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COMPLETE VISION Scientific Research

Zeaxanthin and Lutein

The Effect of Lutein on Eye and Extra-Eye Health *

Lutein is a carotenoid with reported anti-inflammatory properties. A large body of evidence shows that lutein has several beneficial effects, especially on eye health. In particular, lutein is known to improve or even prevent age-related macular disease which is the leading cause of blindness and vision impairment. Furthermore, many studies have reported that lutein may also have positive effects in different clinical conditions, thus ameliorating cognitive function, decreasing the risk of cancer, and improving measures of cardiovascular health. At present, the available data have been obtained from both observational studies investigating lutein intake with food, and a few intervention trials assessing the efficacy of lutein supplementation. In general, sustained lutein consumption, either through diet or supplementation, may contribute to reducing the burden of several chronic diseases. However, there are also conflicting data concerning lutein efficacy in inducing favorable effects on human health and there are no univocal data concerning the most appropriate dosage for daily lutein supplementation. Therefore, based on the most recent findings, this review will focus on lutein properties, dietary sources, usual intake, efficacy in human health, and toxicity.

Source: Silvio Buscemi, Davide Corleo, Francesco Di Pace, Maria Letizia Petroni, Angela Satriano, Giulio Marchesini. “The Effect of Lutein on Eye and Extra-Eye Health” Nutrients (2018): 10(9): 1321.

Diet patterns and the incidence of age-related macular degeneration in the Atherosclerosis Risk in Communities (ARIC) study *

Abstract

Background Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly.

Objective This study aimed to determine the association between dietary patterns and food groups (used to make them) with the 18-year incidence of AMD.

Methods ARIC (Atherosclerosis Risk in Communities) participants who showed change in AMD lesions between retinal photographs taken at visit 3 and visit 5 were graded side by side to determine incident AMD (any=144; early=117; late=27). A 66-line item food frequency questionnaire, administered at visit 1 and visit 3, was used to identify 29 food groups. Principal component analysis was used to derive dietary patterns from average food group servings. Logistic regression was used to estimate ORs and 95% CIs for incident AMD (any, early and late) by tertiles of dietary pattern scores, adjusted for age, race, education, total calories and smoking status. P-trend was estimated using continuous scores.

Results Western (unhealthy) and Prudent (healthy) dietary patterns were identified. No significant associations were observed between either dietary pattern and incident any or incident early AMD. However, a threefold higher incidence of late AMD was observed among participants with a Western pattern score above, as compared with below, the median (OR=3.44 (95% CI 1.33 to 8.87), p-trend=0.014). The risk of developing late AMD was decreased, but not statistically significant, among participants with a Prudent pattern score above, as compared with below, the median (OR=0.51 (95% CI 0.22 to 1.18), p-trend=0.054).

Conclusions Diet patterns were not significantly associated with incident any or incident early AMD. However, consumption of a Western pattern diet may be a risk factor for development of late AMD.

Source: Shruti Dighe, Jiwei Zhao, Lyn Steffen, J A Mares, Stacy M Meuer, Barbara E K Klein, Ronald Klein, Amy E Millen. “Diet patterns and the incidence of age-related macular degeneration in the Atherosclerosis Risk in Communities (ARIC) study,” Ophthalmology (2019): Volume 104, Issue 8.

A phytochemical-rich diet may explain the absence of age-related decline in visual acuity of Amazonian hunter-gatherers in Ecuador *

Abstract

Myopia is absent in undisturbed hunter-gatherers but ubiquitous in modern populations. The link between dietary phytochemicals and eye health is well established, although transition away from a wild diet has reduced phytochemical variety. We hypothesized that when larger quantities and greater variety of wild, seasonal phytochemicals are consumed in a food system, there will be a reduced prevalence of degenerative-based eye disease as measured by visual acuity. We compared food systems and visual acuity across isolated Amazonian Kawymeno Waorani hunter-gatherers and neighboring Kichwa subsistence agrarians, using dietary surveys, dietary pattern observation, and Snellen Illiterate E visual acuity examinations. Hunter-gatherers consumed more food species (130 vs. 63) and more wild plants (80 vs. 4) including 76 wild fruits, thereby obtaining larger variety and quantity of phytochemicals than agrarians. Visual acuity was inversely related to age only in agrarians (r = -.846, P < .001). As hypothesized, when stratified by age (<40 and ≥ 40 years), Mann-Whitney U tests revealed that hunter-gatherers maintained high visual acuity throughout life, whereas agrarian visual acuity declined (P values < .001); visual acuity of younger participants was high across the board, however, did not differ between groups (P > .05). This unusual absence of juvenile-onset vision problems may be related to local, organic, whole food diets of subsistence food systems isolated from modern food production. Our results suggest that intake of a wider variety of plant foods supplying necessary phytochemicals for eye health may help maintain visual acuity and prevent degenerative eye conditions as humans age.

Source: London, Douglas S. “A phytochemical-rich diet may explain the absence of age-related decline in visual acuity of Amazonian hunter-gatherers in Ecuador,” Nutrition Research (2015): 35(2):107-17.

Modulatory Effect of Carotenoid Supplement Constituting Lutein and Zeaxanthin (10:1) on Anti-oxidant Enzymes and Macular Pigments Level in Rats *

Background: Human eye is constantly exposed to different wavelengths and intensities of light. Oxidative stress results in distinct changes to retinal organs and tissues. Macular pigments (lutein and zeaxanthin), present in the central macular region, provide protection from photodamages by absorption of high energy blue light and also by virtue of their anti-oxidant activity. Ocular phototoxicity is thus prevented by our efficient anti-oxidant system, in both young and old. One of the best commercial sources of pure lutein and zeaxanthin is Marigold flowers.

Objective: In the present study, oil-soluble dietary carotenoid supplement constituting lutein and zeaxanthin in the ratio of 10:1 was evaluated for its modulatory effect on anti-oxidant enzymes and macular pigments in the serum and macula of the Swiss albino rats.

Materials and Methods: Male Swiss albino rats were treated with carotenoid supplement constituting lutein and trans-Zeaxanthin (10:1) at two different doses daily, under standard experimental conditions for 42 days. End of the treatment, serum and macula were collected and used for measurement of lutein and zeaxanthin levels along with anti-oxidant parameters.

Statistical Analysis Used: Statistical differences were assessed by analysis of variance (ANOVA) followed by Dunnet’s test. P < 0.05 was considered statistically significant. All the results were expressed as mean ± standard deviation.

Results: The supplement exhibited significant elevation of anti-oxidant enzyme levels in treated animals in dose-dependent manner. Concomitantly, the total anti-oxidant capacity has also been found to show similar increment at the end of the study period. This study revealed significant expression of the two macular pigments investigated.

Conclusions: Our study, therefore, provides a strong claim for the anti-oxidant effect of the oil-soluble dietary carotenoid supplement, and thus substantiates its use in the prevention of phototoxic damage to the eye on long-term supplementation.

Source: Jayashree Madhavan, Sundaram Chandrasekharan, MK Priya, Ashok Godavarthi. “Modulatory Effect of Carotenoid Supplement Constituting Lutein and Zeaxanthin (10:1) on Anti-oxidant Enzymes and Macular Pigments Level in Rats,” Pharmacognosy (2018): 14(54): 268–274.

Interrelationships Between Maternal Carotenoid Status and Newborn Infant Macular Pigment Optical Density and Carotenoid Status *

Abstract

Purpose: Deposition of the macular pigment carotenoids lutein and zeaxanthin in the human retina occurs early in life. In this study, we examined the interrelationships of maternal carotenoid status and newborn infant macular pigment levels and systemic carotenoid status. As a secondary measure, we also evaluated the effects of intrauterine growth restriction (IUGR) on carotenoid status in term newborn infants.

