Cataracts

Cataracts

1 Overview

Summary and Quick Facts

  • Cataracts are the most common cause of blindness and are generally treated with surgery. The formation of cataracts is associated with diabetes, but many people may not be aware that higher-than-normal blood glucose levels, even if not clinically considered diabetes, can contribute to cataracts.
  • In this protocol you will not only learn how cataracts form and what causes them, but also how dietary and lifestyle considerations may help prevent cataracts and slow the progression of lens opacification. Conventional treatment of cataracts will be discussed, as will some novel and emerging therapeutic strategies that may improve treatment outcomes.
  • By proactively managing identified risk factors for cataracts, one may be able to reduce their onset and/or progression. Natural interventions including antioxidants such as vitamin C and riboflavin, as well as glycation inhibitors such as carnosine and carnitine, may help reduce the risk of cataract formation.

What are Cataracts?

Cataracts are opacities that form in the lens of the eye, causing visual obstruction. They arise when proteins in the eye form aggregates due to incorrect three-dimensional structure. There are several factors that cause proteins to aggregate, including oxidative stress and glycation. Cataracts are the most common cause of blindness and are generally treated with surgery.

The formation of cataracts is associated with diabetes, but many people may not be aware that higher-than-normal blood glucose levels, even if not clinically considered diabetes, can contribute to cataracts.

Natural interventions including antioxidants such as vitamin C and riboflavin, as well as glycation inhibitors such as carnosine and carnitine, may help reduce the risk of cataract formation.

What are the Risk Factors for Cataracts?

  • Age
  • Gender – women are more likely to develop cataracts
  • Poor nutrition
  • Diabetes
  • Exposure to ionizing radiation such as X-rays or UV rays
  • Smoking and drinking alcohol
  • Genetic predisposition

What are the Signs and Symptoms of Cataracts?

Note: Depending on the type of cataract, the symptoms can vary. Some common symptoms of the different types of cataracts include:

  • Seeing double or multiple images
  • Difficulty distinguishing colors
  • Glare or halos around lights
  • Impaired ability to see in bright lights

How are Cataracts Conventionally Treated?

  • Surgery

What Emerging Therapies Appear Promising for Cataracts?

  • Combining non-steroidal anti-inflammatory drugs (NSAIDs) with surgery
  • Statins

What Dietary or Lifestyle Changes Can Help Prevent Cataracts?

  • Quitting smoking
  • Limiting exposure to UV radiation by wearing sunglasses
  • Limiting alcohol consumption
  • Increasing intake of fruits and vegetables, as they are natural sources of antioxidants
  • Avoiding foods high in saturated fats and consuming more omega-3 fatty acids
  • Controlling blood glucose levels

What Natural Interventions May Be Beneficial for Preventing Cataracts?

  • Glutathione. Glutathione scavenges free radicals in the lens, preventing oxidative damage to the proteins.
  • Vitamin C. Vitamin C acts as an antioxidant to support healthy proteins in the lens and is linked with lower incidence of cataract development.
  • Vitamin B2 (riboflavin). Riboflavin is an essential component of flavin adenine dinucleotide (FAD), which is used by the enzyme that converts glutathione to its bioactive form. High riboflavin levels have been associated with reduced risk of cataract formation.
  • Vitamin B6. Vitamin B6 has been shown to reduce the production of advanced glycation end products (AGEs) in diabetic lenses.
  • Vitamin E. Vitamin E acts as an antioxidant and low levels are associated with an increased risk of developing cataracts.
  • Other antioxidants and glycation inhibitors that can help prevent cataracts are N-acetylcysteine,lipoic acid, melatonin,carnosine, carnitine, and quercetin.
  • Carotenoids. Carotenoids (a type of plant pigment) such as lutein, zeaxanthin, and meso-zeaxanthin can absorb light and prevent damage caused by UV rays. They are found in high concentrations in the eye and can help prevent cataract formation.
  • Other interventions for healthy eyes include bilberry, green and black tea, resveratrol, and selenium.

2 Introduction

As we age, the lens of the eye can become clouded, impairing vision. These opacities in the normally transparent lens are called cataracts, and represent the most common cause of blindness (MedlinePlus 2012). Almost 25 million people worldwide have vision loss as a result of cataracts, which accounts for over 47% of blindness globally (Resnikoff 2004; West 2010; Allen 2011; Hashim 2012). More than 50% of people in the United States over age 80 either have cataracts or have undergone surgery due to this condition (MedlinePlus 2012).

While cataracts are a significant impairment, they can be surgically treated by removing the original lens and replacing it with a long-lasting synthetic lens. Though there are no FDA-approved drug treatment options for cataracts (Yanoff 2013), cataract surgery represents one of the most successful interventions in medicine (Lichtinger 2012).

Although conventional surgical treatment is an important consideration in the management of advanced cataracts, the medical establishment often fails to emphasize the need to maintain healthy blood glucose levels to slow progression or prevent onset of cataracts. Most physicians appreciate the association between overt diabetes and cataracts, but many overlook the role of elevated blood sugar in cataract formation among non-diabetics (Aoki 2007; Drexler 2001; Jessani 2009). The lens of the eye is particularly susceptible to glycation reactions, in which high glucose concentrations damage proteins and contribute to tissue dysfunction (Jain 2002; Pereira 1996; Franke 2003). A number of human studies have associated higher-than-normal glucose levels with substantially increased risk of various types of cataract (Weintraub 2002; Kanthan 2011; Saxena 2004; Tan 2008). Sadly, although it may be possible to prevent cataracts or slow their progression simply by controlling blood sugar levels (Taylor 1995; Madar 1993, 1994; Cohen-Melamed 1995), many at-risk individuals remain unaware of the profound impact of elevated glucose levels on the lens of the eye.

In this protocol you will not only learn how cataracts form and what causes them, but also how dietary and lifestyle considerations may help prevent cataracts and slow the progression of lens opacification. Conventional treatment of cataracts will be discussed, as will some novel and emerging therapeutic strategies that may improve treatment outcomes. The role of targeted natural interventions in combating specific disease processes that underlie cataract development, such as oxidative stress and glycation, will be examined as well.

3 Understanding the Eye and the Lens

The eye, arguably the most important sensory organ, has evolved to provide detailed imagery of the world around us in much the same way that a camera provides a photographer with a picture. Like a camera, the eye contains a series of internal structures instrumental to its function. Like a camera’s lens shutter, the cornea represents a protective layer of cells that help refract light. As with a camera’s lens, the main function of the optic lens is to refract light and help focus it on the retina, where images are processed into signals that can be interpreted by the brain via the optic nerve. The proper function of the lens hinges on its transparency (MedlinePlus 2012).

The lens can be thought of as a light-permeable barrier consisting of two major components: an epithelium and a mass of fiber cells. The epithelium, which is a single layer of cells nearest the front of the eye, provides protection to the interior layers. The inner mass of elongated fiber cells ensures the transparency of the lens (Bhat 2001). Maintenance of healthy structure and function of the lens depends on proper functioning of complex cellular machinery, which if compromised, can lead to decreased lens transparency (Mathias 2010; Michael 2011).

4 Causes and Risk Factors

Oxidative Stress

Living cells are naturally exposed to free radicals including reactive oxygen species (ROS) (Michael 2011; Colorado State University 2013). Mitochondria (cellular organelles) produce free radicals as a by-product of their normal function (Cadenas 2004). These free radicals can damage other cellular structures such as proteins, lipids, and DNA. Exposure of cells to excess oxidative stress that overwhelms intrinsic antioxidant defenses can lead to cellular dysfunction and destruction (Carper 1999; Uttara 2009). The lens epithelium is particularly sensitive to oxidative stress, and oxidative damage of this layer of cells can result in the formation of lens opacities (Carper 1999; Sharma 2009).

Many diseases are associated with the incorrect folding of proteins as a result of oxidative damage. The three-dimensional structure of proteins dictates their function; therefore, any structural damage to proteins can lead to their malfunction. Since the protein concentration in the lens is the highest in the body, the lens is vulnerable to this type of perturbation (Surguchev 2010).

The transparency of the lens depends on the correct three-dimensional structure of the lens proteins, and protein aggregation in the lens has been linked to the formation of cataracts (Moreau 2012). This is especially true when antioxidant mechanisms fail to prevent oxidative damage, causing a cascade of damage to several types of proteins in the lens (Carper 1999; Babizhayev 2010). One type of lens protein known to cause cataracts when damaged is the crystallins (Sharma 2009). Crystallins provide structural support to lens cells and allow for the optimal bending of light as it enters the lens (Bloemendal 2004; Sharma 2009). 

Glycation

In addition to oxidative stress, studies have uncovered a causative role for another modification, known as glycation, in the opacification of the lens (Swamy 1987). Glycation causes proteins to become damaged and dysfunctional. It is the result of sugar molecules interacting with proteins and modifying their structure. Proteins in the lens, which are among the longest-lived in the body, are particularly susceptible to glycation (Franke 2003).

The result of this interaction is the formation of toxic molecules termed advanced glycation end products, or AGEs. Accumulation of AGEs is associated with several age-related diseases including diabetes, renal failure, and cataracts (Wautier 2001; Hashim 2011; Swamy 1987; Wautier 2001; Franke 2003; Gul 2009). Additionally, AGE accumulation is thought to be directly related to the intensity of yellowing of the lens, which is often observed in cataracts (Shamsi 2000).

Risk Factors

In addition to the pathological roles of oxidative stress and glycation in cataract formation, several factors are known to increase cataract risk. Many of the following risk factors are associated with increased glycation and/or oxidative stress.

Age. There is a strong association of cataract development with age and oxidative damage. Since there is no turnover of lens epithelial cells, the accumulation of oxidative damage over many years is an important component of cataract development (Truscott 2005).

Gender. Although cataracts afflict both men and women, a study in an Australian population revealed that 58% of people who have suffered from cataracts are women, and a higher incidence of cataracts in women is supported by studies on other continents (Giuffrè 1995; Delcourt 2000; Kanthan 2008; Mares 2010; Vashist 2011). 

Poor Nutrition. Lack of a proper diet and low intake of vitamins, minerals, and antioxidants found in fruits and vegetables predispose people to developing cataracts (Jacques 1988; Bunce 1990; Knekt 1992; Christen 2005; Zhou 2012).

Diabetes. There is a strong association between duration of diabetes and the development of cataracts (Kim 2006; West 2010). In people with diabetes, cataracts may begin to form up to 20 years earlier than in non-diabetics (Hashim 2012). Since diabetes is characterized by elevated blood sugar, glycation reactions occur more rapidly and frequently in this population, which explains a great deal of the association between diabetes and cataracts (Hashim 2011).

Exposure to Ionizing Radiation. Occupational or personal exposure to ionizing radiation, such as X-rays or ultraviolet (UV) rays, is associated with an increased risk of developing cataracts (Worgul 1976; Vano 2010; Varma 2011). In order to decrease exposure of the lens to UV radiation, it is recommended that protective eyewear or sunglasses with UV filters be worn during daylight hours.

