Neovascular Morphology and Persistent Disease Activity Among Patients With NV AMD

Neovascular Age-Related Macular Degeneration (NV AMD) remains the leading cause of vision
loss among people over 65. Intravitreal injections with drugs that block VEGF, a major
protein mediator of angiogenesis and vascular leakage, have revolutionized treatment of NV
AMD. However, less than 40% of treated patients have clinically significant improvement in
vision. Further, in spite of continuous monthly anti-VEGF therapy, up to 40-50% of patients
demonstrate sustained persistent disease activity (PDA), defined as (1) unresolved
intraretinal, subretinal, or sub-retinal pigment epithelium fluid; (2) progressive lesion
enlargement and fibrosis; and/or (3) persistent or new hemorrhage, assessed after either
loading dose therapy or after sustained treatment with anti-VEGF. Since affected patients are
at increased risk for long-term vision loss, PDA remains a vital clinical unmet need.

We are interested in the relationship between NV lesion morphology and response to therapy.
Specifically, we hypothesize that specific NV morphologic subtypes are more frequently
associated with PDA, based on preliminary retrospective analyses of indocyanine green (ICG)
imaging data from NV AMD patients in our Duke Medical Retina practice. We have observed that
eyes with Capillary pattern, seen as a discrete homogenous focus of microvessels, are highly
responsive to anti-VEGF therapy and rarely exhibit PDA (<20% of cases). In contrast, eyes
with Arteriolar pattern (large-caliber feeding artery, many branching arterioles, and minimal
capillary component) and eyes with polypoidal choroidal vasculopathy (variably sized and
numbered, discrete saccular dilations of choroidal vasculature), demonstrate PDA in up to 70%
of cases. A third subtype, choroidal leak syndrome, visible as choroidal hyperpermeability
and leakage, manifest PDA in over 60% of cases. These data suggest that complex NV lesion
morphology is the primary cause of PDA, and that anti-VEGF therapy alone is insufficient for
these patients. However, the relative frequency of these subtypes and the association of PDA
and NV lesion morphology, in a treatment-naive population free of selection bias, are
unknown.

In this study, we will determine the relative frequency of NV subtypes in two groups: (i) a
representative, treatment-naïve NV AMD patient population, and (ii) a population of patients
who develop recurrent NVAMD activity while off treatment and assess the frequency of PDA
according to specific NV morphologic subtypes. This information will clarify the scope of the
PDA problem, and will identify patients with PDA who may benefit from additional therapeutic
strategies.

Inclusion Criteria:

- Diagnosis of either treatment naive NVAMD or newly reactivated NVAMD which has been
previously quiescent off treatment

- Men and women aged 50 years or older

- Able to provide written informed consent

Exclusion Criteria:

- Potential study eye with ongoing (within previous 6 months of diagnosis of NVAMD
disease activity) treatment for CNV, including anti-VEGF medications, corticosteroids,
photodynamic therapy, thermal laser photocoagulation, transpupillary thermotherapy, or
pneumatic displacement of macular hemorrhage

- CNV secondary to causes other than AMD

- Known or suspected sensitivity or allergy to ICG dye

- Known or suspected sensitivity or allergy to fluorescein dye

- Significant medial opacity (e.g. cataract) precluding clincial imaging adequate for
interpretation

- Prior history of vitrectomy surger in potential study eye