Anatomy & Physiology Of The Anterior Segment Module 1.1_FINAL.pptx

1. ANATOMY AND
PHYSIOLOGY OF THE
ANTERIOR SEGMENT
Module 1.1

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The International Association of Contact Lens Educators
First Edition 1997
The International Association of Contact Lens Educators 1996
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5. CONTRIBUTORS
Anatomy and Physiology of the
Anterior Segment:
Lewis Williams, AQIT(Optom),
MOptom, PhD

6. THE EYE

7. ANATOMY

8. CORNEA

9. 11.5 mm
(after Hogan et al., 1971)
10.6 mm
11.7 mm
CORNEAL DIMENSIONS

10. The cornea
is not symmetrical
and
corneal curvature flattens
towards the periphery
CORNEAL SHAPE

11. CORNEAL SHAPE
• Meniscus lens
• Not a solid of rotation about any axis
• Front apical radius 7.8 mm K= 43.27 D
• Back apical radius 6.5 mm -6.15 D
• Actual refractive index, cornea = 1.376
- Not optically homogenous
- nground substance = 1.354, ncollagen = 1.47

12. CORNEAL PROFILE

13. CORNEAL COMPOSITION
• 78% water
• 15% collagen
• 5% other parts
• 1% GAGs
• Epithelium  10% of
cornea’s wet weight

14. TRANSVERSE SECTION OF THE CORNEA

15. EPITHELIUM
• Regular and smooth
• Uniform thickness
• Tear layer substrate

16. LAYERS OF EPITHELIUM

17. ELECTRON MICROGRAPH OF THE
EPITHELIUM

18. EPITHELIUM
• 50 microns thick
• 5-layered structure
- Squamous cells (surface)
- Wing cells
- Columnar cells (basal)
• Cell turnover (basal to surface ≈ 7 days

19. EPITHELIUM CELLS
SURFACE CELLS (2 Layers)
• Thin
• Squamous
• Overlapping polygonal cells
WING CELLS (2 Layers)
• Overlays Basal layer
• ‘Wings’ protruding into space between domes of
basal cells
BASAL CELLS
• Deepest
• Columnar
• Hemispherical anterior surface

20. EPITHELIAL CELLS

21. OTHER CELLS: BASAL LAYER
• Pigmented melanocytes (peripheral epithelium)
• Macrophages
• Lymphocytes

22. MICROPLICAE AND MICROVILLI
• Present on anterior of surface epithelial cells
• Responsible for tear film retention?

23. BASEMENT MEMBRANE (basal lamina)
• Interface between basal cell layer of epithelium and
Bowman’s layer
• Thickness - 10-65 nm

24. EPITHELIAL ADHESION

25. EPITHELIAL ADHESION

26. BOWMAN’S LAYER
• Acellular
• Differentiated anterior stroma
• Mainly collagen, some ground substance
• Collagen fibrils randomly dispersed

27. THIN OPTIC SECTION OF HUMAN CORNEA

28. STROMA
• 0.50 mm thick
• 90% of corneal thickness, mostly collagenous lamellae
• Contains 2-3% keratocytes (fibroblasts) and about 1%
ground substance

29. GROUND SUBSTANCE (GAGs)
• Very hydrophilic
Responsible for:
• Exact spacing of fibrils
• H2O imbibition pressure of cornea (due to hydrophilicity)

30. KERATOCYTES
• Interspersed between collagenous lamellae
• Thin, flat cells 10 µm in diameter with long
processes
• 5-50 µm of intercellular space
• Joined together by macula occludens or
hemidesmosomes

31. KERATOCYTES
(CORNEAL FIBROBLASTS)

32. STROMAL LAMELLAE
• Dense and orderly fibrous connective tissue
• Stable protein collagen fibrils
• Regular arrangement is important for corneal
transparency

33. STROMAL LAMELLAE
• 200 - 250 lamellae superimposed on one
another
Thickness: 2 µm
Width: 9-260 µm
Length: 11.7 mm

34. LAMELLAR ARRANGEMENT
Parallel to:
• Corneal surface
• One another

35. LAMELLAR ARRANGEMENT

36. DESCEMET’S MEMBRANE
• 10-12 µm
• Structureless
• Slightly elastic
• Secreted by the endothelium
• Very regularly arranged stratified layer
• Functions as basement layer of endothelium

37. HASSALL-HENLE WARTS
• Periodic thickenings of Descemet’s membrane
• Can protrude into anterior chamber

38. HASSALL-HENLE WARTS

39. POSTERIOR PERIPHERAL CORNEA
Stroma
Endothelial
Cell
Displaced
Endothelial Nuclei
Thinned altered
Endothelium over H-H
Aqueous
Humor
H-H = Hassall-Henle Bodies (warts)
Incident light lost to observation
(appears black)
Descemet's
Endothelium
H-H
H-H
H-H

