Etiology of cataracts

Genetic and metabolic diseases

DOWN’S SYNDROME

Down’s syndrome may be associated with cataract formation at any age, but it typically presents within the first year of life. The opacities may vary in location and appearance. Other ocular abnormalities associated with Down’s syndrome include epicanthal folds, refractive errors, iris abnormalities (Brushfield spots), strabismus, nasolacrimal duct obstruction, retinal abnormalities, amblyopia, and nystagmus.9

GALACTOSEMIA

This is an autosomal recessive disorder caused by a deficiency of one of three enzymes (galactokinase, galactose-1-phosphate uridyl transferase, or uridine diphosphate galactose epimerase). It frequently leads to bilateral cataracts, which may begin with a classic ‘oildroplet’ appearance. It may be at least partially reversible with the elimination of galactose from the diet. If left untreated, it may progress to complete opacification of the lens.10

LOWE SYNDROME

Lowe syndrome (oculocerebrorenal) is an X- linked recessive disease characterized by cataracts, mental retardation, and renal aminoaciduria. Lens opacities occur in nearly 100% of affected males and may be associated with posterior lenticonus (116).11 Development of glaucoma is also common. Female carriers may have mild peripheral lens opacities as well.12 Diagnosis is confirmed by identifying amino acids in the urine. Life expectancy is significantly reduced with death often in the second decade.

ALPORT SYNDROME

This is an X-linked dominant disorder characterized by anterior lenticonus, deafness, and interstitial nephritis.13 Anterior lenticonus is frequently associated with anterior subcapsular cataract formation (117). Rarely, the lens capsule may spontaneously rupture, leading to complete cataract.14

DIABETES

Diabetes-related cataracts may occasionally be found in children. These cataracts typically appear as diffuse subcapsular or snowflake-like opacities.

HYPOGLYCEMIA

This is often seen in low birth-weight infants. Cataracts are usually bilateral and lamellar, but may cause complete opacity.5

MYOTONIC DYSTROPHY

Myotonic dystrophy is an AD muscular dystrophy characterized by progressive muscle wasting. The classic bilateral lens opacities appear as polychromatic, iridescent ‘Christmastree’ cataracts (118). Additional ocular features include ptosis, extraocular muscle paresis, microphthalmos, and retinal pigmentary degeneration. Nervous system involvement and cardiac abnormalities are also typical.15 Hypoparathyroidism occasionally leads to cataract formation in children. The opacities are related to hypocalcemia and consist of multicolored flecks (similar to the ‘Christmastree’ cataract seen in myotonic dystrophy).

FABRY’S SYNDROME

This is a rare X-linked recessive disease caused by a defect in the activity of the alphagalactosidase A enzyme. It leads to abnormal glycosphingolipid storage, which then accumulates in the eyes, central and peripheral nervous systems, cardiac muscle, kidneys, and vascular tissue. Early signs of the disease include pain and burning in the extremities as well as reddish-purple punctate skin lesions (angiokeratoma corporis diffusum). Affected males generally die in their 3rd–4th decades from cardiovascular disease and renal failure. Lens opacities are common and have a characteristic appearance. They appear as posterior spokelike cataracts, which are pathognomonic for the condition. Anterior subcapsular cataracts may also be seen. Other ocular features of this disease include classic corneal subepithelial whorl-like opacities and vascular abnormalities of the conjunctiva and retina.16

116

116 Slit-lamp view of a posterior polar cataract associated with posterior lenticonus in a 10-year-old.

REFSUM SYNDROME

This is a disorder of phytanic acid metabolism that results from defects in phytanoyl-CoA hydroxylase. Ocular associations include pupil abnormalities, retinitis pigmentosa, nystagmus, and cataract.17 Nonocular associations include deafness, anosmia, cerebellar ataxia, and peripheral polyneuropathy. Treatment consists of restriction of dietary phytanic acid.

WILSON’S DISEASE

This is a rare, AR disorder characterized by abnormal copper metabolism. Copper accumulates in various organs, including the liver, central nervous system, and eye. The classic ocular findings include a Kayser–Fleischer ring (a greenish-brown accumulation in the peripheral cornea) and a yellowish, petaloid, anterior subcapsular opacity termed a ‘sunflower’ cataract.18

CONRADI SYNDROME

This is an X-linked dominant form of chondrodysplasia punctata characterized by asymmetric limb shortening, skin abnormalities, and sparse hair. Cataracts are an occasional feature of this disorder.19

MANNOSIDOSIS

This is a rare AR lysosomal storage disease due to a deficiency in alphaor beta-mannosidase (type 1 and 2 respectively), which leads to defective lipoprotein degradation. An assay for

117

117 Anterior lenticonus associated withAlport syndrome seen by direct slit-lamp examination and retroillumination (inset).(Courtesy of

M.EdwardWilson,Jr.,MD.)

118

118 Classic‘Christmas-tree’ cataract seen in myotonic dystrophy. (Reproduced,with permission,from Johns KJ, Basic and Clinical Science Course:Cataract and Lens,Section 11, AmericanAcademy of Ophthalmology, 2001–2002.)

the specific enzyme is diagnostic. Posterior spokelike or scattered punctate lens opacities are characteristic and generally form within the first year of life.20 Type 1 disease is most severe, generally resulting in progressive mental and motor retardation, leading to death in the first decade of life.

implicated in cataract formation include amiodarone, phenothiazines, chloroquine, busulfan, and the topical anticholinesterase and miotic drugs used to treat chronic open-angle glaucoma.26

Toxic chemicals which come in contact with the eye and cause corneal burns may lead to cataract formation. Exposure to radiation or chronic cigarette smoke is also a risk factor for the development of lens opacities. Iron (siderosis), gold (chrysiasis), silver (argyriasis), and copper (chalcosis) may cause cataracts.

Maternal infection

Intrauterine infections may result in cataracts. These opacities are most often bilateral, but may be unilateral. The majority of these infection-related cataracts are caused by

toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and syphilis (TORCHS). Varicella, measles, mumps, and human immunodeficiency virus (HIV) have also been implicated in some cases.5 Rubella is the most common and most classic etiology of intrauterine infection causing congenital cataracts. Congenital rubella is also associated with a high incidence of sensorineural hearing loss, heart defects, and mental retardation. Other ocular findings may include retinopathy, strabismus, microphthalmos, optic atrophy, keratitis, and glaucoma.27 Live virus particles may remain dormant in the lens and severe inflammation may ensue when the cataract is removed. Congenital rubella syndrome is now extremely rare in the US since the introduction of the vaccine, but the incidence is much higher in unvaccinated populations.