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MACULAR DEGENERATION

Abstract:  Macular Degeneration is an incurable disease of the eye that is the major cause of blindness for our older population.  Its risk usually becomes most serious for those older than about age 70 and increases rapidly after this age.  But its has multiple risk factors that depend on life style habits and a number of these risks as cholesterol, smoking, overweight, blood pressure and exercise parallel those for heart disease. Its risk can be diminished by that taking of adequate antioxidants and by caratenoids lutein +zeaxanthin.  Because most people do not obtain sufficient lutein + z in their diet a supplement of 6 mg per day of this should be taken by men and women as they move past age 50-60 to reduce risk of  this most unwanted disease.  Dietary DHA + EPA from fish oils appear to reduce risk.  But risk is higher for those having cataract surgery, those with diabetes and those having blue or light colored eyes.  Combinations of controllable life style habits can change risk of this disease by up to 50 fold and health-interested persons should initiate corrective action that reduce risk of this disease before age 60.

Background:  Age Related Macular degeneration (AMD)  is an incurable eye disease that it is the leading cause of blindness for those aged 60 and older in the US.  It afflicts more than 10 million older Americans and causes more blindness than does the combined total of cataracts and glaucoma. This disease occurs mostly as people move much past middle age. And with the much increased numbers of people now living longer, it is one of today's most rapidly increasing afflictions that can seriously diminish a quality of life. 

Macular degeneration is caused by the deterioration of the central portion of the retina, the inside back layer of the eye that records the images we see. This section of the eye sends these images via the optic nerve from the eye to the brain. The retina's central portion known as the macula is responsible for focusing central vision in the eye.  It controls our ability to read, recognize faces or colors, drive a car, and see objects in detail.   As people age, their chances for developing eye diseases increase dramatically.  Few people today have the slightest idea about the steps they can take that can greatly reduce the risk of suffering this most debilitating disease. And few people seem to understand the seriousness of this risk before it suddenly strikes them.

Yet the research available identifies a wide range of health habits that can greatly increase or decrease the likelihood that macular degeneration will strike.  Life Ahead version #3 may provide a first broadly useful method that can identify risks of this disease at age and quantify how these risks can change as a result of multiple health habits. This can caution health-interested persons long in advance of the steps they can take to prevent this disease from happening.

The risk and prevalence of macular degeneration disease increases many times as age progresses.  Risks can be increased 3  times by smoking, and even by smoking that was stopped more than a dozen years previous. Its risk can be more than doubled for those overweight, and perhaps halved or more by cardiofitness effective exercise. Its risk factors such as blood pressure, total and HDL cholesterol, and c-reactive protein parallel risks for heart disease  Its risk is increased 2 to 3 fold  for those with family history of the disease, 2.5 times for those having cataract surgery, the same 2.5 times for those with diabetes, and two fold for those having blue or light colored vs. dark colored eyes. 

Adequate intake of caratenoids lutein and zeaxanthin can significantly reduce risk.  Antioxidant vitamins probably can reduce risks at least a quarter.  And risk appears increased for nearly all types of dietary fats except for the DHA and EPA from fish that can reduce risk.  Overall, a poor diet can double average risks, and a good diet can halve these risks. Combinations of  risks of macular degeneration can easily total 50 fold or more. And a high combination of these risks can make the suffering of this disease very likely for a person that moves past age 70.

The Life Ahead version #3 program will compute risks for any individual having any combination of these risks for any time ahead to life expectancy. The program can show what needs to be done to reduce these risks substantially.  Those that do not have some family or other uncontrollable risks may be able to reduce their risks of suffering macular degeneration to 1% or less by age 80.  But they need to take active health-oriented steps long before this age to accomplish this.

Detailed discussion of the various factors that are included in each Life Ahead valuation of macular degeneration risks follows. The writer is unaware of any other published source that provides this organized quantification of today's research of the risks of suffering macular degeneration.  As for all Life Ahead risks, these are risks of life habits in producing or increasing risks of the getting the disease.  Once the disease occurs its progress usually is now irreversible, and its treatment is the role of the specialized doctor.  It is possible but by no means confirmed that the these same life style factors that produce a disease might affect the rate of disease progression and severity after it occurs.  But adequate research on this is largely lacking and Life Ahead does not attempt to compute risks of the progression of most diseases.  Again, treatment is the role of the medical community and the doctor. 

