The Dilemma of Macular Degeneration

Christopher Ramos

Psychology of Perception

Stephen F. Austin State University

February 19, 1999

According to Baily and Hall, while visual impairment early in life is associated with inherited congenital disorders, abnormal fetal devepment, and problems associated with premature birth, most eye conditions are associated with aging. They claim that over 70% of the visually impaired population in the United States is over 65. Age related maculopathy, also called macular degeneration, or AMD, impairs the center of vision in older individuals. The macula is the region in the back of the retina that surrounds and includes the fovea (Goldstein 1999). It is important to understand that when this degeneration progresses enough, the condition constitutes blindness because the foveal area is what is used to focus on something. Most cases do not progress this far, but between five and 20% do. Allikments and Shroyer claim that 11 million people in the United States alone suffer some degree of this impairment, with 75% of those individuals being 75 or older. Seven percent of this older age group reportedly suffer advanced forms. Freidman reports the disease as most common in developed countries.

The high percentages of individuals who endure this impairment justifies and practically demands future research because the causes are not fully understood. The need for future research can be better emphasized if those with normal vision try to empathize with victims of macular degeneration. One can only imagine how frustrating it must be to receive sensatrions only in the periphery of the retina. Because the macula encompassed the cone rich fovea, which is used to focus on objects, the fovea degenerates as well. This occurence inables individuals to interpret the sensations they experience. Reading, recognizing faces, and driving are visual tasks most people take for granted that become very difficult when the central vision is disturbed (Baily & Hall 1989). Danger can exist for victims of the condition when simply walking down the street or even through their own homes. While there is yet no cure for macular degeneration the research is in progress. Two main areas of research include investigating the causes and exploring potential treatments.

According to Friedman, progress in the effort to stop or prevent AMD will be slow until the cause is learned. He claims retinal pigmant epithelium damage to be the prominant theory explaining the choroidal circulation changes that lead to AMD. Although Friedmal himself does not subscribe to this theory, other researchers do and use it as a basis for study. Grunwald, Harisprasad, Dupont, M. G. Mguire, Fine, Bruker, A.M. Maguire, and Ho compared choroidal blood flow in subjects with AMD to a control group. They used laser doppler flowmetry to asess the volume, velocity, and flow of blood in the center of the fovea. Ten subjects with no drusen (cellular debris) were compared to 20 subjects with ten or more large drusen. The average visual acuities of the two groups was very close. No significant differences between age, blood pressure, or intraocular pressure was revealed between the subjects. Spraul, G. E. Lang, Grossnik laus, and G. K. Lang questioned the validity of the study. They claim doppler flowmetry to be an imperfect method for such a study because of multiple light scattering properties of the tissue. They also claim that the volume could not be accurately sampled using this method. Friedman, who explains the conventional theory about retinal epithelium (RPE) damage and its relationship with choroidal blood flow, has actually proposed and alternative theory. He explains that retinal epithelium damage is conventionally considered a cause of altered choroidal blood flow. He proposed, however that hemodynamic factors involving choroidal circulation may cause RPE damage and not be the result of it. If researchers could resolve which of the occurences act as the cause of the other, they would likely make faster, more productive progress in the effort to stop or prevent AMD.

The opposing theories about the phisiological occurences leading to the disease reflect inconclusive research. However, one aspect regarding AMD on which researchers do agree is that two more general factors are at work controlling the probability of an individual acquiring this condition. These factors are , of course, genetics and environment.

Allikmets and Shroyer claim to have found a photoreceptor specific gene called ABCR, or STGD1. They claim there is an association with the gene and AMD including the accumulation of drusen and atrophy of the RPE. They tested the hypothesis that ABCR defects contribute to AMD by screening for alterations in the gene using independent, unrelated groups of patients with the condition. They found no obvious correlation between the type of alterations and visual impairment, indicating that if the gene is present, there is a stronger probability for the development of visual impairment. They claim that identifying ABCR will permit presymptomatic testing and possibly lead to earlier diagnosis and and new strategies for prevention and even therapy.

