Choroidal Tumors: Improvements in Imaging and Therapy

The differential diagnosis of choroidal melanoma:

1.          Choroidal nevus

2.          Congenital hypertrophy of retinal pigment epithelium (CHRPE)

3.          Circumscribed choroidal hemangioma

4.          Age-related macular degeneration (AMD)

5.          Optic disc melanocytoma

6.          Choroidal osteoma

7.          Choroidal metastasis

8.          Hemorrhagic choroidal detachment

 

The risk factors of ocular melanoma have been proposed as a mnemonic “To Find Small Ocular Melanoma Using helpful Hints Daily”

To = Thickness of the tumor >2 mm

Find = Subretinal fluid

Small = Symptoms

Ocular = Orange pigment

Melanoma = Margin of the tumor within 3 mm of the optic disc

Using helpful = Ultrasonographic hollowness of the tumor

Hints = Absence of halo

Daily = Absence of drusen

 

It is important that the earlier the detection of uveal melanoma is, the better the outcome of the treatment will be. 

 

In the past, enucleation was performed in any patients with pigmented lesion that was suspected to be ocular melanoma, although 20% of these enucleated eyes were not melanoma.  Hence, an accurate diagnosis is required to avoid dispensable enucleation.  Many modalities are used to help making correct diagnoses in most cases.  In difficult cases, scintigraphy with single-photon emission computed tomography (SPECT) after injection of N-isopropyl-p-[(123)I] iodoamphetamine (123I-IMP) is found to be very helpful.  The uptake of 123I-IMP by melanin-producing cells is with high affinity, making the detection of the eye with uveal melanoma easily with much precision.  The sensitivity and specificity of 123I-IMP scintigraphy in the detection of uveal melanoma are increased up to 92% and 96%, respectively. 

 

Prognosis of patients with uveal melanoma depends on basal diameter, apical thickness, extra ocular extension, histology of the tumor, mitotic rate.  Genetic testing can also provide information for the prognosis.  Patients with monosomy 3, gain of chromosome 8q or 6p are defined to have poor prognostic factors.  New method of gene expression which is classified as Class 1 and Class 2 with or without PRAME.  Genetic testing indicates that patients in whom with high risk systemic therapy might be beneficial in reducing metastasis. 

 

The treatment of choroidal melanoma

            Transpupillary thermotherapy (TTT) can be used in selected cases which help controlling tumor in 90% of patients.  Besides, it can be applied in juxtapapillary melanoma, ciliary body melanoma, large choroidal melanoma and extraocular extension melanoma with successful outcomes. 

 

            Proton therapy involves delivering high energy-charged particles to the affected area.  Its advantages include uniform and highly localized dose distributions, the tumor near optic disc and macula is able to be treated with vision preservation, and large tumor can also be treated.  The treatment protocol starts with the placement of tantalum rings to localize the tumor, thereafter 70 Gy of cobalt is delivered in 5 fractions to the tumor.  This results in tumor regression within 6 months.  However, 8.7% of treated patients underwent enucleation from NVG and tumor regrowth, and 29% of the patients had BCVA of 20/100 or better at 15-year follow-up.  Risk factors that predict visual loss include tumor within 2-disc diameter from macula or optic disc, larger tumor size, diabetes mellitus, VA of 20/30 or worse before the treatment, and complication of tumor such as retinal detachment.  Despite the successful treatment, there are still 2.9% recurrence rate.  Complications from the treatment consist of maculopathy and papillopathy.

 

            Recently developed therapies for uveal melanoma are invented to avoid complications from conventional treatments which may lead to loss of visual acuity or the eye.  Firstly, light-activated AU-011 is one of the promising targeted therapy to the tumor cells.  The procedure involves attachment of chromophore to the HPV capsid which will bind to heparin sulfate matrix surrounding tumor cells.  The laser light will then be used to stimulate the complex resulting in tumor cell dead.  Secondly, drugs, such as sunitinib, act by inhibiting tyrosine kinase and VEGF, and are now used in patients with high risk uveal melanoma identified by genetic testing.  Thirdly, immunotherapy includes checkpoint inhibitors, vaccines, immune cell therapy, immune system modulators.  Checkpoint inhibitors cause activation of T cells to attack the cancer cells.  Vaccines work by producing specific immune response against melanoma. Immune cell therapy in recent research is adoptive cell transfer.  It is done by getting the patient’s lymphocytes and then modifying them to attack melanoma antigens.  After destruction of immune system, the trained T cells are infused back to the body to fight against tumor cells.  Immune modulated T cells against cancer is another type of immunotherapy.  The drug, which binds to the receptor on the tumor cell, and T cell are linked together.  This enhances T cells to kill cancer cells.

 

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