▃Anatomy of Lens (OP7.1)
The adult human lens is located behind the iris and pupil in the anterior compartment of the eye. The lens is held in place by zonules (suspensory ligaments) which run between the lens and ciliary body. The lens continues to grow throughout life. It is a unique characteristic not shared with any other internal organ.
The lens is biconvex, with the anterior surface being less convex than the posterior surface (Fig. 10.1).
■Radius of Curvature
The radius of curvature of anterior surface is 10 mm, while that of posterior surface is 6 mm.
The poles represent the center points of these two surfaces. The anterior pole is the center of anterior surface and posterior pole is the center of posterior surface of lens. The anteroposterior axis runs from the anterior pole to the posterior pole (polar axis). The anterior and posterior surface meet at the equator which is the circumference of lens. The equatorial axis is at right angle to the anteroposterior axis.
Diameter of lens: 8.8 to 9.2 mm.
Thickness (distance from anterior to posterior pole) of lens is 3.5 mm at birth, which reaches up to 5 mm.
■Refractive Index (RI)
RI of lens = 1.39.
RI of nucleus (1.41) > RI of cortex (1.386).
RI of anterior capsule > RI of posterior surface.
The change in RI from surface of lens (cortex) to the center (Nucleus) results from changes in the protein content which is highest in the nucleus. Higher the concentration, the greater is the refractive power.
■Power of Lens
It is approximately 18D. Refractive power of cornea (≈ 43D) is greater than that of lens (≈ 18D).
During early stage of embryonic development, lens is opaque, but as development continues and hyaloid vascular supply is lost, lens becomes transparent. The lens of the eye has a avascular structure. There are no nerves in the lens.
Lens serves the following functions:
•It transmits and refracts the light. Lens absorbs ultraviolet (UV) light of <350 nm wavelength. Thus, prevents damaging UV radiation from reaching the retina.
•It contributes 35% of refractive power of the eye.
•It helps in accommodation: During accommodation, radius of curvature of anterior capsule decreases while that of posterior capsules remains unaltered. Therefore, the front of lens moves forward during accommodation and depth of anterior chamber decreases.
Histologically, the lens consists of three components: capsule, epithelium, and lens fibers (Fig. 10.2).
•Lens capsule: Lens capsule is elastic, acellular, and transparent. It is made up of collagen-like material and is digested by collagenase. It is secreted by lens epithelium, so the most superficial part of lens capsule is the oldest. Its thickest region is close to the equator on both the anterior and posterior surfaces, while its thinnest region is at the posterior pole. The equator and anterior pole are of intermediate thickness (Fig. 10.3).
•Lens epithelium: It is a single layer of cuboidal cells beneath the anterior capsule and not present posteriorly, as posterior epithelial cells elongate to form primary
lens fibers. Cells have nuclei and organelles. Lens epithelium is the area of lens with highest metabolic rate and secretes lens capsule. Epithelium contains Na+K+ ATPase and generates ATP to meet the energy demand of the lens. Lens epithelium regulates transport of metabolites, nutrients, and electrolytes to lens fibers. Proliferative capacity of epithelial cells varies according to their location (Fig. 10.4):
♢Cells in central zone do not proliferate.
♢Cells in pre-germinative zone rarely divide.
♢Cells in germinative zone (preequatorial area) divide actively and give rise to lens fibers.
•Lens fibers (lens substance): Lens fibers are composed of soluble proteins called crystallins, which are of the following three types: α-crystallin, β-crystallin and γ-crystallin. These develop from epithelial cells in the preequatorial germinative zone. These cells divide and get elongated to form lens fibers which lose cell organelles and nuclei (important for transparency of lens). As new fibers are formed, older ones are pushed toward the deeper plane (nucleus of lens), so the youngest lens fibers are most superficial. Thus, lens substance consists of two parts: The central part contains the oldest fibers and is called nucleus, and the peripheral part consists of the youngest fibers and is called cortex. The cortex is composed of all secondary fibers continuously formed after sexual maturation. Nucleus consists of densely compact lens fibers and has a higher RI than cortex. Nucleus can be further divided, according to the period of development, into embryonic, fetal, infantile and adult nucleus. Embryonic nucleus contains original primary lens fibers formed in the lens vesicles. Rests are secondary fibers which are added concentrically at different stages of growth by encircling previously formed nucleus. Fetal nucleus corresponds to the nucleus at birth, that is, it contains embryonic nucleus and all fibers added to the lens before birth. Infantile nucleus contains all fibers added until 4 years of age, that is, embryonic nucleus + fetal nucleus + all fibers added until 4 years of age. The adult nucleus is composed of all fibers added before sexual maturation (Fig. 10.5).
