Ophthalmology – Iris Melanoma

Alert

Any pigmented iris lesion should be examined carefully for features suggesting malignancy, especially tumor seeding, secondary glaucoma, intrinsic tumor vessels, documented growth, and angle involvement.

These findings are much more concerning for iris melanoma than for a stable iris nevus.

Basics

Description

Iris melanoma is a malignant melanocytic tumor arising from the iris stroma. It is uncommon and accounts for only a small proportion of all uveal melanomas.

The tumor may be pigmented or nonpigmented and can vary considerably in size, shape, and appearance.

Important clinical forms include:

• Circumscribed iris melanoma
• Diffuse iris melanoma
• Tapioca melanoma
• Trabecular meshwork melanoma

Iris melanoma may cause:

• Corectopia
• Ectropion uveae
• Secondary glaucoma
• Spontaneous hyphema
• Anterior chamber inflammation
• Tumor seeding onto the iris or angle

More than 80% of iris melanomas arise in the inferior half of the iris.

Although iris melanoma generally has a lower metastatic risk than choroidal melanoma, it can metastasize, particularly to the liver, and less commonly to other organs.

Pediatric Considerations

Iris melanoma is rare in children and young adults, but among younger patients who do develop uveal melanoma, the iris represents a relatively larger proportion of cases than it does in older adults.

Epidemiology

Iris melanoma represents approximately 4–5% of uveal melanomas.

Uveal melanoma itself is uncommon, with an incidence of only several cases per million population per year.

Secondary elevation of intraocular pressure is relatively common in established iris melanoma and may occur because of:

• Direct tumor invasion of the angle
• Tumor seeding
• Pigment or tumor-cell obstruction of aqueous outflow

Risk Factors

Important associations include:

• White race
• Light-colored iris
• Inferior iris location
• Ocular melanocytosis
• Preexisting suspicious iris nevus

Features that increase concern for malignant transformation of a nevus include:

• Documented enlargement
• Pigment dispersion onto adjacent iris
• Angle involvement
• Secondary glaucoma
• Intrinsic vessels
• Tumor seeding

Genetics

Iris melanomas may demonstrate chromosomal abnormalities involving chromosomes 3, 6, and 8.

As with other uveal melanomas, certain cytogenetic features are associated with different metastatic risks.

Monosomy 3 is generally considered a higher-risk feature, whereas disomy 3 is associated with a lower metastatic risk.

Fine-needle aspiration biopsy may be used in selected cases for cytologic or molecular analysis.

General Prevention

There is no proven method to prevent iris melanoma.

Reasonable measures include:

• Limiting excessive ultraviolet exposure
• Wearing UV-protective eyewear
• Regular ophthalmic monitoring of suspicious iris lesions

The most important preventive strategy is early recognition of malignant transformation in a previously observed iris lesion.

Pathophysiology

Iris melanoma develops from malignant transformation of melanocytes within the iris stroma.

The tumor may remain localized or spread:

• Across the iris surface
• Into the anterior chamber angle
• Into the trabecular meshwork
• Into the ciliary body
• Extraocularly in advanced disease

Tumor cells may shed into the anterior chamber and produce visible seeding on the iris or angle.

Angle infiltration and seeding can obstruct aqueous outflow and produce secondary glaucoma.

Etiology

The exact cause is unknown.

Genetic susceptibility, melanocytic abnormalities, and environmental factors may contribute, but no single cause has been established.

Clinical Types

Circumscribed Iris Melanoma

This is the most common presentation.

It appears as a relatively well-defined mass within the iris stroma.

Features may include:

• Nodular or dome-shaped configuration
• Variable pigmentation
• Distortion of the pupil
• Intrinsic vessels
• Ectropion uveae
• Local angle involvement

Localized lesions without extensive seeding may be amenable to surgical excision.

Diffuse Iris Melanoma

Diffuse melanoma spreads across a broad portion of the iris rather than forming a single discrete mass.

It may produce:

• Acquired hyperchromic heterochromia
• Diffuse iris thickening
• Loss of normal iris architecture
• Progressive secondary glaucoma
• Extensive angle infiltration

Because the tumor may be subtle, the diagnosis can be delayed.

Tapioca Melanoma

This rare form has multiple small translucent or lightly pigmented nodules scattered over the iris surface.

The appearance has been compared with tapioca pudding.

