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Sudden-Onset Monocular Blurry Vision in a Young Woman

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 32-year-old woman who was admitted to the hospital for fever, flulike symptoms, and altered mental status developed sudden-onset blurry vision in her right eye. Her history was notable for phthisis in her left eye due to a left orbit clear cell sarcoma with metastatic disease, after surgical excision and radiation, with recent enrollment in a palliative immunotherapy research protocol. After completing 2 days of broad-spectrum intravenous antibiotics and antivirals for presumed septic meningitis, her laboratory and imaging results returned negative and she was transitioned to intravenous methylprednisolone (1 mg/kg). One day later, her mental status improved, and she reported central blurry vision in her right eye. On examination, her visual acuity was 20/40 in this eye, she had normal intraocular pressure, and there was no evidence of anterior chamber or vitreous cells. Dilated fundus examination revealed segmental areas of venous sheathing (Figure 1A) in the right eye and was not possible in the left eye owing to phthisis. An optical coherence tomography scan of the right eye revealed hyperreflective changes along the outer plexiform and outer nuclear layers, small intraretinal cysts, and disruption of the ellipsoid and especially the interdigitation zone (Figure 1B).

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Atezolizumab-associated retinopathy

B. Obtain information about the immunotherapy protocol initiated for her sarcoma

The clinical presentation of this patient is compatible with retinal toxicity associated with atezolizumab, an immune checkpoint inhibitor that targets the programmed death ligand 1.1 Checkpoint inhibitors are increasingly being used to treat metastatic malignancies, and their risk of inducing uveitis is well recognized among ophthalmologists.2 However, atezolizumab can also cause a specific form of retinopathy,1,3 which on optical coherence tomography and near infrared imaging demonstrates features similar to those observed with acute macular neuroretinopathy, with hyperreflective changes at the outer plexiform and outer nuclear layers that colocalize on near infrared to dark areas in addition to venulitis and small intraretinal cystic spaces, which are not typical features of acute macular neuroretinopathy.4

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Article Information

Corresponding Author: Dean Eliott, MD, Massachusetts Eye and Ear, Harvard Medical School, 243 Charles St, Boston, MA, 02114 (dean_eliott@meei.harvard.edu).

Published Online: June 9, 2022. doi:10.1001/jamaophthalmol.2022.1327

Conflict of Interest Disclosures: Dr Eliott reported personal fees from Alcon, Allergan, Dutch Ophthalmic, Genentech, Aldeyra Therapeutics, and Pykus Therapeutics and grants from Neurotech and Unity Biotechnology outside the submitted work. No other disclosures were reported.

References
1.
Emens  LA , Davis  SL , Oliver  SCN ,  et al.  Association of cancer immunotherapy with acute macular neuroretinopathy and diffuse retinal venulitis.   JAMA Ophthalmol. 2019;137(1):96-100. doi:10.1001/jamaophthalmol.2018.5191PubMedGoogle ScholarCrossref
2.
Dalvin  LA , Shields  CL , Orloff  M , Sato  T , Shields  JA .  Checkpoint inhibitor immune therapy: systemic indications and ophthalmic side effects.   Retina. 2018;38(6):1063-1078. doi:10.1097/IAE.0000000000002181PubMedGoogle ScholarCrossref
3.
Ramtohul  P , Freund  KB .  Clinical and morphological characteristics of anti-programmed death ligand 1-associated retinopathy: expanding the spectrum of acute macular neuroretinopathy.   Ophthalmol Retina. 2020;4(4):446-450. doi:10.1016/j.oret.2019.11.006PubMedGoogle ScholarCrossref
4.
Fawzi  AA , Pappuru  RR , Sarraf  D ,  et al.  Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging.   Retina. 2012;32(8):1500-1513. doi:10.1097/IAE.0b013e318263d0c3PubMedGoogle ScholarCrossref
5.
Gass  JD .  Pathogenesis of disciform detachment of the neuroepithelium.   Am J Ophthalmol. 1967;63(3):Suppl:1-139.Google Scholar
6.
Kaye  R , Chandra  S , Sheth  J , Boon  CJF , Sivaprasad  S , Lotery  A .  Central serous chorioretinopathy: an update on risk factors, pathophysiology and imaging modalities.   Prog Retin Eye Res. 2020;79:100865. doi:10.1016/j.preteyeres.2020.100865PubMedGoogle ScholarCrossref
7.
Reichstein  D .  Current treatments and preventive strategies for radiation retinopathy.   Curr Opin Ophthalmol. 2015;26(3):157-166. doi:10.1097/ICU.0000000000000141PubMedGoogle ScholarCrossref
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