Influence of Medications,

 

Diet, and Environment

 on

 

Cataractogenesis

 

 and

 

  Reversal

 

 

Benjamin Clarence Lane, OD

 

 

 

ABSTRACT

 

This course presents the latest epidemiological and clinical developments, lab tests, and technology in identifying risk factors for the individual species of cataracts and discusses relative effectiveness of therapies now under study for the prevention and reversal of cataracts.

 

LEARNING OBJECTIVES

 

First: To understand the appropriate protocols for detecting and classifying small changes in the development and reversal of cataract.

Second: To become familiar with the approaches in use by the major studies investigating cataractogenesis.

Third: To understand current nutritional approaches regarding diagnosis, treatment, and management of cataractogenesis.

 

OUTLINE

 

Recent published studies have identified dietary, medicinal, and environmental risk factors for cataractogenesis as associated with specific crystalline lens strata.

I. Lens strata and cataract category:

A. Anterior Subcapsular (Vacuolar  vs  Polar Opacity)

 B. Anterior Cortical (Spicular [Spoke]  vs  Non-spoke & significance of quadrant differences)

C. Paranuclear or Lamellar

D. Nuclear (Stable  vs  Progressing)

E. Posterior Cortical (Spicular [Spoke]  vs  Non-spoke)

F. Posterior Subcapsular (Vacuolar  vs  Polar Opacity)

II. Coping with the quite rare inherited inborn errors of metabolism as compared to the quite common dietary and environmentally induced degenerations:

The latter are usually caused by exposure to promoters in medications, specific toxins, or superoxide and other free radicals as generated by radiant energy The former may require omission of a class of foods.  (E.g.,  galactosemic pre-schoolers need to omit milk products; homocystinuric children often present with an elevated pyridoxine [vitamin B6] dependency and a need to avoid excessive methionine.)  On the other hand, as recently as 1980, McLaren’s landmark text, Nutritional Ophthalmology, nowhere used the word “antioxidant”!  In 1980 Szent-Györgi, the vitamin C co-discoverer and Nobel laureate, called attention to the electrical nature of vitamin C and the role of the antioxidants in health maintenance and chaperoned in an exciting era of antioxidant research in the commonly experienced diet- and environment-induced eye disorders.

III. Dietary accelerants for precocious cataract:

A. Deficient protein intake associated with posterior subcapsular cataract (PSC), nuclear, & mixed cataracts (Mohan, Sperduto et al, 1989

B. Deficient antioxidant index (composite rbc-glutathione peroxidase (EGPx), Glucose-6-PD, Vits C, E, beta-carotene) assoc w PSC & mixed cataracts (Mohan, Sperduto et al, 1989; Jacques & Chylack, 1991; Leske et al, 1991; West 1991)

C. Decreased beta-carotene assoc w PSC & cortical cataract (Jacques et al, 1988), but especially of other carotenoids (Willett et al, 1995)

D. Excessive intake of large, longer-lived (high-in-the-chain carnivorous) finfish which concentrate natural chemical toxicants, especially including organic mercury, as well as all finfish and shellfish from mercury-polluted waters (Lane, 1982, 1992; Takizawa and Okamura, 1980).

E. Excessive intake of milk products in the face of deficient galactokinase or Gal-1-P-Uridyl transferase enzymes (Bhatnagar, Sharma, Mohan et al, 1989)

F. Excessive intake of foods that elevate triglycerides in hypertriglyceridemic individuals, assoc w combined PSC-nuclear cataract and oil-droplet cataract,  (Janke, Eckerskorn, Jahn & Hockwin, 1989; Lane, 1992)

G. Selenium deficiency and selenium-dependent glutathione peroxidase deficiency as indexed in red blood cells, assoc w PSC in persons consuming excessive large fish. (Subcapsular cases eating ≥3.7 large-fish 3-oz servings/wk are 12x more likely to have abnormal rbc-Glutathione Peroxidase (EGPx) (<4.1 or >6.4µM NADPH /min/mg Hb) than normal EGPx compared to those consuming less large fish, p<0.0001.)

