Review of Evidence for the Usage of Antioxidants for Eye Aging

Choo, Priscilla Peixi; Woi, Pui Juan; Bastion, Mae-Lynn Catherine; Omar, Rokiah; Mustapha, Mushawiahti; Md Din, Norshamsiah

doi:https://doi.org/10.1155/2022/5810373

BioMed Research International

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Review Article | Open Access

Volume 2022 | Article ID 5810373 | https://doi.org/10.1155/2022/5810373

Review of Evidence for the Usage of Antioxidants for Eye Aging

Priscilla Peixi Choo,¹Pui Juan Woi,²Mae-Lynn Catherine Bastion,¹Rokiah Omar,²Mushawiahti Mustapha,¹and Norshamsiah Md Din¹

Academic Editor: Timothy Y. Y. Lai

Received25 Nov 2021

Revised15 Jun 2022

Accepted22 Sept 2022

Published03 Oct 2022

Abstract

Oxidative stress is one of the common factors leading to age-related eye diseases in older adults. Factors such as high oxygen consumption, high concentration of polyunsaturated fatty acids, and cumulative exposure to high-energy visible light in the eyes, lead to excessive generation of reactive oxygen species, hence triggering apoptosis of ocular cells and giving rise to ophthalmic diseases. Dietary supplements such as carotenoids, anthocyanins, and vitamins have antioxidant properties which may be of benefit in retaining better vision or reversing vision impairment; thus, studies have been conducted to understand the role of dietary supplements in the treatment or prevention of ophthalmic diseases. While high concentration of carotenoids such as lutein and zeaxanthin decrease the risk of developing age-related macular disease, anthocyanins and vitamins play a role in the treatment and prevention of other ophthalmic diseases: saffron extract reduced intraocular pressure in glaucoma patients; bilberry extract prevented impairments in lenses and retina, as well as alleviate symptoms of dry eye disease; high concentration of beta-carotene may reduce the risk of developing cataract. Further studies with clinical measurements are required to investigate the effectiveness of antioxidants on visual function and ophthalmic diseases.

1. Main Text

Proper eye healthcare is a vital component of maintaining one’s overall health. Negligent care of the eyes contributes to a multitude of ophthalmic diseases, resulting in impaired vision and affecting daily activities. These diseases may be minor in themselves, resulting in relatively insignificant symptoms such as slight inflammation or irritation. However, over time, more serious diseases may result in significant eye damage, decreased quality of vision, or total blindness.

Approximately 250 million people worldwide suffer from varying degrees of vision loss [1]. The leading causes of vision loss are common eye conditions such as cataracts, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), which largely affect older adults. While the origins and causes of age-related eye diseases are complex and multifactorial, oxidative stress has been implicated as a common conducive mechanism. The eye is susceptible to oxidative stress due to its high oxygen consumption, high concentrations of polyunsaturated fatty acids, and cumulative exposure to high-energy visible light. These factors combined lead to excessive generation of reactive oxygen species (ROS), which are free radicals containing oxygen, and can trigger oxidative damage to deoxyribonucleic acid (DNA), proteins, and lipids [2], inducing apoptosis of ocular cells and resulting in ophthalmic diseases [3]. It has been hypothesized that antioxidants may be of benefit in retaining better vision or even reversing vision impairment. Therefore, there is significant research interest in the role of dietary antioxidants and the potential therapeutic benefits of antioxidant supplements as a simple and cost-effect strategy for disease prevention and/or control [4–7]. This review will focus on the antioxidant properties of carotenoids (lutein and zeaxanthin), anthocyanins (saffron and bilberry), and vitamins (vitamin A) in the context of treating or preventing age-related eye diseases.

1.1. Evidence for Carotenoids

Xanthophyll (oxygen-containing) carotenoids, including lutein and zeaxanthin, are selectively concentrated in vision-related tissues (the eye and brain) [8]. Nearly all human ocular structures except the vitreous, cornea, and sclera contain lutein, zeaxanthin, and metabolites. The macula contains lutein and zeaxanthin with concentrations up to 100-fold higher than elsewhere in the eye [9]. Macular carotenoids are estimated to absorb 40 to 90% of incident blue light (depending on concentration) [10], protecting the retina from light-related damage [11] and reducing light scatter. The presence of oxidized metabolites in the retinal pigment epithelium (RPE), lens, ciliary body, and iris also suggests that lutein and zeaxanthin are protective against oxidative stress [12]. Lutein and zeaxanthin have also been found to prevent the increase in oxidation-induced cytokines and upregulate the expression of inflammation-related genes [13, 14]. In addition to its retinal effects, intake of a lutein supplement has been found to lower circulating levels of a rate-limiting enzyme in the alternative complement activation pathway, which itself plays an important role in the inflammatory response and the development of AMD [15, 16].

Several studies have demonstrated evidence of an inverse relationship between the presence of lutein and zeaxanthin in the retina and the risk for AMD [17–21]. An increase in macular pigment optical density (MPOD) level, where approximately 16.8 to 27.9% change in MPOD (), and a small nonsignificant improvement in visual acuity (VA) have been found in AMD patients who received oral lutein supplements for six months [22] and over one year [23]. An electroretinographic study has shown that the use of carotenoid supplements containing lutein, zeaxanthin, and meso-zeaxanthin may improve the visual function of type 2 diabetes patients [24], where best-corrected visual acuity (BCVA) remained normal (≥9/10) in each eye, while mean central foveal thickness (CFT) increased approximately 5 to 7 μm in each eye (). Multifocal electroretinography (mfERG) has revealed a significantly increased retinal response density surrounding the fovea (all central 3 rings) in both eyes two years after carotenoids supplement intake in type 2 diabetes patients (). Additionally, daily intake of lutein supplements in healthy individuals also showed increased MPOD levels alongside improvement in contrast and glare sensitivity [25]; with a significant increase in MPOD levels at the more central measured eccentricities after 6 months of intervention, significant improvement in contrast sensitivity after 3 months of intervention, and change in glare sensitivity threshold after a year of intervention.

