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 lifeis associated with inherited congenital disorders, abnormal fetaldevepment, and problems associated with premature birth, most eyeconditions are associated with aging. They claim that over 70% of thevisually impaired population in the United States is over 65. Agerelated maculopathy, also called macular degeneration, or AMD,impairs the center of vision in older individuals. The macula is theregion in the back of the retina that surrounds and includes thefovea (Goldstein 1999). It is important to understand that when thisdegeneration progresses enough, the condition constitutes blindnessbecause the foveal area is what is used to focus on something. Mostcases do not progress this far, but between five and 20% do.Allikments and Shroyer claim that 11 million people in the UnitedStates alone suffer some degree of this impairment, with 75% of thoseindividuals being 75 or older. Seven percent of this older age groupreportedly suffer advanced forms. Freidman reports the disease asmost common in developed countries.

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

According to Friedman, progress in the effort to stop or preventAMD will be slow until the cause is learned. He claims retinalpigmant epithelium damage to be the prominant theory explaining thechoroidal circulation changes that lead to AMD. Although Friedmalhimself does not subscribe to this theory, other researchers do anduse it as a basis for study. Grunwald, Harisprasad, Dupont, M. G.Mguire, Fine, Bruker, A.M. Maguire, and Ho compared choroidal bloodflow in subjects with AMD to a control group. They used laser dopplerflowmetry to asess the volume, velocity, and flow of blood in thecenter of the fovea. Ten subjects with no drusen (cellular debris)were compared to 20 subjects with ten or more large drusen. Theaverage visual acuities of the two groups was very close. Nosignificant differences between age, blood pressure, or intraocularpressure 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 astudy because of multiple light scattering properties of the tissue.They also claim that the volume could not be accurately sampled usingthis method. Friedman, who explains the conventional theory aboutretinal epithelium (RPE) damage and its relationship with choroidalblood flow, has actually proposed and alternative theory. He explainsthat retinal epithelium damage is conventionally considered a causeof altered choroidal blood flow. He proposed, however thathemodynamic factors involving choroidal circulation may cause RPEdamage and not be the result of it. If researchers could resolvewhich of the occurences act as the cause of the other, they wouldlikely make faster, more productive progress in the effort to stop orprevent AMD.

The opposing theories about the phisiological occurences leadingto the disease reflect inconclusive research. However, one aspectregarding AMD on which researchers do agree is that two more generalfactors are at work controlling the probability of an individualacquiring this condition. These factors are , of course, genetics andenvironment.

Allikmets and Shroyer claim to have found a photoreceptor specificgene called ABCR, or STGD1. They claim there is an association withthe gene and AMD including the accumulation of drusen and atrophy ofthe RPE. They tested the hypothesis that ABCR defects contribute toAMD by screening for alterations in the gene using independent,unrelated groups of patients with the condition. They found noobvious correlation between the type of alterations and visualimpairment, indicating that if the gene is present, there is astronger probability for the development of visual impairment. Theyclaim that identifying ABCR will permit presymptomatic testing andpossibly lead to earlier diagnosis and and new strategies forprevention and even therapy.

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

Bernstein, Balashov, Tsong, and Rando researched biochemicalmechanisms responsible for the specific uptake, concentration, andstabilization of the carotenoids lutein and zeaxanthin in the macula.These researchers claim that macular carotenoids filter out damagingwavelengths of light or act as antioxidants to protect against lightinduced damage to the retina. They sight one study where monkeys wereput on a caotenoid-free diet. The diet resulted in an abscense ofmacular-yellow pigmant and increased drusen. These changes areconsistent with the early stages of AMD. The carotenoids leutin andzeaxanthin are concentrated in the foveal receptor axon layer withzeaxanthine more in the foveal center and lutien spread morediffusely throughout the retina. They suggest that this distributionimplies a system to take up, concentrate and store the macularcarotenoid pigmants, especially since the lutein and zeaxanthin areminor constituents to the complete carotenoid pool in the bloodstream. Using bovine retinal tissue, the researchers demonstratedthat tubulin, which is found in the receptor-axon layer of the fovea,is the major carotenoid binding protien. They also found that luteinand zeaxanthin were found to copurify with tubulin.

The results of the experiment indicate the importance ofcarotenoids in the diet for protection of the macular caroteniodsagainst light induced damage. Also, by revealing the importance oftubuline, researchers can hopefully better understand how carotenoidsplay an important roll in photoprotective effects against theprogression of AMD. The effects of diet are not relevant only whentrying to determine caused of AMD, but may contribute to treatment aswell.

