Study for Recalcitrant Age Related Macular Degeneration

The rationale for the TURF trial is based on the greater binding affinity of VEGF Trap-eye,
which theoretically may prove to be more effective for recalcitrant wet AMD and therefore
may demonstrate a positive impact on visual acuity and the foveal anatomy of subjects who
have a history of a less than optimal anatomical and visual response to multiple
intravitreal injections of 2.0mg (super-dose) ranibizumab. Based on the anatomical data from
the VIEW1 and VIEW2 trials, approximately 70% of VEGF-Trap eye patients had no evidence of
fluid on OCT compared to approximately 55% of ranibizumab patients. One potential
interpretation of this clinical data is that the increased binding affinity and longer
half-life of VEGF-Trap eye result in the resolution of more fluid for a longer duration of
effect.

Patients to be enrolled in this study have a history of requiring monthly dosing of
ranibizumab 2.0mg to achieve maximum resolution of fluid on OCT and increased visual acuity.
These patients initially showed minimal fluid resolution visual acuity gains while treated
with Lucentis (0.5mg ranibizumab) and were subsequently treated with 2.0mg monthly. It is
expected that treating these same patients with 2.0mg EYLEA™ (aflibercept injection for eye)
will maintain the fluid resolution on OCT and visual acuity gains previously requiring a
super-dose of ranibizumab.

Inclusion Criteria:

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

- Age > 50 years

- Choroidal neovascularization secondary to AMD

- History of treatment with 0.5mg ranibizumab followed by 2.0mg ranibizumab for AMD

- Best corrected visual acuity in the study eye between 20/20 to 20/400 using an ETDRS
chart

Exclusion Criteria:

- Pregnancy (positive pregnancy test) or lactation

- Premenopausal women not using adequate contraception. The following are considered
effective means of contraception: surgical sterilization or use of oral
contraceptives, barrier contraception with either a condom or diaphragm in
conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.

- Participation in another simultaneous medical investigation or trial

- Prior treatment with anti-VEGF therapy in the study eye within 28 days of baseline

- Prior treatment with PDT within the past 3 months or more than 4 prior PDT
treatments.

- Presence of significant subfoveal fibrosis or atrophy.

- Prior treatment with intravitreal aflibercept injection

- Prior treatment with triamcinolone in the study eye within 6 months of BSL.

- Prior treatment with dexamethasone in the study eye within 30 days prior to BSL

- Intraocular surgery (including cataract surgery) in the study eye within 2 months
preceding Baseline

- History of vitrectomy surgery, submacular surgery, or other surgical intervention for
AMD in the study eye

- Active intraocular inflammation (grade trace or above) in the study eye

- Current vitreous hemorrhage in the study eye

- History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the
study eye

- Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either
eye

- Uncontrolled glaucoma in the study eye (defined as IOP ≥ 30 mmHg despite treatment
with anti-glaucoma medication)

- History of cerebral vascular accident, myocardial infarction, transient ischemic
attacks within 3 months of study enrollment.

- History of allergy to fluorescein, ICG or iodine, not amenable to treatment

- History of retinal pigment epithelial tear or rip