Download American Academy of Optometry: Case Report 1

American Academy of Optometry: Case Report 2
Age-Related Macular Degeneration and Nutritional Supplements
Madeline Cohen, O.D.
Abstract
Age-related macular degeneration is one of the leading causes of visual impairment and
blindness in adults over age 651,4. Approximately 1.7 million Americans have some form
of AMD, and approximately 100,000 are blind from this disease1, so reducing the risk of
progression is vital to managing vision loss. The Federal government sponsored the AgeRelated Eye Disease Study (AREDS) which evaluated the risks, course, and prognosis of
AMD. In addition, it studied the effects of certain nutraceuticals on the progression of
AMD in terms of vision loss. The study found that high levels of antioxidants and zinc
can lower the risk of developing advanced AMD by almost 25%1. Another study by the
Department of Veterans’ Affairs was called the Lutein Antioxidant Supplementation
Trial (LAST). It evaluated whether supplementation with lutein alone, or in combination
with other nutrients, can improve vision in AMD. It was found that visual function and
symptoms improved when lutein was used2. The case presented illustrates the effect that
nutraceuticals can have on atrophic AMD.
Key words: Age-related macular degeneration (AMD), Age-Related Eye Disease Study
(AREDS), nutraceuticals, antioxidants, beta-carotene, Lutein Antioxidant
Supplementation Trial (LAST), macular pigment density (MPD), docosahexaenoic acid
(DHA), complement factor H (CFH)
Introduction
Age-related macular degeneration (AMD) is a disease that destroys the central portion of
the retina. It produces a gradual blurring of the central field of view, causing difficulty in
reading and driving. Risk factors include older age, white race, and a family history of
AMD, in addition to blue light and UV exposure, high lipid diet, and vitamin and mineral
uptake4. Certain eye characteristics, like hyperopia and light-colored irides, seem to be
prevalent. As well, hypertension, cardiovascular disease, and smoking increase the risk.
Recently, a gene has been identified that is associated with a person’s risk for developing
AMD20. There are two forms of AMD, wet and dry. The dry form, which accounts for
the majority of cases, produces atrophy, retinal pigment changes, and the development of
drusen, yellowish deposits, in the macula. Until recently, there were no effective
therapies to manage this form of the disease. The wet or neovascular form is caused by
abnormal blood vessels growing under the macular area, which can leak and produce
devastating vision loss. Current treatments are effective only in halting the progression
of wet AMD.
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Case Report
History
Patient # 2, a longstanding patient, was a 76 year-old female who presented to the office
on December 8, 2004. Her chief complaint was slightly blurry vision in both eyes and
scratched spectacle lenses. The patient’s last eye exam was on December 6, 2002. Her
past ocular history included cataract extraction OU with implants and subsequent yag
posterior capsulotomies in both eyes. She wore bifocal spectacles to correct both
distance and near vision. Her medical history was positive for smoking and chronic
obstructive pulmonary disease (COPD) for which she took no medications. Her family
history was negative and she had no known allergies. She was oriented to time, place,
and person.
Examination
Her uncorrected visual acuity was 20/80 OD and 20/40 OS for distance. Her current
bifocal Rx was plano -1.00 x 065 / +2.50 OD and -0.50 sphere / +2.50 OS. Through
these glasses her vision was 20/60 and 20/30 for distance and 20/30 OU for reading. Best
corrected distance visual acuities were 20/30-3 and 20/30 respectively, with a manifest
refraction of plano -2.25 x 075 and -0.75 sphere with a +2.75 add for reading. Her
reading vision improved to 20/20-2 with this prescription.
Amsler grid testing revealed no metamorphopsias or scotomas in both the right and left
eyes. The patient passed all plates OD and OS with Ishihara color vision testing. Pupils
were 3 mm, equally round and reactive to light with no afferent pupillary defect noted
OU. Confrontation visual fields were full to finger counting OD and OS. Extraocular
motilities were unrestricted in all gazes, and cover test demonstrated orthophoria at
distance, and 4∆ exophoria at near.
Anterior segment evaluation by slit lamp examination revealed mild diffuse palpebral
conjunctival papillae OU. Tear film was even with a tear break-up time of 11 seconds
OD and OS. The lashes were clear, but a mild, grade 1 ptosis was noted for both lids.
The corneas were clear OU and the irides were blue. The anterior chamber was deep and
quiet, without cells or flare in both eyes. Angles measured by Von Herrick estimation
were grade 3+-4 OU. Intraocular pressures were 17 mm Hg OD and OS at 1:15 p.m. with
Goldmann applanation tonometry.
The patient was dilated with Tetracaine, 1% Tropicamide and 10% Phenylephrine OU.
Once the patient was fully dilated, an evaluation of the posterior segment was performed
by slit lamp with a 90D lens, and by binocular indirect ophthalmoscopy. This revealed
pseudophakia with clear and centered IOLs and yag capsulotomies OU. The vitreous was
examined and a posterior vitreous detachment was noted inferiorly in the right eye. The
left eye was significant for vitreal syneresis. Fundus assessment revealed optic nerves
with a cup-to-disc ratio of .2/.2 OU. The neuroretinal rims were distinct with mild
peripapillary atrophy OS>OD. Retinal vessels appeared normal with an arterial-venous
ratio of 2/3 OU. In the posterior pole, nasal to the macula in the right eye, some
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geographic choroidal atrophy was noted. There were a couple of small drusen located
near each macula and no foveal reflex was noted OU. The fundus was observed to be
tessellated in both eyes. The peripheral retina was flat and intact with no pathology noted
OU.
Assessment
1) Pseudophakia OU
2) S/P Yag Capsulotomies OU
3) Ptosis OU
4) Mild Allergic Conjunctivitis
5) Dry AMD OD>OS
The differential diagnoses considered in this case include:

