Anatomy of the Cornea

Anatomy of the Cornea

• The cornea is the anterior 1/6 of the globe, consisting of 5 layers: epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium.
• The cornea merges with the sclera and conjunctiva in a transitional region called the limbus.
• Dimensions:
  • Anteriorly: oval appearance, 11.7mm horizontally and 10.6mm vertically.
  • Posteriorly: circular, 11.7mm in diameter.
  • Thinnest centrally: 550 μm, increasing to 700 μm in the periphery.
  • Radius of curvature: 7.7mm anteriorly and 6.9mm posteriorly.

Optical Zones

• Only the central optical zone (central 3-4mm) is responsible for image formation.
• The remainder of the cornea is for mechanical support and peripheral vision with a dilated pupil.
• Central zone: mostly spherical.
• Paracentral zone: generally spherical, but flatter than the central zone.
• Peripheral zone: flattens significantly.
• Limbal zone: transitions into the sclera and conjunctiva.

Corneal Epithelium

• Thickness: 50-60 μm.
• Composed of 5 layers of cells centrally.
• Non-keratinized, stratified squamous epithelial cells.
• Cell layers:
  • Superficial cells: 2-3 layers thick, attached to each other by desmosomes.
  • Wing cells: 2-3 layers, named for their wing-shaped processes, with tight, lateral, intercellular junctions and multiple gap junctions.
  • Basal cells: single layer of tall columnar cells, adherent to the basement membrane.
• Turnover: complete every 10 days, with the X, Y, Z hypothesis of corneal epithelial maintenance.

Basement Membrane

• Thickness: 40-100 nm.
• Composed of type IV collagen, laminin, heparin sulfate proteoglycans (HSPGs), and nidogens.
• Aids in binding of the epithelium to the underlying Bowman's layer.

Bowman's Layer

• Thickness: 12 μm.
• Acellular collagen fibril matrix, mainly composed of type I collagen.
• Collagen is finer and more randomly arranged than in the stroma.

Corneal Stroma

• Thickness: 90% of the corneal thickness.
• Composed of water, collagen arranged into lamellae, keratocytes, proteoglycans, and GAGs.
• Mainly type I collagen, with small amounts of type III, V, and VI.
• Lamellae: 200-300, with all fibrils in the same lamellae running in the same direction.
• Anterior 1/3: lamellae are narrow, branching, and interweaving.
• Posterior 2/3: lamellae are wider and more regular.

Stromal Cells

• Keratocytes (corneal fibroblasts): flattened cells that lie between the lamellae.
• Maintain stromal collagen and ECM.
• Large nuclei with minimal cytoplasm, communicate with each other via numerous long processes and gap junctions.

Descemet's Membrane

• Thickness: 5 μm at birth, increasing to 15 μm over a lifetime.
• Composed of type IV collagen.
• Divided into two laminae: anterior (banded, 3 μm thick) and posterior (non-banded, homogenous).
• Terminates abruptly at the limbus as a thickened area of collagen called Schwalbe's line.

Corneal Endothelium

• Innermost corneal layer, adjacent to the aqueous humour and anterior chamber.
• Continuous with the cells lining the trabecular meshwork and the anterior iris.
• Single layer of flattened polygonal cells.
• 70-80% of cells are hexagonal in shape.
• Around 20 μm in diameter and 4-6 μm thick.
• Gap junctions provide communication between cells.

Why is the Cornea Clear?

• Corneal clarity is maintained by:
  • Regular collagen size, spacing, and lattice pattern.
  • Lattice fibril arrangement, allowing light to pass through without disruption.
  • Even keratocyte spacing.
  • Endothelial fluid pump.

Nutrient Supply to the Cornea

• The cornea is avascular, receiving nutrients by diffusion from the aqueous humour and limbal vessels.
• Limbal vessels are supplied by anterior ciliary arteries.
• Oxygen is mainly obtained from atmospheric oxygen dissolved in the tear film.
• With eyes closed, palpebral capillaries supply the bulk of oxygen.

Corneal Nerves

• The cornea is the most richly innervated body tissue, with approximately 160,000 nerve terminals/mm2.
• Sensory nerves are supplied by long ciliary nerves (ophthalmic branch of CN V).
• Form a unmyelinated plexus, whose branches are mostly within the middle 1/3 of the stroma to Bowman's layer.
• Can become desensitized over time (e.g., contact lens wear).

Anatomy of the Iris

• The iris is the most anterior component of the uvea, dividing the anterior chamber from the posterior chamber.
• It is a highly vascularized, muscular diaphragm with a central opening (pupil), approximately 12 mm in diameter.
• The iris has two zones: the peripheral ciliary zone (3-4 mm) containing the dilator muscle, and the central pupillary zone (1-2 mm) containing the sphincter muscle.

Iris Structure

• The iris has three layers: the anterior border layer, stroma, and pigmented epithelial layer (anterior and posterior).
• The anterior border layer consists of a modified stroma with melanocytes, collagen, and fibroblasts, determining iris color.
• The stroma is a loose collagenous matrix with fibroblasts, melanocytes, and a high degree of vascularization.

Iris Muscles

• There are two muscles in the iris: the sphincter and dilator muscles, which have opposing actions to govern pupil size.
• The sphincter muscle is a flat annulus of smooth muscle at the pupil margin, approximately 0.75-1 mm wide.
• The dilator muscle is composed of radially oriented basal processes of anterior epithelial cells, extending into the stroma.

Pupil

• The pupil is a circular opening between the irises, approximately 3-4 mm in diameter.
• Pupil size is regulated by the opposing actions of the sphincter and dilator muscles, responding to light stimuli.
• Pupil size affects retinal illuminance, depth of focus, and aberrations.

Iris Function

• The iris controls pupil size, modulating retinal illuminance and minimizing aberrations.
• It blocks stray light and plays a role in social signaling, constricting when asleep and dilating when excited.

Iris Histology

• The anterior epithelium is a single layer of lightly pigmented cells divided into apical and basal processes.
• The posterior epithelium is a single layer of heavily pigmented epithelial cells, with a concentration of melanin similar between individuals, regardless of iris color.

Anatomy of the Iris

• The iris is the most anterior component of the uvea, dividing the anterior chamber from the posterior chamber.
• It is a highly vascularized, muscular diaphragm with a central opening (pupil), approximately 12 mm in diameter.
• The iris has two zones: the peripheral ciliary zone (3-4 mm) containing the dilator muscle, and the central pupillary zone (1-2 mm) containing the sphincter muscle.

