Research - Cataracts
Antioxidant May Prevent, Even Cure, Cataracts and Other Degenerative Eye Disorders
Researchers at Missouri University of Science and Technology are working with an antioxidant that could prevent or cure cataracts, macular degeneration and other degenerative eye disorders. The research group, headed by Dr. Nuran Ercal, the Richard K. Vitek/Foundation for Chemical Research Endowed Chair in Biochemistry and professor of chemistry at Missouri S&T, is studying eye drops prepared with the antioxidant N-acetylcysteine amide (NACA) as a treatment for these eye conditions.
Ercal says NACA is an improvement over another experimental treatment, the antioxidant N-acetylcysteine (NAC), because it passes more easily across cell membranes, allowing the medication to be used in lower doses.
“NACA’s characteristics as a drug were improved over NAC by neutralizing the carboxylic group of NAC, which makes the NACA pass cellular membranes easily,” says Ercal. “And because NACA can be administered at a lower dose, the drug has a greater therapeutic index and lowers the risk of side effects traditionally associated with NAC.
“NACA is also an excellent source of glutathione, a cell’s main antioxidant power, which is diminished during degenerative eye disorders,” she adds.
Vision loss from age-related eye disorders affects more than 30 million people in the United States and is expected to double in the coming decades, Ercal says.
In addition, more than $9 billion is spent annually in the U.S. on cataract surgery alone. The total annual cost of all services related to vision problems exceeds $20 billion, she says.
“NACA eye drops could drastically reduce these costs and represent an alternative to costly surgery, while greatly improving the quality of life for those afflicted,” says Ercal.
Ercal and her team have been testing NACA on HIV-related problems, lead poisoning and other toxicities for 10 years. About four years ago they began testing it on eye disorders.
Ercal recently received a $378,000 three-year research grant from the National Eye Institute of the National Institutes of Health. The preliminary data submitted for the funding was based on research by her former Ph.D. student, Joshua Carey.
Carey’s dissertation involved preliminary studies of the effects of NACA to slow down cataract growth on rats that had been given L-buthionine-S,R-sulfoximine (BSO), a solution that causes cataracts to form. “The NACA solution prevented cataracts from forming,” says Ercal. “Our research will build on Josh’s research, to see if NACA can actually reverse the degeneration as well.”
Ercal, who is also an M.D., says further testing will help establish appropriate dosage and frequency, as well as possible side effects and other factors. She says successful results using animal subjects may eventually support the viability of human usage.
Source : Newswise
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Healthy Diet May Reduce Cataracts in Women
Women who eat foods rich in a variety of vitamins and minerals appear to have a lower risk of developing cataracts, according to a large population study.
The study looked at dietary intakes for more than 1,800 postmenopausal women and found that those who ate the overall healthiest dietshad a 37% lower risk of nuclear cataracts, the most common type of age-related eye lens opacity, said Julie A. Mares, PhD, of the department of ophthalmology and visual sciences at the University of Wisconsin Madison, and colleagues.
Higher prevalence of cataracts in women was also associated with other modifiable factors such as smoking and obesity, and with nonmodifiable factors such as brown eyes, myopia, and high pulse pressure, Mares and colleagues wrote in the June issue of the Archives of Ophthalmology.
The women in the cohort were enrolled in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative (WHI). They had filled out food frequency questionnaires at enrollment between 1994 and 1998, which assessed their overall intake of a variety of foods including fruits and vegetables. The multivariate-adjusted odds ratio for nuclear cataracts between the high versus low quintile of women for overall diet scores was 0.63 (95% CI 0.43 to 0.91), according to Mares.
"Diet was the strongest risk factor related to reduced risk of nuclear cataract in this sample of postmenopausal women," the authors noted. "Lifestyle improvements that include healthy diets, smoking cessation, and avoiding obesity may substantively lower the need for and economic burden of cataract surgery in aging American women."
The authors cited several aspects of diet that may lower risk for nuclear cataract by lowering oxidative stress or systemic inflammation (which can lead to oxidative stress). In previous studies, having adequate or high intakes or blood levels of lutein and zeaxanthin and the use of multivitamin supplements have been most consistently related to lower risk for cataracts, they noted.
Only one other study has looked at the overall impact of a healthy diet on cataract occurrence, and that study found that 10-year adherence to the 1990 dietary guidelines for Americans was associated with lower risk for early nuclear lens opacities, the researchers wrote.
To further investigate the relationship between overall diet and cataract formation, the investigators looked at a subset of women enrolled in CAREDS. Participants in CAREDS all had self-reported intakes of lutein plus zeaxanthin that were either higher than the 78th percentile or lower than the 28th percentile as assessed at baseline enrollment into the WHI. WHI enrollees ranged in age from 50 to 79 at baseline.