It may be mistaken for inflammatory or benign nodular iris disease.

Trabecular Meshwork Melanoma

This form primarily involves the anterior chamber angle and trabecular meshwork without an obvious iris mass.

Patients may initially present with unilateral secondary glaucoma.

It can be mistaken for:

• Pigmentary glaucoma
• Other secondary glaucomas

Unexplained unilateral glaucoma with abnormal angle pigmentation should therefore prompt careful gonioscopic examination.

Diagnosis

History

Patients may be asymptomatic, with the lesion found during routine examination.

Possible symptoms include:

• Visible iris spot or mass
• Change in iris color
• Distorted pupil
• Blurred vision
• Eye pain
• Redness
• Symptoms of elevated IOP

Pain and visual loss often occur when secondary glaucoma develops.

A history of a previously documented iris nevus is particularly useful because growth over time is one of the strongest signs of malignancy.

Physical Examination

A complete ophthalmic examination should include:

• Visual acuity
• IOP measurement
• Slit-lamp examination
• Gonioscopy
• Transillumination
• Dilated examination

Concerning features include:

• Documented tumor growth
• Intrinsic tumor vessels
• Feeder vessels
• Corectopia
• Ectropion uveae
• Tumor seeding
• Secondary glaucoma
• Hyphema
• Angle invasion

Secondary Glaucoma

Elevated IOP is an important warning sign.

Glaucoma is unusual in a simple iris nevus, so unilateral glaucoma associated with an iris lesion should raise suspicion for melanoma.

Possible mechanisms include:

• Direct angle invasion
• Trabecular obstruction by tumor cells
• Tumor seeding
• Pigment dispersion
• Neovascular mechanisms in advanced disease

Tumor Seeding

Tumor cells may appear as fine pigmented or nonpigmented deposits on:

• The iris surface
• The anterior chamber angle
• Other anterior segment structures

Seeding is best identified with careful slit-lamp examination and gonioscopy.

Its presence strongly supports malignant behavior.

Diagnostic Tests and Interpretation

Anterior Segment Photography

Serial slit-lamp photographs are extremely useful.

They document:

• Tumor size
• Pigmentation
• Vascularity
• Pupillary distortion
• Growth over time

Documented enlargement is one of the most important criteria for treatment.

Ultrasound Biomicroscopy

UBM is very useful for evaluating iris melanoma.

It can:

• Measure tumor thickness
• Determine posterior extension
• Detect ciliary body involvement
• Distinguish solid tumors from cysts
• Assess angle involvement

Anterior-Segment OCT

AS-OCT may be useful for smaller, superficial, particularly nonpigmented iris lesions.

Its limitation is posterior shadowing, especially with larger or heavily pigmented tumors.

Gonioscopy

Gonioscopy is essential to determine:

• Angle involvement
• Trabecular pigmentation
• Tumor seeding
• Extent in clock hours

This information can significantly alter treatment planning and prognosis.

Transillumination

Transillumination may help determine whether the lesion extends posteriorly into the ciliary body.

Fine-Needle Aspiration Biopsy

FNAB may be useful when the diagnosis remains uncertain.

It can provide material for:

• Cytology
• Cytogenetic analysis
• Molecular prognostic testing

Interpretation should ideally be performed by an experienced ocular pathologist because low-grade melanomas may be difficult to distinguish from nevi histologically.

Systemic Evaluation

Because iris melanoma can metastasize, patients require systemic assessment.

The liver is the most important metastatic site in uveal melanoma.

Systemic surveillance is usually coordinated with ocular oncology and medical oncology and may include:

• Physical examination
• Liver function testing
• Liver imaging
• Other imaging based on risk and institutional protocol

Modern surveillance schedules vary according to tumor biology and metastatic risk.

Differential Diagnosis

Important mimics include:

• Iris nevus
• Iris melanocytoma
• Iris pigment epithelial cyst
• Adenoma of the iris pigment epithelium
• ICE syndrome
• Iris lymphoma
• Iris metastasis
• Iris granuloma
• Juvenile xanthogranuloma
• Retained anterior chamber foreign body
• Inflammatory iris nodules

The most important distinction is usually between iris nevus and iris melanoma.

