PART 5 THE LENS

Epidemiology, Pathophysiology,
Causes, Morphology, and Visual
5.17
Effects of Cataract
Mark Wevill

that need to be done. In developing countries there are other challen­

Key features ges, such as a poor uptake of services because of a lack of patient infor-
■ Cataract visual morbidity will double in the next 20 years and mation, misinformation from traditional healers, superstition, poor
developing countries will share the burden disproportionately quality of services, monetary costs, distance to services, and the need
because they have a higher incidence of cataract and fewer for an escort. Even where facilities are available, there is often a lack of
resources. surgeons, instruments, and other equipment (exacerbated by poor
maintenance), and a shortage of consumables and medications. Devel-
■ Factors in cataract pathogenesis include lens protein oxidation, oping intraocular lens-manufacturing facilities in these countries (such
mitochondrial function, failure of protective mechanisms, protein as the Fred Hollows Foundation in Eritrea and Nepal), will reduce costs
modification, and abnormalities of calcium metabolism, cellular and improve access to surgery.4
proliferation and differentiation.
■ An accumulation of environmental insults (e.g., ultraviolet light,
toxins, drugs, and systemic diseases) results in age-related
Genetics
Congenital or early-onset cataracts are usually inherited as a classic
cataracts. Minor risk factors such as UV-B exposure and smoking
Mendelian disorder. Age-related cataracts are inherited as a multi-
can be modified.
factorial or complex trait. Many genes and mutations responsible for
■ Nutritional, pharmacological, and genetic interventions are being inherited forms of cataract have been identified. Only a small propor-
investigated. tion of the genes currently implicated in age-related cataract have been
■ Anomalies of lens growth are usually associated with other ocular identified. Also, mutations in the same gene may result in different
or systemic disorders. cataract types. In the lens epithelial cells, increased gene expression of
ionic transport (e.g. calcium-ATPase which controls calcium channels)
and extracellular matrix proteins can cause cataracts.7 But most genes
involved in cataract formation show decreased expression. These genes
function in diverse processes, including protein synthesis, oxidative
EPIDEMIOLOGY OF CATARACTS stress (e.g., glutathione peroxidases), structural proteins, chaperones,
and cell cycle control proteins, many of which preserve lens clarity.
The World Health Organization calculated that there were 161 million Decreased expression reduces cell tolerance to stress. Future family and
visually impaired people worldwide in 2002, of which cataract accounts case control studies and next-generation sequencing techniques will
for 47.8%.1 The estimated global costs of blindness and low vision in identify more genetic determinants of inherited and age-related cata-
2000 was estimated at US$42 billion,2 and this does not account for racts and gene–gene and gene–environment interactions. This may
the reduced economic activity of each blind person’s caregiver.3 Over result in nonsurgical treatments for cataract or lifestyle interventions
the next 20 years there will be an approximate doubling in the inci- (e.g., diet) that help to prevent cataract.8, 9
dence of cataract, visual morbidity, and need for cataract surgery, as the
world’s population will increase by about one third (predominantly in
developing countries) and people will live to greater ages. But how
Nutrition, Health, and Diabetes
A number of health-related factors – diabetes, hypertension, and body
much cataract is enough to warrant surgery, how should it be per-
mass index – are associated with various forms of lens opacity, and they
formed and delivered, and how should it be paid for? In the developed
may be interrelated. A high body mass index increases the risk of devel-
world, the threshold for cataract surgery is now 20/30 (6/9) or less,
oping posterior subcapsular, nuclear, and cortical cataracts.10 Diabetes
which has resulted in a three- to fourfold increase in patients receiving
and hypertension are associated with cortical cataracts.8 Severe diarrhea
surgery, with an associated increased need for resources and funding. At
and dehydration was shown to increase the risks of developing cata-
what visual acuity level will governments and insurers pay for surgery
racts in some studies,11 but not in others,12 and severe protein-calorie
in future?4
malnutrition is more common in people with cataract.5 Therefore, a
Developing countries will bear an increasing burden for cataract
moderate calorie intake may be optimal to reduce the risk of developing
blindness, because cataracts occur earlier in life in such places, and the
cataracts.
incidence is higher. In India, visually significant cataract occurs
14 years earlier than in the United States, and the age-adjusted preva-
lence of cataract is three times that of the United States.5,6 In addition Antioxidants
there are fewer surgeons to carry out the surgery. The prevalence of The roles and mechanisms of action of dietary antioxidant vitamins
blindness can be reduced, as illustrated by the Gambian Eye Care pro- and minerals in the biochemistry and metabolism of the lens are not
gram, which reduced the prevalence of blindness from 0.7% to 0.42% clear. Ascorbate, a water-soluble antioxidant, has not been shown to
between 1986 and 1996.3 However, in the developing world, the shift reduce the incidence of cataract in most studies. Vitamin E is a lipid-
412 from intracapsular to extracapsular cataract surgery has resulted in a soluble antioxidant, which inhibits lipid peroxidation, stabilizes cell
lower visual threshold for surgery, increasing the number of operations membranes and enhances glutathione recycling, but had no effect on