The various factors that determine the risk of macular degeneration are detailed following, and the results of all key research on these factors found published are provided the appended table. 

Risks of Macular Degeneration and Age:  The most extensive compilation of the prevalence of this disease vs age found for use in this Life Ahead project was provided by An Eye Diseases Prevalence Research Group in Arch Ophthalmol 2004; 122:564.  This summarized results of seven studies including four from the US and three done in other world countries. Although the actual values obtained in the different studies varied considerably, the average result of all studies probably provides a useful assessment of average population risks vs. age.  These average results for % prevalence of macular degeneration, AMD, for white men and women follow.

Note that the increase in risk moves up nearly 20 fold for men and nearly    50 fold for women for the above age 80 group vs the 60-64 group. It is for ages above 70 that the risk of this disease becomes most serious. Women have lower risks than men for the ages before about 70.  But these are ages during which risk is relatively small. For the higher ages when risks are most serious women's risks are higher than those for men. Blacks had higher risks of the disease at younger ages, but somewhat lower risks above age 65.

Year by year values for the incidence of the disease were developed from statistically smoothed plots of the above values of prevalence.  These values

were extrapolated to reflect the full age range used in Life Ahead.  This permits the program to compute risks of the disease for average men and women of any age for any desired number of years ahead.  The highest age values represented from the actual research were about 91 and 92, the usual mean age for the 80 and above group of men and women.  It is obvious that risks at still higher ages are increasing quite rapidly. The values used for disease incidence in Life Ahead for ages above 92 are assumed to continue higher, but are extrapolated conservatively.

Macular Degeneration and Smoking:  Smoking greatly increases the risk of suffering  blindness from this disease. The results of the twelve research studies on this found published are shown as studies A1-A12 in the table of research results appended.  Every study shows an increased risk for smoking, with an average increase in risk of about 3 times.  And the reported risk values range up to 6-9 times. As is true for risks of smoking on heart disease and cancer, these values vary widely depending on amount smoked, duration of smoking and age.  The general pattern of and level of risks for macular degeneration are quite similar to those found from the much more extensive research on smoking and heart disease. Thus Life Ahead reflects the same risk profile for smoking and macular degeneration as that for smoking and heart disease.

A serious exception is that smoker's risk of macular degeneration probably declines more slowly after smoking is stopped than it declines for heart disease, cancer and other smoking  related diseases. Study A5 found that risks continued seriously 15 years after smoking was stopped.  Study A8 found risk to move higher for several years after smoking was stopped, and continued high 15 years after cessation.  Study A6 did find most risk gone 20 years later, but A12 noted no decline in risk 10 years later.  This research  suggests that smokers have an additional important reason to stop at or soon after age 50-55.  If they do not stop then or earlier, their risk of suffering debilitating partial or total blindness will be multiplied at the crucial older years when risk of macular degeneration can become very high. Thus smoking not only shortens likely length of life but can seriously diminish the quality of life for those smokers that do live but who do not stop smoking early enough to avoid the risk of becoming partially or totally  blind.  Life Ahead recognizes this slower than usual decline in risk after smoking is stopped in computing the risk of macular degeneration.

Macular Degeneration and Dietary Foods:  Only three food nutrient groups are now adequately confirmed by research as beneficial to macular degeneration.  These include the fish oils DHA and EPA, antioxidants Lutein and Zeaxanthin and combinations of other antioxidants.  Results of research studies F1-F4 show published effects of fats in foods on macular degeneration. Each study F1, F2 and F4 shows consistent negative effects of all key types of fats on this disease.  The harmful effects of polyunsaturated, monounsaturated and linolenic acid are surprising and are not consistent with their well established beneficial effects on heart disease. But the reasonably consistent effects from each of these three studies shows a risk of about 1.9 times for a probable difference of 16% of all fats in a diet, or of 1.041 times per percent increase in diet total fat.  Thus this effect of all dietary fat in % of calories  vs. the average US population value of 37% is included in Life Ahead at this rate. The risk of macular degeneration may be reduced by a factor of 0.41, or nearly 60% for use of a low fat diet.  But a  maximum risk benefit accepted for high vs. low total fats in Life Ahead and in accord with that verified from available research is  0.50.