Methods: We measured mother and infant skin carotenoids using resonance Raman spectroscopy (RRS), serum carotenoids by HPLC, and mother breast milk carotenoids by HPLC. We measured infant macular pigment levels using noninvasive blue light reflectometry.

Results: We enrolled 30 healthy term infants, their mothers, and 10 IUGR infants and their mothers. A subset of 16 infants was imaged for macular pigment optical density (MPOD). Infant serum zeaxanthin levels correlated with MPOD (r = 0.68, P = 0.007). Mother serum zeaxanthin levels correlated with infant MPOD (r = 0.59, P = 0.032). Infant and mother serum lutein did not correlate with MPOD. Mother–infant correlations were found for total serum carotenoids (r = 0.42, P = 0.020) and skin carotenoids (r = 0.48, P = 0.001). No difference was seen between IUGR infants and controls in total serum or skin carotenoids. Mothers of IUGR infants had lower total serum carotenoids (P = 0.019) and breast milk carotenoids than controls (P = 0.006).

Conclusions: Our findings suggest that maternal zeaxanthin status may play a more important role than lutein status in macular pigment deposition in utero. Controlled trials are needed to determine whether maternal zeaxanthin prenatal supplementation can raise infant macular pigment levels and/or improve ocular function.

Source: Bradley S. Henriksen, Gary Chan, Robert O. Hoffman, Mohsen Sharifzadeh, Igor V. Ermakov, Werner Gellermann, Paul S. Bernstein. “Interrelationships Between Maternal Carotenoid Status and Newborn Infant Macular Pigment Optical Density and Carotenoid Status”

Clinical and Epidemiologic Research; Investigative Ophthalmology & Visual Science (2013): Vol.54, 5568-5578.

Lutein and Zeaxanthin Isomers in Eye Health and Disease *

Abstract

Current evidence suggests lutein and its isomers play important roles in ocular development in utero and throughout the life span, in vision performance in young and later adulthood, and in lowering risk for the development of common age-related eye diseases in older age. These xanthophyll (oxygen-containing) carotenoids are found in a wide variety of vegetables and fruits, and they are present in especially high concentrations in leafy green vegetables. Additionally, egg yolks and human milk appear to be bioavailable sources. The prevalence of lutein, zeaxanthin, and meso-zeaxanthin in supplements is increasing. Setting optimal and safe ranges of intake requires additional research, particularly in pregnant and lactating women. Accumulating evidence about variable interindividual response to dietary intake of these carotenoids, based on genetic or metabolic influences, suggests that there may be subgroups that benefit from higher levels of intake and/or alternate strategies to improve lutein and zeaxanthin status.

Source: Julie Mares. “Lutein and Zeaxanthin Isomers in Eye Health and Disease” Annual Review of Nutrition (2016): 36: 571–602.

Macular pigment response to a supplement containing meso-zeaxanthin, lutein and zeaxanthin *

Background: Age-related macular degeneration (AMD) is a disease with multiple risk factors, many of which appear to involve oxidative stress. Macular pigment, with its antioxidant and light-screening properties, is thought to be protective against AMD. A result has been the appearance of dietary supplements containing the macular carotenoids, lutein and zeaxanthin. More recently, a supplement has been marketed containing, in addition, the third major carotenoid of the macular pigment, meso-zeaxanthin. The purpose of the study was to determine the effectiveness of such a supplement in raising macular pigment density in human subjects.

Methods: A 120 day supplementation study was conducted in which 10 subjects were given gel-caps that provided 20 mg/day of predominantly meso-zeaxanthin, with smaller amounts of lutein and zeaxanthin. A second group of 9 subjects were given gel caps containing a placebo for the same 120 day period. Prior to and during the supplementation period, blood serum samples were analyzed by high performance liquid chromatography for carotenoid content. Similarly, macular pigment optical density was measured by heterochromatic flicker photometry. Differences in response between the supplementation and placebo groups were tested for significance using a student’s t-test.

Results: During supplementation with the carotenoids, blood samples revealed the presence of all three carotenoids. Macular pigment optical density, measured at 460 nm, rose at an average rate of 0.59 ± 0.79 milli-absorbance unit/day in the 10 supplemented subjects. This was significantly different from the placebo group (9 subjects) for whom the average rate was -0.17 ± 0.42 milli-absorbance units/day.

Conclusion: We have shown for the first time that meso-zeaxanthin is absorbed into the serum following ingestion. The data indicate that a supplement containing predominantly meso-zeaxanthin is generally effective at raising macular pigment density, and may turn out to be a useful addition to the defenses against AMD.

Source: Bone, Richard A. et al. “Macular pigment response to a supplement containing meso-zeaxanthin, lutein and zeaxanthin,” Nutrition & Metabolism (2007): 4(12).

Enrichment of Macular Pigment Enhances Contrast Sensitivity in Subjects Free of Retinal Disease: Central Retinal Enrichment Supplementation Trials – Report *

Abstract

Purpose: The high-performance visual function associated with central vision is mediated by the macula (the central retina), which accumulates three diet-derived pigments (the carotenoids lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]). Our study sought to investigate the impact on visual function, including contrast sensitivity (CS), of supplementation with these naturally occurring carotenoids, in individuals with low retinal concentrations.

Methods: Subjects consumed daily a formulation containing 10 mg L, 2 mg Z, and 10 mg MZ (active group; n = 53) or placebo (n = 52) for a period of 12 months. Study visits were at baseline, 3, 6, and 12 months. Contrast sensitivity at 6 cycles per degree (cpd) was the primary outcome measure (POM). Secondary outcome measures included CS at other spatial frequencies, best-corrected visual acuity (BCVA), glare disability, photostress recovery, and light scatter. Macular pigment optical density (MPOD) was measured using dual-wavelength autofluorescence, and serum carotenoid concentrations were analyzed using high performance liquid chromatography (HPLC).

Results: Compared to placebo, statistically significant improvements from baseline CS were detected at 6 (P = 0.002) and 1.2 (P = 0.004) cpd in the active group. Additionally, improvements in CS were commensurate with the observed increases in retinal concentrations of these carotenoids (r = 0.342, P = 0.002 at 6 cpd).

Conclusions: These results indicate that dietary fortification with the macular carotenoids can have meaningful effects on visual function.

Source: Nolan, John M. et al. “Enrichment of Macular Pigment Enhances Contrast Sensitivity in Subjects Free of Retinal Disease: Central Retinal Enrichment Supplementation Trials – Report 1,” Investigative Ophthalmology & Visual Science (2016): 57(7), 3429-3439.

Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial *

Abstract

Purpose: To examine the effects of lutein and zeaxanthin supplementation on retinal function using multifocal electroretinograms (mfERG) in patients with early age-related macular degeneration (AMD).

Design: Randomized, double-masked, placebo-controlled trial.

Methods: One hundred eight subjects with early AMD were randomly assigned to receive 10 mg/d lutein (n = 27), 20 mg/d lutein (n = 27), 10 mg/d lutein plus 10 mg/d zeaxanthin (n = 27), or placebo (n = 27) for 48 weeks. Thirty-six age-matched controls without AMD were also enrolled to compare baseline data with early AMD patients. MfERG responses and macular pigment optical densities (MPODs) were recorded and analyzed at baseline and at 24 and 48 weeks.

Results: There were significant reductions in N1P1 response densities in ring 1 to ring 3 in early AMD patients compared with the controls (P < .05), whereas neither N1P1 response densities in ring 4 to ring 6 nor P1 peak latencies significantly changed. After 48-week supplementation, the N1P1 response densities showed significant increases in ring 1 for the 20 mg lutein group and for the lutein and zeaxanthin group, and in ring 2 for the 20 mg lutein group. The increases in MPOD related positively to the increases in N1P1 response density in ring 1 and ring 2 for nearly all active treatment groups. N1P1 response densities in ring 3 to ring 6 or P1 peak latencies in all rings did not change significantly in any group.

