Case Presentation: An 86-year-old female with hypertension, hyperlipidemia, and pre-existing left eye vision loss presented to an outside hospital after a fall with acute painless right eye vision loss. High dose IV methylprednisone was initiated at the OSH on day 2 due to concerns for giant cell arteritis (GCA) given acute vision loss and optic disc edema. Temporal artery biopsy on day 4 was found to be negative, prompting consideration of alternative etiologies. An MRI demonstrated bilateral optic neuritis with left lacrimal gland enlargement, raising concern for atypical ON. She was then transferred to our hospital on day 6 for more extensive laboratory evaluation. Autoimmune, infectious, and demyelinating panels were all found to be negative.Between days 8–12, the patient’s visual acuity improved with continued IV steroids, supporting an inflammatory process. However, on day 16, repeat MRI revealed a new left temporal lobe infarct, prompting neurology consultation and escalation of therapy to plasma exchange.During therapy, she developed a painless vesicular eruption on her lower back. Given her age and immunosuppression, there was initial concern for disseminated VZV, but NAAT testing confirmed HSV-2. She was treated with IV acyclovir with resolution of her symptoms. She then completed five sessions of plasma exchange and continued a prolonged prednisone taper. At discharge, vision in her right eye remained improved.
Discussion: In this case, extensive evaluation of vascular, infectious, autoimmune, malignant, and demyelinating etiologies was unrevealing. The absence of a clear underlying cause despite multimodal diagnostic testing suggested a truly atypical presentation. Collaboration was essential in narrowing the differential and guiding treatment, particularly given overlapping features with giant cell arteritis, neurosarcoidosis, and ischemic optic neuropathy.Although no definitive infectious trigger for the optic neuritis was identified, the patient’s HSV-2 reactivation during immunosuppressive therapy raises the possibility that viral reactivation could have contributed. While HSV-associated optic neuropathy is rare and typically occurs in younger or immunocompromised patients, its role in elderly individuals undergoing high-dose steroids warrants further study. This case underlines how atypical ON often requires high-dose corticosteroids and, in refractory or complex cases, plasma exchange. These therapies carry significant risks, including susceptibility to opportunistic infections.
Conclusions: Atypical optic neuritis (ON) in elderly patients is uncommon and presents significant diagnostic and management challenges. Because classic ON typically occurs in younger adults and incidence declines after age 50, presentations in patients over 70 require a broad differential that includes infectious, vascular, and autoimmune causes. This case illustrates the complexity of diagnosing atypical ON when extensive testing is unrevealing, and how treatment with high-dose immunosuppression can lead to complications such as viral reactivation. Overall, the rarity, heterogeneous presentation, and diagnostic uncertainty surrounding atypical ON in older adults underscore the need for further research to better understand its underlying mechanisms and optimize management strategies.