Objective: The Dark Adaptation Extension study allows us to continue with the follow-up
of participants who were enrolled in the clinical trial, 11-EI-0147, Longitudinal
Investigation of Dark Adaptation in Participants with Age-Related Macular Degeneration,
investigating long-term changes in dark adaptation in participants with a range of
age-related macular degeneration severity who have already been characterized and
followed under that protocol. To that aim, correlating structural features (obtained from
multimodal imaging) as well as genetic and systemic factors obtained from biospecimens
with functional measures (including dark adaptation, visual acuity and low luminance)
will be done to understand the relationship of disease relevant factors and to create a
model of disease pathogenesis and progression.
Study Population: Participants will be recruited from participants already enrolled in
11-EI-0147. Participants will have varying degrees of severity of AMD (Groups 0, 1, 2, 3
and 4). Group 0 (N=40) is defined as participants without AMD meaning no large drusen (>=
125 microns) or advanced AMD in either eye. Group 1 (N=40) is defined as participants
with large drusen (>= 125 microns) in the study eye and no large drusen or advanced AMD
(choroidal neovascularization (CNV) or geographic atrophy (GA)) in the fellow eye. Group
2 (N=40) is defined as participants with bilateral large drusen (>= 125 microns) with or
without retinal pigment epithelial hypo/hyperpigmentary changes. Group 3 (N=40) is
defined as participants with large drusen (>= 125 microns) in the study eye and advanced
AMD (CNV or GA) in the fellow eye. Group 4 (N=40) is defined as participants with
findings of reticular pseudodrusen (RPD) in the study eye, without advanced AMD in the
study eye, and any level of AMD in the fellow eye. RPD is defined as having (1) the
presence of reticular inter-lacing patterns on at least one en face imaging method (color
photography, autofluorescence or infrared) and (2) confirmation of previously described
findings of hyper-reflective material located between the retinal pigment epithelium
(RPE) and the photoreceptor ellipsoid zone on SD OCT in those areas. Up to 40 diabetic
participants will be recruited.
Design: This is a single center, exploratory, observational, longitudinal evaluation of
dark adaptation response in AMD participants who have been followed over five years and
will be followed over an additional five years to determine long-term evaluation of dark
adaptometry (DA) change as a predictor for AMD progression and visual acuity (VA) loss.
For the second five-year study period, participants will have six required study visits
(baseline, 12, 24, 36, 48 and 60), continuing on an annual basis following exit from
11-EI-0147, for a total follow-up period of 11 years across both protocols. The windows
surrounding each study visit will be plus or minus 6 weeks, except for the baseline visit
which will be plus or minus 8 weeks.
Outcome Measures: The primary objective will be to determine mean change, including
distribution of change in dark adaptation response between baseline and months 12, 24 and
48 in participants with varying degree of severity of AMD (Groups 0, 1, 2, 3 and 4).
Primary outcome data collected at Month 48 will be compared to the initial baseline
testing done in 11-EI-0147 which will be 10-year data across both protocols. Dark
adaptation parameters will be measured using the AdaptDxTM technology. The secondary
outcomes include the mean change in dark adaptation and other characteristic parameters
of the dark adaptation response from baseline at months 12, 24, 36, 48 and 60 from the
two methods, and the mean change in best-corrected visual acuity (BCVA) of the study eye
from baseline and months 12, 24, 36, 48 and 60. Exploratory outcomes for each of the five
groups are to correlate mean BCVA of the study eye with mean dark adaptation response at
baseline and months 36, 48, and 60 and to correlate AMD severity, including grading by an
external Reading Center, with dark adaptation response at baseline and months 12, 24, 36,
48 and 60. Images from all visits may be sent to the Reading Center.
Outcome measures for the genetic testing and RNA sequencing performed on participants
co-enrolled in the Biobank protocol (12-EI-0042) include the interaction of key
parameters of phenotype (such as visual acuity, dark adaptation, and retinal features on
ocular imaging) with genetic variants and other biomarkers identified from biospecimens,
and the characterization of new experimental models of eye health and disease.
