Choroidal Nevus Management: Latest Guidelines and Innovations

Choroidal Nevus: Diagnosis, Management, and Innovative Treatments

Choroidal nevus is a common benign pigmented lesion that arises from melanocytes in the choroid, the vascular layer of the eye between the retina and sclera. While most choroidal nevi are harmless and remain stable throughout life, there is a small but significant risk of transformation into choroidal melanoma, a malignant tumor with serious consequences. As such, early detection, regular monitoring, and risk stratification are essential to prevent malignant progression.

This article will provide an in-depth exploration of the diagnosis, management, and innovative treatments for choroidal nevi.

What is a Choroidal Nevus?

A choroidal nevus is a benign melanocytic lesion found in the choroid, similar to a mole on the skin. These lesions typically present as flat or slightly elevated, pigmented spots in the eye. While common in the general population, choroidal nevi can occasionally transform into choroidal melanoma, making it important for healthcare professionals to differentiate benign lesions from those at higher risk of malignancy.

Epidemiology

Choroidal nevi are relatively common, with an estimated prevalence of 6-7% in the adult Caucasian population. They are less common in people of African or Asian descent, reflecting the overall lower incidence of melanocytic lesions in individuals with darker skin. Choroidal nevi are usually asymptomatic, and many are discovered incidentally during routine eye exams.

Pathophysiology

Choroidal nevi are clusters of melanocytes located within the choroid. These pigmented cells are responsible for the lesion’s dark appearance and may vary in color from gray to dark brown. The exact cause of a choroidal nevus is unknown, but like skin moles, they likely result from genetic and environmental factors that regulate melanocyte activity. Some nevi remain stable throughout life, while others grow and undergo transformation into melanoma.

Clinical Presentation

Most patients with choroidal nevi are asymptomatic, and the lesion is often detected during routine eye exams. However, larger nevi or those located near the macula may cause symptoms.

Symptoms

• Blurry vision: If the nevus causes retinal elevation or if subretinal fluid accumulates, the patient may experience blurry vision.
• Visual distortion: Lesions located near the macula may cause metamorphopsia (visual distortion), which can interfere with central vision.
• Floaters or flashes: In rare cases, patients may report floaters or flashes of light, typically associated with retinal traction or secondary retinal detachment.

Risk Factors for Malignant Transformation

Although most choroidal nevi are benign, there are several factors that increase the risk of progression to melanoma. These risk factors include:

1. Tumor Thickness: Nevi thicker than 2 mm have a higher risk of malignant transformation.
2. Subretinal Fluid: The presence of subretinal fluid, which can cause retinal detachment, suggests more aggressive behavior.
3. Symptoms: Symptoms such as blurry vision or visual distortion may indicate growth or activity.
4. Orange Pigment: The presence of orange pigment (lipofuscin) on the surface of the nevus is an indicator of potential malignancy.
5. Proximity to the Optic Disc: Lesions located close to the optic nerve are more likely to become malignant.
6. Ultrasonographic Hollowness: Low internal reflectivity on ultrasound imaging is associated with choroidal melanoma.
7. Diameter: Nevi larger than 5 mm in diameter are at a higher risk of becoming melanomas.

The mnemonic “To Find Small Ocular Melanomas” helps clinicians remember these risk factors:

• T: Thickness >2 mm
• F: Fluid (subretinal)
• S: Symptoms (blurred vision, flashes)
• O: Orange pigment
• M: Margin within 3 mm of the optic disc

Diagnosis of Choroidal Nevus

A thorough and systematic approach is necessary to differentiate a benign nevus from a potential melanoma. The diagnostic process involves a combination of clinical evaluation, imaging studies, and sometimes molecular analysis.

1. Fundoscopic Examination

The primary tool for diagnosing a choroidal nevus is a comprehensive dilated fundus examination using ophthalmoscopy or slit-lamp biomicroscopy. Nevi typically appear as flat or slightly elevated, pigmented lesions with well-defined margins. They are usually grayish-brown, though some may be amelanotic (lacking pigment).

2. Optical Coherence Tomography (OCT)

Optical coherence tomography (OCT) is a non-invasive imaging technique that provides high-resolution cross-sectional images of the retina and choroid. OCT is especially useful for detecting subtle changes in the retina overlying a nevus, such as subretinal fluid or retinal thinning, which may indicate malignant transformation.

• Retinal elevation: OCT can detect if the nevus is causing the retina to lift, which may impact vision.
• Subretinal fluid: The presence of fluid under the retina can be visualized with OCT, a key indicator of possible melanoma development.

3. Fundus Autofluorescence (FAF)

Fundus autofluorescence (FAF) is a technique that detects lipofuscin, a pigment associated with metabolic activity in the retinal pigment epithelium. The presence of orange pigment overlying a nevus, which is visible on FAF imaging, is a warning sign for potential malignancy.

4. Ultrasound (B-Scan)

B-scan ultrasonography provides critical information about the internal characteristics of a nevus, including its thickness, shape, and reflectivity. Choroidal nevi generally have higher internal reflectivity compared to melanomas, which tend to be hollow on ultrasound.

5. Fluorescein Angiography (FA)

Fluorescein angiography can help evaluate the blood supply to the nevus and assess for leakage, which may indicate malignant transformation. Nevi typically have normal vascular profiles, while melanomas often exhibit abnormal blood vessel growth and leakage.