Higher lutein and zeaxanthin levels in the diet or blood are associated with decreased risk of macular disease [26–35]. However, many factors affect the degeneration of macular pigments, including physical inactivity, poor diet, low levels of lutein and zeaxanthin in the diet and serum, smoking, components of metabolic syndrome (i.e., obesity, diabetes, and hypertension), and common variants in genes related to macular pigment optical density (MPOD) and/or serum lutein and zeaxanthin [36]. These factors help in predicting the odds of developing early/intermediate AMD [37].

A reduction in genetic risk for AMD among individuals with high lutein and zeaxanthin intake has been observed among several cohorts (the Rotterdam Study [38], a pooled analysis of the Rotterdam and Blue Mountain Eye studies [39], and Carotenoids in Age-related Eye Disease Study (CAREDS) [40]). Despite the lowest rates of AMD being reported in individuals consuming 5 to 6 mg/day [41–44], diets high in lutein and zeaxanthin are also high in other carotenoids which may contribute to lower risk [44]. Lutein and zeaxanthin supplements alone did not influence AMD progression or have significant changes in BVCA over three years [45], as a significant increase in macular pigment (MP) was observed despite having significant improvements in contrast sensitivity at 36 months of intervention. However, slowed AMD progression was seen when combined with other antioxidant supplements [46]. Average BCVA in patients receiving an oral preparation containing lutein, zeaxanthin, vitamin C, vitamin E, copper, and zinc was approximately 4.8 letters better than the placebo group after 36 months (). While these patients showed insignificant improvement in contrast sensitivity, slower AMD progression along a morphologic severity scale was observed.

The results of primary analyses in the Age-Related Eye Disease Study 2 (AREDS2) [47] trial suggest that including 10 mg of lutein and 2 mg of zeaxanthin in high-dose antioxidant supplements does not lower the progression to advanced AMD, as the hazard ratio (HR) compared with placebo were 0.89 to 0.97 () in all intervention groups. However, secondary analyses [48] have indicated a modestly lower five-year risk of progression in participants who began the study with low levels of lutein and zeaxanthin in their diets, or when the antioxidant supplements did not contain beta-carotene, as the hazard ratio appear to be less than 1 during the exploratory analyses and in eyes with bilateral large drusen at baseline ( for development of late AMD and neovascular AMD). While there is no recommended daily intake for lutein and zeaxanthin, the intake of lutein is recommended to be higher than zeaxanthin among all age groups [49]. The health benefits of a daily intake of 10 mg of lutein and 2 mg of zeaxanthin have been shown in a randomized, double-blind, placebo-controlled human study [28].

Exposure to light at the retinal level increases phagocytosis in the outer segment (OS) of photoreceptors and induces the formation of ROS by RPE cells [50], followed by photooxidative stress in the retina when an imbalance develops between ROS and endogenous antioxidative systems [51]. Moreover, the impaired retinal antioxidant status may lead to the overexpression of proinflammatory and angiogenic mechanisms, which accounts for injured retinal microvasculature [52]. Nutritional supplements such as polyphenol and xanthophyll that scavenge ROS have been shown to prevent or delay the progression of early AMD by direct interaction with rhodopsin, modulate visual pigment function, and protect retinal cells from oxidative stress-induced cell death [53, 54]. Anthocyanins have been found to act directly as antioxidants to neutralize ROS by donating hydrogen ions and modulating cell signaling pathways [55], as well as effects on anti-inflammatory and antiapoptotic pathways and gene expression [56].

1.2. Evidence for Saffron

Crocus sativus L. (Iridaceae), commonly known as saffron, has been studied for its main components (crocins, crocetin, picrocrocin, and safranal) and its potent antioxidant activity [57–60], as well as the binding capacity of saffron metabolites to biomolecules, which protects them from free radicals [57, 61]. Saffron components have also been found to possess anti-inflammatory and antiapoptotic effects, possibly by the inhibition of caspase-mediated apoptosis after retinal damage [62–65], as well as to increase oxygen diffusion and improve retinal and choroidal blood flow [66, 67]. Studies on saffron extract suggest that it may exert a protective effect in patients with glaucoma. Oral consumption of aqueous saffron extract for three weeks was able to reduce intraocular pressure (IOP) in primary open-angle glaucoma [68], from a mean IOP of mmHg to mmHg after three weeks of intervention as compared to the control group (mean baseline IOP of mmHg and mmHg after three weeks). Hydrophilic saffron extracts standardized to 3% crocin was also found to decrease the neuroinflammation associated with increased IOP by decreasing microglion numbers and morphological signs of their activation including soma size and process retraction, as well as reversed ocular hypertension induced down-regulation of P2RY12, preventing retinal ganglion cell death in a glaucoma model [69].

An electroretinographic study has shown an increase in the amplitude of “a” and “b” waves in rabbits with experimental retinal dystrophy on the fifth day after receiving an injection of the saffron extract [70]. Several studies have evaluated the impact of oral saffron supplementation (daily dose between 20 and 50 mg) on vision-related parameters in AMD patients. Both short-term and longer-term follow-ups demonstrated that saffron supplementation improved visual functions, despite variable formulation, doses, intervention durations, test methods, and outcome measures in these studies [60, 71–76]. Toxicology research has found that saffron is safe for human consumption. The dose of 30 mg/day seems efficacious, and toxic effects have been reported with 5 g or more, with a lethal dose of approximately 20 g [57, 77], although long-term and large-scale research works are yet to be conducted to confirm its effect on human health.

1.3. Evidence for Bilberry

Bilberry (Vaccinium myrtillus L.) from Ericaceae is particularly rich in anthocyanins, such as delphinidin, malvidin, petunidin, cyanidin, and peonidin [78], and it has been shown that bilberry anthocyanins modulate oxidative stress defense enzyme heme oxygenase-1 (HO-1) and glutathione S-transferase-pi in human RPE cells [79]. Fursova et al. found that long-term (1.5 to 3 months) supplementation with bilberry extract to OXYS rats affected by accelerated aging, which is associated with high sensitivity to oxidative stress, was effective in preventing degeneration. Approximately 70% of the control OXYS rats were found to have macular degeneration after 3 months of treatment, while bilberry supplementation prevented impairments in the lenses and retina [80]. Furthermore, Osada et al. found that bilberry extract attenuates photo-induced apoptosis and visual dysfunction, which is most likely due to ROS reduction and subsequent endoplasmic reticulum stress attenuation in a murine model of the photo-stressed retina (750 mg/kg body weight) [81].