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cataract incidence in most studies. Beta-carotene, the best-known caro- PATHOPHYSIOLOGY OF CATARACTS
tenoid, is a lipid-soluble antioxidant, a vitamin A precursor and is one 5.17
of 400 naturally occurring carotenoids. There are mixed reports in the The lens transmits, filters, and focuses light onto the retina. The high
literature, with some studies showing no benefit and others showing refractive index and transparency of the lens is due to the high concen-
some benefit with vitamin A, carotenoids, and combinations of vita- tration and orientation of intracellular structural proteins: α, β, and γ

Epidemiology, Pathophysiology, Causes, Morphology, and Visual Effects of Cataract

mins C and E and beta-carotene supplements.13 crystallins. The anterior subcapsular layer of cuboidal lens epithelial
cells is nucleated, actively dividing, and accounts for almost all the
Sunlight and Irradiation metabolic activity of the lens. Cuboidal cells in the equatorial zone of
Ultraviolet (UV) B light causes oxidative damage which is catarac- the lens differentiate and elongate their cytoplasm into lens fiber cells,
togenic. The level of free UV filters in the lens decreases with age, and lose their intracellular organelles and ability to perform metabolic func-
the breakdown products of the filters act as photosensitizers which tions, and form mature lens fibers. As the lens fibers age, other bio-
promote the production of reactive oxygen species and oxidation of chemical, physiological, and structural changes occur. Aging changes
proteins in the aging lens. The risk of cortical and nuclear cataract is share some similarities with age-related cataract changes, however,
highest in those with high sun exposure at a younger age. Exposure there are also unique cataract changes.26,27
later in life was more weakly associated with these cataracts. Wearing The transparency of the lens is dependent on the regular organiza-
sunglasses, especially when younger, has some protective effect.14 tion of the lens cells and intracellular lens proteins. Genetic, metabolic,
Unfortunately, the risk attributable to sunlight exposure is small,15 and nutritional, and environmental insults and ocular and systemic dis-
cortical cataracts are less debilitating than nuclear or posterior subcap- eases disrupt cellular organization and intracellular homeostasis, even-
sular cataracts. Therefore, reducing sunlight exposure may have a tually causing light scattering and absorption, which compromise
limited benefit in delaying the onset of cataracts. Exposure to high lev- vision. Once damaged, the lens has limited means of repair and regen-
els of X-rays and whole-body irradiation also causes cataracts. eration, and may lose its transparency by the formation of opaque lens
fibers, fibrous metaplasia, epithelial opacification, accumulation of pig-
ment, or formation of extracellular materials. Several interlinked
Smoking and Alcohol mechanisms for cataract formation have been proposed, and no single
Smoking causes a threefold increase in the risk of developing nuclear theory completely explains age-related cataract (the commonest form).27
cataracts, and cessation of smoking reduces this risk. Smoking may Much is still unknown about cataractogenesis, but many of the impor-
also be associated with posterior subcapsular cataracts. Smokers are tant components are becoming clearer.
also more likely to have a poor diet and high alcohol consumption,
which are also risk factors for cataract. Smoking causes a reduction
in endogenous antioxidants, and tobacco smoke contains heavy metals
such as cadmium, lead, and copper, which accumulate in the lens Cell Proliferation and Differentiation
and cause toxicity. No association between passive smoking and Aqueous growth factors control the proliferation, differentiation and
cataract has been demonstrated.16 Chronic alcoholism is associated maturation of the lens epithelial cells. Fibroblast growth factor (FGF),
with a significantly increased risk of cataract.17 Consumption of produced in the ciliary epithelium stimulates epithelial proliferation in
alcohol, particularly hard liquor and wine, is associated with nuclear low concentrations near the central anterior lens surface but induces
opacities. Wine drinking was inversely related to cortical opacity.18 lens fiber differentiation in higher concentrations near the lens equator.
Some studies have not shown an association between alcohol con- Other growth factors, such as epidermal growth factor (EGF), insulin-
sumption and cataracts.19 like growth factor (IGF), platelet-derived growth factor (PDGF), and
transforming growth factor (TGF-β) are also involved in these proc-
esses. Differentiation of the epithelial cells will not occur if growth
Age, Education, and Other Factors factor or cytokine concentrations are incorrect, then undifferentiated
Age is the greatest risk factor for cataract. There is a cumulative expo-
cells migrate to the posterior pole causing posterior subcapsular
sure to toxins (e.g. steroids) and other risk factors, an age-related
cataracts.26
decline in antioxidants and antioxidant enzymes20 and an increased
incidence of diseases such as diabetes.21 A higher level of education is
associated with a lower risk of age-related cataract; however, this may
be related to smoking, alcohol intake, and increased sun exposure in Metabolic Disturbance and
people with less education.
Osmotic Regulation Failure
Altered gene expression changes enzyme, growth factor, membrane
Myopia protein, and other protein levels, which reduces energy production,
After controlling for age, gender, and other cataract risk factors (diabe- changes ion transport, calcium metabolism and antioxidant path-
tes, smoking, and education), posterior subcapsular cataracts were ways, and breaks down protective mechanisms.26 For example the
found to be associated with myopia, deeper anterior chambers, and lens maintains high intracellular potassium and low sodium levels
longer vitreous chambers. with the opposite extracellular concentrations via the action of the
sodium-potassium ATPase pump. Pump inactivation causes increased
Pharmacological Prevention of Cataracts intracellular osmolality, which results in water accumulation and
Potential anti-cataract compounds include aldose reductase inhibitors, light scatter.26
pantethine, and aspirin-like drugs such as ibuprofen. Population stud- The aqueous humor is a source of nutrients and mineral ions
ies have also revealed a decreased risk of nuclear sclerosis with estrogen including calcium (Ca2+). Ca2+ is an intracellular signal that regulates
replacement therapy. However, none of these agents has been shown to many functions including the permeability of the cell membranes. The
prevent cataracts in a trial setting. New drugs are under investiga- extracellular Ca2+ concentration is 10 times the intracellular Ca2+ con-
tion.22–25 Anti-cataract agents would need to be safe for long-term use centration which drives Ca2+ into the epithelial cell. Low intracellular
and sufficiently inexpensive to compete with increasingly cost-effective Ca2+ levels are also maintained by intracellular organelle membrane
cataract surgery.8 pumps (on the endoplasmic reticulum, golgi apparatus, and mitochon-
Understanding the causes of age-related cataract will be helpful in dria) and by binding to complex proteins (e.g., crystallins). Extracellular
preventing or delaying cataract formation but our knowledge is incom- Ca2+ can also be bound to the outer layer of the cell membrane.
plete. Minor risk factors such as UV-B exposure and smoking can be Reduced binding of Ca2+ by membrane proteins increases cell mem-
modified but are not likely to result in large reductions in visual dis- brane permeability and causes a rise in intracellular Ca2+ levels, the
ability. Aging, the most important risk factor, cannot be modified. formation of calcium oxylate crystals, binding of Ca2+ to insoluble lens
Other strategies such as nutritional, pharmacological, and specific proteins, increased light scattering, and nuclear cataract formation.
medical and genetic interventions may be helpful in future, but are Increased intracellular Ca2+ levels also affect lens epithelial cell differ-
of unproved benefit at present. Integrated and innovative approaches entiation causing posterior subcapsular cataracts. Steroids have been
to the provision of surgery, resource management, training, start-up shown to mobilize intracellular Ca2+ in other tissues which can
capital equipment and consumables, and cost recovery mechanisms increase Ca2+ levels. In the future Ca2+ regulating drugs may be devel- 413
are required.4 oped to prevent cataracts.28