If the results are as conclusive as the study indicates, researchers have made a significant breakthrough regarding one cause of this disorder. Of course genetics are not alone in dictating who will end up with AMD. These genetic researchers also acknowledge that environment plays a prominant roll. One environmental factor on which some recent research has been focused is diet.

Bernstein, Balashov, Tsong, and Rando researched biochemical mechanisms responsible for the specific uptake, concentration, and stabilization of the carotenoids lutein and zeaxanthin in the macula. These researchers claim that macular carotenoids filter out damaging wavelengths of light or act as antioxidants to protect against light induced damage to the retina. They sight one study where monkeys were put on a caotenoid-free diet. The diet resulted in an abscense of macular-yellow pigmant and increased drusen. These changes are consistent with the early stages of AMD. The carotenoids leutin and zeaxanthin are concentrated in the foveal receptor axon layer with zeaxanthine more in the foveal center and lutien spread more diffusely throughout the retina. They suggest that this distribution implies a system to take up, concentrate and store the macular carotenoid pigmants, especially since the lutein and zeaxanthin are minor constituents to the complete carotenoid pool in the blood stream. Using bovine retinal tissue, the researchers demonstrated that tubulin, which is found in the receptor-axon layer of the fovea, is the major carotenoid binding protien. They also found that lutein and zeaxanthin were found to copurify with tubulin.

The results of the experiment indicate the importance of carotenoids in the diet for protection of the macular caroteniods against light induced damage. Also, by revealing the importance of tubuline, researchers can hopefully better understand how carotenoids play an important roll in photoprotective effects against the progression of AMD. The effects of diet are not relevant only when trying to determine caused of AMD, but may contribute to treatment as well.

According to Steve Langer of Better Nutrition, Jonathin Wright M. D. of Kent, Washington claims to have come upon a "formula" to treat macular degeneration. He claims to have had the condition and made substantial improvements following doses of selenium and vitamine E. He also claims that a number of his patients reported improvements with the regemine, and consequently the diagnosing opthomologists began to doubt their initial conclusions. Wright reportedly felt moved to study publications on the subject and added other nutrients to the formula. He added zinc and taurine to the formula and reported even better results. He claims that one woman began to read a poster across the room that she could not read before the the I.V. was started. Wright does concede however, that many of his patients experienced no improvement with a halt in deterioation while some endured continued deterioation.

Although Wrights claims are attractive, they have not yet been emperically tested. If empirical research confirms his claims regarding the effects of diet, the direction of study on the condition could be revolutionized. As it stands now, medicine is where most researchers focus their attention. The following study however, indicates how not all trials are sucessful when attempting to produce effective medicine.

The Journal of the American Medical Association reported that Interferon alpha 2a was tested on choroidal neovascularization, which is secondary to AMD. Forty-five opthamolic centers world wide employed 481 patients. The patients were split into four groups and givin either a placebo or one of three doses of the drug. The results indicated no significant differences in the treatments. The results also indicated that the higher dosed even seemed to be associated with poorer visual outcome. Of course not all medicine oriented research flops as domonstrated by a recent Canadian study.

An article which appeared in McCleans indicated that a Canadian developed drug, vertoporphine may provide an effective treatment and even a cure for AMD. The drug reportedly blocked blood vessel leakeage in the patients tested and even prevented futher loss of vision with administration of the optimum dose. A two step process called photodynamic therapy is how the drug is administered. First, the drug is injected into the bloodstream and then activated by a laser beam aimed directly at the retina. The drug seems promising, but it is only effective at the onset of the disease; it is not for people who have already lost their vision.

Even the article boasts the drug as a cure, it still specifies that it is not for individuals who have suffered more advanced effects of the disease. According to Goldstein, these five to 20% of more advanced cases involve small new blood vessels growing underneath the macular area of the retina. They form rapidly and begin to kill the cone receptors by leaking fluid into the macula. This occurence requires laser photocoaculation, which involves hitting the leaking blood vessels with a laser beam. The laser seals up the leaking vessels to stop the bleeding. The National Eye Institute has indicated that this method can only work in some patients and that only if the problem is caught in the earlier severe stages (Goldstein 1999).