40. ENDOTHELIUM
• Single layer
• 500,000 mainly hexagonal cells
• 18-20 µm diameter
• 5 µm thick
• Non-replicating

41. ENDOTHELIUM

42. ENDOTHELIUM

43. ENDOTHELIUM CELL NUCLEI
• Centrally located
• Uniformly spaced in the young

44. AGE-RELATED CELLULAR CHANGES
• Cell degeneration and non-replacement
- Decreased uniformity
- Decreased thickness with age
• Polymegethism

45. ENDOTHELIAL CELL ULTRASTRUCTRURE
• Rich in organelles engaged in active transport (active
pump)
• Protein synthesis for secretory purposes
• Large number of mitochondria
• Mitochondria more numerous around nucleus

46. PERIPHERAL CORNEAL VASCULATURE
• Peripheral cornea (and sclera adjacent to
Schlemm’s canal) supplied by circumcorneal
vessels
• Minor role in corneal nutrition
• Remainder of cornea is avascular

47. CORNEAL INNERVATION
• One of the richest sensory nerve supplies
• Ophthalmic division of trigeminal nerve (N5)
• Fibres become more visible in oedema

48. MEDULAR CHANGES OF CORNEAL
NERVES

49. PHYSIOLOGICAL CHARACTERISTICS OF
CORNEAL NERVES
• Sensory
• Parasympathetic
• Sympathetic innervation?

50. CONJUNCTIVA

51. CONJUNCTIVA
• Mucous membrane
• Translucent rather than transparent

52. CONJUNCTIVA
Continuous with:
• Lining of globe beyond cornea
• Upper and lower fornices
• Innermost layer of upper and lower lids
• Skin at lid margin
• Corneal epithelium at limbus
• Nasal mucosa at lacrimal puncta

53. DIMENSIONS AND CONTOURS OF THE
CONJUCTIVA AND FORNICES
14 - 16 mm
9 - 11 mm
5
(After Whitnall & Ehlers, 1965)

54. CONJUNCTIVA
• Loose
- Moves freely
- Allows independent movement of
globe
• Thinnest over Tenon’s capsule

55. REGIONAL DIVISIONS OF THE
CONJUNCTIVA
• Palpebral
• Fornices
• Bulbar
• Plica semilunaris
• Caruncle

56. REGIONAL DIVISIONS OF THE
CONJUNCTIVA

57. Conjunctiva is composed of 2 layers:
• Epithelium
• Stroma
CONJUNCTIVA

58. CONJUNCTIVAL EPITHELIUM
• 5 layers of the corneal epithelium cells becomes 10-15
layers of the conjunctival epithelium at limbus due to
increasing wing cell numbers
• Surface not as smooth as cornea
• Basement membrane present
• Surface cells have microplica and microvilli

59. CONJUNCTIVAL STROMA
• Loosely arranged bundles of coarse collagen
• Bundles are approximately parallel to surface
• Numerous fibroblasts (main cell type)
• Some immunological cells present

60. CONJUNCTIVAL GLANDS
• Goblet Cells
• Glands of Wolfring
• Glands of Krause
• Crypts of Henle

61. CONJUNCTIVAL GLANDS

62. CONJUNCTIVAL GLANDS

63. CONJUNCTIVAL ARTERIES
• Palpebral branches of nasal and lacrimal
arteries of lids
- Larger branches form peripheral and
marginal arterial arcades
- Lower lid peripheral arcade not always
present
• Anterior ciliary arteries

64. CONJUNCTIVAL ARTERIES

65. LIMBUS
• Transition zone between cornea and
conjunctiva/sclera
• Anatomical reference

66. LIMBUS

67. CORNEA TO CONJUCTIVA
SCLERA TRANSITION
5 layer epithelium
Bowman’s layer
Stroma
10-15 layer epithelium
Stroma and Tenon’s
capsule
Sclera proper
CORNEA CONJUNCTIVA

68. CORNEA TO CONJUCTIVA/
SCLERA TRANSITION

69. LIMBAL EPITHELIUM
Goblet cells
Melanocytes
Underlying
blood vessels
Bulbar Conjunctival
Corneal Limbal

70. DIMENSIONS OF THE LIMBAL REGION
Depth:
Width:
1.0 mm
1.5 mm (horizontally)
2.0 mm (vertically)

71. LIMBAL FUNCTION
• Nourishment
• Aqueous humor drainage

72. LIMBAL VASCULATURE VESSEL TYPES
• Terminal arteries
• Recurrent arteries

73. LIMBAL VASCULATURE VESSEL TYPES

74. LIMBAL INNERVATION

75. SCLERA

76. SCLERA
• Approximately spheroidal
• Collagenous
• Relatively avascular
• Relatively inactive metabolically
• Durable and tough