Conclusion: Early functional abnormalities of the central retina in the early AMD patients could be improved by lutein and zeaxanthin supplementation. These improvements may be potentially attributed to the elevations in MPOD.

Source: Ma, Le et al. “Improvement of Retinal Function in Early Age-Related Macular Degeneration After Lutein and Zeaxanthin Supplementation: A Randomized, Double-Masked, Placebo-Controlled Trial,” American Journal of Ophthalmology (2012): 154(4): 625-634.

Randomized, double-blind, placebo-controlled study of zeaxanthin and visual function in patients with atrophic age-related macular degeneration: the Zeaxanthin and Visual Function Study (ZVF) FDA IND #78, 973 *

Abstract

Background: The purpose of this study is to evaluate whether dietary supplementation with the carotenoid zeaxanthin (Zx) raises macula pigment optical density (MPOD) and has unique visual benefits for patients with early atrophic macular degeneration having visual symptoms but lower-risk National Institute of Health/National Eye Institute/Age-Related Eye Disease Study characteristics.

Methods: This was a 1-year, n = 60 (57 men, 3 women), 4-visit, intention-to-treat, prospective, randomized controlled clinical trial of patients (74.9 years, standard deviation [SD] 10) with mild-to-moderate age-related macular degeneration (AMD) randomly assigned to 1 of 2 dietary supplement carotenoid pigment intervention groups: 8 mg Zx (n = 25) and 8 mg Zx plus 9 mg lutein (L) (n = 25) or 9 mg L (“Faux Placebo,” control group, n = 10). Analysis was by Bartlett’s test for equal variance, 3-way repeated factors analysis of variance, independent t test (P < 0.05) for variance and between/within group differences, and post-hoc Scheffé’s tests. Estimated foveal heterochromic flicker photometry, 1° macular pigment optical density (MPOD QuantifEye(®)), low- and high-contrast visual acuity, foveal shape discrimination (Retina Foundation of the Southwest), 10° yellow kinetic visual fields (KVF), glare recovery, contrast sensitivity function (CSF), and 6° blue cone ChromaTest(®) color thresholds were obtained serially at 4, 8, and 12 months.

Results: Ninety percent of subjects completed ≥ 2 visits with an initial Age-Related Eye Disease Study report #18 retinopathy score of 1.4 (1.0 SD)/4.0 and pill intake compliance of 96% with no adverse effects. There were no intergroup differences in 3 major AMD risk factors: age, smoking, and body mass index as well as disease duration and Visual Function Questionnaire 25 composite score differences. Randomization resulted in equal MPOD variance and MPOD increasing in each of the 3 groups from 0.33 density units (du) (0.17 SD) baseline to 0.51 du (0.18 SD) at 12 m, (P = 0.03), but no between-group differences (Analysis of Variance; P = 0.47). In the Zx group, detailed high-contrast visual acuity improved by 1.5 lines, Retina Foundation of the Southwest shape discrimination sharpened from 0.97 to 0.57 (P = 0.06, 1-tail), and a larger percentage of Zx patients experienced clearing of their KVF central scotomas (P = 0.057). The “Faux Placebo” L group was superior in terms of low-contrast visual acuity, CSF, and glare recovery, whereas Zx showed a trend toward significance.

Conclusion: In older male patients with AMD, Zx-induced foveal MPOD elevation mirrored that of L and provided complementary distinct visual benefits by improving foveal cone-based visual parameters, whereas L enhanced those parameters associated with gross detailed rod-based vision, with considerable overlap between the 2 carotenoids. The equally dosed (atypical dietary ratio) Zx plus L group fared worse in terms of raising MPOD, presumably because of duodenal, hepatic-lipoprotein or retinal carotenoid competition. These results make biological sense based on retinal distribution and Zx foveal predominance.

Source: Richer, S. et al., “Randomized, double-blind, placebo-controlled study of zeaxanthin and visual function in patients with atrophic age-related macular degeneration: The Zeaxanthin and Visual Function Study,” Optometry (2011): 82(11): 667-680.

Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up *

Abstract

Importance  Despite strong biological plausibility, evidence from epidemiologic studies and clinical trials on the relations between intakes of lutein and zeaxanthin and age-related macular degeneration (AMD) has been inconsistent. The roles of other carotenoids are less thoroughly investigated.

Objective  To investigate the associations between intakes of carotenoids and AMD.

Design, Setting, and Participants  Prospective cohort study, with cohorts from the Nurses’ Health Study and the Health Professionals Follow-up Study in the United States. A total of 63 443 women and 38 603 men were followed up, from 1984 until May 31, 2010, in the Nurses’ Health Study and from 1986 until January 31, 2010, in the Health Professionals Follow-up Study. All participants were aged 50 years or older and were free of diagnosed AMD, diabetes mellitus, cardiovascular disease, and cancer at baseline.

Main Outcomes and Measures  Predicted plasma carotenoid scores were computed directly from food intake, assessed by repeated food frequency questionnaires at baseline and follow-up, using validated regression models to account for bioavailability and reporting validity of different foods, and associations between predicted plasma carotenoid scores and AMD were determined.

Results  We confirmed 1361 incident intermediate and 1118 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse by medical record review. Comparing extreme quintiles of predicted plasma lutein/zeaxanthin score, we found a risk reduction for advanced AMD of about 40% in both women and men (pooled relative risk comparing extreme quintiles = 0.59; 95% CI, 0.48-0.73; P for trend < .001). Predicted plasma carotenoid scores for other carotenoids, including β-cryptoxanthin, α-carotene, and β-carotene, were associated with a 25% to 35% lower risk of advanced AMD when comparing extreme quintiles. The relative risk comparing extreme quintiles for the predicted plasma total carotenoid index was 0.65 (95% CI, 0.53-0.80; P for trend < .001). We did not identify any associations of carotenoids, either as predicted plasma score or calculated intake, with intermediate AMD.

Conclusions and Relevance  Higher intake of bioavailable lutein/zeaxanthin is associated with a long-term reduced risk of advanced AMD. Given that some other carotenoids are also associated with a lower risk, a public health strategy aimed at increasing dietary consumption of a wide variety of fruits and vegetables rich in carotenoids may reduce the incidence of advanced AMD.

Source: Juan Wu, MS, Eunyoung Cho, ScD, Walter C. Willett, MD, MPH, DrPH, et al Srinivas M. Sastry, MD, MPH, Debra A. Schaumberg, ScD, OD, MPH. “Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up” Ophthalmology (2015):133(12):1415-1424.

Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial) *

Abstract

Background: Age-related macular degeneration (ARMD) is the leading cause of vision loss in aging Westem societies. The objective of the lutein antioxidant supplementation trial (LAST) is to determine whether nutritional supplementation with lutein or lutein together with antioxidants, vitamins, and minerals, improves visual function and symptoms in atrophic ARMD.

Methods: The study was a prospective, 12-month, randomized, double-masked, placebo-controlled trial conducted at an urban midwestern Veterans Administration Hospital from August 1999 to May 2001. Ninety patients with atrophic ARMD were referred by ophthalmologists at two Chicago-area veterans medical facilities. Patients in Group 1 received lutein 10 mg (L); in Group 2, a lutein 10 mg/antioxidants/vitamins and minerals broad spectrum supplementation formula (L/A); and in Group 3, a maltodextrin placebo (P) over 12 months.