Mares and colleagues enrolled a total of 1,808postmenopausalwomen living in Iowa, Wisconsin, and Oregon who had been in both CAREDS and the WHI. Exclusion criteria included unreliable diet data, history of trauma to both eyes, reported cataract extraction before age 40, missing or ungradable nuclear lens photographs, and missing covariate data.
Estimates of basic daily food and nutrient intake were made from responses to a food frequency questionnaire given at baseline (1994-1998). Adherence to the 1990 dietary guidelines for Americans and the 1992 food guide pyramid was estimated by the 1995 Healthy Eating Index (HEI-1995) scores, which were adapted to the WHI questionnaire. HEI scores were updated in 2005 to reflect new dietary guidelines that not only included the consumption of food groups but also increased intake of foods within those groups (e.g., dark green leafy vegetables).
As part of the CAREDS study, the women underwent lens photography and eye examinations between 2001 and 2004. Both eyes were examined with slitlamp biomicroscopy. After pupils were dilated, a single nonstereoscopic photograph was taken of each eye. Severity of nuclear sclerosis was determined in eyes that had not previously undergone cataract extraction.
The primary outcome was presence of a nuclear cataract, defined as a nuclear sclerosis severity score of 4 or greater in the worse eye and/or a history of cataract extraction in either eye. A secondary outcome was nuclear sclerosis, defined as a severity score of 4 or greater, in women who had at least one natural lens for which lens photographs were gradable.
Nuclear cataract was found in 454 of 1577 women who had lenses in at least one eye. An additional 282 of the 1,808 women reported cataract extractions in either eye. Overall, 736 women (41%) either had nuclear cataracts evident from lens photographs or reported having a cataract extracted.
After adjustment for other risk factors, being in the third to fifth quintiles for the HEI-1995 score (having HEI-1995 scores >68) was associated with 37% lower odds for nuclear cataract. The association remained significant after adjusting for smoking, body mass index, supplement use, and physical activity, according to the researchers.
This association did not appear to be related to any single part of a healthy diet. Taking vitamins and other supplements was not associated with decreased risk for nuclear cataracts.
The authors noted that their own previous work showed that prevalence of nuclear cataract in this sample was associated with diets high in fat and speculated that this might reflect the possibility that dietary fat intake is a marker for diet poor in a wide variety of micronutrients.
"Indeed, dietary fat intake was highly correlated with the HEI-1995 score (r=0.7; P<0.001), and adjusting associations for dietary fat attenuated the odds ratio more than adjusting for any other nutrient (multivariate OR=0.86; 95% CI 0.54 to 1.37)," they said.
The authors noted several limitations to their study, including whether the 1995 Healthy Eating Index to the questionnaire adequately captures the protective aspects of foods,the possibility that the findings may theoretically represent poor diets that occur as a result of having nuclear cataracts, or comorbid conditions associated with them. In addition, some risk factors were not measured, such as lead exposure, or may have been unknown. Also, some misclassification of nuclear cataracts among those previously extracted may have occurred.
Source : Medical News
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Estrogen Replacement Linked to Cataract Risk
Women who receive hormone replacement therapy (HRT) to counter the drop in estrogen levels after menopause are more likely to suffer from cataracts, a new Swedish study found.
Compared with women who never had HRT, the risk of needing cataract surgery was 14% higher among those who received HRT at any point their lives (RR 1.14; 95% CI 1.07 to 1.21) and 18% higher for women currently taking hormones (RR 1.18; 95% CI 1.10 to 1.26), according to the report published online March 1 in Ophthalmology.
Women undergoing HRT who reported drinking more than one alcoholic drink per day were at 42% higher risk of cataracts (RR 1.42; 95% CI 1.11 to 1.80).
"A longer duration of HRT usage was associated with an increased risk of cataract extraction," Birgitta Ejdervik Lindblad, MD, of Sundsvall in Sweden, and colleagues wrote.
"Higher intake of alcohol seemed to potentiate the harmful effect of HRT on cataract development. If other studies confirm this association, an increased rate of cataract extraction should be added to the list of potential negative outcomes associated with HRT."
Naturally occurring (endogenous) estrogen is thought to protect the eyes from cataracts, and estrogen receptors have been found on the lens, the part of the eye damaged by cataracts.
"Prevalence of cataract is higher in postmenopausal women compared with men of equivalent age," the authors wrote. "This may be related to hormonal differences between women and men and suggests a possible role for estrogen in cataract development."
Exogenous estrogens, such as those used for HRT, have been associated with increases in C-reactive protein levels, which have been linked to cataract development. "Exogenous estrogen in form of HRT is not to be regarded as a physiological substitution and could have other effects on the lens," the authors wrote.
