~Cataracts

~Cataracts
Reprinted with permission of Life Extension®.
OVERVIEW

Cataract is clouding of the eye lens that reduces the amount of incoming light and results in deteriorating vision. Cataract is often described as being similar to looking through a waterfall or waxed paper. Daily functions such as reading or driving a car may become difficult or impossible. Eyeglass prescriptions may require frequent changes. An estimated 200 million people worldwide have cataracts.

Minor lens opacities at birth may never progress to cataract in adulthood, while others progress to a degree requiring surgery or causing blindness. Many factors influence vision and cataract development including age, nutrition, heredity, medications, toxins, health habits, sunlight exposure, and head trauma. Hypertension, kidney disease, diabetes, or direct trauma to the eye can also cause cataract.

Today, cataract surgery is a common surgery in the United States, with over 1.5 million surgeries done yearly. Annual costs associated with cataract treatment are estimated to be over $3.4 billion.1,2 Cataract surgery costs Medicare more than any other medical procedure: 60% who initially qualify for Medicare already have cataracts.3

There are three main types of cataracts. The most common is nuclear cataract. Nuclear cataract occurs when proteins of the nucleus (center) degenerate and darken, causing light to scatter. The second most common type, cortical cataract, occurs in the cortex (or periphery) of the lens. Cortical cataract forms when the order of fibers in the cortex is disturbed and the gaps fill with water and debris, thus altering the pathophysiology of light by scattering and/or absorbing it. The least common type affects the back of the lens and is called posterior subcapsular cataract.

EPIDEMIOLOGY AND GENETICS
  • Prevalence
  • Risk Factors
  • Genetics
  • Symptoms and Disease Progression
Prevalence

Estimates are that 20.5 million Americans older than 40 years, representing 17.2% of that population, have a cataract in at least one eye and that 6.1 million (or 5.1%) have had cataract surgery to remove a lens (aphakia) or to replace a lens with an artificial lens (pseudophakia).4 There is evidence that genetics plays a role in the formation of cataract, especially congenital cataract.5 Cataract is seen primarily in adults, and the incidence grows rapidly after age 50, affecting 50% of individuals between 65 to 74 and 70% of individuals age 75 and older.6 Because of the growing elderly population, by the year 2020, the number of individuals with a cataract could climb to 30.1 million; 9.5 million would be expected to have aphakia or pseudophakia.4

Risk Factors

Identification and awareness of risk factors for cataract could have an important benefit. Estimates are that if cataract onset could be delayed by 10 years, the number of cataract surgeries could be reduced annually by 45%.2

Gender. In the United States, women have a significantly higher age-adjusted prevalence of cataract, with 58% of cataract cases.4 Women have a higher risk for most types of cataracts,7 though evidence suggests estrogen may protect against cataract formation.8 The anti-estrogen drug tamoxifen (used to block estrogen receptors) increases risk of cataract when taken long-term.9

Education Status and Socioeconomic Factors. Risk for cataract is greater among individuals with lower socioeconomic status or educational level. This is attributed to nutritional deficiencies from poor diet, increased exposure to disease, poor general health, and greater exposure to conditions inducing cataract development.2

Exposure to Excessive Sunlight. Geographical areas with more hours of sunshine have a greater prevalence of cataract, showing an association between ultraviolet B irradiation and cataract formation.10

Exposure to Radiation. Exposure to X-rays or gamma radiation is a risk factor for cortical and posterior subcapsular cataracts in humans. Radiologists routinely minimize exposing the lens to ionizing radiation. When this is not possible, cataracts frequently develop and require surgical treatment.11

Nutrition. A diet lacking a high intake of antioxidants, particularly vitamins A, C, and E, fails to protect the lens from cataract formation.12,13

Smoking and Alcohol. There is an increased risk of nuclear cataract smokers.14,15 Risks for all cataract types increase with heavy alcohol consumption.7

Diabetes. Diabetics are more likely to develop cortical opacities or require cataract surgery.16

Corticosteroids. Corticosteroid use is associated with posterior subcapsular cataracts.17