■Formation of Sutures
The ends of each lens fiber run toward the poles of both capsular surfaces. Overlapping of the ends of each secondary fibers result in the formation of sutures at both the anterior and posterior poles. No sutures are found between primary fibers in the embryonic nucleus.
Secondary fibers formed before birth have anterior suture—“Y-shaped” (erect Y) and posterior suture—“λ-shaped” (inverted Y).
■Zonules (Suspensory Ligaments of Lens)
Zonules stretch from ciliary body to anterior and posterior lens capsule at the lens equator in a continuous fashion.
The zonules attach to the lens capsule 2 mm anterior and 1 mm posterior to the equator. The anterior fibers arise from anterior ciliary processes and insert posterior to the equator. The middle fibers from ciliary processes insert at the equator, while the posterior fibers arise from pars plana region of ciliary epithelium and insert into lens capsule anterior to the lens equator.
Chemically, they are made of collagen-like glycoprotein and acidic mucopolysaccharide (chondroitin sulfate). Zonules are broken by α–chymotrypsin, a proteolytic enzyme. Zonules contain 7% cysteine (amino acid). In homocystinuria, enzyme cystathionine synthetase is absent. Therefore, amino acid homocysteine is not converted into cysteine, resulting in broken zonules and dislocated lens. Excessive homocysteine is also present in the urine.
▃Physiology of Lens
■Composition of Lens
The lens is composed of the following:
•Proteins 33%: Protein content of the lens is highest amongst body organs/tissues. These comprise:
♢Soluble proteins (crystallins): α, β, and γ—crystallins are mostly found in the lens cortex.
♢Insoluble proteins (albuminoids) constitute the membranes of lens fibers and are mostly found in the lens nucleus.
•Lipids, carbohydrates, and electrolytes 1%.
■Transport of Ions
Lens epithelium is metabolically active and contains Na+K+ ATPase and calmodulin regulated Ca++– ATPase for active transport of electrolytes between lens and aqueous.
The Na+ and K+ move asymmetrically across the lens. Na+ and K+ diffuse through both the anterior and the posterior poles of the lens, down their concentration gradient, and are pumped out/in by Na+K+ ATPase in the epithelial layer. The Na+ removed are exchanged actively for K+. There is a net movement of Na+ ions from posterior to anterior and of K+ ions from anterior to posterior.
Ca++ level in aqueous and vitreous is higher than that of lens, which plays an important role in the control of membrane permeability to both Na+ and K+ ions. Ca++ enters the cell down its electrochemical gradient but low-intracellular concentration of Ca++ is maintained by calmodulin-regulated Ca++-ATPase which actively pumps Ca++ out of the cell.
■Transport of Amino Acids
Amino acid content of lens is higher than that of surrounding ocular fluids (aqueous and vitreous). Amino acids enter the lens against the concentration gradient through active transport localized to the epithelial layer beneath the anterior capsule and passively “leak” out through the posterior capsule.
After involution of hyaloid blood supply to lens, the metabolic needs of lens are met by the aqueous and vitreous humors (Fig. 10.6).
■Lens Metabolism (OP7.1)
Lens, like tissues, require energy to drive various reactions. The fact that aqueous in aphakic eyes contain more glucose than in normal (phakic) eye confirms that glucose is the essential source of energy in the lens. Lens has a respiratory quotient (CO2/O2) of 1.0.
Glucose metabolism occurs through the four mechanisms (Flowchart 10.1), namely, glycolysis, pentose phosphate pathway, Kreb’s cycle (TCA cycle) and sorbitol pathway. Approximately, 90 to 95% of glucose that enters the normal lens is phosphorylated into glucose-6-phosphate by hexokinase enzyme. Glucose-6-phosphate is used either in the glycolytic pathway (80%) or pentose phosphate pathway (10%).
Glycolysis: 80% of total glucose is metabolized by anaerobic glycolysis, that is, metabolism of lens is anaerobic. Bulk of pyruvate produced by glycolysis is reduced to lactate by lactate dehydrogenase which diffuses into aqueous. So, lactic acid is found in considerable amount in the aqueous of phakic (and not so in aphakic) eyes.