Iris Structure

• The iris has three layers: the anterior border layer, stroma, and pigmented epithelial layer (anterior and posterior).
• The anterior border layer consists of a modified stroma with melanocytes, collagen, and fibroblasts, determining iris color.
• The stroma is a loose collagenous matrix with fibroblasts, melanocytes, and a high degree of vascularization.

Iris Muscles

• There are two muscles in the iris: the sphincter and dilator muscles, which have opposing actions to govern pupil size.
• The sphincter muscle is a flat annulus of smooth muscle at the pupil margin, approximately 0.75-1 mm wide.
• The dilator muscle is composed of radially oriented basal processes of anterior epithelial cells, extending into the stroma.

Pupil

• The pupil is a circular opening between the irises, approximately 3-4 mm in diameter.
• Pupil size is regulated by the opposing actions of the sphincter and dilator muscles, responding to light stimuli.
• Pupil size affects retinal illuminance, depth of focus, and aberrations.

Iris Function

• The iris controls pupil size, modulating retinal illuminance and minimizing aberrations.
• It blocks stray light and plays a role in social signaling, constricting when asleep and dilating when excited.

Iris Histology

• The anterior epithelium is a single layer of lightly pigmented cells divided into apical and basal processes.
• The posterior epithelium is a single layer of heavily pigmented epithelial cells, with a concentration of melanin similar between individuals, regardless of iris color.

Ciliary Body Anatomy

• The ciliary body is part of the uvea, located at the corneoscleral junction and attached to the iris.
• It consists of 5 layers: supracillaris, ciliary muscle, ciliary stroma, pigmented epithelium, and non-pigmented epithelium.
• The ciliary body is divided into two parts: pars plicata and pars plana.

Pars Plicata

• The anterior ciliary body, containing around 70 ciliary processes.
• Each ciliary process is approximately 2 mm long, 0.5 mm wide, and 1 mm deep.
• Pars plicata is responsible for producing aqueous humor.

Pars Plana

• The posterior ciliary body, extending from the pars plicata to the ora serrata.
• The retinal extension into the pars plana is called the dentate process.
• Ora serrata is the serrated junction between the retina and the ciliary body, located approximately 5 mm anterior to the equator.

Ciliary Body - Supraciliaris

• The junction between the ciliary body and the sclera, composed of ribbons of connective tissue.
• It also contains fibroblasts and melanocytes, allowing the ciliary muscle to contract without detaching from the sclera.

Ciliary Body - Ciliary Muscle

• The ciliary muscle has three muscle groups: longitudinal/meridional/Brucke's muscle, radial, and circular/Muller's muscle.
• The longitudinal muscle is closest to the sclera, attaching to the scleral spur.
• The radial muscle is located in the middle, and the circular muscle is closest to the lens, functioning as a sphincter.
• In accommodation, the parasympathetic innervation is dominant over the sympathetic innervation.
• The ciliary muscles move anterior to the lens, reducing zonular fiber contraction, and the lens bulges to accommodate.

Accommodation

• The lens zonules (or zonule of Zinn) connect the ciliary body to the lens, originating from the pars plana.
• The neural control of accommodation involves a blur signal sent to the primary visual cortex, then to the pretectal area, and finally to the Edinger Westphal nucleus.
• Two signals are then sent: one via the parasympathetic pathway to the ciliary ganglion and the ciliary muscle, and the other via CNIII to the medial rectus.
• The accommodation/near reflex involves accommodation, pupil constriction, and convergence.

Ciliary Stroma

• The ciliary stroma lies over the ciliary muscle, being heavily pigmented, vascularized, and innervated.
• It is continuous with the choroid posteriorly and the iris anteriorly.
• The ciliary beds within the stroma are fenestrated, allowing exchange between the blood and the stroma.

Ciliary Epithelium

• The ciliary epithelium is the site of aqueous production and facilitates immune privilege of the eye.
• There are two types of ciliary epithelium: pigmented (inner, cuboidal) and non-pigmented (outer, columnar/cuboidal).
• The non-pigmented cells contain tight junctions (zonula occludens) to prevent leakage and maintain the ocular blood-aqueous barrier.

Aqueous Production

• The production rate of aqueous humor is approximately 2.5 µL/min, with a turnover of around 2.4 µL/min.
• Aqueous humor is produced through a combination of active secretion (80-90%) and passive diffusion (10-20%).
• There are three mechanisms of aqueous production: passive diffusion, passive ultrafiltration, and active secretion.

Aqueous Production Mechanisms

• Passive diffusion: transportation of substances down their concentration gradient across the lipid portion of the membrane.
• Passive ultrafiltration: flow of water and water-soluble substances through fenestrated capillaries, driven by osmotic gradient or hydrostatic pressure.
• Active secretion: energy-dependent transport of selected substances against a concentration gradient through specific transporters.

Aqueous Production Steps

• Step 1: NaCl is transferred from the stroma by two sets of electroneutral transporters.
• Step 2: Passage of NaCl from the pigmented epithelium to the non-pigmented epithelium through gap junctions.
• Step 3: Secondary active transport of Cl- and HCO3-, and primary active transport of Na+ and K+.

Aqueous Drainage

• Aqueous humor is drained through two sites: the posterior trabecular meshwork into Schlemm's canal, and the uveoscleral route (~10% outflow).
• Intraocular pressure (IOP) is determined by the balance between aqueous production and clearance.