6. Indocyanine Green Angiography (ICG)

Indocyanine green angiography (ICG) provides further insights into the choroidal circulation and is particularly useful in distinguishing nevi from other vascular lesions, such as hemangiomas.

7. Genetic Testing and Cytogenetics

While genetic testing is not typically performed for all choroidal nevi, molecular analysis can be useful in cases where malignant transformation is suspected. Mutations in genes such as BAP1 have been associated with a higher risk of melanoma. As genetic testing becomes more accessible, it may play an increasing role in the risk stratification of choroidal nevi.

Management of Choroidal Nevus

The management of choroidal nevi depends on the size, location, and risk factors for malignant transformation. For most patients, observation with regular follow-up is the preferred approach, though some cases may warrant closer monitoring or intervention.

1. Observation and Monitoring

For asymptomatic nevi that lack risk factors for malignancy, the standard management approach is observation. Patients should undergo routine eye exams every 6 to 12 months, with fundus photography and OCT imaging to monitor for any changes in the size, thickness, or appearance of the lesion.

• Fundus photography: Baseline photography allows for accurate monitoring of nevus growth over time.
• OCT and ultrasonography: These imaging modalities provide detailed information about any changes in the lesion’s structure or impact on the retina.

2. Monitoring for Malignant Transformation

Nevi with high-risk features, such as thickness greater than 2 mm or subretinal fluid, require more frequent follow-up and closer monitoring. These patients should be examined every 3 to 6 months to detect early signs of melanoma.

3. Laser Photocoagulation

Laser photocoagulation is not typically used for benign nevi but may be considered for small nevi that show signs of growth or malignant transformation. However, the use of laser therapy for nevi is controversial, as it may not effectively prevent melanoma development and could cause collateral damage to surrounding ocular tissues.

4. Transpupillary Thermotherapy (TTT)

Transpupillary thermotherapy (TTT) is a laser-based treatment that uses heat to shrink small choroidal melanomas. In cases where a nevus shows signs of malignant transformation but is still relatively small, TTT may be an option to control tumor growth while preserving vision.

5. Plaque Brachytherapy

In cases where a choroidal nevus has progressed to melanoma, plaque brachytherapy becomes a treatment option. This involves placing a radioactive plaque on the sclera directly over the tumor. Plaque brachytherapy is commonly used for small to medium-sized melanomas and has been shown to be highly effective in controlling tumor growth and preserving vision.

6. Enucleation

For large melanomas or those that cause significant complications, enucleation (removal of the eye) may be necessary. This is a last resort when vision cannot be preserved or when the tumor poses a serious risk to the patient’s life due to metastasis.

Innovative Treatments and Research

As our understanding of choroidal nevi and their potential for malignant transformation grows, new diagnostic tools and treatment modalities are being developed to improve patient outcomes.

1. Genetic and Molecular Profiling

Advances in genetic testing are allowing for better risk stratification of choroidal nevi. Researchers are investigating the role of specific gene mutations, such as BAP1 and GNAQ, in predicting which nevi are likely to become melanomas. As this technology becomes more widespread, genetic profiling could become a standard part of nevus management.

2. Optical Coherence Tomography Angiography (OCT-A)

Optical coherence tomography angiography (OCT-A) is a non-invasive imaging modality that provides detailed images of the choroidal vasculature. This technology allows clinicians to assess the blood supply to a nevus, helping to identify neovascularization or other changes suggestive of malignancy.

3. Artificial Intelligence (AI) in Diagnosis

Artificial intelligence (AI) is being explored as a tool for diagnosing and monitoring choroidal nevi. AI algorithms can analyze large datasets of fundus images, OCT scans, and other diagnostic tests to detect early signs of malignancy with high accuracy. This technology has the potential to improve early detection and reduce the risk of melanoma development.

4. Proton Beam Therapy

For patients with nevi that progress to melanoma, proton beam therapy is an emerging treatment that offers precise targeting of the tumor while minimizing damage to surrounding tissues. Proton therapy is particularly useful for tumors located near critical structures like the optic nerve or macula.

Prognosis and Long-Term Outcomes

The prognosis for patients with choroidal nevi is generally excellent, as most nevi remain stable and do not transform into melanoma. However, regular monitoring is essential to detect early signs of malignant transformation. Patients with high-risk nevi should be closely followed to prevent progression to melanoma, which carries a more guarded prognosis.

• Benign nevi: For most patients, choroidal nevi remain stable throughout life, requiring only routine monitoring.
• Nevi with risk factors: Nevi with features such as thickness greater than 2 mm, subretinal fluid, or orange pigment require more frequent follow-up, as they carry a higher risk of becoming malignant.
• Malignant transformation: In cases where a nevus transforms into melanoma, early detection and treatment are crucial to prevent metastasis and preserve vision.

Conclusion

Choroidal nevus is a common benign ocular lesion, but its potential for malignant transformation requires careful monitoring and risk stratification. Advances in imaging techniques, genetic testing, and treatment modalities are improving our ability to diagnose and manage choroidal nevi, helping to prevent progression to melanoma and preserve vision. As research into genetic and molecular factors continues, we can expect further innovations in the diagnosis and treatment of choroidal nevi.