Interestingly, the effect of DHA+EPA, the dietary fat in fish oils does appear to be an exception - and the only one found - to the usual effect of fats on macular degeneration.  Very large study F2 found beneficial effects for both DHA and EPA.  And studies F1 and F4 noted beneficial effects of either DHA+EPA or fish.  These confirming results provide good evidence that fish oils do reduce risk of this disease.  But the noted reduction of  risk of about 25% or to a factor of 0.75 is modest.  Life Ahead uses this risk value for a diet plus supplement difference of 480 mg of DHA+EPA.  This develops a risk improvement of 0.9994 times per mg of added DHA+EPA.  An average population amount of DHA+EPA is estimated at 65 mg per day, and a maximum benefit in macular risk from a diet change in this nutrient is set at a risk of 0.70 of average.  Study F3 found that added portions of fruits and vegetables reduced risk of macular degeneration.  This effect also is included in Life Ahead via its valuation of antioxidants from foods, supplements, and their combination as described following for antioxidant supplements.  Another important benefit from DHA + EPA is that its effect probably does not accrue gradually over long times as is true for most other foods and antioxidants.  Rather, it appears to produce its benefits in fairly short time.

Note that if a serum cholesterol value is not entered into Life Ahead, the program will compute a likely value for this based on exercise and diet. And this value for cholesterol will be related to dietary fat. This can further increase the health debit for a high fat diet. If cholesterol values are entered, it is assumed that the cholesterol value will directly reflect an effect of this dietary factor.

Lutein and Zeaxanthin are antioxidant caratenoids that appear specifically involved in the health of the eye. Research studies E2 to E4, E6,E12 and E13 appended each contribute to identifying the benefits of lutein + z. These nutrients do occur in usual combinations in diet and supplements with the majority amount being lutein.  Probable dietary amounts of these nutrients are incomplete in the references found but those taken from the large nurses and health professionals studies should be roughly representative of US population values.  Dietary intake values in these studies of lutein + z for successively  higher  20% population segments  for men and women averaged 1.4, 2.3, 3.1, 4.2, and 6.3 mg/day.  This 6 mg per day of intake appears to be the maximum amount of lutein + z usefully valued, and this level produced maximum benefit. An average for these groups was about 3 mg/day.  Some other estimates suggest that average US population dietary values of these nutrients may be closer to 2-2.5 mg/day.  A listing of some key foods that including lutein + z follows:

Only a limited number of foods appear valued for lutein + z, but most foods apparently include very little of these nutrients. And the values found for each food vary considerably by reference.  By far the most important usual food providing useful lutein + z is spinach. But it would require a portion of this on most days of the week to meet the desired healthy amount. Lettuce that contributes little to other calories or nutrients does included lutein + z in a useful amount.   Life Ahead includes the values found for lutein + z for all included foods for which values of this nutrient were found.  But some foods not now included in the Life Ahead library because of their minor contribution to calories and other nutrients or because of lack of popularity do include good lutein + z content.  Notably here is kale that can have 17 mg per 1/2 cup, turnip greens and collards that can add  8-9 mg per 1/2 cup..  But not many people will be eating large amounts of these other high lutein + z foods and users can add nutrient values from any desired food to the life ahead food library if they wish. 

The research published suggests that the risk of macular degeneration increased about 2 times for a decrease in lutein + z level from 7 mg/day to 1.4 mg/day.  This provided a relationship of risk ratio = Exp(0.433 - 0.1382 * lz)  where lz is mg/day of lutein + z.   This formula produces a risk of 0.59 of average for 7 mg/day and 1.29 times average for a minimum of 1.4 mg/day.  Life Ahead uses this relationship but with limiting amounts of lutein + z accepted from 1.4 minimum to 7 mg/day maximum.  No research confirms benefits of higher amounts than this.  But no research was found on the benefits of supplements of lutein + z that might extend this relationship. 