Results: In Groups 1 L and 2 L/A, mean eye macular pigment optical density increased approximately 0.09 log units from baseline, Snellen equivalent visual acuity improved 5.4 letters for Group 1 L and 3.5 letters for Group 2 L/A, and contrast sensitivity improved. There was a net subjective improvement in Amsler grid in Group 1 L. VFO-14 questionnaires conceming subjective glare recovery were nearly significant at 4 months for Group 2 L/A. Patients who received the placebo (Group 3) had no significant changes in any of the measured findings.

Conclusion: In this study, visual function is improved with lutein alone or lutein together with other nutrients. Further studies are needed with more patients, of both genders, and for longer periods of time to assess long-term effects of lutein or lutein together with a broad spectrum of antioxidants, vitamins, and minerals in the treatment of atrophic age-related macular degeneration.

Source: Richer, S et al., “Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial),” Optometry (2004): 75(4), 216-230.

Macular Carotenoid Supplementation Improves Visual Performance, Sleep Quality, and Adverse Physical Symptoms in Those with High Screen Time Exposure *

Abstract

The dramatic rise in the use of smartphones, tablets, and laptop computers over the past decade has raised concerns about potentially deleterious health effects of increased “screen time” (ST) and associated short-wavelength (blue) light exposure. We determined baseline associations and effects of 6 months’ supplementation with the macular carotenoids (MC) lutein, zeaxanthin, and mesozeaxanthin on the blue-absorbing macular pigment (MP) and measures of sleep quality, visual performance, and physical indicators of excessive ST. Forty-eight healthy young adults with at least 6 h of daily near-field ST exposure participated in this placebo-controlled trial. Visual performance measures included contrast sensitivity, critical flicker fusion, disability glare, and photostress recovery. Physical indicators of excessive screen time and sleep quality were assessed via questionnaire. MP optical density (MPOD) was assessed via heterochromatic flicker photometry. At baseline, MPOD was correlated significantly with all visual performance measures (p < 0.05 for all). MC supplementation (24 mg daily) yielded significant improvement in MPOD, overall sleep quality, headache frequency, eye strain, eye fatigue, and all visual performance measures, versus placebo (p < 0.05 for all). Increased MPOD significantly improves visual performance and, in turn, improves several undesirable physical outcomes associated with excessive ST. The improvement in sleep quality was not directly related to increases in MPOD, and may be due to systemic reduction in oxidative stress and inflammation.

Source: Stringham, J.M. et al. “Macular Carotenoid Supplementation Improves Visual Performance, Sleep Quality, and Adverse Physical Symptoms in Those with High Screen Time Exposure.” Foods (2017): 6 (7), 47.

The Photobiology of Lutein and Zeaxanthin in the Eye *

Lutein and zeaxanthin are antioxidants found in the human retina and macula. Recent clinical trials have determined that age- and diet-related loss of lutein and zeaxanthin enhances phototoxic damage to the human eye and that supplementation of these carotenoids has a protective effect against photoinduced damage to the lens and the retina. Two of the major mechanisms of protection offered by lutein and zeaxanthin against age-related blue light damage are the quenching of singlet oxygen and other reactive oxygen species and the absorption of blue light. Determining the specific reactive intermediate(s) produced by a particular phototoxic ocular chromophore not only defines the mechanism of toxicity but can also later be used as a tool to prevent damage.

Source: Joan E. Roberts, Jessica Dennison. “The Photobiology of Lutein and Zeaxanthin in the Eye” Ophthalmology (2015): 687173.

Oral Lutein Supplementation Enhances Macular Pigment Density and Contrast Sensitivity but Not in Combination With Polyunsaturated Fatty Acids *

Abstract

Purpose: It has been shown that lutein and zeaxanthin accumulate in the macula where they enhance contrast sensitivity and may reduce the risk of progression to advanced age-related macular degeneration (AMD). Furthermore, omega-3 long-chain polyunsaturated fatty acids (PUFA) might further reduce this risk. However, controversy exists regarding whether PUFA may reduce the bioavailability of lutein.

Methods: This was a prospective 12-month, randomized, open label study evaluating the effect of supplementation with lutein, other antioxidants, and minerals on contrast sensitivity (CS) and macular pigment optical density (MPOD) in patients with age-related maculopathy. A total of 79 patients were randomized to either lutein (10 mg) and antioxidant supplement or lutein and antioxidant supplement in combination with PUFA. Patients received supplementation for a period of 6 months and were followed for a total of 12 months.

Results: Serum lutein and zeaxanthin increased significantly by the first follow-up visit at 1 month, and remained elevated throughout the intervention period of 6 months in the lutein-only group but not in the lutein+PUFA group. Macular pigment optical density and CS increased significantly in the lutein-only group (P < 0.005) but not in the lutein+PUFA group (P = 0.059) compared to baseline. Best-corrected visual acuity remained unchanged during the entire study period in both groups.

Conclusions: Addition of PUFA may reduce the bioavailability of lutein and therefore lessen the beneficial effect on macular pigment and CS. This needs to be considered when prescribing lutein supplements to patients with low lutein levels. (ClinicalTrials.gov number, NCT00563979.).

Source: Ute E. K. Wolf-Schnurrbusch, Martin S Zinkernagel, Marion R Munk, Andreas Ebneter, Sebastian Wolf. “Oral Lutein Supplementation Enhances Macular Pigment Density and Contrast Sensitivity but Not in Combination With Polyunsaturated Fatty Acids” Investigative Ophthalmology and Visual Science (2015): 56(13):8069-74.

Macular carotenoid supplementation improves disability glare performance and dynamics of photostress recovery *

Abstract

Background: The so-called macular carotenoids (MC) lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) comprise the diet-derived macular pigment (MP). The purpose of this study was to determine effects of MC supplementation on the optical density of MP (MPOD), repeated-exposure photostress recovery (PSR), and disability glare (DG) thresholds.

Methods This was a double-blind, placebo-controlled trial. Fifty-nine young (mean age = 21.7), healthy volunteers participated in this study. Subjects supplemented their daily diet with either 10 mg L + 2 mg total Z (1 mg Z + 1 mg MZ; n = 24), 20 mg L + 4 mg total Z (2 mg Z + 2 mg MZ; n = 25), or placebo (n = 10) for 12 months. The primary outcome was a composite measure of visual performance in glare, defined by change in DG and PSR. Secondary outcomes included MPOD and visual fatigue. The primary endpoint for outcomes was 12 months. MPOD was assessed with customized heterochromatic flicker photometry. PSR times for an 8 cycle /degree, 15 % contrast Gabor patch target were determined after each of five successive exposures to intense LED lights. DG threshold was defined as the intensity of a ring of lights through which subjects were able to maintain visibility of the aforementioned target. Measures of all parameters were conducted at baseline, 6 months, and 12 months. Repeated-measures ANOVA, and Pearson product-moment correlations were used to determine statistically significant correlations, and changes within and between groups.

Results MPOD for subjects in both supplementation groups increased significantly versus placebo at both 6- and 12-month visits (p < 0.001 for all). Additionally, PSR times and DG thresholds improved significantly from baseline compared to placebo at 6- and 12-month visits (p < 0.001 for all). At baseline, MPOD was significantly related to both DG thresholds (r = 0.444; p = 0.0021) and PSR times (r = -0.56; p < 0.001). As a function of MPOD, the repeated-exposure PSR curves became more asymptotic, as opposed to linear. The change in subjects’ DG thresholds were significantly related to changes in PSR times across the study period (r = -0.534; p < 0.001).

Conclusions Increases in MPOD lead to significant improvements in PSR times and DG thresholds. The asymptotic shape of the repeated-exposure PSR curves suggests that increases in MPOD produce more consistent steady-state visual performance in bright light conditions. The mechanism for this effect may involve both the optical filtering and biochemical (antioxidant) properties of MP.