Oral consumption of bilberry extract supplement for 8 weeks has been shown to reduce the video display terminals (VDT) load-induced ocular fatigue sensation including ocular pain, eye heaviness, uncomfortable sensation, and foreign body sensation, as reduced critical flicker fusion (CFF) was alleviated after 8 weeks of intervention (95% confidence interval, 0.10-1.60; ), although no change in near point variation (NPA) was seen [82]. A longer period of consumption of bilberry extract (12 weeks) relieved the tonic accommodation of the ciliary muscle caused by VDT tasks and near-vision tasks, as the postload high-frequency component- (HFC-) 1 value at week 12 was significantly improved in the bilberry group (), with significantly better task load at week 12 (ΔHFC-1) at week 12 () [83]. Bilberry extract may also alleviate the symptoms of dry eye disease (DED). The volume of tear secretion has shown improvement with bilberry extract supplement among subjects with DED over four weeks (), as well as a significant improvement of biological antioxidant potential (BAP, ) and increased in modified BAP/diacron-reactive oxygen metabolites (d-ROMs) ratio, an indicator of overall balance between antioxidant potential and oxidative stress [84]. Apart from that, long-term consumption of bilberry extract can slow down axial elongation and control myopia progression in children with high myopia. Mean increase in spherical diopter was significantly lower D to D) compared to controls D to D). The increase in axial length was also significantly lesser ( mm to mm) compared to the control ( mm to mm) after 24 months [85]. A larger prospective study over a longer duration could reveal the true efficacy of these supplements against their cost.

1.4. Evidence for Beta-Carotene

Beta-carotene is a naturally occurring retinol (vitamin A) precursor obtained from certain fruits and vegetables with potential antineoplastic and chemopreventive activities. As an antioxidant, beta-carotene inhibits free radical damage to DNA and is typically associated with eye health [86]. The Age-Related Eye Disease Study (AREDS) demonstrated that daily oral supplementation with antioxidative vitamins and minerals (vitamin C, vitamin E, beta-carotene, zinc, and copper) reduced the risk of developing advanced AMD by 25% at five years (odds ratio (OR), 0.72; 99% confidence interval (Cl), 0.52-0.98), as well as a significant reduction in rates of at least moderate visual acuity loss (OR, 0.73; 99% Cl, 0.54-0.99) [86]. However, a secondary analysis of the Age-Related Eye Disease Study 2 (AREDS2) shows that more lung cancers are diagnosed in participants with beta-carotene intake than those without [47]. Despite epidemiologic studies showing no association between dietary intake of vitamin A and reduced risk of AMD [43, 87], high levels of vitamin A, α-carotene, lycopene, and lutein intake were associated with low risk of cataract. Risk of nuclear cataract was lowest in people with high plasma concentration of α-carotene (OR, 0.5; 95% Cl, 0.3-0.9, ) or β-carotene (OR, 0.7; 95% Cl, 0.4-1.4, ), risk of cortical cataract was lowest in people with high plasma concentration of lycopene (OR, 0.4; 95% Cl, 0.2-0.8; ), and risk of posterior subcapsular cataract was lowest in people with high plasma concentration of lutein (OR, 0.5; 95% Cl, 0.2-1.0, ) [88].

2. Recommended Clinical Measurements of Antioxidant Effects on Vision

Given the fact that most antioxidants are not considered essential nutrients, most health authorities have yet to establish recommended daily intakes. Factors such as diet, gender, the existence of food intolerances, and the quantities of nutrients in foods also affect the daily average intakes of individuals. While it is more beneficial to consume whole food sources as they contain various other nutrients, supplements are available in the market for individuals who require greater quantities of specific nutrients that they might otherwise lack or insufficiently consume. Lutein supplements were available ranging from 5 mg to 25 mg, some with <5 mg of zeaxanthin, while recommended dose for eye health is 10 mg of lutein per day and 2 mg of zeaxanthin per day [28]. Daily intake of 50 mg of anthocyanins per day was recommended by the Chinese authorities to reduce oxidative stress levels and consequently the risk of degenerative diseases [89], where 50–88.5 mg of saffron extracts and 80–100 mg of bilberry extracts is available in each capsule. The recommended dietary allowance for vitamin A is 900 μg and 700 μg per day for adult males and females, respectively [90], with a tolerable upper intake level of 3000 μg per day.

Doses, regimes, methods of extraction, and drug interactions in the setting of a randomized trial must be elucidated to ensure the safety and efficacy of these treatments when given in combination. While we have presented the current evidence on the role of antioxidants on various ocular symptoms, such as dry eyes and presbyopia, one inherent limitation of these studies is the lack of objective outcomes, especially studies investigating presbyopia symptoms.

For example, a decrease in reduced antioxidant levels in the lens may promote the onset of presbyopia [91]. Hesperidin, a major flavonoid in citrus fruits and a natural antioxidant, was found to reduce the number of apoptotic cells, prevent premature cataract symptoms, maintain lens elasticity, and upregulate the mRNA expression of antioxidative enzymes in the selenite-induced cataract rat plasma and lens, hence delaying the formation of nuclear cataract [92] as well as the onset of presbyopia [93]. The challenges of such trials examining antioxidant effects include the influences of diet, environment, and various other patient characteristics, which are difficult to standardize.

Despite having some evidence for specific antioxidants with recommended doses impeding certain age-related eye diseases, there was a lack of extensive studies on the antioxidants’ effects on various ophthalmic diseases, and most studies available were concluded within a short period of time. The following table (Table 1) describes the clinical measurements which can be performed to understand the effectiveness of antioxidants on visual function and ophthalmic diseases.

3. Conclusion

In conclusion, prevention and treatment of age-related eye diseases with antioxidant substances and other supplements including polyphenol, xanthophyll carotenoids, anthocyanins, and other medicinal plants and natural products [105] have shown promising effects for a multitude of eye diseases. While polyphenols and xanthophyll carotenoids are the most commonly reported natural products used for AMD treatment with positive results, more research and clinical trials are necessary to understand their mechanisms of action.

