Uveal melanoma associated with nevus of Ota: From genetic predisposition to clinical management

Background: Nevus of Ota, also known as oculodermal melanocytosis (ODM), is a congenital or acquired condition characterized by the proliferation of dermal and uveal melanocytes, leading to hyperpigmentation of periocular skin, sclera, and intraocular structures. Although benign, it is clinically relevant due to its established role as a risk factor for uveal melanoma (UM). The condition predominantly affects women and is more prevalent among Asian populations (0.1–0.2%), being rare in Caucasians (0.04%). Clinically, it manifests as unilateral, ill-defined, bluish-gray pigmentation. Approximately 3% of patients with ODM may develop UM, with onset typically between the ages of 50 and 60. Additionally, ODM confers a 1.6-fold higher risk of metastasis, mainly hepatic, compared with patients without melanocytosis.

Objective: This study aimed to review the association between Nevus of Ota and UM, exploring genetic predisposition, clinical features, diagnostic challenges, and management strategies.

Methods: A narrative literature review was conducted through PubMed, Embase, ScienceDirect, American Journal of Ophthalmology, Acta Ophthalmologica, and Graefe’s Archive for Clinical and Experimental Ophthalmology. A total of 228 articles were identified, and 15 were included after applying eligibility criteria.

Results: Nevus of Ota represents a significant risk factor for UM. The mean age at diagnosis ranged from 56 to 62 years. Tumor localization occurred most frequently in the sclera (92%), iris (17%), choroid (12%), and eyelid (8%). Tumors typically presented as medium to large, with mean basal diameter of 11–13 mm and thickness of 6–7 mm. Pigmentation was brown in 61.5% of cases, and extraocular extension was observed in 4.5%. Genetic mutations commonly involved GNAQ and GNA11, present in both blue nevi and UM. Germline mutations in BAP1 were associated with increased metastatic potential, while alterations in CYSLTR2, PLCB4, SF3B1, EIF1AX, and GRM1/PKC fusions highlighted the molecular heterogeneity. The presence of subretinal fluid, ciliary body involvement, older age, and larger basal diameter were predictive of poor prognosis.

Conclusion: Nevus of Ota is a rare but clinically significant condition that increases the risk of UM and metastasis. Multimodal imaging (fundoscopy, OCT, autofluorescence, ultrasonography, and UBM) and regular ophthalmologic follow-up every 6–12 months are essential for early detection. Management depends on tumor size and location, with treatment options including brachytherapy, transpupillary thermotherapy, local resection, and enucleation. Genetic insights into GNAQ, GNA11, and BAP1 mutations provide potential future therapeutic targets. Continuous surveillance and timely intervention remain crucial to improve ocular preservation and survival outcomes.