Source: Stringham, J.M., O’Brien, K.J. & Stringham, N.T. “Macular carotenoid supplementation improves disability glare performance and dynamics of photostress recovery” Eye and Vision  (2016): Vol 3, article 30.

Bilberry (anthocyanosides)

Effects of black current anthocyanoside intake on dark adaptation and VDT work-induced transient refractive alteration in healthy humans *

Abstract

The effects of oral intake of a black currant anthocyanosides (BCA) concentrate on dark adaptation, video display terminal (VDT) work-induced transient refractive alteration, and subjective asthenopia symptoms (visual fatigue) were examined in a double-blind, placebo-controlled, crossover study with healthy human subjects. In a dark adaptation study, intake of BCA at three dose levels (12.5-, 20-, and 50 mg/subject, n = 12) appeared to bring about dose-dependent lowering of the dark adaptation threshold. Statistical analysis comparing the values before and after intake indicated there was a significant difference at the 50 mg dose (p= 0. 011). Comparing the refraction values for the dominant eye, BCA intake (50 mg/subject, n = 21) resulted in no decrease in the average value after the visual task; whereas, a placebo trial resulted in a large decrease in the average value, resulting in borderline significance (p = 0.064). In the assessment of subjective asthenopia symptoms by questionnaire, significant improvement was recognized on the basis of the statements regarding the eye and lower back after BCA intake.

Source: Nakaishi H, Matsumoto H, Tominaga S, Hirayama M. “Effects of black currant anthocyanoside intake on dark adaptation and VDT work-induced transient refractive alteration in healthy humans,” Alternative Medicine Review (2000): 5(6):553-62.

Preventive medical treatment of senile cataract with vitamin E and anthocyanosides: clinical evaluation *

Abstracts

Bilberry extract (180 mg twice daily of a 25-percent anthocyanoside extract) was given with vitamin E, demonstrated arrested cataract formation in 48 of 50 patients with senile cortical cataracts.   (Bravetti, 1989)

Effect of fermented bilberry extracts on visual outcomes in eyes with myopia: a prospective, randomized, placebo-controlled study.  (Kamiya et al., 2013)

PURPOSE:  To investigate clinically the effects of yeast-fermented bilberry extract on visual outcomes in myopic eyes. METHODS:  In a prospective, randomized, placebo-controlled, cross-over study, we examined 30 eyes of 30 middle-aged healthy volunteers (mean age±standard deviation, 39.5±7.2 years) with myopia [manifest spherical equivalent, -2.40±1.88 diopters (D)], who were randomly assigned to 1 of 2 oral regimens: fermented bilberry extract (400 mg/day) or placebo. We quantitatively assessed visual acuity, refraction, pupil constriction rate, accommodation, and mesopic contrast sensitivity (CS), before and 1 month after treatment. Only the right eyes were tested. The amplitude of accommodation and CS were measured with an accommodometer (D’ACOMO; WOC) and a CS unit (VCTS-6500; Vistech), respectively. From the CS, the area under the log contrast sensitivity function (AULCSF) was calculated. RESULTS:  The mean amplitude of accommodation increased significantly, from 4.62±1.88 D before treatment, to 5.33±2.03 D after treatment in the study group (Wilcoxon signed-rank test, P=0.002). Moreover, the mesopic AULCSF was significantly increased, from 1.04±0.16 before, to 1.13±0.17 after, treatment (P=0.009). However, we found no significant changes in accommodation or AULCSF in the control group (P>0.05), or any significant changes in any other parameters in either group (P>0.05).

CONCLUSIONS: The present data show that fermented bilberry extract is effective in causing increases in subjective accommodation and in mesopic CS in myopic eyes.

Source: Bravetti G. “Preventive medical treatment of senile cataract with vitamin E and anthocyanosides: clinical evaluation” Ann Otall Clin Ocul 1989;115:109.

Clinical Overview: Bilberry Vaccinium myrtillus L. *

OVERVIEW Bilberry is the name of a small European blueberry. Dietary supplements made from the standardized extract of bilberry have become popular in the U.S. over the past decade. Sales in the mainstream retail markets ranked 13th of all herbs in 2000. The standardized, concentrated extract of bilberry fruit is used by consumers primarily for ocular, microcirculatory and vascularrelated disorders.

PRIMARY USES • Retinopathy, hypertensive • Retinopathy, diabetic • Peripheral vascular disorders, blood purpuras • Venous insufficiencies, varicose veins, capillary fragility, kidney capillary fragility • Diarrhea (the bilberry fruits, not the standardized extracts) OTHER

POTENTIAL USES • Blindness, night and day • Cataracts • Macular degeneration • Retinitis pigmentosa • Retinopathy, hemorrhagic • Dysmenorrhea • Reduction of surgical bleeding

PHARMACOLOGICAL ACTIONS Astringent; antiplatelet aggregation; collagen-stabilizing activity; decreased vascular permeability associated with injury.

DOSAGE AND ADMINISTRATION Ranges from 160−480 mg daily depending on the conditions being treated. Therapeutic benefits appear to take effect in 4–8 weeks. DRIED, RIPE FRUIT: 20–60 g daily (4–8 g with water, several times daily). INFUSION/DECOCTION: 20–60 g daily. COLD MACERATE: 20–60 g daily. GARGLE: Mouthwash containing 10% decoction. FLUID EXTRACT: 2–4 ml, 3 times daily [1:1 (g/ml)]. FOR DIARRHEA: Crude preparations (nonstandardized) for no more than 3−4 days. DRY STANDARDIZED EXTRACT: (25% anthocyanidins) 80–160 mg, 3 times daily. CONTRAINDICATIONS None known. PREGNANCY AND LACTATION: No known restrictions. ADVERSE EFFECTS None known (at therapeutic dosages). DRUG INTERACTIONS Pharmacological studies suggest that very high doses (>170 mg anthocyanins per day for 30–60 days) may interact with warfarin or other antiplatelet drugs. Bilberry (form unstated) reportedly may reduce insulin requirements; therefore, conventional antidiabetic therapy would need close monitoring or dosage adjustment. Bilberry Vaccinium myrtillus L. [Fam. Ericaceae] Clinical Overview Bilberry Clinical Overview The ABC Clinical Guide to Her

CLINICAL REVIEW Fifteen clinical studies on bilberry that included a total of 694 participants were reviewed. All but one of the studies demonstrated positive effects for indications, including various ocular conditions (night/day vision and retinopathy), and vascular conditions, including venous insufficiencies and micro- and macroperipheral circulation. Two double-blind, placebo-controlled (DB, PC) studies focused on retinopathy and confirmed results of two earlier open studies. One DB, PC study on nighttime vision confirmed preliminary findings of five previous open studies. A recent DB, PC, crossover study failed to find that bilberry extract (25% anthocyanosides) had an effect on night vision or night contrast sensitivity. One DB, PC study conducted on peripheral vascular disorder concluded positive results for Raynaud’s sufferers. Another DB, PC study on chronic dysmenorrhea was positive and further supports pharmacological findings. One single-blind (SB), PC study on venous insufficiencies in 60 participants further supported the findings of four similar studies, including two open studies and two using pregnant subjects. Bleeding was investigated in a SB, PC study finding bilberry reduced intra- and postoperative bleeding and prevented subsequent hemorrhaging. Another study focused on bleeding associated with intrauterine devices.

Source: “Clinical Overview: Bilberry Vaccinium myrtillus L.” ABC Clinical Guide to Herbs (2003).

