Recognising and categorising uveal melanoma

At the completion of this article, the reader should be able to improve uveal melanoma management. Including:

Understand the risk factors and predisposing factors for uveal melanoma
Identify where uveal melanomas are most likely to arise in clinical presentations
Identify the symptoms of ocular melanomas
Categorise lesions and provide informed referral to ophthalmological specialists

Uveal melanoma can be difficult to diagnose – but treated, if caught early. To assist optometrists in early detection, the authors discuss the condition’s risk factors and epidemiology while introducing the MOLES acronym and scoring system to estimate risk of malignancy and facilitate informed referrals.

Dr Lily Rolfe
MD, BSc

Dr Daniel McKay
MBBS, BComm, FRCPA, FRANZCO
Ocular Oncology Clinic, The Royal Victorian Eye and Ear Hospital

Dr Rod O’Day
MBBS, LLB, BSc, FRANZCO
Ocular Oncology Clinic, The Royal Victorian Eye and Ear Hospital
Centre for Eye Research Australia, The Royal Victorian Eye and Ear Hospital

Uveal melanoma (UM) is a relatively rare disease with an estimated incidence of 4-6 per million per year globally; approximately 250 patients in all of Australia per year are diagnosed with UM.¹ Although rare, it is the most common intraocular malignancy in adults and is associated with substantial morbidity and mortality.

Despite advances in the diagnosis and management of UM, metastatic disease develops in up to 67% of patients with the condition at 20 years.² Median survival time is less than 12 months if this occurs.

Optometrists play a vital role for patients with UM through prompt recognition and referral of suspicious lesions.

In contrast to the rarity of UM, uveal naevi are very common, occurring in up to 6% of the adult Caucasian population in Australia.³

The majority of choroidal naevi detected incidentally in the community are benign and can be managed safely by optometrists.⁴ Biopsy of intraocular lesions carries a significant risk to patients, so the clinical and multimodal imaging features of uveal lesions are used to distinguish between a mole, or another benign condition, and a melanoma.

Epidemiology and Risk factors

A consideration of UM risk factors may be appropriate when assessing uveal lesions. UM most often affects males and Caucasian populations, and is rare in pigmented races.^5-7 Unlike cutaneous melanoma, sunlight exposure has not been demonstrated to have a strong association with UM.^8,9 Other predisposing factors include fair skin colour,^5,7 lightly pigmented irides¹⁰and a tendency to sunburn.¹¹

Differential diagnosis

Although the main differential diagnosis of UM is a benign naevus, there are many other potential diagnoses to consider, depending on the anatomical location of the lesion. For example:

Choroidal: choroidal naevus, metastasis, osteoma and haemangioma; congenital hamartoma of the retinal pigment epithelium; eccentric disciform lesion (peripheral haemorrhagic chorioretinopathy); inflammatory lesion.

Iris: naevus; iris pigment epithelial cyst or adenoma; metastasis, leiomyoma; inflammatory lesion.

Figure 2. Choroidal melanoma with overlying lipofuscin (visible on colour image as orange collections overlying the pigmented tumour, left, and fundus autofluorescence as hyper-autofluorescence collections in the same location, bottom right) and subretinal fluid (visible around the tumour on colour image, left, and on the surface of the tumour on OCT). This lesion has a MOLES score of 6 (M0, O2, L2, E0, S2) and would have warranted an urgent referral to an ophthalmologist/ ocular oncologist. Prompt diagnosis and treatment – most often with ruthenium plaque brachytherapy – may allow long-term retention of vision and also potentially prevent development of lethal mutations within the tumour.

Clinical Presentation

UM is often asymptomatic and detected on routine optometric examination. Approximately 90% of UMs arise from the choroid, while the ciliary body and iris only account for 6% and 4% of melanomas, respectively.²

Choroidal Melanoma

Although around 30% of choroidal melanomas are asymptomatic at diagnosis, presenting symptoms may include blurred vision, photopsia, floaters, visual field loss, pain or metamorphopsia.¹² They may be pigmented, non-pigmented or a combination thereof.

The clinical features conferring a higher likelihood of the lesion being a melanoma (as well as an increased risk of growth and metastasis) are summarised by the mnemonic: ‘To Find Small Ocular Melanoma Doing Imaging’ (Table 1).¹³

Table 1. Mnemonic summary of risk factors predictive of transformation of choroidal lesions.

