Prithvi Ramtohul1, K Bailey Freund2. 1. Centre Hospitalier Universitaire de l'Hôpital Nord, Marseille, France. Electronic address: pramtohul@me.com. 2. Vitreous Retina Macula Consultants of New York, New York, New York; Department of Ophthalmology, New York University School of Medicine, New York, New York; LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York.
Abstract
PURPOSE: Immunotherapy with atezolizumab, a checkpoint inhibitor targeting the programmed cell death 1 (PD-1) axis, has shown promising results for the treatment of certain metastatic cancers. Atezolizumab-associated acute macular neuroretinopathy (AMN) with retinal venulitis is a newly reported immune-related adverse event (irAE) that further expands the range of adverse effects associated with checkpoint inhibitor therapy. We describe the clinical course and imaging findings of a similar AMN-like retinopathy after treatment with atezolizumab. DESIGN: Retrospective case series. PARTICIPANTS: Three patients treated with atezolizumab for metastatic breast cancer (n = 1) and non-small-cell lung cancer (n = 2). METHODS: Inclusion criterion was a clinical diagnosis of AMN-like retinopathy with or without retinal vasculitis after atezolizumab administration. MAIN OUTCOME MEASURES: Clinical course and multimodal retinal imaging including color photographs, spectral-domain OCT, near-infrared reflectance, and fluorescein angiography were investigated. RESULTS: Three patients (1 woman and 2 men; mean age, 51 years) experienced the acute onset of reduced visual acuity and paracentral scotomas 2 weeks after their first infusion of atezolizumab. Visual symptoms corresponded to focal areas of pericentral photoreceptor disruption in all cases. In 1 patient imaged with fluorescein angiography, focal segments of retinal venulitis were detected. After treatment cessation, incomplete visual recovery was related to persistent photoreceptor damage. All patients died of their cancer within 6 months after the onset of retinopathy. CONCLUSIONS: To our knowledge, there are 3 previously published cases of atezolizumab-associated AMN with retinal vasculitis. This series of 3 similar cases strengthens the association of programmed death ligand 1 (PD-L1) inhibition with this rare form of retinopathy that was termed "anti-PD-L1-associated retinopathy." This irAE seems to be a consistent occurrence in the second week postadministration with lasting structural and functional deficits seen after treatment cessation. Pathophysiologic mechanisms may include loss of tolerance in an immune-privileged organ and subsequent development of T-cell-driven inflammation. In this emerging field, expanding the spectrum and pathogenesis of irAEs is essential to define strategies for prevention, early detection, and appropriate management.
PURPOSE: Immunotherapy with atezolizumab, a checkpoint inhibitor targeting the programmed cell death 1 (PD-1) axis, has shown promising results for the treatment of certain metastatic cancers. Atezolizumab-associated acute macular neuroretinopathy (AMN) with retinal venulitis is a newly reported immune-related adverse event (irAE) that further expands the range of adverse effects associated with checkpoint inhibitor therapy. We describe the clinical course and imaging findings of a similar AMN-like retinopathy after treatment with atezolizumab. DESIGN: Retrospective case series. PARTICIPANTS: Three patients treated with atezolizumab for metastatic breast cancer (n = 1) and non-small-cell lung cancer (n = 2). METHODS: Inclusion criterion was a clinical diagnosis of AMN-like retinopathy with or without retinal vasculitis after atezolizumab administration. MAIN OUTCOME MEASURES: Clinical course and multimodal retinal imaging including color photographs, spectral-domain OCT, near-infrared reflectance, and fluorescein angiography were investigated. RESULTS: Three patients (1 woman and 2 men; mean age, 51 years) experienced the acute onset of reduced visual acuity and paracentral scotomas 2 weeks after their first infusion of atezolizumab. Visual symptoms corresponded to focal areas of pericentral photoreceptor disruption in all cases. In 1 patient imaged with fluorescein angiography, focal segments of retinal venulitis were detected. After treatment cessation, incomplete visual recovery was related to persistent photoreceptor damage. All patients died of their cancer within 6 months after the onset of retinopathy. CONCLUSIONS: To our knowledge, there are 3 previously published cases of atezolizumab-associated AMN with retinal vasculitis. This series of 3 similar cases strengthens the association of programmed death ligand 1 (PD-L1) inhibition with this rare form of retinopathy that was termed "anti-PD-L1-associated retinopathy." This irAE seems to be a consistent occurrence in the second week postadministration with lasting structural and functional deficits seen after treatment cessation. Pathophysiologic mechanisms may include loss of tolerance in an immune-privileged organ and subsequent development of T-cell-driven inflammation. In this emerging field, expanding the spectrum and pathogenesis of irAEs is essential to define strategies for prevention, early detection, and appropriate management.
Authors: Helio V Neves da Silva; John Placide; Anne Duong; Yasmyne Ronquillo; Shannon McCabe; Majid Moshirfar Journal: Ther Adv Ophthalmol Date: 2022-04-26