77. SCLERA COMPOSITION
• 65% H2O (c.f. cornea 72-82%)
Dry weight figures:
• 75% Collagen
• 10% other protein
• 1% GAGs (c.f. cornea 4%)
* Irregular arrangement of collagen results in
an opaque tissue

78. SCLERAL DIMENSIONS
• Approximately spheroid
• 22 mm diameter
• >80% of eye external surface
• Thickness
- 0.8 mm at limbus
- 0.6 mm at front of rectus muscle tendon
- 0.3 mm behind rectus muscle insertions
- 0.4-0.6 mm at equator of globe
- 1.0 mm at optic nerve head

79. (after Duke-Elder, 1961)
0.5
0.6
10.6
11.6
to 11.6
3.0
3.5
to
1.5
2.0
to
0.8
0.3
1.0
SCLERAL DIMENSIONS

80. LACRIMAL GLAND

81. LACRIMAL GLAND
• Located under supero-temporal orbit
• Sits in Lacrimal Fossa
Divided by Levator Palpebrae Superioris into:
• Orbital portion (larger, upper)
• Palpebral portion (smaller, lower)

82. LACRIMAL GLAND INNERVATION
Superior orbital margin
Lateral expansion of LPS
Palpebral portion of
lacrimal gland
Lateral expansion of LPS
Inferior orbital margin
Communicating branch
of zygomaticotemporal
nerve (N5)
Lacrimal nerve (N5)
LPS
Superior rectus
Orbital portion
of lacrimal gland
Incomplete oblique view (from superior temporal)

83. LACRIMAL GLAND
• 12 lacrimal ducts
- 2-5 from upper (orbital) portion
- 6-8 from lower (palpebral) portion
• Ducts open onto superior palpebral conjunctiva

84. ACCESSORY LACRIMAL GLANDS
GLANDS OF KRAUSE
• Similar structure to lacrimal gland
• In conjunctival mucosa near fornices
• 20 in upper lid, 8 in lower lid
• More numerous laterally
• Supply aqueous phase of basal tear film

85. ACCESSORY LACRIMAL GLANDS
GLANDS OF WOLFRING
• Similar structure to lacrimal gland
• Near upper border of tarsal plate
• Supply aqueous phase of basal tear film

86. ACCESSORY LACRIMAL GLANDS
GLANDS OF ZEIS
• Sebaceous glands
• Associated with lash follicles
• Partially supply lipid layer of tears

87. ACCESSORY LACRIMAL GLANDS
MEIBOMIAN GLANDS
• Sebaceous glands
• Main supply of lipid layer of tears
• 25 in upper lid, 20 in lower lid (shorter)
• Prevent tear spillage

88. ACCESSORY LACRIMAL GLANDS
CRYPTS OF HENLE
• Invaginations of superior peripheral palpebral
conjunctiva
• Mucous crypts

89. ACCESSORY LACRIMAL GLANDS
GOBLET CELLS
• Unicellular sero-mucous glands
• In epithelium of conjunctiva
• Provides mucoid layer of tears
• Have a single-discharge life-cycle

90. TEAR FILM

91. TEAR DISTRIBUTION
• By eyelid action
• By movement of the globe
• Helps form lacrimal lake
• Each blink ‘resurfaces’ tear film

92. TEAR FLOW
Tear flow aided by:
• Capillary action
• Gravity
• Blinking

93. (after Mahmood et al., 1984)
DISTRIBUTION OF TEAR VOLUMES
1 µL
3 µL
4 µL
TEAR
VOLUMES

94. TEAR FILM STABILITY
• Mucin layer spread by lid action enhances wettability of
epithelium
• Evaporation leaves an oil and mucin admixture
• Admixture does not ‘wet’ epithelium causing a break-up
of tear film

95. MECHANICS OF TEAR FILM SPREADING
• Upward lid movement draws aqueous component over
the surface
• Lipid layer spreading over surface increases film
thickness and stability

96. TEAR FLOW: LID CLOSURE
MOVEMENT TOWARDS THE MEDIAL CANTHUS
• Lid closure is scissor-like towards the nose
• Tears move towards the medial canthus

97. TEAR FLOW: LACRIMAL PUMP
• Upper part of lacrimal sac distends when orbicularis
oculi contracts
• Distention induces negative pressure which draws
tears into lacrimal sac
• Capillary action and gravity play a part
• Turnover rate of tears » 16% per minute

98. TEAR FLOW DIRECTION
(after Haberich, 1968)

99. Tears
upper and lower puncta
lower canaliculi
lacrimal sac
naso-lacrimal duct
nose (Valve of Hasner)
TEAR DRAINAGE

100. EYELIDS

101. CROSS SECTIONAL VIEW OF EYE LIDS

102. EYELIDS 4-LAYERED STRUCTURE
• Cutaneous layer (the skin)
• Muscular layer (mainly orbicularis oculi)
• Fibrous tissue layer (tarsal plates)
• Mucosal layer (palpebral conjunctiva)