Anterior Chamber Angle

• Forms the junction between the cornea and iris
• Responsible for the drainage of aqueous humour

Trabecular Meshwork

• Located between Schwalbe's Line and the scleral spur
• Consists of three regions: uveal, corneoscleral, and juxtacanalicular/cribriform meshwork
• Uveal meshwork: closest to the anterior chamber, collagen and elastic lamellae network, and large openings between lamellae
• Corneoscleral meshwork: middle layer, perforated collagen and elastin plates covered by TM cells, and connects the scleral spur to the anterior wall of the scleral sulcus
• Juxtacanalicular/cribriform meshwork: loose connective tissue, sieve-like plates, and main source of resistance to aqueous flow

Trabecular Cells

• Endothelial: maintain passageway patency, neutralize reactive oxygen species
• Macrophage: biological filter/phagocytosis, immune mediation
• Fibroblastic: ECM turnover/tissue repair
• Smooth muscle: contractile tone, mechanotrasduction

Schlemm's Canal

• Outer wall: closest to sclera, monolayer of endothelial cells, well-developed basement membrane, and no transcellular microchannels
• Inner wall: closest to TM, monolayer of endothelial cells, incomplete sub-endothelial layer, no basement membrane, and tight junctions between cells

Scleral Spur

• Posterior wall of Schlemm's canal
• Site of anterior ciliary muscle attachment
• Prevents Schlemm's canal from collapsing under ciliary muscle contraction

Outflow Routes of Aqueous Humor

• Trabecular outflow: TM → Schlemm's canal → collector channel → episcleral plexus
• Uveoscleral drainage: fluid passes between the uveal trabeculae and ciliary muscle bundles → drain to the episclera
• Uveoscleral drainage affected by drugs and state of accommodation (ciliary muscle)

Ciliary Muscle on Aqueous Flow

• Ciliary muscle relaxed: decreases trabecular outflow, increases uveoscleral outflow
• Ciliary muscle contracted: increases trabecular outflow, decreases uveoscleral outflow

Anterior Chamber Angle

• Forms the junction between the cornea and iris
• Responsible for the drainage of aqueous humour

Trabecular Meshwork

• Located between Schwalbe's Line and the scleral spur
• Consists of three regions: uveal, corneoscleral, and juxtacanalicular/cribriform meshwork
• Uveal meshwork: closest to the anterior chamber, collagen and elastic lamellae network, and large openings between lamellae
• Corneoscleral meshwork: middle layer, perforated collagen and elastin plates covered by TM cells, and connects the scleral spur to the anterior wall of the scleral sulcus
• Juxtacanalicular/cribriform meshwork: loose connective tissue, sieve-like plates, and main source of resistance to aqueous flow

Trabecular Cells

• Endothelial: maintain passageway patency, neutralize reactive oxygen species
• Macrophage: biological filter/phagocytosis, immune mediation
• Fibroblastic: ECM turnover/tissue repair
• Smooth muscle: contractile tone, mechanotrasduction

Schlemm's Canal

• Outer wall: closest to sclera, monolayer of endothelial cells, well-developed basement membrane, and no transcellular microchannels
• Inner wall: closest to TM, monolayer of endothelial cells, incomplete sub-endothelial layer, no basement membrane, and tight junctions between cells

Scleral Spur

• Posterior wall of Schlemm's canal
• Site of anterior ciliary muscle attachment
• Prevents Schlemm's canal from collapsing under ciliary muscle contraction

Outflow Routes of Aqueous Humor

• Trabecular outflow: TM → Schlemm's canal → collector channel → episcleral plexus
• Uveoscleral drainage: fluid passes between the uveal trabeculae and ciliary muscle bundles → drain to the episclera
• Uveoscleral drainage affected by drugs and state of accommodation (ciliary muscle)

Ciliary Muscle on Aqueous Flow

• Ciliary muscle relaxed: decreases trabecular outflow, increases uveoscleral outflow
• Ciliary muscle contracted: increases trabecular outflow, decreases uveoscleral outflow

Lens Anatomy

• The lens is a transparent, biconvex, ellipsoid structure with a refractive power of +20D.
• It is composed of 66% water and 33% protein.
• The lens is avascular, meaning it has no blood vessels, and it has no nerves.
• Lens cells divide, but they do not shed, and the lens increases in size and weight with age.

Lens Development

• The lens develops from the optic pit, which forms during the 4th week of gestation.
• The lens placode invaginates to form the lens pit during the 5th week.
• The lens vesicle forms during the 6th week, and it is surrounded by an intact basement membrane.
• The posterior cells begin to elongate anteriorly during the 6th week, and they reach the anterior wall during the 7th week.
• The primary lens fibers fill the lens vesicle during the 8th week, and the intracellular organelles disappear.

Lens Parameters

• The lens thickness increases by about 0.02mm/year.
• At birth, the lens thickness is 3.5-4.0mm, and it increases to 4.75-5.0mm by 90 years.
• The equatorial diameter of the lens is 6.0-6.5mm at birth and 9.0-10.0mm in adults.
• The anterior radius of curvature is 8.0-14.0mm, and the posterior radius of curvature is 4.5-7.5mm.

Lens Capsule

• The lens capsule is a basement membrane with elastic properties.
• It is the point of attachment for the lens zonules.
• The capsule envelops the lens and has regional variations in thickness.

Lens Epithelium

• The lens epithelium is responsible for the growth and development of the entire lens.
• It is composed of simple cuboidal cells that become columnar near the equator.
• The epithelium is restricted to the anterior surface of the lens.
• The basal aspect of the epithelium is in contact with the capsule.
• The epithelium contains a nucleus and organelles.
• Gap junctions between cells maintain lens transparency.

Lens Fibers

• Lens fibers are the main component of the lens.
• They arise from the epithelium in the germinative zone.
• The cells elongate and then turn meridionally.
• The nucleus is displaced anteriorly, forming the lens bow.
• The fibers are hexagonal in cross-section and form rows.
• The fibers are thinner posteriorly, and their tips meet at a suture.

Lens Fiber Nucleus

• As lens fibers migrate to deeper layers, the cell organelles and nucleus degenerate.
• The cytoplasm becomes homogenous.
• The basal attachment of the fiber to the posterior capsule terminates.

Lens Sutures

• Lens sutures are formed by the overlap of the ends of secondary fibers.
• Primary fibers do not form sutures.
• Fetal secondary fibers form Y-shaped sutures, which become more complex in adolescence and adulthood.

Lens Zonules/Zonule of Zinn

• The lens zonules are fibers that pass from the ciliary body to the lens.
• They hold the lens in place and allow the ciliary muscle to act on the lens during accommodation.
• The zonules are composed of non-collagenous glycoprotein.

Lens Hydration

• Lens hydration is essential for transparency.
• The lens maintains hydration through a 'pump-leak' system.
• The posterior part of the lens has no epithelial barrier, allowing for free diffusion of ions, solutes, and water between the lens and vitreous.
• The anterior part of the lens actively transports K+ and amino acids into the lens.

Crystallin Proteins

• Crystallin proteins make up ~40% of the wet weight of the lens fiber cells.
• They have a higher refractive index than the surrounding fluid.
• They maintain hydration during lens deformation due to accommodation.
• The high concentration and dense packing of crystallin proteins mean that the majority of light scatter is cancelled out.
• There are three types of crystallin proteins: α-crystallin, β-crystallin, and γ-crystallin.