Smoking Status and Alcohol Consumption. There is a significantly increased risk for cataracts for those who smoke and among those who drink alcohol heavily (Delcourt 2000; Klein 2003; Jun 2009).

Genetics. When cataracts form in newborns, they are often associated with mutations in proteins involved in metabolic pathways related to the metabolism of a sugar called galactose, while mutations in structural proteins like crystallins occur frequently in childhood cataracts (Churchill 2011; Santana 2011; Chan 2012; Clark 2012).

Additional factors have been implicated in the development of some types of cataracts, but more studies need to be conducted to determine the strength of these relationships (Heiba 1995; Merriam 1996; Sanderson 2000; Zhou 2007; Jun 2009; Hashim 2012; Worgul 1976; Alapure 2012; Paine 2010; Tsai 2003; Vano 2010):

  • Imbalanced calcium ion signaling
  • Long-term steroid (glucocorticoid) use
​​​

5 Signs and Symptoms

There are three main types of age-related cataract, determined by which part of the eye they affect; they each can cause different symptoms:

  • Nuclear cataracts. Nuclear cataracts affect the central part of the lens. Nuclear cataracts arise as a result of normal age-related accumulation of lens fibers in the central region of the lens. Patients with nuclear cataracts may see double or multiple images. As the cataract progresses, the lens transitions to yellow or brown, and this may lead to even more difficulties in distinguishing colors (Medline 2012; Bollinger 2008).
  • Cortical cataracts. Cortical cataracts are the result of the formation of whitish opaque regions at the outer edge of the lens, or the cortex. This type of cataract is associated with diabetes (Chang 2011). Cortical cataracts may not significantly impair vision if the lens opacities remain outside the visual axis, but they can cause glare during activities such as driving (Medline 2012; Bollinger 2008).
  • Posterior subcapsular cataracts. Posterior subcapsular cataracts first appear on the backside of the lens. They typically impair near vision to a greater degree than distance vision. In addition, they may affect the ability to see in bright light and cause the appearance of halos around lights during nighttime (Medline 2012; Bollinger 2008).

In addition to age-related cataracts that appear in adults, some children are either born with cataracts or develop them early in childhood. About half of congenital cataracts have genetic causes, while some of the remaining ones are caused by metabolic diseases or infections during development (Santana 2011; Medline 2012). 

Early Stages of Cataract Development

Age-related cataracts cause a slow, painless loss of vision typically not associated with other signs or symptoms. The first sign of cataracts is usually a significant loss in transparency in a small region of the lens. This affects one’s ability to discern the detailed contours of objects in bright light during the day or when viewing objects near bright light at night. In addition, it leads to a loss of contrast sensitivity, which is the ability to distinguish between relative differences in light intensity (Regan 1993; Cheng 2001; Zigler 2011; Sia 2012).

Similar to a loss in contrast sensitivity is the increased incidence of glare. This occurs when cataracts begin to cause an aura around objects, and it happens most often during the daytime (Lasa 1995; Howes 2008; Mayo Clinic 2010).  Glare, which can occur in all forms of cataract, can develop anywhere on the optic lens.

In many cases of nuclear cataract formation, there is also a change in how light bends, or refracts, as it moves from outside the eye through the lens. This is termed myopic shift, and is clinically defined as a hardening of the lens that causes a change from farsightedness to nearsightedness (Younan 2002; Aslam 2007; Samarawickrama 2007; Zigler 2011).

Late Stages of Cataracts

As cataracts continue to progress, the severity of these initial symptoms increases. The extent of cataract progression is defined by the degree of opacity in that part of the lens and the overall state of visual acuity.  Immature cataracts are determined as those occurring in lenses with significant areas of translucency. Progression to mature cataracts is marked by significant opaque structures occurring in the lens, while hypermature cataracts are those where liquefaction of the lens structure has occurred. This final stage of cataract development results in the leakage of a milky white liquid into the lens capsule, resulting in substantial inflammation and pain (Hemalatha 2012).

6 Diagnosis and Conventional Treatment

Cataracts are diagnosed by an ophthalmologist using the Snellen visual acuity test. In this test, the patient is asked to read letters that become smaller on every line, and the ability to recognize them is measured (Levy 2005; Medline 2012). Once suspected, cataracts are assessed using a specialized microscope that focuses light into a slit to examine the lens structure. It measures not only the visual acuity, but also the degree of light scattering, which is the transmission of the light in random directions when the environment that it crosses presents irregularities (van der Mooren 2011; Medline 2012). Cataracts are also detected using a device known as a funduscope or ophthalmoscope, which is used to examine the retinal blood vessels and other structures of the eye by inspection (Schneiderman 1990; Merck 2012). The inability to see the retinal blood vessels usually occurs because of an opacity that interferes with the ability of the light to pass through the eye, and this is usually caused by cataracts or bleeding inside the eye (Schneiderman 1990).

Once diagnosed, and after the stage and severity of the cataracts are assessed, a patient may elect to undergo surgical removal of the lens containing the cataract(s) and replacement with a synthetic intraocular lens (IOL). In these procedures, which usually last for less than an hour and are normally performed on an outpatient basis, surgeons make a small incision on the lens, disrupt the lens either ultrasonically or by using lasers, and insert the IOL into the capsule bag where the natural lens used to be located (Medline 2012).

If a cataract is so advanced that this procedure is unable to break up the lens, then a larger incision is made, and the lens nucleus is removed through the exposed lens capsule. The soft portions of the lens near the edges are removed using a vacuum, leaving a shell for IOL implantation. Referred to as extracapsular extraction, this surgical process can result in higher rates of secondary infection and other complications (eg, secondary cataracts) (Smith 1982; Ruit 1991; Apple 1992; Gyldenkerne 1998; Clark 2000; Haripriya 2012; Medline 2012; Merck 2012).

Other complications that may occur include swelling of the cornea, retinal detachment, internal eye infections, secondary glaucoma, excessive post-operative inflammation, capsular opacification, and other conditions that may result in permanent partial or complete loss of eyesight (Morikubo 2004; Franzco 2010; Speeg-Schatz 2011; Haug 2012; Taravati 2012).

Even without suffering from a serious complication, a significant number of people who have cataract surgery go on to develop clouding of the lens capsule (Pandey 2004; Eichenbaum 2012; Lichtinger 2012). This complication may occur at various times after surgery, usually three months to four years later (Pandey 2004). In these cases, the lens capsule, which was originally part of the lens previously removed, will require additional laser surgery. This complication has medical and financial implications, including additional medical care costs, time off from work, and patient suffering (Pandey 2004; Eichenbaum 2012). Younger patients are at higher risk for this complication (Pandey 2004).

If surgical removal of a lens with a cataract is inadvisable, or if significant loss of visual acuity has not occurred, ophthalmologists may suggest delaying surgery (National Eye Institute 2009; Medline 2012). Cataract surgery may also be inadvisable if the patient suffers from other forms of ocular disease, such as age-related macular degeneration, which was reported by some clinicians to worsen after cataract surgery (Casparis 2012). In the interim, patients are advised to use soft contact lenses or eyeglasses with stronger prescriptions and to adopt alternative treatment strategies (National Eye Institute 2009).

Secondary Cataracts

Secondary cataracts arise when, after surgery, lens epithelial cells divide and move to the back side of the lens where they transform into another cell type; the light-scattering changes they cause result in the secondary loss of vision (Coombes 1999; Marcantonio 1999; Wormstone 2009). This complication can also be thought of as a wound healing response that occurs after surgery (Bertelmann 2001). The rates of secondary cataract formation vary; some sources indicate that they may occur in up to 50% of patients, and while advances in surgical techniques helped lower their frequency in recent years, they were still reported to occur in 14-18% of patients, and remain a major complication (Coombes 1999; Spalton 1999; West-Mays 2010). They occur even more frequently and have a quicker onset in children (Awashti 2009). Secondary cataracts are easy to treat using laser treatment, and the risk of complications is small (Emery 1998; Spalton 1999). Immunological and gene therapy approaches to prevent this complication are under development and appear promising (Bertelmann 2001; Saika 2008).

7 Novel and Emerging Medical Therapies and/or Drug Strategies

Combining NSAIDs with Surgical Removal of the Affected Lens

One active area of anti-cataract research is that of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs work by inhibiting enzymes that promote inflammation (Kim 2010). NSAIDs have been evaluated in several clinical trials, and there is evidence that when applied locally, they can reduce inflammation after cataract surgery (Kim 2010). NSAIDs appear from some studies to be more effective than corticosteroids in certain respects, and other studies reported that the two have additive effects (Kim 2010). When administered after the surgical removal of the lens, NSAIDs have been shown to help reduce post-surgical complications (eg, excessive fluid build-up, pain, and swelling) by reducing inflammation (Wittpenn 2008; McColgin 1999). Research is ongoing to compare NSAIDs and determine which are the most effective after cataract surgery (Cho 2009; Bucci 2011; Bradley 2013).

Statin Drugs

Some early observational studies suggested an association between long-term statin use and an increased chance of developing cataracts, while others found marginal or no risks (Derby 2000; Jick 2001; Machan 2012). However, clinical research showed that statins may actually lower the risk of developing cataracts, with a 50% decrease in the risk of mainly nuclear and cortical cataracts in one study (Klein 2006; Tan 2007). Another study demonstrated that the potential beneficial effects of statins are present with longer duration of statin administration, finding protective effects against cataract surgery in patients aged 50-64 (Fong 2012). Although these discoveries may provide a new therapeutic application for statins, additional research is required to understand what formulations of statins are required to prevent cataract formation as well as how statins may prevent cataracts.

8 Dietary and Lifestyle Management Strategies

By proactively managing identified risk factors for cataracts, one may be able to reduce their onset and/or progression. The following lifestyle management strategies center on avoiding oxidative damage and glycation reactions in the lens (National Eye Institute 2009):

  • Quitting smoking, since toxins from tobacco smoke damage proteins such as crystallins (Randerath 1992; Paik 2000)
  • Limiting or eliminating exposure to UV radiation from the sun
  • Avoiding work-related exposure to X-rays and gamma irradiation
  • Limiting or reducing the consumption of alcohol

In addition to these lifestyle changes, numerous studies revealed that food-based antioxidants are useful in the treatment of cataracts (Agte 2010). By increasing the consumption of foods rich in antioxidants and phytochemicals, such as vegetables and fruits, the human body may be able to more effectively scavenge and eliminate free radicals and reactive oxygen species. 

Other dietary considerations include avoiding meats high in cholesterol and saturated fats (eg, fatty cuts of beef, processed meats) and consuming more fish rich in omega-3-fatty acids (eg, salmon). Nuts and seeds, particularly walnuts and flaxseed oil, are additional sources of omega-3 fatty acids (Psota 2006). Omega-3 fatty acids were shown to protect against oxidative damage caused by UV radiation in other tissues, and since the development of cataracts was causally linked to oxidative damage in the lens, this action could represent another mechanism by which they protect against cataract formation or progression (Rhodes 2003; van der Pols 2011).