Conflicts of Interest

The authors report no conflict of interest.

Authors’ Contributions

Writing—original draft preparation was done by PPC and PJW. Writing—review and editing was done by MLCB, RO, MM, and NMD. All authors have read and agreed to the published version of the manuscript.

References

S. R. Flaxman, R. R. A. Bourne, S. Resnikoff et al., “Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis,” Lancet Glob. Health, vol. 5, no. 12, pp. e1221–e1234, 2017.
View at: Publisher Site | Google Scholar
M. Nita and A. Grzybowski, “The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 3164734, 23 pages, 2016.
View at: Publisher Site | Google Scholar
G. Tezel, “Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences,” Progress in Retinal and Eye Research, vol. 25, no. 5, pp. 490–513, 2006.
View at: Publisher Site | Google Scholar
K. A. Weikel, C. J. Chiu, and A. Taylor, “Nutritional modulation of age-related macular degeneration,” Molecular Aspects of Medicine, vol. 33, no. 4, pp. 318–375, 2012.
View at: Publisher Site | Google Scholar
O. Sideri, K. T. Tsaousis, H. J. Li, M. Viskadouraki, and I. T. Tsinopoulos, “The potential role of nutrition on lens pathology: a systematic review and meta-analysis,” Survey of Ophthalmology, vol. 64, no. 5, pp. 668–678, 2019.
View at: Publisher Site | Google Scholar
E. Loskutova, C. O’Brien, I. Loskutov, and J. Loughman, “Nutritional supplementation in the treatment of glaucoma: a systematic review,” Survey of Ophthalmology, vol. 64, no. 2, pp. 195–216, 2019.
View at: Publisher Site | Google Scholar
C. Li, X. Miao, F. Li et al., “Oxidative stress-related mechanisms and antioxidant therapy in diabetic retinopathy,” Oxidative Medicine and Cellular Longevity, vol. 2017, Article ID 9702820, 15 pages, 2017.
View at: Publisher Site | Google Scholar
E. J. Johnson, “Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan,” Nutrition Reviews, vol. 72, no. 9, pp. 605–612, 2014.
View at: Publisher Site | Google Scholar
D. M. Snodderly, “Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins,” The American Journal of Clinical Nutrition, vol. 62, no. 6, pp. 1448S–1461S, 1995.
View at: Publisher Site | Google Scholar
J. T. Landrum and R. A. Bone, “Mechanistic evidence for eye diseases and carotenoids,” Carotenoids in Health and Disease, Marcel Dekker, New York, USA, pp. 445–472, 2004.
View at: Publisher Site | Google Scholar
F. M. Barker, D. M. Snodderly, E. J. Johnson et al., “Nutritional manipulation of primate retinas, V: effects of lutein, zeaxanthin, and n-3 fatty acids on retinal sensitivity to blue-light-induced damage,” Investigative Ophthalmology & Visual Science, vol. 52, no. 7, pp. 3934–3942, 2011.
View at: Publisher Site | Google Scholar
P. S. Bernstein, F. Khachik, L. S. Carvalho, G. J. Muir, D. Y. Zhao, and N. B. Katz, “Identification and quantitation of carotenoids and their metabolites in the tissues of the human eyes,” Experimental Eye Research, vol. 72, pp. 215–223, 2011.
View at: Google Scholar
Q. Bian, S. Gao, J. Zhou et al., “Lutein and zeaxanthin supplementation reduces photooxidative damage and modulates the expression of inflammation-related genes in retinal pigment epithelial cells,” Free Radical Biology & Medicine, vol. 53, no. 6, pp. 1298–1307, 2012.
View at: Publisher Site | Google Scholar
M. Sasaki, Y. Ozawa, T. Kurihara et al., “Neuroprotective effect of an antioxidant, lutein, during retinal inflammation,” Investigative Ophthalmology & Visual Science, vol. 50, no. 3, pp. 1433–1439, 2009.
View at: Publisher Site | Google Scholar
T. T. J. M. Berendschot, Y. Tian, I. Murray, and M. Makridaki, “Lutein supplementation leads to a decreased level of circulating complement factors,” Investigative Ophthalmology & Visual Science, vol. 54, p. 4124, 2013.
View at: Google Scholar
Y. Tian, A. Kijlstra, C. A. B. Webers, and T. T. J. M. Berendschot, “Lutein and factor D: two intriguing players in the field of age-related macular degeneration,” Archives of Biochemistry and Biophysics, vol. 572, pp. 49–53, 2015.
View at: Publisher Site | Google Scholar
Age-Related Eye Disease Study Research Group, “The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study AREDS report no. 22,” Archives of Ophthalmology, vol. 125, pp. 1225–1232, 2007.
View at: Google Scholar
S. Beatty, I. J. Murray, D. B. Henson, D. Carden, H. H. Koh, and M. E. Boulton, “Macular pigment and risk for age-related macular degeneration in subjects from a northern European population,” Investigative Ophthalmology & Visual Science, vol. 42, no. 2, pp. 439–446, 2001.
View at: Google Scholar
J. M. Nolan, J. Stack, E. O’Connell, and S. Beatty, “The relationships between macular pigment optical density and its constituent carotenoids in diet and serum,” Investigative Ophthalmology & Visual Science, vol. 48, no. 2, pp. 571–582, 2007.
View at: Publisher Site | Google Scholar
R. Liu, T. Wang, B. Zhang et al., “Lutein and zeaxanthin supplementation and association with visual function in age-related macular degeneration,” Investigative Ophthalmology & Visual Science, vol. 56, no. 1, pp. 252–258, 2015.
View at: Publisher Site | Google Scholar
L. Ma, R. Liu, J. H. Du, T. Liu, S. S. Wu, and X. H. Liu, “Lutein, zeaxanthin and meso-zeaxanthin supplementation associated with macular pigment optical density,” Nutrients, vol. 8, no. 7, p. 426, 2016.
View at: Publisher Site | Google Scholar