Lens Anatomy

• The lens is a transparent, biconvex, ellipsoid structure with a refractive power of +20D.
• It is composed of 66% water and 33% protein.
• The lens is avascular, meaning it has no blood vessels, and it has no nerves.
• Lens cells divide, but they do not shed, and the lens increases in size and weight with age.

Lens Development

• The lens develops from the optic pit, which forms during the 4th week of gestation.
• The lens placode invaginates to form the lens pit during the 5th week.
• The lens vesicle forms during the 6th week, and it is surrounded by an intact basement membrane.
• The posterior cells begin to elongate anteriorly during the 6th week, and they reach the anterior wall during the 7th week.
• The primary lens fibers fill the lens vesicle during the 8th week, and the intracellular organelles disappear.

Lens Parameters

• The lens thickness increases by about 0.02mm/year.
• At birth, the lens thickness is 3.5-4.0mm, and it increases to 4.75-5.0mm by 90 years.
• The equatorial diameter of the lens is 6.0-6.5mm at birth and 9.0-10.0mm in adults.
• The anterior radius of curvature is 8.0-14.0mm, and the posterior radius of curvature is 4.5-7.5mm.

Lens Capsule

• The lens capsule is a basement membrane with elastic properties.
• It is the point of attachment for the lens zonules.
• The capsule envelops the lens and has regional variations in thickness.

Lens Epithelium

• The lens epithelium is responsible for the growth and development of the entire lens.
• It is composed of simple cuboidal cells that become columnar near the equator.
• The epithelium is restricted to the anterior surface of the lens.
• The basal aspect of the epithelium is in contact with the capsule.
• The epithelium contains a nucleus and organelles.
• Gap junctions between cells maintain lens transparency.

Lens Fibers

• Lens fibers are the main component of the lens.
• They arise from the epithelium in the germinative zone.
• The cells elongate and then turn meridionally.
• The nucleus is displaced anteriorly, forming the lens bow.
• The fibers are hexagonal in cross-section and form rows.
• The fibers are thinner posteriorly, and their tips meet at a suture.

Lens Fiber Nucleus

• As lens fibers migrate to deeper layers, the cell organelles and nucleus degenerate.
• The cytoplasm becomes homogenous.
• The basal attachment of the fiber to the posterior capsule terminates.

Lens Sutures

• Lens sutures are formed by the overlap of the ends of secondary fibers.
• Primary fibers do not form sutures.
• Fetal secondary fibers form Y-shaped sutures, which become more complex in adolescence and adulthood.

Lens Zonules/Zonule of Zinn

• The lens zonules are fibers that pass from the ciliary body to the lens.
• They hold the lens in place and allow the ciliary muscle to act on the lens during accommodation.
• The zonules are composed of non-collagenous glycoprotein.

Lens Hydration

• Lens hydration is essential for transparency.
• The lens maintains hydration through a 'pump-leak' system.
• The posterior part of the lens has no epithelial barrier, allowing for free diffusion of ions, solutes, and water between the lens and vitreous.
• The anterior part of the lens actively transports K+ and amino acids into the lens.

Crystallin Proteins

• Crystallin proteins make up ~40% of the wet weight of the lens fiber cells.
• They have a higher refractive index than the surrounding fluid.
• They maintain hydration during lens deformation due to accommodation.
• The high concentration and dense packing of crystallin proteins mean that the majority of light scatter is cancelled out.
• There are three types of crystallin proteins: α-crystallin, β-crystallin, and γ-crystallin.

Anatomy Underpinning Accommodation

• Accommodation involves a dioptre change in the optical power of the eye, with an increase in curvature of the lens to focus on objects up close.

Accommodative Apparatus

• The ciliary muscle is arranged in three bundles: outer longitudinal, middle radial, and inner circular fibers.
• It attaches anteriorly to the scleral spur and trabecular meshwork, and posteriorly to the elastic network of Bruch's membrane and the choroid.
• The ciliary muscle has a primary function of stabilizing the lens and facilitating accommodation.

Zonules

• Zonules arise from the pars plana and are composed of non-collagenous glycoprotein secreted by the ciliary epithelium.
• They have three groups of fibers: anterior, equatorial, and posterior zonules.
• Zonules serve to stabilize the lens and facilitate accommodation.

Lens

• The lens is surrounded by a continuous basement membrane, known as the lens capsule, which has elastic properties and envelops the lens.
• The lens capsule has regional variations in thickness and serves as the point of attachment for the lens zonules.

Accommodation – Ciliary Muscle

• During accommodation, the outer longitudinal fibers of the ciliary muscle contract, causing the main mass of the muscle to move forward along the curved inner wall of the sclera.
• This forces the inner radial fibers and overlying ciliary processes to bulge inwards towards the posterior chamber.

Accommodation – Theories

• The mechanism of accommodation is still debated, with various studies and theories proposed.

Accommodation – Capsule

• The lens capsule plays a crucial role in accommodation, drawing the lens into a more accommodated form.
• Decapsulation results in flattening and an increase in focal length.

Lens Shape and Displacement

• During accommodation, the anterior pole of the lens is displaced, with the most displacement occurring in the nucleus rather than the cortex.
• This leads to increased nucleus thickness, shallowing of the anterior chamber, increased lens convexity, and closer proximity of the cornea to the anterior lens.

Neural Control of Accommodation

• The neural control of accommodation involves a blur signal sent to the primary visual cortex, then to the pretectal area, and finally to the Edinger-Westphal nucleus.
• Two signals are then sent: one via the parasympathetic pathway to the ciliary ganglion and ciliary muscle, and another via the CNIII to the medial rectus (convergence).

Accommodation and Convergence Reflex

• The accommodation/near reflex involves accommodation, pupil constriction, and convergence.

Presbyopia

• Presbyopia is a common presentation in clinic, typically occurring around 40 years old, characterized by a gradual inability to accommodate.
• It is caused by various contributors, including increased stiffness of the crystalline lens and changes in zonule insertion with age.

Anatomy Underpinning Accommodation

• Accommodation involves a dioptre change in the optical power of the eye, with an increase in curvature of the lens to focus on objects up close.

