OCULAR PHYSIOLOGY-: OPT-234

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OCULAR PHYSIOLOGY-: OPT-234

CARL HALLADAY ABRAHAM DEPARTMENT OF OPTOMETRY AND VISION SCIENCE UNIVERSITY OF CAPE COAST

3.0 - CORNEA AND SCLERA

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objectives

The basic anatomy of the cornea Factors that ensure the transparency of the cornea Protective mechanism of the cornea The basic anatomy and function of the sclera

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CORNEA

The cornea is made up of five layer: Epithelium Bowman’s layer Stroma Descemet’s membrane Endothelium

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CORNEAL ANATOMY

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Tears Epithelium Bowman's layer Stroma (collagen fibrils/filaments, proteoglycans, keratocytes) Descemet's membrane Endothelium D 10 gm Stromal nerves 470 urn 4-15 gm 4-6 urn

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Epithelium

Stratified epithelium 5-7 cells thick measuring 50 μ m Enhances tear film stability Many projections (microplicae and microvilli) on the apical surfaces of outermost cell increase surface area Prevent uptake of excess fluid from the tears Tight junctions (zonula occludens ) join the surface cells along the lateral wall near the apical surfaces

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Tear film Glycocalyx Microvilli Superficial cells Wing cells Basal cells Basal lamina Desmosomes Hemidesmosomes

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Epithelium

Quick regeneration Cell proliferation occurs in the basal layer, Only cells in contact with basement membrane have the ability to divide Stem cells located in a 0.5-1mm wide band around the corneal periphery are responsible for renewal of the basal cell layer A slow migration of cells occurs from the periphery to the centre of the cornea Turn over time for the entire epithelium is 7 days

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Shedding 49 Migration Proliferation and movement toward surface Limbal stem cells @ TA cells S Basal epithelial cells Wing cells Squamous cells

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Bowman’s Layer

Approximately 8-14 μ m thick Dense fibrous sheet of inter-woven collagen fibrils randomly arranged in a mucoprotein ground substance. Layer commonly referred to as a “membrane” but more correctly it is a transition layer to the stroma.

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Bowman’s Layer

It is acellular and contains collagen fibrils of lesser diameter than those in the stroma . It is produced prenatally by the epithelium and is not believed to regenerate due to absence of fibroblasts If injured, the layer is replaced by epithelial cells or stromal scar tissue. The layer is very resistant to damage by shearing, penetration, or infection.

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Surface cells Wing ælls — Basal ælls — Stromal keratæyte

Bowman'slayer < , Anterior stroma

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Stroma / Substantia Propria

Approximately 500 μ m thick, or about 90% of the corneal thickness. It is composed of collagen fibrils, keratocytes, and extracellular ground substance. The fibrils have a uniform 25-35nm diameter and run parallel to each other, forming flat bundles called lamellae. The 200 to 300 lamellae are distributed throughout the stroma and lie parallel to the corneal surface.

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01 r anterior chamber Corneal stroma: Parallel type I collagen fibers , perpendicular lamellae, (EM).

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Stroma

Keratocytes (corneal fibroblasts) are flattened cells that lie between and occasionally within the lamellae. They maintain the stroma by synthesizing collagen and extracellular matrix components. Other cells may be found between lamellae including white blood cells, lymphocytes, macrophages, and polymorphonuclear leucocytes. These increase in number in pathological conditions

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Stroma

Ground substance fills the areas between fibrils, lamellae, and cells. It contains proteoglycans, a core protein with an anionic polysaccharide side chain called glycosaminoglycan (GAG) portion. Proteoglycans Provide tissue volume Maintain spatial order of collagen fibrils Resist compressive forces Gives viseoelastic properties to the tissue GAG’s attract and bind with water, maintaining the precise spatial relationship between individual fibrils. Dermatan sulphate is found in oxygen rich environments (anterior cornea) Keratan is found in low oxygen environments (posterior cornea)

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Core protein

GAGs

decorin

lumican

keratocan

mimecan

Dermatan sulphate

Keratan sulphate

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2

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Stroma

The very regular arrangement of the stromal components and the small diameter of collagen fibrils contribute to the stromal transparency. The very specific spacing between fibrils allows destructive interference of rays reflected from adjacent fibrils . Overall, the cornea scatters less than 1% of light that enters it.

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Descemet’s Membrane

Considered to be the basement membrane of the endothelium. It is produced constantly throughout life such that its thickness doubles by the age of 40 yrs. In children it is 5 μ m and increases to 15 μ m over a life time.