G. Weigert, S. Kaya, B. Pemp et al., “Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age-related macular degeneration,” Investigative Ophthalmology & Visual Science, vol. 52, no. 11, pp. 8174–8178, 2011.
View at: Publisher Site | Google Scholar
I. J. Murray, M. Makridaki, R. L. P. van der Veen, D. Carden, N. R. A. Parry, and T. T. J. M. Berendschot, “Lutein supplementation over a one-year period in early AMD might have a mild beneficial effect on visual acuity: the CLEAR study,” Investigative Ophthalmology & Visual Science, vol. 54, no. 3, pp. 1781–1788, 2013.
View at: Publisher Site | Google Scholar
M. M. Moschos, M. Dettoraki, M. Tsatsos, G. Kitsos, and C. Kalogeropoulos, “Effect of carotenoids dietary supplementation on macular function in diabetic patients,” Eye Vision, vol. 4, pp. 1–6, 2017.
View at: Google Scholar
Y. Yao, Q. H. Qiu, X. W. Wu, Z. Y. Cai, S. Xu, and X. Q. Liang, “Lutein supplementation improves visual performance in Chinese drivers: 1-year randomized, double-blind, placebo-controlled study,” Nutrition, vol. 29, no. 7-8, pp. 958–964, 2013.
View at: Publisher Site | Google Scholar
J. A. Mares, “Relationships of lutein and zeaxanthin to age-related macular degeneration: epidemiological evidence,” Carotenoids and Retinal Disease, CRC Press, Boca Raton, Florida, USA, pp. 63–74, 2013.
View at: Publisher Site | Google Scholar
N. I. Krinsky, J. T. Landrum, and R. A. Bone, “Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye,” Annual Review of Nutrition, vol. 23, no. 1, pp. 171–201, 2003.
View at: Publisher Site | Google Scholar
B. R. Hammond, L. M. Fletcher, F. Roos, J. Wittwer, and W. Schalch, “A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast,” Investigative Ophthalmology & Visual Science, vol. 55, no. 12, pp. 8583–8589, 2014.
View at: Publisher Site | Google Scholar
B. Yu, J. Wang, P. M. Suter et al., “Spirulina is an effective dietary source of zeaxanthin to humans,” The British Journal of Nutrition, vol. 108, no. 4, pp. 611–619, 2012.
View at: Publisher Site | Google Scholar
J. M. Nolan, R. Power, J. Stringham 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, vol. 57, no. 7, pp. 3429–3439, 2016.
View at: Publisher Site | Google Scholar
B. Olmedilla, F. Granado, I. Blanco, and M. Vaquero, “Lutein, but not α-tocopherol, supplementation improves visual function in patients with age-related cataracts: a 2-y double-blind, placebo-controlled pilot study,” Nutrition, vol. 19, no. 1, pp. 21–24, 2003.
View at: Publisher Site | Google Scholar
J. M. Stringham and B. R. Hammond, “Macular pigment and visual performance under glare conditions,” Optometry and Vision Science, vol. 85, no. 2, pp. 82–88, 2008.
View at: Publisher Site | Google Scholar
H. T. V. Vu, L. Robman, A. Hodge, C. A. McCarty, and H. R. Taylor, “Lutein and zeaxanthin and the risk of cataract: the Melbourne Visual Impairment Project,” Investigative Ophthalmology & Visual Science, vol. 47, no. 9, pp. 3783–3786, 2006.
View at: Publisher Site | Google Scholar
B.-J. Hu, Y.-N. Hu, S. Lin, W.-J. Ma, and X.-R. Li, “Application of lutein and zeaxanthin in nonproliferative diabetic retinopathy,” International Journal of Ophthalmology, vol. 4, no. 3, pp. 303–306, 2011.
View at: Publisher Site | Google Scholar
S. Gao, T. Qin, Z. Liu et al., “Lutein and zeaxanthin supplementation reduces H₂O₂-induced oxidative damage in human lens epithelial cells,” Molecular Vision, vol. 17, pp. 3180–3190, 2011.
View at: Google Scholar
K. J. Meyers, E. J. Johnson, P. S. Bernstein et al., “Genetic determinants of macular pigments in women of the carotenoids in age-related eye disease study,” Investigative Ophthalmology & Visual Science, vol. 54, no. 3, pp. 2333–2345, 2013.
View at: Publisher Site | Google Scholar
K. J. Meyers, J. A. Mares, R. P. Igo Jr. et al., “Genetic evidence for role of carotenoids in age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS),” Investigative Ophthalmology & Visual Science, vol. 55, no. 1, pp. 587–599, 2014.
View at: Publisher Site | Google Scholar
L. Ho, R. van Leeuwen, J. C. Witteman et al., “Reducing the genetic risk of age-related macular degeneration with dietary antioxidants, zinc, and ω-3 fatty acids: the Rotterdam study,” Archives of Ophthalmology, vol. 129, no. 6, pp. 758–766, 2011.
View at: Publisher Site | Google Scholar
J. J. Wang, G. H. Buitendijk, E. Rochtchina et al., “Genetic susceptibility, dietary antioxidants, and long-term incidence of age- related macular degeneration in two populations,” Ophthalmology, vol. 121, no. 3, pp. 667–675, 2014.
View at: Publisher Site | Google Scholar
K. J. Meyers, Z. Liu, A. E. Millen et al., “Joint associations of diet, lifestyle, and genes with age-related macular degeneration,” Ophthalmology, vol. 122, no. 11, pp. 2286–2294, 2015.
View at: Publisher Site | Google Scholar
J. A. Mares-Perlman, A. I. Fisher, R. Klein et al., “Lutein and zeaxanthin in the diet and serum and their relation to age-related maculopathy in the third national health and nutrition examination survey,” American Journal of Epidemiology, vol. 153, no. 5, pp. 424–432, 2001.
View at: Publisher Site | Google Scholar
S. M. Moeller, N. Parekh, L. Tinker et al., “Associations between intermediate age-related macular degeneration and lutein and zeaxanthin in the Carotenoids in Age-related Eye Disease Study (CAREDS),” Archives of Ophthalmology, vol. 124, no. 8, pp. 1151–1162, 2006.
View at: Publisher Site | Google Scholar