Peripheral drusen-drusen are located outside of the macular area, not
within it.

Myopic degeneration-typically high myopia with characteristic
peripapillary changes in addition to the macular degeneration; drusen are
not seen.

Central serous chorioretinopathy-parafoveal serous retinal elevation,
RPE detachments, and mottled RPE atrophy, without drusen, usually in
patients younger than 50 years of age.

Inherited central retinal dystrophies-variable macular pigmentary
changes, atrophy, or accumulation of lipofuscin or a combination of
these; usually younger than 50 years, without drusen, familial
occurrence.

Toxic retinopathies-mottled hypopigmentation with ring of
hyperpigmentation, without drusen; history of drug ingestion.

Inflammatory maculopathies-variable chorioretinal atrophy, often with
vitreous cells and without drusen.

Nonexudative age-related macular degeneration-may present with
macular drusen, pigment clumping, RPE and geographic atrophy, and
dystrophic calcification.
There was no evidence of retinal elevation, RPE detachments, or vitreous cells. Also, the
patient had no history of high myopia prior to her cataract extraction, and no history of
drug ingestion. Due to her age and the appearance of her fundus, this patient was
diagnosed with very early dry age-related macular degeneration (AMD).
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Management
The patient was counseled on the nature of AMD and instructed to return in 2 weeks for
retinal photos and a fluorescein angiography to rule out any occult subretinal neovascular
membrane. In addition, she was started on a nutritional supplement called Visivite Green
i-Defense®, specifically formulated for past or present smokers. It does not contain betacarotene as this is thought to be a risk factor in the development of lung cancer. This
supplement is based on the AREDS recommendations, plus it adds lutein and zeaxanthin,
in addition to some other ingredients believed to have beneficial effects on the retina.
The usual dosage is one capsule twice a day.
The vitamin formulation is as follows19:
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Follow up # 2
The patient returned 2 weeks later on December 22, 2004 for additional testing to
confirm the diagnosis of dry AMD. Her visual acuities remained stable and she had
started on the nutraceutical prescribed. She was taking the recommended dosage of one
capsule twice a day.
The following fundus photograph was obtained at this visit:
It revealed choroidal atrophy OD both temporal and inferior to the disc. The left eye
showed no atrophy, but did indicate more peripapillary atrophy temporally and inferiorly.
A few macular drusen were noted OD>OS.
Fluorescein angiography was also performed at this visit:
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The above FA was read top to bottom and right to left. No occult membrane or leakages
were noted OU which confirms the diagnosis of atrophic or dry AMD. The patient was
scheduled for another follow up visit in 7 months and was instructed to continue the
nutritional supplement. Also, a home Amsler grid was given and the patient was to
monitor at home for any changes.
Follow up # 3
The patient returned on July 20, 2005 for her 7 month visit. She denied any changes in
her medical status and the home Amsler grid testing. The patient stated that her vision
seemed better since she started taking the vitamins, and she felt that her overall health
had improved, as well. Her manifest refraction remained fairly stable at plano -2.00 x
070 OD and -0.75 sphere OS. However, at this visit, her best corrected distance acuities
were now slightly improved at 20/25 and 20/30+2.
Amsler grid testing still revealed no defects OD and OS. Pupils were 3 mm, equally
round and reactive to light, with no afferent pupil defect noted OU. Applanation
tonometry measured pressures of 15 mm Hg OD and 16 mm Hg OS at 10:30 a.m. Slit
lamp findings remained unchanged in both eyes.
Dilated fundus assessment was performed after instilling Tetracaine, 1% Tropicamide,
and 10% Phenylephrine. In the right eye, it revealed less choroidal atrophy inferior to the
optic nerve, but still atrophic areas were observed temporally. Foveal drusen were
unchanged in both eyes.
The following fundus photograph was taken at this visit:
The right eye photo clearly shows an improvement in the atrophy inferior to the disc
compared to the prior photo taken at the last visit. Along with this, a visual increase was
noted for the same eye. The patient was instructed to continue on the nutritional
supplements and return in 7 months time.
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Follow up # 4
On February 8, 2006, patient # 2 came to the office for another 7 month visit, still
reporting good vision and a general feeling of well-being. She was compliant with taking