Pentose phosphate pathway or hexose mono phosphate shunt (HMP shunt): 10% of total glucose is metabolized in HMP shunt. It does not produce ATP. The primary function of HMP shunt is to produce NADPH (reduced NADP) which maintains lens glutathione in the reduced state and also used in the conversion of glucose to sorbitol. HMP shunt also produces pentose sugars needed for synthesis of nucleic acids. End products of this pathway are converted into glyceraldehydes PO4 which enters the glycolytic pathway.
Kreb’s cycle or tricarboxylic acid cycle (TCA cycle): Due to avascularity and low-oxygen content of lens, 70% of lens ATP are produced by anaerobic glycolysis, a relatively insufficient mechanism for the production of ATP. Approximately, 3% of glucose is metabolized aerobically by Kreb’s cycle which generates approximately 25% of lens ATP. It occurs more prominently in the lens epithelium.
Sorbitol pathway: Activity of this pathway increases if glucose levels are increased above normal as in diabetes and galactosemia.
Because the lens grows throughout life, protein synthesis also must occur throughout life. It predominantly involves production of crystallins.
It is a polypeptide synthesized in the lens made of three amino acids: glycine, cysteine and glutamic acid. Most of lens glutathione is in the reduced state. Reduced glutathione retains integrity of the lens transport pump (as thiol groups [-SH] are needed for the enzyme Na+ K+ ATPase) and also maintains lens proteins in reduced state. The reduced lens protein prevents formation of high-molecular weight (HMW) crystalline aggregates and, thus, helps to maintain lens transparency.
Because lens is susceptible to oxidative damage, so lens has a complex antioxidant system which protects against reactive oxygen species (superoxide anion, singlet oxygen, Hydrogen peroxide H2O2) produced during photochemical reactions in the lens. Glutathione is synthesized in lens and protects it from oxidative damage. Ascorbic acid (vitamin C) appears to play a major role in the antioxidant system in the lens.
▃Lens Changes with Age
Lens exhibits age-related changes in structure, light transmission, metabolic capacity and enzyme activity. Characteristic changes in lens with age include the following:
•Diameter increases with increasing age.
•Thickness increases with increasing age. Thickness of nucleus decrease with age as a result of compaction, while that of cortex increases as more fibers are added at the periphery. Radius of curvature of anterior surface decreases with increasing age but that of posterior surface remains almost constant.
•Sutures at birth become complex with increasing age.
•Weight of lens increase with increasing age.
•Elasticity of lens decreases with age, leading to decreased accommodation. It results in presbyopia.
•Light transmission decreases with age partly through increased brunescence of the lens.
•Metabolic activity of lens decreases with age.
•Reduction in antioxidant system with age: Lens is more prone to oxidative damage with increasing age.
•Changes in crystallins:
♢Aggregation of lens proteins.
♢Appearance of lens opacities.
Lens abnormalities may be one of the following:
•Abnormalities in shape and size of the lens:
♢Coloboma of lens.
♢Lenticonus and lentiglobus.
•Abnormalities in position of the lens:
♢Subluxation of lens.
♢Dislocation of lens.
•Abnormalities in the lens transparency:
■Abnormal Shape or Size of Lens
These are largely developmental.
Coloboma of Lens
It is characterized by segmental agenesis (notching), usually at the inferior margin, and is due to localized absence of zonules (suspensory ligament of lens). It is usually unilateral and may be associated with coloboma of iris, ciliary body and choroid. It is not a true coloboma as there is no focal absence of a tissue layer due to the failure of closure of the optic fissure.
It is a bilateral condition. It is a developmental anomaly with defect in the development of lens zonules (Flowchart 10.2). It may occur as an isolated familial defect or may be associated with Marfan’s syndrome or Weil–Marchesani syndrome.
Lenticonus and Lentiglobus
These are abnormalities of central lens curvature which are associated with thinning of lens capsule.
Thinning of lens capsule results in protrusion of lens surface. If protrusion is conical, the condition is called lenticonus (Fig. 10.7) which may be anterior or posterior. If protrusion is spherical, the condition is called lentiglobus.
Both lenticonus and lentiglobus may cause lenticular myopia with irregular astigmatism.
Internal lenticonus: Surface of capsule has a normal contour but the nucleus within forms a cone. It is very rare.