J. M. Seddon, U. A. Ajani, R. D. Sperduto et al., “Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group,” Journal of the American Medical Association, vol. 272, no. 18, pp. 1413–1420, 1994.
View at: Google Scholar
J. Wu, E. Cho, W. C. Willett, S. M. Sastry, and D. A. Schaumberg, “Intakes of lutein, zeaxanthin, and other carotenoids and age-related macular degeneration during 2 decades of prospective follow-up,” JAMA. Ophthalmology, vol. 133, no. 12, pp. 1415–1424, 2015.
View at: Publisher Site | Google Scholar
K. O. Akuffo, J. M. Nolan, A. N. Howard et al., “Sustained supplementation and monitored response with differing carotenoid formulations in early age-related macular degeneration,” Eye (London, England), vol. 29, no. 7, pp. 902–912, 2015.
View at: Publisher Site | Google Scholar
S. Beatty, U. Chakravarthy, J. M. Nolan et al., “Secondary outcomes in a clinical trial of carotenoids with coantioxidants versus placebo in early age-related macular degeneration,” Ophthalmology, vol. 120, no. 3, pp. 600–606, 2013.
View at: Publisher Site | Google Scholar
“Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration,” Journal of the American Medical Association, vol. 309, no. 19, pp. 2005–2015, 2013.
View at: Publisher Site | Google Scholar
E. Y. Chew, T. E. Clemons, J. P. SanGiovanni et al., “Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3,” JAMA Ophthalmology, vol. 132, no. 2, pp. 142–149, 2014.
View at: Publisher Site | Google Scholar
E. J. Johnson, J. E. Maras, H. M. Rasmussen, and K. L. Tucker, “Intake of lutein and zeaxanthin differ with age, sex, and ethnicity,” Journal of the American Dietetic Association, vol. 110, no. 9, pp. 1357–1362, 2010.
View at: Publisher Site | Google Scholar
Y. P. Jang, J. L. Zhou, K. Nakanishi, and J. R. Sparrow, “Anthocyanins protect against A2E photooxidation and membrane permeabilization in retinal pigment epithelial cells,” Photochemistry and Photobiology, vol. 81, no. 3, pp. 529–536, 2005.
View at: Publisher Site | Google Scholar
L. Fernández-Sánchez, P. Lax, A. Noailles, A. Angulo, V. Maneu, and N. Cuenca, “Natural compounds from saffron and bear bile prevent vision loss and retinal degeneration,” Molecules, vol. 20, no. 8, pp. 13875–13893, 2015.
View at: Publisher Site | Google Scholar
S. K. Gupta, B. Kumar, B. P. Srinivasan et al., “Retinoprotective effects of Moringa oleifera via antioxidant, anti-inflammatory, and anti-angiogenic mechanisms in streptozotocin-induced diabetic rats,” Journal of Ocular Pharmacology and Therapeutics, vol. 29, no. 4, pp. 419–426, 2013.
View at: Publisher Site | Google Scholar
H. L. Ramkumar, J. Tuo, D. F. Shen et al., “Nutrient supplementation with n3 polyunsaturated fatty acids, lutein, and zeaxanthin decrease A2E accumulation and VEGF expression in the retinas of Ccl2/Cx3cr1-deficient mice on Crb1rd8 background,” The Journal of Nutrition, vol. 143, no. 7, pp. 1129–1135, 2013.
View at: Publisher Site | Google Scholar
W. Kalt, A. Hanneken, P. Milbury, and F. Tremblay, “Recent research on polyphenolics in vision and eye health,” Journal of Agricultural and Food Chemistry, vol. 58, no. 7, pp. 4001–4007, 2010.
View at: Publisher Site | Google Scholar
R. J. Williams, J. P. E. Spencer, and C. Rice-Evans, “Flavonoids: antioxidants or signalling molecules?” Free Radical Biology & Medicine, vol. 36, no. 7, pp. 838–849, 2004.
View at: Publisher Site | Google Scholar
T. Tsuda, “Dietary anthocyanin-rich plants: biochemical basis and recent progress in health benefits studies,” Molecular Nutrition & Food Research, vol. 56, no. 1, pp. 159–170, 2012.
View at: Publisher Site | Google Scholar
E. Christodoulou, N. P. Kadoglou, N. Kostomitsopoulos, and G. Valsami, “Saffron: a natural product with potential pharmaceutical applications,” The Journal of Pharmacy and Pharmacology, vol. 67, no. 12, pp. 1634–1649, 2015.
View at: Publisher Site | Google Scholar
S. Rahaiee, S. Moini, M. Hashemi, and S. A. Shojaosadati, “Evaluation of antioxidant activities of bioactive compounds and various extracts obtained from saffron (Crocus sativus L): a review,” Journal of Food Science and Technology, vol. 52, no. 4, pp. 1881–1888, 2015.
View at: Publisher Site | Google Scholar
G. K. Broadhead, A. Chang, J. R. Grigg, and P. McCluskey, “Efficacy and safety of saffron supplementation: current clinical findings,” Critical Reviews in Food Science and Nutrition, vol. 56, no. 16, pp. 2767–2776, 2016.
View at: Publisher Site | Google Scholar
S. Di Marco, V. Carnicelli, N. Fraceschini et al., “Saffron: a multitask neuroprotective agent for retinal degenerative diseases,” Antioxidants (Basel), vol. 8, no. 7, p. 224, 2019.
View at: Publisher Site | Google Scholar
C. D. Kanakis, P. A. Tarantilis, C. Pappas, J. Bariyanga, H. A. Tajmir-Riahi, and M. G. Polissiou, “An overview of structural features of DNA and RNA complexes with saffron compounds: models and antioxidant activity,” Journal of Photochemistry and Photobiology B: Biology, vol. 95, no. 3, pp. 204–212, 2009.
View at: Publisher Site | Google Scholar
K. N. Nam, Y.-M. Park, H.-J. Jung et al., “Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells,” European Journal of Pharmacology, vol. 648, no. 1-3, pp. 110–116, 2010.
View at: Publisher Site | Google Scholar
M. Yamauchi, K. Tsuruma, S. Imai et al., “Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity,” European Journal of Pharmacology, vol. 650, no. 1, pp. 110–119, 2011.