Controlling Blood Glucose Levels to Prevent Cataracts – Even in Non-Diabetics

Diabetes is a well-known risk factor for cataracts (Rowe 2000; Heydari 2012), but the link between elevated blood glucose levels and cataracts is less appreciated in non-diabetics.

Even in people without overt diabetes, elevated blood sugar causes significant damage throughout the body by increasing oxidative stress and promoting protein-destroying glycation reactions, leading to a number of chronic diseases (Paik 2012; McNeilly 2011; Nitenberg 2006; Miyazawa 2012; Lindsey 2009). The lens of the eye is particularly susceptible to damage associated with elevated glucose (Jain 2002; Pereira 1996; Franke 2003).

Researchers at Harvard University conducted a meticulous analysis on more than 87 000 individuals over a 16-year period and concluded that “[posterior subcapsular] cataract may be mediated in part by glucose intolerance and insulin resistance, even in the absence of clinical diabetes” (Weintraub 2002). Several subsequent studies corroborated these findings:

  • In an analysis of nearly 3600 people 49 or older, fasting glucose levels above 108 mg/dL were associated with a 79% greater risk of cortical cataract development over a 10-year period compared to concentrations below 108 mg/dL. Moreover, for each 18 mg/dL increase above this level, risk of progression of some types of cataracts increased by up to 25% (Kanthan 2011).
  • In a similarly designed study on more than 2300 people, fasting glucose levels above 108 mg/dL were associated with a 2.2-fold higher risk of cortical cataracts over a 5-year period (Saxena 2004).
  • Another analysis of 3654 elderly subjects in Australia showed that glucose concentrations between 108 and 126 mg/dL were predictive of doubled risk of cortical cataracts over a 10-year period (Tan 2008).

Interventions associated with improved glucose control have been shown to reduce cataract risk. For example, in an animal model of cataracts, caloric restriction, that is, the reduction of calorie intake to a level short of malnutrition, was associated with a 27% reduction in glucose levels, fewer incidence of cataracts, and less cataract progression (Taylor 1995). Other animal studies showed that use of the anti-diabetic drug acarbose, which inhibits carbohydrate absorption and suppresses glucose concentrations, both reduced incidence and lessened progression of cataracts (Madar 1993, 1994; Cohen-Melamed 1995).

The dangers posed by impaired fasting glucose concentrations are, sadly, often underappreciated by the medical establishment (Jessani 2009). Conventional physicians, in many cases, fail to take preventive action until clinical diabetes manifests, which is defined as fasting blood glucose levels of 126 mg/dL or higher (Aoki 2007; Drexler 2001). In order to avert unnecessary disease, Life Extension® suggests that most individuals strive for an optimal fasting blood glucose level of 70 - 85 mg/dL. More information about glucose control is available in the Weight Loss protocol.

9 Targeted Natural Interventions

Antioxidant Protection

Glutathione.  Since glutathione is present in very high concentrations in the lens and is essential for lens transparency, it is an important endogenous antioxidant molecule in the lens (Giblin 2000). Glutathione directly scavenges reactive oxygen species and free radicals, preventing the oxidation of structural proteins in the lens; this is particularly important in several types of cataracts, where oxidative damage to lens proteins appears to play a key role (Kamei 1993; Boscia 2000).  After scavenging reactive oxygen species and free radicals, the oxidized form of glutathione is readily recycled by a specialized enzyme (Lou 2003). As we age, the recycling of glutathione decreases progressively, the pool of reduced glutathione decreases, and oxidized forms of glutathione begin to build up (Xing 2010). This is especially true in the center of the adult lens, known as the nucleus, where even small amounts of UV exposure can drive free radical formation and the generation of cataracts (Giblin 2000; Spector 1995). Nutrients currently taken by most Life Extension customers, such as N-acetylcysteine, lipoic acid, melatonin, and selenium, naturally increase glutathione activity in the body (Atkuri 2007; Jariwalla 2008; Limon-Pacheco 2010; Jiang 2012).

Vitamin C.  Also known as ascorbic acid, vitamin C provides extra antioxidant support in the lens by acting as a “sink” for ROS and free radicals. Its oxidized form, dehydroascorbic acid, is then converted back to ascorbic acid by glutathione and indirectly in reactions that depend on glutathione (Giblin 2000; Lou 2003; Michael 2011). Therefore, vitamin C and glutathione are thought to work together to promote proper water balance within the lens and prevent protein clumping.

The importance of vitamin C for the health of the eye is supported by the finding that vitamin C concentrations in the lens are 20-30 times higher than those in the plasma (Ravindran 2011). In addition, its importance is supported by experiments showing that inhibitors of the enzyme that recycles glutathione cause a marked increase in dehydroascorbic acid, and that dehydroascorbic acid can cause loss of transparency in the lens in animals if it is not converted back into vitamin C (Giblin 2000; Michael 2011). A study examining the effect of long-term dietary supplementation with vitamin C in women showed that supplementation over 10 years significantly decreased the incidence of early age-related cataracts at any location in the lens. Importantly, this study excluded women previously diagnosed with cataracts, to make sure that those who started vitamin C supplementation at the recommendation of their doctors, and as a result of their diagnoses, were not included (Jacques 1997). Another study, which included a large number of men and women, revealed that high consumption of vitamin C, alone or together with other antioxidants (vitamin E, beta-carotene, and zinc), protected against the development of nuclear cataracts (Tan 2009). A study that enrolled over 4000 participants reported that for every 1 mg/dL increase in vitamin C in the serum, there was a 26% decrease in cataracts (Simon 1999). Additionally, in a study in India that enrolled over 5600 individuals, a strong association was found between high serum vitamin C levels and low incidences of cataract (Ravindran 2011).

Vitamin B2.  Also known as riboflavin, vitamin B2 is a vital component of flavin adenine dinucleotide (FAD). FAD, which is directly involved in breaking down carbohydrates and lipids, is important for proper cellular energy balance, and is also used by the enzyme that recycles glutathione back into its bioactive form. It was shown in several animal models that deficiency of dietary riboflavin can lead to cataracts (Bunce 1990). Several studies in humans reported that riboflavin is important in preventing the formation of cataracts. In one study, women with the highest dietary riboflavin intake, as compared to those with the lowest intake, had a lower risk for cataracts (Mares-Perlman 1995). Another study reported that individuals with the highest dietary riboflavin intake had an approximately 50% lower risk of developing cataracts (Cumming 2000).

Vitamin E. Vitamin E naturally occurs in eight different chemical forms, including alpha-tocopherol and gamma-tocopherol (Albanes 1996; MayoClinic 2012). It possesses distinct antioxidant properties and prevents the accumulation of free radicals produced during fatty acid breakdown. Since it is fat-soluble, vitamin E protects fatty tissues and cellular membranes by neutralizing free radicals and ROS. One study among women revealed that those with the highest intake of vitamin E from food and supplements had a 14% lower risk of cataracts (Christen 2008). Another study that examined participants 40–79 years old revealed lens opacities were more frequent in people with lower vitamin E levels (Leske 1995). Yet another study showed that the level of total tocopherol, which is the sum of the serum alpha-tocopherol and gamma-tocopherol, was associated with a decreased risk of developing cataracts (Lyle 1999).

Lipoic acid. Evidence suggests the potent antioxidant lipoic acid may help prevent diabetic cataract formation (Packer 1995; Maitra 1996; Kojima 2007). Since it is distributed in fat-soluble and water-soluble areas of cells and tissues, lipoic acid neutralizes a variety of free radicals (Bast 1988; Packer 1995). Lipoic acid exists in two forms: R-lipoic acid and S-lipoic acid. Of these two, R-lipoic acid in isolation was shown to prevent cataract formation (Maitra 1996). The higher efficacy of R-lipoic acid as compared to alpha-lipoic acid, which is a mixture of both forms, may be related to the higher rate of R-lipoic acid absorption by the lens.

N-acetylcysteine. N-acetyl-L-cysteine (NAC), which is a powerful antioxidant and derivative of the amino acid cysteine, has been shown to prevent opacification in the lens (Wang 2009). NAC also supports the production of glutathione (Pizzorno 1999; Zafarullah 2003; Radtke 2012). By combining NAC with diallyl disulfide, a major organosulfide found in garlic oil, researchers discovered that the latter could boost the antioxidant properties of the former, and the combination prevented the formation of cataracts (Zhao 1998). In animal models, NAC has been shown to prevent lens opacification and inhibit cataract formation (Wang 2009; Carey 2011). Another study found that the combination of NAC and glutathione ethyl ester (GSH-EE), administered as eye drops, slightly inhibited the progression of diabetic cataracts at early stages in rats (Zhang 2008).

Melatonin.  Melatonin, a naturally occurring hormone, has been shown to reduce oxidative stress in the lens and protect against cataract formation (Yaqci 2006; Taysi 2008). Although the mechanism(s) involved have yet to be determined, the increased production of glutathione or direct scavenging of free radicals are thought to be involved (Abe 1994). Given that melatonin levels decline with age, and in light of the rising incidence of cataracts in the latter part of life, melatonin supplementation may be useful for cataract prevention among aging individuals (Abe 1994).

Combating Glycation Reactions and Protecting Lens Structure and Function

Carnosine. Carnosine, along with one of its derivatives N-acetyl-carnosine, is a potent inhibitor of glycation reactions and oxidative damage; it has been shown to efficiently penetrate the lens (Hipkiss 2000; Babizhayev 2012; Wang 2000). Like glutathione, carnosine levels decrease with age (Bellia 2009; Everaert 2011). At moderately high concentrations, carnosine was able to attenuate UV-induced aggregation of lens proteins (Babizhayev 2009). When delivered topically as eye drops twice daily, a solution of N-acetyl-carnosine has been shown to delay onset of diabetes-induced cataracts (Attanasio 2009; Shi 2009;). 

N-acetyl-carnosine eye drops have also been shown to be effective in dogs. Visual improvements were reported in 80% of the participating dogs administered eye drops containing N-acetyl-carnosine (Williams 2006). Taken together with information from human trials and experiments in rodents, it appears that N-acetyl-carnosine eye drops may offer considerable protection against the formation and progression of cataracts (Quinn 1992; Attanasio 2009; Babizhayev 2009; Shi 2009).

Carnitine and Acetyl-L-Carnitine. Carnitine is a naturally occurring, amino acid-like compound found in all mammals with essential roles in normal function of the mitochondria, the energy powerhouses of cells; its derivative, acetyl-L-carnitine, is a powerful antioxidant and has been shown to combat glycation reactions (Reuter 2012; AMR 2010; Swamy-Mruthinti 1999). An examination of extracted human cataractous lenses showed that as opacification increased, carnitine concentrations decreased, with lenses containing the greatest opacification having about 30% lower carnitine concentrations than those with the least opacification (Gawecki 2004). In an animal model of cataracts, acetyl-L-carnitine strongly inhibited chemical-induced cataractogenesis. The researchers attributed the effects of acetyl-L-carnitine to its role as an antioxidant within the lens (Elanchezhian 2007). In a subsequent study, researchers from this same group showed that acetyl-L-carnitine also guards against “self-destruction”, or apoptosis of lens cells (Elanchezhian 2010). Evidence also indicates acetyl-L-carnitine protects against cataract development subsequent to ionizing radiation exposure by upregulating intrinsic antioxidant defense mechanisms (Kocer 2007).

