Pilot study data indicate macular degeneration responds to nutrition

Issue: December 1999

Dr. Richer: We have a plethora of emerging therapeutic options available to us as we enter the next millennium. In addition to submacular surgery and photodynamic therapy, other therapies that will become available in just the next few years include:

retinal pigment epithelium transplantation,
gene therapy,
improvements in imaging,
radiation therapy,
lasering drusen,
growth factor inhibitors,
RheoTherapy,
the exciting work that’s being done in cancer with angiogenic inhibitors and
Transepithelial Neuronal Stimulation of the Macula (TENSMAC).

At the North Chicago VA Medical Center, I am involved in a small clinical trial involving lutein and antioxidant supplementation. This dovetails with what we call integrative optometry, which involves looking at cardiovascular health, exercise, smoking, alcohol, polypharmacy, drug abuse, all the issues that affect ocular health because they affect systemic health.

What do you tell patients about nutrition and retinal disease?

Dr. Pesin: Everyone in the room, and everyone who sees these patients, has the same question. What do we do?

Patients want something and you want to provide something because that’s your job. We’re all looking for that, and that’s why studies on vitamins are critical: because we don’t know the answer; no body does. These are observational studies we’re referring to. There are very few clinically controlled studies.

The National Eye Institute study called AREDS [Age-Related Disease Study] is being conducted, and we’re excited about learning from the NIH [National Institutes of Health] what its recommendations are, but there is no right answer at this time.

I usually will recommend a multi vitamin for the patient’s overall health, not just for the eye, because some people just don’t eat balanced diets. I don’t go into the details behind which vitamins to take and why to take them, because nobody knows the details. Many retinal specialists who see more macular degeneration patients than I do don’t recommend anything.

Sometimes it’s more difficult not to recommend something than to recommend. So I tell them that their cardiologist or oncologist or any of their other physicians would probably tell them that if they’re not eating everything they’re supposed to they should take a multivitamin. Something inexpensive, something simple, over the counter. That’s usually the way I go.

Dr. Miller: I generally agree; I tell most of my patients the same thing. If they’re not already taking a vitamin and they ask, I would say a general multivitamin is probably the way to go. I sometimes add that, if they want to be a little more aggressive, some studies have shown that dark green, leafy vegetables, such as spinach and kale, may be a benefit if they can stomach that in their diet. But most patients frown and decide to go with a multivitamin.

I don’t recommend any particular ocular vitamin. Frequently, patients who are already taking an ocular vitamin are referred to me and they ask if they should continue taking them. I tell them it’s probably not hurting the eye, but we don’t know if it’s really helping.

If the vitamins are expensive and they’re on a tight budget, I recommend taking their other medications, such as insulin, over these unproven eye vitamins. Some vitamins can be quite expensive, and elderly patients may be on fixed incomes.

Ninety patients with a diagnosis of dry macular degeneration are involved in our VA-approved clinical trial. This prospective, 1-year trial is double-masked, randomized and placebo-controlled. There are no age or severity of disease limitations. All patients with a treatable lesion are accepted. There are three treatment groups. Patients in the placebo group receive a maltodextran capsule. The second group receives 10 mg of Floraglo (lutein, Kemin Foods) and the third group receives 10 mg of Floraglo and antioxidants.

A nutrition-responsive disorder

---Stuart P. Richer, OD, PhD

Data from our 1996 VA Multicenter Nutritional Ophthalmic ARMD study (Journal of the American Optometric Association, 67(2), pages 12-49) indicated that macular degeneration appeared to be, in part, a nutrition-responsive disorder. Patients placed in a double-masked fashion and placebo-controlled fashion on a broad-spectrum antioxidant mineral formulation did not get worse compared to the natural downward progression of the disorder.

As further background, in 1999 we placed people on sautéed spinach four times a week. Because of the emerging data on the importance of nutrients in spinach or other dark, green, leafy vegetables (lutein, folic acid, vitamin C, magnesium), we measured patients’ visual function over time (JAOA, 70(1), pages 13-36).

Measuring macular pigmentation

In our new clinical trial we are measuring macular pigmentation and indeed finding less pigmentation in our population. Macular pigment density is 20% lower in females. It is lower in individuals with light-colored irises as well as in smokers. Previous data has indicated that macular density and some functional measures of vision are positively correlated. We presented our pilot data at ARVO [Association for Research in Vision and Ophthalmology] showing that spinach intake tended to improve multiple parameters of visual function. And spinach, of course, contains quite a bit of lutein.

Our grant sponsors are Kemin Foods, manufacturers of Floraglo, and Nature’s Wealth, a Springfield, Ill.-based company that manufactures an antioxidant capsule called Ocupower, which contains Floraglo.

