Intravitreal Aflibercept for Neovascular Polypoidal Choroidal Vasculopathy (RIVAL Trial)

This is an open-label, non-randomized, unmasked, study of IAI in patients with choroidal
neovascularization secondary to polypoidal choroidal vasculopathy (PCV). Twenty treatment
naïve and previously treated PCV eyes will be enrolled (only one study eye per patient will
be enrolled). A maximum of 10 previously treated eyes will be enrolled. Consented, enrolled
patients will be followed monthly. All patients will receive monthly IAI 2.0 mg
intravitreally for 3 months (Baseline, Months 1 and 2), followed by mandatory IAI 2.0 mg
every 2 months (Months 4, 6, 8 and 10) for 12 months. Patients can receive additional IAI
treatment (Months 3, 5, 7, 9, and 11) if the re-treatment criteria are met. Starting at
Month 3, patients can receive non-anti vascular endothelial growth factor (VEGF) rescue
therapy (ie: Photodynamic Therapy (PDT), laser, intravitreal steroids) if the pre-defined
criteria are met.

Inclusion Criteria:

- Males and females ≥ 18 years of age. Females of child bearing potential will undergo
urine pregnancy testing and be required to use appropriate methods of birth control

- ICG and fluorescein angiographic characteristics consistent with active, leaking PCV
with subfoveal lesions and/or subfoveal hemorrhage, lipid exudates, PED or fluid

- Best corrected early treatment of diabetic retinopathy study (ETDRS) visual acuity at
4 meters between 20/20 - 20/400 (BCVA ETDRS letter score 85 - 20 letters in the study
eye)

- Lesion Characteristics - leaking lesions consistent with PCV. (No limitations on
hemorrhage, fibrosis or atrophy)

- Clear ocular media to allow for photography/angiography

- Willing and able to comply with clinic visits and study-related procedures

- Patients with bilateral disease will only be able to enroll one eye

- Provide signed informed consent

Exclusion Criteria:

- Any history of systemic Anti-VEGF therapy

- Current ocular or periocular infection

- Active intraocular inflammation

- Any comorbid condition that may decrease visual acuity

- Any patients who have had intraocular surgery within the past 30 days for any
condition

- For treatment naïve patients: No prior anti-VEGF, PDT, intravitreal steroids or laser
(subfoveal or non foveal)

- For previously-treated patients :

- Prior anti-VEGF (ranibizumab, bevacizumab, pegaptanib) within 30 days

- Prior IAI

- Prior PDT , transpupillary thermal therapy (TTT) or radiation within 90 days (a
maximum of 3 PDTs allowed)

- Prior intravitreal steroids within 90 days

- Prior non-foveal laser within 90 days

- Prior subfoveal laser

- Patients with features of dry age-related macular degeneration such as abundant
drusen and symptoms/demographic features inconsistent with the diagnosis of PCV

- Allergy to fluorescein, ICG, iodine, shellfish

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

- Participation in another simultaneous medical investigation or trial

- History of previous subfoveal laser

- Advanced glaucoma (IOP > 25 or cup/disc ratio > 0.8)

- Pregnant or breast-feeding women

- Sexually active men* or women of childbearing potential** who are unwilling to
practice adequate contraception during the study (adequate contraceptive measures
include stable use of oral contraceptives or other prescription pharmaceutical
contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device
(IUD); bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam,
or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) *Contraception is
not required for men with documented vasectomy. **Postmenopausal women must be
amenorrheic for at least 12 months in order not to be considered of child bearing
potential. Pregnancy testing and contraception are not required for women with
documented hysterectomy or tubal ligation.