103. EYELIDS
• Modified folds of skin
• Protect eyes from foreign bodies and sudden
increases in light level
• Spread tears over the ocular surface
• Lid margins are shelf-like and about 2mm wide

104. EYELIDS: GLANDS
ZEIS GLANDS
• Sebaceous glands associated with lash follicle
MOLL’S GLANDS
• Modified sweat glands open into Zeis glands, lash
follicles, lid margins
MEIBOMIAN GLANDS
• Sebaceous glands in the tarsal plate

105. EYELIDS: GLANDS

106. MEIBOMIAN GLAND ARRAY

107. EYELIDS: BLOOD VESSELS
Supply oxygen to the cornea via palpebral
conjunctival vessels

108. PHYSIOLOGY

109. PHYSIOLOGY OF THE CORNEA
• Sources of energy
• Transparency

110. CORNEAL PERMEABILITY
WATER
• Endothelial permeability is greater than
that of the epithelium
OXYGEN
• Derived from the atmosphere
CARBON DIOXIDE
• Permeability is 7X that of oxygen

111. CORNEAL PERMEABILITY OTHER
SUBSTANCES
• Sodium: endothelium greater than the epithelium by
100X
• Glucose and amino acids: metabolically active
• Associated molecules
• Fluorescein

112. EPITHELIAL PERMEABILITY
• Low sodium permeability
• Relatively impermeable to water, lactic acid,
amino acid, glucose and large molecules
• Relatively permeable to associated and fat-
soluble entities

113. ROLE OF CELL JUNCTIONS
• Communication
• Electrical coupling
• Barrier to: - Electrolytes
- Fluids
- Macromolecules

114. GENERAL CLASSIFICATIONS OF
JUNCTIONS
• Occluding or tight
• Adhering
• Each further subdivided according to shape
and size of cell contact
- zonulae (belts)
- fasciae (bands)
- maculae (focal)

115. SCHEMATIC COMPOSITE VIEW OF
ALL JUNCTION TYPES

116. FIBRONECTIN
• Cell surface glycoprotein
• Involved with cell adhesion to surfaces
• Released beneath regenerating epithelium
• Synthesized by cornea
• Found in basal and apical surfaces of cultured
endothelial cells

117. OXYGEN
The
most important
metabolite

118. OXYGEN SUPPLY TO THE CORNEA
Endothelium
Descemet’s
Epithelium
Tear film
Stroma
Terminal
vessels
Recurrent
vessels
A
T
M
O
S
P
H
E
R
E
A
Q
U
E
U
O
U
S
H
U
M
O
R
O2 O2

119. SOURCES OF OXYGEN
EPITHELIAL SURFACE
• Atmosphere (20.9%)
ENDOTHELIAL SURFACE
• Aqueous humor (7.4%)

120. CARBON DIOXIDE EFFLUX
OPEN-EYE
• From the cornea and aqueous humor into the tear
film
CLOSED-EYE
• Into the aqueous humor

121. OPEN EYE
55 mm Hg
O2
O2
O2
CO2
155 mm Hg
5µL O /cm cornea/h
2
2
21 µL CO2 /cm cornea/h
2
O2

122. CLOSED EYE
O2
CO2

123. CONTACT LENSES ARE A BARRIER TO OXYGEN
AND CARBON DIOXIDE TRANSMISSION

124. CONTACT LENSES ARE A BARRIER TO OXYGEN
AND CARBON DIOXIDE TRANSMISSION

125. CORNEAL ENERGY BY
CARBOHYDRATE METABOLISM
• Glucose enters cornea from the aqueous humor
• Energy: ATP (Adenosine Triphosphate)
• 2 main pathways:
- Anaerobic: ATP from breakdown of glucose into lactic
acid
- Aerobic: ATP from breakdown of glucose by TCA into
carbon dioxide and water

126. SOURCES OF GLUCOSE
CORNEAL EPITHELIUM
• Aqueous humor (90%)
• Limbal blood vessels and tears (less than 10%)

127. GLUCOSE CONSUMPTION
• 38-90 µg/hour
• 40-66% of total consumption is by the epithelium

128. GLUCOSE METABOLIC PATHWAYS
EMBDEN-MEYERHAOF PATHWAY
• Produces lactate (anaerobic) + 2 ATP
TRICARBOXYLIC ACID CYCLE
• Aerobic (along with epithelial cell mitochondria
produces CO2, H2O and 36 ATP)
HEXOSE MONOPHOSPHATE SHUNT
• Aerobic: produces NADPH, CO2, and H2O