Accommodative Apparatus

• The ciliary muscle is arranged in three bundles: outer longitudinal, middle radial, and inner circular fibers.
• It attaches anteriorly to the scleral spur and trabecular meshwork, and posteriorly to the elastic network of Bruch's membrane and the choroid.
• The ciliary muscle has a primary function of stabilizing the lens and facilitating accommodation.

Zonules

• Zonules arise from the pars plana and are composed of non-collagenous glycoprotein secreted by the ciliary epithelium.
• They have three groups of fibers: anterior, equatorial, and posterior zonules.
• Zonules serve to stabilize the lens and facilitate accommodation.

Lens

• The lens is surrounded by a continuous basement membrane, known as the lens capsule, which has elastic properties and envelops the lens.
• The lens capsule has regional variations in thickness and serves as the point of attachment for the lens zonules.

Accommodation – Ciliary Muscle

• During accommodation, the outer longitudinal fibers of the ciliary muscle contract, causing the main mass of the muscle to move forward along the curved inner wall of the sclera.
• This forces the inner radial fibers and overlying ciliary processes to bulge inwards towards the posterior chamber.

Accommodation – Theories

• The mechanism of accommodation is still debated, with various studies and theories proposed.

Accommodation – Capsule

• The lens capsule plays a crucial role in accommodation, drawing the lens into a more accommodated form.
• Decapsulation results in flattening and an increase in focal length.

Lens Shape and Displacement

• During accommodation, the anterior pole of the lens is displaced, with the most displacement occurring in the nucleus rather than the cortex.
• This leads to increased nucleus thickness, shallowing of the anterior chamber, increased lens convexity, and closer proximity of the cornea to the anterior lens.

Neural Control of Accommodation

• The neural control of accommodation involves a blur signal sent to the primary visual cortex, then to the pretectal area, and finally to the Edinger-Westphal nucleus.
• Two signals are then sent: one via the parasympathetic pathway to the ciliary ganglion and ciliary muscle, and another via the CNIII to the medial rectus (convergence).

Accommodation and Convergence Reflex

• The accommodation/near reflex involves accommodation, pupil constriction, and convergence.

Presbyopia

• Presbyopia is a common presentation in clinic, typically occurring around 40 years old, characterized by a gradual inability to accommodate.
• It is caused by various contributors, including increased stiffness of the crystalline lens and changes in zonule insertion with age.

Vitreous Anatomy

• The vitreous is a flattened sphere that takes up approximately 80% of the globe's volume.
• It is a gel surrounded by a thin collagenous membrane.
• The anterior indentation, also known as the hyaloid/patellar fossa, surrounds the lens.
• The vitreous has a firm attachment to the retina.

Vitreous Composition

• The vitreous is composed of 99% water, 1% structural proteins, and few hyalocytes in the periphery.
• 15-20% of the water is bound to structural proteins.
• The structural proteins include:
  • 75% type II collagen
  • 15% type IX collagen
  • Rest: V, VI, XI collagen, and hyaluronic acid (major GAG)

Vitreous Functions

• The vitreous maintains optical clarity due to its biochemical structure.
• It provides structural support to the globe, making up approximately 80% of the globe's volume.
• The vitreous supports the lens anteriorly and keeps the retinal adherence to the choroid/sclera.
• It absorbs external forces and reduces mechanical deformation of the globe.
• The vitreous acts as a molecule repository, receiving metabolites from the ciliary body and retina, and containing ions and organic molecules.
• It promotes intraocular wound healing via vitamin C reservoir and serves as an antioxidant.

Anatomical Zones

• The central/medullary zone is cell-free, contains collagen fibrils and hyaluronic acid, and is in a gel state.
• The cortex is approximately 100 µm thick, has a higher collagen concentration, and is 2% of the vitreous volume.
• The basal zone is located at the ora serrata, has dense, thickened collagen fibers, and is the site of strongest adherent to the retina.

Vitreous Biochemistry

• Type II collagen forms fibrils, while type IX collagen provides structural support to the fibrils.
• Type V/XI collagen co-assembles fibrils with type II collagen, and type VI collagen links fibrils to hyaluronan.
• Hyaluronic acid is a large glycosaminoglycan arranged in a network of long chains, interconnected to collagen fibrils, and ensures proper vitreous hydration and collagen spacing.

Aging Changes

• Liquefaction originates in the central region due to changes in hyaluronic acid conformation.
• Floaters occur when collagen fibril networks become free-floating bundles.

Vitreous Anatomy

• The vitreous is a flattened sphere that takes up approximately 80% of the globe's volume.
• It is a gel surrounded by a thin collagenous membrane.
• The anterior indentation, also known as the hyaloid/patellar fossa, surrounds the lens.
• The vitreous has a firm attachment to the retina.

Vitreous Composition

• The vitreous is composed of 99% water, 1% structural proteins, and few hyalocytes in the periphery.
• 15-20% of the water is bound to structural proteins.
• The structural proteins include:
  • 75% type II collagen
  • 15% type IX collagen
  • Rest: V, VI, XI collagen, and hyaluronic acid (major GAG)

Vitreous Functions

• The vitreous maintains optical clarity due to its biochemical structure.
• It provides structural support to the globe, making up approximately 80% of the globe's volume.
• The vitreous supports the lens anteriorly and keeps the retinal adherence to the choroid/sclera.
• It absorbs external forces and reduces mechanical deformation of the globe.
• The vitreous acts as a molecule repository, receiving metabolites from the ciliary body and retina, and containing ions and organic molecules.
• It promotes intraocular wound healing via vitamin C reservoir and serves as an antioxidant.

Anatomical Zones

• The central/medullary zone is cell-free, contains collagen fibrils and hyaluronic acid, and is in a gel state.
• The cortex is approximately 100 µm thick, has a higher collagen concentration, and is 2% of the vitreous volume.
• The basal zone is located at the ora serrata, has dense, thickened collagen fibers, and is the site of strongest adherent to the retina.

Vitreous Biochemistry

• Type II collagen forms fibrils, while type IX collagen provides structural support to the fibrils.
• Type V/XI collagen co-assembles fibrils with type II collagen, and type VI collagen links fibrils to hyaluronan.
• Hyaluronic acid is a large glycosaminoglycan arranged in a network of long chains, interconnected to collagen fibrils, and ensures proper vitreous hydration and collagen spacing.

Aging Changes

• Liquefaction originates in the central region due to changes in hyaluronic acid conformation.
• Floaters occur when collagen fibril networks become free-floating bundles.