the nutraceutical prescribed and doing the home Amsler testing. Her only complaint at
this visit was itching in both eyes. Medical status was unchanged. Her best corrected
visual acuities were now 20/25 with plano -2.00 x 068 OD and 20/25-1 with -0.50 -0.25 x
103 OS. This demonstrated a one-line improvement in her vision since she started on the
nutritional supplement.
Amsler grid testing remained normal OU. Pupils were equally round and reactive to light
with no afferent pupil defect OU. Intraocular pressures by applanation tonometry were
15 mm Hg in both eyes at 9:10 a.m. Slit lamp findings were positive for the presence of
grade 2+-3 palpebral conjunctival papillae OU. Otherwise, the exam findings were
unchanged since her last visit.
Thirty minutes after instilling Tetracaine, 1% Tropicamide, and 10% Phenylephrine,
dilated fundus assessment revealed only trace choroidal atrophy in the right eye temporal
to the disc, and no atrophy inferiorly. The small drusen appeared unchanged. Findings
for the left eye remained stable.
The following retinal photograph was taken:
The photo clearly shows a decrease in the atrophy that was present at earlier visits and the
improvement in her visual acuity corresponds with this finding. The patient was
instructed to continue on the nutritional supplement to maintain her good results. In
addition, she was prescribed Patanol bid OU since she was also symptomatic for allergic
conjunctivitis. She was to take it for one month, and, after that, she would continue it as
needed. She was, also, to continue with her weekly Amsler grid testing at home and was
to return in 7 months for another visit.
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Discussion
Macular degeneration occurs when the macula is damaged and breaks down. The macula
is responsible for central and color vision and is essential for visual acuity. This disease
causes a gradual decline in sharp, central vision, which is needed for reading, driving, and
a variety of other activities. It is the leading cause of blindness in people over 50 years of
age1,2,4,6.
Drusen are risk factors for AMD and negatively affect the retinal pigment epithelium
(RPE) and retina. They are non-degradable pigments that accumulate as lipofuscin
deposits. Photoreceptors overlying and next to drusen exhibit morphologic and
biochemical deterioration8. This process is thought to begin with the photo-oxidation of
A2-PE5. A2-PE is a pigment that forms in the outer segment of the photoreceptors as a
by-product of the visual cycle. It is believed that the blue region of the spectrum may
contribute to the accumulation of this product and its damaging intermediates14. It is
deposited in the RPE cells after the breakdown of the photoreceptors’ outer segment
membrane. Clearance by the RPE of shed photoreceptor outer segments, a tissue with
one of the highest turnover rates in the body, is critical to the maintenance and normal
function of the retina10. These pigments then undergo hydrolysis to form lipofuscin, or
drusen, which are insoluble deposits that lie under the RPE, leading to changes in Bruch’s
membrane. These changes eventually impact on the delivery of oxygen and nutrients to
the RPE and outer neural retina. This is due to decreased blood flow in the
choriocapillaris, impairment of lysosomal or enzymatic functions, and decreased
diffusion7. This process eventually produces RPE cell death which manifests as
geographic atrophy.
The nutritional factors involved in the pathogenesis of AMD include antioxidants or
antioxidant cofactors, such as vitamins A and C, and zinc. Also involved are anti-freeradicals like beta-carotene and the carotenoids, including lutein and zeaxanthin. Lastly,
components of the photoreceptors outer membranes, like docosahexaenoic acid (DHA),
an omega 3 poly-unsaturated fatty acid, play a role.
Understanding the mechanism of action of lutein and zeaxanthin can help to explain their
role in eye health. They are classified as xanthophyll carotenoids which are found in
fruits, vegetables, and egg yolks. Lutein and zeaxanthin are the predominant carotenoids
found in the lens and macula. They are known as the macular pigments, which are
important for absorbing visible light, providing antioxidant protection, and reducing light
scatter.
Increased exposure to blue light or sunlight increases the risk of AMD3. Blue
wavelengths of light are similar to the invisible ultraviolet A and B wavelengths and, like
UV, can produce cell damage in the eyes. Intense blue light exposure promotes the
reduction of oxygen into oxygen-free radicals, which attack DNA and cause cell defects.
The macular pigments are lipid-soluble antioxidants that absorb the dangerous short
wavelength part of the spectrum and, also, destroy harmful free radicals that are produced