Supplements of lutein and zeaxanthin usually are sold in amounts of 6 mg, 20 mg and even 40 mg per day. The maximum amount now verified as protective in research is about 6-8 mg/day. Although research to date has been for dietary amounts,  supplements have been confirmed to raise the blood values that actually provide the protection and thus should be protective. Because it can be difficult for many individuals and especially those not fond of spinach to reach healthful values from foods,  it seems prudent for most health-interested person to take a supplement of 6 mg per day of lutein and zeaxanthin as a simple and potentially very important protection from this most unwanted disease. Adding this to a possible 2.5 mg value from diet would bring intake up to or above protective amounts now verified.  Study E13 appended confirmed that taking a 10 mg/day supplement improved the vision of those suffering macular degeneration. But this was an arbitrary amount, and does not necessary mean that 10 mg was better than 6 mg or that a higher intake would provide more benefit..  No harm has now been found for use of higher amounts of these nutrients, but again no further benefit has yet been identified for supplement amounts in the 20 to 40 mg/day range.  And the benefits of antioxidants and zinc that will follow may simply duplicate the benefits of higher lutein and zeaxanthin that in a total almost surely will reach a limit. As for other antioxidants, it is possible that lutein + z may require many years of use before useful benefits accrue. Again this duration of use factor has not been researched for these nutrients.

Macular Degeneration and Vitamin Supplements:  Benefits of other antioxidant vitamins and nutrients were developed in six of the appended studies E1, E2, E5, E8, E10, and E10.  An average risk benefit of about 0.67 from various combinations tested is indicated by pooled results of these studies.  Randomized study E10 of Vitamin E did not confirm a benefit, but its duration of only 4 years appears too short for a statistically useful effect to develop within its substantial error range of 0.69 to 1.6.  Quite large amounts of multiple antioxidants were used in most of these studies, and no useful effect was obtained for the individual vitamins A, beta carotene, C, E and selenium.  A benefit of dietary zinc was noted in E3 and a very large amount of zinc produced a modest benefit in study E8.

An average benefit from the above six studies was a risk ratio of 0.67 for various antioxidant combinations studied, and this was mostly for combinations of antioxidants in substantial amounts. This is a lesser benefit than that found for heart disease, and is a level difficult to measure within the accuracy of the individual studies.  But the results did suggest a significant overall benefit for antioxidant combinations.  Thus Life Ahead uses the combined effect of four antioxidants vitamins A or beta carotene, C, E, and selenium in both diet and supplements for identifying their risks for heart disease and cancer. This method includes a limit on amount of each individual nutrient accepted, and a limit on risk accepted from any nutrient combinations. This approach is needed to protect against probable duplication in the effects of the individual antioxidants. The risk accepted for antioxidants on macular degeneration is about half of their much better established risks on heart disease. Life Ahead uses the above combined effect of the above four antioxidants in computing risk of macular degeneration.

There also may be some duplication of benefits from lutein + z and other antioxidants.  Life Ahead acknowledges this by limiting computed risk benefits of lutein + z to 0.55, risk benefits for all other antioxidant combinations to 0.70, and risks from a combination of Lutein +z  and other antioxidants to 0.50.  These values provide reasonable consistency with the results provided in Studies E1 through E13.  Health-interested persons will be taking the other antioxidants as a key protection from the major risks of heart disease and cancer.  But the addition of 6 mg per day of lutein + z to daily supplement intake that now is confirmed adequately mainly for macular degeneration should provide a well worth while and inexpensive protection against what could be a major loss in the quality of the later years of a life.

Macular Degeneration and Body Weight in BMI:  Just three useful studies, B1 to B3 in the appended table,  were located relating risk of macular degeneration to body weight in BMI.  Two of these were obtained on reasonably large sized populations and all three studies produced near identical results for what probably were similar differences in BMI.  The average risk found for a probable difference between a BMI of 21 and that of 34 was a risk of 2.3 times. This works out to an increase in risk of 1.066 times for each unit increase in BMI.  Life Ahead computes this risk vs. an average population BMI of 24, and limits the range accepted to from 18 to 38 BMI.  It is likely that higher risks will be obtained for higher values of BMI, but no actual research data confirming this was found.

Thus as a general guide, a typical obese person will have about twice the risk of macular degeneration as that of a normal or somewhat below normal weight person.  Studies were carried out on populations of men and women, and no useful difference is risks for gender was noted in the research found published. This further extends the considerable harm of being overweight.  Not only does overweight  increase risk of heart disease, cancer and of premature loss of life, but many of those overweight that do live to older age will expect to experience years of suffering diabetes, arthritis, and alzheimer's and dementia,   And now in addition all this is the increased risk of serious loss of vision from macular degeneration.  Are the joys of overeating really worth all of this?

