Genetic Analysis of Patients Responsive to Ranibizumab But Resistant to Aflibercept

A cohort of patients responsive to treatment with ranibizumab but resistant to

aflibercept were identified in a previously conducted retrospective study. Identified

patients will have their blood drawn for genome wide sequencing. The sequencing

data will be compiled and analyzed in an attempt to identify a common genetic basis

for patients susceptible to ranibizumab but resistant to aflibercept.

Blood samples will be drawn for genetic analysis for all patients enrolled in the study.

The sample (1 tube- 6mL of blood) will be collected using - 8.5mL PAXgene Blood DNA

Tubes (http://www.qiagen.com/products/catalog/sample-technologies/dna-sample-

technologies/genomic-dna/paxgene-blood-dna-tubes).

Samples will be stored at -80 until time for analysis. Note that some blood draws will be
performed at

satellite clinics and transported to main facility for storage in -80 freezer. It is the
understanding of

ARC PI and staff that the PAXgene Blood DNA Tubes keep samples stable at room temp for 1-2

days.

However, staff will transport samples in timely fashion (room temp, on ice, dry ice,

etc), to -80 freezer for storage until all samples are collected. Once all samples are

collected, they will be shipped to Genentech for analysis. DNA extraction, the generation of
genetic

data, and subsequent analysis will be performed at Genentech or via third party. DNA will be
assayed

for polymorphisms through genome wide SNP chip or whole genome sequencing. The subject's

genotype or haplotype will be correlated with their visual response and OCT response.

Inclusion Criteria:

- Subjects will be eligible if the following criteria are met:

- Demonstrate worsening of exudation when switched from ranibizumab to aflibercept

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

Exclusion Criteria:

- Any other condition that the investigator believes would pose a significant hazard to
the subject