CHAPTER 6

Lens

Anatomy and Physiology

EMBRYOLOGY Derived from surface ectoderm, with inward sequestration instead of desquamation of aging cells. Majority of lens development occurs at 3 to 8 weeks in utero.

At the 4 mm stage, the optic vesicle that is apposed to the surface ectoderm initiates the formation of the lens placode. A single layer of columnar cells is seen as the fovea lentis (lens pit) and invaginates concomitantly with the optic vesicle conversion to a double-layered optic cup. The lens vesicle separates from the cornea at the 9 mm stage, with basal cell membranes external and apices facing the lumen.

The lens capsule forms at the 10 mm stage, as does the tunica vasculosa lentis, which fully encompasses the lens by the 40 mm stage. The posterior vascular capsule begins from the hyaloid artery anteriorly to join with the choroidal vein, then proceeds to join the long ciliary artery to form the anterior vascular capsule (pupillary membrane).

The posterior cells of the lens vesicle elongate to obliterate the lumen by 16 mm (forming the primary lens fibers, later known as the embryonic nucleus). Anterior vesicle cells remain as the lens epithelium and at 25 mm begin to proliferate at the germinative zone, then differentiate at the equatorial transitional zone and are added internally as secondary lens fibers. Secondary fibers never reach both the anterior and posterior poles, and thus form the anterior upright Y suture and posterior inverted Y (the Y sutures enclose the fetal nucleus). Later adult fibers form more complex stellate sutures.

ANATOMY (Fig. 6–1) Elongated adult lens fibers have a basal process posterior beneath the capsule and an apical process anterior beneath the epithelium. The nucleus assumes a more anterior position as the fibers internalize, producing the lens bow. Fibers denucleate, lose organelles, and form complex interdigitations with other fibers; the lens cortex contains the most recently created fibers. Anterior radius of curvature is about 10 mm, and the posterior surface curvature is 6 mm.

Capsule: the basement membrane of the lens epithelial cells. Composed of type IV collagen with heparin sulfate, it is thinnest at the posterior pole (2–9 mm) and thickest paraequatorial (12–21 mm).

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202 LENS

Figure 6–1 Anatomy of the adult lens in cross section.

Lens epithelium: an anterior cuboidal monolayer. The equatorial cells form lens cell ‘‘fibers’’ by inward sequestration throughout life (older cells are in the nucleus). Arranged in lamellae, the fibers meet at the Y sutures.

Lens proteins: 33% of the lens is protein that is either water soluble or insoluble. Water-soluble crystallines are labeled alpha (30%), beta (55%), and gamma (15%), derived from two unrelated protein superfamilies (alpha proteins are the most highly conserved). Waterinsoluble proteins are characterized as urea soluble or insoluble; they increase with age and are responsible for cataract genesis.

PHYSIOLOGY Nearly all of the lens metabolic needs are supplied by glucose that is converted into adenosine triphosphate (ATP) from glycolysis. Most energy is derived from anaerobic glycolysis (70–90%), and to a lesser extent, from the hexose monophosphate shunt, the sorbitol pathway, and the tricarboxylic acid (TCA) cycle. The lens has limited immune

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sequestration (not complete but diminished access to immune system). It receives passive nutrition from the aqueous. Accommodation is from zonular relaxation, allowing the central anterior lens to bulge.

Hardening of the lens, not loss of ciliary muscle tone, causes presbyopia.

In diabetes, the lens converts excess glucose into sorbitol, which is not transported out; as sorbitol collects, it causes lens hydration and myopic shift.

OPTICAL PROPERTIES Progressive increase of refractive index, from 1.38 in the periphery to 1.50 at the center. The lens is transparent because lens cells lack nuclei. It has homogeneous cytoplasm, with ordered crystalline proteins and fibers ordered in a paracrystalline array. It has minimal extracellular space and is avascular.

ZONULES Comprising the tertiary vitreous, zonules arise from the pars plana and are composed of elastic fibrillin.

Signs and Symptoms

ECTOPIA LENTIS May be from trauma, inherited as autosomal dominant or autosomal recessive, or secondary to systemic disease, such as Marfan syndrome (‘‘sun rise’’ dislocation), Weill-Marchesani syndrome (dislocates anterior into the AC), homocystinuria (‘‘sun set’’ luxation), hyperlysinemia, sulfite oxidase deficiency, aniridia (20% incidence), megalocornea, Kniest syndrome, coloboma (absence of zonules; may be part of the CHARGE association), PHPV, tertiary syphilis (always do work-up for syphilis), and Ehlers-Danlos syndrome. Classified as subluxation (partial loss of zonular support), luxation (total loss of zonular support), or dislocation (lens out of place). In general, avoid surgery if possible.

GLAUKOMFLECKEN White epithelial and anterior cortical opacities that represent focal anterior lens epithelium necrosis following acute glaucoma.

RETAINED NUCLEI IN LENS Asssociated with rubella (epithelial cell migration into lens), microphthalmia, dermal aplasia, and sclerocornea (MIDAS) syndrome, Leigh syndrome, trisomy 13, Lowe’s syndrome, and Down syndrome.

