This is a longitudinal observational study that will look at 300 subjects, 200 with
intermediate AMD in at least one eye, or with AMD in one eye, either early or intermediate,
and with late AMD (exudative) in the other eye, and 100 subjects with nGA or GA in at least
one eye. At baseline, subjects will receive visual acuity testing, low luminance acuity
testing, a complete ophthalmological exam, color fundus photos, fundus autofluorescence
imaging, infrared reflectance imaging, and OCT imaging with SS-OCTA. SS-OCTA imaging is a
non-invasive technique that can be used to evaluate the retinal and choroidal vasculature
without the need for intravenous dyes. OCTA uses scanning patterns and algorithms that detect
the flow of erythrocytes in the retina and choroid by evaluating the changes in the OCT
reflected signal that occur from the movement of erythrocytes. Subjects will be followed with
OCTA at 3-month intervals for a total of 2 years. Interim analysis will also be conducted
when all subjects have completed a 1-year follow up. All subjects will be imaged with the
Zeiss SS-OCT/OCTA system. This SS-OCTA system is being used because it provides better
visualization of the choroid compared with spectral domain OCT imaging. Moreover, the faster
scanning speed and the acquisition of multiple volumetric data sets allows for variable
interscan time flow analysis, which enables the detection of variable flow rates in subjects
with late AMD as shown previously by our group (Choi et al Ophthalmology 2015). Moreover, the
ability to cross-register OCTA with OCT B scans allows for correlation between structure and
flow information. All other imaging will be performed at baseline and at months 12 and 24 The
target population is all subjects who are at least 50 years of age and have a clinical
diagnosis of non-exudative AMD in at least one eye. There will be 2 subject cohorts. Cohort 1
consists of subjects with iAMD in both eyes, and at least one eye with a drusen volume in the
central 3 mm circle centered on the fovea of at least 0.02 mm3 in the absence of GA or nGA as
diagnosed with OCT en face imaging. Nascent GA will be defined as a bright area of hyper
transmission with a greatest linear dimension of 125 microns as seen on en face OCT imaging
using the sub-RPE slab image and confirmed on structural B-scan images OR subjects with AMD
(early or intermediate) diagnosed in one eye and exudative AMD diagnosed in the fellow eye.
There can be no evidence of nGA or GA in the eye with early/intermediate AMD. The eye with
early/intermediate AMD can be enrolled in the study regardless of drusen volume. Cohort 2
consists of subjects with a diagnosis of late AMD and have presence of GA or NGA secondary to
AMD that is at least the size of a large druse (125 microns in diameter; 0.05 mm2) and no
greater than 7 disc areas (17 mm2) in at least one eye. During the study, the non-study
fellow eye will be imaged and data collected irrespective of the level and type of AMD in the
fellow eye The sample size for each cohort is based on the observed rates of conversion from
iAMD eyes with pure drusen to geographic atrophy and MNV of around 10% in 2 years and the
expected growth rate of GA as observed in the preliminary natural history study and the
COMPLETE study. (Garcia, Rosenfeld et al 2014; Schaal, Rosenfeld, et al 2016). Based on these
rates, a sample size over 100 per AMD type (iAMD, dry/wet, nGA/GA) does not result in any
significant narrowing of the projected 95% confidence intervals.
Cohort 1 will have the option to be monitored using the DigiSight Checkup Vision Assessment
System to evaluate whether this provides an early indication of onset or progression of MNV
in subjects with asymptomatic early MNV All subjects will also receive optional genetic
testing to correlate to their exam findings and disease progression. Subjects who convert to
exudative AMD during the study will be treated as per the enrolling physician's standard of
care and will continue to be scanned per protocol, allowing for a wider interval of +/- 30
days around the standard timing of scanning to avoid excessively frequent visits.