ANATOMY AND

PHYSIOLOGY OF THE
ANTERIOR SEGMENT
Module 1.1

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


THE EYE
ANATOMY
CORNEA
11.5 mm
(after Hogan et al., 1971)
10.6 mm
11.7 mm
CORNEAL DIMENSIONS
The cornea
is not symmetrical
and
corneal curvature flattens
towards the periphery
CORNEAL SHAPE
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
- n
ground substance
= 1.354, n
collagen
= 1.47
CORNEAL PROFILE
CORNEAL COMPOSITION
78% water
15% collagen
5% other parts
1% GAGs
Epithelium " 10% of
corneas wet weight
TRANSVERSE SECTION OF THE CORNEA
EPITHELIUM
Regular and smooth
Uniform thickness
Tear layer substrate
LAYERS OF EPITHELIUM
ELECTRON MICROGRAPH OF THE
EPITHELIUM
EPITHELIUM
50 microns thick
5-layered structure
- Squamous cells (surface)
- Wing cells
- Columnar cells (basal)
Cell turnover (basal to surface ! 7 days
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
EPITHELIAL CELLS


OTHER CELLS: BASAL LAYER

Pigmented melanocytes (peripheral epithelium)
Macrophages
Lymphocytes
MICROPLICAE AND MICROVILLI
Present on anterior of surface epithelial cells
Responsible for tear film retention?
BASEMENT MEMBRANE (basal lamina)
Interface between basal cell layer of epithelium and
Bowmans layer
Thickness - 10-65 nm
EPITHELIAL ADHESION
EPITHELIAL ADHESION
BOWMANS LAYER
Acellular
Differentiated anterior stroma
Mainly collagen, some ground substance
Collagen fibrils randomly dispersed
THIN OPTIC SECTION OF HUMAN CORNEA
STROMA
0.50 mm thick
90% of corneal thickness, mostly collagenous lamellae
Contains 2-3% keratocytes (fibroblasts) and about 1%
ground substance
GROUND SUBSTANCE (GAGs)
Very hydrophilic
Responsible for:
Exact spacing of fibrils
H
2
O imbibition pressure of cornea (due to hydrophilicity)
KERATOCYTES
Interspersed between collagenous lamellae
Thin, flat cells 10 "m in diameter with long
processes
5-50 "m of intercellular space
Joined together by macula occludens or
hemidesmosomes
KERATOCYTES
(CORNEAL FIBROBLASTS)
STROMAL LAMELLAE
Dense and orderly fibrous connective tissue
Stable protein collagen fibrils
Regular arrangement is important for corneal
transparency
STROMAL LAMELLAE
200 - 250 lamellae superimposed on one
another
Thickness: 2 "m
Width: 9-260 "m
Length: 11.7 mm
LAMELLAR ARRANGEMENT
Parallel to:
Corneal surface
One another
LAMELLAR ARRANGEMENT
DESCEMETS MEMBRANE
10-12 "m
Structureless
Slightly elastic
Secreted by the endothelium
Very regularly arranged stratified layer
Functions as basement layer of endothelium
HASSALL-HENLE WARTS
Periodic thickenings of Descemets membrane
Can protrude into anterior chamber
HASSALL-HENLE WARTS
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
ENDOTHELIUM
Single layer
500,000 mainly hexagonal cells
18-20 "m diameter
5 "m thick
Non-replicating
ENDOTHELIUM
ENDOTHELIUM
ENDOTHELIUM CELL NUCLEI
Centrally located
Uniformly spaced in the young
AGE-RELATED CELLULAR CHANGES
Cell degeneration and non-replacement
- Decreased uniformity
- Decreased thickness with age
Polymegethism
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
PERIPHERAL CORNEAL VASCULATURE
Peripheral cornea (and sclera adjacent to
Schlemms canal) supplied by circumcorneal
vessels
Minor role in corneal nutrition
Remainder of cornea is avascular
CORNEAL INNERVATION
One of the richest sensory nerve supplies
Ophthalmic division of trigeminal nerve (N5)
Fibres become more visible in oedema
MEDULAR CHANGES OF CORNEAL
NERVES
PHYSIOLOGICAL CHARACTERISTICS OF
CORNEAL NERVES
Sensory
Parasympathetic
Sympathetic innervation?
CONJUNCTIVA
CONJUNCTIVA
Mucous membrane
Translucent rather than transparent
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