UNILATEAL MATURE CATARACT May be normal variant, but rule out underlying chronic RD, trauma, or tumor.

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204 LENS

Congenital and Genetic Disease

CATARACT, CONGENITAL OR INFANTILE Present at birth (congenital) or during first year (infantile) in 1/2000 live births. One third of cases are associated with systemic disease, one third are inherited, and one third are from undetermined cause. Important to obtain a red reflex history, family history, full pediatric exam, date of onset, and associated signs and symptoms. Can characterize based on laterality (bilateral vs. unilateral) and by morphology of cataract.

CATARACT, LATERALITY Narrows the differential diagnosis.

Bilateral: 60% idiopathic, 30% herditary (usually autosomal dominant), 10% from a metabolic or systemic disorder such as diabetes, galactosemia, Lowe’s, Down, Alport’s, or Marfan syndromes, Fabry’s disease, trisomies 13–15, hypoglycemia, myotonic dystrophy, hypoparathyroidism, aniridia, anterior segment dysgenesis, corticosteroids, radiation, and TORCH, especially rubella. Work-up with TORCH titers, VDRL, RBC galactokinase level, urine for reducing substances, and calcium and phosphorus levels.

Unilateral: 80% idiopathic, 10% traumatic (rule out NAT), 10% from local dysgenesis and not inherited such as PHPV, anterior segment dysgenesis, posterior lenticonus, anterior polar, posterior pole tumors, or rubella. Check TORCH titers.

CATARACT, MORPHOLOGY Lamellar is the most common.

Cerulean: bluish, central, and not visually significant.

Coronary: crownlike peripheral.

Lamellar: most common congenital cataract (40%) from involvement of secondary lens fibers, zonular, with disk-shaped layers of opacification surrounding a clearer center. Bilateral, symmetrical, usually autosomal dominant, or sporadic cases usually from transient toxic influence (e.g., prenatal tetany).

Membranous: traumatized lens resorbs proteins and forms dense white anterior membrane.

Nuclear (pulverulent, Coppock cataract, cuneiform): opacification of embryonic nucleus (from disturbance in first 3 fetal months). May be bilateral (usually autosomal dominant) or unilateral, typically in a small eye.

Persistent hyperplastic primary vitreous (PHPV): usually posterior cortical opacification that progresses to complete cataract that is unilateral and sporadic. Bilateral cases usually seen with chromosomal trisomies.

Polar: subcapsular cortex and lens capsule opacity.

Anterior polar: small, bilateral, symmetric, nonprogressive; usually autosomal dominant but may be unilateral and sporadic. May be

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associated with microphthalmos, PPMD, anterior lenticonus, and Peters’ anomaly.

Posterior polar: more visual impairment than anterior, progressive, usually autosomal dominant and bilateral, but may be sporadic and unilateral. Associated with remnants of tunica vasculosa lentis, PHPV, and lentiglobus or lenticonus. May have capsular fragility during CE.

Posterior lenticonus: sporadic, unilateral, polar.

Posterior subcapsular: acquired, developmental. Usually associated with Down syndrome, steroid use, RP, or trauma if unilateral.

Sutural: common fetal stellate cataract from opacified Y suture; bilateral, symmetric, and usually autosomal dominant, but not visually significant.

Capsular: protrudes into the AC, unlike anterior polar cataract; usually not visually significant.

CATARACT, FROM ASSOCIATED SYSTEMIC OR

SYNDROMIC CONDITIONS

Aniridia: anterior and posterior lens opacities at birth and cortical, subcapsular, and lamellar opacities in 50 to 85% of cases within first two decades. Associated with poor zonular integrity and ectopia lentis.

Galactosemia: autosomal recessive inability to convert galactose to glucose from an enzyme defect in galactose-1-phosphate uridyl transferase (most common), galactokinase, or UDP-galactose-4-epimerase. Classic ‘‘oil droplet’’ cataract in 75% of cases from accumulation of galactose and galactitol, with osmotic lens swelling; early cataract may be reversed with dietary changes. Patients also have mental retardation, malnutrition, hepatomegaly, and jaundice within a few weeks of birth. Galactosemia is fatal if not treated by elimination of milk from diet.

Lowe’s (oculocerebrorenal) syndrome: X-linked recessive disorder, with bilateral anterior lenticonus or micropunctate cortical cataracts with flat discoid lens and retained nuclei. Female carriers may have cortical lens opacities and aminoaciduria. Associated with glaucoma in 67% of cases from trabeculodysgenesis; also microphthalmia, nystagmus, strabismus, mental retardation, renal tubular acidosis (Fanconi syndrome), renal rickets, and hypotonia. CE is often difficult (total cataract).

Myotonic dystrophy: autosomal dominant disorder, with ‘‘Christmas tree’’ polychromatic iridescent crystals in the lens cortex, that progresses to complete opacity. Associated with delayed relaxation of contracted muscles (patients cannot let go when they shake your hand), frontal balding in males, ptosis, and cardiac conduction defects.

