By IOM 19th batch

1. HUMAN CRYSTALLINE LENS
:APPLIED ANATOMY AND
PHYSIOLOGY
Moderator: Presenters:
Dr.Sanjeev Bhattarai Srijana
Lamichhane
Aayush Chandan

2. Presentation layout
 Introduction
 Embryology
 Anatomy
 Biochemical composition
 Physiology
 Clinical Significance
 References

3. INTRODUCTION
 Transparent ,biconvex ,crystalline structure
 Asymmetric oblate spheroid
 Doesnot posses nerves,blood vessels,or connective tissue
Prolate
spheroid
Oblate spheroid

4. EMBRYOLOGY
 Derived from surface ectoderm
 First apparent at about 27 days of gestation
(embryo 4-4.5mm) as a dics shaped thickening
of surface epithelial cells over the optic vesicles.
 As the optic vesicle grows laterally (3rd week of
gestation)it comes in relation with the surface
ectoderm

5. Lens placode:
 Appears on 27th day of gestation
 The area of surface ectoderm
overlying optic vesicles thickened to
form lens placode or lens plate

6. Lens pit:
 Appears at the 29th day of gestation
 Lens placode and adjacent cells of
optic vesicle invaginates inward to
form lens pit
 Also known as fovea lentis

7. Lens vesicle:
 Formed at about 33rd day of gestation
 Lens pit separates from the surface
ectoderms and forms lens vesicle
 Consists of single layer of cuboidal cells
covered by basal lamina

8. PRIMARY LENS FIBRES AND THE EMBRYONIC
NUCLEUS:
 Cells of posterior wall of lens
vesicles rapidly elongate and
obliterate the cavity of lumen
 By 45th day of gestation the lumen is
completely obliterated and this
transparent elongated cells are
called primary lens fibres
 Make up the embryonic nucleus that
will ultimately occupy the central
area of lens in adult life

9. DEVELOPMENT OF LENS
EPITHELIUM:
 Cells of the anterior lens vesicle still
remain cuboidal and form lens epithelium

10. SECONDARY LENS FIBRES:
 Pre-equatorial cells of lens epithelium retain their
mitotic activity throughout life and form the
Secondary lens fibers
 Starting from the 7th week of gestation
 Anterior aspect of fibers grow towards the anterior
pole and posterior aspect grows towards posterior
pole of the lens
 Subsequently get displaced and meet on the vertical

11. Lens suture and fetal nucleus:
These are formed only during fetal
life
As secondary fibers are added, the
sutures become more complex and
dendriform
The secondary lens fibers formed
between 2nd to 8th months of
gestation make up the fetal nucleus
Erect Y anteriorly and inverted Y
posteriorly

12. Applied anatomy
 Sutural catract:
 Opacification of Y-sutures
of fetal nucleus
 Usually static ,bilateral
and symmetric
 Not visually significant
and does not progress
 Effects on vision are
minimal

13. Formation of lens capsule:
 By the lens epithelium,anteriorly and elongating lens fibre
posteriorly as a basement membrane
 Capsule formation is initiated by the appearance of a second
basal lamina deposited in a discontinuous manner beneath the
original basement membrane of the lens vesicle cells

14. Tunica vasculosa lentis:
 A vascular mesenchymal layer
 Forms around the lens during it’s
development
 At 1st month of gestation, Hyaloid artery
gives rise to small capillaries which forms
the Posterior pupillary membrane, a
network covering posterior surface of the
lens capsule
 Grows towards the equator of the lens
 Fully developed at 9th week of gestation

15. Cont:
 Consist of three component:
1.Posterior pupillary membrane
2.Capsulopupillary portion
3.Anterior pupillary membrane
 Posterior vascular capsule/membrane branches
into smallcapillaries that then grow towards the
equator of the lens
 They anastomose with choroidal veins and forms
the capsulopupillary portion of tunica vasculosa
lentis
 Branches of long ciliary arteries anastomose with
branches of capsulopupillary portion to form
anterior pupillary membrane
 Dissapear by an orderly process of programmed