DIMENSIONS AND CONTOURS OF THE
CONJUCTIVA AND FORNICES
14 - 16 mm
9 - 11 mm
5
(After Whitnall & Ehlers, 1965)
CONJUNCTIVA
Loose
- Moves freely
- Allows independent movement of
globe
Thinnest over Tenons capsule
REGIONAL DIVISIONS OF THE
CONJUNCTIVA
Palpebral
Fornices
Bulbar
Plica semilunaris
Caruncle
REGIONAL DIVISIONS OF THE
CONJUNCTIVA
Conjunctiva is composed of 2 layers:
Epithelium
Stroma
CONJUNCTIVA
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
CONJUNCTIVAL STROMA
Loosely arranged bundles of coarse collagen
Bundles are approximately parallel to surface
Numerous fibroblasts (main cell type)
Some immunological cells present
CONJUNCTIVAL GLANDS
Goblet Cells
Glands of Wolfring
Glands of Krause
Crypts of Henle
CONJUNCTIVAL GLANDS
CONJUNCTIVAL GLANDS
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
CONJUNCTIVAL ARTERIES
LIMBUS
Transition zone between cornea and conjunctiva/
sclera
Anatomical reference
LIMBUS
CORNEA TO CONJUCTIVA
SCLERA TRANSITION
5 layer epithelium
Bowmans layer
Stroma
10-15 layer epithelium
Stroma and Tenons
capsule
Sclera proper
CORNEA CONJUNCTIVA
CORNEA TO CONJUCTIVA/
SCLERA TRANSITION
LIMBAL EPITHELIUM
Goblet cells
Melanocytes
Underlying
blood vessels


Bulbar Conjunctival Corneal Limbal
DIMENSIONS OF THE LIMBAL REGION
Depth:
Width:
1.0 mm
1.5 mm (horizontally)
2.0 mm (vertically)
LIMBAL FUNCTION
Nourishment
Aqueous humor drainage
LIMBAL VASCULATURE VESSEL TYPES
Terminal arteries
Recurrent arteries
LIMBAL VASCULATURE VESSEL TYPES
LIMBAL INNERVATION
SCLERA
SCLERA
Approximately spheroidal
Collagenous
Relatively avascular
Relatively inactive metabolically
Durable and tough
SCLERA COMPOSITION
65% H
2
O (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
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
(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
LACRIMAL GLAND
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)
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)
LACRIMAL GLAND
12 lacrimal ducts
- 2-5 from upper (orbital) portion
- 6-8 from lower (palpebral) portion
Ducts open onto superior palpebral conjunctiva
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
ACCESSORY LACRIMAL GLANDS
GLANDS OF WOLFRING
Similar structure to lacrimal gland
Near upper border of tarsal plate
Supply aqueous phase of basal tear film
ACCESSORY LACRIMAL GLANDS
GLANDS OF ZEIS
Sebaceous glands
Associated with lash follicles
Partially supply lipid layer of tears
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
ACCESSORY LACRIMAL GLANDS
CRYPTS OF HENLE
Invaginations of superior peripheral palpebral
conjunctiva
Mucous crypts
ACCESSORY LACRIMAL GLANDS
GOBLET CELLS
Unicellular sero-mucous glands
In epithelium of conjunctiva
Provides mucoid layer of tears
Have a single-discharge life-cycle
TEAR FILM
TEAR DISTRIBUTION
By eyelid action
By movement of the globe
Helps form lacrimal lake
Each blink resurfaces tear film
TEAR FLOW
Tear flow aided by:
Capillary action
Gravity
Blinking
(after Mahmood et al., 1984)
DISTRIBUTION OF TEAR VOLUMES
1 !L
3 !L
4 !L
TEAR
VOLUMES
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
MECHANICS OF TEAR FILM SPREADING
Upward lid movement draws aqueous component over
the surface
Lipid layer spreading over surface increases film
thickness and stability
TEAR FLOW: LID CLOSURE
MOVEMENT TOWARDS THE MEDIAL CANTHUS
Lid closure is scissor-like towards the nose
Tears move towards the medial canthus
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
TEAR FLOW DIRECTION
(after Haberich, 1968)
Tears
upper and lower puncta
lower canaliculi
lacrimal sac
naso-lacrimal duct
nose (Valve of Hasner)
TEAR DRAINAGE
EYELIDS
CROSS SECTIONAL VIEW OF EYE LIDS
EYELIDS 4-LAYERED STRUCTURE

