This study will evaluate whether docosahexaenoic acid (DHA) dietary supplementation can
improve macular function in patients with Stargardt macular dystrophy and Stargardt-like
macular dystrophy. Stargardt macular dystrophy is a recessive inherited trait that causes a
severe form of macular degeneration. (The macula is the center part of the retina in the
back of the eye that is responsible for fine vision.) The disorder begins in late childhood
and progresses to a significant decrease in central vision. One of the earliest signs of the
disorder is accumulation in and under the macula of a fatty pigment called lipofuscin.
Stargardt-like macular dystrophy is a dominant inherited trait involving loss of central
vision, but it begins later than Stargardt macular dystrophy, and the accumulation of
lipofuscin extends beyond the central region of the macula. DHA is a fatty acid that is
essential for normal brain and eye development. It is normally found in the diet, but not in
large amounts. Supplements may help prevent or slow the progression of some eye diseases.
Patients with autosomal dominant Stargardt-like macular dystrophy or autosomal recessive
Stargardt macular dystrophy are eligible for this study. Candidates will be screened with
the following tests and procedures:
- Medical history and physical examination.
- Blood test to measure levels of DHA and vitamins.
- Eye examination: The patient's vision and eye pressure are tested, then the pupils are
dilated to examine structures inside the eye. Photographs are also taken.
- Visual field test: The patient looks at a tiny spot of light projected onto a white
screen and is asked to note when other lights appear at other places on the screen.
- Electroretinogram (ERG): An electrode (small silver disk) is taped to the patient's
forehead. Drops are given to numb the eyes and special contact lenses are inserted in
the eyes. For the first part of the test, the patient looks at the center of a black
and white checkerboard screen that flickers for 30 seconds at a time. This is repeated
16 or more times. For the second part of the test, the patient looks inside a sphere,
in which flashes of light flicker for 20 seconds at a time. This is repeated four or
more times. The contact lenses sense small electrical signals generated by the retina
during the tests.
Participants will begin taking DHA capsules or a placebo (look-alike capsules with no active
ingredient) from 1 week to 3 months after enrolling in the study and will repeat several of
the screening tests at follow-up visits scheduled 3, 6, 9, 12, and 15 months after they
start taking the capsules. They will also be interviewed about any treatment side effects.
We propose to undertake a double-masked, randomized, placebo-controlled, crossover study on
the effect of docosahexaenoic acid (DHA) dietary supplementation in subjects with macular
dystrophy to determine whether DHA can improve macular function. Subjects will receive
either oral DHA supplementation (5x200 mg BID, 2,000 mg/day) or placebo. Subjects will
'crossover' to the opposite treatment twice during this study. Primary outcomes will measure
the change in macular function during periods with and without DHA supplementation.
Zhang and colleagues found a mutation in the gene, ELOVL4 (elongation of the very long chain
fatty acid-4), in individuals with Stargardt-like macular dystrophy. The gene is presumed to
function in the pathway of synthesis of very long chain polyunsaturated fatty acids,
including DHA. DHA is the major very long chain polyunsaturated fatty acid of the retina. As
our North American diet is poor in DHA, we hypothesize that a DHA dietary supplement might
improve macular function in individuals with the ELOVL4 mutation. Since the effect of DHA
supplementation may be non-specific, we propose to study a second cohort with Stargardt
macular dystrophy, which has a different genotype involving a different metabolic pathway in
the eye, but presents with a similar phenotype. Two cohorts of up to 10 subjects for
analysis will be recruited from patients with either Stargardt-like macular dystrophy or
Stargardt macular dystrophy.
- INCLUSION CRITERIA:
To be eligible to enroll in this study, a prospective participant must satisfy the
following inclusion criteria.
1. Understand and sign the informed consent.
2. Able to comply with all study procedures (likely to exclude participants less than 10
years of age, but not necessarily).
Autosomal Recessive Stargardt Macular Dystrophy Participants (must be observed in at
least one study eye):
3. Have a pattern of inheritance that indicates autosomal recessive inheritance.
4. Have a phenotype consistent with the diagnosis of autosomal recessive Stargardt
macular dystrophy including the following clinical features: fundus examination
showing bilateral central maculopathy and/or fundus flecks, or characteristic changes
on an intravenous fluorescein angiogram.
Autosomal Dominant Stargardt-like Macular Dystrophy Participants (must be observed in
at least one study eye):
5. Have a pattern of inheritance that indicates autosomal dominant inheritance.
6. Have a phenotype consistent with the diagnosis of Stargardt-like macular dystrophy
that may include: fundus examination showing bilateral central maculopathy and fundus
flecks confined to the central macula, or intravenous fluorescein angiogram.
To be eligible to enroll in this study, a prospective participant must not satisfy any of
the following exclusion criteria.
1. Have a non-recordable multi-focal ERG.