The entrance criteria is the CPT [Current Procedural Terminology] diagnosis 362.51, dry macular degeneration; at least one measured functional deficit; and some type of subjective complaint specific to age-related macular degeneration (AMD), such as poor night vision or problems reading. A surprising number of patients with 20/25, 20/30 and even 20/20 vision have reading disturbances.

Enrollment status

We have thus far enrolled 50 patients. Baseline and phase 2 will begin sometime in January. Phase 3 will be an 8-month visit and phase 4 will be a 1-year completion. The reason this study is short is because our pilot data demonstrate that we can see positive changes with spinach intake in as little as 6 to 8 weeks. The basic science data indicates that lutein will accumulate in the retina within a few weeks. And then it takes 6 to 7 weeks up to approximately 1 year before one sees changes in function.

An interdisciplinary research team is involved. Co-investigator Dr. William Stiles is an ophthalmologist and attorney. We have a full-time research associate physician, and family medicine and geriatrics input. We also have a biochemist and professor of medicine from Chicago Medical School, and an RN research coordinator who handles patient compliance.

Our assessment includes demographics and psychophysical, ocular, nutritional and laboratory data. We record age, weight, height, smoking history, iris color, physical activity and primary-secondary medical diagnoses.

Early changes shown

Our published pilot data demonstrated that seven of eight patients placed on spinach showed early changes on the Amsler grid, either complete or partial resolution over a short period of time. One patient on spinach for 3 months had resolved Amsler grid findings, improvements in contrast sensitivity over time and improvements in low luminance/low contrast vision.

In the clinical trial we are expanding our pilot study by using the international retinal classification, and measuring cataract opacification with LOCS III and macular pigmentation with a heterochromic flicker photometer. The latter is a very nice, robust instrument for quickly determining the macular pigmentation density in the human eye.

We’re employing the Harvard School of Public Health food frequency evaluation. This is not available to the private practitioner, but it is an inexpensive way of obtaining dietary information through a questionnaire that’s provided to the patient.

On the clinical medicine side, we’re looking at laboratory data — a comprehensive view of cardiovascular disease — because the literature suggests AMD is associated with cardiovascular disease. We’re looking at iron, total iron binding capacity, ferritin, C-reactive protein, (an indication of acute inflammation in the eye), oxidative stress, fibrinogen and apo B/apo A-1 ratio — a more sensitive test than the traditional cholesterol HDL ratio.

Out of 38 patients, four had low serum iron and one had high serum iron; five had high total iron binding capacity. Average transferrin saturation was 25%; there was only one patient in our study who had 60% transferrin saturation. My colleagues in family medicine at Chicago Medical School tell me that particular patient, when you looked at the ferritin level indicating body stores of iron, was not therapeutically significant. Three had low levels of ferritin and four had high levels. So far, iron status seems to be marginally important.

Association with heart disease

In summary, we’re looking at heart disease because of its association with macular degeneration. We consider “heart disease” to be a label we ascribe to the final product of multiple metabolic and genetic variations that give rise to arterial sclerosis. We’re teasing out the complex factors of lipid status, insulin resistance, homocysteine metabolism and other factors such as inflammation and genetics. All of these can interact. So if macular degeneration is associated with cardiovascular disease, then it’s likely to be very complex, and we’re likely to see multiple therapeutic modalities to approach it.

We consider heart disease through a comprehensive cardiovascular analysis where we measure C-reactive protein, homocysteine, fibrinogen and the conventional total cholesterol LDL/HDL and triglycerides known as the so-called cholesterol model. Our preliminary data, involving 17 patients, shows a smattering of effects: two with high triglycerides; one with high cholesterol; three with high LDL; and four with high apo B, which is a little bit more sensitive.

But we had one patient who was genetically predisposed to cardiovascular disease with a very high lipoprotein A. One patient had elevated homocysteine. One patient had a high C-reactive protein. Eight out of 17 patients had high fibrinogen, a blood clotting factor that would implicate blood flow. It has been implicated that blood flow is decreased in both dry and wet macular degeneration.

There seems to be a smattering of factors, and it may very well be the interaction of all of these. It looks as if two-thirds of the patients who have macular degeneration had at least one cardiovascular abnormality in their serum profile. Interestingly, the protective factors, apo A-1 and HDL cholesterol seem to be normal.

For Your Information:

Stuart P. Richer, OD, PhD, FAAO, is chief of the Optometry Section at the VA Medical Center and clinical associate professor of family medicine at the Finch University of Health Sciences/The Chicago Medical School. He can be reached at Optometry Section 112e, DVA Medical Center, North Chicago, IL 60064-3095; (847) 688-1900, ext. 5406; fax: (847) 578-6924; e-mail: stuart.richer@med.va.gov. Dr. Richer has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.