Name

Caractéristiques cliniques et morphologiques de la rétinopathie associée aux anti-PD-L1

: Immunotherapy with atezolizumab, a checkpoint inhibitor targeting the programmed cell death 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 which further expands the range of adverse effects associated with checkpoint inhibitor therapy.Wedescribe the clinical course and imaging findings of a similar AMN-like retinopathy following treatment with atezolizumab.

Retrospective case series. Three patients treated with atezolizumab for metastatic breast cancer (n=1) and non-small-cell lung cancer (n=2) respectively. : Inclusion criterion was a clinical diagnosis of AMN-like retinopathy with or without retinal vasculitis following atezolizumab administration. Clinical course and multimodal retinal imaging including color photographs, spectral-domain optical coherence tomography, near-infrared reflectance, and fluorescein angiography were investigated.

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 succumbed to their cancer within 6 months following the onset of retinopathy. 

To our knowledge, there are 3 previously published cases of atezolizumab-associatedAMN with retinal vasculitis. This series of 3 similar cases strengthens the association of programmed death-ligand 1 inhibition with this rare form of retinopathy which was termed: Anti-PD-L1 associated retinopathy. This immune-related adverse event seems to be a consistent occurrence in the second week post-administration with lasting structural and functional deficits seen after treatment cessation. Pathophysiologic mechanisms may include loss of tolerance in an immune-privilege organ and subsequent development of T-cell-driven inflammation. In this emerging field, expanding the spectrum and pathogenesis of immune-related adverse events is essential to define strategies for prevention, early detection and appropriate management.

In conclusion, our description of 3 patients experiencing vision loss due to AMN-like lesions occurring shortly after initiation of anti-PD-L1 therapy with atezolizumab strengthens this association. We suggest the nomenclature: “Anti-PD-L1-Associated Retinopathy” to describe this entity.