■Abnormal Position of Lens
Ectopia lentis refers to the displacement of lens from its normal position. Displacement of lens may be partial, termed as subluxation of lens, or complete, termed as dislocation of lens (luxation). When zonules are torn in one segment, the lens is displaced to the opposite segment of torn zonules but still remains in the pupillary area (Subluxation of lens). When all fibers of zonules are torn, the lens is displaced anteriorly or posteriorly (luxation or dislocation of lens). The basic defect involves the breakage or weakening of zonules. The following are the causes of abnormal position of lens:
•Familial: It may be associated with iris coloboma, microspherophakia, or aniridia.
•Systemic conditions (due to deficient development of zonules) such as:
•Eye diseases (secondary to weakening of zonules) such as:
♢Ciliary body tumors.
–Displacement of lens may be (Fig. 10.8).
•Anterior in anterior chamber or incarceration in pupil.
•Posterior in vitreous.
Subluxation of lens presents with poor vision and uniocular diplopia (Flowchart 10.3).
Clinical signs depicted in case of subluxation of lens are:
•Irregular depth of anterior chamber.
•Tremulousness of iris (iridodonesis)
•Tremulousness of lens (phacodonesis)
Complications include secondary glaucoma (Flowchart 10.4) in case of anterior dislocation of lens and lens-induced uveitis due to irritation of ciliary body caused by posterior dislocation of lens.
In subluxated lens:
•If lens is clear, spectacle correction is done. Aphakic correction gives better visual acuity than phakic.
•If excessive lenticular astigmatism results in poor vision, removal of lens is done.
•If lens is cataractous, removal of lens by pars plana lensectomy or cataract extraction with capsule tension ring (CTR) with IOL implantation is performed.
In dislocated lens:
•In anterior dislocation with secondary glaucoma, lens removal after controlling intraocular pressure (IOP) is done.
•In posterior dislocation: If uveitis is
present with posterior dislocation, removal of lens via pars plana followed by anterior chamber IOL or scleral fixated IOL is implanted. If there is no uveitis, no treatment is required.
■Abnormal Lens Transparency: Cataract
The crystalline lens is a transparent structure. Any opacity in the lens that causes it to lose its transparency and/or scatter light is called a cataract. A cataract does not necessarily have any demonstrable effect on vision. A cataract may be either developmental cataract or acquired cataract.
Transparency of lens is maintained by multiple factors:
•Avascularity of lens.
•Regular arrangement of lens fibers.
•Dense packing of crystallins.
•Absence of cell organelles and nuclei from lens fibers.
•Reduced glutathione synthesized in lens and vitamin E present in lens membrane, which act as antioxidants and protect lens against oxidative damage.
Many factors that are evident in the process of cataract formation are:
•Alterations in cation permeability: Increase in Na+ content and decrease in K+ content of lens correlates with increase in the optical density of lens.
Increase in intralenticular CA2+ levels causes increased activity of proteolytic enzymes, which break down the proteins into amino acids. This may cause the lens contents to liquefy.
•Biochemical changes: Alterations in many of the biochemical processes that take place within normal lens can lead into a cataractous lens such as:
•Soluble protein content decreases.
•Insoluble protein content increases.
•Accumulation of HMW aggregates.
Hydration: It may be due to osmotic changes within lens or changes in semipermeability of capsule, as in diabetes, galactosemia, and trauma. Droplets of fluid gather under capsule. Lacunae between fibers are formed, and entire tissue swells (intumescence) and becomes opaque.
Changes in glutathione: Glutathione is found at higher concentration in the lens epithelium. It exists in both oxidized and reduced form. A major percentage (95%) of lens glutathione is found in reduced form. Glutathione is synthesized from L-glutamate, L-cysteine and glycine. Glutathione reductase, an enzyme that uses NADPH, converts oxidized glutathione into reduced glutathione. Glutathione plays following important roles in the lens:
•It maintains protein thiols in the reduced state which maintain lens transparency by preventing the formation of HMW crystallin aggregates.
•It protects against oxidative damage.
•It protects the thiol groups involved in cation transport and permeability (oxidation of thiol group of Na+K+ ATPase pump results in increased permeability of these ions).
•It detoxifies hydrogen peroxide which is normally present in the aqueous humor and is a reactive oxygen species. The glutathione peroxidase (found in both epithelial cells and fibers) provide protection against H2O2 by detoxifying it.
