BACKGROUND: Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss. OBJECTIVE: To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity. DESIGN: The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. MAIN OUTCOME MEASURES: (1) Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline (>or =15 letters). Primary analyses used repeated-measures logistic regression with a significance level of.01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. RESULTS: Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations. CONCLUSIONS: Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study.

OBJECTIVES:This study aimed to characterize the association of lifestyle and nutritional risk profiles with age-related macular degeneration (AMD) in two subpopulations with differing AMD prevalence.

METHODS:This case-control study (n = 1992) included 768 patients with AMD and 1224 age- and sex-matched participants without AMD with a single visit at a primary health care unit. Enrolled participants completed a validated lifestyle and food frequency questionnaire. A score to measure adherence to the Mediterranean diet (mediSCORE; Range, 0-9) was constructed from individual food intakes, which were further analyzed by conversion to nutrient consumption.

RESULTS:Higher adherence to the Mediterranean diet (mediSCORE≥6) was significantly associated with no AMD (odds ratio [OR] = 0.73; P = 0.009). The subpopulation with lower AMD prevalence presented significantly higher adherence to the Mediterranean diet in relation to all individual food groups that comprised the mediSCORE (P < 0.014) with the exception of cereals. Food group analysis showed significant associations between the increased consumption of vegetables (OR = 0.63; P < 0.001) and fruit and nuts (OR = 0.78; P = 0.010) with no AMD. Nutrient analysis revealed that an increased ingestion of water, fibers, total fat, monounsaturated and polyunsaturated fatty acids, linoleic acid, vitamins A and C, carotene, alpha-tocopherol, folate, magnesium, iron, and zincwere significantly associated with no AMD (P < 0.0013). Finally, regular physical activity was associated with no AMD (P = 0.003).

CONCLUSIONS:High adherence to a Mediterranean diet and regular physical activity seem to be protective factors for AMD in a Portuguese population. The effect of the diet is likely driven by the increased consumption of vegetables, fruits, and nuts.

PURPOSE:To characterize the lifestyle and nutritional risk profile associated with the Mediterranean diet in a Portuguese population with and without age-related macular degeneration (AMD).

METHODS:Nested case-control study (n = 883) within the Coimbra Eye Study, including 434 subjects with AMD and 449 age- and sex-matched subjects without AMD. All enrolled subjects underwent a full risk assessment, including lifestyle-related risk factors and a thorough food frequency questionnaire. This allowed us to build an adherence score to the Mediterranean diet (mediSCORE, range 0-9) constructed from individual food intakes. Food intake was also further analysed by conversion to micronutrient consumption.

RESULTS:Our results suggest that physical activity has a protective role in AMD [p = 0.018 after multivariate adjustment, OR: 0.69 (0.51-0.93)]. High (mediSCORE ≥6) was also found to be protective [p = 0.041, OR: 0.62 (95% CI: 0.38-0.97)]. Food group analysis unveiled a specific protective role for increased fruits consumption (p = 0.029). Finally, micronutrient analysisrevealed a protective role associated with increased consumption of caffeine, fibres, beta-carotene, vitamin C and vitamin E (p < 0.05).

CONCLUSION:High mediSCORE appears to confer protection against the development of AMD in a Mediterranean population. This effect is driven by increased consumption of fruits and some antioxidant micronutrients, which emerged as statistically significant protective factors. Further studies are required to establish dietary recommendations with clinical application.

PURPOSE: Determine whether antioxidant supplements alter the plasma glutathione and/or cysteine redox potential in age-related macular degeneration (AMD) patients. DESIGN: This was an ancillary study to the Age-Related Eye Disease Study (AREDS), where subset of AREDS subjects at two sites were studied at two time points, an average of 1.7 and 6.7 years after enrollment. METHODS: Plasma glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), and cystine (CySS) were measured by high-performance liquid chromatography, and redox potentials of GSH/GSSG (E(h) GSH) and Cys/CySS (E(h) Cys) were calculated. The means of the metabolites and redox potentials were compared by repeated-measures analysis of variance for subjects receiving antioxidants and those not receiving antioxidants. RESULTS: At the first blood draw, the means for the antioxidant group (n = 153) and no antioxidant group (n = 159) were not significantly different for any of the metabolites or redox potentials. At the second draw, the GSH parameters were not significantly different between the antioxidant (n = 37) and no antioxidant (n = 45) groups; however, mean Cys was significantly higher in the antioxidant group (9.5 vs 7.2 micromol/l, P = .008). Also, mean E(h) Cys was significantly more reduced in the antioxidant group (-74 vs -67.3 mV, P = .03). CONCLUSIONS: The AREDS antioxidant supplements reduced oxidation of E(h) Cys but had no effect on GSH. Because Cys is important for cell growth, apoptosis, and immune function, the beneficial effect of antioxidant supplementation on progression to advanced AMD may be partially explained by its effect on E(h) Cys and/or its effect on Cys availability.