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 Fig. 5-17-1  Conformational changes in lens proteins

5 CONFORMATIONAL CHANGES IN LENS PROTEINS (unfolding) exposes thiol groups (-SH). Oxidization to
disulfides (–S–S–) causes protein aggregation and
scatters light.
The Lens

unfolding

oxidation

protein
thiol groups (–SH)
disulfide bonds (–S–S–)

Calpains filters in the nucleus also produces unstable, reactive molecules that
The roles of calpains in the lens are poorly understood, but they may bind to proteins, especially if antioxidant glutathione (GSH) levels are
degrade accumulated, damaged lens proteins. A lack of calpains can low. Ascorbate also becomes reactive with proteins in the absence of
lead to elevated levels of damaged proteins, reduce optical performance, GSH. These oxidative changes can be detected even in the earliest cata-
and cause cataract. Also, excessive stimulation of calpain activity by racts and are progressive. Elevated levels of superoxide H2O2 in the
raised Ca2+ levels can increase proteolysis and cause cataracts. Calpain aqueous may also cause cortical cataracts since the cortex is closest to
inhibitors, therefore, could be useful in the nonsurgical treatment of the aqueous. Copper and iron are present in higher concentrations in
cataract. However, calpain inhibitors of high molecular weight are cataract lenses, and are also involved in redox reactions, which produce
unable to cross membranes so have been of no therapeutic use, while hydroxyl radicals.27
others are poorly water-soluble or are toxic to lenses.29