Bioflavonoids.  Bioflavonoids, a class of plant-derived molecules with antioxidant properties, that may be beneficial in cataracts by helping combat the accumulation of water within lens cells, which disrupts normal light refraction (Head 2001; Matsuda 2002). Specifically, the bioflavonoid quercetin, the most widely consumed flavonoid in the human diet, was shown to inhibit diabetic cataract development, possibly acting on multiple pathways, and maintain the transparency of the lens in response to oxidative stress (McLauchlan 1997; Stefek 2011). Another animal experiment showed that quercetin helped maintain lens transparency by balancing calcium, sodium, and potassium ions within the lens (Ramana 2007).

Vitamin B6. Vitamin B6, or pyridoxine, is an important water-soluble cofactor necessary for the metabolism of amino acids and the synthesis of nucleic acids required for DNA replication and repair. It has been shown to significantly reduce the production of AGEs in the diabetic lens (Jain 2002; Padival 2006). Though human studies in cataract patients still need to be conducted, a trial in which vitamin B6 and vitamin B1 were administered to diabetic patients showed the combination significantly inhibited DNA glycation in white blood cells, suggesting systemic benefit (Polizzi 2012).

Additional Support for Healthy Eyes

Carotenoids.  Carotenoids, a type of pigment found in plants, absorb light and safeguard against the oxidative effects of UV rays. Several carotenoids, including lutein, zeaxanthin and meso-zeaxanthin are not only present at high levels in the retina, but also help prevent cataract formation and macular degeneration (Arnal 2009; Gao 2011; Kijlstra 2012). A study on a large group of women, ages 45–71, revealed that dietary lutein and zeaxanthin, and foods rich in these carotenoids, reduced the risk of cataracts that were sufficiently severe to require surgery (Chasan-Taber 1999). Another large study that enrolled people >40 years old found that those with a high dietary intake of lutein and zeaxanthin had a lower risk for nuclear cataracts (Vu 2006). In another study on 1802 women, subjects in the highest quintile (one-fifth) of distribution for blood levels or dietary intake of lutein and zeaxanthin were 32% less likely to have nuclear cataract compared to women in the lowest quintile (Moeller 2008). In a small double-blind, randomized clinical trial on 17 patients with cataracts, supplementation with lutein (15 mg, 3 times weekly for up to 2 years) was associated with improved visual acuity (Olmedilla 2003).

Bilberry.  Bilberry is rich in anthocyanins, which are plant pigments that exert a variety of beneficial effects in the human body, including functioning as antioxidants and modulating inflammatory processes (Tsuda 2012; Karlsen 2010). Importantly, these anti-inflammatory and antioxidant effects were observed within the eye in an animal model (Miyake 2012). In an experimental model involving animals prone to age-related eye diseases such as macular degeneration and cataracts, long-term administration of bilberry extract completely abrogated impairments in the lens and retinas, whereas 70% of control animals developed cataract and macular degeneration (Fursova 2005). Bilberry has yet to be studied in large trials to assess its effects on cataracts in humans, but controlled studies have found benefits associated with bilberry supplementation, alone or in combination with other nutrients that support eye health, for eye strain and glaucoma (Kawabata 2011; Shim 2012).

Green tea and back tea. Green and black teas contain antioxidant molecules called catechins and polyphenols, which have been studied in many human health conditions (Singh 2011; Miyazawa 2000; Kerio 2013). Several animal studies show that green and/or black tea can mitigate cataract formation or progression. In one such study on rats with chemical-induced diabetes, green and black teas, administered in drinking water, were shown to retard cataract development by reducing the detrimental effects of elevated glucose on the lenses (Vinson 2005). Another study found that green tea extract bolstered antioxidant defenses and reduced the incidence of chemical-induced cataracts in an animal model (Gupta 2002). A similar study on an animal model of chemical-induced cataracts revealed that green and black tea extracts slowed progression of lens opacification (Thiagarajan 2001).

Resveratrol. Resveratrol, a natural polyphenol found in several plants (including grapes, peanuts, and pines), has multiple health benefits due to its function as an antioxidant (Zheng 2010). In an animal model of chemically-induced cataracts, resveratrol was shown to reduce oxidative stress in the lens and suppress cataract formation (Doganay 2006). Resveratrol was also able to increase the survival of human lens epithelial cell cultures that were subjected to oxidative stress, and it decreases the cellular markers of aging (Li 2011). These effects could be explained by its ability to increase the activity of intrinsic antioxidant enzymes – superoxide dismutase, catalase, and heme oxygenase (Zheng 2010).

Selenium.  Selenium is a trace mineral involved in many biologic functions within the human body. Studies have shown that selenium can slow the development of cataracts by lowering oxidative stress in the lens (Zhu 2012). Although additional studies are required to determine how selenium prevents oxidative damage in the lens, it has been shown to enhance recycling of glutathione (Chada 1989; Baker 1993).

Abe M, Reiter RJ, Orhii PB, Hara M, Poeggeler B. Inhibitory effect of melatonin on cataract formation in newborn rats: evidence for an antioxidative role for melatonin. Journal of Pineal Research. 1994;17(2):94-100.

Agte V, Tarwadi K. The importance of nutrition in the prevention of ocular disease with special reference to cataract. Ophthalmic Research. 2010;44:166-172.

Alapure BV, Praveen MR, Gajjar DU, Vasavada AR, Parmar TJ, Arora AI. Matrix metalloproteinase-2 and -9 activities in the human lens epithelial cells and serum of steroid induced posterior subcapsular cataracts. Molecular Vision. 2012;18:64-73.

Albanes D, Heinonen OP, Taylor PR, Virtamo J, Edwards BK, Rautalahti M, et al. Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. Journal of the National Cancer Institute. 1996;88 :1560-1570.

Allen D. Cataract. Clinical Evidence (Online). 2011;pii:0708.

AMR. Acetyl-L-carnitine. Monograph. Alternative medicine review : a journal of clinical therapeutic. Apr 2010;15(1):76-83.

Aoki TJ, White RD. Initiating insulin in patients with type 2 diabetes. The Journal of family practice. Aug 2007;56(8 Suppl Hot Topics):S12-20.

Apple DJ, Solomon KD, Tetz MR, Assia EI, Holland EY, Legler UF, et al. Posterior capsule opacification. Survey of Ophthalmology. 1992;37:73-116.

Arnal E, Miranda M, Almansa I, et al. Lutein prevents cataract development and progression in diabetic rats. Graefe’s Archives in Clinical and Experimental Ophthalmology. 2009;247(1):115-120.

Aslam TM, Haider D, Murray IJ. Principles of disability glare measurement: an ophthalmological perspective. Acta Ophthalmologica Scandinavica. 2007; 85(4):354-360.

Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency. Current opinion in pharmacology. Aug 2007;7(4):355-359.

Attanasio F, Cataldo S, Fisichella S, et al. Protective effects of L- and D-carnosine on alpha-crystallin amyloid fibril formation: implications for cataract disease. Biochemistry. 2009;48(27):6522-6531.

Awasthi N, Guo S, Wagner BJ. Posterior capsular opacification: a problem reduced but not yet eradicated. Archives of Ophthalmology. 2009;127(4):555-562.

Babizhayev MA, Burke L, Micans P, Richer SP. N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population. Clinical Interventions in Aging. 2009;4:31-50.

Babizhayev MA, Deyev AI, Yermakova VN, Brikman IV, Bours J. Lipid peroxidation and cataracts: N-acetylcarnosine as a therapeutic tool to manage age-related cataracts in human and in canine eyes. Drugs Research and Development. 2004;5(3):125-139.

Babizhayev MA, Micans P, Guiotto A, et al. N-acetylcarnosine lubricant eyedrops possess all-in-one universal antioxidant protective effects of L-carnosine in aqueous and lipid membrane environments, aldehyde scavenging, and transglycation activities inherent to cataracts: a clinical study of the new vision-saving drug N-acetylcarnosine eyedrop therapy in a database population of over 50,500 patients.  American Journal of Ophthalmology. 2009;16(6):517-533.

Babizhayev MA. Structural and functional properties, chaperone activity and posttranslational modifications of alpha-crystallin and its related subunits in the crystalline lens: N-acetylcarnosine, carnosine and carcinine act as alpha- crystallin/small heat shock protein enhancers in prevention and dissolution of cataract in ocular drug delivery formulations of novel therapeutic agents. Recent Patents on Drug Delivery & Formulation. 2012;6(2):107-148.

Baker RD, Baker SS, LaRosa K, Whitney C, Newburger PE. 1993. Selenium regulation of glutathione peroxidase in human hepatoma cell line Hep3B. Archives of Biochemistry and Biophysics. 304:53-57.

Barbosa-Sabanero K, Hoffmann A, Judge C, Lightcap N, Tsonis PA, Del Rio-Tsonis K. Lens and retina regeneration: new perspectives from model organisms. The Biochemical Journal. 2012;447(3):321-334.

Bast A, Haenen GR. Interplay between lipoic acid and glutathione in the protection against microsomal lipid peroxidation. Biochimica et Biophysica Acta. 1988 16;963(3):558-561.

Bellia F, Calabrese V, Guarino F, Cavallaro M, Cornelius C, De Pinto V, Rizzarelli E. Carnosinase levels in aging brain: redox state induction and cellular stress response. Antioxidants & Redox Signaling. 2009;11(11): 2759-2775.

Bertelmann E, Kojetinsky C. Posterior capsule opacification and anterior capsule opacification. Current Opinion in Ophthalmology. 2001;12(1):35-40.

Bhat SP. The ocular lens epithelium. Bioscience Reports. 2001;21(4):537-563.Bloemendal H, de Jong W, Jaenicke R, Lubsen NH, Slingsby C,Tardieu A. Ageing and vision: structure, stability and function of lens crystallins. Progress in Biophysics and Molecular Bioliology. 2004;86(3):407-485.

Bollinger KE, Langston RH. What can patients expect from cataract surgery? Cleveland Clinic journal of medicine. Mar 2008;75(3):193-196, 199-200.

Boscia F, Grattagliano I,  Vendemiale G,  Micelli-Ferrari T, Altomare E. Protein oxidation and lens opacity in humans." Investigative Ophthalmology and Visual Science. 2000;41(9):2461-2465.

Bucci FA Jr, Waterbury LD. A randomized comparison of to-aqueous penetration of ketorolac 0.45%, bromfenac 0.09% and nepafenac 0.1% in cataract patients undergoing phacoemulsification. Current Medical Research and Opinion. 2011;27(12):2235-2239.

Bunce GE. Nutritional factors in cataract. Annual Review of Nutrition. 1990;10:233-254.

Cadenas E. Mitochondrial free radical production and cell signaling. Molecular Aspects of Medicine. 2004;25(1-2):17-26.