However, this classification requires B-Scan ultrasound to determine the thickness of a tumour and ultrasonographic hollowness, which is not available to many non-specialist practitioners.

The MOLES scoring system is a sensitive tool developed to assist non-specialists in making referral and management decisions regarding pigmented choroidal lesions when more limited imaging techniques are available (Table 2).¹⁴ The MOLES scoring system may be used to categorise lesions as ‘common naevus’, ‘low-risk naevus’, ‘high-risk naevus’ or ‘probable melanoma’.

The MOLES protocol also suggests appropriate management based on scoring (Table 3).¹⁴ Non-pigmented (also known as amelanotic) choroidal lesions have a much broader differential diagnosis, including choroidal metastasis, and most should be referred to an ophthalmologist.

Table 3. MOLES tumour categories and recommended management.[14]

Ciliary Body Melanoma

Ciliary body melanomas have the worst prognosis of all UM, as their anatomical location impedes early diagnosis. These tumours are often diagnosed at a relatively advanced stage, with clinical features such as involvement of the visual axis, focal cataract, extraocular spread or progressive refractive disturbance.

Iris Melanoma

Iris melanomas may be diagnosed de novo, or via documented growth of a pre-existing lesion. They are typically diagnosed at a relatively small size compared to choroidal melanoma. This appears to account for the relatively low overall mortality of iris melanoma.

Estimating the risk of malignant transformation of an iris naevus may be assessed according to presence of risk factors summarised by the ABCDEF guide (Table 4).¹⁵

Table 4. Malignant risk factors for iris lesions.[15]

Other clinical features may include heterochromia, correctopia, secondary glaucoma, angle seeding and extraocular extension.¹⁶

The diagnosis of diffuse iris melanoma is difficult due to its flat, ill-defined growth pattern. Diffuse iris melanoma may present as acquired hyperchromic heterochromia iridis and ipsilateral glaucoma.¹⁷

Impact of imaging technologies on detection and referral

The increasing availability of wide-field fundus imaging technologies may facilitate the earlier detection of ciliary body and choroidal tumours, particularly peripheral lesions. High-resolution multimodal imaging including ultrasonography, fundus autofluorescence and OCT is central in evaluating choroidal lesions. Almost always, the diagnosis can be accurately made based on clinical history, examination and the imaging characteristics of a tumour – without the need for tumour biopsy, which carries a risk of complications and vision loss.

Iris lesion diagnosis may also be aided by imaging techniques such as anterior segment photography, anterior segment OCT and ultrasonography. Similarly, ciliary body lesions may be visualised with ultrasonography. These imaging modalities are used to measure tumour dimensions and evaluate for differential diagnoses based on typical imaging characteristics.

Imaging modalities available to optometrists such as anterior segment or fundus photography and OCT are useful for diagnosing and monitoring lesions, and should be included in referrals to assist specialists in triaging.

Access to prior imaging is essential to determine if a lesion has grown or not and can be incredibly useful in informing management decisions, including facilitating early treatment of a melanoma. It is worthwhile doing a full set of imaging, with all modalities available to a clinician, at first diagnosis (colour imaging, OCT through the lesion, fundus autofluorescence, ultrasound, if available) and at follow-up visits to assess for growth or document change.

How to provide an informed referral

In general, a uveal lesion showing any of the TFSOM-DiM or ABCDEF risk factors warrants referral to an ophthalmologist, ideally with a subspecialty interest in retina or ocular oncology. Documented growth of a previously diagnosed lesion – regardless of the presence of other risk factors – should also prompt referral. The urgency of referral depends on the level of suspicion and can be guided using the MOLES scoring system.

The importance of collaborative care

Ocular oncologists – ophthalmologists whom have undergone fellowship training in management of ocular oncology patients – specialise in the diagnosis and management of UM. There are ocular oncologists in most of the states of Australia. Management of UM patients often requires involvement of radiation oncology teams in prescribing brachytherapy or stereotactic radiotherapy.

The involvement of other medical and surgical specialties is often required to treat metastatic disease. General practitioners coordinate care as well as monitor for evidence of metastasis through regular blood tests and imaging. Other allied health professionals such as ocularists create and fit prosthetic eyes, while cancer support services and psychologists provide support to patients in navigating psychosocial aspects of disease.

Caring for patients with UM requires multi-disciplinary collaboration. The role of the optometrist is vital in the early detection of UM, hopefully enabling diagnosis in the early phases before metastasis occurs.

References

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