Michel M Sun1, Nicolas Seleme, John J Chen, Anastasia Zekeridou, Elia Sechi, Ryan D Walsh, Johanna D Beebe, Osama Sabbagh, Luis J Mejico, Sean Gratton, Philip M Skidd, David A Bellows, Julie Falardeau, Clare L Fraser, Cecilia Cappelen-Smith, Scott R Haines, Bahareh Hassanzadeh, Meagan D Seay, Prem S Subramanian, Zoë Williams, Lynn K Gordon. 1. Department of Ophthalmology (MMS, NS, LKG), Jules Stein Eye Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California; Department of Ophthalmology (JJC), Mayo Clinic, Rochester, Minnesota; Department of Neurology (JJC, AZ, ES), Mayo Clinic, Rochester, Minnesota; Department of Ophthalmology & Visual Sciences (RDW), Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Ophthalmology (JDB), Park Nicollet Health Services, Minneapolis, Minnesota; Department of Ophthalmology (OS), University of Kentucky/Retina Associates of Kentucky, Lexington, Kentucky; Department of Neurology (LJM), SUNY Upstate Medical University, Syracuse, New York; Department of Ophthalmology (LJM), SUNY Upstate Medical University, Syracuse, New York; Department of Neurology (SG), University of Missouri-Kansas City, Kansas City, Missouri; Department of Ophthalmology (PMS), University of Vermont Medical Center, Burlington, Vermont; The Medical Eye Center (DAB), Manchester, New Hampshire; Department of Ophthalmology (JF), Oregon Health & Science University, Portland, Oregon; Department of Ophthalmology (CLF), University of Sydney, Sydney, Australia; Department of Neurology & Neurophysiology (CC-S), Liverpool Hospital, NSW, Australia; Department of Neurology (SRH), Virginia Commonwealth University School of Medicine, Richmond, Virginia; Department of Neurology (BH), INI Eye Center, OSF Healthcare, University of Illinois College of Medicine, Peoria, Illinois; Department of Ophthalmology (MDS), University of Utah, Salt Lake City, Utah; Department of Ophthalmology (PSS), University of Colorado, Aurora, Colorado; and Department of Ophthalmology (ZW), University of Rochester Medical Center, Rochester, New York.
Abstract
BACKGROUND: In recent years, CTLA-4 and PD-1/PD-L1 checkpoint inhibitors have proven to be effective and have become increasingly popular treatment options for metastatic melanoma and other cancers. These agents work by enhancing autologous antitumor immune responses. Immune-related ophthalmologic complications have been reported in association with checkpoint inhibitor use but remain incompletely characterized. This study seeks to investigate and further characterize the neuro-ophthalmic and ocular complications of immune checkpoint blockade treatment. METHODS: A survey was distributed through the secure electronic data collection tool REDCap to neuro-ophthalmology specialists in the North American Neuro-Ophthalmology Society listserv. The study received human subjects approval through the University of California at Los Angeles Institutional Review Board. The survey identified patients sent for neuro-ophthalmic consultation while receiving one or more of a PD-1 inhibitor (pembrolizumab, nivolumab, or cemiplimab); PD-L1 inhibitor (atezolizumab, avelumab, or durvalumab); or the CTLA-4 inhibitor ipilimumab. Thirty-one patients from 14 institutions were identified. Patient demographics, neuro-ophthalmic diagnosis, diagnostic testing, severity, treatment, clinical response, checkpoint inhibitor drug used, and cancer diagnosis was obtained. RESULTS: The checkpoint inhibitors used in these patients included pembrolizumab (12/31), nivolumab (6/31), combined ipilimumab with nivolumab (7/31, one of whom also received pembrolizumab during their course of treatment), durvalumab (3/31), ipilimumab (2/31), and cemiplimab (1/31). Malignant melanoma (16/31) or nonsmall cell lung carcinoma (6/31) were the most common malignancies. The median time between first drug administration and the time of ophthalmological symptom onset was 14.5 weeks. Eleven patients had involvement of the optic nerve, 7 patients had inflammatory orbital or extraocular muscle involvement, 6 patients had ocular involvement from neuromuscular junction dysfunction, 4 patients had cranial nerve palsy, and 4 patients had non neuro-ophthalmic complications. Use of systemic corticosteroids with or without stopping the checkpoint inhibitor resulted in improvement of most patients with optic neuropathy, and variable improvement for the other ophthalmic conditions. CONCLUSION: This study describes the variable neuro-ophthalmic adverse events associated with use of immune checkpoint inhibitors and contributes a more thorough understanding of their clinical presentations and treatment outcomes. We expect this will increase awareness of these drug complications and guide specialists in the care of these patients.
BACKGROUND: In recent years, CTLA-4 and PD-1/PD-L1 checkpoint inhibitors have proven to be effective and have become increasingly popular treatment options for metastatic melanoma and other cancers. These agents work by enhancing autologous antitumor immune responses. Immune-related ophthalmologic complications have been reported in association with checkpoint inhibitor use but remain incompletely characterized. This study seeks to investigate and further characterize the neuro-ophthalmic and ocular complications of immune checkpoint blockade treatment. METHODS: A survey was distributed through the secure electronic data collection tool REDCap to neuro-ophthalmology specialists in the North American Neuro-Ophthalmology Society listserv. The study received human subjects approval through the University of California at Los Angeles Institutional Review Board. The survey identified patients sent for neuro-ophthalmic consultation while receiving one or more of a PD-1 inhibitor (pembrolizumab, nivolumab, or cemiplimab); PD-L1 inhibitor (atezolizumab, avelumab, or durvalumab); or the CTLA-4 inhibitor ipilimumab. Thirty-one patients from 14 institutions were identified. Patient demographics, neuro-ophthalmic diagnosis, diagnostic testing, severity, treatment, clinical response, checkpoint inhibitor drug used, and cancer diagnosis was obtained. RESULTS: The checkpoint inhibitors used in these patients included pembrolizumab (12/31), nivolumab (6/31), combined ipilimumab with nivolumab (7/31, one of whom also received pembrolizumab during their course of treatment), durvalumab (3/31), ipilimumab (2/31), and cemiplimab (1/31). Malignant melanoma (16/31) or nonsmall cell lung carcinoma (6/31) were the most common malignancies. The median time between first drug administration and the time of ophthalmological symptom onset was 14.5 weeks. Eleven patients had involvement of the optic nerve, 7 patients had inflammatory orbital or extraocular muscle involvement, 6 patients had ocular involvement from neuromuscular junction dysfunction, 4 patients had cranial nerve palsy, and 4 patients had non neuro-ophthalmic complications. Use of systemic corticosteroids with or without stopping the checkpoint inhibitor resulted in improvement of most patients with optic neuropathy, and variable improvement for the other ophthalmic conditions. CONCLUSION: This study describes the variable neuro-ophthalmic adverse events associated with use of immune checkpoint inhibitors and contributes a more thorough understanding of their clinical presentations and treatment outcomes. We expect this will increase awareness of these drug complications and guide specialists in the care of these patients.
Authors: Jacek Baj; Alicja Forma; Joanna Kobak; Magdalena Tyczyńska; Iga Dudek; Amr Maani; Grzegorz Teresiński; Grzegorz Buszewicz; Jacek Januszewski; Jolanta Flieger Journal: Int J Environ Res Public Health Date: 2022-03-06 Impact factor: 3.390