Carey JW, Pinarci EY, Penugonda S, Karacal H, Ercal N. In vivo inhibition of l-buthionine-(S,R)-sulfoximine-induced cataracts by a novel antioxidant, N-acetylcysteine amide. Free Radical Biology & Medicine. 2011;50(6):722-729.

Carper DA, Sun JK, Iwata T, Zigler JS Jr, Ibaraki N, Lin LR, Reddy V. "Oxidative Stress Induces Differential Gene Expression in a Human Lens Epithelial Cell Line." Investigative Ophthalmology and Visual Science. 1999;40(2):400-406.

Casparis H, Lindsley K, Kuo IC, Sikder S, Bressler NB. Surgery for cataracts in people with age-related macular degeneration. Cochrane Database Systems Review. 2012;13(6):CD006757.

Chada S, Whitney C, Newburger PE. Post-transcriptional regulation of glutathione peroxidase gene expression by selenium in the HL-60 human myeloid cell line. Blood. 1989;74(7):2535-2541.

Chan E, Mahroo OA, Spalton DJ. Complications of cataract surgery. Clinical and Experimental Optometry. 2010;93(6):379-389.Chan WH, Biswas S, Ashworth JL, Lloyd IC. Congenital and infantile cataract: aetiology and management. European Journal of Paediatrics. 2012;171(4):625-630.

Chang JR, Koo E, Agron E, Hallak J, Clemons T, Azar D, . . . Chew EY. Risk factors associated with incident cataracts and cataract surgery in the Age-related Eye Disease Study (AREDS): AREDS report number 32. Ophthalmology. Nov 2011;118(11):2113-2119.

Chasan-Taber L, Willett WC, Seddon JM, et al. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. American Journal of Clinical Nutrition. 1999;70(4):509-516.

Cheng CY, Yen MY, Chen SJ, Kao SC, Hsu WM, Liu JH. Visual acuity and contrast sensitivity in different types of posterior capsule opacification. Journal of Cataract & Refractive Surgery. 2001;27(7):1055-1060.

Cho H, Wolf KJ, Wolf EJ. Management of ocular inflammation and pain following cataract surgery: focus on bromfenac ophthalmic solution. Clinical Ophthalmology. 2009;3:199-210.

Christen WG, Liu S, Glynn RJ, Gaziano, JM, Buring JE. A prospective study of dietary carotenoids, Vitamins C and E, and risk of cataract in Women." Archives of Ophthalmology. 2008;126(1):102-109.

Christen WG, Liu S, Schaumberg DA, Buring JE. Fruit and vegetable intake and the risk of cataract in women. American Journal of Clinical Nutrition. 2005;81(6):1417-1422.

Churchill A, Graw, J. Clinical and experimental advances in congenital and paediatric cataracts. Philosophical transactions of the Royal Society B in Biological Sciences. 2011;366(1568):1234-1249.

Clark AR, Lubsen NH, Slingsby C. sHSP in the eye lens: crystalline mutations, cataract and proteostasis. International Journal of Biochemical Cell Biology. 2012;44(10):1687-1697.

Clark DS. Posterior capsule opacification. Current Opinion in Ophthalmology. 2000;11(1):56-64.

Cohen-Melamed E, Nyska A, Pollack A, Madar Z. Aldose reductase (EC 1.1.1.21) activity and reduced-glutathione content in lenses of diabetic sand rats (Psammomys obesus) fed with acarbose. The British journal of nutrition. Nov 1995;74(5):607-615.

Congdon N, Vingerling JR, Klein BE, et al. Prevalence of cataract and pseudophakia/aphakia among adults in the United States. Archives of Ophthalmology. 2004;122(4):487-494.

Coombes A, Seward H. Posterior capsular opacification prevention: IOL Design and Material. The British Journal of Ophthalmology. 1999;83(6):640-641.

Cumming RG,  Mitchell P, Smith W. Diet and cataract: The Blue Mountains Eye Study. Ophthalmology. 2000;107(3): 450-456.

Delcourt C, Cristol JP, Tessier F, Leger CL, Michel F, Papoz L. Risk factors for cortical, nuclear, and posterior subcapsular cataracts: the POLA study. Pathologies Oculaires Liees a l'Age. American Journal of Epidemiology. 2000;151(5):497-504.

Derby L, Maier WC. Risk of cataract among users of intranasal corticosteroids. Journal of Allergy and Clinical Immunology. 2000;105(5):912-916.

Doganay S, Borazan M, Iraz M, Cigremis Y. The effect of resveratrol in experimental cataract model formed by sodium selenite. Current eye research. Feb 2006;31(2):147-153.

Drexler AJ, Robertson C. Type 2 diabetes. How new insights, new drugs are changing clinical practice. Geriatrics. Jun 2001;56(6):20-24, 32-23.

Eichenbaum JW. Geriatric vision loss due to cataracts, macular degeneration, and glaucoma. Mount Sinai Journal of Medicine. 2012;79(2):276-294.

Elanchezhian R, Ramesh E, Sakthivel M, Isai M, Geraldine P, Rajamohan M, et al. Acetyl-L-carnitine prevents selenite-induced cataractogenesis in an experimental animal model. Current Eye Research. 2007;32(11):961-71.

Elanchezhian R, Sakthivel M, Geraldine P, Thomas PA. Regulatory effect of acetyl-l-carnitine on expression of lenticular antioxidant and apoptotic genes in selenite-induced cataract. Chemico-biological interactions. Mar 30 2010;184(3):346-351.

Emery J. Capsular opacification after cataract surgery and capsule. Current Opinion in Ophthalmology. 1998;9(1):60-5.

Everaert I, Mooyaart A, Baguet A, Zutinic A, Baelde H, Achten E, et al. Vegetarianism, female gender and increasing age, but not CNDP1 genotype, are associated with reduced muscle carnosine levels in humans. Amino Acids. 2011;40(4):1221-1229.

Feher J, Papale A, Mannino G, Gualdi L, Balacco Gabrieli C. Mitotropic compounds for the treatment of age-related macular degeneration. The metabolic approach and a pilot study. Ophthalmologica. 2003;217(5):351-357.

Fernandez MM, Afshari NA. Cataracts: we have perfected the surgery, but is it time for prevention? Current Opinions in Ophthamology. 2011;22(1):2-3.

Fine BS, Brucker AJ. Macular edema and cystoid macular edema. American Journal of Ophthalmology. 1981;92(4):466-481.

Fong DS, Poon KY. Recent statin use and cataract surgery. American Journal of Ophthalmology. 2012;153(2):222-228e1.

Franke S, Dawczynski J, Strobel J, Niwa T, Stahl P, Stein G. Increased levels of advanced glycation end products in human cataractous lenses. Journal of Cataract & Refractive Surgery. 2003;29(5):998-1004.

Franke S, Dawczynski J, Strobel J, Niwa T, Stahl P, Stein G. Increased levels of advanced glycation end products in human cataractous lenses. Journal of cataract and refractive surgery. May 2003;29(5):998-1004.

Fursova A, Gesarevich OG, Gonchar AM, Trofimova NA, Kolosova NG. [Dietary supplementation with bilberry extract prevents macular degeneration and cataracts in senesce-accelerated OXYS rats]. Advances in gerontology = Uspekhi gerontologii / Rossiiskaia akademiia nauk, Gerontologicheskoe obshchestvo. 2005;16:76-79.

Fursova AZ, Gesarevich OG, Gonchar AM, et al. Dietary supplementation with bilberry extract prevents macular degeneration and cataracts in senescence-accelerated OXYS rats. Advanced Gerontology. 2005;16:76-79.

Gao S, Qin T, Liu Z, Caceres MA, Ronchi CF, Chen CY. Lutein and zeaxanthin supplementation reduces H2O2-induced oxidative damage in human lens epithelial cells. Molecular Vision. 2011(17):3180-3190.

Gawecki M, Raczynska K, Homziuk M, Iwaszkiewicz-Bilikiewicz B. [Carnitine level in human lens and density of cataract]. Klinika oczna. 2004;106(3 Suppl):409-410.

Giblin FJ.  Glutathione: a vital lens antioxidant. Journal of Occupational Pharmacology Therapy. 2000;16(2)121–135. 

Giuffrè G, Giammanco R, Di Pace F, Ponte F. Casteldaccia eye study: prevalence of cataract in the adult and elderly population of a Mediterranean town. International Ophthalmology. 1995;18(6):363-371.

Gul A, Rahman MA, Salim A, Simjee SU. Advanced glycation end products in senile diabetic and nondiabetic patients with cataract. Journal of Diabetes and its Complications. 2009;23(5):343-348.

Gupta SK, Halder N, Srivastava S, Trivedi D, Joshi S, Varma SD. Green tea (Camellia sinensis) protects against selenite-induced oxidative stress in experimental cataractogenesis. Ophthalmic Research. 2002;34(4):258-263.

Gupta SK, Halder N, Srivastava S, Trivedi D, Joshi S, Varma SD. Green tea (Camellia sinensis) protects against selenite-induced oxidative stress in experimental cataractogenesis. Ophthalmic research. Jul-Aug 2002;34(4):258-263.

Gyldenkerne GJ. [The frequency of secondary cataract after extracapsular cataract extraction]. [Article in Danish]. Ugeskr Laeger. 1998;160(25):3718-3719.

Harding JJ. Viewing molecular mechanisms of ageing through a lens. Ageing Research Reviews.  2002;1(3)465–479.

Haripriya A, Chang DF, Reena M, Shekhar M. Complication rates of phacoemulsification and manual small-incision cataract surgery at Aravind Eye Hospital. Journal of Cataract & Refractive Surgery. 2012;38(8):1360-9.

Hashim Z, Zarina S. Advanced glycation end products in diabetic and non-diabetic human subjects suffering from cataract. Age (Dordrecht, Netherlands). Sep 2011;33(3):377-384.

Hashim Z, Zarina S. Osmotic stress induced oxidative damage: possible mechanism of cataract formation in diabetes. Journal of Diabetes and its Complications. 2012;26(4):275-279.

Haug SJ, Bhistikul RB. Risk factors for retinal detachment following cataract surgery. Current Opinion in Ophthamology.  2012;23(1):7-11.

Head KA. Natural therapies for ocular disorders, part one: diseases of the retina. Alternative Medicine Reviews. 1999;4(5):342-359.

Head KA. Natural therapies for ocular disorders, part two: Cataracts and glaucoma. Alternative Medicine Reviews. 2001;6(2):141-166.

Heiba IM, Elston RC, Klein BE, Klein R. Evidence for a major gene for cortical cataract. Investigative Ophthalmology & Visual Science. 1995;36(1):227-235.

Hemalatha C, Norhafizah H, Shatriah I. Bilateral spontaneous rupture of anterior lens capsules in a middle-aged woman. Clinical Ophthalmology. 2012;6:1955-7.

Heydari B, Kazemi T, Zarban A, Ghahramani S. Correlation of cataract with serum lipids, glucose and antioxidant activities: a case-control study. The West Indian medical journal. Jun 2012;61(3):230-234.