Retinal Landmarks

• Posterior pole landmarks include macula, perifovea, parafovea, fovea, foveola, and umbo.
• The optic nerve head (optic disc) is a pinkish, oval area approximately 2 * 1.5 mm in size, located 17° (4.5 to 5 mm) nasal to the fovea.
• The foveal avascular zone has minimal overlying inner retina, and its centre is the point of fixation.

Retina Structure

• The retina is a circular disc of between 30 and 40 mm in diameter.
• The central retina is thicker than the peripheral retina.
• The retina has ten distinct layers, including the retinal pigmented epithelium (RPE), photoreceptor layer, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fibre layer, and inner limiting membrane.

Retinal Layers

• The retinal pigmented epithelium (RPE) is the outermost layer, supporting the retina and playing a crucial role in photopigment regeneration and the blood-retinal barrier.
• The photoreceptor layer contains the outer and inner segments of rod and cone photoreceptors.
• The outer nuclear layer contains the cell bodies of rods and cones.
• The outer plexiform layer is the junction between rod and cone axons and the dendrites of horizontal and bipolar cells.
• The inner nuclear layer contains the cell bodies of horizontal, bipolar, amacrine, and Müller cells.
• The inner plexiform layer is the junction between the axons of bipolar and amacrine cells and the dendrites of ganglion cells.
• The ganglion cell layer contains the nuclei of the ganglion cells and displaced amacrine cells.
• The retinal nerve fibre layer contains the fibres from ganglion cells traversing the retina to leave the eyeball at the optic disc.
• The inner limiting membrane is the end feet of the Müller cells.

Photoreceptors

• There are 126 million rods and cones in the human retina, converging to 1 million ganglion cells.
• Rods have a higher convergence ratio than cones, with an average of 120 rods to one ganglion cell.
• Cones have a lower convergence ratio, with an average of 6 cones to one ganglion cell.
• Cones in the fovea have a 1:1 connection to ganglion cells.

Visual Pathways

• The through pathway consists of photoreceptors, bipolar cells, and ganglion cells.
• The lateral pathway involves horizontal and amacrine cells, providing local feedback to optimize the through pathway.

Glial Cells

• There are three types of glial cells: Müller cells, astrocytes, and microglia.
• Müller cells span the entire retina, clearing metabolic waste, facilitating neurotransmitter recycling, and maintaining ionic balances.
• Astrocytes are found in the retinal nerve fibre layer, with a peak distribution on the optic nerve head.
• Microglia are found in every retinal layer and function as macrophages in response to trauma.

Retinal Pigment Epithelium (RPE)

• The RPE is a single-layer cell between the photoreceptors and choroid, connected by tight junctions.
• The RPE acts as a sieve between the choriocapillaris and photoreceptors, and forms part of the blood-retina barrier.
• The RPE also plays a crucial role in photopigment regeneration and recycling.

Retinal Landmarks

• Posterior pole landmarks include macula, perifovea, parafovea, fovea, foveola, and umbo.
• The optic nerve head (optic disc) is a pinkish, oval area approximately 2 * 1.5 mm in size, located 17° (4.5 to 5 mm) nasal to the fovea.
• The foveal avascular zone has minimal overlying inner retina, and its centre is the point of fixation.

Retina Structure

• The retina is a circular disc of between 30 and 40 mm in diameter.
• The central retina is thicker than the peripheral retina.
• The retina has ten distinct layers, including the retinal pigmented epithelium (RPE), photoreceptor layer, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fibre layer, and inner limiting membrane.

Retinal Layers

• The retinal pigmented epithelium (RPE) is the outermost layer, supporting the retina and playing a crucial role in photopigment regeneration and the blood-retinal barrier.
• The photoreceptor layer contains the outer and inner segments of rod and cone photoreceptors.
• The outer nuclear layer contains the cell bodies of rods and cones.
• The outer plexiform layer is the junction between rod and cone axons and the dendrites of horizontal and bipolar cells.
• The inner nuclear layer contains the cell bodies of horizontal, bipolar, amacrine, and Müller cells.
• The inner plexiform layer is the junction between the axons of bipolar and amacrine cells and the dendrites of ganglion cells.
• The ganglion cell layer contains the nuclei of the ganglion cells and displaced amacrine cells.
• The retinal nerve fibre layer contains the fibres from ganglion cells traversing the retina to leave the eyeball at the optic disc.
• The inner limiting membrane is the end feet of the Müller cells.

Photoreceptors

• There are 126 million rods and cones in the human retina, converging to 1 million ganglion cells.
• Rods have a higher convergence ratio than cones, with an average of 120 rods to one ganglion cell.
• Cones have a lower convergence ratio, with an average of 6 cones to one ganglion cell.
• Cones in the fovea have a 1:1 connection to ganglion cells.

Visual Pathways

• The through pathway consists of photoreceptors, bipolar cells, and ganglion cells.
• The lateral pathway involves horizontal and amacrine cells, providing local feedback to optimize the through pathway.

Glial Cells

• There are three types of glial cells: Müller cells, astrocytes, and microglia.
• Müller cells span the entire retina, clearing metabolic waste, facilitating neurotransmitter recycling, and maintaining ionic balances.
• Astrocytes are found in the retinal nerve fibre layer, with a peak distribution on the optic nerve head.
• Microglia are found in every retinal layer and function as macrophages in response to trauma.

Retinal Pigment Epithelium (RPE)

• The RPE is a single-layer cell between the photoreceptors and choroid, connected by tight junctions.
• The RPE acts as a sieve between the choriocapillaris and photoreceptors, and forms part of the blood-retina barrier.
• The RPE also plays a crucial role in photopigment regeneration and recycling.

Retinal Landmarks

• Posterior pole landmarks include macula, perifovea, parafovea, fovea, foveola, and umbo.
• The optic nerve head (optic disc) is a pinkish, oval area approximately 2 * 1.5 mm in size, located 17° (4.5 to 5 mm) nasal to the fovea.
• The foveal avascular zone has minimal overlying inner retina, and its centre is the point of fixation.

Retina Structure

• The retina is a circular disc of between 30 and 40 mm in diameter.
• The central retina is thicker than the peripheral retina.
• The retina has ten distinct layers, including the retinal pigmented epithelium (RPE), photoreceptor layer, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fibre layer, and inner limiting membrane.