Reduced activity of glutathione synthetase and depletion of glutathione reductase causes fall in reduced glutathione, which is an antioxidant, and lens is susceptible to oxidative damage.
Antioxidants vitamins such as vitamins C, E, and β-carotene may be important in the prevention of cataract.
•Fibrous metaplasia of fibers may occur in complicated cataract.
•Opacification of lens epithelium in trauma or chemical injury.
Following are the common etiological factors for the formation of cataract:
♢Nonionizing (infrared) radiations.
•Local ocular diseases (complicated cataract):
Cataract may be classified as follows:
•Developmental: Different types of developmental cataract are as follows:
♢Lamellar (zonular) cataract.
♢Anterior polar cataract.
♢Posterior polar cataract.
♢Central “oil droplet” opacities.
•Acquired—It may be:
•Secondary due to:
♢Local ocular diseases (complicated cataract).
♢Drugs and chemicals (toxic).
The new lens fibers are continuously laid down under the capsule throughout life. The fibers formed earlier lie deeper within the lens substance and the newer ones occupy a more superficial plane. Thus, the central nucleus of lens consists of the oldest fibers and the cortex comprises the youngest ones (Fig. 10.5).
The nucleus is subdivided into:
•Embryonic nucleus: It contains the original primary lens fibers formed in the lens vesicle.
The fetal, infantile, and adult nucleus are composed of secondary fibers added concentrically at the different stages of growth.
Developmental cataract may be present at birth (congenital, Fig. 10.9), and is limited to embryonic or fetal nucleus, or may develop after birth; therefore, it may involve infantile or adult nucleus and deeper cortex. It has a tendency to affect particular fibers, depending upon the time of disturbance in normal development of lens. Thus, the location of developmental cataract may indicate the stage of development at which disturbance occurred. The fibers laid down previously and subsequently are often normally formed and remain clear. Most development opacities are partial and stationary.
♢The most common cause is genetic mutation and is usually autosomal dominant.
♢Deficient oxygenation due to placental hemorrhage.
•Intrauterine infections such as:
•Toxic: Maternal drug ingestion during pregnancy, for example, corticosteroids and thalidomide.
It may exist in nonprogressive and progressive forms:
Nonprogressive form: It is confined to embryonic or fetal nucleus and dominantly inherited. It is a nonprogressive biconvex or spheroid-shaped opacity and consists of fine, white, powdery (pulverulent) dots (cataracta centralis pulverulenta).
Progressive form: The progressive form of nuclear cataract is associated with Rubella (German measles) infection in the mother during the second month of pregnancy. Risk to fetus is closely related to the stage of gestation at the time of maternal infection. After the gestational age of 6 weeks, the virus is incapable of crossing the lens capsule, so that lens is immune. The lens nucleus is found to be necrotic and a total opacification of lens may occur. Virus is capable of persisting within the lens for up to 3 years after birth. Unless all the lens matter is removed, aspiration of cataract may be followed by a chronic inflammatory endophthalmitis associated with the presence of residual lens matter.
Classical manifestations of rubella infection (Rubella triad)
•Congenital heart defects: Patent ductus arteriosus.
Other malformations in Rubella infection include microcephaly, mental retardation. Besides cataractous lens, other ocular features in rubella infections include:
•Pigmentary retinopathy represents involvement of cells of RPE (retinal pigment epithelium). Retina has a “salt and pepper” appearance.
Lamellar (Zonular) Cataract
It accounts for nearly 50% of all developmental cataracts.
It is usually dominantly inherited but may have a metabolic or inflammatory cause. Deficiency of vitamin D is apparently a potent factor. Hypoparathyroidism during pregnancy and disturbances of CA++ metabolism may cause a zonular cataract.
•It is generally, bilateral and symmetrical.
•Occurs usually in the area of fetal nucleus surrounding the clear embryonic nucleus.
Opacity is sharply demarcated and has disc-shaped opacity when viewed from the front (Fig. 10.10).
•Lens area within and around the opacity is clear, although linear opacities resembling spokes of a wheel (called riders) may run outward toward the equator. Visual impairment is frequently present. With time, opacity is pushed deeper, as normal lens fibers are laid down around it and diameter of opacity decreases with time as nucleus becomes compressed.
Sutural (Stellate) Cataract
It affects one or both fetal sutures, so opacities are Y-shaped. It is almost always bilateral.