Genetic Study of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) represents the most common cause of blindness in
patients over the age of 50. While both hereditary and environmental factors appear to play
a role in the pathogenesis of the disease, no common genetic mutations have been identified.
This pilot study is intended to test the feasibility of evaluating the patterns of
expression of genes that may be involved in the pathogenesis of AMD. The genes of interest
are involved in the process of wound repair, cell injury and cell death. We hope to access
the expression of these genes, but in tissues taken from non-ocular sites, in patients with
AMD and in patients without AMD.

Biopsied skin fibroblasts and circulating monocytes from 62 patients will be obtained; 14
without AMD, 14 with at least one large (greater than 125 microns) druse, with geographic
atrophy and/or choroidal neovascularization from AMD, 10 with geographic atrophy only, and
20 with choroidal neovascularization and/or disciform scar. The gene expression patterns
from these tissues will be examined through various techniques including polymerase chain
reaction, Northern blot analysis, differential display and microarray technology. The
genetic expression patterns in patients with AMD will then be compared to age-matched
control subjects. The primary outcome will be to determine the feasibility of obtaining skin
and monocyte samples from patients with AMD, extracting RNA from these samples, and studying
gene expression patterns. This study will provide investigators with information needed to
develop subsequent studies of potential diagnostic tests.

- INCLUSION CRITERIA:

INCLUSION CRITERIA 1 THROUGH 3 APPLY TO THE FIRST TWELVE PARTICIPANTS ENROLLED. INCLUSION
CRITERIA 4 THROUGH 6 APPLY TO THE LAST 50 PARTICIPANTS ENROLLED.

1. AMD Patients: Diagnosis of AMD defined by the presence of at least one druse greater
than 125 microns in diameter (4 patients) or geographic atrophy in at least one eye
or choroidal neovascularization with drusen of any size in at least one eye (4
patients). (AMD cases only)

2. Age 60 years or older.

3. Age-matched control patients, absence of drusen or no more than 5 drusen less than 63
microns, absence of other diagnostic criteria for AMD, and age 60 years or older. The
distribution of ages in the control group will be as similar as possible to the
distribution of ages in the disease groups (4 patients).

4. AMD Patients: Diagnosis of AMD defined by the presence of at least one druse greater
than 125 microns in diameter (10 patients), geographic atrophy (10 patients) and
choroidal neovascularization with drusen of any size in at least one eye and/or
disciform scar (20 patients). (AMD cases only) Presence of neovascularization and
disciform scar formation will be verified by color photography.

5. Age 50 years or older.

6. Age-matched control patients: absence of drusen or no more than 5 drusen less than 63
microns, absence of other diagnostic criteria for AMD, and age 50 years or older. The
distribution of ages in the control group.

EXCLUSION CRITERIA:

Patient age less than 50 years.

Presence of retinal disease involving the photoreceptors and/or outer retinal layers other
than AMD loss such as high myopia, retinal dystrophies, central serous retinopathy, vein
occlusion, diabetic retinopathy and uveitis or similar outer retinal diseases which have
been present prior to the age of 50.

Opacities of the ocular media, limitations of pupillary dilation or other problems
sufficient to preclude adequate stereo fundus photography.

Medical problems which make consistent follow-up over the treatment period unlikely (e.g.,
stroke, severe MI, terminal carcinoma).

Inability or inaccessibility to obtain dermal biopsy from the inner aspect of both arms
due to previous trauma, underlying skin disorder which would preclude good wound healing,
previous surgery of the arm or breast which could prevent good wound healing or induce
other changes at the biopsy site.