129. CORNEAL GLUCOSE METABOLISM
Glycogen
(storage)
Glucose -6-
Phosphate
Glycolytic
(E-M)
Pathway
TCA
Cycle & oxidation
mitochondrial activity
36ATP CO2
CO 2
H O
2
H O
2
NADPH
NADP
+
NADP
(main function
of HMS)
H O
2
LDH
O
(Aerobic)
2
Lactic acid Pyruvic acid
2ATP (Anaerobic)
Ribose-5-phosphate
O2
O 2
Hexose-Monophosphate
Shunt
(pentose phosphate pathway)
Glucose
Anaerobic
8ATP

130. GLUCOSE PATHWAYS
TCA Cycle, also known as the Tricarboxylic Acid
Cycle, Krebs's Cycle, or Citric Acid Cycle is an
important pathway for energy production.

131. AEROBIC GLYCOLYSIS:
TCA CYCLE (& Mitochondria)
• Efficient
• 15% of glucose utilized
• Energy contribution: 3x that of anaerobic glycolysis

132. AEROBIC GLYCOLYSIS:
TCA CYCLE (& Mitochondria)
Pyruvic acid from E-M pathway
Complete oxidation
36 moles ATP: 1 mole of glucose

133. ATP
• ‘Charged’ form of energy
• When ATP imparts energy it is converted to ADP
(adenosine diphosphate)
• ADP recharged by mitochondria
• Recycling of ADP into ATP every 50 seconds

134. ANAEROBIC GLYCOLYSIS:
EMBDEN-MEYERHOF PATHWAY
G-6-P
(by phosphorylation)
pyruvic acid
lactic acid & ATP
2 moles ATP: 1 mole glucose
• 35% of glucose used

135. HEXOSE MONOPHOSPHATE SHUNT
(Pentose Phosphate Pathway)
• H-M Shunt NOT efficient as energy source
• NO net gain in ATP
• 60-70% of glucose used
• Limited recycling of glucose: 85% catabolized to
lactate

136. HEXOSE MONOPHOSPHATE SHUNT
(Pentose Phosphate Pathway)
G-6-P
Ribose-5-phosphate & NADPH (reduced
Nicotinamide Adenine Dinucleotide Phosphate)
Ribose - 5 - phosphate
Glycolytic pathway
NADPH
NADP
Substrate for
RNA & DNA

137. CORNEAL GLUCOSE METABOLISM
Glycogen
(storage)
Glucose -6-
Phosphate
Glycolytic
(E-M)
Pathway
TCA
Cycle & oxidation
mitochondrial activity
36ATP CO2
CO 2
H O
2
H O
2
NADPH
NADP
+
NADP
(main function
of HMS)
H O
2
LDH
O
(Aerobic)
2
Lactic acid Pyruvic acid
2ATP (Anaerobic)
Ribose-5-phosphate
O2
O 2
Hexose-Monophosphate
Shunt
(pentose phosphate pathway)
Glucose
Anaerobic
8ATP

138. NORMOXIC CONDITIONS
• Glycogen storage: outermost cell layers of the
epithelium
• Glycogen reserves are in preparation for a lack of
oxygen and/or mechanical trauma
• ATP production/consumption is normal

139. EFFECTS OF HYPOXIA AND ANOXIA
ATP production
Lactate production
Stored glycogen
E-M Pathway
Lactate dehydrogenase
Glucose level
ATP production
Lactate production
Glycogen level
TCA cycle ceases
Lactate dehydrogenase
(LDH)
Glucose flux and
utilization adequate
HYPOXIA ANOXIA

140. LACTIC ACID
• Not metabolized by cornea
• Removed by diffusion into aqueous humor
• Accumulation results in epithelial and stromal oedema
• Hypoxia doubles lactic acid concentration resulting in
an osmotic gradient

141. CORNEAL TRANSPARENCY: STROMA
• Transmits 90% of incident light
• Potentially a non-transparent layer
• Fibrils: n=1.47
• Ground substance: n=1.354
• Regular fibril spacing of 60nm

142. CORNEAL TRANSPARENCY DIFFRACTION
THEORY OF MAURICE
• Depends on ordered arrangement of collagen fibrils
• Transparency is maintained if the disruption is less
than a few wavelengths
• Scattering effect increases as swelling increases
(fibrils become larger optically)

143. DISRUPTION OF COLLAGEN FIBRILS

144. CORNEAL SWELLING
• Lactate and metabolite accumulation -osmotic gradient
causes water imbibition
• Hydrophilicity of GAGs causes a natural water
imbibition
• Swelling during sleep is due to:
- Hypoxia (50%)
- Lower tear osmolarity
- Increased temperature and humidity