Macular Degeneration, Exercise, Cardiofitness and CFR: Only two useful studies numbers C1 and C2 in the appended table were found for the effect of exercise on this disease.  Although this is lesser evidence than that usually desired for acceptance in Life Ahead, it seems highly likely that cardio type exercise will provide important protection from macular degeneration.  Study C1 was one of the largest available population studies of macular degeneration, and the question "Does your exercise work up a sweat 5 times a week"  provides a powerful identification of the kind and amount of exercise that will substantially improve the CFR.  And the large reduction in risk of nearly four times obtained for those exercising at this level is similar to the risk change involved in heart disease for this change in cardiofitness. Results of C2 are consistent with a much lesser improvement in CFR that would be expected from the difference in exercise involved in this study. 

The aerobic type exercise that produces cardiofitness pushes blood at a much increased pace throughout the entire circulatory system. This exercise achieves its key benefit for heart disease by keeping arteries larger and more open.  It seems logical that this same process should keep the blood vessels elsewhere including those in the eyes more healthy and open. The entire pattern of factors that affect risk of macular degeneration appears to parallel with few exceptions their effect on heart disease. It would be very surprising it this parallel behavior would not be true for cardiofitness.  And nearly all  research does confirm that the effects of key factors on the two diseases are quite similar.

Macular Degeneration and Blood Pressure:  Studies D1 to D3 provide the available useful research relating blood pressure to macular degeneration.  The most direct study D3 identified a risk increase of 1.22 times for each 10 mm hg increase in blood pressure. An average result from D1 that involved a different level of the disease and D2 that was less quantitative suggested a somewhat similar risk.

Interestingly, the effect of blood pressure on heart disease developed from multiple research and that is now used in Life Ahead suggests a value of about 1.20 increase per 10 mm hg increase in blood pressure. Thus again we have similar risks of a factor for both heart disease and macular degeneration.  Life Ahead uses as a risk an average of systolic and diastolic pressures minus the average value for the base US population.  Values used in Life Ahead for the average US population of age 50 are 134/79 for men and 125/76 for women. Risks of macular degeneration are taken as 1.20 for each difference of 10 mm hg in average blood pressure of an individual from the average of these population values.  Those with hypertension typically will have about a twice higher than usual risk of macular degeneration. 

Macular Degeneration and Diabetes:  Only two useful studies relating risk of macular degeneration to diabetes - Studies G1 and G2 appended - were found.  Study G1 found a risk of 1.88 times at good significance.  But study G2 provides a prime example of the statistical confusion that that has kept health research controversial for decades.  The risks of 10.2 at highest significance for men and small  risk of 1.1 for women appear dramatically different on the surface. And this is what conventionally is now reported. But this  is near meaningless. Note the study error margin of 2.4 to 44 for men and 0.4 to 3 for women.  A value between 2.4 and 3 would be statistically consistent as within the error margins of each of these individual risks.  Thus the large purported difference for men and women probably is not significant, and in combination study G2 indicates a likely risk of about 2.5 times.

Diabetes increases the risk of heart disease from 1.5 to 11 times, mostly depending on gender and how long the diabetes has been present. It is highly probable from the biochemical mechanisms involved that diabetes should have an important role in increasing risk of macular degeneration. Life Ahead assigns an added risk of 2 times for diabetes in increasing risk of macular degeneration and this probably will be a conservative valuation of this risk.  No research showing the effect of diabetes duration on macular degenerations was found, but it remains possible that the same age-related effect as that for heart disease could apply similarly.

Once more we have another problem descending from being overweight. The biggest thing that leads to diabetes is overweight and high BMI.  And this diabetes from overweight doubles risk of macular degeneration and loss of vision.

Macular Degeneration and NSAID's:  Only one useful study appended as H1 was found for NSAID's that include as example aspirin and ibuprofen.  The result of a risk reduction of nearly 5 times seems inconsistent with the effect of these nutrients on heart disease and with effects of other factors.  Because this was for only a single study this risk factor  is not now included in Life Ahead.