BACKGROUND:Light exposure and more specifically the spectrum of blue light contribute to the oxidative stress in Age-related macular degeneration (AMD). The purpose of the study was to establish whether blue light filtering could modify proangiogenic signaling produced by retinal pigmented epithelial (RPE) cells under different conditions simulating risk factors for AMD.

METHODS:Three experiments were carried out in order to expose ARPE-19 cells to white light for 48 h with and without blue light-blocking filters (BLF) in different conditions. In each experiment one group was exposed to light with no BLF protection, a second group was exposed to light with BLF protection, and a control group was not exposed to light. The ARPE-19 cells used in each experiment prior to light exposure were cultured for 24 h as follows: Experiment 1) Normoxia, Experiment 2) Hypoxia, and Experiment 3) Lutein supplemented media in normoxia. The media of all groups was harvested after light exposure for sandwich ELISA-based assays to quantify 10 pro-angiogenic cytokines.

RESULTS:A significant decrease in angiogenin secretion levels and a significant increase in bFGF were observed following light exposure, compared to dark conditions, in both normoxia and hypoxia conditions. With the addition of a blue light-blocking filter in normoxia, a significant increase in angiogenin levels was observed. Although statistical significance was not achieved, blue light filters reduce light-induced secretion of bFGF and VEGF to near normal levels. This trend is also observed when ARPE-19 cells are grown under hypoxic conditions and when pre-treated with lutein prior to exposure to experimental conditions.

CONCLUSIONS:Following light exposure, there is a decrease in angiogenin secretion by ARPE-19 cells, which was abrogated with a blue light - blocking filter. Our findings support the position that blue light filtering affects the secretion of angiogenic factors by retinal pigmented epithelial cells under normoxic, hypoxic, and lutein-pretreated conditions in a similar manner.

OBJECTIVE:To evaluate the influence of short-term carotenoid and antioxidant supplementation on retinal function in nonadvanced age-related macular degeneration (AMD).

DESIGN:Randomized controlled trial.

PARTICIPANTS:Twenty-seven patients with nonadvanced AMD and visual acuity>or =0.2 logarithm of the minimum angle of resolution were enrolled and randomly divided into 2 age-similar groups: 15 patients had oral supplementation of vitamin C (180 mg), vitamin E (30 mg), zinc (22.5 mg), copper (1 mg), lutein (10 mg), zeaxanthin (1 mg), and astaxanthin (4 mg) (AZYR SIFI, Catania, Italy) daily for 12 months (treated AMD [T-AMD] group; mean age, 69.4+/-4.31 years; 15 eyes); 12 patients had no dietary supplementation during the same period (nontreated AMD [NT-AMD] group; mean age, 69.7+/-6.23 years; 12 eyes). At baseline, they were compared with 15 age-similar healthy controls.

METHODS:Multifocal electroretinograms in response to 61 M-stimuli presented to the central 20 degrees of the visual field were assessed in pretreatment (baseline) conditions and, in nonadvanced AMD patients, after 6 and 12 months.

MAIN OUTCOME MEASURES:Multifocal electroretinogram response amplitude densities (RAD, nanovolt/deg(2)) of the N1-P1 component of first-order binary kernels measured from 5 retinal eccentricity areas between the fovea and midperiphery: 0 degrees to 2.5 degrees (R1), 2.5 degrees to 5 degrees (R2), 5 degrees to 10 degrees (R3), 10 degrees to 15 degrees (R4), and 15 degrees to 20 degrees (R5).