Protein Modification Defensive Mechanisms

Antioxidant enzymes and antioxidants such as ascorbate, glutathione,
Additive modifications of lens proteins (e.g., crystallins) include meth- tocopherols, and carotenoids maintain lens proteins in the reduced
ylation, acetylation, carbamylation, glycation in diabetics, and binding state and are the primary defense mechanisms. In advanced, age-
of ascorbate, which may be the cause of lens discoloration. These addi- related, nuclear cataracts more than 90% of protein sulfhydryl groups
tions occur especially in disease and can alter the function or properties and almost half of all methionine residues in the nuclear proteins
of a protein. Diabetes (reducing sugars), renal failure (cyanate generated become oxidized. Secondary defenses include proteolytic and repair
from urea), aging (photo-oxidation products), and steroid use (ketoam- processes, which degrade and eliminate damaged proteins, UV filters,
ines) have been linked to cataracts. Additive modifications can also and other molecules such as glutathione reductase and free radical
make proteins more susceptible to photo-oxidation by UV light.26,27 scavenging systems. Failure of these protective mechanisms, a shortage
Subtractive modifications include cleavage by enzymes (such as cal- of antioxidants, and increased free radicals result in cell membrane and
pains) of crystallin which causes precipitation of lens proteins. Cleav- protein damage.26,27
age of channel proteins can affect intercellular communication. Neutral
modifications such as isomerization can denature proteins, affecting
their function. Deamidation changes the charge and affects protein–
protein interactions. Other Factors
Proteins in the center of the lens are as old as the individual and are Crystallins may have a number of functions. For example α-crystallin
very stable, but over several decades they can undergo conformational may be a chaperone that binds to other lens proteins to prevent precipi-
changes (unfolding) that expose thiol groups, which are usually ‘hidden’ tation. Decreased crystallin levels cause proteins to precipitate, which
in the folds of the protein (Fig. 5-17-1). The exposed glutathione groups leads to cataract formation. Phase separation of proteins refers to the
can be oxidized to form disulfide bonds (GSSG) causing aggregation of hydrophobic aggregation of lens proteins causing protein-rich and-poor
proteins. The conformation changes and aggregation result in scatter- regions in the lens fibers, which results in light scatter. The lipid com-
ing and absorption of light. 27 position of the cell membranes also changes with age, which may have
functional consequences.

Oxidation
Oxidation is a key feature in the pathogenesis of most cataracts. Low CAUSES OF CATARACT
oxygen levels (O2) are important for maintaining a clear lens. There is
a steep oxygen gradient from the outer part of the lens to the center. Age
Mitochondria in the lens cortex remove most of the oxygen, thus keep- The cumulative effect of many environmental factors (UV light,
ing nuclear O2 levels low. However, in older people mitochondrial func- X-irradiation, toxins, metals, steroids, drugs, and diseases including
tion diminishes and superoxide production by the mitochondria diabetes) causes age-related cataracts. Gene expression changes result
increases, resulting in increased nuclear oxygen and superoxide levels. in altered enzyme, growth factor, and other protein levels. Protein
As the lens ages, a lens barrier develops at approximately the cortex– modification, oxidation, conformational changes, aggregation and
nuclear interface, which impedes the flow of molecules such as antioxi- phase separation, formation of the nuclear barrier, increased proteoly-
dants (including glutathione) into the nucleus. Unstable nuclear mol- sis, defective calcium metabolism, and defense mechanisms are also
ecules such as peroxide (H2O2), which are generated in the nucleus or important factors. Compromised ion transport leads to osmotic imbal-
414 which penetrate the barrier, therefore cause protein oxidation. Also, ances and intercellular vacuolation. Abnormal cellular proliferation and
there is a lower concentration of antioxidants. Decomposition of UV differentiation also produces opacities (Fig. 5-17-2).
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 anterior and posterior subcapsular opacities.30 Ionizing radiation, such
as from X-rays, damages the capsular epithelial cell DNA, affecting 5.17
protein and enzyme transcription and cell mitosis. An enlarging poste-
rior pole plaque develops. Non-ionizing radiation, such as infrared, is
the cause of cataract in glassblowers and furnace workers working with-

Epidemiology, Pathophysiology, Causes, Morphology, and Visual Effects of Cataract

out protective lenses. A localized rise in the temperature of the iris
pigment epithelium causes a characteristic posterior subcapsular cata-
ract, which may be associated with exfoliation of the anterior capsule.