16. Clinical significance of vasculosa lentis:
 REMANANT OF ANTERIOR
PUPILLARY MEMBRANE
Persistent pupillary membrane
 Often visible in young healthy patients
as pupillary strands
 One end of strands insert into iris
colarette and other end in the anterior
lens capsule or floats in AC

17. Epicapsular star
 Star shaped distributin of tiny golden
flecks on central lens capsule
 Single/multiple,unilateral/bilateral
REMANANT OF POSTERIOR
PUPILLARY MEMBRANE
Mittendorf dot
 Small dense white spot located
mostly inferonasally to posterior pole
of lens
 Marks the place where hyaloid artery
comes into contact

18. Persistant fetal vasculature:
 Rare , unilateral in 90% cases
 When the fetal hyaloid vasculature fails
to regress
 Also k/a persistent hyperplastic primary
vitreous (PHPV)
 White fibrous,retrolental tissue in
association with posterior cotical
opacities
 Present with white pupillary reflex
 Relentless progressive cataract
formation and anterior chamber
shallowing

19. Develpmental anolmalies of lens
1. Lenticonus/lentiglobus
2. Coloboma
3. Microphakia/microspheriophakia

20. Lenticonus
 Circumscribed conical protrusion of the lenticular
pole
 Anterior lenticonus is seen in patients with Alport
syndrome (glomerulonephritis accompanied by
bilateral sensorineural hearing loss and
anomalies of lens shape)
 Posterior lenticonus, more common may be
associated with a lens opacity or seen in patient
with lowe’s syndrome

21. lentiglobus
 Hemispherical protrusion of the lens
 Localized deformation of the lens surface
is spherical
 Symptoms include myopia and reduced
visual acuity
 Appear as an "oil droplet” on
retroillumination

22. lens coloboma
PRIMARY:
 wedge shaped defect or indentation of the lens
in periphery. It mostly occurs as an isolated
anomaly.
SECONDARY:
 a flattening or indentation of the lens periphery
caused by lack of ciliary body or zonular
development.
 These are typically inferior and may be
associated with colobomas of uvea.
Zonular attachments in the region of the coloboma

23. Microspherophakia
 Lens is spherical in shape (instead of normal
biconvex) and small in size
 Due to faulty development of secondary lens
fibres
 Entire lens equator can be visualized at slit
lamp( dilated pupil)
 Results in increased refractive power i.e. high
myopia
 Often can block the pupil, causing secondary
angle closure glaucoma
 May be isolated or associated with Weill-
Marchesani syndrome,Peters

24. Congenital aphakia
 Very rare
 Complete absence of lens
 May be primary or secondary.
PRIMARY:
 lens placode fails to develop from the surface ectoderm
 Occurs only with gross malformations like anophthalmia
or microphthalmia
SECONDARY:
 more common
 The lens placode has developed but has been resolved
before birth
 Remanant of lens such as lens capsule are present

25. Congenital cataract
Polar cataract
 Small opacities of the lens capsule &
adjacent cortex
 on the anterior or posterior pole of the lens
Capsular cataract
Small opacifications of the lens epithelium and
anterior lens capsule that spare the cortex

26. Nuclear cataract
 Opacities of embryonic nucleus alone or both embryonic or
fetal nuclei
 Usually bilateral
 Catracta centralis pulverulenta
 Lamellar cataract
 Sutural and axial cataract
 Total nuclear cataract
Lamellar cataract
 Most common type
 Round central shell-like opacity surrounding the nucleus

27. Coronary cataract(cataracta coronaria)
 Club-shaped opacities developed in the
periphery of the cortex near the lens
equator
 Found in significant % of people
Blue dot catract
a/k cataracta punctate caerulea
Punctate opacities are found in the form of
rounded bluish dots
Lies in the pheripheral part of adolescent
nucleus and deeper layer layer of cortex

28. STRUCTURAL ANATOMY
DIMENSION
Equatorial diameter
 At birth: 6.5 mm
 In adult: 9-10 mm (by 2nd decade)
Antero posterior/Axial length/Thickness
 At birth: 3.5 mm
 In adult: 6 mm
Shape
Oblate spheroid