View at: Publisher Site | Google Scholar
Y. Ohno, T. Nakanishi, N. Umigai, K. Tsuruma, M. Shimazawa, and H. Hara, “Oral administration of crocetin prevents inner retinal damage induced by N -methyl-d-aspartate in mice,” European Journal of Pharmacology, vol. 690, no. 1-3, pp. 84–89, 2012.
View at: Publisher Site | Google Scholar
E. Tamaddonfard, A. A. Farshid, K. Eghdami, F. Samadi, and A. Erfanparast, “Comparison of the effects of crocin, safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats,” Pharmacological Reports, vol. 65, no. 5, pp. 1272–1280, 2013.
View at: Publisher Site | Google Scholar
B. Xuan, Y. H. Zhou, N. Li, Z. D. Min, and G. C. Chiou, “Effects of crocin analogs on ocular blood flow and retinal function,” Journal of Ocular Pharmacology and Therapeutics, vol. 15, no. 2, pp. 143–152, 1999.
View at: Publisher Site | Google Scholar
M. Giaccio, “Crocetin from saffron: an active component of an ancient spice,” Critical Reviews in Food Science and Nutrition, vol. 44, no. 3, pp. 155–172, 2004.
View at: Publisher Site | Google Scholar
M. H. J. Bonyadi, S. Yazdani, and S. Saadat, “The ocular hypotensive effect of saffron extract in primary open angle glaucoma: a pilot study,” BMC Complementary and Alternative Medicine, vol. 14, pp. 1–6, 2014.
View at: Google Scholar
J. A. Fernandez-Albarral, A. I. Ramires, R. De Hoz, and N. Lopez-Villarin, “Neuroprotective and anti-inflammatory effects of a hydrophilic saffron extract in a model of glaucoma,” International Journal of Molecular Sciences, vol. 20, pp. 1–22, 2019.
View at: Google Scholar
P. Shukurova and R. Babaev, “A study into the effectiveness of the application of saffron extract in ocular pathologies in experiment,” Georgian Medical News, vol. 182, pp. 38–42, 2010.
View at: Google Scholar
B. Falsini, M. Piccardi, A. Minnella et al., “Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration,” Investigative Ophthalmology & Visual Science, vol. 51, no. 12, pp. 6118–6124, 2010.
View at: Publisher Site | Google Scholar
A. Lashay, G. Sadough, E. Ashrafi, M. Lashay, M. Movassat, and S. Akhondzadeh, “Short-term outcomes of saffron supplementation in patients with age-related macular degeneration: a double-blind, placebo-controlled, randomized trial,” Medical Hypothesis, Discovery and Innovation in Ophthalmology, vol. 5, no. 1, pp. 32–38, 2016.
View at: Google Scholar
A. Riazi, Y. Panahi, A. A. Alishiri, M. A. Hosseini, A. A. K. Zarchi, and A. Sahebkar, “The impact of saffron (Crocus sativus) supplementation on visual function in patients with dry age-related macular degeneration,” Italian Journal of Medicine, vol. 11, pp. 196–201, 2017.
View at: Google Scholar
G. K. Broadhead, J. R. Grigg, P. McCluskey, T. Hong, T. E. Schlub, and A. A. Chang, “Saffron therapy for the treatment of mild/moderate age-related macular degeneration: a randomised clinical trial,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 257, no. 1, pp. 31–40, 2019.
View at: Publisher Site | Google Scholar
M. Piccardi, D. Marangoni, A. M. Minnella et al., “A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function,” Evidence-based Complementary and Alternative Medicine, vol. 2012, Article ID 429124, 9 pages, 2012.
View at: Publisher Site | Google Scholar
D. Marangoni, B. Falsini, M. Piccardi et al., “Functional effect of saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report,” Journal of Translational Medicine, vol. 11, no. 1, p. 228, 2013.
View at: Publisher Site | Google Scholar
A. H. Mohamadpour, Z. Ayati, M. R. Parizadeh, O. Rajbai, and H. Hosseinzadeh, “Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers,” Iranian Journal of Basic Medical Sciences, vol. 16, no. 1, pp. 39–46, 2013.
View at: Google Scholar
Q. You, B. Wang, F. Chen, Z. Huang, X. Wang, and P. G. Luo, “Comparison of anthocyanins and phenolics in organically and conventionally grown blueberries in selected cultivars,” Food Chemistry, vol. 125, no. 1, pp. 201–208, 2011.
View at: Publisher Site | Google Scholar
P. E. Milbury, B. Graf, J. M. Curran-Celentano, and J. B. Blumberg, “Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells,” Investigative Ophthalmology & Visual Science, vol. 48, no. 5, pp. 2343–2349, 2007.
View at: Publisher Site | Google Scholar
A. Z. H. Fursova, O. G. Gesarevich, A. M. Gonchar, N. A. Trofimova, and N. G. Kolosova, “Dietary supplementation with bilberry extract prevents macular degeneration and cataracts in senesce-accelerated OXYS rats,” Advances in Gerontology, vol. 16, pp. 76–79, 2005.
View at: Google Scholar
H. Osada, T. Okamoto, H. Kawashima et al., “Neuroprotective effect of bilberry extract in a murine model of photo-stressed retina,” PLoS One, vol. 12, no. 6, p. e0178627, 2017.
View at: Publisher Site | Google Scholar
Y. Ozawa, M. Kawashima, S. Inoue et al., “Bilberry extract supplementation for preventing eye fatigue in video display terminal workers,” The Journal of Nutrition, Health & Aging, vol. 19, no. 5, pp. 548–554, 2015.
View at: Publisher Site | Google Scholar
M. Kosehira, N. Machida, and N. A. Kitaichi, “A 12-week-long intake of bilberry extract (Vaccinium myrtillus L.) improved objective findings of ciliary muscle contraction of the eye: a randomized, double-blind, placebo-controlled, parallel-group comparison trial,” Nutrients, vol. 12, no. 3, p. 600, 2020.
View at: Publisher Site | Google Scholar
