Prophylactic Ranibizumab for Exudative Age-related Macular Degeneration

This is a multicenter, prospectively randomized, masked and controlled, interventional
investigator sponsored phase I/II study of subjects with high-risk nonexudative age-related
macular degeneration (AMD) treated with intravitreal ranibizumab quarterly for prophylaxis
of conversion to exudative age-related macular degeneration.

The objective of this study is to investigate the safety and efficacy of prophylactic
anti-vascular endothelial growth factor (VEGF) therapy with ranibizumab to prevent the
development of exudative AMD in eyes with high-risk nonexudative AMD. In addition, baseline
characteristics of high-risk eyes (fundus features, optical coherence tomography (OCT)
parameters and genetic profile) will be evaluated to determine their predictive value in
conversion to exudative AMD. The effect of ranibizumab on the atrophic component of AMD will
also be monitored.

Inclusion Criteria:

- Adult over 50 years old

- Able to sign informed consent and comply with the study protocol for the duration of
two years

- Nonexudative age-related macular degeneration (AMD) in one eye (study eye)

- History of exudative AMD in one eye only (fellow eye) diagnosed within 5 years of
study enrollment

Exclusion Criteria:

- Participation in another simultaneous medical investigation or clinical trial

- Patient is pregnant, lactating, or premenopausal and not using adequate contraception

- Known serious allergies to ranibizumab, fluorescein dye, drugs for pupillary
dilation, topical anesthetic, sterilizing solution (e.g. Betadine solution)

- Presence of ocular conditions with increased risk of choroidal neovascularization
(CNVM) or pigment epithelial detachment (PED), including presumed ocular
histoplasmosis syndrome (POHS), traumatic choroidal rupture, angioid streaks,
pathologic myopia (spherical equivalent of ≥ -8 diopters or axial length of ≥ 25 mm),
multifocal choroiditis, macular choroidal nevus, polypoidal choroidal vasculopathy
(PCV), idiopathic central serous chorioretinopathy (ICSC), etc.

- History of vitrectomy in the study eye

- History of cataract surgery within 3 months of enrollment

- History of yttrium aluminum garnet (YAG) capsulotomy within 1 month of enrollment

- History of intraocular or periocular corticosteroid therapy within the past 90 days

- History of therapeutic radiation in the region of the study eye.

- Presence of media opacity that would preclude adequate examination and/or imaging

- Concurrent macular conditions that would affect the study parameters (epiretinal
membrane, macular hole, macular edema) or require treatment within the duration of
the study

- Any progressive ocular condition (uncontrolled glaucoma, diabetic retinopathy,
uveitis) that may affect the visual acuity for the duration of the study

- Active ocular infection (i.e., bacterial, viral, parasitic, or fungal) in either eye
at enrollment

- Presence of any advanced systemic condition that may hinder the patients
participation and completion of the study

- Concurrent use of systemic anti-VEGF therapy