Cutaneous layer (the skin)
Muscular layer (mainly orbicularis oculi)
Fibrous tissue layer (tarsal plates)
Mucosal layer (palpebral conjunctiva)
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
EYELIDS: GLANDS
ZEIS GLANDS
Sebaceous glands associated with lash follicle
MOLLS GLANDS
Modified sweat glands open into Zeis glands, lash
follicles, lid margins
MEIBOMIAN GLANDS
Sebaceous glands in the tarsal plate
EYELIDS: GLANDS
MEIBOMIAN GLAND ARRAY
EYELIDS: BLOOD VESSELS
Supply oxygen to the cornea via palpebral
conjunctival vessels
PHYSIOLOGY
PHYSIOLOGY OF THE CORNEA
Sources of energy
Transparency
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
CORNEAL PERMEABILITY OTHER
SUBSTANCES
Sodium: endothelium greater than the epithelium by
100X
Glucose and amino acids: metabolically active
Associated molecules
Fluorescein
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
ROLE OF CELL JUNCTIONS
Communication
Electrical coupling
Barrier to:
- Electrolytes
- Fluids
- Macromolecules
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)
SCHEMATIC COMPOSITE VIEW OF
ALL JUNCTION TYPES
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
OXYGEN
The
most important
metabolite
OXYGEN SUPPLY TO THE CORNEA
Endothelium
Descemets
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

O
2
O
2
SOURCES OF OXYGEN
EPITHELIAL SURFACE
Atmosphere (20.9%)
ENDOTHELIAL SURFACE
Aqueous humor (7.4%)
CARBON DIOXIDE EFFLUX
OPEN-EYE
From the cornea and aqueous humor into the tear
film
CLOSED-EYE
Into the aqueous humor
OPEN EYE
55 mm Hg
O
2
O
2
O
2
CO
2
155 mm Hg
5"L O /cm cornea/h
2
2
21 "L CO
2
/cm cornea/h
2
O
2
CLOSED EYE
O
2
CO
2

CONTACT LENSES ARE A BARRIER TO OXYGEN
AND CARBON DIOXIDE TRANSMISSION


CONTACT LENSES ARE A BARRIER TO OXYGEN
AND CARBON DIOXIDE TRANSMISSION

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
SOURCES OF GLUCOSE
CORNEAL EPITHELIUM
Aqueous humor (90%)
Limbal blood vessels and tears (less than 10%)
GLUCOSE CONSUMPTION
38-90 "g/hour
40-66% of total consumption is by the epithelium
GLUCOSE METABOLIC PATHWAYS
EMBDEN-MEYERHAOF PATHWAY
Produces lactate (anaerobic) + 2 ATP
TRICARBOXYLIC ACID CYCLE
Aerobic (along with epithelial cell mitochondria
produces CO
2
, H
2
O and 36 ATP)
HEXOSE MONOPHOSPHATE SHUNT
Aerobic: produces NADPH, CO
2
, and H
2
O
CORNEAL GLUCOSE METABOLISM
Glycogen
(storage)
Glucose -6-
Phosphate
Glycolytic
(E-M)
Pathway
TCA
Cycle & oxidation
mitochondrial activity
36ATP CO
2
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
O
2
O
2
Hexose-Monophosphate
Shunt
(pentose phosphate pathway)
Glucose
Anaerobic
8ATP
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.
AEROBIC GLYCOLYSIS:
TCA CYCLE (& Mitochondria)
Efficient
15% of glucose utilized
Energy contribution: 3x that of anaerobic glycolysis
AEROBIC GLYCOLYSIS:
TCA CYCLE (& Mitochondria)
Pyruvic acid from E-M pathway
Complete oxidation
36 moles ATP: 1 mole of glucose
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
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
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
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
CORNEAL GLUCOSE METABOLISM
Glycogen
(storage)
Glucose -6-
Phosphate
Glycolytic
(E-M)
Pathway
TCA
Cycle & oxidation
mitochondrial activity
36ATP CO
2
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
O
2
O
2
Hexose-Monophosphate
Shunt
(pentose phosphate pathway)
Glucose
Anaerobic
8ATP
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
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
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
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
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)
DISRUPTION OF COLLAGEN FIBRILS
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
CORNEAL SWELLING: EFFECTS
Change in refractive index of intra and
extracellular spaces
Sattlers veil
Haloes
ENDOTHELIAL PUMP
Each cell pumps its own volume every 5 minutes
Active transport mechanism
Na
+
+ K
+
+ ATPase-dependent pump
Glucose fueled
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
ENDOTHELIAL PUMP
H O (leak)
2
+ -
H O
2
Stroma
Glucose O 2
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
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)
EPITHELIAL PUMP
Tears Epithelium Stroma
Cl

H O
(leak)
2
CO
2
Lactate
Glucose
(from aqueous
humor)
Cl
(modulator =
cyclic AMP)