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Descemet’s Membrane

Consists of two lamellae, an anterior lamina 3 μ m thick has a banded appearance. And a posterior nonbanded lamina secreted by the endothelium throughout life. The collagen fibrils are arranged such that Descemet's membrane exhibits an elastic property If injured, the membrane will curl into the anterior chamber. It is very resistant to trauma, proteolytic enzymes, and some pathological conditions and can be regenerated when damaged.

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Endothelium

Innermost layer of the cornea Lies adjacent to the anterior chamber. Composed of a single layer of cells and Normally 5 μ m thick. Basal part of each cell rests on Descemet’s membrane and Apical surface from which microvilli extend lines the anterior chamber. Cells are polyhedral. In normal cornea, five sided and seven sided cells can be found. But 70-80% of cells are hexagonal. Regular arrangement of the cells is referred to as the endothelial mosaic.

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Endothelial cells do not divide or replicate.(a limited proliferative region has been found near the Schwalbe line) They are in an arrested phase of growth in the cell cycle. Cells migrate and spread out to cover a defect resulting in cell thinning. Cell density decreases normally with ageing because of cell disintegration

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Endothelium

Endothelial cell density (ECD) is 5000 cells/mm 2 in new borns and reduces to 1000 to 2000 cells/mm 2 at age 80. The loss of endothelium cells is divided into 2 phases (fast and slow) Fast phase By Age 5: 3500cells/mm2 By age 14-20 : 3000 cells /mm2 Slow phase 0.4-0.6% loss per year Minimum cell density necessary for adequate function is in the range of 400 to 700 cells/mm 2

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Tight junctional complexes joining the cells are located near the apexes of the cells. The barrier formed by these adhesions is slightly leaky due to 10nm wide intercellular spaces Allows the entrance of nutrients, including glucose and amino acids, from aqueous humor. Permeability can be measured with confocal microscopy (ECD) and fluorophotometery to measure permeability Excessive loss of cells can disrupt intercellular junctions and allow excess aqueous flow into the stroma. And the endothelial pumps may be unable to compensate for the loss of barrier function.

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EPI Stroma Barrier Pump

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Pump H20 NalKATPase HC03- Gap junction ExtraceUular pathway

There is an active pump which works in opposition to the leaky barrier The active pump is located in the enthothelial cells’s basolateral cell membrane There are 3 million Na+/K+-ATPase proteins sites are found at the basolateral membrane of a single endothelial cell (4.4trillion /mm2) It transports sodium and bicarbonate ions into the stroma to create an osmotic gradient Endothelial pump function can be measured clinically by Pachymetry pre –post wear of oxygen-impermeable contact lens resulting in swelling of corneal Measure degree of diurnal fluctuation in corneal thickness

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Anterior chamber

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Factors that affect endothelial pump function Pharmacological inhibition of Na+/K+-ATPase Decreased temperature Lack of bicarbonate Carbonic anhydrase inhibitors Mechanical injury Chemical injury Disease states When these happen in corneas with ECD 2000-750 cells/mm2 edema is prevented either by An increase in metabolic activity of Na+/K+-ATPase Or increasing the total number and density of pump sites on viable endothelial cells

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Endothelium

When ECDs are 500cells/mm2 or less Edema can occur Corneal edema is a cornea that is more hydrated than its normal physiologic state of 78% water Physiology of corneal oedema Swelling pressure (+55mmHg) due to anionic charges of the proteoglycan GAG side chains Imbibition pressure (-40mmHg) pulls in Na+ A balance of these pressures keeps the cornea properly hydrated A hydration of 5% or more above 78% hydration will result in edema .

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Na+

Na+

Hydrostatic pressure(IOP)

Swelling pressure(SP)

imbibing pressure(IP)

IP = IOP-SP

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Permeability increases with decease in ECD Endothelial cells are also rich in cellular organelles. Mitochondria in these cells are more numerous than in other cells of the eye except retinal photo receptors.

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LIMBUS

located at the corneoscleral junction approximately 1.5 to 2 mm wide It encircles the periphery of the cornea. The radius of curvature abruptly changes at this junction of cornea and sclera, creating a shallow, narrow furrow, the external scleral sulcus .

