anatomy & physiology of the anterior segment module 1.1_final
TRANSCRIPT
ANATOMY AND
PHYSIOLOGY OF THE
ANTERIOR SEGMENT Module 1.1
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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
- nground substance = 1.354, ncollagen = 1.47
CORNEAL PROFILE
CORNEAL COMPOSITION
• 78% water
• 15% collagen
• 5% other parts
• 1% GAGs
• Epithelium ≈ 10% of cornea’s 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 Bowman’s layer
• Thickness - 10-65 nm
EPITHELIAL ADHESION
EPITHELIAL ADHESION
BOWMAN’S 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
• H2O imbibition pressure of cornea (due to hydrophilicity)
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
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 µm
Width: 9-260 µm
Length: 11.7 mm
LAMELLAR ARRANGEMENT
Parallel to:
• Corneal surface
• One another
LAMELLAR ARRANGEMENT
DESCEMET’S MEMBRANE
• 10-12 µm
• Structureless
• Slightly elastic
• Secreted by the endothelium
• Very regularly arranged stratified layer
• Functions as basement layer of endothelium
HASSALL-HENLE WARTS
• Periodic thickenings of Descemet’s 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 µm diameter
• 5 µm 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 Schlemm’s 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 Tenon’s 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 Bowman’s layer
Stroma
10-15 layer epithelium
Stroma and Tenon’s 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% 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
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 µL
3 µL
4 µL
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
MOLL’S 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 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
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
O2 O2
CO2
155 mm Hg
5µL O /cm cornea/h 2 2
21 µL CO2 /cm cornea/h 2
O 2
CLOSED EYE
O2
CO2
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 µg/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 CO2, H2O and 36 ATP)
HEXOSE MONOPHOSPHATE SHUNT • Aerobic: produces NADPH, CO2, and H2O
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
• Sattler’s 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
7µm 50µm
Glucose (little)
BA
SAL
CEL
LS
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:
CO2 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 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
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)
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 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
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
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
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)
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 µL
Flow rate 0.6 µL/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)
cont’d…
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 Müller’s muscle
• Sleep: tonic stimulation of OO and inhibition of LPS
cont’d….
OPENING OF EYLIDS
• Contractions of levator palpebrae superioris muscle
• Some assistance from Müller’s 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
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