Genetics. Lens-specific genes include genes encoding proteins for growth and transformation of lens fiber cells (cystallins) and mediation of cellular respiration and metabolism, such as major intrinsic polypeptide (MIP) and certain connexins.18,19 Mutations in lens-specific genes are associated with hereditary cataracts possibly through a mechanism which produces a protein interfering with normal proteins, thus disrupting normal function and cataract formation.20

Numerous hereditary syndromes manifest cataracts as a characteristic feature. The gene mutations are identified for some syndromes: Lowe's syndrome, neurofibromatosis type 2, galactosemia, and Werner syndrome.21,22 In most diseases identifying the genes responsible for the development of the cataract offers no explanation as to why cataracts manifest.20 A better understanding of biochemical and molecular mechanisms underlying cataract formation may provide more information about cataract formation.5,23

Symptoms and Disease Progression

Symptoms

Decreased visual acuity. Decrease in visual acuity, a measure of eyesight sharpness and focus, is one of the first signs of cataract. Measurement of visual acuity is most commonly used to detect changes in visual function caused by cataracts (and other causes) over time.24 Often an individual with a cataract will notice worsening vision that requires frequent changes to a stronger lens correction. Visual acuity testing uses the Snellen Visual Acuity Chart.

A Snellen test is not always the best measure of cataract or indicator for surgery. Clinically, visual acuity can remain high despite age-related lens opacities. The Snellen test may not always reflect visual disabilities occurring under less than ideal (clinical) circumstances, as with contrast sensitivity.24 The Preferred Practice Pattern of the American Academy of Ophthalmology recommends Snellen acuity tests as the best guide for appropriateness of surgery with respect to the patient's functional and visual needs, environment, and risk factors.25

Reduced contrast sensitivity and glare. Common complaints are loss of ability to see objects in bright sunlight and being blinded by strong lights at night, such as oncoming headlights.26 All cataracts lower contrast sensitivity, but do so most severely in posterior subcapsular cataract. Cataracts that reduce contrast sensitivity normally occur within the pupil diameter.

Complaints of glare are another symptom of cataracts. Even minor degrees of lens opacity produce glare because of the scatter of light toward the front of the lens. All cataract forms can cause glare, especially cortical and posterior subcapsular types. Patients with glare symptoms frequently have poorer vision in daylight conditions and when driving. Unlike contrast sensitivity reduction, some glare can be produced by opacities not within the pupil diameter.24

Myopic shift. The natural aging process in human lens produces a progressive shift toward hyperopia (i.e., farsightedness). When a cataract is forming in the nucleus of the lens, clouding of the lens changes the way light bends (or refracts). This produces greater nearsightedness (a myopic shift). Myopic shift enables an aging person who previously needed reading glasses to read without corrective lens. This phenomenon called "second sight" is indicative of hardening of the lens nucleus, a predictor of a developing nuclear cataract.27

Double vision and color shift. Other common signs of cataract are double vision in one eye and change in color vision. Monocular diplopia (double vision in one eye) occurs with lens opacities, particularly cortical spoke cataracts. In cortical spoke cataracts, water clefts form radial wedge shapes that contain a fluid with a lower refractive index than the surrounding lens. All light entering the lens is not bent to the same extent; producing double or multiple images. There may be a perception of haloes around light.28

Color shift is produced by a lens that is more absorbent at the blue end of the spectrum, causing color perception to fade. Color shift is common with nuclear cataracts. Usually patients are not aware of a defect in color perception, although it becomes apparent after cataract surgery when they readjust to normal color perception.28

Disease Progression

Observation and assessment. Cataracts are usually observed and assessed with a slit lamp biomicroscope; a microscope with two eyepieces. Different magnifications combined with a strong light are focused into a slit to examine the eye. A slit lamp examination measures visual acuity and the amount of light scattered in the eye.27 Cataracts can be detected with a funduscope, an optical instrument that inspects the retina. Retinal blood vessels are blurred by light scattering caused by opacity in the lens.