Systemic Disorders
In uncontrolled type 1 diabetes mellitus in young people, hypergly­
cemia causes glucose to diffuse into the lens fiber, where aldose reduct-
ase converts it to sorbitol. The cell membrane is impermeable to sorbi-
tol, therefore it accumulates and the osmotic effect draws water into
the lens fibers which swell, and then rupture. The cataract progresses
rapidly with the development of white, anterior and posterior subcap-
sular and cortical opacities.
In type 2 diabetic adults, an early-onset age-related type of cataract
Fig. 5-17-2  Age-related cataract. Nuclear sclerosis and cortical lens opacities are occurs and is more prevalent with longer duration of the diabetes.
present. Many mechanisms are involved and include sorbitol accumulation,
protein glycosylation, increased superoxide production in the mito-
chondria, and phase separation. During hyperglycemia, glucose is
reduced to sorbitol, depleting antioxidant reserves and less glutathione
is maintained in the reduced form, which causes other oxidative dam-
age. Levels of lens Ca2+ are also elevated, which activates calpains caus-
ing unregulated proteolysis of crystallins. The cataracts are usually
cortical or posterior subcapsular, or less frequently nuclear, and progress
more rapidly than age-related cataract.31,32
Galactosemia is an autosomal recessive disorder where a lack of one
of the three enzymes involved in the conversion of galactose into glu-
cose causes a rise in serum galactose levels. There is an accumulation
of galactitol within the lens fibers, and water inflow. Anterior and pos-
terior subcapsular opacities occur during infancy, which later become
nuclear. Galactose-1-phosphate uridyltransferase galactosemia is also
associated with failure to thrive, mental retardation, and hepato­
splenomegaly. Progression of the cataract can be prevented if galactose
is removed from the diet. Galactokinase deficiency is associated with
galactosemia and cataract but without the systemic manifestations.33
A Fabry’s disease is an X-linked lysosomal storage disorder that results
in accumulation of the glycolipid ceramide trihexoside. The patient
suffers from episodic fever, pains, hypertension, renal disease, and a
characteristic rash. In the affected man and the carrier woman, a typi-
cal mild, ‘spoke-like’, visually insignificant cataract develops.
Lowe’s or oculocerebrorenal syndrome is a severe X-linked disorder
that results in mental retardation, renal tubular acidosis, aminoacido-
sis, and renal rickets. Associated congenital glaucoma, congenital cata-
racts, and corneal keloids can all lead to blindness. The lens is small,
discoid and with a total cataract. Female carriers may show focal dot
opacities in the cortex.
Alport’s syndrome is a dominant, recessive, or X-linked trait disease
causing hemorrhagic nephropathy and sensorineural deafness. Ocular
features include congenital or postnatal cortical cataract, anterior or
posterior lenticonus, and microspherophakia.
Dystrophia myotonica is a dominantly inherited disorder and results
in muscle wasting and tonic relaxation of skeletal muscles. Other fea-
tures include premature baldness, gonadal atrophy, cardiac defects, and
mental retardation. Cataract is a key diagnostic criterion and may
B
develop early, but usually occurs after 20 years of age and progresses
slowly, eventually becoming opaque. Early cataract consists of poly-
Fig. 5-17-3  Traumatic cataract. (A) Typical flower-shaped pattern with coronary lens chromatic dots and flakes in the superficial cortex. As the opacities
opacities. (B) Seen in retroillumination in anterior subcapsular region.
mature, a characteristic stellate opacity appears at the posterior pole.
Other ocular features include hypotony, blepharitis, abnormal pupil
responses, and pigmentary retinopathy.
Trauma Rothmund-Thompson syndrome is an autosomal recessive disorder
Blunt trauma that does not result in rupture of the capsule may allow characterized by poikiloderma, hypogonadism, saddle-shaped nose,
fluid influx and swelling of the lens fibers. The anterior subcapsular abnormal hair growth, and cataracts, which develop between the sec-
region whitens and may develop a characteristic flower-shaped pattern ond and fourth decades of life and progress rapidly.
(Fig. 5-17-3), or a punctate opacity. A small capsular-penetrating injury Werner’s syndrome is an autosomal recessive disorder with features
results in rapid fiber hydration and a localized lens opacity; a larger that include premature senility, diabetes, hypogonadism, and arrested
rupture results in complete lens opacification. Penetrating injuries can growth. Juvenile cataracts are common. The condition usually leads to
be caused by accidental or surgical trauma such as a peripheral iridec- death at about 40 years of age.
tomy or during a vitrectomy. Cockayne’s syndrome causes dwarfism, but with disproportionately
Electric shocks as a result of lightning or industrial accident cause long limbs with large hands and feet, deafness, and visual loss from 415
coagulation of proteins, osmotic changes and fern-like, grayish white retinal degeneration, optic atrophy, and cataracts.

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 Dermatological Disorders mechanism of action is unknown. Phenothiazines, such as chlorpro-
5 The skin and the lens are of ectodermal origin embryologically. There-
fore, skin disorders may be associated with cataract formation.
mazine, may cause deposition of fine, yellow-brown granules under the
anterior capsule in the pupillary zone and may develop into large stel-
Atopic dermatitis and eczema may affect any part of the body, espe- late opacities but are not usually visually significant. The development
of the opacities may be related to the cumulative dose of the medica-
The Lens