Hipkiss AR, Brownson C. Carnosine reacts with protein carbonyl groups: another possible role for the anti-ageing peptide? Biogerontology. 2000;1(3):217-223.

Howes FW. Indications for lens surgery/indications for application of different lens surgery techniques. In: Yanoff M, Duker JS, eds. Ophthamology. 3rd ed. St. Louis, Mo: Mosby Elsevier; 2008:chapter 5.4.

Jacques PF, Hartz SC, Chylack LT, McGandy RB, Sadowski JA. Nutritional status in persons with and without senile cataract: blood vitamin and mineral levels. American Journal of Clinical Nutrition. 1988;8(1):152-158.

Jacques PF, Taylor A, Hankinson SE, Willett WC, Mahnken B, Lee Y, Vaid K, Lahav M. Long-term vitamin C supplement use and prevalence of early age-related lens opacities. American Journal of Clinical Nutrition. 1997;66:911-916.

Jain AK, Lim G et al. Effect of high-glucose levels on protein oxidation in cultured lens cells, and in crystalline and albumin solution and its inhibition by vitamin B6 and N-acetylcysteine: its possible relevance to cataract formation in diabetes. Free Radical Biology and Medicine. 2002;15;33(12):1615-1621.

Jain AK, Lim G, Langford M, Jain SK. Effect of high-glucose levels on protein oxidation in cultured lens cells, and in crystalline and albumin solution and its inhibition by vitamin B6 and N-acetylcysteine: its possible relevance to cataract formation in diabetes. Free radical biology & medicine. Dec 15 2002;33(12):1615-1621.

Jariwalla RJ, Lalezari J, Cenko D, Mansour SE, Kumar A, Gangapurkar B, Nakamura D. Restoration of blood total glutathione status and lymphocyte function following alpha-lipoic acid supplementation in patients with HIV infection. Journal of alternative and complementary medicine (New York, N.Y.). Mar 2008;14(2):139-146.

Jessani S, Millane T, Lip GY. Vascular damage in impaired glucose tolerance: an unappreciated phenomenon? Current pharmaceutical design. 2009;15(29):3417-3432.

Jia Z, Song Z, Zhao Y, Wang X, Liu P. Grape seed proanthocyanidin extract protects human lens epithelial cells from oxidative stress via reducing NF-кB and MAPK protein expression. Molecular Vision. 2011;(17):210-217.

Jiang X, Dong J, Wang B, Yin X, Qin L. [Effects of organic selenium supplement on glutathione peroxidase activities: a meta-analysis of randomized controlled trials]. Wei sheng yan jiu = Journal of hygiene research. Jan 2012;41(1):120-123.

Jick SS, Vasilakis-Scaramozza C, Maier WC. The risk of cataract among users of inhaled steroids. Epidemiology. 2001;12(2):229-234.

Jun G, Guo H, Klein BE, Klein R, Wang JJ, Mitchell P, et al. EPHA2 is associated with age-related cortical cataract in mice and humans. PLoS Genetics. 2009;5(7):e1000584.

Kamei A. Glutathione levels of the human crystalline lens in aging and its antioxidant effect against the oxidation of lens proteins. Biological & Pharmaceutical Bulletin. 1993;16(9):870-875.

Kanthan GL, Mitchell P, Burlutsky G, Wang JJ. Fasting blood glucose levels and the long-term incidence and progression of cataract -- the Blue Mountains Eye Study. Acta ophthalmologica. Aug 2011;89(5):e434-438.

Kanthan GL, Wang JJ, Rochtchina E, et al. Ten-year incidence of age-related cataract and cataract surgery in an older Australian population. Ophthamology. 2008;115(5):808-814e1.

Karlsen A, Paur I, Bohn SK, Sakhi AK, Borge GI, Serafini M, . . . Blomhoff R. Bilberry juice modulates plasma concentration of NF-kappaB related inflammatory markers in subjects at increased risk of CVD. Eur J Nutr. Sep 2010;49(6):345-355.

Kawabata F, Tsuji T. Effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans. Biomedical research (Tokyo, Japan). Dec 2011;32(6):387-393.

Kerio LC, Wachira FN, Wanyoko JK, Rotich MK. Total polyphenols, catechin profiles and antioxidant activity of tea products from purple leaf coloured tea cultivars. Food chemistry. Feb 15 2013;136(3-4):1405-1413.

Kern HL, Zolot SL. Transport of vitamin C in the lens. Current Eye Research. 1987;6(7):885-896.

Kernt M, Hirneiss C, Neubauer AS, Ulbig MW, Kampik A. Coenzyme Q10 prevents human lens epithelial cells from light-induced apoptotic cell death by reducing oxidative stress and stabilizing BAX/Bcl-2 ratio. Acta Ophthalmologica. 2010;88(3):78-86.

Kijlstra A, Tian Y, Kelly ER, Berendschot TT. Lutein: more than just a filter for blue light. Progress in Retinal and Eye Research. 2012;31(4):303-315.

Kim SI, Kim SJ. Prevalence and risk factors for cataracts in persons with type 2 diabetes mellitus. Korean Journal of Ophthalmology. 2006;20(4):201-204.

Kim SJ, Flach AJ, Jampol LM. Nonsteroidal anti-inflammatory drugs in ophthalmology. Survey of Ophthalmology. 2010;55(2):108-133.

Klein BE, Klein R, Lee KE, Grady LM. Statin use and incident nuclear cataract. Journal of the American Medical Association.  2006;295(23):2752-2758.

Klein BE, Klein R, Lee KE, Meuer SM. Socioeconomic and lifestyle factors and the 10-year incidence of age-related cataracts. American Journal of Ophthalmology. 2003;136(3):506-512.

Klein BE, Klein R, Lee KE. Incidence of age-related cataract over a 10-year interval: the Beaver Dam Eye Study. Ophthalmology. 2002;109(11):2052-2057.

Knekt P, Heliövaara M, Rissanen A, Aromaa A, Aaran RK. Serum antioxidant vitamins and risk of cataract. British Medical Journal. 1992;305(6866):1392-1394.

Kocer I, Taysi S, Ertekin MV, Karslioqlu, Gepdiremen A, Sezen O, Serifoqlu K. The effect of L-carnitine in the prevention of ionizing radiation-induced cataracts: a rat model. Graefes Archives in Clinical and Experimental Ophthalmology. 2007;245(4):588-594.

Kojima M, Sun L, Hata I, Sakamoto Y, Sasaki H, Sasaki K. Efficacy of alpha-lipoic acid against diabetic cataract in rat. Japanese Journal of Ophthalmology. 2007;51(1):10-13.

Lasa MS, Datiles MB III, Feidlin V. Potential vision tests in patients with cataracts. Ophthalmology. 1995;102(7):1007-1011.

Lee W, Chung SK, Chung SS. Demonstration that polyol accumulation is responsible for diabetic cataract by the use of transgenic mice expressing the aldose reductase gene in the lens. Proceedings of the National Academy of Sciences USA. 1995;92:2780-2784.

Leske MC, Chylack LT, He Q, Wu SY, Schoenfeld E, Friend J, Wolfe J.  Antioxidant vitamins and nuclear opacities: the longitudinal study of cataract. Ophthamology. 1998;105:831-836.

Leske MC, Wu SY, Hyman L, Sperduto R, Underwood B, Chylack LT, Milton RC, Srivastava S, Ansari N. Biochemical factors in the lens opacities. Case-control study. The Lens Opacities Case-Control Study Group. Archives of Ophthalmology. 1995;113(9):1113-1119.

Levy AH, McCulley TJ, Lam BL, Feuer WJ. Estimating visual acuity by character counting using the Snellen visual acuity chart. Eye. 2005;19(6):622-624.

Li G, Luna C, Navarro ID, Epstein DL, Huang W, Gonzalez P, et al. Resveratrol prevention of oxidative stress damage to lens epithelial cell cultures is mediated by forkhead box O activity. Investigative Ophthalmology & Visual Science. 2011;52(7):4395-401.

Lichtinger A, Kim P, Yeung SN, Amiran MD, Alangh M, Rootman DS. Secondary intraocular lens interventions: predisposing factors, indications and coincidence procedures. International Ophthamology. Sep 2012; Epub ahead of print.

Limon-Pacheco JH, Gonsebatt ME. The glutathione system and its regulation by neurohormone melatonin in the central nervous system. Central nervous system agents in medicinal chemistry. Dec 1 2010;10(4):287-297.

Lindsey JB, Cipollone F, Abdullah SM, McGuire DK. Receptor for advanced glycation end-products (RAGE) and soluble RAGE (sRAGE): cardiovascular implications. Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease. Jan 2009;6(1):7-14.

Lou MF. Redox regulation in the lens. Progress in Retinal and Eye Research. 2003;22:657–682. 

Lu M, Cho E, Taylor A, Hankinson SE, Willett WC, Jacques PF. Prospective study of dietary fat and risk of cataract extraction among US women. American Journal of Epidemiology. 2005;161(10) :948-959.

Lyle BJ, Mares-Perlman JA, Klein BE, et al. Serum carotenoids and tocopherols and incidence of age-related nuclear cataract. American Journal of Clinical Nutrition. 1999;69(2):272-277.

Machan CM, Hrynchak PK, Irving EL. Age-related cataract is associated with type 2 diabetes and statin use. Optometry & Vision Science. 2012;89(8):1165-1171.

Madar Z, Hazan A. Effect of miglitol and acarbose on starch digestion, daily plasma glucose profiles and cataract formation. Journal of basic and clinical physiology and pharmacology. Apr-Jun 1993;4(1-2):69-81.

Maitra I, Serbinova E, Tritschler HJ, Packer L. Sterospecific effects of R-lipoic acid on buthionine sulfoximine-induced cataract formation in bewborn rats. Biochemical and Biophysical Research Communications. 1996;221(2) :422-429.

Marcantonio JM, Vrensen GF. Cell biology of posterior capsular opacification. Eye. 1999 (Pt 3b):484-488.

Mares JA, Voland R, Adler R, Tinker L, Millen AE, Moeller SM, et al. Healthy diets and the subsequent prevalence of nuclear cataract in women. Archives of Ophthalmology. 2010;128(6):738-749.

Mares-Perlman JA, Brady WE, Klein BE, Klein R, Haus GJ, Palta M, et al. Diet and nuclear lens opacities. American Journal of Epidemiology. 1995;141(4):322-34.

Martinez G, de Longh RU. The lens epithelium in ocular health and disease. International Journal of Biochemistry and Cellular Biology. 2010;42(12):1945-1963.

Mathias RT, White TW, Gong X.  Lens gap junctions in growth, differentiation, and homeostasis. Physiological Reviews. 2010;90(1):179-206.

Matsuda H, Morikawa T, Toguchida I, Yoshikawa M. Structural requirements of flavonoids and related compounds for aldose reductase inhibitory activity. Chemical and Pharmaceutical Bulletin (Tokyo). 2002;50(6):788-795.