According to Steve Langer of Better Nutrition, Jonathin Wright M.D. of Kent, Washington claims to have come upon a "formula" to treatmacular degeneration. He claims to have had the condition and madesubstantial improvements following doses of selenium and vitamine E.He also claims that a number of his patients reported improvementswith the regemine, and consequently the diagnosing opthomologistsbegan to doubt their initial conclusions. Wright reportedly feltmoved to study publications on the subject and added other nutrientsto the formula. He added zinc and taurine to the formula and reportedeven better results. He claims that one woman began to read a posteracross the room that she could not read before the the I.V. wasstarted. Wright does concede however, that many of his patientsexperienced no improvement with a halt in deterioation while someendured continued deterioation.

Although Wrights claims are attractive, they have not yet beenemperically tested. If empirical research confirms his claimsregarding the effects of diet, the direction of study on thecondition could be revolutionized. As it stands now, medicine iswhere most researchers focus their attention. The following studyhowever, indicates how not all trials are sucessful when attemptingto produce effective medicine.

The Journal of the American Medical Association reported thatInterferon alpha 2a was tested on choroidal neovascularization, whichis secondary to AMD. Forty-five opthamolic centers world wideemployed 481 patients. The patients were split into four groups andgivin either a placebo or one of three doses of the drug. The resultsindicated no significant differences in the treatments. The resultsalso indicated that the higher dosed even seemed to be associatedwith poorer visual outcome. Of course not all medicine orientedresearch flops as domonstrated by a recent Canadian study.

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

Even the article boasts the drug as a cure, it still specifiesthat it is not for individuals who have suffered more advancedeffects of the disease. According to Goldstein, these five to 20% ofmore advanced cases involve small new blood vessels growingunderneath the macular area of the retina. They form rapidly andbegin to kill the cone receptors by leaking fluid into the macula.This occurence requires laser photocoaculation, which involveshitting the leaking blood vessels with a laser beam. The laser sealsup the leaking vessels to stop the bleeding. The National EyeInstitute has indicated that this method can only work in somepatients and that only if the problem is caught in the earlier severestages (Goldstein 1999).

The research on this topic is vast and plentiful, but many aspectsof the disease are still under study. The causes, internalphisiologies, and possible treatments and cures are still beingresearched. The phisiological working of the disesase is a likelycandidate for future research because current studies have raisedmany questions.

Ruckmann, Frederick, and Bird have looked at spacial distributionsin various components in the eye to detect for deviations from normalin AMD patients. This study will prospectively offer clues andinspire futher research in the pathogenesis and process of aging inthe human eye. The previously mentioned study conducted by Grunwaldand company regarding choroidal blood flow revealed no significancebut has suggested a need for futher research. The researchers claimthat futher studies are needed to elucidate whether choroidal bloodflow measurements may help in knowing if subjects who currently haveAMD are at risk for developing other eye disorders such asneovascularization. Elsner, Burns, Beausencourt, and Weiter mappedout central foveal cones in healthy and AMD subjects for comparison.They found differences in the foveal cone photopigmant distributionsand this finding raised another question. The researchers speculatethat larger alterations in the older subjects could indicate a changein the foveal architecture with age. All in all the more recentphisiological studies of the eye, whether conclusive or not, haveraised questions for future research.

While phisiological studies will continue, external causal factorsshould not be neglected. Because prevention seems to be the onlycertain way to effectively deal with AMD, researchers should aim tolearn what, if anything can be done to aviod it. It seems that withthe given prevelance of this disease, that avoidance would be acommon concern for those who are knowledgable of it. In addition toprevention, Dr. Wright's profound calims of proper diet regimeneshould 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

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Baily, Ian L., & Hall, Amanda, (1989). Common Vision Problems.Editor not listed. Visual Impairment: An Overview. New York: AmericanFoundation 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: Smallalterations associated macular pigmant distribution. InvestigativeOpthamology and Visual Science 39(12), 2394-2403.

Friedman, Ephraim, (1997). A hypodemic model of pathogenesis ofage related macular degeneration. American Journal of Opthamology124(5) 677.

Goldstein, Bruce E., (1999). Clinical Aspects of Vision andHearing. Maurine Taulfinger (Ed.) Sensation & Perception 5thEdition. 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 maculardegeration. Investigative Opthamology and Visual Science 39(2),385-389.

Guyer, David R., (1997). Interferon alpha 2a is ineffective forpatients with choroidal neovascularization secondary to age relatedmacular degeneration: results of a prospective randomizedplacebo-controlledclinical trial. The Journal of the American MedicalAssociation, 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 imagedwith a laser scanning opthalmoscope. Investigative Opthamology andVisual 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.