Lindblad and colleagues conducted an eight-year prospective study of more than 30,000 postmenopausal Swedish women, whom they followed from September 1997 through October 2005. The women initially completed a questionnaire about hormone status, HRT, and lifestyle factors. Researchers later compared these records with registers of cataract extraction.
During the study, 4,324 of the women had cataracts surgically removed. Although the length of HRT therapy and drinking more than one alcoholic drink per day were associated with risk of cataracts, smoking was not.
The authors cautioned that the vast majority of women shared the same ethnicity and had equal access to healthcare, so the results may only be applicable to the Swedish population.
The study was also limited by a lack of data on the type of estrogen therapy the women received and the type of cataract they developed. Nor did the study account for sunlight exposure, a risk factor for cataracts.
The authors noted that their results differed from previous American studies that found that HRT lowered a woman's risk of cataracts or had no influence, depending on the type of cataract.
However, they wrote that estrogen types and treatment regimens differ among countries, so comparison between the studies is difficult.
Source : Med Page Today
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SSRIs Linked to Cataracts
Use of selective serotonin reuptake inhibitor (SSRI) antidepressants may be associated with cataract risk among older adults, a large population study from Canada found.
In a nested case-control study involving more than 200,000 residents of Quebec, current users of SSRIs ages 65 and older carried a 15% greater relative risk of cataracts (95% CI 0.08 to 1.23) compared with nonusers -- even after adjustment for blood pressure, other medication use, and gender, reported Mahyar Etminan, PharmD, MSc, of the University of British Columbia in Vancouver, and colleagues.
These findings are the first to support the ocular risk seen with SSRIs in an animal model, the researchers wrote in the June issue of Ophthalmology.
If the relationship is proven to be causal, roughly 22,000 cataract cases in the U.S. each year could be attributed to SSRI use, Etminan's group estimated. According to background information in the study, 10% of U.S. residents are taking antidepressants, mostly SSRIs and newer selective serotonin-norepinephrine reuptake inhibitors (SNRIs).
Serotonin receptors are found in the lens of the eye. In animal studies, serotonin has been shown to play a role in opacification of the lens and formation of cortical cataracts, the researchers noted.
Older-generation antidepressants, particularly amitriptyline (Elavil), have also been associated with increased risk of cataracts, but it wasn't clear whether the newer-generation of receptor-selective antidepressants would have the same effect, Etminan's group wrote.
Using the linked administrative databases of the universal healthcare plan in Quebec province, the researchers searched within a cohort of residents who had received coronary revascularization between 1995 and 2004. From this cohort, the study included all 18,784 adults ages 65 and older diagnosed with a first cataract along with 187,840 matched controls.
Those who received a diagnosis of cataracts while on SSRI therapy had been on the drugs for an average of nearly two years (656 days) before their cataract diagnosis.
Whereas use of an SSRI within 30 days of the cataract diagnosis did appear to have a significant effect, any past use did not (adjusted rate ratio 1.06, 95% CI 0.97 to 1.17).
The only significant impact of past use was with sertraline (Zoloft), which was associated with a 19% elevated risk of cataract (95% CI 1% to 41%). However, current use of this drug within 30 days of cataract diagnosis showed no significant effect on cataract risk (adjusted RR 1.06, 95% CI 0.92 to 1.22).
Among the available SSRIs, the risk of cataracts was most elevated among those on fluvoxamine (Luvox) with a 39% higher rate ratio compared with controls (95% CI 7% versus 80%).
Close behind it was the SNRI venlafaxine (Effexor) with a 33% elevated relative risk of cataract compared with nonuse (95% CI 1.14 to 1.55).
Other SSRIs citalopram (Celexa) and fluoxetine (Prozac) showed a tendency toward a 13% elevation in cataract risk with current use and paroxetine (Paxil), a tendency toward a 7% elevation, but none were statistically significant.
In an analysis considering only cataract cases actually treated with outpatient surgery, the results were generally similar, except that paroxetine became significantly associated with cataracts (adjusted RR 1.23, 95% CI 1.05 to 1.45).
The results "may suggest the importance of selectivity of serotonin receptors in the formation of cataracts," Etminan's group wrote in the paper.
However, the researchers cautioned that it's possible that the lack of association of certain SSRIs with cataracts may simply have reflected lack of power in the study for individual drugs.
"Whether the catarogenic effects of SSRIs are a class effect or are limited to specific agents must be investigated further," they concluded.
Limitations of the study included its design; using an administrative database, which made it impossible to check for confounders and risk factors for cataracts such as smoking; as well the use of the International Classification of Diseases, ninth revision, codes for cataracts, which may not necessarily confirm cataract surgery had taken place.
Source : Med Page Today
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