Mayo Clinic. http://www.mayoclinic.com/health/vitamin-e/NS_patient-vitamine Last updated September 1 2012. Accessed January 18, 2013

McColgin AZ, Raizman MB. Efficacy of topical Voltaren in reducing the incidence of postoperative cystoid macular edema. Investigative Ophthalmology & Visual Science. 1999;40(suppl):S289.

McLauchlan WR, Sanderson J, Williamson G. Quercetin protects against hydrogen peroxide-induced cataract. Biochemical Society Transcations. 1997;25(4):S581.

McNeilly AM, Davison GW, Murphy MH, Nadeem N, Trinick T, Duly E, . . . McEneny J. Effect of alpha-lipoic acid and exercise training on cardiovascular disease risk in obesity with impaired glucose tolerance. Lipids in health and disease. 2011;10:217.

Medline Plus Website. Article on Cataract page. Available at: http://www.nlm.nih.gov/medlineplus/cataract.html. Last updated August 27, 2012. Accessed December 12, 2012.

Merck Manual Professional. Article on Cataract page. Available at : http://www.merckmanuals.com/professional/eye_disorders/cataract/cataract.html.  Last updated August 2012.  Accessed December 14, 2012.

Merriam JC. The concentration of light in the human lens. Transactions of the American Ophthalmological Society. 1996;94:803-918.

Michael R, Bron AJ.  The ageing lens and cataract: a model of normal and pathological ageing.  Philosophical Translations of the Royal Society B. 2011;366(1568):1278-1292.

Miyake S, Takahashi N, Sasaki M, Kobayashi S, Tsubota K, Ozawa Y. Vision preservation during retinal inflammation by anthocyanin-rich bilberry extract: cellular and molecular mechanism. Laboratory Investigation. 2012;92(1):102-109.

Miyake S, Takahashi N, Sasaki M, Kobayashi S, Tsubota K, Ozawa Y. Vision preservation during retinal inflammation by anthocyanin-rich bilberry extract: cellular and molecular mechanism. Laboratory investigation; a journal of technical methods and pathology. Jan 2012;92(1):102-109.

Miyazawa T, Nakagawa K, Shimasaki S, Nagai R. Lipid glycation and protein glycation in diabetes and atherosclerosis. Amino acids. Apr 2012;42(4):1163-1170.

Miyazawa T. Absorption, metabolism and antioxidative effects of tea catechin in humans. BioFactors. 2000;13(1-4):55-59.

Moeller SM, Voland R, Tinker L, Blodi BA, Klein ML, Gehrs KM, . . . Mares JA. Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in the Age-Related Eye Disease Study, an Ancillary Study of the Women's Health Initiative. Archives of ophthalmology. Mar 2008;126(3):354-364.

Moreau KL, King JA. Protein misfolding and aggregation in cataract disease and prospects for prevention. Trends in Molecular Medicine. 2012;18(5):273-282.

Morikubo S, Takamura Y, Kubo E, Tsuzuki S, Akagi Y. Corneal changes after small-incision cataract surgery in patients with diabetes mellitus. Archives of Ophthalmology. 2004;122(7):966-969.

National Eye Institute. Facts about cataracts. http://www.nei.nih.gov/health/cataract/cataract_facts.asp Last updated September 2009. Last accessed January 21, 2013.

Nitenberg A, Cosson E, Pham I. Postprandial endothelial dysfunction: role of glucose, lipids and insulin. Diabetes & metabolism. Sep 2006;32 Spec No2:2S28-33.

Olmedilla B, Granado F, Blanco I, Vaquero M. Lutein, but not alpha-tocopherol, supplementation improves visual function in patients with age-related cataracts: a 2-y double-blind, placebo-controlled pilot study. Nutrition (Burbank, Los Angeles County, Calif.). Jan 2003;19(1):21-24.

Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radical Biology Medicine. 1995;19(2):227-250.

Packer L. Antioxidant properties of lipoic acid and its therapeutics effects in prevention of diabetes complications and cataracts. Annals of the New York Academy of Sciences. 1994;738:257-264.

Padival S, Nagaraj RH. Pyridoxamine inhibits maillard reactions in diabetic rat lenses. Ophthalmic Research. 2006;38(5):294-302.

Paik DC, Dillon J. The Nitrite/alpha crystallin reaction: a possible mechanism in lens matrix damage. Experimental Eye Research. 2000;70(1):73-80.

Paik JK, Kim M, Kwak JH, Lee EK, Lee SH, Lee JH. Increased arterial stiffness in subjects with impaired fasting glucose. Journal of diabetes and its complications. Nov 22 2012.

Paine et al. Cataracts. http://www.emedicinehealth.com/cataracts/page2_em.htm

Pandey SK, Apple DJ, Werner L, Maloof AJ, Milverton EJ. Posterior capsule opacification: a review of the aetiopathogenesis, experimental and clinical studies and factors for prevention. Indian Journal of Ophthalmology. 2004;52(2):99-112.

Pereira PC, Fernandes R, Ramalho JS, Mota MC, Oliveira CR. A technical approach to the evaluation of glucose oxidation: implications for diabetic cataract. Ophthalmic research. 1996;28(5):275-283.

Pizzorno JN, Murray M Eds. Textbook of Natural Medicine, Second Edition.

Polizzi FC, Andican G, Cetin E, Civelek S, Yumuk V, Burcak G. Increased DNA-glycation in type 2 diabetic patients: the effect of thiamine and pyridoxine therapy. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. Jun 2012;120(6):329-334.

Psota TL, Gebauer SK, Kris-Etherton P. Dietary omega-3 fatty acid intake and cardiovascular risk. The American Journal of Cardiology. 2006;98(4A):3i-18i.

Quinn PJ, Boldyrev AA, Formazuyk VE. Carnosine: Its properties, functions and potential therapeutic applications. Molecular Aspects of Medicine. 1992;13(5):379-444.

Radtke KK, Coles LD, Mishra U, Orchard PJ, Holmay M, Cloyd JC. Interaction of N-acetylcysteine and cysteine in human plasma. Journal of Pharmaceutical Sciences. 2012;101(12):4653-4659.

Ramakrishnan S, Sulochana KN, Punitham R. Two new functions of inositol in the eye lens: antioxidation and antiglycation and possible mechanisms. Indian Journal of Biochemistry and Biophysics. 1999;36(2):129-133.

Ramana BV, Raju TN, Kumar VV, Reddy PU. Defensive role of quercetin against imbalances of calcium, sodium, and potassium in galactosemic cataract. Biological trace element research. Oct 2007;119(1):35-41.

Randerath E, Danna TF, Randerath K. DNA damage induced by cigarette smoke condensate in vitro as assayed by A2p-postlabeling. Comparison with cigarette smoke-associated DNA adduct profiles in vivo. Mutation Research. 1992;268(1):139-153.

Ravindran RD, Vashist P, Gupta SK, Young IS, Maraini G, Camparini M, et al. Inverse association of vitamin C with cataract in older people in India. Ophthalmology. 2011;118(10):1958-1965 e2.

Regan D, Giaschi DE, Fresco BB. Measurement of glare sensitivity in cataract patients using low-contrast letter charts. Ophthalmic and Physiological Optics. 1993;13(2):115-123.

Resnikoff S, Pascolini D, Etya'ale D, et al. Global data on visual impairment in the year 2002. Bulletin of the World Health Organizaton. 2004;82:844-851.

Reuter SE, Evans AM. Carnitine and acylcarnitines: pharmacokinetic, pharmacological and clinical aspects. Clinical pharmacokinetics. Sep 1 2012;51(9):553-572.

Rhodes LE, Shahbakhti H, Azurdia RM, Moison RM, Steenwinkel MJ, Homburg MI. Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers. Carcinogenesis. 2003;24(5):919-925.

Rowe NG, Mitchell PG, Cumming RG, Wans JJ. Diabetes, fasting blood glucose and age-related cataract: the Blue Mountains Eye Study. Ophthalmic epidemiology. Jun 2000;7(2):103-114.

Ruit S, Robin AL, Pokhrel RP, Sharma A, DeFaller J, Maguire PT. Long-term results of extracapsular cataract extraction and posterior chamber intraocular lens insertion in Nepal. Transactions of the American Ophthalmological Society. 1991 (89):59-72.

Saika S, Yamanaka O, Sumioka T, Miyamoto T, Miyazaki K, Okada Y, . . . Ikeda K. Fibrotic disorders in the eye: targets of gene therapy. Progress in retinal and eye research. Mar 2008;27(2):177-196.

Samarawickrama C, Wang JJ, Burlutsky G, Tan AG, Mitchell P. Nuclear cataract and myopic shift in refraction. American Journal of Ophthalmology. 2007;144(3):457-459.

Sanderson J, Marcantonio JM, Duncan G. A human lens model of cortical cataract: Ca2+-induced protein loss, vimentin cleavage and opacification. Investigative Ophthalmology & Visual Science. 2000;41(8):2255-2261.

Santana A, Waiswo M. The genetic and molecular basis of congenital cataract. Arquivos Brasileiros de Oftalmologia. 2011;74(2):136-142.

Saxena S, Mitchell P, Rochtchina E. Five-year incidence of cataract in older persons with diabetes and pre-diabetes. Ophthalmic epidemiology. Oct 2004;11(4):271-277.

Schneiderman H. The Funduscopic Examination. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 117. Available from: http://www.ncbi.nlm.nih.gov/books/NBK221/.

Shamsi FA, Sharkey E, Creighton D, Nagaraj RH. Maillard reactions in lens proteins: methylglyoxal-mediated modifications in the rat lens. Experimental Eye Research. 2010;70(3):369-380.

Sharma KK, Santhoshkumar P. Lens aging: effects of crystallins. Biochimica et Biophysica Acta. 2009;1790(10):1095-1108.

Shi Q, Yan H, Li MY, Harding JJ. Effect of a combination of carnosine and aspirin eye drops on streptozotocin – induced diabetic cataract in rat. Molecular Vision. 2009;15:2129-2138.

Shim SH, Kim JM, Choi CY, Kim CY, Park KH. Ginkgo biloba extract and bilberry anthocyanins improve visual function in patients with normal tension glaucoma. Journal of medicinal food. Sep 2012;15(9):818-823.

Shoss BL, Tsai LM. Postoperative care in cataract surgery. Current Opinion in Ophthalmology. 2013;24(1):66-73.

Sia DI, Martin S, Wittert G, Casson RJ. Age-related change in contrast sensitivity among Australian male adults: Florey Adult Male Ageing Study. Acta Ophthalmologica. 2012 Mar 16.  [E-pub ahead of print].

Simon JA, Hudes ES. Serum ascorbic acid and other correlates of self-reported cataract among older Americans. Journal of Clinical Epidemiology. 1999;52(12):1207-1211.

Singh BN, Shankar S, Srivastava RK. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochemical pharmacology. Dec 15 2011;82(12):1807-1821.

Smith RJ, Doran R, Caswell A. Extracapsular cataract extraction-some problems.". The British Journal of Ophthalmology.  1985;66(3):183-185.

