A Study of Disease Progression in Genetically Defined Subjects With Geographic Atrophy Secondary to Age-Related Macular Degeneration

Dry AMD is a disease of the retina that results in loss of vision in the macula
(center of the eye). When Dry AMD progresses, this can lead to a condition
called Geographic Atrophy (GA) causing further loss of vision due to
degeneration of the cells in the retina. Eventually, this may lead to blurred
or loss of vision that affects one or both eyes.

There is currently no treatment available for Dry AMD.

A family history of Dry AMD increases the risk of developing the disease, which
suggests there is a genetic link. It has also been shown that over-activation
of a part of the immune system called the complement system further contributes
to the disease.

A recent study has shown that subjects with a known family history risk who
have an over-active complement system are at an even higher risk of developing
severe Dry AMD disease than subjects that do not have these two risk factors.

To evaluate the natural progression of anatomical and functional visual
parameters in genetically defined subjects with Geographic Atrophy (GA) due to
Age-related Macular Degeneration (AMD).

This is an observational study to evaluate the natural progression of
anatomical and functional visual parameters in genetically defined subjects
with GA due to AMD. For each subject, the study will consist of 7 visits over
approximately 96 weeks. Subjects may be withdrawn if they become eligible for
an interventional study. All participating subjects will undergo functional
visual and retinal imaging/anatomical assessments over the study period.

Subjects will be screened for eligiblity over a 4 to 6 week period and then
observed over a 96 week period. Subjects may be withdrawn if they become
eligible for an interventional study.

Subjects being considered for inclusion will be required to sign a genotyping
consent form, agreeing to provide a sample for genetic testing/or permit the
analysis of an existing sample. Samples will be collected and shipped to a
Central Laboratory for genotyping. A remote sample kit may be sent by the
investigator site to the subject*s home address, with instuctions on how to
collect a saliva sample and ship to the Central Laboratory. If more practical,
the subject may be invited to the investigator site clinic for sample
collection. In some cases blood or saliva samples that have been taken prior to
study entry and stored within the investigator site*s biobank may be used for
genotyping.

At the screening/baseline visit, subjects will be required to sign the full
study informed consent form for participation in the study. Following signature
of the full study informed consent form, the following assessments will be
completed at the subjects* study site:
- Baseline demographics, medical/surgical history, current/ongoing medications
- Blood samples for CFI and biomarker analyses
- Standard ophthalmic examination for both eyes
- ETDRS BCVA. Measured for both eyes in standard and in low luminance
conditions.
- FAF
- 3-field Colour Fundus Photography (CFP)
- SD-OCT
- Retinal sensitivity via mesopic Microperimetry
- Monocular and binocular reading speed using MnRead tool
- QoL using NEI VFQ-25

Subsequent follow-up visits will be scheduled at 12, 24, 48, 72, and 96 weeks.
Both eyes will be assessed and analysed for disease progression.