ANATOMY AND

PHYSIOLOGY OF THE

ANTERIOR SEGMENT Module 1.1

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Published in Australia by The International Association of Contact Lens Educators

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

-  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

THANK YOU

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