by exposure to light. Therefore, these xanthophylls can provide protection against the
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oxidation of the A2-PE free radicals and the phototoxic damage that contributes to
AMD5.
A low amount of macular pigment will allow more blue light damage to the eye and
increase the risk of AMD. One study found that AMD patients had lower levels of
macular pigments than patients without AMD3. Macular pigment density (MPD) can be
increased by consuming foods and supplements that are high in lutein and zeaxanthin.
This, in turn, may slow the disease’s progression or, possibly, help to prevent it.
Omega-3 fatty acids exhibit protective and therapeutic actions within the retina15. DHA
is an omega-3 fatty acid that is a major structural lipid of retinal photoreceptor outer
segment membranes. It may affect photoreceptor functions such as permeability,
signaling mechanisms, and rhodopsin regeneration15. Therefore, this fatty acid is
required for RPE functional integrity. It may regulate metabolic processes and lessen the
effects of ischemia, chronic light exposure, oxidative stress, inflammation, cellular
signaling mechanisms, and aging15.
The AREDS results showed that, over a 6 year period, high risk AMD patients, who took
vitamins C, E, and beta carotene, and minerals, zinc and copper, reduced their risk of
progression by 25%. They also found that this combination of antioxidants plus zinc
decreased the risk of central vision loss by 19%. The participants who took zinc alone
reduced their risk of developing advanced AMD by 21% and their risk of central vision
loss by about 11%. The antioxidant only group ended up with 17% and 10% reductions,
respectively.[1]
The LAST study evaluated the effect of lutein alone, or in combination with additional
carotenoids, antioxidants, vitamins, and minerals, on macular pigment density (MPD) and
central vision outcome2. Lutein is the primary carotenoid xanthophyll pigment
responsible for macular pigment density. AREDS did not examine lutein and its potential
effects on AMD. The LAST study measured MPD, visual acuity, and contrast sensitivity
over a 12 month period. It concluded that visual function was improved with lutein alone
or lutein together with other nutrients2.
Inflammation may also play a role in AMD. Histochemical evidence suggests an
inflammatory component in drusen formation4. In addition, a commonly inherited
variant of a gene, called complement factor H (CFH) has been determined to be strongly
associated with an increased risk for developing macular degeneration20. A change in
one of the amino acids in complement factor H on chromosome 1 results in the formation
of the CFH gene variant. This sequence change is in a region of CFH that binds heparin
and C-reactive protein, which is an inflammatory marker. The protein encoded by this
CFH gene variant increases AMD risk by failing to bind to receptors on retinal and
choroidal cells, which prevents the inhibition of the inflammatory pathway20. Therefore,
this would cause excessive inflammation in the retina and the surrounding blood vessels.
Intravitreal fine needle injections and slow release implants of steroid derivatives are
currently being investigated as a remedy22. Possibly, in the future, gene therapies may be
used in the treatment of this disease.
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The wet or exudative form of AMD is a major cause of rapid and severe visual loss. It is
characterized by pathological choroidal neovascularization and vascular permeability.
Laser photocoagulation, photodynamic therapy with intravenous verteporfin (Visudyne),
and intravitreal administration of pegaptanib sodium (Macugen) or bevacizumab
(Avastin) all can reduce the risk of vision loss in certain cases of exudative AMD.
Visudyne is taken up by the abnormal blood vessels under the macula and the drug is
activated by a non-thermal laser which destroys those vessels. Both Macugen and
Avastin block the action of vascular endothelial growth factor (VEGF) which makes
blood vessels leaky and proliferate. In selected cases of hemorrhagic choroidal
neovascularization, submacular surgery can decrease the risk of severe vision loss.
Dry age-related macular degeneration is thought to be the result of a lifetime of oxidative
damage that results in photoreceptor death within the macula17. Increased risk of AMD
may result from low levels of certain nutrients in the diet and excessive exposure to blue
light. The impact of nutrition on manifestation and progression of retinal diseases has
become an important and controversial subject recently. Theoretically, supplementation
of antioxidants could have a beneficial impact on a variety of retinal diseases, or as a
preventive measure by limiting the degree of oxidative damage.
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