Cornea Limbus Conjunctiva Lunbu• Cornea Limbus Coinea. Limbus Conjunctiva

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Internally at this juncture, there is a larger furrow, the internal scleral sulcus , which has a scooped-out appearance. Contains all major aqueous drainage pathways

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LIMBAL CONJ

epithelium

Loose connective tissue

Connective tissue derived from tenons

episclera

Limbal stroma

Conj vessels

Peripheral corneal arcades

Episcleral vessels

Intrascleral vessels

Deep scleral plexus

Scleral spur

Ant part of longitudinal portion of ciliary body

Trabecular meshwork

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regular squamous corneal epithelium becomes the thicker columnar conjunctival epithelium, regular corneal stroma becomes the irregularly arranged scleral stroma the corneal endothelial sheet becomes discontinuous to wrap around the strands of the trabecular meshwork, Bowman’s layer and Descemet’s membrane terminate at the anterior border, the conjunctival stroma , episclera , and Tenon’s capsule begin within the limbal area.

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EPITHELIAL / MESENCHYMAL INTERACTION IN THE LIMBUS 'I'DC PMC TAC LESC MSC LANGERHANS MELANOCYTES BLOOD VESSEL NERVE CELL

Blood vessels

Mescenchymal stem cell

Limbal epithelial stem cells

Transcient amplifying cells

T erminal differentiated cells

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CONJUNCTIVA PMID: 17211449 LIMBUS LC MC M: Melanocytes LC: Langerhan•s cells pMC 'TAC eTAC CORNEA TOC Bo BV o — BM: Basement membrane o N: Nerve BV: Bood vessels TOC. Terminal differentiated cells PMC: Post mitotic ceas ÆAC.• Late transtent amplifying cetts TAC: Earty transient amp!tfyng cells SC: Stem cells MC: Mesenchymal cells BO: Bowman's membrane

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The cornea is the largest refracting optical component of the eye. The cornea has a central and peripheral optical zone It has 3 major reference point at the optical zone The corneal apex Located in reference to the The Device Axis point (DAP) or line of sight he corneal apex is 0.5mm temporal and 0.5mm superior to the corneal intercept of the line of sight It helps to determine geometrical properties of the corneal shape It is important in selecting and fitting contact lenses

4iis Central optical zone Peripheral optiæl zone

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The corneal sighting centre (CSC) This is the corneal intercept of the line of sight Helps to describe to optical properties of the cornea and the whole optical system The thinnest corneal point (TCP) The thinnest point or zone on the entire retina TCP is located 0.4 inf and 0.4 temporal to CSC and 5 ?m thinner than the central corneal thickness It helps to identify corneas with current or previous keratectasia Regular and irregular astigmatism is dependent on the central optical zone

Pupillary axis Line of sight Device axis Entrance to pupil csc DAP Real pupil Fovea

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Optical properties of the cornea

There anterior cornea is aspheric The asphericity of the cornea is denoted by a mathematical quantity Q. A normal eye is prolate with an asphericity (Q)= -0.25

Oblate Elliptical Asphericity (Q) -2.00 -1.00 -0.25 0.00 +2.00 Spherical Corneal Condition Severe keratoconus Mild keratoconus Normal Spherical 8 cut RK 16 cut RK

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CORNEAL POWER

The total corneal power can be determined using the gaussian formula D= D1 +D2 –d(D1XD2) Average corneal power is 42.4 If RIC =1.376, RIA=1 , RIA chamber = 1.336, ACR = 0.0078m, PCR=0.0065m, CT = 0.00054 Corneal should act a minus lens but the aqueous neutralizes all its minus power What is likely to happen if the cornea is surrounded by air or the anterior cornea is submerged in air?

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Interesting…

Light transmission The cornea transmits 99% of incident light this is due to its high level of transparency It absorbs all UV radiation and transmits all visible light (400-700nm) and infrared up to 2500nm. Why is the cornea transparent ? Regular arrangement of collagen fibrils in the stroma Collagen fibrils are ineffective at scattering light (Spaces between collagen fibres is less than the wavelength of light ) Avascular Regular diameter of fibres Relative dehydration Lack of myelin sheath Regular or mosaic arrangement of epithelial cells

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SCLERA

It forms the posterior five sixths of the connective tissue coat of the globe. The sclera maintains the shape of the globe, Offers resistance to internal and external forces and Provides an attachment for the extraocular muscle insertions.

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SCLERA

Thickness of the sclera varies from 1mm at the posterior pole to 0.3mm just behind the rectus muscle insertions. The episclera is a loose, vascularised, connective tissue that lies just outer to the sclera. The larger episcleral blood vessels are visible through the conjunctiva The episclera is joined to the Tenon’s capsule by strands of connective tissue and progressively becomes thinner towards the back of the eye. The sclera itself is continuous with the corneal stroma at the limbus .

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