Stimulatory Effect of Cyanidin 3-Glycosides on the Regeneration of Rhodopsin *

Abstract

Anthocyanins have been suggested to improve visual functions. This study examined the effect of four anthocyanins in black currant fruits on the regeneration of rhodopsin using frog rod outer segment (ROS) membranes. Cyanidin 3-glycosides, glucoside and rutinoside, stimulated the regeneration, but the corresponding delphinidins showed no significant effect. The formation of a regeneration intermediate was suggested to be accelerated by cyanidin 3-rutinoside. Their effects on the cGMP-phosphodiesterase activity in the ROS membranes were also investigated but found to be negligible. It was concluded that the major effect of anthocyanins in rod photoreceptors is on the regeneration of rhodopsin.

Source: Matsumoto H, Nakamura Y, Tachibanaki S, Kawamura S, Hirayama M. “Stimulatory effect of cyanidin 3-glycosides on the regeneration of rhodopsin,” Journal of Agricultural and Food Chemistry (2003): 51(12):3560-3563.

Bilberry (Vaccinium myrtillus L.) *

Introduction

Bilberry (Vaccinium myrtillus L.) is one of the richest natural sources of anthocyanins. These polyphenolic components give bilberry its blue/black color and high antioxidant content, and they are believed to be the key bioactives responsible for the many reported health benefits of bilberry and other berry fruits. Although bilberry is promoted most commonly for improving vision, it has been reported to lower blood glucose, to have anti-inflammatory and lipid-lowering effects, and to promote antioxidant defense and lower oxidative stress. Therefore, bilberry is of potential value in the treatment or prevention of conditions associated with inflammation, dyslipidemia, hyperglycemia or increased oxidative stress, cardiovascular disease (CVD), cancer, diabetes, and dementia and other age-related diseases. There are also reports that bilberry has antimicrobial activity. In this chapter, bilberry and its components and characteristics are described, and evidence for the health benefits of bilberry is presented and

Source: Chu W, Cheung SCM, Lau RAW, et al. “Bilberry – Vaccinium myrtillus L.” Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition (2011): Chapter 4.

Ginkgo biloba Extract and Bilberry Anthocyanins Improve Visual Function in Patients with Normal Tension Glaucoma *

Ginkgo biloba extract (GBE) and anthocyanins are considered beneficial for various vascular diseases. This study was performed to evaluate the effect of GBE and anthocyanins on visual function in patients with normal tension glaucoma (NTG) based on the vascular theory of mechanisms of glaucomatous optic nerve damage. Retrospective analysis was carried out by a chart review of 332 subjects (209 men and 123 women) who were treated with anthocyanins (n=132), GBE (n=103), or no medication (control, n=97). Humphrey Visual Field (HVF) test, logarithm of the minimal angle of resolution best-corrected visual acuity (logMAR BCVA), intraocular pressure, blood pressure, and fasting blood glucose were determined before and after treatment. Complete ocular and systemic examinations were performed. The mean follow-up duration was 23.82±9.84 (range, 12–59) months; the mean anthocyanin treatment duration was 24.32±10.43 (range, 6–53) months, and the mean GBE treatment duration was 23.81±10.36 months (range, 6–59) months. After anthocyanin treatment, the mean BCVA for all eyes improved from 0.16 (±0.34) to 0.11 (±0.18) logMAR units (P=.008), and HVF mean deviation improved from −6.44 (±7.05) to −5.34 (±6.42) (P=.001). After GBE treatment, HVF mean deviation improved from −5.25 (±6.13) to −4.31 (±5.60) (P=.002). A generalized linear model demonstrated that the final BCVA was not affected by demographic differences among the groups. These results suggest that anthocyanins and GBE may be helpful in improving visual function in some individuals with NTG.

Source: Seong Hee Shim, Joon Mo Kim, Chul Young Choi, Chan Yun Kim, Ki Ho Park. “Ginkgo biloba Extract and Bilberry Anthocyanins Improve Visual Function in Patients with Normal Tension Glaucoma” Journal of Medicinal Food (2012): 15(9): 818–823.

Vitamin C, E, Zinc, & Copper

The Age-Related Eye Disease Study (AREDS): Design Implications AREDS Report No. 1 *

The Age-Related Eye Disease Study (AREDS) was initially conceived as a long-term multicenter, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. Data on progression rates and risk factors from the study will increase understanding of the clinical course of both conditions, generate hypotheses about etiology, and aid in the design of clinical trials of potential interventions. In addition to collecting natural history data, AREDS includes a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacologic doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. Important design issues for the clinical trials include: defining cataract and AMD, estimating event rates, determining the type and dosage of vitamins and minerals to be tested for each condition, and identifying the parameters necessary for monitoring safety and efficacy. This paper describes the AREDS design, including the study rationale and operational structure, and the approach adopted to combine, for two diseases, clinical trials with a natural history study.

Source: Age-Related Eye Disease Study Research Group. “The Age-Related Eye Disease Study (AREDS): design implications. AREDS report no. 1” Control Clinical Trials (1999): 20(6):573-600.

Vitamin E Inadequacy in Humans: Causes and Consequences *

It is estimated that >90% of Americans do not consume sufficient dietary vitamin E, as α-tocopherol, to meet estimated average requirements. What are the adverse consequences of inadequate dietary α-tocopherol intakes? This review discusses health aspects where inadequate vitamin E status is detrimental and additional vitamin E has reversed the symptoms. In general, plasma α-tocopherol concentrations <12 μmol/L are associated with increased infection, anemia, stunting of growth, and poor outcomes during pregnancy for both the infant and the mother. When low dietary amounts of α-tocopherol are consumed, tissue α-tocopherol needs exceed amounts available, leading to increased damage to target tissues. Seemingly, adequacy of human vitamin E status cannot be assessed from circulating α-tocopherol concentrations, but inadequacy can be determined from “low” values. Circulating α-tocopherol concentrations are very difficult to interpret because, as a person ages, plasma lipid concentrations also increase and these elevations in lipids increase the plasma carriers for α-tocopherol, leading to higher circulating α-tocopherol concentrations. However, abnormal lipoprotein metabolism does not necessarily increase α-tocopherol delivery to tissues. Additional biomarkers of inadequate vitamin E status are needed. Urinary excretion of the vitamin E metabolite α-carboxy-ethyl-hydroxychromanol may fulfill this biomarker role, but it has not been widely studied with regard to vitamin E status in humans or with regard to health benefits. This review evaluated the information available on the adverse consequences of inadequate α-tocopherol status and provides suggestions for avenues for research.

Source: Maret G. Traber. “Vitamin E Inadequacy in Humans: Causes and Consequences” Advances in Nutrition, (2014) Sep; 5(5): 503–514.

Nutrients for the aging eye *

Abstract

The incidence of age-related eye diseases is expected to rise with the aging of the population. Oxidation and inflammation are implicated in the etiology of these diseases. There is evidence that dietary antioxidants and anti-inflammatories may provide benefit in decreasing the risk of age-related eye disease. Nutrients of interest are vitamins C and E, β-carotene, zinc, lutein, zeaxanthin, and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. While a recent survey finds that among the baby boomers (45–65 years old), vision is the most important of the five senses, well over half of those surveyed were not aware of the important nutrients that play a key role in eye health. This is evident from a national survey that finds that intake of these key nutrients from dietary sources is below the recommendations or guidelines. Therefore, it is important to educate this population and to create an awareness of the nutrients and foods of particular interest in the prevention of age-related eye disease.

Nutrient content of the Age-Related Eye Disease Study (AREDS) formulation

NutrientDaily dosage% daily value
Vitamin C (ascorbic acid)452 mg754
Vitamin E (dl-α-tocopheryl acetate)400 IU1334
Zinc (zinc oxide)69.6 mg464
Copper (cupric oxide)1.6 mg80
Vitamin A (β-carotene)28,640 IU (17 mg)572

Source: Rasmussen HM, Johnson EJ. “Nutrients for the aging eye.” Clinical Interventions in Aging (2013): 8:741-748.

