CATARACTS
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
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
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
ANATOMY AND PHYSIOLOGY (STRUCTURE AND FUNCTION)
The Lens
A lens is formed from specialized epithelial cells during embryonic
development. The epithelium is a sheet of cube-shaped cells covering
the anterior surface of the lens near the cornea. The major part of
the lens consists of concentric layers of elongated fiber cells. The
outermost shells of fiber cells extend from beneath the epithelium to
the posterior lens surface near the vitreous body. The lens is one centimeter
from front to back, surrounded by the capsule--an elastic matrix of
cells produced during embryonic development by secretions from epithelial
and fiber cells on the lens surface.40
In an adult lens, only a few epithelial cells replicate, proliferating
slowly, producing new fiber cells that elongate and accumulate crystallins
(lens proteins). Crystallins give the lens its refractive power to focus
light on the retina.41 During
maturation layers of fiber cells build up.42
After the elongation process, a differentiation begins that degrades
all intracellular, membrane-bound organelles.43
Mature fiber cells are buried deeper within the lens as generations
of fiber cells go this process. The lens increases in size and cell
numbers throughout life.44
Because protein synthesis stops with organelle degradation, mature fiber
cells are more stable than cells having other functions in the body.45
Zonules
The lens is suspended by inelastic microfibrils called zonules located
above and below the lens in the anterior part of the lens and extending
into the lens capsule. Zonules are inelastic compared to other fibrils
in the body (e.g., in the skin and arterial walls), but stretch enough
to create the tension responsible for altering lens curvature. This
is required for focusing on objects at different distances, a process
known as accommodation.46
Refractive Properties of the Lens
The refractive properties of the lens result from the high concentration
of crystallins in the cytoplasm of lens fiber cells and the curvature
of the lens. Lens crystallins are water-soluble proteins in lens fibers
that provide a high refractive index. The lens is able to focus light
on photoreceptors in the retina.47
In a healthy lens, refractive error is caused by abnormalities in corneal
curvature or length of the ocular globe, but rarely from defects in
the curvature or refractive index of the lens itself.20
An essential component of lens transparency is a high concentration
of lens crystallins and minimization of light scattering and absorption.
Light passes through the lens because of the regular structure of lens
fibers, an absence of membrane-bound organelles, and small, uniform
spaces between the cells. This reduced light scattering is due to short-range
interactions among densely packed crystalline molecules.48
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