Photopsias in the Setting of Nivolumab Therapy

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Photopsias in the Setting of Nivolumab Therapy Aneesha Ahluwalia, BS, Anita A. Kohli, MD I Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 05/04/2022 mmune checkpoint inhibitors (ICIs) have gained popularity as treatment options for various malignancies due to survival benefits (1). Cases of ocular immune-related adverse events (irAEs) have therefore been more frequently reported. Optic neuritis is a rare unintended irAE that has been observed in patients receiving varying doses of ICIs, including nivolumab, ipilimumab, and atezolizumab, occurring between 4 and 52 weeks after treatment (1,2). Although a sudden decrease in visual acuity has been the most commonly reported initial symptom, we present a case with photopsias as the sole presentation. A 35-year-old woman with stage IIB cutaneous melanoma of the leg underwent wide excision, and sentinel lymph node biopsy after positron emission tomography scan revealed a hypermetabolic right inguinal node (positive for malignancy). She elected to undergo adjuvant chemotherapy with nivolumab and had completed 8 cycles, after which she developed flashes of light in her right eye for 1 week. She denied blurry vision or pain with eye movement. Nivolumab was held, and ophthalmology was consulted. Her visual acuities were 20/20 in both eyes, without dyschromatopsia, afferent pupillary defect, or anterior inflammation. However, the dilated examination revealed circumferential optic disc edema of the right eye only (Fig. 1), without vitritis. Humphrey visual field demonstrated blind spot enlargement, and optical coherence tomography of the retinal nerve fiber layer (OCT RNFL) showed severe nerve fiber layer edema in the right eye. Magnetic resonance (MR) imaging of the brain and orbits with and without contrast was normal without significant enhancement of the right optic nerve (Fig. 2). MR venogram did not show venous sinus thrombosis. Owing to the severity of the optic disc swelling and the known association with nivolumab use, optic neuritis was suspected. Given the unilaterality of the disc edema and lack of meningeal enhancement, lumbar puncture was deferred. She received 3 days of IV methylprednisone (1 g daily) and 2 days of IVIG (2 g/kg), with a subsequent prednisone taper. Within 10 days, there was improvement in her symptoms and in the right optic nerve edema, with normalization of RNFL thickness on OCT within 2 months. This report illustrates the first case of ICI-related optic neuritis presenting only with photopsias. Ophthalmic evaluation was essential in establishing the diagnosis, as she otherwise demonstrated no significant MRI findings, FIG. 1. Fundus photographs demonstrating optic disc edema in the right eye and a normal left optic disc. Department of Ophthalmology and Visual Science (AA, AAK), Yale University School of Medicine, New Haven, Connecticut; and Department of Neurology (AAK), Yale University School of Medicine, New Haven, Connecticut. The authors report no conflicts of interest. Address correspondence to Anita A. Kohli, MD, Department of Ophthalmology and Visual Science, 40 Temple Street, New Haven, CT 06510; E-mail: [e-mail] Ahluwalia and Kohli: J Neuro-Ophthalmol 2021; 41: e25-e26 unlike previously reported cases, or overt signs of optic neuropathy, except for significant optic nerve edema (1,2). The heterogeneity in presenting symptoms and imaging findings of immune modulation-related optic neuritis may reflect a similar diversity in its pathophysiologic mechanisms, of which there is a limited understanding. Traditionally, irAEs are believed to be related to tolerance e25 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence biomarkers or human leukocyte antigen haplotypes (4). However, until these methods are established, early detection of ocular irAEs remains critical for preventing permanent vision loss. As knowledge of ocular irAEs and their presenting symptoms grows, patients can be informed of visual changes, including photopsias, that may indicate a need for urgent evaluation. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: A. Ahluwalia and A. A Kohli; b. Acquisition of data: A. Ahluwalia and A. A Kohli; c. Analysis and interpretation of data: A. Ahluwalia and A. A Kohli. Category 2: a. Drafting the manuscript: A. Ahluwalia and A. A Kohli; b. Revising it for intellectual content: A. Ahluwalia and A. A Kohli. Category 3: a. Final approval of the completed manuscript: A. Ahluwalia and A. A Kohli. FIG. 2. Postcontrast T1-weighted axial views on MR imaging of the orbits demonstrating lack of optic nerve enhancement. of pre-existing, peripheral self-reactive T-cells (3,4). In addition, a recently proposed theory suggests that targets of the anti-tumor immune response may be expressed in normal tissues, resulting in cross-reactivity (4). Ocular irAEs could occur via disruption of the blood–retinal barrier by deregulated proinflammatory T-cells or by dysregulation of the balance between immunomodulating cytokines and proteins in the local immunologically privileged environment of the eye. Indeed, a recent study of nivolumabinduced uveitis reported increased levels of proinflammatory interleukins and interferons in intraocular fluid samples (5). In the future, avoidance of ocular irAEs may be possible via identification of populations of autoreactive T-cells by e26 REFERENCES 1. Mori S, Kurimoto T, Ueda K, Enomoto H, Sakamoto M, Keshi Y, Yamada Y, Nakamura M. 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Ahluwalia and Kohli: J Neuro-Ophthalmol 2021; 41: e25-e26 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.