A 64-year-old female receiving sintilimab treatment for cervical cancer developed acute retinal necrosis syndrome caused by a varicella-zoster virus infection, according to a case report published in January 2024. The patient experienced vision loss, floaters, and left eye redness before improving with antiviral and anti-inflammatory therapy.
Acute retinal necrosis is an inflammatory condition primarily triggered by herpesvirus infections. According to a case report published on January 23, 2024, in Frontiers in Immunology (Front Immunol. 2024 Jan 23:15:1301329. doi: 10.3389/fimmu.2024.1301329. eCollection 2024) by Pei Wang et al., the syndrome most frequently stems from the varicella-zoster virus, followed by the herpes simplex virus and occasionally the cytomegalovirus. The affiliations listed for the authors include the Department of Ophthalmology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, Shandong, China; the School of Medicine, Qingdao University, Qingdao, Shandong, China; and the Department of Pathology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, Shandong, China.
Sintilimab Treatment and Viral Reactivation in Cervical Cancer
Sintilimab functions as an immune checkpoint inhibitor that can enhance the body’s anti-tumor immune response. However, treatment with immune checkpoint inhibitors may lead to reactivation of the varicella-zoster virus.
In this documented case, the 64-year-old female patient developed vision loss and floaters with left eye redness for one week after 22 cycles of sintilimab for cervical cancer, which is identified in the report as a cervical malignant tumor. Figure 1 illustrates squamous cell carcinoma of the cervix, where the histological section is stained with Hematoxylin and Eosin (H&E) and captured at an original magnification of X200. This view reveals round or oval-shaped cancer cells with irregularly round or oval nuclei that exhibit deep staining, alongside an increased ratio of nuclear to cytoplasmic volume and pathological mitosis, plus a significant infiltration of inflammatory cells surrounding the cancerous mass.
Ophthalmological Findings and Clinical Diagnosis
Medical staff diagnosed the patient with acute retinal necrosis syndrome secondary to varicella-zoster virus based on clinical manifestations, ophthalmological examination, and a vitreous humor biopsy.
Figure 2 (A) shows the fundus photograph of the patient during their first visit, indicating severe opacity in the vitreous body, extremely thin retinal arteries, and multiple yellow-white necrotic lesions with clear boundaries of varying sizes visible in the peripheral retina outside the vascular arch. Partially fused necrotic lesions can be seen inside the necrotic lesions, accompanied by flake-shaped bleeding.
Therapeutic Intervention and Recovery Outcomes
Following diagnosis, the patient received systemic antiviral and anti-inflammatory therapy, and her retinal necrosis lesions and visual function improved.
Figure 2 (B) shows the fundus photograph of the patient at their last follow-up after 40 weeks of anti-inflammatory and antiviral treatment. By this time, the opacity in the vitreous body has disappeared, and the retinal arteries appear as white lines, while the previously yellow-white necrotic lesions have disappeared, leaving multiple retinal atrophic lesions with pigmentary disturbances remaining.
This case highlights the intersection between modern cancer immunotherapy and unexpected ocular complications.
In conclusion, clinicians should be aware of the risk of ARN when using sintilimab and should actively monitor patients for prompt diagnosis and optimal management of this rare adverse drug reaction. The
Unresolved Questions in Atypical Herpetic Retinal Infections
Additional clinical contexts, such as a separate case report concerning an immunocompetent child with herpes simplex virus-2 (HSV-2) acute retinal necrosis syndrome considered to have idiopathic unilateral panuveitis sensitive to steroid treatment, demonstrate wider diagnostic challenges. In that background, methods included polymerase chain reaction for detection of viral DNA applied to ocular fluids, in situ hybridization performed on a retinal sample, and HSV serology using ELISA, Western blot techniques, and an in-house indirect immunofluorescence technique. That analysis revealed that serological assays for HSV were negative using ELISA at the time of diagnosis and one year after, though HSV-2 infection was confirmed using polymerase chain reaction of an aqueous humor specimen and in situ hybridization of a retinal biopsy, while retrospective analysis with the Western blot technique detected low titers of anti-HSV antibodies when sera were concentrated 5-fold.
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