Safety and Efficacy of Silicone Oil Tamponade for Surgical Attenuation of Radiation Damage in Choroidal Melanoma

Melanoma arising from the choroid and ciliary body is the most common primary intraocular
cancer. The Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of I-125
brachytherapy versus enucleation for medium-sized choroidal melanoma (2.5-10.0 mm in
thickness and ≤ 16 mm in diameter) showed that, for patients who met the eligibility
criteria, there was no statistically significant difference in all-cause mortality between
I-125 brachytherapy and enucleation 5, 10, and 12 years following treatment. The COMS trial
supported the use of globe-conserving I-125 brachytherapy. Following brachytherapy, however,
visual acuity in the treated eye generally declined at a rate of approximately 2 lines of
visual acuity per year and nearly 45% of patients lost ambulatory vision (≤20/200) in the
treated eye by 3 years.

Adverse effects of plaque brachytherapy include cataract, radiation-associated proliferative
retinopathy, maculopathy and papillopathy. Radiation maculopathy, which may result in
decreased central vision, cystoid macular edema (CME), macular ischemia, and chorioretinal
atrophy, was reported in other series in 18% to 43% of treated eyes within 5 years after
brachytherapy. Typical onset occurred 18-24 months following treatment. Primary risk factors
for radiation papillopathy and maculopathy were total radiation dose to the affected
structures, proximity of the tumor to the affected structures and systemic conditions such as
diabetes mellitus. No treatment for radiation maculopathy or papillopathy has been proven to
be effective in a randomized clinical trial.

Radiation injury to vital structures may be avoided or shielded with the use of materials
such as lead that have a higher effective atomic number and density than tissue. However,
solid metals are not amenable to use within the eye (Figure 1).

There have been previous efforts to try to use a vitreous substitute in order to protect
intraocular structures from the deleterious effects of radiations. In an animal study, Finger
et al, demonstrated that iodinated contrast agents (iophendylate, iohexol, and iopamidol)
could block radiation intraocularly. But these substances were highly toxic and could not be
retained in the eye due to high water solubility.

The technique of vitrectomy and oil tamponade during plaque brachytherapy has been performed
previously in humans by Dr. Tara McCannel at UCLA. During a paper presentation at the 2010
meeting of the American Society of Retina Specialist in Vancouver, BC, the first series of 10
patients were presented, and no complications of the technique were reported. It is now a
commonly applied technique at this center for treatment of choroidal melanoma (Oncology Times
2010; 32(14):36, UCLA, Clinical Update 2011; 20(1):1, 4)

In this prospective pilot study the investigators propose that patients will undergo standard
plaque placement for treatment of their ocular melanoma in addition to pars plana vitrectomy
and silicone oil infusion. When patients return for their scheduled plaque removal one week
later, they will also undergo removal of the silicone oil from the eye. Placement of silicone
oil should not alter the radiation dose delivered to the tumor, as there is no physical space
between the tumor and the radioactive plaque for silicone oil to be present. The reduction in
radiation to healthy ocular structures by using the oil technique may be sufficient to avoid
the clinical complications caused by radiation-induced injury.

Inclusion Criteria:

- All treatment-naïve patients with clinical diagnosis of primary choroidal melanoma,
amenable to treatment with plaque brachytherapy, aged 18 or older regardless gender,
race/ethnicity or existing medical condition unless they are specifically mentioned as
exclusion criteria.

- Patients with best corrected visual acuity of 20/400 or better in the study eye.

- Patients in whom the calculated dose of radiation to the optic nerve or macula is > 25
Gray (Gy).

Tumor inclusion criteria:

- Unilateral choroidal melanoma, medium size as defined by COMS classification:

1. At least 2.5 mm in height, but no more than 10 mm in height (no more than 8.0 mm
whenever the tumor was near the optic disc), and

2. No more than 16.0 mm In diameter, regardless the shape by ultrasound.

Exclusion Criteria:

- History of previous treatment for the choroidal melanoma.

- Pregnancy.

- Patients with any impairment which prevent attending follow-up appointments.

- The presence of concomitant significant life-treating medical conditions that
significantly reduces the life expectancy to less than three years.

- The presence of other vision-treating ophthalmic condition, not directly related with
choroidal melanoma which is likely to going to require intraocular surgery in the next
three years.

- Clinical or radiological evidence of the presence of metastatic disease.

- The presence of significant media opacity (e.g. cataract) that precludes the
investigator's ability to grade the tumor, performs retina surgery, or performs
follow-up assessments.

- Patients that do not accept the informed consent

Tumor exclusion criteria:

- Inability to successfully grade, stage and delineate the tumor by ultrasound.

- Tumor location that will prevent the correct placement of the plaque or have
significant risk of optic nerve damage during plaque placement.

- Tumors that involved the anterior chamber angle, the iris or have detectable
extrascleral extension.

- Tumor margin location < 1000 µm from the fovea.