Intravitreal Aflibercept Injection for the Treatment of Submacular Vascularized Pigment Epithelial Detachment

Inclusion Criteria:

- Subject is ≥ 50 years of age

- Subject is willing to participate in this study and to follow the criteria and
protocol of this study.

- The study eye is treatment naïve regarding treatment of neovascular AMD.

- Subject is not involved with another clinical study currently.

- Subject is willing to follow the protocol outlined in the study.

- Ability to understand the informed consent and willingness to sign the informed
consent.

- Presence of a submacular vascularized or fibrovascular PED. The investigator must
search for the characteristic features of a vascularized PED summarized here:

1. A notch of irregularity associated with an orange-yellow round, oval, or
bean-shaped elevation of the RPE with a smooth, convex surface is seen on
examination and fundus photography (FP). Fluorescein angiography (FA) shows
uniform staining of the PED with a well-defined margin, and more intense
staining (hot-spot) for the focus of the CNV.

2. A fibrovascular PED with occult neovascularization typically shows stippled
hyperfluorescence in the early phase with increasing hyperfluorescent staining
and leakage in later phases of FA and a variable surrounding margin. There may
be RPE folds.

3. Regarding PED with a component of retinal angiomatous proliferation (RAP), the
early features on FP including intraretinal neovascularization (IRN) frequently
with adjacent small retinal hemorrhages in its lateral expansion in an
irregularly stellate pattern before the development of retinal-choroidal
anastomosis and the eventual PED in the later phases. The investigator is
required to perform indocyanine-green (ICG) angiography at baseline to establish
a RAP lesion and to rule-out polypoidal vasculopathy lesions, since the FA
images may not be distinct.

4. The investigator must also search for other features associated with a PED
indicating the presence of a vascular component, i.e. hemorrhage, exudates,
and/or chorioretinal folds.

5. The investigator must confirm the presence of a PED on FA/FP and OCT. Spectral
Domain OCT will be utilized. Specifically, the Spectralis OCT manufactured by
Heidleberg to maintain uniformity for all the sites. The PED height, SA, GLD,
and volume will be measured from the OCT images. The characteristic OCT findings
of the vascularized PED must be confirmed, including a distinct elevation of the
highly hyperreflective RPE layer with mild backscattering of the underlying
choroidal layer in the portion of the PED without any CNV. For the portion of
the PED with underlying CNV, typical OCT findings consist of moderate
hyperreflectivity contiguous to the overlying markedly hyperreflective detached
RPE corresponding to the CNV that usually extends to the choroidal layer.
Besides the OCT characteristics confirmation must be made on the FP/FA images of
the vascularized PED, as outlined above in detail.

- Central foveal involvement by the PED or the CNV due to age-related macular
degeneration (AMD). The CNV may be classic, occult, or mixed, as long as it is
associated with a PED. The CNV may be within the PED or adjacent to the margin of the
PED.

- PED ≤ 12 disc area in size.

- BCVA with ETDRS of ≥ 19 letters and ≤ 73 letters (20/400 to 20/40).

- Evidence of submacular fluid outside or surrounding the PED.

- Surface area of the submacular hemorrhage needs to be < 50% of the entire PED.

- Submacular fibrosis needs to be < 50% of the entire PED.

- Sufficiently clear media (cornea, anterior chamber, lens, vitreous) for OCT, FA and
FP.

- Intraocular pressure (IOP) of 25mmHg or less in the study eye, with or without use of
ocular hypotensive agents.

- Prior treatment of neovascular AMD or any other forms of neovascularization in the
fellow eye, including anti-VEGF or other forms of therapy targeted specifically for
the fellow eye does not exclude the fellow eye from enrollment in this study. Prior
focal corticosteroid treatment is allowed, as long as there is a lack of involvement
of the study eye. However prior (within 90 days of Day 0) or current systemic
corticosteroid therapy (oral or intravenous corticosteroid treatment) is not
permitted.

Exclusion Criteria:

- Any prior treatment of neovascular AMD in eye for proposed enrollment (non-naïve
eye), including previous anti-vascular endothelial factor (anti-VEGF) therapy,
photodynamic therapy (PDT), radiation therapy, corticosteroid treatment, surgical
treatment for CNV, thermal laser treatment, and any other prior treatment for
neovascular AMD.

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

- Contraindication to pupillary dilation in study eye.

- Any condition (including inability to read visual acuity charts, or language barrier)
that may preclude subjects ability to comply with the study protocol and
requirements.

- Presence of any advanced systemic condition or end-stage disease, advanced Alzheimer
Syndrome, end-stage cancer, etc., which will likely prevent subject from completing
study.

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

- Prior retinal pigment epithelial (RPE) tear in study eye.

- Prior ocular surgery (except YAG laser capsulotomy) for study within the past 90
days.

- Anticipated ocular surgery (except YAG laser capsulotomy) for the next 12 months

- Prior therapy for AMD (except minerals and vitamins), including laser.

- Prior vitrectomy

- Presence of any causes of CNV and PED other than due to AMD.

- Presence of any substantial ocular disease (other than the CNV and PED) that may
compromise vision in the study eye and/or confound interpretation of the data; e.g.
substantial cataracts, concomitant diabetic retinopathy affecting the macula,
advanced glaucoma, optic neuritis, optic neuropathy, or atrophy, marked macular
atrophy, ocular vascular occlusion, history of retinal detachment, uveitis, viral or
other forms of chorioretinitis, etc.

- Presence of ocular disease other than AMD affecting study eye, i.e. presumed ocular
histoplasmosis syndrome, android streaks, pathologic myopia (spherical equivalent of
≥ -8 diopters of myopia or axial length of ≥ 25mm), choroidal rupture, multifocal
choroiditis, etc.

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

- Serous PED without neovascularization and polypoidal choroidal vasculopathy (PCV)
lesions are excluded.

- Prior or current systemic anti-VEGF

- Prior (within 90 days of Day 0) or current corticosteroid therapy (oral or
intravenous corticosteroid treatments).

- Sexually active men* or women of child-bearing potential** who are unwilling to
practice adequate contraception during the study (adequate contraception 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. ** Post-menopausal 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.