Ocular melanoma: improving outcomes through early detection and care

Management relies heavily on appropriate initial treatment. Standard care involves wide local excision using a no-touch technique with adjunctive cryotherapy, often combined with mapping biopsies to determine disease extent. In practice, many patients are referred to ocular oncologists following incomplete excision elsewhere, frequently with positive margins. Given the importance of accurate staging and the impact of the first surgery on outcomes, early referral of suspicious lesions is strongly recommended.

Recurrence remains relatively common and adjuvant treatments such as topical mitomycin C or radiotherapy are often required. Given the molecular similarities between conjunctival and cutaneous melanoma, targeted systemic therapies, including BRAF and KIT inhibitors, may be considered in selected cases and can play an important role in disease control, sometimes allowing avoidance of more disfiguring procedures such as exenteration³.

Iris melanoma

Iris melanocytic lesions, most commonly naevi, are frequently encountered and typically present as well-defined pigmented lesions. Importantly, naevi and melanomas can appear very similar clinically, making differentiation challenging. While melanomas may present as discrete lesions, they can also be more subtle, with diffuse involvement associated with heterochromia, secondary glaucoma, recurrent uveitis, or spontaneous hyphaema.

Despite this, the prognosis is generally favourable, with a low metastatic risk and an iris melanoma–related mortality of approximately 5% at five years following diagnosis⁴. Careful longitudinal assessment is therefore essential. Serial anterior segment photography allows detection of change over time and any lesion demonstrating growth, elevated intraocular pressure or other concerning features should prompt referral.

A key consideration is distinguishing iris from ciliary body melanoma, since the latter carries a significantly higher risk of metastasis. Imaging plays an important role: anterior segment OCT can assist in measuring tumour thickness, but ultrasound biomicroscopy is critical for evaluating posterior involvement.

Many iris melanomas can be safely observed. When treatment is required, options include surgical excision or radiotherapy. In many centres, plaque brachytherapy or proton beam therapy is used as primary treatment, particularly for lesions with ciliary body involvement, offering effective tumour control with low recurrence rates.

Choroidal melanoma

Choroidal melanoma is the most common primary intraocular malignancy and carries a significant risk of metastatic disease. Lesions at the posterior pole are more likely to present earlier due to visual symptoms, whereas peripheral tumours often remain asymptomatic. Up to 40% of patients are asymptomatic at diagnosis, often presenting with larger, more advanced tumours¹.

This highlights the critical role of both optometrists and ophthalmologists. However, routine dilation is not consistently performed in clinical practice, influenced by patient factors, time pressures and underappreciation of its importance. Even within ophthalmology, not all consultations routinely include fundus examination. There are numerous examples of delayed diagnosis in patients followed long-term without posterior segment assessment, reinforcing the need for greater consistency in examination practices.

Distinguishing a benign choroidal naevus from melanoma is a common challenge. The MOLES scoring system (see Tables 1 and 2) provides a practical framework for risk stratification, guiding referral without the need for ultrasound⁵. Low-risk lesions can be monitored, while higher-risk lesions should be referred promptly.

Management continues to be guided by the Collaborative Ocular Melanoma Study (COMS), which demonstrated no survival advantage of enucleation over plaque brachytherapy⁶. As a result, eye-conserving treatments are now standard. In New Zealand, plaque brachytherapy remains the most commonly utilised modality, while stereotactic radiotherapy offers a non-surgical alternative with higher rates of visual complications.

Emerging therapies are expanding treatment options. Belzupacap sarotalocan (Bel-sar, previously known as AU-011), currently in phase 3 trials, represents a targeted therapy inducing tumour necrosis following light activation. Neoadjuvant agents such as darovasertib are also under investigation to preserve vision and reduce enucleation rates.

Despite advances in local tumour control, survival outcomes have not significantly improved, largely due to early micrometastasis⁷. Prognostication has therefore become increasingly sophisticated. In addition to the American Joint Committee on Cancer’s guidance on tumour staging, molecular profiling, including chromosomal alterations and gene expression profiling, plays a key role, with PRAME (preferentially expressed antigen in melanoma) expression further refining metastatic risk.

There is also increasing interest in less invasive methods of detecting systemic disease. Circulating tumour cells show promise for earlier detection of metastasis, although these technologies are not yet commercially available.

Systemic treatment of metastatic uveal melanoma remains challenging. Unlike cutaneous melanoma, immune checkpoint inhibitors have shown limited efficacy. However, newer therapies are beginning to improve outcomes. Tebentafusp has demonstrated a survival benefit in HLA-A*02:01-positive patients, while combination targeted therapies such as darovasertib with crizotinib have shown encouraging results in early clinical trials^8,9.

Conclusion

While a growing number of novel therapies are emerging, these advances remain, in many ways, an ambulance at the bottom of the cliff. The most meaningful impact on outcomes still comes from early detection.

For optometrists and ophthalmologists, this means maintaining a high index of suspicion, performing thorough posterior segment examination, including routine dilation, and referring suspicious lesions early to subspecialist centres. Ultimately, earlier detection is what most improves both visual and life outcomes in ocular melanoma.

References

1. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118(9):1881–5.
2. Shields CL, Shields JA. Tumours of the conjunctiva and cornea. Surv Ophthalmol. 2004;49(1):3–24.
3. Griewank KG, Westekemper H, Murali R, et al. Conjunctival melanomas harbor BRAF and NRAS mutations. Invest Ophthalmol Vis Sci. 2013;54(2):1363–9.
4. Sabazade S, Herrspiegel C, Gill V, Stålhammar G. No differences in the long-term prognosis of iris and choroidal melanomas when adjusting for tumor thickness and diameter. BMC Cancer. 2021 Nov 24;21(1):1270.
5. Damato B, Taktak AFG, Heimann H. The MOLES system for planning management of melanocytic choroidal tumours: is it safe? Br J Ophthalmol. 2019;103(10):1490–5
6. Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy. Arch Ophthalmol. 2001;119(7):969–82.
7. Jager MJ, Shields CL, Cebulla CM, et al. Uveal melanoma. Nat Rev Dis Primers. 2020;6(1):24.
8. Hassel JC, Piperno-Neumann S, Rutkowski P, Baurain JF, Schlaak M, Butler MO, Sullivan RJ, Dummer R, Kirkwood JM, Orloff M, et al. Three-year overall survival with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2023;389(24):2256–2266.
9. Carvajal RD, Piperno-Neumann S, Kapiteijn E, et al. Darovasertib in combination with crizotinib in metastatic uveal melanoma: early clinical results. J Clin Oncol. 2023;41(15_suppl):9506.