29. WEIGHT
 at birth: 65-90 mg
 in adult: 255 mg
 Increases by rate of 2 mg/year
SURFACES
 Anterior surface:
 Less convex (8-14 mm)
 Posterior surface:
 More curved (4.5-7.5 mm)
 Posterior pole
Optical Axis: line joining the two
poles

30. EQUATOR
 Marginal circumference of lens, where
and posterior surface meets
 Encircled by ciliary processes of cilliary body
held in position by zonules laterally
 Shows a number of dentations due to
of zonular fibers

31. Refractive properties
Nucleus:1.41
Pole:1.385
Equator:1.375
Refractive power:
(16-17)D

32. Accomodative power:
 At birth: 14-16 D
 25yrs: 7-8 D
 50 yrs:1-2 D
Color of lens:
 At bith,infants: transparent
 Adult:colorless
 At about 30 yrs :yellow tinge
 Old age: amber color

33. Anatomical relation:
Anterior:
 AC of the eye through the pupillary
aperture, and
 with the posterior surface of the iris
Lateral:
 PC of the eye and to the zonules
through ciliary processes

34. Posterior surface:
 Placed b/w iris and the vitreous in the
patellar fossa
 Attached posteriorly to vitreous in a circular
manner with ligamentum hyaloideocapsular
also called Wiegert’s ligament
 B/W the hyloid face and lens capsule there
is a small potential space called retrolental
or berger’s space

35. Structure of lens
Lens capsule
Anterior lens epithelium
Lens fibre

36. Lens capsule
 Thin ,transparent,hyaline collagenous
membrane
 Surrounds lens completely
 Elastic in nature but doesnot contain
any elastic tissue
 Anteriorly secreted by lens epithelium
and posteriorly by basal cells of
elongating fibres
 Composed of type IV collagen and
GAG’S

37. Thickness of lens capsule
Lens capsule is
the thickest
basement
membrane of the
body

38. Clinical significance
True Exfoliation
 Superficial zonular lamella of the capsule splits off
from the deeper layer
 Exposure to infrared radiation
PseudoExfoliation
 Basement membrane-like fibrillo-granular white
material deposited on the lens, cornea, iris,
anterior hyaloid face, ciliary processes, zonular
fibers and trabecular meshwork
 Can lead to glaucoma

39. Voissius ring
 Imprinted iris pigments in the
anterior surface of anterior lens
capsule
 Due to blunt trauma to eye

40. Anterior lens epithelium
 Single layer of cuboidal nucleated epithelial
cells
 Lies deep to anterior capsule extending up to
equatorial lens bow
 Increased density towards periphery
 Actively dividing and elongating to form lens
fiber
 Metabollically active layer
 Posterior lens epithelium absent because the
cells are used in filling the central cavity of

41. Zones of lens epithelium
central zone
 Consist of cuboidal cells
 Normally do not mitose
Intermediate zone
 Consists of comparatively samller and cylindrical cells
 Located peripheral to central zone
Germinative zone
 Consists of columnar cells which are most peripheral
 Located just pre-equatorial
 Actively dividing to form lens fibre

43. Lens fibres
 Hexagonal in cross section
 Formed constantly throught life by elongation of lens epithelim
 Primary lens fibres are formed from posterior epithelium
 Secondary lens fibre are formed by differentiation from germinative cells
 As the lens fibre are formed throughout life, these are arranged compactly
as nucleus and cortex of the lens

44. Nucleus
 Central part containing the oldest fibres
 Depending upon the period of development
different zones of nucleus are
1. Embryonic nucleus ( 1-3mnth of
gestation)
2. Fetal nucleus (3mnth of gestation – birth)
3. Infantile nucleus (from birth –puberty)
4. Adult nucleus (puberty –rest of life)

45. Cortex
 Peripheral part of lens lies just
outside the adult nucleus
 Comprises youngest (recently
formed ) lens fibres
Nucleus; fibres arranged in compact fashion (harder in
consistency)
Cortex; lossely arranged(soft in consistency)

46. The ciliary zonules
 a/k zonules of zinn or suspensory ligament
 Transparent,stiff and not elastic
 Extend from ciliary body to lens equator circumferentially
 Holds the lens in position
 Helps in accomodation