Spalton DJ. Posterior capsular opacification after cataract surgery. Eye. 1999;(Pt 3b):489-492.

Spector A. Oxidative stress-induced cataract: mechanism of action. Federation of American Societies for Experimental Biology Journal. 1995;9(12):1173-1182.

Speeg-Schatz C. [Results and complications of surgery of congenital cataract]. Journal français d'ophtalmologie. 2011;34(3):203-207.

Stefek M, Karasu C. Eye lens in aging and diabetes: effect of quercetin. Rejuvenation Research. 2011;14(5):525-534.

Stefek M. Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract. Interdisciplinary Toxicology. 2011;4(2):69-77.

Surguchev A, Surguchov A. Conformational diseases: looking into the eyes. Brain Research Bulletin. 2010;81(1):12-24.

Swamy MS, Abraham EC. Lens protein composition, glycation and high molecular weight aggregation in aging rats. Investigative Ophthalmology & Visual Science. 1987;28(10):1693-1701.

Swamy-Mruthinti S, Carter AL. Acetyl-L-carnitine decreases glycation of lens proteins: in vitro studies. Experimental Eye Research.  1999;69(1):109-115.

Tan AG, Mitchell P, Flood VM, Burlutsky G, Rochtchina E, Cumming RG, et al. Antioxidant nutrient intake and the long-term incidence of age-related cataract: the Blue Mountains Eye Study. American Journal of Clinical Nutrition. 2008;87(6):1899-1905.

Tan JS, Mitchell P, Rochtchina E, Wang JJ. Statin use and the long-term risk of incidence cataract: the Blue Mountains Eye Study. American Journal of Ophthamology. 2007;143(4):687-689.

Tan JS, Wang JJ, Mitchell P. Influence of diabetes and cardiovascular disease on the long-term incidence of cataract: the Blue Mountains eye study. Ophthalmic epidemiology. Sep-Oct 2008;15(5):317-327.

Tao RV, Takahashi Y, Kador PF. Effect of aldose reductase inhibitors on naphthalene cataract formation in the rat. Investigative Ophthalmology & Visual Science. 1991;32(5):1630-1637.

Taravati P, Lam DL, Leveque T, Van Gelder RN. Postcataract surgical inflammation. Current Opinion in Ophthamology. 2012;23(1):12-18.

Taylor A, Jacques PF, Chylack LT, et al. Long-term intake of vitamins and carotenoids and odds of early age-related cortical and posterior subcapsular lens opacities. American Journal Clinical Nutrition. 2002;75(3):540-549.

Taylor A, Lipman RD, Jahngen-Hodge J, Palmer V, Smith D, Padhye N, . . . et al. Dietary calorie restriction in the Emory mouse: effects on lifespan, eye lens cataract prevalence and progression, levels of ascorbate, glutathione, glucose, and glycohemoglobin, tail collagen breaktime, DNA and RNA oxidation, skin integrity, fecundity, and cancer. Mechanisms of ageing and development. Mar 31 1995;79(1):33-57.

Taysi S, Memisoqullari R, Koc M, Yazici AT, Aslankurt M, Gumustekin K, Al B, Ozabacigil F, Yilmaz A, Tahsin Ozder H. Melatonin reduces oxidative stress in the rat lens due to radiation-induced oxidative injury. International Journal of Radiation Biology. 2008;84(10):803-808.

Thiagarajan G, Chandani S, Sundari CS, Rao SH, Kulkarni AV, Balasubramanian D. Antioxidant properties of green and black tea, and their potential ability to retard the progression of eye lens cataract. Experimental eye research. Sep 2001;73(3):393-401.

Truscott RJ. Age-Related Nuclear Cataract-Oxidation Is the Key. Experimental Eye Research. 2005;80(5):709-725.

Tsai SY, Hsu WM, Cheng CY, Liu JH, Chou P. Epidemiologic study of age-related cataracts among an elderly Chinese population in Shih-Pai, Taiwan. Ophthalmology. 2003;110(6):1089-1095.

Tsuda T. Dietary anthocyanin-rich plants: biochemical basis and recent progress in health benefits studies. Molecular nutrition & food research. Jan 2012;56(1):159-170.

Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Current Neuropharmacology. 2009;7(1):65-74.

van der Mooren M, van den Berg T, Coppens J, Piers P. Combining in vitro test methods for measuring light scatter in intraocular lenses. Biomedical Optics Express. 2011;2(3):505-510.

van der Pols JC, Xu C, Boyle GM, Hughes MC, Carr SJ, Parsons PG, et al. Serum omega-3 and omega-6 fatty acids and cutaneous p53 expression in an Australian population. Cancer epidemiology, Biomarkers & Prevention. 2011;20(3):530-6.

Vano E, Kleiman NJ, Duran A, Rehani MM, Echeverri D, Cabrera M. Radiation cataract risk in interventional cardiology personnel. Radiation Research. 2010;174(4):490-495.

Varma SD, Kovtun S, Hegde, KR. Role of UV irradiation and oxidative stress in cataract formation. Medical prevention by nutritional antioxidants and metabolic agonists. Eye Contact Lenses. 2011;37(4):233-245.

Vashist P, Talwar B, Gogoi M, Maraini G, Camparini M, Ravindran RD, et al. Prevalence of cataract in an older population in India: the India study of age-related eye disease. Ophthalmology. 2011;118(2):272-278 e1-2.

Vinson JA, Zhang J. Black and green teas equally inhibit diabetic cataracts in a streptozotocin-induced rat model of diabetes. Journal of Agricultural and Food Chemistry. 2005;53(9):3710-3713.

Vinson JA, Zhang J. Black and green teas equally inhibit diabetic cataracts in a streptozotocin-induced rat model of diabetes. Journal of agricultural and food chemistry. May 4 2005;53(9):3710-3713.

Vu HT, Robman L, Hodge A, McCarty CA, Taylor HR. Lutein and zeaxanthin and the risk of cataract : the Melbourne visual impairment project. Investigative Ophthalmology & Visual Science. 2006;47(9):3783-3786.

Wang AM, Ma C, Xie ZH, Shen F. Use of carnosine as a natural anti-senescence drug for human beings. Biochemistry (Mosc). 2000;65(7):869-871.

Wang P, Liu XC, Yan H, Li, M. Hyperoxia-induced lens damage in rabbit: protective effects of N-acetylcysteine. Molecular Vision. 2009;15:2945-2952.

Wautier JL, Guillausseau PJ. Advanced glycation end products, their receptors and diabetic angiopathy. Diabetes & Metabolism. 2001;27(5 Pt 1):535-542.

Weintraub JM, Willett WC, Rosner B, Colditz GA, Seddon JM, Hankinson SE. A prospective study of the relationship between body mass index and cataract extraction among US women and men. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. Dec 2002;26(12):1588-1595.

West SK. The Epidemiology of Cataract. In: Encyclopedia of the Eye, 2010:76-81.

West-Mays J, Sheardown H. Posterior Capsule Opacification. Chapter 31. In: Ocular Disease Mechanisms and Management, 2010:238-242.

Williams DL, Munday P. The effect of a topical antioxidant formulation including N-acetyl carnosine on canine cataract: a preliminary study. Veterinarian Ophthalmology. Sep-Oct 2006;9(5):311-316.

Wittpenn JR, Silverstein S, Heier J, et al. A randomized, masked comparison of topical ketorolac 0.4% plus steroid vs steroid alone in low-risk cataract surgery patients. American Journal of Ophthamology. 2008;146(4):554-560.

Worgul BV, Merriam GR, Szechter A, Srinivasan D. Lens epithelium and radiation cataract. I. Preliminary studies. Archives of Ophthalmology. 1976;94(6):996-999.

Wormstone IM, Wang L, Liu CS. Posterior capsule opacification. Experimental Eye Research. 2009;88(2):257-269.

Xing KY, Lou MF. Effect of age on the thioltransferase (glutaredoxin) and thioredoxin systems in the human lens. Investigative Ophthalmology & Visual Science. 2010;51(12):6598–6604.

Yanoff M and Baustian GH. Cataract. MD Consult web page. Available at: http://www.mdconsult.com/das/pdxmd/body/404334407-2/0?type=med&eid=9-u1.0-_1_mt_1014153#Contributors. Last updated 1/15/2013. Accessed March 1, 2013.

Yaqci R, Aydin B, Erdurmus M, Karadaq R, Gurel A, Durmus M, Yiqitoglu R. Use of melatonin to prevent selenite-induced cataract formation in rat eyes. Current Eye Research. 2006;31(10):845-850.

Younan C, Mitchell P, Cumming RG, Rochtchina E, Wang JJ. Myopia and incident cataract and cataract surgery: the blue mountains eye study. Investigative Ophthalmology & Visual Science. 2002;43(12):3625-3632.

Zafarullah M, Li WQ, Sylvester J, Ahmad M. Molecular mechanisms of N-acetylcysteine actions. Cellular and Molecular Life Sciences. 2003;60(1):6-20.

Zhang J, Wang S. Topical use of coenzyme Q10-loaded liposomes coated with trimethyl chitosan: tolerance, precorneal retention and anti-cataract effect. International Journal of Pharmacology.  2009;372(1-2):66-75.

Zhang P, Xing K, Randazzo J, Blessing K, Lou MF, Kador PF. Osmotic stress, not aldose reductase activity, directly induces growth factors and MAPK signaling changes during sugar cataract formation. Experimental Eye Research. 2012;101:36-43.

Zhang S, Chai FY, Guo Y, Harding JJ. Effects of N-acetylcysteine and glutathione ethyl ester drops on streptozotocin-induced diabetic cataract in rats. Molecular Vision. 2008;14:862-870.

Zhang S, Chai FY, Yan H, Guo Y, Harding JJ. Effects of N-acetylcysteine and glutathione ethyl ester drops on streptozotocin-induced diabetic cataract in rats. Molecular Vision. 2008 (14):862-870.

Zhao C, Shichi H. Prevention of acetaminophen-induced cataract by a combination of diallyl disulfide and N-acetylcysteine. Journal of Ocupational Pharmacology Therapy. 1998;14(4):345-355.

Zheng Y, Liu Y, Ge J, Wang X, Liu L, Bu Z, et al. Resveratrol protects human lens epithelial cells against H2O2-induced oxidative stress by increasing catalase, SOD-1, and HO-1 expression. Molecular Vision. 2010;16:1467-1474.

Zhou J, Leonard M, Van Bockstaele E, Menko AS. Mechanism of Src kinase induction of cortical cataract following exposure to stress: destabilization of cell-cell junctions. Molecular Vision. 2007 (13):1298-1310.

Zhu X, Lu Y.  Selenium supplementation can slow the development of naphthalene cataract. Current Eye Research. 2012;37:163-169.

Zigler JS, Datiles MB. Pathogenesis of cataracts.  In: Tasman W, Jaeger EA, Eds. Duane’s Ophthalmology. 15th ed. Philadelphia, PA: Lipincott Williams & Wilkins; 2011:chapter 72B.