Yet the result of H1 was one of the larger study populations researched for macular degeneration. And it seems likely that NSAID's should also reduce risk of this disease.  Most health-interested persons will be taking aspirin or another NSAID regularly for heart disease, and thus will achieve any risk benefit for macular degeneration as an added bonus.  The impressive  result of study H1 suggests that there is an important need for more research of the potential benefit of NSAID's on this disease.

Macular Degeneration and Cataract Surgery:   Five research studies I1 to I5 appended each show that risk of macular degeneration is substantially increased for those having prior cataract surgery.  Results of four studies providing risk factors varying from 1.53 to 4.3 suggest an average risk of 2.56 times.  A problem in quantifying this risk is that many of the risk factors for macular degeneration are the same ones that increase risk of cataracts.  These factors include body weight in BMI, cardiovascular risk factors including hypertension, and smoking.  Thus the risk of cataract surgery duplicates other risks already included in the macular degeneration model.

But the actual fact of prior cataract surgery does add some further risk for macular degeneration.  Life Ahead uses an added risk factor for cataract surgery of 1.5 for macular degeneration.  This conservative approach should provide a quite conservative valuation of the risk of this factor, and acknowledges less than one third of the actual risk of cataract surgery as non-duplicative. 

Macular Degeneration and Eye Color:  It long has been noted by observers that individuals with light colored eyes as blue or green seem to have higher risks of macular degeneration than do those with brown or dark colored eyes. Eye composition varies somewhat with the more pigmentation and melanin in darker colored eyes.  Each of the four studies J1 to J4 appended that measured risk differences based on eye color found that lighter colored eyes had a higher risk of macular degeneration. Risks values from the studies varied considerably from 1.15 to 3.5 with an average a risk of about 2 fold for the light vs. dark colored eyes.  Life Ahead assumes a unit risk of 1.0 for all factors for an average US population.  Thus this factor difference of 2 would suggest an  increased risk vs. this average of about 1.4 for light colored eyes, and a risk of 0.70 for dark colored eyes.  If eye color is not entered or known, the average population risk of 1.0 is assumed.

Macular Degeneration and Family History:  Only two useful studies, K1 and K2 appended, were found relating risk of macular degeneration to family history of the disease. K2 was for ARM, or an early state of macular degeneration. The risks of 2.9, 2.17 and 3.9 all are very high and suggest a quite high risk for family history.

The more extensive research on family history for other diseases show that risk is sharply related to age at which a family member contracted a disease, and this relationship as a parent, sibling.  Insufficient information was available here to confirm this general model.  Another problem with family history risks are parallelisms of an individual's and family member's other risk factors that can involve duplicative risks.   A family history of macular degeneration is noted in Life Ahead to double an individual's risk of the disease as a conservative approach to recognize this possible duplication.

Serum Cholesterol and Macular Degeneration:  Studies M1 and M2 confirm the strong relationship between risk of macular degeneration and coronary or cardiovascular diseases.  Study M3 found direct and high macular risks for those with both higher total cholesterol and lower amounts of HDL.   The risk of the difference in total cholesterol on heart disease for the difference in cholesterol in measured in study M3 is about 2.5 times, a value well within the statistical error margin of the higher value of 3.84 found  And the relation for HDL on macular disease is similar to the risk found for heart disease. Thus Life Ahead uses the far more accurately  measured risk for heart disease as a probable similar risk for macular degeneration.

Effect of C-Reactive Protein (CRP) on Macular Degeneration:  Three studies L1 to L3 show effect of CRP on the risk of macular degeneration. The effects found are not large, with a risk from L1 about 1.5 for a very large difference in CRP, only 1.23 in L2 for a fairly substantial difference in CRP.  Although CRP is cited as an independent risk factor, it is in turn heavily dependent on the usual cardiovascular risks of cholesterol, cardiofitness, weight in BMI etc.  No effect of CRP is appropriate in Life Ahead because the program already values the factors that mostly determine the value of this factor.  Use of an added CRP factor would involve duplicative risks. 

The table following includes all of the useful research found published via the Medline index and in references cited elsewhere that relates lifestyle and other factors to risk of contracting macular degeneration.  A similar comprehensive organization of this research has not be located elsewhere.  Various published articles describing these risks probably be derived from some of but not all of this same research data.  Health-interested persons can view below for themselves the actual research results found and their significance.  See the Life Ahead Health Library for a more detailed discussion of how to interpret health research study results from what is provided in these tables.