IV. Environmental accelerants for precocious cataract:

A. Decreased cloud cover & increased ultra-violet-B (uv-B) associated with all types incl cortical cataract (Mohan, Sperduto et al, 1989; Italian-American Cataract Study Group, 1991); Jacques & Chylack, 1991)

B. Ultraviolet-B (uv-B) exposure (as well as diabetes, steroid therapy) assoc w PSC (Bochow, West et al, 1989)

C. Tobacco smoking associated with nuclear cataracts & PSC (West et al, 1989).

V. Medications long recognized as risk factors in cataractogenesis:

A. Thiazides (including aldactazide, corzide, diuril, diutensin, dyazide, esidrix, hydrodiuril, minizide, meduretic, and naturetin)

B. Loop diuretics (including furosemide [=lasix] and bumetaside [=bumex];

C. Other potassium-sparing diuretics (including aldactone and maxzide); corticosteroids {causing PSC}
D. Several anti-psychotics (including haldol, mellaril {causing stellate anterior-lenticular opacities}
E. Phenothiazine tranquillizers (including compazine, phenergan, sparine, stellazine, and thorazine)
F. Known toxic agents (including  2-4-dinitrophenol {which uncouples oxidative phosphorylation in mitochondria}; naphthalene, tegretol {causing scattered punctate cortical lens opacities}, triparanol, and quinoids [Cuthbert, Clayton et al, 1987].
G. Mercurials as attributed to use of chronic topical organic mercury (phenyl mercuric nitrate previously used as preservative in pilocarpine drops (Abrams & Mazjoub, 1970).

VI.  The Fish-Methylmercury Study:

In his dissertation case-control panel study reported late in 1992 to the American College of Nutrition and to the American Academy of Optometry, Lane reviewed more than 1200 consecutive nutrition workups of 414 eye patients for whom mineral assays and/or red-blood-cell enzyme concentrations had been determined.   He found that non-diabetic subcapsular-cataract cases, not on implicated medications,  42-90 years old 

A. Consumed large-fish Hg-equivalent averaging 7.3 ounces of tuna/week, 3.4 oz more  than non-cataractous controls, p=0.002

B. Had elevated cold-vapor-technique assayed hair Hg (3.1 ppm vs 2.1 ppm mean), p=0.007
C. Consumed less total food carotenoids (9,004 vs 13,165 iu), p=0.018
D. Had higher serum triglycerides (131.4 vs 94.0 mg/dL) than controls, p=0.029

Comparing cases with only subcapsular vacuole aggregations (including oil-droplet or ruddy-colored subcapsular vacuoles with clear nuclear areas) and/or opacities vs cases with only cortical “spoke” cataract, Lane found the former associated with high large-fish intake and hair MeHg, whereas the pure spoke-cortical cases have extremely low large-fish intake, low hair MeHg (p=0.004) and are significantly 12 years older in mean age, p=0.007, and typically have experienced long outdoors exposures to bright sun without sunglasses (Lane, 1992).

Cases with subcapsular plus progressing-nuclear cataract average 5 yrs older than pure subcapsular cases, p=0.03.

Subcapsular cases eating ≥3.7 large-fish 3-oz servings/wk are 12x more likely to have abnormal rbc-Glutathione Peroxidase (EGPx) (<4.1 or >6.4µM NADPH /min/mg Hb) than normal EGPx compared to those consuming less large fish, p<0.0001.

Persons ≥42 years old averaging three 3-oz tuna servings/week have 3x the risk [Odds Ratio = 3, p = 0.0009, 95% Odds Ratio Confidence Interval = 1.52 to 5.34.] for subcapsular cataract development compared to persons consuming an average of less than one 3-oz serving of tuna in two weeks.

This study found that subcapsular cataractous lenses average significantly greater Hg concentration than normal control lenses and confirmed  strong associations of excessive weekly consumption of large, carnivorous marine fish  with  insidiously bioaccumulated erythrocyte and hair MeHg, abnormal EGPx [as an index of  GPx which defuses both H2O2 and Hg] and significantly increased risk for precocious development of subcapsular and progressing nuclear cataracts (Lane, 1992).

VII. Lab tests to identify diet-responsive risk factors for cataractogenesis.

 

A. Optometric Baseline Tests:

 

1. Meticulous direct ophthalmoscopy (+40D, +20D) of the lens with drawings of frontal plane (poles in center), profile plane (equator in center), and horizontal plan-view plane (posterior capsule at top), especially sketching location and extent of vacuoles and other early lens changes.

2.  Slit-lamp cross-section photo or sketch of each lens section, especially to catch early changes in the lens nucleus and subcapsular zones.

3. Meticulous threshold subjective refraction with high motivation imbued in patient to persist in attempting to read the finest detail as the examiner refines the prescription, "so that when you believe you may be seeing better next year and when we retest you, it won't just seem that you are seeing better because we did not try hard enough today." 