cially the limb flexures. Localized proliferation of lens epithelium

occurs in some atopic adults, usually as a bilateral, rapidly progressive tion; photosensitization of the lens may play a role. Allopurinol used in
‘shield cataract’ (a dense, anterior subcapsular plaque with radiating the treatment of gout is associated with cataracts.34 Psoralen-UV-A
cortical opacities, and wrinkling of the anterior capsule). Posterior sub- therapy for psoriasis and vitilligo has been shown to cause cataracts in
capsular opacities may also occur. very high doses in animal studies, but is rare in humans; concomitant
Ichthyosis is an autosomal recessive disorder that features hyper- UV exposure may be a risk factor. Antimitotic drugs, such as busulfan,
trophic nails, atrophic sweat glands, cuneiform cataracts, and nuclear used in the treatment of chronic myeloid leukemia, may cause poste-
lens opacities. rior subcapsular cataract. The antimalarial chloroquine (but not
Incontinentia pigmenti is an X-linked dominant disorder that affects hydroxychloroquine), which is also used in the treatment of arthritis,
skin, eyes, teeth, hair, nails, and the skeletal, cardiac, and central nerv- may cause white, flake-like posterior subcapsular lens opacities. Amio-
ous systems. Blistering skin lesions occur soon after birth, followed by darone is used to treat cardiac arrhythmias and causes insignificant
warty outgrowths. Ocular pathology includes leukokoria, cataract, cho- anterior subcapsular opacities and corneal deposits.35
rioretinal changes, and optic atrophy. Siderosis, from a ferrous intraocular foreign body, causes iron depos-
its in the lens epithelium and iris, and results in a brown discoloration
of the iris and a flower-shaped cataract. Wilson’s disease, an autosomal
Central Nervous System Disorders recessive disorder of copper metabolism, causes a brown ring of copper
Neurofibromatosis type II is an autosomal dominant disorder causing deposition in Descemet’s membrane and the lens capsule, resulting in
numerous intracranial and intraspinal tumors and acoustic neuromata. a sunflower cataract – an anterior and posterior capsular disc-shaped
Ocular features include combined hamartoma of the retina and retinal polychromatic opacity in the pupillary zone with petal-like spokes that
pigment epithelium, epiretinal membranes, iris Lisch nodules (a diag- is not usually visually significant.36 Hypocalcemia in hypoparathy-
nostic sign), and posterior subcapsular, or cortical cataracts that devel- roidism is associated with cataracts. In children, the cataract is lamel-
op in the second or third decade of life. lar; in adults it produces an anterior or posterior punctate subcapsular
Zellweger syndrome, also known as hepatocerebrorenal syndrome, is opacity.
an autosomal recessive disorder, characterized by renal cysts, hepato­
splenomegaly, and neurological abnormalities. Ocular features include
corneal clouding, retinal degeneration, and cataracts. Congenital and Juvenile Cataracts
Norrie’s disease is an X-linked recessive disorder that causes leuko­ Congenital cataracts are noted at birth, infantile cataracts occur in the
ria, congenital infantile blindness, and is associated with mental retar- first year, and juvenile cataracts develop during the first 12 years of life.
dation and cochlear deafness. In the eye, vitreoretinal dysplasia, retinal Hereditary cataracts may be associated with other systemic syndromes,
detachment, vitreous hemorrhage, and formation of a white retrolental such as dystrophia myotonica. About one third of all congenital cata-
mass occur. Eventually, a cataract forms. racts are hereditary and unassociated with any other metabolic or sys-
temic disorders.
Ocular Disease and Cataracts Trisomy 21, or Down’s syndrome, is the most common autosomal
Inflammatory uveitis (e.g., Fuchs’ heterochromic cyclitis and juvenile trisomy, with an incidence of 1 per 800 births. Systemic features
idiopathic arthritis) usually results in posterior subcapsular or posterior include mental retardation, stunted growth, mongoloid facies, and
cortical lens opacities. Infective uveitis (e.g., ocular herpes zoster and congenital heart defects. Ocular features include visually disabling
toxoplasmosis, syphilis, and tuberculosis) can cause cataracts, but the lens opacities in 15% of cases, narrow and slanted palpebral fissures,
organism does not penetrate the lens. In maternal rubella infection, blepharitis, strabismus, nystagmus, light-colored and spotted irises
after 6 weeks of gestation, the virus can penetrate the lens capsule (Brushfield spots), keratoconus, and myopia.37 Cataract is also associ-
causing unilateral or bilateral, dense, nuclear opacities at birth, or they ated with trisomy 13 (Patau’s syndrome), trisomy 18 (Edwards’
may develop several weeks or months later. Corticosteroid treatment syndrome), Cri du chat syndrome (deletion of short arm of chromo-
can also cause cataracts, usually posterior subcapsular. Retinal pigment some 5), and Turner’s syndrome (X chromosome deletion).
degenerations such as retinitis pigmentosa, Usher’s syndrome, and A total cataract is a complete opacity present at birth. It may be
gyrate atrophy are associated with cataracts, which are usually posterior hereditary (autosomal dominant or recessive) or associated with sys-
subcapsular opacities. Retinal detachment and retinal surgery may temic disorders such as galactosemia, rubella, or Lowe’s syndrome.
cause a posterior subcapsular cataract particularly in association with Infantile cataracts cause amblyopia if unilateral and may cause strabis-
vitrectomy, silicone oil injection and tamponade, or an anterior subcap- mus and nystagmus if bilateral. The incidence is about 0.4% of new-
sular form may develop because of metaplasia of the lens epithelium borns, but the majority of cases are not associated with poor vision.
after vitreoretinal surgery. High myopia is associated with posterior Amblyopia depends on the size, location, and density of the cataract.
cortical, subcapsular, and nuclear cataracts. Ciliary body tumors may The causes of infantile cataracts are many and include maternal infec-
be associated with cortical or lamellar cataract in the affected quadrant. tions (such as rubella), systemic diseases, hereditary disorders, and
Anterior segment ischemia may cause a subcapsular or nuclear cata- ocular disease.
ract, which progresses rapidly.
MORPHOLOGY
Toxic Causes
Topical, inhaled, and systemically administered steroids can cause pos- Age-related changes in the lens affect the lens power and light trans-
terior subcapsular cataracts. Direct mechanisms included interaction of missibility, causing fluctuations in vision and scattering of light. Slit-
steroids with enzymes which affects their function, e.g., steroid modu- lamp biomicroscopy can be used to grade and differentiate lens opaci-
lation of Na+,K+-ATPase may cause sodium-potassium pump inhibi- ties. Each type of opacity has different clinical effects, and combina-
tion affecting osmotic regulation. Steroids also induce crystallin confor- tions of the different types occur.
mational changes, causing aggregation and affecting intracellular Ca2+ Nuclear opacities are caused by a gradual increase in the optical
homeostasis, which causes protein bonding. Indirectly, steroids affect density of the deepest layers of the nucleus, progressing slowly to
DNA/RNA synthesis of proteins and enzymes causing metabolic involve more superficial layers (see Fig. 5-3-1). The nucleus may also
changes, and may also affect ciliary body growth hormone levels change color from clear to yellow to brown (catataracta brunescence)
responsible for lens cellular differentiation, which cause posterior sub- and sometimes to black (catataracta nigra). Patients may experience
capsular opacities.26 increased myopia (because of the increased refractive index of the lens)
Chronic use of long-acting anticholinesterases previously used in the and a progressive, slow reduction in visual acuity and loss of contrast
treatment of chronic open-angle glaucoma may cause anterior subcap- sensitivity. Cortical opacities cause few symptoms initially as the visual
416 sular vacuoles and posterior subcapsular and nuclear cataracts. Pilo- axis remains clear, but later the opacities may involve most of the cor-
carpine, a shorter-acting agent, causes less marked changes. The tex of the lens (Fig. 5-3-2).