H
+
Na
+
Evaporation
7"m 50"m
Glucose
(little)
B
A
S
A
L

C
E
L
L
S

STROMAL PUMP
Relatively inactive except for keratocyte metabolism
Lactate per se has no effect on corneal function
FACTORS INFLUENCING CORNEAL
THICKNESS
Individual variations
Tear evaporation and osmotic response (hypertonic) -
thinning
Reflex tearing in CL (hypotonic)
- Thickening
CL induce hypoxia - thickening
TEAR FILM OSMOLALITY
NORMAL OSMOLALITY

294-334 mOsm/litre (0.91-1.04%)
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)
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
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
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
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
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
EFFECT OF REMOVING CORNEAL
LAYERS
Epithelial oedema
STROMA with impermeable membrane implant
ENDOTHELIUM
Rapid swelling and increased thickness
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
CORNEAL INTEGRITY
Essential to avoid pH and metabolic changes
requires:
CO
2
ELIMINATION
GLUCOSE
Main source: anterior chamber
CARBON DIOXIDE PERMEABILITY
21x more than oxygen
HYDROGELS
RGPs
7x more than oxygen
CORNEA
7x more than oxygen
pH
More comfortable than Schirmers 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
TEMPERATURES
Cornea
Open eye
- 34.2 (0.4)
o
C
- 34.3 (0.7)
o
C
- 34.5 (1.0)
o
C
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)
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
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
TEARS
TEAR FUNCTIONS
Optical
Physiologic
Bactericidal/bacteriostatic
Metabolic
Protective
TEAR COMPOSITION
3-layered structure
Mucus layer (pertains to cornea?)
Aqueous layer
Lipid layer
Some believe the tears should be regarded as 2-layered
CROSS-SECTION OF THE TEAR FILM
Evaporation
STABLE
TEAR FILM
Superficial lipid
layer
Aqueous fluid
Adsorbed mucin layer
Corneal epithelium
TEARS: MUCUS LAYER
0.02 - 0.05 "m 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
TEARS: AQUEOUS LAYER
Bulk of tears 7 "m thickness (range 6-9)
The only layer involved in true tear flow
Vehicle for most of tears components
Transfer medium for oxygen and carbon dioxide
Produced by lacrimal gland and accessory lacrimal
glands of Wolfring and Krause
TEARS: LIPID LAYER
Thin film, 0.1 "m
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
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)
pO
2
= 155 mm Hg (open eye), 55 mm Hg
(closed eye)
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
TEAR DIMENSIONS
Volume 6.5-8 "L
Flow rate 0.6 "L/min
Turnover rate 16%/min
Daily production controversial (range 1-15 g)
TEAR SECRETION RATE
Stimuli
- Psychogenic
- Sensory
Previous divisions
- Basal (immeasurable, <0.3 ml/min)
- Reflex (lacrimation)
TEAR FILM STABILITY
Time taken for the tear film to break up
following blink cessation
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
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
NIBUT (Non-Invasive BUT)
BUT test which does not require staining
More consistent and reliable
DRY SPOTS FORMATION
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
TEAR FUNCTION TESTS
BUT (TBUT)
NIBUT
Schirmer test
Fluorophotometry
Phenol-red thread test
Rose Bengal staining
Tear film osmolality test
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
SCHIRMER TEST
FLUOROPHOTOMETRY
Used to measure tear flow rates
FLUOROPHOTOMETER
PHENOL-RED THREAD TEST
Assesses tear volume
More comfortable than Schirmer test
(Hamano et al., 1983)
PHENOL-RED THREAD TEST
ROSE BENGAL STAINING
Decreased lacrimation produces cell
degeneration.
Rose Bengal stains the resulting necrotic cells.
ROSE BENGAL STAINING

TEAR PROTEINS LOW CONCENTRATIONS

Albumin*
Prealbumin*
Lysozyme*
Lactoferrin* (25% of tear protein wt.)
Transferrin (low concentration)
* principal proteins


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)
contd#
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
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 Mllers
muscle
Sleep: tonic stimulation of OO and inhibition
of LPS
contd#.
OPENING OF EYLIDS
Contractions of levator palpebrae superioris
muscle
Some assistance from Mllers muscle (smooth,
sympathetic)
Main innervation from N3 (oculomotor)
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
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)
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
EYELID FUNCTION
Protection from:
Threat
Bright light
Foreign bodies
Desiccation (eye closure)
Visual stimulation during sleep
1
2
3
4
IDENTIFICATION OF 1,2,3,4
IDENTIFICATION OF 4a,4b,4c
IDENTIFICATION OF 5,6,7
IDENTIFICATION OF 8a,8b,8c, 8d, 8e
IDENTIFICATION OF 9a, 9b, 9c
IDENTIFICATION OF 10
THANK YOU
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ACRONYMS