Vitamin A Palmitate Supplementation in People With Age-Related Macular Degeneration (and Without Reticular Pseudodrusen) and Delayed Dark Adaptation

Objective: The objective of this study is to investigate the potential efficacy of vitamin A
palmitate in improving dark adaptation in participants with age-related macular degeneration
(AMD) and abnormal dark adaptation.

Study Population: Ten participants will be initially accrued, however, up to twenty
participants with AMD who meet the eligibility criteria may be enrolled. In the event that a
participant withdraws from the study prior to receiving two months of study supplementation
for a reason unrelated to an adverse reaction, an additional participant will be accrued. A
maximum of ten additional participants may be accrued in order to obtain ten participants for
the primary outcome analysis.

Design: This is a pilot, uncontrolled, prospective, single center study to investigate the
potential efficacy of vitamin A palmitate in improving dark adaptation in participants with
AMD and abnormal dark adaptation.

Outcome Measures: The primary outcome is the measurement of dark adaptation parameters
(thresholds and kinetics) by the following: dark adaptation times as measured by the AdaptDx
comparing before and after vitamin A palmitate supplementation and dark adaptation parameters
as measured by the Medmont comparing before and after vitamin A palmitate supplementation.
The secondary outcomes are changes in low luminance visual acuity (LLVA) and changes in
patient reported outcomes as measured by the low luminance questionnaire (LLQ).

- INCLUSION CRITERIA:

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

- Participant must be 50 years of age or older.

- Participant must understand and sign the protocol s informed consent document.

- Any participant of childbearing potential must be willing to undergo urine pregnancy
tests throughout the study.

- Any participant of childbearing potential and any participant able to father children
must have (or have a partner who has) had a hysterectomy or vasectomy, be completely
abstinent from intercourse, or must agree to practice two acceptable methods of
contraception throughout the course of the study and for one week after study
supplement discontinuation. Acceptable methods of contraception include:

- Hormonal contraception (i.e. birth control pills, injected hormones, dermal patch
or vaginal ring),

- Intrauterine device,

- Barrier methods (diaphragm, condom) with spermicide, or

- Surgical sterilization (tubal ligation).

- Participants must agree to notify the study investigator or coordinator if any of
their doctors initiate a new prescription medication during the course of this study.

- Participant must agree to not take greater than or equal to 8000 IU vitamin A
palmitate outside the study supplementation.

- For supplementation eligibility, participant must have normal liver function as
demonstrated by the Chemistry 20 panel, or have mild abnormalities not above grade 1
as defined by the Common Terminology Criteria for Adverse Events v4.0 (CTCAE).

EXCLUSION CRITERIA:

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

- Participant is in another investigational study and actively receiving study therapy.

- Participant is unable to comply with study procedures or follow-up visits.

- Participant is already taking vitamin A palmitate supplements greater than or equal
to.

- Participant has a history of vitamin A deficiency.

- Participant has a condition that, in the opinion of the investigator, would preclude
participation in the study (e.g., unstable medical status including blood pressure and
glycemic control).

- Participant has a history of hepatitis or liver failure.

- Participant has chronic gastrointestinal disease.

- Participant will be excluded if the participant has serologic evidence of an active
hepatitis infection.

STUDY EYE ELIGIBILITY CRITERIA:

The participant must have at least one eye meeting all inclusion criteria and none of the
exclusion criteria listed below.

STUDY EYE INCLUSION CRITERIA:

- The eye must have a best-corrected ETDRS visual acuity score better than or equal to
20/80 (i.e., equal to or better than 54 letters).

- Participant must have at least one large druse.

- Abnormal dark adaptation, which is defined as having an Adapt Dx test with a RIT of 16
minutes or more at the screening visit. This is at least one standard deviation
greater than the average normal RIT and includes room to account for variability in
testing. If at any point during current testing or under a previous NEI protocol, a
participant has exceeded the 40 minute test ceiling, they will have satisfied the
inclusion criteria.

STUDY EYE EXCLUSION CRITERIA:

- Presence of advanced macular degeneration with central geographic atrophy or choroidal
neovascularization.

- Presence of definite reticular pseudodrusen.

- An ocular condition is present (other than retinal vein occlusion) that, in the
opinion of the investigator, might alter visual acuity during the course of the study
(e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular
glaucoma, Irvine-Gass Syndrome, etc.).

- Substantial cataract that, in the opinion of the investigator, is likely to be
decreasing visual acuity by three lines or more (i.e., cataract would be reducing
acuity to 20/40 or worse if eye was otherwise normal).

- History of major ocular surgery (e.g. cataract extraction, scleral buckle, any
intraocular surgery, etc.) within three months prior to study entry.

- History of YAG (Yttrium-Aluminum Garnet) capsulotomy performed within two months prior
to study entry.