RESULTS:At baseline, we observed highly significant reductions of N1-P1 RADs of R1 and R2 in T-AMD and NT-AMD patients when compared with healthy controls (1-way analysis of variance P<0.01). N1-P1 RADs of R3-R5 observed in T-AMD and NT-AMD were not significantly different (P>0.05) from controls. No significant differences (P>0.05) were observed in N1-P1 RADs of R1-R5 between T-AMD and NT-AMD at baseline. After 6 and 12 months of treatment, T-AMD eyes showed highly significant increases in N1-P1 RADs of R1 and R2 (P<0.01), whereas no significant (P>0.05) change was observed in N1-P1 RADs of R3-R5. No significant (P>0.05) changes were found in N1-P1 RADs of R1-R5 in NT-AMD eyes.

CONCLUSIONS:In nonadvanced AMD eyes, a selective dysfunction in the central retina (0 degrees -5 degrees ) can be improved by the supplementation with carotenoids and antioxidants. No functional changes are present in the more peripheral (5 degrees -20 degrees ) retinal areas.

Optical spectrum of the sunlight consists of visible or chromatic spectrum, with the range of wavelengths of electromagnetic vibrations from 7700 to 3900 AU, and the invisible spectrum: infrared and ultraviolet. Chromatic spectrum gives rise to the sensation of colour, capable for simulating specialized retinal photoreceptors and is perceptible as light. This rule of perception of the particular range of the optical spectrum goes mainly for man, while particular deviations, more or less, are applicable to the rest of animal and plant life. The optical part of the spectrum belongs to nonionizing radiation. It created the life on the Earth, maintaining it nowadays and even threatening the human organ of vision, because the retina had not been yet adequately accommodated through evolution with its photoreactive metabolism. Human retina is very sensitive about possible harmful influence of ultraviolet and blue light even today in evolution, but also phototoxic on complete strong visible light. In their clinical and experimental work on animals, the authors prove with their own patent (P 20020077A)-Vojniković B&D, and in collaboration with Essilor Optic Austria GmbH, that particular medical filters in the range of green-yellow colour especially (565 to 570 nm), and in combination with"Transitions"successfully threat macular degeneration-AMD, slowing down its progression and having positive psychoorganic effect on the depressive mood of such patients with threatened sight. Full attention has been paid to the design of medical filter, so the periphery of the lens plays a positive role in blood concentration of melatonin, while the central part stimulates the sight and the concentration of serotonine. Thus the physiological balance of melatonin and serotonin and the stability of psychophysical disturbances have been achieved.

BACKGROUND:Cumulative light exposure is significantly associated with ageing and the progression of age-related macular degeneration. To prevent the retina from blue-light damage in pseudophakia, blue light-absorbing intraocular lenses have been developed. This study compares the possible protective effects of a blue light-absorbing intraocular lens to an untinted ultraviolet-absorbing intraocular lens with regard to light-induced oxidative stress and senescence of human retinal pigment epithelium.

METHODS:As primary human retinal pigment epithelium cells were exposed to white light, either an ultraviolet- and blue light-absorbing intraocular lens or ultraviolet-absorbing intraocular lens was placed in the light beam. After 60 min of irradiation, cells were investigated by electron microscopy for viability, induction of intracellular reactive oxygen species, and senescence-associatedβ-galactosidase activity. Expression and secretion of matrix metalloproteinases 1 and 3 and their mRNA were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay.

RESULTS:Light exposure induced structural damage, decreased retinal pigment epithelium cell viability, and increased reactive oxygen species, senescence-associatedβ-galactosidase activity and matrix metalloproteinases 1 and 3 expression and secretion. Although both types of intraocular lens significantly reduced these effects, the protective effects of the ultraviolet- and blue light-absorbing intraocular lens were significantly stronger than those of the ultraviolet-absorbing intraocular lens.

CONCLUSIONS:The ultraviolet- and blue light-absorbing intraocular lens demonstrated significantly better protection against light-induced oxidative stress, senescence and structural damage than the ultraviolet-absorbing intraocular lens. These in vitro findings support the hypothesis that the ultraviolet- and blue light-absorbing intraocular lens may prevent retinal damage in clinical use.