Retinal Layers

• The retinal pigmented epithelium (RPE) is the outermost layer, supporting the retina and playing a crucial role in photopigment regeneration and the blood-retinal barrier.
• The photoreceptor layer contains the outer and inner segments of rod and cone photoreceptors.
• The outer nuclear layer contains the cell bodies of rods and cones.
• The outer plexiform layer is the junction between rod and cone axons and the dendrites of horizontal and bipolar cells.
• The inner nuclear layer contains the cell bodies of horizontal, bipolar, amacrine, and Müller cells.
• The inner plexiform layer is the junction between the axons of bipolar and amacrine cells and the dendrites of ganglion cells.
• The ganglion cell layer contains the nuclei of the ganglion cells and displaced amacrine cells.
• The retinal nerve fibre layer contains the fibres from ganglion cells traversing the retina to leave the eyeball at the optic disc.
• The inner limiting membrane is the end feet of the Müller cells.

Photoreceptors

• There are 126 million rods and cones in the human retina, converging to 1 million ganglion cells.
• Rods have a higher convergence ratio than cones, with an average of 120 rods to one ganglion cell.
• Cones have a lower convergence ratio, with an average of 6 cones to one ganglion cell.
• Cones in the fovea have a 1:1 connection to ganglion cells.

Visual Pathways

• The through pathway consists of photoreceptors, bipolar cells, and ganglion cells.
• The lateral pathway involves horizontal and amacrine cells, providing local feedback to optimize the through pathway.

Glial Cells

• There are three types of glial cells: Müller cells, astrocytes, and microglia.
• Müller cells span the entire retina, clearing metabolic waste, facilitating neurotransmitter recycling, and maintaining ionic balances.
• Astrocytes are found in the retinal nerve fibre layer, with a peak distribution on the optic nerve head.
• Microglia are found in every retinal layer and function as macrophages in response to trauma.

Retinal Pigment Epithelium (RPE)

• The RPE is a single-layer cell between the photoreceptors and choroid, connected by tight junctions.
• The RPE acts as a sieve between the choriocapillaris and photoreceptors, and forms part of the blood-retina barrier.
• The RPE also plays a crucial role in photopigment regeneration and recycling.

Optic Nerve Head (ONH) Anatomy and Function

• The optic nerve head (ONH) is the exit point for ganglion cell axons from the globe, carrying visual information to the brain.
• The optic nerve consists of four main sections: intraocular, intraorbital, intracanalicular, and intracranial.

Retina Structure

• The retina consists of 10 layers:
  • Internal limiting membrane
  • Nerve fibre layer
  • Ganglion cell layer
  • Inner plexiform layer
  • Inner nuclear layer
  • Outer plexiform layer
  • Outer nuclear layer
  • Photoreceptor layer (inner and outer segments)
  • External limiting membrane
  • Retinal pigment epithelium
  • Choroid

Optic Disc/Optic Nerve Head (ONH)

• The optic disc is the area where the optic nerve meets the eye.
• The optic disc has a vertical oval shape and is slightly raised due to the convergence of nerve fibers.
• The optic cup is a funnel-shaped depression in the optic disc.
• The optic disc is pink due to a rich capillary supply to its rim.
• The white portion is the base of the cup.

ONH Divisions

• The optic nerve head (ONH) extends from the inner retina to a plane level with the posterior sclera.
• The ONH can be divided into four sections:
  • Superficial nerve fibre layer (A)
  • Prelaminar region (B)
  • Lamina cribrosa (C)
  • Retrolaminar region (D)

Superficial Nerve Fibre Layer (RNFL)

• The superficial nerve fibre layer consists of nerve fibres organized into bundles that converge towards the disc.
• There is no overlap between the upper and lower halves of the retinal fibres.
• The nerve fibres at the edge of the nerve serve the retina furthest from the nerve.

Prelaminar Region

• The prelaminar region consists of astrocytes and nerve fibres arranged in bundles.
• The astrocytes increase in number posteriorly, forming a sieve-like structure, the glial lamina cribrosa.

Lamina Cribrosa

• The lamina cribrosa is a band of dense, specialized extracellular matrix that provides mechanical protection to the ONH against IOP.
• It is composed of fenestrated sheets of connective tissue and occasional elastic fibres.
• It bridges the scleral canal and allows passage of RGC axons and blood vessels.

Retrolaminar Region

• The retrolaminar region is the transition zone from the optic nerve head to the orbital optic nerve.
• Nerve axons become myelinated, increasing the nerve diameter and allowing for faster and more efficient signal conduction.
• The optic nerve is surrounded by the meningeal sheath, which consists of dura mater, arachnoid mater, and pia mater.

Blood Supply

• The optic disc surface is supplied by the central retinal artery (CRA) and choroid.
• The prelaminar and laminar regions are supplied by short posterior ciliary arteries, which form a circular arterial anastomosis at the scleral level, the circle of Zinn-Haller.
• The retrolaminar region is supplied by pial blood vessels.

Blood-Retina Barrier

• The blood-retina barrier is formed by a series of tight junctions between the lining glial cells and the adjacent RPE.
• Plasma proteins readily leak from the choroid into the ONH directly and through the sclera.
• The entry of proteins from the ONH into the retina is blocked by the blood-retina barrier.

Optic Nerve Head (ONH) Anatomy and Function

• The optic nerve head (ONH) is the exit point for ganglion cell axons from the globe, carrying visual information to the brain.
• The optic nerve consists of four main sections: intraocular, intraorbital, intracanalicular, and intracranial.

Retina Structure

• The retina consists of 10 layers:
  • Internal limiting membrane
  • Nerve fibre layer
  • Ganglion cell layer
  • Inner plexiform layer
  • Inner nuclear layer
  • Outer plexiform layer
  • Outer nuclear layer
  • Photoreceptor layer (inner and outer segments)
  • External limiting membrane
  • Retinal pigment epithelium
  • Choroid

Optic Disc/Optic Nerve Head (ONH)

• The optic disc is the area where the optic nerve meets the eye.
• The optic disc has a vertical oval shape and is slightly raised due to the convergence of nerve fibers.
• The optic cup is a funnel-shaped depression in the optic disc.
• The optic disc is pink due to a rich capillary supply to its rim.
• The white portion is the base of the cup.