 

B. Nutriture Indications from Blood & Urine Tests

 

1. ESOD [Erythrocyte Superoxide Dismutase], when depressed <9.5 units/mg hemoglobin, is an index for increased likelihood of cataract, vitreopathy, and/or maculopathy.  SOD is the first line of defense against the superoxide radical, defusing it to H2O2. Deficiency in ESOD is suggestive of either inadequate copper (Cu) or zinc (Zn) or both.  Normal range for young adults not long ago was considered to be 12.0 to 15.4 units/mg Hb.

2. EGPx [Ery. Glutathione Peroxidase] may be implicated as a factor in cataractogenesis if it is depressed below 4.6 micromoles (µM) NADPH/min/mg Hb or if >6.6 µM NADPH/min/mg Hb.  GPx defuses H2O2, a principal instigator of senescent cataract. Deficiency suggests a need to increase selenium (Se) intake, since Se is the limiting mineral in the body's ability to synthesize GPx.  Normal range for young adults is listed as 4.23 to 7.23 µM NADPH/min/mg Hb.  EGPx is an inducible enzyme.  High values indicate a challenge that the body is able to meet as long as Se reserves are available.  EGPx is vital in protecting against (organic) methylmercury (MeHg), just as MeHg defuses EGPx.
3. Catalase/RBC also defuses H2O2  and lipid peroxides. Deficiency is known to increase the risk for at least several eye disorders including cataract. Patients may often report problems in thermoregulation to cold if catalase is extremely low. Abnormal concentrations of long-chain fatty acids and excessive intake of dried concentrates of greens may contribute to the deficiency situation.
4. BCL Metal Profile [Chromium/RBC (Cr/RBC), Copper/RBC (Cu/RBC), Manganese/RBC (Mn/RBC), Vanadium/RBC (V/RBC), Zinc/RBC (Zn/RBC)]. Watch for antagonisms  and balances (ratios): Cu/Zn, Cr/V, Cr/Mn, Cr/Zn.  The printed Cr/RBC and V/RBC ranges are misleading.  We should like to see Cr/RBC exceed 0.3 µg/mL (300 ng/mL) and the ratio of Cr/RBC to V/RBC should approximate 1.0.   Americans have been getting too little Cr and too much V since the early 1970s because of dietary shifts from beef and whole milk products to commercially bred poultry and large marine fish and low-fat milk products. Currently, the Cr/RBC and V/RBC are the best individual tests for Cr and V balance.

This profile as well as other cellular and functional blood tests and assays of extracellular concentrations of vitamins by the UMDNJ method are available through Vitamin Diagnostics, Route 35, Cliffwood Beach, NJ 07735, tel: 1-732-583-7773.

Some of the tests (e.g., EGPx and ESOD) are also available through •Great Smokies Diagnostic Laboratory, tel: 1-800-522-4762, and other tests (e.g., quantitative galactokinase and galactose-1-phosphate uridyl transferase) are available through •Mayo Medical Laboratories (tel: 1-507-284-3631)

5. EGOT (Ery. Glutamic-Oxaloacetic-Transaminase) or EGPT (Ery. Glutamic-Pyruvic Transaminase) are generally considered functional indices of pyridoxine (vit B6) sufficiency. When elevated (≥1.25), they provide evidence of failure of transamination ability––the ability to convert available amino acids to required amino acids––a problem generally associated with excessive intake of well-cooked (denatured) proteins. This is a key test, when high,  for identifying the increased risk for exudative (wet) maculopathy.
6. Organic Mercury (Hg)/RBC and Inorganic Mercury (Hg)/RBC are a pair of tests that provide the most meaningful assays of all the blood and urine measurements for assessing long-term chronic accumulation of mercury and especially methylmercury (MeHg) accumulating from multiple or low-grade small exposures. Hair Hg provides a better archive of old endogenous exposures chronicled linearly in each hair strand, depending on length and growth rate. MeHg depresses all of the body's antioxidant protective enzymes, since they are all thiol proteins.
7. Vitamin C/WBC [Ascorbic Acid in Leukocytes]. A paradoxical low finding in the face of megadose supplementation tested after a 12 hour fast is indication of excessive ascorbic-acid supplementation.  When the supplementation is decreased, the Vit C/WBC finding normalizes.
8. Platelet Vitamin E reveals more eye anomaly and vision-syndrome meaningful associations than the other blood tests for vitamin E currently available.
9. GPUT (Galactose-1-Phosphate Uridyl Transferase) when depressed provides evidence for type 1 of galactosemia and resulting cataract development related to intake of milk products. Lactose digestive aids and live-culture yogurt may be contraindicated in some pat’ts.
10. Galactokinase when depressed provides evidence for type 2 of galactosemia and resulting cataract development related to intake of milk products.
11. Serum Beta Carotene and Serum Vitamin A.  Beta Carotene acts as a singlet-oxygen quencher; vitamin A does not have this property, although it is required by the retinal receptors as is well known.
12. FIGLU [Formimino-Glutamic Acid/24-Hour Urine]. Elevated FIGLU may indicate a functional need for food-folic acid––even possible in the face of heavy supplementation of pharmacological folic acid known as pteroylglutamic acid––the deconjugated, oxidized, shelf-life version of folate.
13. BUN [Blood Urea Nitrogen]––one of the routinely performed SMA-series tests. Elevation indicates increased risk for age-related cataract as well as kidney failure. Reduction of dietary protein aids in the control of BUN.  This test is available through any clinical medical laboratory.