OBJECTIVE:To investigate associations of adherence to the Mediterranean diet (MeDi) with incidence of advanced AMD (the symptomatic form of AMD) in two European population-based prospective cohorts.

DESIGN:Prospective cohorts: the Rotterdam Study I (RS-I) and the Alienor Study.

PARTICIPANTS:4 446 participants aged≥55 years from RS-I (The Netherlands) and 550 French adults aged 73 years or older from Alienor Study with complete ophthalmologic and dietary data were included in the present study.

METHODS:Examinations were performed approximately every 5 years over a 21-year period (1990 to 2011) in RS-I and every 2 years over a 4-year period (2006 to 2012) in Alienor Study. Adherence to the MeDi was evaluated using a 9 component score based on intake of vegetables, fruits, legumes, cereals, fish, meat, dairy products, alcohol and the monounsaturated-to-saturated fatty acids ratio. Associations of incidence of AMD with MeDi were estimated using multivariate Cox proportional Hazard models.

MAIN OUTCOMES MEASURES:Incidence of advanced AMD based on retinal fundus photographs.

RESULTS:Among the 4 996 included participants, 155 developed advanced incident AMD (117 from RS-I and 38 from Alienor Study). The mean follow-up time was 9.9 years (range 0.6 to 21.7) in RS-I and 4.1 years (range 2.5 to 5.0) in Alienor Study. Pooling data for both RS-I and Alienor study, participants with a high (6-9) MeDi score had a significantly reduced risk for incident advanced AMD compared to participants with a low (0-3) MeDi score in the fully-adjusted Cox model (HR, 0.59 [95% CI, 0.37-0.95], p for trend=0.04).

CONCLUSION:Pooling data from RS-I and Alienor, higher adherence to the MeDi was associated with a 41% reduced risk of incident advanced AMD. These findings support the role of a diet rich in healthful nutrient-rich foods such as fruits, vegetables, legumes and fish in the prevention of AMD.

PURPOSE:To examine associations between adherence to a Mediterranean diet and prevalence of age-related macular degeneration (AMD) in countries ranging from Southern to Northern Europe.

DESIGN:Cross-sectional, population-based epidemiologic study.

PARTICIPANTS:Of 5060 randomly sampled people aged 65 years or older from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain), full dietary data were available in 4753. The mean age of participants was 73.2 years (standard deviation, 5.6), and 55% were women.

METHODS:Participants underwent an eye examination and digital retinal color photography. The images were graded at a single center. Dietary intake during the previous 12 months was assessed by using a semiquantitative food-frequency questionnaire (FFQ). A previously published Mediterranean Diet Score (MDS) was used to classify participants according to their responses on the FFQ. Multivariable logistic regression was used to investigate the association of the MDS score and AMD, taking account of potential confounders and the multicenter study design.

MAIN OUTCOME MEASURES:Images were graded according to the International Classification System for age-related maculopathy and stratified using the Rotterdam staging system into 5 exclusive stages (AMD 0-4) and a separate category of large drusen (≥125 μm). Age-related macular degeneration 4 included neovascular AMD (nvAMD) and geographic atrophy (GA).

RESULTS:Increasing MDS was associated with reduced odds of nvAMD in unadjusted and confounder-adjusted analysis. Compared with the lowest MDS adherence (≤4 score), those in the highest category MDS adherence (>6 score) showed lower odds of nvAMD (odds ratio, 0.53; 0.27-1.04; P trend = 0.01). The association with MDS did not differ by Y204H risk allele (P = 0.89). For all early AMD (grade 1-3), there was no relationship with MDS (P trend = 0.9). There was a weak trend (P = 0.1) between MDS and large drusen; those in the highest category of MDS had 20% reduced odds comparedwith those in the lowest (P = 0.05).

CONCLUSIONS:This study adds to the limited evidence of the protective effect of adherence to a Mediterranean dietary pattern in those with late AMD, although it does not support previous reports of a relationship with genetic susceptibility. Interventions to encourage the adoption of the Mediterranean diet should be developed, and methods by which such behavior change can be achieved and maintained investigated.