Optic neuropathy associated with copper deficiency after gastric bypass surgery *

Abstract

Purpose: Patients undergoing gastric bypass procedures are predisposed to many vitamin and mineral deficiencies including copper, which can lead to optic neuropathy.

Methods: A 35-year-old woman complained of progressive vision loss bilaterally 3 years after gastric bypass surgery (GBS).

Results: Ophthalmic examination revealed the presence of subnormal visual acuity and pale optic nerves bilaterally. Laboratory testing showed copper deficiency. Complete improvement in vision was noted after copper was replenished.

Conclusion: Nutritional deficiencies occurring after gastric bypass procedures are well reported. They happen and occur due to reduced gastric and enteral absorption and cause many systemic and neurologic manifestations. Optic neuropathy occurring after GBS is often due to vitamin B12 and folic acid deficiency. Copper deficiency causing systemic symptoms is very rare and usually takes decades to manifest. Our case is unique in that copper deficiency was noted as early as 3 years after GBS. Moreover rapid copper replenishment led to a dramatic recovery of vision. Our case underscores the need for maintaining high suspicion when evaluating patients with suspected optic neuropathy occurring after GBS since prompt diagnosis and treatment may lead to reversal of visual loss.

Source: Ankoor R Shah, Madhura A Tamhankar. “Optic neuropathy associated with copper deficiency after gastric bypass surgery” Retinal Cases & Brief Reports (2014): 8(1):73-6.

Combined optic neuropathy and myelopathy secondary to copper deficiency *

Abstract

We report two patients, both with a history of gastric surgery, who presented with progressive optic neuropathy and myelopathy. The patients’ symptoms were initially attributed to vitamin B12 deficiency and/or neuromyelitis optica; however, after the neurologic deficits continued to progress with the use of conventional treatments, further evaluation was initiated, and a severe copper deficiency was revealed. Copper deficiency is a rare cause of progressive optic neuropathy and myelopathy and should be considered in the differential diagnosis. It is crucial to elicit a history of gastric surgery or other risk factors for hypocupremia in those patients undergoing an evaluation for subacute or chronically progressive optic neuropathy or myelopathy.

Source: Stacy L Pineles, Christina A Wilson, Laura J Balcer, Robert Slater, Steven L Galetta. “Combined optic neuropathy and myelopathy secondary to copper deficiency” Survey of Ophthalmology (2010): 55(4):386-92.

Eyebright  (Euphrasia rostkoviana)

Prospective cohort trial of Euphrasia single-dose eye drops in conjunctivitis *
Abstract

Introduction: Eye drops made from Euphrasia rostkoviana Hayne have been used in anthroposophical medicine for more than 70 years for the structuring of the fluid organism in the eye, especially in inflammatory and catarrhal conjunctivitis. The aim of this prospective cohort trial was to describe the efficacy and tolerability of these eye drops in a community-based setting. To evaluate these questions, prospective cohort studies are the best method. This enables the investigator to attain real insights as to which treatment administered related to specific results in a specific group of patients.

Design: Prospective, open label, one-armed, multicentered, multinational cohort trial.

Setting: The trial was carried out in the clinics of 12 experienced anthroposophical general practitioners and ophthalmologists in Germany and Switzerland.

Patients: Patients with inflammatory or catarrhal conjunctivitis, treated with Euphrasia single-dose eye drops were included in the trial.

Intervention: One drop of Euphrasia single-dose eye drops 1-5 times a day was prescribed. The prescription was determined solely by medical therapeutic needs.

Outcome measures: Efficacy variables were: redness, swelling, secretion, burning of the conjunctiva, and foreign body sensation. Tolerability variables were: conjunctival reddening, burning of the conjunctiva, foreign body sensation, and veiled vision. All symptoms were given for the right or left eye separately, with degree of severity in relation to baseline after approximately 7 days (+/-3 days; first follow-up examination) and after approximately 14 days (+/-3 days; second follow-up examination). If, after the first follow-up, all symptoms had disappeared, no second follow-up was done.

Results: Sixty-five (65) patients fulfilled the inclusion criteria for the protocol evaluation. A complete recovery was seen in 53 patients (81.5%) and a clear improvement in 11 patients (17.0%). A slight worsening could only be determined in 1 patient in the second week of treatment (1.5%). No serious adverse events were observed during the entire trial. The efficacy and tolerability were evaluated by the patients and doctors as “good” to “very good” in more than 85%.

Conclusion: Euphrasia single-dose eye drops can effectively and safely be used for various conjunctival conditions by general practitioners and ophthalmologists. A dosage of one drop three times a day seems to be the general prescribed dosage.

Source: M Stoss , C Michels, E Peter, R Beutke, R W Gorter. “Prospective cohort trial of Euphrasia single-dose eye drops in conjunctivitis” Journal of Alternative and Complementary Medicine (2000): 6(6):499-508.

Assessment of Eyebright (Euphrasia Officinalis L.) Extract Activity in Relation to Human Corneal Cells Using In Vitro Tests *

Background: Euphrasia officinalis L. is an herb traditionally used in folk medicine, mainly in the treatment of eye disorders.

Aims: The present study analyzed the activity of three extracts of E. officinalis L. (ethanol, ethyl acetate and heptane) on cultured human corneal epithelial cells (10.014 pRSV-T).

Study Design: In vitro study.

Methods: Toxicity, free radical scavenging activity and the immunomodulatory effects of the extracts were tested using the thiazolyl blue tetrazolium bromide (MTT) or Neutral Red, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and ELISA tests, respectively. Moreover, nitric oxide levels and cytoskeleton architecture were analyzed after corneal cell incubation with the plant extracts.

Results: We show that the biological effect depended on both the concentration and the extraction solvent used. Heptane extracts, distinct from those in ethanol and ethyl acetate, were toxic to 10.014 pRSV-T cells at low concentrations (25 μg/mL) and did not demonstrate free radical scavenging effects. All tested extracts decreased pro-inflammatory cytokine expression (IL-1β, IL-6 and TNF-α) and also anti-inflammatory IL-10 expression by human corneal cells when the extracts were added to the cell culture medium for 24 h.

Conclusion: In conclusion, we show that the promising effects of the application of E. officinalis L. preparations as a supplementary therapy for eye disorders are associated with the ethanol and ethyl acetate extracts, not the heptane extract.

Source: Roman Paduch, Anna Woźniak, Piotr Niedziela, Robert Rejdak. “Assessment of Eyebright (Euphrasia Officinalis L.) Extract Activity in Relation to Human Corneal Cells Using In Vitro Tests” Balkan Medical Journal (2014): 31(1): 29–36.

Assessment of eyebright (euphrasia officinalis L.) extract activity in relation to human corneal cells using in vitro tests *

Abstract

Background: Euphrasia officinalis L. is an herb traditionally used in folk medicine, mainly in the treatment of eye disorders.

Aims: The present study analyzed the activity of three extracts of E. officinalis L. (ethanol, ethyl acetate and heptane) on cultured human corneal epithelial cells (10.014 pRSV-T).

Study design: In vitro study.

Methods: Toxicity, free radical scavenging activity and the immunomodulatory effects of the extracts were tested using the thiazolyl blue tetrazolium bromide (MTT) or Neutral Red, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and ELISA tests, respectively. Moreover, nitric oxide levels and cytoskeleton architecture were analyzed after corneal cell incubation with the plant extracts.

Results: We show that the biological effect depended on both the concentration and the extraction solvent used. Heptane extracts, distinct from those in ethanol and ethyl acetate, were toxic to 10.014 pRSV-T cells at low concentrations (25 μg/mL) and did not demonstrate free radical scavenging effects. All tested extracts decreased pro-inflammatory cytokine expression (IL-1β, IL-6 and TNF-α) and also anti-inflammatory IL-10 expression by human corneal cells when the extracts were added to the cell culture medium for 24 h.

