Effective Strategies for Treating Uveal Melanoma: A Review

Overview of Uveal Melanoma and Its Treatment Options

Uveal melanoma (UM) is recognized as the most common primary intraocular malignancy in adults. It typically arises from melanocytes within the uveal tract, which consists of the iris, ciliary body, and choroid. The annual incidence of UM ranges from 5 to 8 cases per million people, with a higher prevalence noted in Caucasian individuals compared to other ethnic groups (Hanratty et al., 2025). Despite its rarity, uveal melanoma poses a significant challenge in oncology due to its unique biological behavior, including a high propensity for metastasis, primarily to the liver (Hanratty et al., 2025).

The treatment landscape for UM has evolved over the years, with several local and systemic therapies available. Localized treatments, such as plaque brachytherapy, provide targeted radiation to the tumor while preserving the eye’s integrity. Alternatives include enucleation, which remains a standard procedure for larger tumors, and transpupillary thermotherapy, used for smaller lesions that might not require more invasive approaches (Hanratty et al., 2025).

Unfortunately, survival rates post-metastasis remain low, averaging less than one year, necessitating innovative therapeutic strategies to improve patient outcomes. Current systemic treatments for metastatic UM are limited; traditional chemotherapies exhibit low efficacy rates, prompting the exploration of advanced modalities like immunotherapy (Hanratty et al., 2025).

Current Advances in Immunotherapy for Uveal Melanoma

Recent advancements in immunotherapy have revolutionized the treatment of various malignancies, including cutaneous melanoma. However, the application of immunotherapies in uveal melanoma has been met with challenges due to the tumor’s distinct immune microenvironment and low tumor mutational burden (TMB). Immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1, have demonstrated limited success in UM, with response rates largely below those seen in cutaneous melanoma (Hanratty et al., 2025).

The disparity in efficacy is attributed to the immunologically “cold” nature of UM tumors, which harbor fewer neoantigens due to their low TMB, making them less recognizable to the immune system. Consequently, there is a growing interest in combining immunotherapeutic agents with other treatment modalities to enhance immune response and improve patient outcomes. For instance, the combination of darovasertib (a PKC inhibitor) with immune checkpoint inhibitors is under investigation in clinical trials to determine its efficacy in patients with GNAQ or GNA11 mutations, which are prevalent in UM (Hanratty et al., 2025).

Table 1: Overview of Immunotherapeutic Strategies in Uveal Melanoma

Role of Local Therapies in Uveal Melanoma Management

Local therapies are essential in the management of uveal melanoma, particularly in controlling the primary tumor. Plaque brachytherapy remains a cornerstone treatment, allowing for localized radiation delivery that minimizes collateral damage to surrounding tissues. Studies indicate that plaque brachytherapy is effective in achieving local control with relatively low complication rates compared to enucleation (Hanratty et al., 2025).

In addition to brachytherapy, transpupillary thermotherapy has emerged as a viable alternative for smaller tumors, leveraging infrared light to induce hyperthermia and promote tumor necrosis. This method is particularly beneficial in cases where traditional surgical options are not feasible due to tumor location or patient health status (Hanratty et al., 2025).

Understanding the Impact of Biomarkers on Patient Outcomes

Research continues to elucidate the role of specific biomarkers in predicting outcomes in uveal melanoma. Genetic mutations, such as those in BAP1 and GNAQ, serve as critical prognostic indicators. Loss of BAP1 expression correlates with increased metastatic risk, while the presence of GNAQ mutations is associated with tumor aggressiveness (Hanratty et al., 2025).

Furthermore, ongoing studies are investigating the implications of tumor mutational burden (TMB) and other molecular signatures in tailoring personalized treatment plans. Identifying patients likely to respond to specific therapies based on their tumor’s genetic profile can potentially enhance treatment success and overall survival rates (Hanratty et al., 2025).

Future Directions in Uveal Melanoma Treatment and Research

The future of uveal melanoma treatment hinges on the integration of innovative therapeutic strategies and a deeper understanding of the tumor’s biology. As research progresses, the focus is shifting towards multimodal approaches that combine local treatments with systemic therapies, including immunotherapies and targeted agents. The concept of patient stratification based on molecular profiles is emerging as a pivotal aspect of personalized medicine, allowing for more effective and tailored treatment options (Hanratty et al., 2025).

Additionally, the exploration of novel therapeutic agents targeting specific molecular pathways involved in UM progression holds promise. For instance, therapies aimed at inhibiting the MEK pathway, alongside investigational drugs targeting the tumor microenvironment, are being actively pursued in clinical settings (Hanratty et al., 2025).

Table 2: Future Directions in Uveal Melanoma Research

Frequently Asked Questions (FAQ)

What is uveal melanoma?

Uveal melanoma is the most common type of primary intraocular cancer, arising from melanocytes in the uveal tract of the eye.

How is uveal melanoma treated?

Treatment options for uveal melanoma include local therapies like plaque brachytherapy, enucleation, and transpupillary thermotherapy, as well as systemic therapies such as immunotherapy and chemotherapy for metastatic disease.

What are the prognostic factors for uveal melanoma?

Prognostic factors include genetic mutations (such as BAP1 and GNAQ), tumor size, and the presence of metastasis at diagnosis.

How effective are immunotherapies for uveal melanoma?

Immunotherapies have shown limited efficacy in uveal melanoma compared to cutaneous melanoma, primarily due to the low mutational burden of uveal melanoma tumors.

What is the role of biomarkers in uveal melanoma?

Biomarkers help predict patient outcomes and guide treatment decisions by identifying genetic mutations that correlate with a higher risk of metastasis or treatment response.

References

1. Hanratty, K., Finegan, G., Rochfort, K. D., & Kennedy, S. (2025). Current Treatment of Uveal Melanoma. Cancers, 17(9), 1403. https://doi.org/10.3390/cancers17091403

2. Galor, A., Gallar, J., Acosta, M. C., Meseguer, V., Benítez‐Del‐Castillo, J. M., Stachs, O., & Szentmáry, N. (2025). CORONIS symposium 2023: Scientific and clinical frontiers in ocular surface innervation. Acta Ophthalmologica, 103, e240–e255

3. Anitua, E., de la Fuente, M., Merayo‐Lloves, J., Muruzabal, F., & Orive, G. (2017). Allogeneic blood‐based therapies: hype or hope? Eye, 31(4), 509–510. https://doi.org/10.1038/eye.2016.268

4. Badami, K. G., & McKellar, M. (2012). Allogeneic serum eye drops: time these became the norm? The British Journal of Ophthalmology, 96(8), 1151–1152. https://doi.org/10.1136/bjophthalmol-2012-301668

5. Gazzard, G., Konstantakopoulou, E., Garway-Heath, D., et al. (2019). Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet, 393, 1505–16 18)32213-X