Peters’ anomaly: may have adhesions between the lens and the cornea, with anterior polar or cortical cataract, microspherophakia, and anterior lens displacement.

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206 LENS

Rubella cataract: RNA togavirus infection in the first trimester, with cardiac defects, deafness, and mental retardation (Gregg’s syndrome, rubella embryopathy). Usually bilateral (20% are unilateral). May have complete or pearly white nuclear opacifications in 15% of cases, with retention of live virus (no women of childbearing age should be in the OR during CE; may have postoperative inflammation from viral endophthalmitis) and retention of lens nuclei. May also have diffuse pigmentary retinopathy (salt and pepper fundus), microphthalmos, glaucoma, and corneal clouding.

CONGENITAL APHAKIA Primary lens plate fails to form; more commonly from secondary spontaneous resorption of lens.

ECTOPIA LENTIS FROM CONGENITAL CAUSES Trauma is the most common cause, but may be inherited as autosomal dominant (simple) or recessive (et pupillae) or secondary to systemic disease. In general, avoid surgery if possible.

Ectopia lentis et pupillae: bilateral, progressive autosomal recessive displacement of the lens and pupil in opposite directions. Associated with axial myopia, RD, enlarged cornea, early cataract, and TID with poor dilation from hypoplastic iris sphincter muscle.

Homocystinuria: autosomal recessive inborn error of methionine metabolism, most commonly from deficiency of beta-synthase, that converts homocysteine to cystathionine; 1:15,000 incidence. Seen in tall, blond, Marfan-like patients, except they have mental retardation and stiff joints. Patients are normal at birth, then develop seizures, osteoporosis, and progressive mental retardation in 50% of cases.

Lens dislocation occurs in 30% of affected infants and in 80% by age 15. Ectopia lentis is bilateral and symmetric from brittle cysteine-deficient zonular fibers. The lens displaces into the AC in 77% and posteriorly in 23% of cases (although classic answer is inferonasally on exams). Pathology shows periodic acid–Schiff (PAS) stained material on the zonules and on the surface of the ciliary epithelium.

Patients have increased serum and urine homocysteine (check sodium nitroprusside urinary test) and methionine. Increased homocysteine increases risk of thrombosis and small vessel disease (small strokes); patients are prone to thromboembolic events, especially during general anesthesia.

Fifty percent mortality by age 20. Treat with low-methionine

(no meat) and high-cysteine diet, along with extra vitamin B6. Patients need heparin and a beta-blocker.

Hyperlysinemia: inborn error of lysine metabolism associated with mental retardation, muscular hypotony, and ectopia lentis, typically with Louisiana Cajun ancestry.

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Marfan syndrome: autosomal dominant (however, no family history in 15% of cases) gene defect of glycoprotein fibrillin 15, which is the major component of elastic tissue throughout the body, including zonules.

Seen in tall patients with arachnodactyly, normal intelligence, hyperextensible joints, chest wall abnormalities, and often a dilated aortic root (large vessel disease, unlike homocystinuria) and mitral valve prolapse.

Eighty percent of patients have ectopia lentis that is bilateral and symmetric, from stretched zonular fibers. Seventy-five percent have subluxation superotemporal (mnemonic: picture Abraham Lincoln, who was probably marfanoid, holding his arms up and out), often associated with cataract.

Patients also may have megalophthalmos (abnormal scleral fibrillin) with high axial myopia, enophthalmos (absence of retrobulbar fat), increased corneal diameter (13–14 mm), flat cornea (K 38– 39 D), deep AC, glaucoma, poor dilation from hypoplasia of the iris dilator muscle, TID, increased vitreous loss with cataract extraction, a normal vitreous (unlike Stickler’s syndrome), RD (usually can treat with just a buckle), staphyloma and Fuchs’ spots, strabismus (in 20% of patients), and often amblyopia.

Treat with good optical correction (meticulous retinoscopy; cylinder is usually in the axis of lens dislocation), as patients can have good VA and will need reading aid. Treat cataract and glaucoma (may have RPB from microspherophakia) if needed, but may be hazardous and may need lensectomy using vitrectomy. Typically suture a large single-piece IOL, and trabeculectomy usually works well (because this is a connective tissue disorder). Prescribe a beta-blocker early to delay aortic aneurysm formation.

Simple ectopia lentis: autosomal dominant; is likely the milder end of a spectrum with Marfan syndrome (less severe mutation in fibrillin 15 gene).

Sulfite oxidase deficiency: autosomal recessive disorder of sulfur metabolism; associated with severe mental retardation, myoclonus, seizures, and ectopia lentis in 50% of cases.

LENS COLOBOMA May be primary and isolated or secondary from lack of ciliary body or zonular development, usually inferonasal. Also may be acquired from ciliary body tumors (especially medulloepithelioma).

LENTICONUS AND LENTIGLOBUS Localized cone-shaped (conus) or spherical deformation (globus) of the lens. Posterior location is more common and is usually seen in females, both unilateral and axial. Anterior lenticonus usually affects males and is bilateral; associated with Alport’s

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