47. Arrangement of zonular fibers
 Zonular fibers arise from the posterior end of pars
plana (~1.5mm from ora serrata)
 Zonular complex can be divided into 4 zones
Pars orbicularis :- Passes forward over the pars
plana from its origin
Zonular plexus :- Zonular fibers segments into
Zonular plexus

48. Cont
Zonular fork :- Zonular plexus consolidate into Zonular
bundles and bends at right angle to proceed to lens.
Zonular limbs :- 3 in number
1.Anterior zonular limbs / orbiculo-anterior capsular fibers
2.Equatorial zonular limbs /cilio-equatorial fibers
3.Posterior zonular limbs / orbiculo-posterior capsular fibers

49. INSERTION OF THE ZONULAR FIBRES
 Anteriorly and posteriorly at periphery and at equator of the
lens
 The layer of inserting zonular fibers and the related capsular
layer are termed Zonular lamella
 Non-elastic
 Collectively referred to as the suspensory ligaments of the

51. ZONULAR LAMELLA
 Less compact
 Richer in glycosaminoglycans than the rest of the
capsule
 The lamella contributes to the zonular adhesive
mechanism
 Pericapsular membrane

52. Ectopia lentis
Displacement of lens from its normal
position
May be congenital, developmental or
acquired
May be dislocated or subluxated
Subluxation: partially displaced from
normal position but remains in the pupillary
area.
Dislocation: complete displacement from
pupil i.e. separation of all zonular

53. Ectopia lentis
 Developmental
 Deficient development of zonules causes ectopia lentis in
association with other conditions
 Presents with:
 decreased vision
 marked astigmatism
 monocular diplopia
 Iridodonesis
Acquired lens displacement
 Most commonly due to trauma

54. Ectopia lentis
Associated with systemic feature
1. Marfan syndrome :- upward & temporal displacement
2. Homocystinuria :- downward and nasal subluxation
3. Weil-Marchesani syndrome :- forward subluxation

55. Biochemical
Composition

56. I.Water-65%
II.Protein-34%
III.Others(lipids,inorganic ions,glucose
and its derivatives,ascorbic acid & amino
acids)-1%
water
65%
protein
34%
others
1%
water protein others
Biochemical composition of lens

57. Water
 65% (80% free & 20% bound)
 Present in dehydrated state (maintained by active Na pump)
 plays Important role in maintenance of lens transparency and
refractive index
 Cortex is more hydrated than nucleus

58. Proteins
 Content is higher than that of any other organ
in the body
 Divided in two major groups : insoluble
Albuminoids & soluble Crystallins
 Cortex contain more soluble proteins than
nucleus which contain more insoluble proteins
Albuminoids 12.5%
Alpha-crystallins 31.7%
Beta-crystallins 53.4%
Gamma-crystallins 1.5%
Mucoproteins 0.8%
Nucleoproteins 0.07%

59. Functions of crystallins
 Refractive properties of the lens.
 Change in shape observed during the
differentiation of an epithelial cell into a lens
fiber.
 Provide lens with stress-resistant properties.
 Chaperone-like function
 Hardness of lens

60. • Proteogenic & Non-proteogenic
• Actively transported into the lens
Amino acids
• Glucose:1/10th of aqueous
• Fructose
• Glycogen
• Sorbitol
• Inositol
Carbohydrates
• 2.5%
• Cholesterol,phospholipids(cephalin,isolecithin,sphingomyelin,g
lycerides etc)
lipids

61. • K (114-130mEq/Kg lens matter)
• Na (14-25mEq/Kg lens matter)
• Ca (0.14mg/mg dry weight)
• Anions(chloride,bicarbonate,phosphate,sulphates)
Electrolytes
• 3.5-5.5mg/g wet weight of lens
Glutathione
• 30mg/100gm of wet weight of lens
Ascorbic Acid

62. Metabolic activities of lens

63. Metabolism
 Major site – Epithelium
 Lens require a continuous supply of energy for:
- active transport of ions and amino acids
- maintenance of lens dehydration and transparency
-for continuous protein and GSH Synthesis
 Most of the energy produced is utilized in the epithelium
which is the major site of all active transport process

64. Source of nutrient supply
 Being an avascular structure the lens takes nutrient from two
sources by diffusion
1. Aqueous humor(main source)
2. Vitreous humor

65. Glucose Metabolism
 Main source of energy
 Enters the lens from aqueous & vitreous by
simple diffusion & is metabolized through 4
main pathways
-Anaerobic glycolysis
-Krebs cycle
-HMP shunt
-Sorbital pathwayBecause both sorbitol and fructose have the potential to
increase osmotic pressure , and so cause water to enter cells,
these sugars may help regulate the volume of the lens.