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 Posterior subcapsular opacities begin at the posterior polar region, VISUAL EFFECTS OF CATARACTS
then spread toward the periphery. Patients have significant glare dis­ 5.17
ability because of light scattering at the nodal point of the eye. The effect of cataract on vision varies according to the degree of the
Complete opacification of the lens eventually occurs. The crystalline cataract and the cataract morphology.
lens may then swell (intumescent cataract; see Fig. 5-3-3). The cortical

Epidemiology, Pathophysiology, Causes, Morphology, and Visual Effects of Cataract

material may liquefy (Morgagnian cataract; see Fig. 5-3-4) and then
re-absorbed causing the solid nucleus to ‘sink’ to the bottom of the
Visual Acuity
Visual acuity is reduced, and this has been the standard measure of the
capsular bag.
visual effect of cataracts. However, visual acuity can remain good
despite other lens opacity-related effects on vision, which compromise
ASSESSMENT AND GRADING OF CATARACTS the patient’s ability to function.
Grading and classifications of cataracts (Box 5-17-1) are useful in cata-
ract research, in studies to explore causation, and in trials of anti- Contrast Sensitivity, Glare, and
cataract drugs. Direct ophthalmoscopy with retroillumination can be Wavefront Aberrometry
used to assess and grade cataracts.38 The Lens Opacification Classifica- Cataract-related reduction in contrast sensitivity causes reduced acuity
tion System II (LOCS-II) slit-lamp grading system is reproducible and at low ambient light levels. Contrast sensitivity measurements based
has been validated. Using slit-lamp direct and retroillumination, on linear sine-wave gratings have resulted in improved understanding
nuclear, cortical, and posterior subcapsular cataracts are graded by com- and quantifying of visual quality and function. Wavefront aberrometry
parison with a set of standard photographs.39 Devices for quantifying measures the optical quality in terms of spatial distortion. Both meas-
lens opacification have also been developed (such as the Kowa Early urements are useful for understanding the effects of cataracts on
Cataract Detector and the Scheimpflug Photo slit lamp). vision.40 Glare, which occurs as a result of forward scatter of light, may
be produced by opacities that do not lie within the pupil diameter and,
therefore, also affects visual function.41