The research on this topic is vast and plentiful, but many aspects of the disease are still under study. The causes, internal phisiologies, and possible treatments and cures are still being researched. The phisiological working of the disesase is a likely candidate for future research because current studies have raised many questions.

Ruckmann, Frederick, and Bird have looked at spacial distributions in various components in the eye to detect for deviations from normal in AMD patients. This study will prospectively offer clues and inspire futher research in the pathogenesis and process of aging in the human eye. The previously mentioned study conducted by Grunwald and company regarding choroidal blood flow revealed no significance but has suggested a need for futher research. The researchers claim that futher studies are needed to elucidate whether choroidal blood flow measurements may help in knowing if subjects who currently have AMD are at risk for developing other eye disorders such as neovascularization. Elsner, Burns, Beausencourt, and Weiter mapped out central foveal cones in healthy and AMD subjects for comparison. They found differences in the foveal cone photopigmant distributions and this finding raised another question. The researchers speculate that larger alterations in the older subjects could indicate a change in the foveal architecture with age. All in all the more recent phisiological studies of the eye, whether conclusive or not, have raised questions for future research.

While phisiological studies will continue, external causal factors should not be neglected. Because prevention seems to be the only certain way to effectively deal with AMD, researchers should aim to learn what, if anything can be done to aviod it. It seems that with the given prevelance of this disease, that avoidance would be a common concern for those who are knowledgable of it. In addition to prevention, Dr. Wright's profound calims of proper diet regimene should be studied for potential treatments. Concidering the reported "slow" progress in gaining complete understanding of this disease, and all of the the different angles of study which require research, reseachers seem to face the dilemma of macular degeneration.

References

Allikmets, Rando & Shroyer, Noah F., (1997). Mutation of the Stargardt disease in age related macular degeneration. Science 277

Baily, Ian L., & Hall, Amanda, (1989). Common Vision Problems. Editor not listed. Visual Impairment: An Overview. New York: American Foundation for the Blind.

Bernstein, Paul S., Balashov, Nikita A., Tsong, Edward D., & Rando, Robert R., (1997). Retinal tubulin binds macular carotenoids. Investigative Opthamology and Visual Science 38(1)167-171.

Elsner, Ann A., Burns, Stephen A., Beausencourt, Eva, & Weiter, John J., (1998). Foveal cone photopigment distribution: Small alterations associated macular pigmant distribution. Investigative Opthamology and Visual Science 39(12), 2394-2403.

Friedman, Ephraim, (1997). A hypodemic model of pathogenesis of age related macular degeneration. American Journal of Opthamology 124(5) 677.

Goldstein, Bruce E., (1999). Clinical Aspects of Vision and Hearing. Maurine Taulfinger (Ed.) Sensation & Perception 5th Edition. Pacific Grove : Brooks/Cole Publishing Company.

Grunwald, Juan E., Harisprad, Seenu M., Dupont, Joan, Maguire, M. G., Fine, Stuart L., Brucker, Alexander J., Maguire, A. M., & Ho, Allen C., (1998). Foveal choroidal blood flow in age related macular degeration. Investigative Opthamology and Visual Science 39(2), 385-389.

Guyer, David R., (1997). Interferon alpha 2a is ineffective for patients with choroidal neovascularization secondary to age related macular degeneration: results of a prospective randomized placebo-controlledclinical trial. The Journal of the American Medical Association, 278(18), 1470.

Hunter, M., (1997). Blocking blindness. McLeans, 110 (21), 62.

Langer, Stephen, (1996). Set your sights on better nutrition. Better Nutrition, 58 (4), 58.

Ruckmann, Adrea von, Fitzke, Fredrick W., & Bird, Alan C., (1997). Fundus autofluorescence in age related macular disease imaged with a laser scanning opthalmoscope. Investigative Opthamology and Visual Science, 38 (2), 478-485.

Spraul, Christoph W., Lang, Gabriel E., Grossniklaus, Hans E., & Lang, Gerhard D., (1998). Choroidal blood flow in AMD. Investigative Opthamology and Visual Science, 39 (11), 2201.