Introduction: Complete surgical excision with clear margins is the standard treatment for cutaneous squamous cell carcinoma (cSCC). Historically, orbital invasion required high-dose radiation, with or without chemotherapy or exenteration. However, if the orbital involvement is limited to perineural spread within a nerve and remains distal to the skull base foramen, a neurectomy offers a globe-sparing option that may more definitively prevent intracranial spread. This study is the first to report outcomes of globe-sparing neurectomy for isolated frontal nerve perineural spread in cSCC. Methods: A retrospective chart review was performed to identify patients with zone 1 (distal to the superior orbital fissure) cSCC who underwent globe-sparing frontal nerve (FN) resection for perineural spread (PNS). Patient demographics, medical history, and treatment details were obtained from electronic medical records. Radiographic measurements of nerve thickness and enhancement were obtained from pre- and post-gadolinium coronal T1-weighted MRI orbit images, with or without fat suppression. Surgical margin and resection lengths were based on pathology report measurements. Results: Five consecutive patients underwent frontal nerve resection via anterior orbitotomy. Four patients with negative proximal margins received subsequent radiation and/or chemotherapy/immunotherapy and remained alive and free of intracranial disease at 18–54 months postoperatively. One patient, despite undergoing extended resection beyond the radiographically involved segment, had a positive margin and subsequently required exenteration. Up to 80% of the frontal nerve length (maximum 44 mm) was safely resected without injury to the vision, globe, or orbit. Conclusion: Frontal nerve excision via orbitotomy, combined with radiation and/or chemotherapy/immunotherapy, prevented intracranial tumor extension in all cases with negative proximal margins and avoided orbital exenteration in 80% of patients. Given the risk of microscopic spread beyond visible radiographic margins, maximal excision should be considered. Globe-sparing neurectomy is a viable, low-morbidity surgical option that can be integrated into multidisciplinary treatment strategies to achieve local disease control in appropriately selected patients.

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