14. Glyco Hb A1C [Glycosylated Hemoglobin] affords a long-term, time-weighted index of average blood glucose. This test is available through any clinical medical laboratory.

4. B

 

C. Nutriture Indications from Hair-Mineral Assays

 

Only the best of the multiple-element clinical hair-mineral assay laboratories remain in business after an aggressive medical campaign  which did address abuses that needed correction, but also almost succeeded in "throwing out the baby with the  bath water."  Blood is a well-regulated medium and will often appear virtually normal when the body may have no reserve ability to maintain normal function.  As a time-indexed linear excretion tissue, properly sampled hair can provide an index of mineral excretion which combined with a comprehensive diet history affords insights into mineral conservation, export, and storage balances.

1. Hair Hg (Hair Mercury)––indexes a significant risk factor promoting human cataractogenesis if ≥ 1.6 ppm by cold-vapor spectrophotometry.  Of the several remaining U.S. multiple-element clinical hair mineral assay laboratories mostly only  •Great Smokies Diagnostic Laboratory, tel: 1-800-522-4762, and •Doctor's Data, P.O. Box 111, 30W101 Roosevelt Road, West Chicago, IL 60185; tel: 1-800-323-2784, are providing appropriate digest techniques for mercury analysis.  It is important when ordering hair mineral assays specifically to request either Cold-Vapor Mercury Analysis or technology that entraps the vaporized mercury until it can be measured (worth an extra charge), since this is the most valuable test available for detection of chronic endogenous MeHg excretion––a measure which enables us to estimate relative amounts of organic mercury becoming stored in tissues that accumulate MeHg, such as the crystalline lens!

2. Hair Zn (Hair Zinc)––quite meaningful if the finding is below the normal range, an indication that the body is conserving Zn and not excreting it into a relatively non-essential tissue.  But if the finding is in the normal or high range, it may simply represent slow hair growth––a possible consequence of marginal Zn deficiency, since Zn is required for DNA synthesis.  Of course, it is important to rule out exogenous sources, such as Zn from Head & Shoulders Shampoo adsorbed onto the hair.

3. Hair Cu (Hair Copper)––extremely meaningful and important if the finding is below the normal range.  In order to interpret properly a normal or elevated finding, we need to rule out exogenous adsorption of copper from bathing in a swimming pool (almost invariably treated with copper sulfate or copper salts as deflocculents incorporated with the chlorine) or bathing in a bath tub, especially in a tall building where the water is distributed from a rooftop water tank after traveling a long distance through copper pipes and especially if the water is somewhat acidic.  Note: Cu and Zn are essential nutritional minerals limiting the body's ability to synthesize superoxide dismutase, said to be the most prevalent non-structural protein in the body.

4. Hair Cr (Hair Chromium).  Disregard this reading unless the lab protocols allow Cr to be measured with an appropriate digest and best sensitivity.  Great Smokies Lab’s method is producing meaningful Cr findings.

5. Hair V (Hair Vanadium). Disregard this reading unless the lab  has taken special care to measure V with appropriate sensitivity.

6. Hair Se (Hair Selenium)–– can be superbly correlated with pathology if anti-dandruff shampoos containing Se [Selsun, etc.] have not been used in recent months.

VIII. Background for Dietary Considerations in Cataractogenesis

 

A.