145. CORNEAL SWELLING: EFFECTS
• Change in refractive index of intra and
extracellular spaces
• Sattler’s veil
• Haloes

146. ENDOTHELIAL PUMP
• Each cell pumps its own volume every 5 minutes
• Active transport mechanism
• Na+ + K+ + ATPase-dependent pump
• Glucose fueled

147. ENDOTHELIAL PUMP
• Sodium ions move between the stroma and aqueous
humor, water follows passively
• Bicarbonate from stroma into the aqueous humor is
about equal to sodium ion outflow
• Bicarbonate transport is electroneutral
• Only the sodium ions pumped into the cornea produce
a potential difference

148. ENDOTHELIAL PUMP
H O (leak)
2
+ -
H O
2
Stroma
Glucose
O2
H O
2
DM Endo
H O (leak)
2
Na+
(low endo. Na+ permeability)
(Na ± induced potential
difference)
(Na, K & ATPase-dependent)
++
H+
HCO-
Na
3
+
ATP-ase
K+
{

ATP

149. EPITHELIAL PUMP
• Active process drives chloride into cornea from the
tears and sodium into tears
• Epithelial pH regulated by basal cell sodium (IN) -
hydrogen (OUT) exchanger
(Klyce, 1977)

150. EPITHELIAL PUMP
Tears Epithelium Stroma
Cl
–
H O
(leak)
2
CO2
Lactate
Glucose
(from aqueous
humor)
Cl
(modulator =
cyclic AMP)
–
H
+
Na
+
Evaporation
7µm 50µm
Glucose
(little)
BASAL
CELLS

151. STROMAL PUMP
• Relatively inactive except for keratocyte metabolism
• Lactate per se has no effect on corneal function

152. FACTORS INFLUENCING CORNEAL
THICKNESS
• Individual variations
• Tear evaporation and osmotic response (hypertonic) -
thinning
• Reflex tearing in CL (hypotonic)
- Thickening
• CL induce hypoxia - thickening

153. TEAR FILM OSMOLALITY
NORMAL OSMOLALITY
294-334 mOsm/litre (0.91-1.04%)

154. TEAR FILM OSMOLALITY:
CONTACT LENS EFFECTS
• Initial HCL wear: decreased tear osmolality
• Cornea swells (stromal) 2-4%
• Initial SCL wear: increased tear osmolality (blink rate
affects evaporation??)
• Return to pre-lens value: 1 week (HCL), 2-3 days (SCL)

155. CORNEAL EPITHELIAL REPAIR
• Complete stripping rapid regeneration:
- 6 wks for complete cell regeneration
- Conjunctival and corneal cells provide coverage
• Smaller wounds:
- Wing cells and squamous cells slide
- Basal (columnar) cells flatten

156. Epithelial wound with basement membrane intact
1 hour
15 hours
24-48 hours
Sliding of adjacent epithelial cells
Formation of pseudopods (PMNs active)
Cells become more cuboidal
(DNA synthesis and hemidesmosomal attachment begins)
EPITHELIAL REPAIR

157. CORNEAL EPITHELIAL REPAIR
• Limited area, basal cells in place:
- desquamation of surface cells
- Basal cells become less columnar
- Wounding stops mitosis in adjacent cells
- Mitosis is resumed once full epithelial thickness is achieved

158. CORNEAL EPITHELIAL REPAIR
• Basement membrane layer loss:
- Initially re-epithelialization by sliding or migration
- By 6 weeks regeneration almost complete
• Epithelium will alter cell thickness and arrangement to
maintain corneal curvature
• Protein synthesis 3X during epithelial sheet movement
• Cell migration necessitates shape change

159. EFFECT OF REMOVING CORNEAL
LAYERS
• Temperature reversal effect still present
• With plastic substitute normal corneal thickness is maintained
• Barrier to passive influx of salts and water Loss results in rapid
corneal swelling
EPITHELIUM

160. EFFECT OF REMOVING CORNEAL
LAYERS
• Epithelial oedema
STROMA with impermeable membrane implant
ENDOTHELIUM
• Rapid swelling and increased thickness

161. CORNEAL INTEGRITY
• 15% - 20.9% for regular function
• 13.1% to prevent suppression of epithelial
mitosis
• 8% to prevent sensitivity loss
• 5% to prevent glycogen depletion
requires:
OXYGEN

162. CORNEAL INTEGRITY
• Essential to avoid pH and metabolic changes
requires:
CO2 ELIMINATION
GLUCOSE
• Main source: anterior chamber

163. CARBON DIOXIDE PERMEABILITY
• 21x more than oxygen
HYDROGELS
RGPs
• 7x more than oxygen
CORNEA
• 7x more than oxygen

164. pH
• More comfortable than Schirmer’s test
• pH of tears in open eye: 7.34 - 7.43
• pH tolerance of the endothelium: 6.8 - 8.2
• Eye drops outside pH range 6.6 - 7.8 sting

