AMD Phenotype and Genotype Study

Objective: Late age-related macular degeneration (AMD) is the leading cause of blindness
among elderly in the United States. At present the current classification systems do not take
into consideration advances in imaging technology and genotyping and phenotyping.

Clinical centers in the US and around the world will conduct a pilot cohort study that will
bring together resources and commitment to test the feasibility of developing a new
classification scheme for AMD using imaging and visual function biomarkers, with the
potential of correlating genetic information obtained in the future. These data could
eventually help develop an understanding of the mechanisms involved in the development and
progression of AMD. A database of men and women with and without AMD will be established and
maintained. The project will recruit participants who have various stages of AMD and
controls. The pilot study will identify the feasibility of obtaining imaging and visual
function data and help identify which of these modalities should be included in a full scale
longitudinal study, as well as how frequently and at which sites they should be obtained. All
data, images and any potential biospecimens from the full scale longitudinal study will be
available to researchers worldwide to help in the development of biomarker identification and
classification development. The initiative should provide an unparalleled state-of-the-art
standardized phenotype/genotype including AMD status with information on imaging, visual
function, and biospecimen biomarkers. This study is the first phase of this initiative to
test the feasibility and logistics of defining a standard database including enhanced
phenotype and genotype data.

Study Population: This cohort study will recruit a minimum of 200 total participants with
various stages of AMD, including controls and obtain the appropriate images and measures of
visual function needed for the investigation and validation of an AMD phenotype.

Design: This cohort study is a multi-national, multi-center, observational study focused on
AMD. The study is a pilot to test the ability to create an archive of data, biological
samples (collected at other study sites), measures of visual function and ophthalmic images
collected over time from a very well clinically characterized population of participants with
a diagnosis of AMD. The database will also include a control group consisting of participants
without a diagnosis of AMD.

Outcome Measures: The design of this cohort study and the data being collected will allow
users to assess phenotypes of AMD, develop and evaluate potential markers and risk factors,
develop and evaluate an AMD classification scheme(s), and assess the progression of the
disease and investigate factors that shape it. It is not practical to anticipate all of the
potential uses of the data, or all the types of analyses that will be performed to address
user-defined questions.

- INCLUSION CRITERIA:

To be eligible, the following inclusion criteria must be met, where applicable.

-Male or female participants must fall into any of the following categories:

- No drusen or any AMD-associated pigment abnormalities (no apparent aging changes)

- Small drusen (less than or equal to 63 micro millimeters in diameter) and the absence
of AMD-associated pigment abnormalities in either eye (normal aging changes)

- Medium (>63 (Micro)m and less than or equal to 125 micro millimeters in diameter)
drusen in either eye (Early AMD)

- Large (>125 (Micro)m in diameter) drusen with or without pigmentary abnormalities in
either eye (Intermediate AMD)

- Neovascular AMD in only one eye or the presence of geographic atrophy in either eye
but with vision >20/60 in the better-seeing eye (Late AMD)

- Presence of reticular Drusen in either eye

AMD classification will be based on clinical evaluation.

- 60 years of age or older

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

- Retinal photographs of sufficient quality to allow assessment of the macular area for
AMD lesions including drusen

EXCLUSION CRITERIA:

A participant is not eligible if any of the following exclusion criteria are present:

- Presence of lens or vitreous opacity in eye(s) with AMD to preclude adequate
ophthalmic imaging

- Presence of ocular conditions that may now or in the future complicate the evaluation
of AMD [e.g., vascular occlusion, diabetic retinopathy (>4 microaneurysms), etc.] in
the eye(s) with AMD

- High myopia -6 Diopters or more severe

- Diagnosis of nystagmus

- Glaucoma with definite visual field defects. Participants with a history of the
diagnosis of glaucoma, past or present use of medications to control intraocular
pressure, or disc/nerve fiber layer defects suggestive of glaucoma can be eligible for
the study if they have a documented normal Goldmann, Humphrey, or Octopus perimetry
test within 6 months prior to qualification.