Other Effects
BOX 5-17-1  INFANTILE CATARACTS The natural aging of the human lens produces a progressive hyperopic
shift. Nuclear changes induce a modification of the refractive index of
Anterior Polar Cataract
the lens and produce a myopic shift. Cortical opacities may cause local-
 Dominantly inherited, well-defined opacities of the anterior capsule may
ized changes in the refractive index of the lens, which may result in
affect the vision
monocular diplopia or even polyopia. As the lens nucleus becomes
 Caused by imperfect separation of lens from surface ectoderm, by epi-
more yellow, it absorbs blue light. The slow change is not apparent to
thelial damage, or by incomplete reabsorption of the vascular tunic of
the patient until after cataract surgery. The morphology, density, and
the lens
location of lens opacities may cause changes in the visual field. These
 May have anterior or posterior conical projections; if it extends into the
changes may be progressive and may obscure the disk; therefore, diag-
cortex in a rod shape, it is called a ‘fusiform’ cataract
nosis and monitoring of glaucoma may be compromised.
Spear Cataract
 Dominantly inherited, polymorphic cataract with needle-like clusters of ANOMALIES OF LENS GROWTH
opacities in the axial region, which may not affect vision
Coralliform Cataract The lens is ectodermal and the vascular capsule is mesodermal in ori-
 Dominantly inherited cataract, which consists of round and oblong gin. A number of exogenous or endogenous influences can affect ecto-
opacities, grouped toward the center of the lens; they resemble coral dermal or mesodermal development and can have multiple manifesta-
tions in the eye.
Floriform Cataract
 A rare, ring-shaped, bluish white, flower-shaped cataract in the axial
region Aphakia
Aphakia is the absence of the lens. Primary aphakia is rare and is asso-
Lamellar Cataract ciated with a primary defect in the surface ectoderm. It is associated
 A common, bilateral and symmetrical, round, gray shell of opacity that with other abnormalities of the anterior segment, such as microphthal-
surrounds a clear nucleus; usually dominantly inherited cataract, which mos, microcornea, and nystagmus. Secondary aphakia is more com-
may have a metabolic or inflammatory cause mon and is characterized by the presence of lens remnants. The cause
 Fibers become opacifed in response to a specific insult during their most is unknown. It may be associated with the same malformations, or
active metabolic stage and are pushed deeper into the cortex as normal may be found in an otherwise normal eye.42
lens fibers are laid down around it
Cataracta Centralis Pulverulenta
 Dominantly inherited, nonprogressive cataract consisting of fine, white,
powdery dots within the embryonic or fetal nucleus (Fig. 5-17-4)
Congenital Punctate Cerulean Cataract
 Bilateral, nonprogressive, small, bluish dots scattered throughout the
lens with little effect on vision
Congenital Suture (Stellate) Cataract
 Dominantly inherited bluish dots or a dense, chalky band around the
sutures affecting one or both fetal sutures, especially posteriorly and
may interfere with vision
Mittendorf’s Dot
 A small (about 1 mm diameter), nonprogressive, white condensation
occurs on the posterior pole of the lens capsule; it may be decentered
slightly inferonasally and may be attached to a free-floating thread in the
vitreous gel, which represents the anterior part of the hyaloid artery
remnant
Congenital Disciform Cataract
 Central thinning creates a doughnut shape, which may arise from failure
of development of the embryonic nucleus 417
Fig. 5-17-4  Cataracta centralis pulverulenta. Opacification of fetal nucleus.

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 may be associated with coloboma of the iris, ciliary body, or choroid, or
5 with ectopia lentis, sperophakia, or localized lens opacities. It may
occur because persistence of mesodermal vascular capsules remnants
prevents the development of zonules in that area.
The Lens

Ectopia Lentis
Ectopia lentis, or displaced lens, is usually a bilateral condition caused
by extensive zonular malformation. The lens is displaced in the oppo-
site direction to the weak zonules (usually superomedially) and usually
presents in childhood or young adulthood. The lens may sublux out of
the central posterior chamber or may dislocate completely into the
anterior chamber or vitreous or become cataractous. It may be an auto-
somal dominant or recessive trait or may be associated with other
developmental abnormalities of the eyes, such as iris coloboma, micro-
spherophakia, aniridia, or ectopia pupillae congenita. It may also be
associated with systemic disorders such as Marfan syndrome (Fig.
5-17-5), Weill-Marchesani syndrome, homocystinuria, sulfite oxidase
deficiency, and hyperlysinemia. The clinical features of a subluxed lens
include iridodinesis (tremulous iris), fluctuating anterior chamber
depth and vision, and phacodinesis (a visibly mobile lens). Vitreous
Fig. 5-17-5  Marfan syndrome. A retroillumination slit-lamp photograph of ectopia may herniate into the anterior chamber. Pupil block may occur with iris
lentis associated with Marfan syndrome. apposition to the vitreous face or an anterior dislocated lens (into the
anterior chamber).

Microspherophakia
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