A. Riva, S. Togni, F. Franceschi et al., “The effect of a natural, standardized bilberry extract (Mirtoselect®) in dry eye: a randomized, double blinded, placebo-controlled trial,” European Review for Medical and Pharmacological Sciences, vol. 21, no. 10, pp. 2518–2525, 2017.
View at: Google Scholar
I. A. N. Omar, “Effect of bilberry extract on slowing high-myopia progression in children: 2-year follow-up study,” Clinical Ophthalmology, vol. Volume 12, pp. 2575–2579, 2018.
View at: Publisher Site | Google Scholar
Age-Related Eye Disease Study Research Group, “A randomized, placebo-controlled, clinical trial of High-Dose Supplementation With vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision Loss,” Archives of Ophthalmology, vol. 119, no. 10, pp. 1417–1436, 2001.
View at: Publisher Site | Google Scholar
C. Delcourt, J. P. Cristol, F. Tessier, C. L. Léger, B. Descomps, and L. Papoz, “Age-related macular degeneration and antioxidant status in the POLA study,” Archives of Ophthalmology, vol. 117, no. 10, pp. 1384–1390, 1999.
View at: Publisher Site | Google Scholar
C. R. Gale, N. F. Hall, D. I. W. Phillips, and C. N. Martyn, “Plasma antioxidant vitamins and carotenoids and age-related cataract,” Ophthalmology, vol. 108, no. 11, pp. 1992–1998, 2001.
View at: Publisher Site | Google Scholar
Chinese Nutrition Society, Chinese DRIs Handbook, Standards Press of China, Beijing, China, 2013.
N. Pescosolido, A. Barbato, R. Giannotti, C. Komaiha, and F. Lenarduzzi, “Age-related changes in the kinetics of human lenses: prevention of the cataract,” International Journal of Ophthalmology, vol. 9, no. 10, pp. 1506–1517, 2016.
View at: Google Scholar
Y. Nakazawa, M. Aoki, S. Ishiwa et al., “Oral intake of α-glucosyl-hesperidin ameliorates selenite-induced cataract formation,” Molecular Medicine Reports, vol. 21, no. 3, pp. 1258–1266, 2020.
View at: Publisher Site | Google Scholar
Y. Nakazawa, M. Aoki, Y. Doki et al., “Oral consumption of α-glucosyl-hesperidin could prevent lens hardening, which causes presbyopia,” Biochemistry and Biophysics Reports, vol. 25, p. 100885, 2021.
View at: Publisher Site | Google Scholar
Institute of Medicine Food and Nutrition Board, Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc, National Academy Press, Washington, DC, 2001.
J. R. Hayes, J. E. Sheedy, J. A. Stelmack, and C. A. Heaney, “Computer use, symptoms, and quality of life,” Optometry and Vision Science, vol. 84, no. 8, pp. E738–E755, 2007.
View at: Publisher Site | Google Scholar
M. González-Pérez, R. Susi, B. Antona, A. Barrio, and E. González, “The computer-vision symptom scale (CVSS17): development and initial validation,” Investigative Ophthalmology & Visual Science, vol. 55, no. 7, pp. 4504–4511, 2014.
View at: Publisher Site | Google Scholar
M. del Mar Seguí, J. Cabrero-García, A. Crespo, J. Verdú, and E. Ronda, “A reliable and valid questionnaire was developed to measure computer vision syndrome at the workplace,” Journal of Clinical Epidemiology, vol. 68, no. 6, pp. 662–673, 2015.
View at: Publisher Site | Google Scholar
J. S. Wolffsohn, R. Arita, R. Chalmers et al., “TFOS DEWS II diagnostic methodology report,” The Ocular Surface, vol. 15, no. 3, pp. 539–574, 2017.
View at: Publisher Site | Google Scholar
R. M. Schiffman, M. D. Christianson, G. Jacobsen, J. D. Hirsch, and B. L. Reis, “Reliability and validity of the ocular surface disease index,” Archives of Ophthalmology, vol. 118, no. 5, pp. 615–621, 2000.
View at: Publisher Site | Google Scholar
R. L. Chalmers, C. G. Begley, and B. Caffery, “Validation of the 5-Item Dry Eye Questionnaire (DEQ-5): discrimination across self-assessed severity and aqueous tear deficient dry eye diagnoses,” Contact Lens & Anterior Eye, vol. 33, no. 2, pp. 55–60, 2010.
View at: Publisher Site | Google Scholar
L. Abetz, K. Rajagopalan, P. Mertzanis et al., “Development and validation of the impact of dry eye on everyday life (IDEEL) questionnaire, a patient-reported outcomes (PRO) measure for the assessment of the burden of dry eye on patients,” Health and Quality of Life Outcomes, vol. 9, no. 1, p. 111, 2011.
View at: Publisher Site | Google Scholar
C. W. McMonnies and A. Ho, “Responses to a dry eye questionnaire from a normal population,” Journal of the American Optometric Association, vol. 58, no. 7, pp. 588–591, 1987.
View at: Google Scholar
D. A. Schaumberg, A. Gulati, W. D. Mathers et al., “Development and validation of a short global dry eye symptom index,” The Ocular Surface, vol. 5, no. 1, pp. 50–57, 2007.
View at: Publisher Site | Google Scholar
A. J. Bron, M. B. Abelson, G. Ousler et al., “Methodologies to diagnose and monitor dry eye disease: report of the diagnostic methodology subcommittee of the international Dry Eye Workshop,” The Ocular Surface, vol. 2007, pp. 108–152, 2007.
View at: Google Scholar
D. C. Hood, M. Bach, M. Brigell et al., “International Society For Clinical Electrophysiology of Vision. ISCEV standard for clinical multifocal electroretinography (mfERG) (2021 update),” The International Society for Clinical Electrophysiology, vol. 124, no. 1, pp. 1–23, 2021.
View at: Google Scholar
F. Bosch-Morell, V. Villagrass, T. Ortega et al., “Medicinal plants and natural products as neuroprotective agents in age-related macular degeneration,” Neural Regeneration Research, vol. 15, no. 12, pp. 2207–2216, 2020.
View at: Publisher Site | Google Scholar

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