ProspectiveTrial of Proton Beam Combined With Anti-VEGF Therapy for Exudative Age-related Macular Degeneration (AMD)

Radiation combined with anti-VEGF therapy has been shown to be synergistic in treating cancer
and result in sustained tumor regression. On-going clinical trials have shown potential
synergism between intravitreal anti-VEGF therapy and epiretinal brachytherapy administered
during vitrectomy surgery in treating eyes with exudative age-related macular degeneration
(eAMD). In this study, we test the hypothesis that radiation to the macula administered
noninvasively via proton beam is well-tolerated in eyes with eAMD when combined with
intravitreal anti-VEGF therapy and that this combination therapy may act synergistically to
result in sustained treatment effect in eyes with eAMD.

Inclusion Criteria:

- Subjects will be eligible if the following criteria are met:

- Ability to provide written informed consent and comply with study assessments for
the full duration of the study

- Age > 50 years

- Patient related considerations

- Able to maintain follow-up for at least 24 months.

- Women must be postmenopausal without a period for at least one year.

- Diagnosed with Age-related Macular Degeneration (ARMD) with active subfoveal
choroidal neovascular membrane (CNVM), newly diagnosed or treated with first dose
of anti-VEGF therapy within 6 weeks of enrollment

- Visual acuity 20/40 to 20/400

- Lesion size < 12 Disc Area

- Submacular hemorrhage less than 75% of total lesion and not involving foveal
center

- Submacular fibrosis less than 25% of total lesion

- Candidate for intravitreal anti-VEGF therapy

Exclusion Criteria:

- Subjects who meet any of the following criteria will be excluded from this study:

- Prior enrollment in the study

- Pregnancy (positive pregnancy test) or lactation

- Any other condition that the investigator believes would pose a significant
hazard to the subject if the investigational therapy were initiated

- Participation in another simultaneous medical investigation or trial

- Previous treatment with Photodynamic Therapy (PDT) or thermal laser in study eye

- Anti-VEGF therapy within 6 weeks

- Intravitreal or subtenon's Kenalog within 6 months

- Intraocular surgery within 3 months or expected in the next 6 months

- Current or planned participation in other experimental treatments for wet AMD

- Other concurrent retinopathy or optic neuropathy

- Other causes of CNVM, i.e. myopic degeneration or ocular histoplasmosis (POHS)

- Significant media opacity precluding adequate view of the fundus for exam,
photography or OCT

- History of radiation therapy to the head or study eye

- Diabetes mellitus or hemoglobin A1c > 6

- Head tremor or h/o claustrophobia precluding positioning for proton irradiation

- Inability to maintain steady fixation with either eye

- History of Malignancy treated within 5 years

- Allergy to Fluorescein dye