 

Elevated glycosylated hemoglobin and depressed Cr/V ratio are indices of increased risk for sugar cataracts.  Elevated Hg ≥ 1.6 ppm as indexed in hair can be a major source of inhibition of thiol-protein enzymes throughout the body––including enzymes such as Na,K-ATPase, glutathione peroxidase, SOD, and catalase––enzymes that directly protect the lens from oxidative insult––and G-6-PD, required for effective access to the hexose monophosphate shunt (HMS), and consequently resulting in reduced ability of the body to use reduced glutathione (GSH) to clear H2O2 from the lens when this pathway is blocked.

 

B.

 

Fortunately, all of these enzymes are diet responsive, just as elevation of MeHg is diet responsive.  Part of the overall key is increased intake of food folate––essential for efficient uptake of nutrients from the gut [and the most heat labile of all the vitamins]––and adequate intake of food pyridoxine (vit B6), partly because of its importance in transamination of amino acids.  Especially important are appropriately balanced intakes of Cu and Zn, Cr and V and also calcium and phosphorus.  These strategies are outlined on pages 279-281 of Dr. Lane's chapter on "Nutrition and Vision" in 1984-'85 Yearbook of Nutritional Medicine (New Canaan, CT: Keats Publishing, 1985).

IX. Overview of what is now reported in refereed journals as the best prudent advice on cataract prevention

 

REFERENCES

 

Abrams JD, Majzoub U. Mercury content of the human lens.  Brit J Ophthalmol 1970; 54: 59-61.

tnagar R, Sharma Y, Mohan M, Vajpayee RB, Azad RV, Mukesh K. Does milk have a cataractogenic effect? A weighing of clinical evidence; in Hockwin O, Sasaki K, & Leske MC (eds):  Developments in Ophthalmology, vol 17: Risk Factors for Cataract Development.  Basel: Karger Publishers, 1989, pp 93-6.
Bochow TW, West SK, Azar A, Muńoz, Sommer, Taylor. Ultraviolet light exposure and risk of posterior subcapsular cataracts. Arch Ophthalmol 1989; 107(3):369-72.
Cuthbert J, Clayton RM, Phillips CI, Seth J. Diuretic drugs as risk factors in cataractogenesis. Metabolic Ped Syst Ophthalmol 1987; 10(2): 48-54.
Italian-American Cataract Study Group. Risk factors for age-related cortical, nuclear, and posterior subcapsular cataracts. Am J Epidem 1991; 133(6): 541-53.
Jacques PF, Chylack LT, Jr. Epidemiologic evidence of a role for the antioxidant vitamins and carotenoids in cataract prevention.  Am J Clin Nutr 1991; 53(1): 352S-5S.
Jacques PF, Hartz SC, Chylack LT, Jr, McGandy RB, Sadowski JA. Nutritional status in persons with and without senile cataract: blood vitamin and mineral levels. Am J Clin Nutr 1988; 48(1=Jul): 152-8.
Lane BC. Fish methylmercury and human cataractogenesis. J Am Coll Nutr 1992; 11(5): 637. (abstr 133, changed to abstr 109, presented October 12, 1992, Gastrointestinal/Micronutrients Session, American College of Nutrition).
Leske MC, Chylack LT, Wu S-Y. The lens opacities case-control study: Risk factors for cataract. Arch Ophthalmol 1991; 109(2): 244-51.
Mohan, Sperduto RD, Angra SK, Milton RC, Mathur RL, Underwood BA,  Jaffery    N, Pandya CB, Chhabra VK, Vajpayee RB, Kalra VK, Sharma YR, the India-US Case-Control Study Group. India-US Case-control study of age-related cataracts.                 Arch Ophthalmol 1989; 107(5): 670-6.
Takizawa Y, Okamura R. Mercury in the crystalline lens. Igaku No Ayumi [Medicine in Progress] 1980; 112(1): 23-4. [Japanese]

West SK. Who develops cataracts?  Arch Ophthalmol 1991; 109(2): 196-8.

West S, Muńoz B, Emmett E, Taylor HR. Cigarette smoking and risk of nuclear cataracts. Arch Ophthalmol 1989; 107(8): 1166-9.

Willett WC.  Keynote lecture to the Nutritional Epidemiology Research in Vision and Ophthalmology (NERVO) SIG at ARVO, 5/15/95.

“In the Vanguard of Dietary Research and Integrative Therapy in the Prevention and Reversal of Eye and Vision Disorders”

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