Nevus Versus Melanoma

Features favoring melanoma include:

• Documented growth
• Larger size
• Greater thickness
• Intrinsic vascularity
• Ectropion uveae
• Corectopia
• Tumor seeding
• Angle involvement
• Secondary glaucoma
• Spontaneous hyphema

A stable, small lesion without these features is more likely to be benign.

Treatment

There is no established systemic medication that eradicates a localized primary iris melanoma.

Treatment is primarily local and depends on:

• Tumor size
• Location
• Circumscribed versus diffuse configuration
• Angle involvement
• Seeding
• Secondary glaucoma
• Visual potential

Observation

Small indeterminate lesions without clear malignant features may be observed closely.

Serial examination should include:

• Slit-lamp photography
• UBM
• Gonioscopy
• IOP measurement

Documented growth generally warrants treatment.

Surgical Excision

Localized circumscribed melanoma may be treated with surgical excision.

Procedures include:

• Iridectomy
• Iridocyclectomy
• Iridogoniocyclectomy

The choice depends on whether the tumor extends into:

• The angle
• Ciliary body
• Adjacent structures

Excision is most appropriate when the tumor is sufficiently localized and there is no extensive seeding.

Plaque Brachytherapy

Plaque radiotherapy is an important globe-preserving treatment.

It may be considered for:

• Larger tumors
• Diffuse tumors
• Tumors not suitable for excision
• Angle involvement
• Anterior chamber seeding
• Eyes in which preservation of useful vision is especially important

Radiation allows treatment of tissue beyond the visibly apparent tumor margin.

Enucleation

Enucleation is now reserved for advanced cases.

Indications may include:

• Extensive diffuse melanoma
• Involvement of a large portion of the iris and angle
• Severe uncontrolled secondary glaucoma
• Painful blind eye
• Extensive tumor seeding
• Extraocular extension in selected circumstances

Visual status of the fellow eye should be considered before proceeding.

Management of Glaucoma

Glaucoma should initially be treated medically when possible.

Filtering surgery such as trabeculectomy is generally avoided in eyes with active or incompletely controlled melanoma, because creating a surgical fistula could theoretically facilitate extraocular tumor spread.

When pressure cannot be controlled medically, options may include cyclodestructive procedures or other carefully selected interventions coordinated with an ocular oncologist.

Postoperative Treatment

After local excision or radiotherapy, topical medications may be used to control:

• Inflammation
• Pain
• Posterior synechiae

Cycloplegics and corticosteroid-containing regimens may be prescribed depending on the procedure and postoperative findings.

Follow-Up

Patients require long-term ocular surveillance.

Follow-up commonly includes:

• Slit-lamp examination
• Gonioscopy
• IOP measurement
• Anterior segment photography
• UBM
• Transillumination when appropriate

After treatment, follow-up is often performed approximately every 6 months, although intervals depend on tumor risk and stability.

Patient Monitoring

Monitoring focuses on:

• Tumor regression
• Recurrence
• New seeding
• Progressive angle involvement
• Secondary glaucoma
• Cataract
• Radiation complications

Systemic metastatic surveillance should continue long term.

Patient Education

Patients should understand that iris melanoma is malignant but generally has a better metastatic prognosis than choroidal melanoma.

They should be educated regarding the importance of:

• Long-term eye follow-up
• Lifelong systemic surveillance
• Reporting new eye pain or visual loss
• Monitoring previously suspicious iris lesions

Avoiding excessive ultraviolet exposure is reasonable.

Prognosis

The metastatic risk of iris melanoma is lower than that of choroidal or ciliary body melanoma.

Reported long-term metastatic rates are relatively low, but risk is not zero.

Features associated with a worse prognosis include:

• Older age
• Secondary glaucoma
• Angle involvement
• Extraocular extension
• More diffuse disease
• Higher-risk cytogenetic features

Early, localized lesions generally have a favorable ocular and systemic prognosis when appropriately treated.

Complications

Potential complications include:

• Secondary glaucoma
• Cataract
• Recurrent tumor
• Tumor seeding
• Angle invasion
• Radiation-related keratopathy
• Neovascular glaucoma
• Need for eventual enucleation
• Metastatic disease

After plaque radiotherapy, cataract is a particularly common late complication.

The key clinical warning is: an iris lesion with documented growth, intrinsic vessels, tumor seeding, angle involvement, or secondary glaucoma should be considered suspicious for iris melanoma until proven otherwise.