Conclusion: In conclusion, we show that the promising effects of the application of E. officinalis L. preparations as a supplementary therapy for eye disorders are associated with the ethanol and ethyl acetate extracts, not the heptane extract.

Source: Roman Paduch, Anna Woźniak, Piotr Niedziela, Robert Rejdak. “Assessment of eyebright (euphrasia officinalis L.) extract activity in relation to human corneal cells using in vitro tests” Balkan Medical Journal (2014): 31(1):29-36.

Pharmacological activities of an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts in UVB-induced oxidative stress and inflammation of human corneal cells *

Abstract

Ultraviolet B (UVB) exposure is a risk factor for corneal damage resulting in oxidative stress, inflammation and cell death. The aim of this study was to investigate the potential protective effects of a commercial eye drop (Dacriovis™) containing Matricaria chamomilla and Euphrasia officinalis extracts on human corneal epithelial cells (HCEC-12) against UVB radiation-induced oxidative stress and inflammation as well as the underlying mechanisms. The antioxidant potential of the eye drops was evaluated by measuring the ferric reducing antioxidant power and the total phenolic content by Folin-Ciocalteu reagent. HCEC-12 cells were exposed to UVB radiation and treated with the eye drops at various concentrations. Cell viability, wound healing assay, reactive oxygen species (ROS) levels, protein and lipid oxidative damage and COX-2, IL-1β, iNOS, SOD-2, HO-1 and GSS gene expression, were assessed. Eye drops were able to protect corneal epithelial cells from UVB-induced cell death and ameliorated the wound healing; the eye drops exhibited a strong antioxidant activity, decreasing ROS levels and protein and lipid oxidative damage. Eye drops also exerted anti-inflammatory activities by decreasing COX-2, IL-1β, iNOS expression, counteracted UVB-induced GSS and SOD-2 expression and restored HO-1 expression to control levels. These findings suggest that an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts exerts positive effects against UVB induced oxidative stress and inflammation and may be useful in protecting corneal epithelial cells from UVB exposure.

Source: Elisabetta Bigagli, Lorenzo Cinci, Mario D’Ambrosio, Cristina Luceri. “Pharmacological activities of an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts in UVB-induced oxidative stress and inflammation of human corneal cells” Journal of Photochemistry & Photobiology B (2017): 173:618-625.

Prospective cohort trial of Euphrasia single-dose eye drops in conjunctivitis *

Abstract

Introduction: Eye drops made from Euphrasia rostkoviana Hayne have been used in anthroposophical medicine for more than 70 years for the structuring of the fluid organism in the eye, especially in inflammatory and catarrhal conjunctivitis. The aim of this prospective cohort trial was to describe the efficacy and tolerability of these eye drops in a community-based setting. To evaluate these questions, prospective cohort studies are the best method. This enables the investigator to attain real insights as to which treatment administered related to specific results in a specific group of patients.

Design: Prospective, open label, one-armed, multicentered, multinational cohort trial.

Setting: The trial was carried out in the clinics of 12 experienced anthroposophical general practitioners and ophthalmologists in Germany and Switzerland.

Patients: Patients with inflammatory or catarrhal conjunctivitis, treated with Euphrasia single-dose eye drops were included in the trial.

Intervention: One drop of Euphrasia single-dose eye drops 1-5 times a day was prescribed. The prescription was determined solely by medical therapeutic needs.

Outcome measures: Efficacy variables were: redness, swelling, secretion, burning of the conjunctiva, and foreign body sensation. Tolerability variables were: conjunctival reddening, burning of the conjunctiva, foreign body sensation, and veiled vision. All symptoms were given for the right or left eye separately, with degree of severity in relation to baseline after approximately 7 days (+/-3 days; first follow-up examination) and after approximately 14 days (+/-3 days; second follow-up examination). If, after the first follow-up, all symptoms had disappeared, no second follow-up was done.

Results: Sixty-five (65) patients fulfilled the inclusion criteria for the protocol evaluation. A complete recovery was seen in 53 patients (81.5%) and a clear improvement in 11 patients (17.0%). A slight worsening could only be determined in 1 patient in the second week of treatment (1.5%). No serious adverse events were observed during the entire trial. The efficacy and tolerability were evaluated by the patients and doctors as “good” to “very good” in more than 85%.

Conclusion: Euphrasia single-dose eye drops can effectively and safely be used for various conjunctival conditions by general practitioners and ophthalmologists. A dosage of one drop three times a day seems to be the general prescribed dosage.

Source: M. Stoss, C. Michels, E. Peter, R. Beutke, R. W. Gorter. “Prospective cohort trial of Euphrasia single-dose eye drops in conjunctivitis” Journal of Alternative & Complementary Medicine (2000): 6(6):499-508.

Prospective Cohort Trial of Euphrasia Single-Dose Eye Drops in Conjunctivitis *

Abstract

Introduction: Eye drops made from Euphrasia rostkoviana Hayne have been used in anthroposophical medicine for more than 70 years for the structuring of the fluid organism in the eye, especially in inflammatory and catarrhal conjunctivitis. The aim of this prospective cohort trial was to describe the efficacy and tolerability of these eye drops in a community-based setting. To evaluate these questions, prospective cohort studies are the best method. This enables the investigator to attain real insights as to which treatment administered related to specific results in a specific group of patients.

Design: Prospective, open label, one-armed, multicentered, multinational cohort trial.

Setting: The trial was carried out in the clinics of 12 experienced anthroposophical general practitioners and ophthalmologists in Germany and Switzerland.

Patients: Patients with inflammatory or catarrhal conjunctivitis, treated with Euphrasia single-dose eye drops were included in the trial.

Intervention: One drop of Euphrasia single-dose eye drops 1–5 times a day was prescribed. The prescription was determined solely by medical therapeutic needs.

Outcome Measures: Efficacy variables were: redness, swelling, secretion, burning of the conjunctiva, and foreign body sensation. Tolerability variables were: conjunctival reddening, burning of the conjunctiva, foreign body sensation, and veiled vision. All symptoms were given for the right or left eye separately, with degree of severity in relation to baseline after approximately 7 days (±3 days; first follow-up examination) and after approximately 14 days (±3 days; second follow-up examination). If, after the first follow-up, all symptoms had disappeared, no second follow-up was done.

Results: Sixty-five (65) patients fulfilled the inclusion criteria for the protocol evaluation. A complete recovery was seen in 53 patients (81.5%) and a clear improvement in 11 patients (17.0%). A slight worsening could only be determined in 1 patient in the second week of treatment (1.5%). No serious adverse events were observed during the entire trial. The efficacy and tolerability were evaluated by the patients and doctors as “good” to “very good” in more than 85%.

Conclusion: Euphrasia single-dose eye drops can effectively and safely be used for various conjunctival conditions by general practitioners and ophthalmologists. A dosage of one drop three times a day seems to be the general prescribed dosage.

Source: Matthias Stoss, Christoph Michels, Ellen Peter, Ramona Beutke, Robert William Gorter. “Prospective Cohort Trial of Euphrasia Single-Dose Eye Drops in Conjunctivitis” The Journal of Alternative and Complementary Medicine (2007): (6)6.

 

References:
  1. https://bjo.bmj.com/content/early/2019/12/06/bjophthalmol-2019-314813
  2. https://pubmed.ncbi.nlm.nih.gov/25636674/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909327/
  4. https://iovs.arvojournals.org/article.aspx?articleid=2128624
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5611842/
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  17. https://tahomaclinic.com/Research/Abstracts/Bilberry1.html
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