Lens clouding. Disease progression in all types of cataract is indicated by increased lens opacity, though opacity manifests differently in each type.
  • Nuclear cataract. In nuclear cataract, lens density initially increases in the central lens nucleus. Opacity follows producing color changes beginning clear, changing to yellow, and to brown at more advanced states.28
  • Cortical cataract. Changes in transparency involve the periphery (or cortex) of the lens. Water gets into the lens cortex and creates pockets under the lens capsule called vacuoles. The vacuoles gradually lengthen into ray-like spaces and fill with fluid which is first transparent and later opaque. Vacuoles begin at the periphery and gradually spread toward the center, taking on an appearance of wedges or spokes. Because a cortical cataract begins at the periphery, vision may not be affected at first, but eventually visual acuity decreases.28
  • Posterior subcapsular cataract. Cataracts form in front of the posterior capsule as a cluster of swollen cells. The posterior capsule is the lens casing at the back of the lens. These cataracts develop as independent, isolated entities, but are associated with cataract formation in nuclear or cortical regions. Granules and vacuoles in front of the posterior capsule are signs of posterior subcapsular cataract. Although they are not common, progression and severity can be more extreme than other types.28
Cataract classification. Cataracts are immature, mature, and hypermature. A lens with remaining clear areas is an immature cataract. A mature cataract is completely opaque. A hypermature cataract has a liquefied surface that leaks through the capsule. The leaking material can cause inflammation in other eye structures.6

ETIOLOGY AND MECHANISMS OF ACTION
  • Cataract: Underlying Causal Mechanisms
  • Age-Related Cataracts: Specific Causal Mechanisms
Cataract: Underlying Causal Mechanisms

Cataract is any type of opacification of the lens. Cataract is considered clinically significant when opacification interferes with visual function. Decreased lens transparency results in increased light scattering as light passes through the lens and then to the retina where the diminished focus of light impairs vision. Cataract adversely impacts vision by light absorption in a less transparent lens.

The underlying mechanism for cataracts involves: disruption of the structure of the lens fiber cells, increases in protein aggregation, or cytoplasm dysfunction in the lens cell.29

Age-Related Cataracts: Specific Causal Mechanisms

Each type of age-related cataract has a specific mechanism that leads to their development. These include: oxidative damage, protein aggregation, breakdown of the glutathione, damage to fiber cell membranes, protein breakdown, elevated calcium, abnormal lens epithelial cell migration, or aberrant changes in lens fiber cells.

Nuclear Cataract

Nuclear cataracts show increased oxidative damage to lens proteins and lipids30 causing protein-to-protein interactions that cause aggregation and increase light scattering. A lens with a cataract has increased interaction between crystallins and lens fiber cell membranes.31

Evidence suggests a strong connection between aging and increased amounts of oxidized glutathione in the lens nucleus indicative of an imbalance between protein and lipid oxidation, and glutathione-dependent reduction.32,33 Nuclear cataract formation may be caused by separation of lens cell cytoplasm (a jelly-like substance) into protein-rich and protein-poor liquid phases,34 accounting for the opacity.35

Cortical Cataract

Cortical opacities start in small regions of the lens periphery. Opacity may spread around the circumference of the lens. Several mechanisms may initiate the cortical cataract: damage to the fiber cell plasma membrane, loss of protective molecules such as glutathione, excessive breakdown of proteins (proteolysis), and damage to systems responsible for calcium homeostasis. These factors are interrelated because any one of them leads to the others in the initial formation of cortical cataracts.20

Loss of calcium homeostasis spreads opacification around the lens periphery and towards the nucleus. Calcium levels are elevated in damaged cells in cortical cataracts.36 Elevated calcium leads to proteolysis, protein aggregation, and light scattering.37

Posterior Subcapsular Cataract

These cataracts are caused by environmental stresses such as ultraviolet light, diabetes, and drug ingestion.2,38 Light scattering occurs in a cluster of swollen cells at the back of the lens, beneath the lens capsule. Because opacity produced by the cell cluster is within the optical axis (or the line of sight), these cataracts can be particularly debilitating. These cataracts are associated with abnormal migration of lens epithelial cells or aberrant changes in lens fiber cells at the back of the lens.39

Continued . . .


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