, 34 mg/dL protein (reference 14– 45), and 74 mg/dL glucose (reference 50–80 mg/dL). He was followed off ustekinumab. At 3-week follow-up, his optic disc Oakland University William Beaumont School of Medicine (DR), Rochester, Michigan; and John A. Moran Eye Center, University of Utah (NM, SV, MDS), Salt Lake City, Utah. The authors report no conflicts of interest D. Randall and N. Modersitzki contributed equally to this work. Address correspondence to Meagan Seay, DO, 65 Mario Capecchi Drive, Salt Lake City, UT 84132; E-mail: [e-mail] e32 edema was essentially unchanged and his symptoms persisted. He continued to have normal visual acuity, and AVF showed mild improvement in the inferior visual field defect in the right eye. At follow-up 3 months later, the patient’s episodes of transient monocular vision loss had resolved, optic disc edema was improved, and AVF normalized. We believe this patient’s ustekinumab exposure may have caused optic disc edema. Ustekinumab is a human IgG1 monoclonal antibody that directly targets the p40 subunit of IL-12 and IL-23 cytokines, which are involved in the pathogenesis of plaque psoriasis skin lesions. By preventing IL-12 and IL-23 from binding to their receptors, ustekinumab blocks the T1 and T17 inflammatory pathways. Reported side effects include respiratory tract infections, nasopharyngitis, headache, and mild injection site reactions, although there are no robust associations with optic disc edema (1). We believe that ustekinumab may have been causal because of the resolution of disc edema after discontinuation of ustekinumab and the absence of an alternate etiology despite extensive investigation. Although the patient did have psoriasis, there is no clear association between psoriasis and isolated papillitis without comorbid uveitis, which was not observed during either the initial or follow-up examinations (2,3). There are also rare reports of FIG. 1. Color fundus photographs of the right eye (A) and left eye (B) at initial presentation showing anomalous-appearing optic nerves with optic disc edema bilaterally. Six months after discontinuation of ustekinumab (C, D), the optic nerves continue to appear anomalous, although the optic disc edema is improved. Randall et al: J Neuro-Ophthalmol 2024; 44: e32-e33 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Optical coherence tomography of the retinal nerve fiber layer at presentation (A) showing diffuse optic disc edema. The right eye (displayed on left side) has optic nerve head drusen, creating an anomalous appearance to the measurement. Six months after discontinuation of ustekinumab (B), there is improvement in the optic disc edema bilaterally. ustekinumab associated with autoimmune thyroiditis and interstitial lung disease (4). Ustekinumab’s modulation of the cytokine and T-cell population might plausibly lead to rare, adverse autoimmune events. The relevance of the optic disc drusen which were discovered in the right eye is unclear. Given the reduction in disc edema over time and the normalization in afferent visual function, we believe that either direct structural residua of optic disc drusen or drusen-associated nonarteritic anterior ischemic optic neuropathy were unlikely. Although toxic optic neuropathies generally do not result in optic disc edema, the potential for optic disc edema and afferent visual dysfunction in association with amiodarone and tacrolimus use is widely accepted (5). Ustekinumab may be another such medication. STATEMENT OF AUTHORSHIP Conception and design: M. D. Seay. Acquisition of data: N. Modersitzki, D. Randall. Analysis and interpretation of data: N. Randall et al: J Neuro-Ophthalmol 2024; 44: e32-e33 Modersitzki, D. Randall, M. D. Seay, S. Vegunta. Drafting the manuscript: N. Modersitzki, D. Randall. Revising the manuscript for intellectual content: N. Modersitzki, D. Randall, M. D. Seay, S. Vegunta. Final approval of the completed manuscript: N. Modersitzki, D. Randall, M. D. 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