165. TEMPERATURES
Cornea
• Open eye
- 34.2 (0.4)oC
- 34.3 (0.7)oC
- 34.5 (1.0)oC
• Closed eye
- 36.2 (0.1) oC
• Other
- dry eye 34.0 (0.5) oC
- under 0.07 mm SCL 34.6oC
- under 0.30 mm SCL 34.9oC
Conjunctiva
- 34.9 (0.6) oC
- 35.4oC in 20 - 30 year old
- 34.2oC >60years of age
(Fujishima et al., 1996)
(Efron et al., 1989)
(Martin & Fatt, 1986)
(Martin & Fatt, 1986)
(Fujishima et al., 1996)
(Martin & Fatt, 1986)
(Martin & Fatt, 1986)
(Isenberg & Green, 1985)

166. AGE-RELATED CORNEAL
CHANGES ANATOMICAL
• Arcus senilis
• White limbal girdle of Vogt
• Decreased nerve elements in cornea and eyelid
• Dystrophies/degenerations
• Pinguecula and pterygium
• ATR astigmatism
• Decreased transparency
• Peripheral thinning
• Endothelial cell loss
• Polymegethism

167. AGE-RELATED CORNEAL CHANGES
FUNCTIONAL CHANGES
• Increase in permeability of limbal vasculature
• Decrease in endothelial pump activity
• Decrease in metabolic activity
• Increase in refractive index
• Increase in visibility of nerves

168. TEARS

169. TEAR FUNCTIONS
• Optical
• Physiologic
• Bactericidal/bacteriostatic
• Metabolic
• Protective

170. TEAR COMPOSITION
• 3-layered structure
• Mucus layer (pertains to cornea?)
• Aqueous layer
• Lipid layer
• Some believe the tears should be regarded as 2-layered

171. CROSS-SECTION OF THE TEAR FILM
Evaporation
STABLE
TEAR FILM
Superficial lipid
layer
Aqueous fluid
Adsorbed mucin layer
Corneal epithelium

172. TEARS: MUCUS LAYER
• 0.02 - 0.05 µm thick
• Extremely hydrophilic
• Greatly enhances epithelial wettability
• Microvilli and microplicae
• Maintains stability of tear film
• Secreted by goblet cells of conjunctiva
• Some may come from lacrimal gland

173. TEARS: AQUEOUS LAYER
• Bulk of tear’s 7 µm thickness (range 6-9)
• The only layer involved in true tear flow
• Vehicle for most of tear’s components
• Transfer medium for oxygen and carbon dioxide
• Produced by lacrimal gland and accessory lacrimal
glands of Wolfring and Krause

174. TEARS: LIPID LAYER
• Thin film, 0.1 µm
• Main function is anti-evaporative
• Prevents tear fluid overflow
• Anchored at orifices of Meibomian gland
• Compressed and thickened during blinking
• Drags aqueous fluid producing increased film thickness
• Mainly secreted by Meibomian glands
• Some produced by Zeis glands
• Contains some dissolved lipids and mucus

175. TEAR PROPERTIES
• 98.2% water
• Normal osmolality range 294-334 mOsm/litre (0.91-1.04%)
- Osmolality is flow-rate dependent
- Decreased osmolality following eye closure (reduced
evaporation)
• n=1.336
• Some glucose (mainly from aqueous humor)
• pO2 = 155 mm Hg (open eye), 55 mm Hg (closed eye)

176. TEAR PROPERTIES
• Bactericidal/bacteriostatic components:
- Lysozyme
- Lactoferrin
- Beta-lysin (b-lysin)
• In addition to Na+ and Cl- ions there are:
- K+, HCO-
3, Ca+, Mg+, Zn+
• Amino acids
• Urea
• Lactate and pyruvate

177. TEAR DIMENSIONS
Volume 6.5-8 µL
Flow rate 0.6 µL/min
Turnover rate 16%/min
Daily production controversial (range 1-15 g)

178. TEAR SECRETION RATE
• Stimuli
- Psychogenic
- Sensory
• Previous divisions
- Basal (immeasurable, <0.3 ml/min)
- Reflex (lacrimation)

179. TEAR FILM STABILITY
Time taken for the tear film to break up
following blink cessation

180. BUT (Break-Up Time) OR
TBUT (Tear BUT)
• Sodium fluorescein instilled onto eye
• Tear film monitored under ‘blue’ light
• Record occurrence of first ‘dry spot’
• Repeat measurements required due to:
- Defects in anterior segment
- Surfactants in paper strip
- Abnormal eyes may not form a complete film
• <10 seconds is abnormal
• 15 - 45 seconds is considered normal