66. S.no Pathway Main intermediate End product Glucose
through
pathway(%)
ATP
1. Anaerobic glycolysis Glucose-6-phosphate
Fructose-1,6-diphosphate
Pyruvic acid
Lactic acid 80 2
2. Krebs cycle Tricarboxylic acid & O2 CO2 & H2O 3 36
3. HMP shunt pathway Pentose CO2 , NADPH 14 ___
4. Sorbital pathway Sorbitol *Lactic acid 3 2

67. Protein metabolism
 Synthesized from free Amino acids which are actively
transported into the lens from aqueous
 Synthesis of protein is slowest in nucleus
 Protein breakdown is catalyzed by peptidases & proteases

68. Transport Mechanism
 To provide nutrients for metabolism
 To regulate water & cation balance in lens
 To dispose waste product of metabolism
2 transport mechanisms:
 Active transport: amino acids ,K , taurine , inositol & extrusion
of Na
 Passive transport: water,ions,lactic acid & CO2

69. Water & electrolyte transport
 By pump-leak
mechanism

70. Transport of amino acids &
inositol
 Majority of amino acids are pumped into lens through the
amterior capsule
 In addition, lens can also convert ketoacids into amino acids.
 Inositol is also actively transported into the lens
Glucose transport
By simple & facilitated diffusion across both anterior & posterior
surface of lens.

71. Lens transparency
 Factors playing significant role in maintaining outstanding clarity &
transparency of lens are:
1.Thin epithelium
2.Regular arrangement of lens fibers
3.Little cellular organelles
4.Little extracellular space
5.Lamellar conformation of lens protein

72. 6.Relative dehydration
7.Semipermeable character of lens capsule
8.Avascularity
9.Autooxidation
10. Pump mechanism of lens fibers(which
regulates the electrolyte and water
balance)

73. Accommodation
 Mechanism by which the eye changes refractive power by
altering the shape of lens in order to focus objects at variable
distance.
 Purpose: Focus and maximize spatial contrast of the foveal
retinal image.

74. Accommodative apparatus
 Ciliary body and Ciliary muscle fibers
 Lens capsule
 Zonules

75. Ciliary Body & Ciliary Muscle
fibres
 Forward continuation of choroid at ora
serrate
 3 types of ciliary muscle fibres
1. Circular Fibers
2. Longitudinal/ Meridional Fibers
3. Radial Fibers
Function :- Slacken the suspensory
ligaments of lens & thus helps in

76. Mechanism of Accommodation
 Explained by relaxation
theory(HELMHOLTZ)
 Also known as the “capsular theory”
 He considered that lens is elastic and in
normal state it is stretched and flattened by
tension of the suspensory ligaments.
 During accommodation , contraction of ciliary
muscle shortens ciliary ring and moves
towards the equator of the lens
 Relax the suspensory ligaments,relieving
strain
 Lens assumes more spherical
form,increasing thickness and decreasing

78. Mechanism of accommodation contd..
 The mechanism of accommodation can be divided
into physical and physiological process.
 Physical accommodation is the measure of
change in shape of lens during accommodation
process, measured in terms of diopter.
 Physiological accommodation is a measure of the
force of ciliary muscle contraction per diopter ,
measured with the unit of myodiopter.