METHODS:Primary human RPE cells were exposed to white light and either a SN60AT or SA60AT IOL was placed in the light beam. After 15-60 min of irradiation, viability, induction of apoptosis and cell death were determined in primary human RPE cells. Expression of vascular endothelial growth factor A (VEGF-A) and the anti-apoptotic XIAP protein and their mRNA were determined by RT-PCR, Western blot analysis and ELISA.

RESULTS:Light exposure decreased cell viability depending on the duration of irradiation. Light-induced cell death and apoptosis as well as decrease of XIAP expression and cellular viability were significantly reduced by both the SN60AT and SA60AT IOL. In addition, these protective effects regarding light-induced cell damage were significantly stronger in the presence of the blue light-filtering SN60AT IOL compared to the SA60AT IOL.

CONCLUSION:Both UV-filtering and blue light-absorbing IOLs reduce light-induced RPE damage. The blue light-absorbing IOL further reduced damage compared to the conventional IOL, which supports the hypothesis of possibly also preventing retinal damage in clinical use.

OBJECTIVES:Biofeedback training (BT) is a modern method for enhancing the use of preferred retinal loci (PRL) retraining for new retinal loci (TRL), hence improving far and near vision. This article attempts to clarify the optimal methodology for BT and the types of patients who can benefit most from BT.

METHODS:This is a retrospective review of cases who received BT with the macular integrity assessment (MAIA) microperimetre. Outcome measures selected for analysis were visual acuity, PRL location, fixation stability, fixation pattern orientation, reading acuity, critical print size, and reading speed.

RESULTS:Out of 30 cases who received BT, only those with age-related macular degeneration and visual acuity of logMAR 0.8 (20/126) or poorer showed a visual acuity gain (statistically significant of 12 letters) after BT. Those with other diagnoses and those with residual Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of logMAR of 0.7 (20/100) or better showed only positive trends for visual acuity and a negative trend for fixation stability. All subjects showed a shift in PRL location toward the superior quadrant of the retina (p<0.02) in those who received BT.

CONCLUSION:BT seems to offer patients a unique and efficient modality to improve distance vision outside of using optical devices.

The sungazing method has been known for thousands of years as healing method based on chromotherapeutic principle. Our examinations on the island of Rab show that it is acceptable only if applied 10 min before the sunset. Gazing has to be directed towards the green-yellow part of the spectrum, since the remaining part of the sun halo contains harmful energy. However, authors suggest that it would be preferable to use spectacles with medical filters transmitting wavelight of green-yellow colour, especially for treatment of macular degeneration.

The sungazing method has been known for thousands of years as healing method based on chromotherapeutic principle. Our examinations on the island of Rab show that it is acceptable only if applied 10 min before the sunset. Gazing has to be directed towards the green-yellow part of the spectrum, since the remaining part of the sun halo contains harmful energy. However, authors suggest that it would be preferable to use spectacles with medical filters transmitting wavelight of green-yellow colour, especially for treatment of macular degeneration.

A2E-laden ARPE-19 cells were exposed to a blue light to induce cytotoxicity, in order to investigate the protective effects of various tinted ophthalmic lenses against photo-induced cytotoxicity in human retinal pigment epithelial (RPE) cells laden with A2E, known to be among the etiologies of age-related macular degeneration (AMD). Different-colored tinted lenses with varying levels of tint and different filtering characteristics, such as polarized, blue-cut, and photochromatic lenses, were placed over the cells, and the protective efficacies thereof were evaluated by lactate dehydrogenase assay. When tinted lenses were placed over ARPE-19 cells, there were different reductions in cytotoxicity according to the colors and tint levels. The level of protection afforded by brown-tinted lenses was 6.9, 36.1, and 49% with a tint level of 15, 50, and 80%, respectively. For gray-tinted lenses, the protective effect was 16.3, 35, and 43.4% for the corresponding degree of tint, respectively. In the case of blue-tinted lenses, a protective effect of 20% was observed with 80% tinted lenses, but 15 and 50% tinted lenses provided no significant protection. In addition, photochromic lenses showed a protective effect but blue-cut lenses and polarized lenses provided no significant protection. Tinted lenses significantly reduced cytotoxicity in RPE cells irradiated with blue light. The protection was more efficient in lenses with a brown or gray tint than in blue-tinted lenses. Tinted glasses may provide significant protection against potential blue-light-induced photochemical and photo-oxidative damage in RPE cells.