69-year-old Caucasian female presented for yearly dilated fundus exam for diabetic screening
Patient had no visual complaints
PMH: Well controlled T2DM, Lasik OU few years prior
ROS negative
Exam Findings
BCVA 20/20 OD, 20/25 OS, IOP WNL and EOMI OU with no APD
Anterior segment exam on slit lamp only notable for 1+ NSC of the lens OU
DFE revealed choroidal lesion nasal and inferior to optic nerve OD, WNL OS
Figure 1: Dilated fundus exam on the left revealed a pigmented lesion located inferior and nasal to the optic nerve in the right eye with a central area of retinal invasion. Ultrasonography of the right eye illustrated a dome shaped choroidal lesion with measurements of 9.64 mm at the base, with thickness of 3.37 mm.
Differential Diagnosis
Choroidal melanoma: most common primary intraocular tumor in adults
Risk factors include:
Ages 50-70 years
Caucasian
Sun exposure especially in fair skinned individuals
Visual symptoms are variable with 30% of patients asymptomatic at diagnosis
Choroidal Nevus (present in ~5% of Caucasians, by strict size definitions <1x5mm)
High risk features for growth of nevus include:
Thickness greater than 2 mm
Subretinal fluid
Visual symptoms
Orange pigment
Margin near the optic disc
Ultrasonographic hollowness
Absence of halo or drusen
Peripheral exudative hemorrhagic chorioretinopathy (however, no fluid, no drusen, no anticoagulation or other risk factors)
Congenital hypertrophy of the RPE (however, would not be a new finding; color of lesion is atypical)
Circumscribed choroidal hemangioma (however, this lesion is the wrong color)
Choroidal metastasis (however, generally amelanotic unless from melanoma)
Additional Investigations
CT chest, abdomen, pelvis done for evaluation of metastatic disease and staging was negative
Diagnosis
Choroidal melanoma
Pathophysiology
Melanomas arise from the abnormal proliferation of melanocytes, which are melanin-producing cells derived embryologically from neural crest cells
It is the most common primary intraocular tumor, although accounting for only 5% of all cases of melanoma with an incidence of 5.1 per million per year in the United States
Genetic alterations such as monosomy of chromosome 3 or mutation/inactivation of BRCA associated protein 1 (BAP1) have been found to have a higher risk of metastasis
Treatment
Depending on the tumor’s size, treatment options include:
Plaque radiotherapy
Proton beam therapy
Stereotactic radio surgery
Enucleation
Given that the tumor dimensions were classified as medium-sized, iodine-125 radioactive episcleral plaque brachytherapy was pursued with the USC Eye Physics Plaque, developed at the University of Southern California. A CT orbits was done for 3D treatment planning.
Figure 2:Panel A shows the digitized retina tumor margins. Panel B shows an iodine-125 plaque with collimating slots. Panel C shows the use of Plaque Simulator software as it integrates the fundus photography and ocular ultrasonography with CT images to create a three-dimensional model of the eye, tumor, plaque and seeds for planning purposes. Panel D presents an example of plaque placement measurement from the limbus along meridians (clock hours) on the eye (Taken from Berry et al, JAMA Ophthalmol 2013).
The plaque was placed in the right eye with an Rx of 85 Gy to the apex of the tumor and then removed one week later after the completion of brachytherapy
The USC Ocular Oncology Service has described a novel method for plaque placement using a toric marker
A surgical video of placement of the USC Eye Physics Plaques can be found online here (link: http://www.eyephysics.com/PS/PS6/UserGuide/EyePlaqueMovie.html) or on the USC Ocular Oncology Facebook page (link: https://www.facebook.com/usceyeonc/)
A fine needle aspiration biopsy for gene expression profiling was offered to the patient, which she declined
Prognosis and Future Directions
As described in COMS report No. 28, the risk of metastatic disease is similar whether patients undergo enucleation or brachytherapy for medium-size melanoma. This risk is 17-21% at 12 years.
The most common site of metastasis is to the liver
As reported by Berry et al, JAMA Ophthalmol 2013, the USC Eye Physics Plaques have compared favorably to the COMS plaques given its customization to the patient’s tumor characteristics (Table 1 below):
Key findings illustrated in Table 1 are:
Reduced tumor recurrence and enucleation rates at 5 years compared to the COMS plaques
Reduced adverse radiation effects including radiation optic neuropathy, retinopathy and cataracts from USC Eye Physics Plaques, in a smaller cohort of patients
Figure 3: At six month post-operative follow-up, fundus imaging shows early choroidal atrophy and ultrasonography demonstrates regression of tumor parameters with measurements of 8.07 mm at the base, with thickness of 2.86 mm.
Patient BCVA 20/20 OU with no adverse symptoms of optic neuropathy, radiation retinopathy, or accelerated cataracts noted, however she will be followed closely for adverse effects
Patient undergoes liver ultrasound and liver function tests every six months, which have been negative to date
While declined by this patient, many patients choose to have a biopsy for a PCR-based Gene expression profiling of 15 genes, which classifies tumors as Class 1A, 1B and 2. The risk of developing metastatic disease at five years, as reported by Castle Biosciences, is 2%, 21% and 72% respectively. Class 2 tumors have a much higher risk of metastatic disease and imaging surveillance can be appropriately targeted with this information
Patient follows-up with the USC Ocular Oncology Service every three-to-four months to monitor for tumor regression, surveillance for recurrence, and adverse effects of radiation
References
Berry JL, Dandapani SV, Stevanovic M, Lee TC, Astrahan M, Murphree AL, Kim JW. Outcomes of Choroidal Melanomas Treated with Eye Physics: A 20-Year Review. JAMA Ophthalmol. 2013; 131(11):1435-1442.
Berry JL, Kim JW, Jenelle R, Astrahan M. Use of the Toric Surgical Marker to Aid in Intraoperative Plaque Placement for the USC Eye Physics Plaques to Treat Uveal Melanoma: A New Surgical Technique. Ophthalmic Surg Lasers Imaging Retina. 2015 Sep; 46(8):866-70.
Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998 Oct 15; 83(8):1664-78.
The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Collaborative Ocular Melanoma Study Group. Arch Ophthalmol. 2006 Dec; 124(12):1684-93.
Eskelin S, Pyrhönen S, Summanen P, Hahka-Kemppinen M, Kivelä T. Tumor doubling times in metastatic malignant melanoma of the uvea: tumor progression before and after treatment.Ophthalmology.2000 Aug; 107(8): 1443-9.
Shields CL, Furuta M, Thangappan A et al: Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol. 2009; 127(8):989-998.
Weis E, Shah CP, Lajous M, Shields JA, Shields CL. The association between host susceptibility factors and uveal melanoma: a meta-analysis. Arch Ophthalmol. 2006 Jan; 124(1): 54-60.
Contact
Jesse L. Berry, MD, Assistant Professor of Clinical Ophthalmology and Assistant Director of Ocular Oncology, jesse.berry@med.usc.edu