79. Ocular changes in accommodation
 Slackening of zonules due to contraction of ciliary
muscle.
 Decrease in the radius of curvature of anterior
surface(from 11mm to 6mm in periphery & 3mm in
the central part)
 Forward movement of lens (shallowing of
anterior chamber)
 Axial thickness of lens is increased

80. Contd..
 Lens sinks down
 Pupillary constriction and convergence of eyes
 Choroid is stretched forward
 Ora serrate moves forward

81. Age-related change in
accommodation

82. Changes in ageing lens
 Changes in ageing lens can be grouped as :
1.Physical change
2.Metabolic change
3.Changes to Crystallins
4.Changes to plasma membrane & cytoskeleton

83. 1.Physical changes
 Lens weight & Thickness increases
 Light transmission at lower wavelength
decreases while absorbance increases
 Light scattering is increased
 Fluorescence property of lens increases

84. 2.Metabolic changes
 Proliferative capacity of epithelial cells
decreases
 Enzyme activities decreases
 Glutathione & Ascorbate level decreases

85. 3.Changes in Crystallins
 Alpha-crystallins have been reported to almost
disappear from soluble extracts of nucleus &
Beta-crystallins become more polydisperse.
 Age-related loss of gamma-crystallins.

86. 4.Changes of plasma membrane &
cytoskeleton
 Loss of hexagonal cross-section of fibre cells
 Lack of cytoskeleton in the lens nucleus
 Age-related loss of membrane proteins and
lipids and of cytoskeletal proteins
 Decrease in large membrane polypeptides
 Changes in membrane rigidity

87. Cataractogenesis
 “Cataract” is any opacity on or within the lens
due to loss of transparency due to;
i.Hydration of lens fiber
ii.Denaturation of lens protein

88. Cataract
Congenital Acquired

89. Congenital Cataract
1.Associated Metabolic Disorders
Oil Droplet lens opacity in galactosaemia
Dense nuclear cataract in lowe’s syndrome

90. 2. Associated intrauterine infections
a.Rubella
b.Toxoplasmosis
c.Cytomegalovirus infection
d.Drug Ingestion during Pregnancy
(Thalidomide,Corticosteroids)

91. 3.Generalised
Coronary
Cataract
Blue Dot
Cataract
Total congenital cataract

92. B. Acquired Cataract
1.Age-Related Cataract
Posterior subcapsular Cortical
Nuclear

93. Retrodots
 small, discrete, birefringent, rounded, or
lobular objects typically found in the
cortical regions of the lens with a higher
refractive index than the surrounding lens
material
 also known as spheroliths , cystoid
spaces , calcium-containing opacities , or
white anterior cortical opacities.
 More recently, retrodots have been found
to be associated with visual impairment.

94. Lens Vacuole
 clear, spherical, and fluid-filled spaces
within the lens cortex
 contain fluid of lower refractive index than
the surrounding lens material
 typically occur in isolation, although they
can also be a component of posterior
subcapsular (PSC) cataract
 appear to have minimal effect on vision.

95. Grading of nucleus hardness on slit
lamp biomicroscopy
Grade I Soft White or
Greenish yellow
Grade II Soft-medium Yellowish
Grade III Medium-Hard Amber
Grade IV Hard Brownish
Grade V Ultra Hard (Rock-
Hard)
Blackish

96. Grading of cortical Cataract
 CS 1: ⅛ to ¼ of the total area
CS 2: ¼ to ½ of the total area
CS 3: ½ or more of the total area

97. Grading of Posterior Subcapsular Cataract
 WHO criteria, graded on vertical height (in mm)
 PSC 1: 1 mm to 2 mm
PSC 2: 2 mm to 3 mm
PSC 3: >3 mm

98. Risk factors for senile cataract
 Heredity
 Exposure to UV irradiation
 Dietary factors
 Severe diarrhea
 Renal failure
 Hypertension & Diuretics
 Myopia
 Alcohol consumption & Smoking
 High BMI

99. 2.Cataract in Systemic Disease
Diabetes Mellitus Myotonic Dystrophy
Atopic Dermatitis
Wilson’s Disease
Hypocalcaemic

100. 3.Secondary Cataract
Chronic Anterior Uveitis Acute congestive angle closure Retinitis pigmentosa

101. 4.Traumatic Cataract
Penetrating trauma
Blunt trauma
Electric shock & lighting strike

102. Infrared radiation Ionizing Radiation

103. 5.Drug Induced cataract
a.Corticosteroid
b.Miotics
c.Phenothiazines
d.Amiodarone
e.Statins

104. REFERENCES