181. STABLE
TEAR FILM
LOCAL
THINNING
DRY SPOT
FORMED BY
RECEDING TEARS
Superficial lipid layer
Aqueous fluid
Adsorbed mucin layer
Corneal epithelium
flow
flow
Diffusion
Breakup
(after Smolin & Thoft, 1987)
Evaporation
TEAR BREAK-UP PHENOMENON

182. NIBUT (Non-Invasive BUT)
• BUT test which does not require staining
• More consistent and reliable

183. DRY SPOTS FORMATION

184. WETTING THE CORNEA
• Glycocalyx binds mucus layer
- Glycocalyx: an ‘irregularity filler’
• Surface will WET if:
- Surface tension (ST) of tear film - epith./tear interface< bare
epith.
- ST of epithelium/tear interface is kept low by mucus
- ST of tear film depends on, and is reduced by, the lipid layer
and palpebral fissure width

185. TEAR FUNCTION TESTS
• BUT (TBUT)
• NIBUT
• Schirmer test
• Fluorophotometry
• Phenol-red thread test
• Rose Bengal staining
• Tear film osmolality test

186. SCHIRMER TEST
• Thin strip of filter paper is bent into an L shape
and inserted into lower fornix
• Wet length after a fixed time period (5 minutes)
is measured
• Short wet length means a possible dry eye
• Test is subject to many artifacts
• Cheap and readily available

187. SCHIRMER TEST

188. FLUOROPHOTOMETRY
Used to measure tear flow rates

189. FLUOROPHOTOMETER

190. PHENOL-RED THREAD TEST
• Assesses tear volume
• More comfortable than Schirmer test
(Hamano et al., 1983)

191. PHENOL-RED THREAD TEST

192. ROSE BENGAL STAINING
Decreased lacrimation produces cell
degeneration.
Rose Bengal stains the resulting necrotic cells.

193. ROSE BENGAL STAINING

194. TEAR PROTEINS LOW CONCENTRATIONS
• Albumin*
• Prealbumin*
• Lysozyme*
• Lactoferrin* (25% of tear protein wt.)
• Transferrin (low concentration)
* principal proteins

195. TEAR PROTEINS
IMMUNOLGLOBULINS
• Mainly secretory lgA* (2 x lgA - secretory
component)
• lgA
• lgG lower concentration than lgA
• lgM, lgD and lgG (lower concentration than lgA)
cont’d…

196. CLOSURE OF EYELIDS
• Contraction of orbicularis oculi muscle (OO)
• No reciprocal innervation between OO and
levator palpebrae superioris muscle (LPS)
• Innervation by N7 facial nerve
• ‘Zipper-like’ from temporal to nasal

197. CLOSURE OF EYELIDS
• Rate: 15 blinks/min
• Duration: 0.3-0.4 s
• Globe moves up and in towards nose and
backwards
• Forced closure involves OO and Müller’s
muscle
• Sleep: tonic stimulation of OO and inhibition
of LPS
cont’d….

198. OPENING OF EYLIDS
• Contractions of levator palpebrae superioris
muscle
• Some assistance from Müller’s muscle (smooth,
sympathetic)
• Main innervation from N3 (oculomotor)

199. BLINKING
• Lower lid hardly moves during normal blink
• Spontaneous blinking usually a response to:
- Corneal dryness and irritants
- Anxiety
- Sustained sound level
- Air pollution
• Relative humidity is not a blink stimulus

200. BLINK REFLEXES
• Facial nerve nucleus connects with:
- Superior colliculus (optic impulses)
- Trigeminal nucleus (sensory impulses)
- Superior olive (acoustic impulses)
• Optic reflex
• Sensory reflex
• Auro-palpebral and cochleo-palpebral reflexes
• Stretching or striking reflex
• Psychogenic reaction (non-reflex)

201. EYELIDS AND TEARS
• Lids spread tears
• Resurfacing with mucus later increases tear film stability
• Blinking pumps tears into nose via puncta
• Lid closure compresses lipid tear layer
• Eye opening drags aqueous phase of tears, thickening
tear film
• Lids act on lacrimal gland and gravity moves tear over
cornea
• Lid muscle action has a role in accessory lacrimal gland
output

202. EYELID FUNCTION
Protection from:
• Threat
• Bright light
• Foreign bodies
• Desiccation (eye closure)
• Visual stimulation during sleep

203. 1
2
3
4
IDENTIFICATION OF 1,2,3,4

204. IDENTIFICATION OF 4a,4b,4c

205. IDENTIFICATION OF 5,6,7

206. IDENTIFICATION OF 8a,8b,8c, 8d, 8e

207. IDENTIFICATION OF 9a, 9b, 9c

208. IDENTIFICATION OF 10

209. THANK YOU
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210. SYMBOLS

211. ABBREVIATIONS

212. ACRONYMS

213. ACRONYMS