ONH Divisions

• The optic nerve head (ONH) extends from the inner retina to a plane level with the posterior sclera.
• The ONH can be divided into four sections:
  • Superficial nerve fibre layer (A)
  • Prelaminar region (B)
  • Lamina cribrosa (C)
  • Retrolaminar region (D)

Superficial Nerve Fibre Layer (RNFL)

• The superficial nerve fibre layer consists of nerve fibres organized into bundles that converge towards the disc.
• There is no overlap between the upper and lower halves of the retinal fibres.
• The nerve fibres at the edge of the nerve serve the retina furthest from the nerve.

Prelaminar Region

• The prelaminar region consists of astrocytes and nerve fibres arranged in bundles.
• The astrocytes increase in number posteriorly, forming a sieve-like structure, the glial lamina cribrosa.

Lamina Cribrosa

• The lamina cribrosa is a band of dense, specialized extracellular matrix that provides mechanical protection to the ONH against IOP.
• It is composed of fenestrated sheets of connective tissue and occasional elastic fibres.
• It bridges the scleral canal and allows passage of RGC axons and blood vessels.

Retrolaminar Region

• The retrolaminar region is the transition zone from the optic nerve head to the orbital optic nerve.
• Nerve axons become myelinated, increasing the nerve diameter and allowing for faster and more efficient signal conduction.
• The optic nerve is surrounded by the meningeal sheath, which consists of dura mater, arachnoid mater, and pia mater.

Blood Supply

• The optic disc surface is supplied by the central retinal artery (CRA) and choroid.
• The prelaminar and laminar regions are supplied by short posterior ciliary arteries, which form a circular arterial anastomosis at the scleral level, the circle of Zinn-Haller.
• The retrolaminar region is supplied by pial blood vessels.

Blood-Retina Barrier

• The blood-retina barrier is formed by a series of tight junctions between the lining glial cells and the adjacent RPE.
• Plasma proteins readily leak from the choroid into the ONH directly and through the sclera.
• The entry of proteins from the ONH into the retina is blocked by the blood-retina barrier.

Choroid Anatomy

• Located underneath the retina, highly vascularized
• Supplied by short posterior ciliary arteries (SPCA) and long posterior ciliary arteries (LPCA), drains via vortex veins
• Thickness decreases with age, from ~200 µm at birth to 80 µm by 90 years old

Choroid Functions

• Supplies nutrients and oxygen to outer retina
• Regulates temperature through heat dissipation
• Modulates intraocular pressure (IOP) via blood flow control
• Drains aqueous humour via uveoscleral pathway, accounting for approximately 10-15% of drainage in humans

Choroid Layers

• Arterial vessels are interspersed with veins
• Consists of 5 layers, including:
  • Sattler's layer (~ 100 µm thick, contains medium to small-sized vessels)
  • Haller's layer (~ 200 µm thick, contains large-sized vessels)
  • Note: Haller's and Sattler's layers are histologically defined but do not have precise borders in imaging

Bruch's Membrane

• Thickness: ~ 2-4 µm
• Composition: elastin and collagen-rich extracellular matrix (ECM)
• Function: regulates movement of molecules between RPE and choroidal circulation
• Aging changes: fibre calcification, increased fibre cross-linkage, accumulation of fat and advanced glycation end products

Choriocapillaris

• Thickness: ~ 10 µm at fovea, thinning to ~7 µm peripherally
• Feeder arteriole from Sattler's layer supplies a hexagonal area

Suprachoroid

• Thickness: ~ 30 µm
• Transition zone between choroid and sclera
• Composition: collagen fibres, fibroblasts, and melanocytes
• Of pharmacological interest as a drug delivery target for chorioretinal layer

Clinical Assessment of the Choroid

• Indocyanine green (ICG) angiography: aka choroidal angiography, appears as generalized hyperfluorescence
• Optical coherence tomography angiography (OCTa): non-invasive, detects movement of red blood cells, produces enface imaging of retina and choroid vessels

Clinical Relevance

• Choroid is critical in retinal homeostasis
• Associated with diseases such as Vogt-Koyanagi-Harada's disease and age-related macular degeneration (AMD)

Choroid Anatomy

• Located underneath the retina, highly vascularized
• Supplied by short posterior ciliary arteries (SPCA) and long posterior ciliary arteries (LPCA), drains via vortex veins
• Thickness decreases with age, from ~200 µm at birth to 80 µm by 90 years old

Choroid Functions

• Supplies nutrients and oxygen to outer retina
• Regulates temperature through heat dissipation
• Modulates intraocular pressure (IOP) via blood flow control
• Drains aqueous humour via uveoscleral pathway, accounting for approximately 10-15% of drainage in humans

Choroid Layers

• Arterial vessels are interspersed with veins
• Consists of 5 layers, including:
  • Sattler's layer (~ 100 µm thick, contains medium to small-sized vessels)
  • Haller's layer (~ 200 µm thick, contains large-sized vessels)
  • Note: Haller's and Sattler's layers are histologically defined but do not have precise borders in imaging

Bruch's Membrane

• Thickness: ~ 2-4 µm
• Composition: elastin and collagen-rich extracellular matrix (ECM)
• Function: regulates movement of molecules between RPE and choroidal circulation
• Aging changes: fibre calcification, increased fibre cross-linkage, accumulation of fat and advanced glycation end products

Choriocapillaris

• Thickness: ~ 10 µm at fovea, thinning to ~7 µm peripherally
• Feeder arteriole from Sattler's layer supplies a hexagonal area

Suprachoroid

• Thickness: ~ 30 µm
• Transition zone between choroid and sclera
• Composition: collagen fibres, fibroblasts, and melanocytes
• Of pharmacological interest as a drug delivery target for chorioretinal layer

Clinical Assessment of the Choroid

• Indocyanine green (ICG) angiography: aka choroidal angiography, appears as generalized hyperfluorescence
• Optical coherence tomography angiography (OCTa): non-invasive, detects movement of red blood cells, produces enface imaging of retina and choroid vessels

Clinical Relevance

• Choroid is critical in retinal homeostasis
• Associated with diseases such as Vogt-Koyanagi-Harada's disease and age-related macular degeneration (AMD)

Inflammation

• Inflammation is the body's immune system response to an irritant, and can be acute or chronic
• Involves cells, proteins, and other mediators from both innate and adaptive immune systems
• Initiated by signals from injured cells or immune system cells
• Causes controlled destabilization of blood vessels and associated exudation of blood contents
• Alters blood flow in the local area

Purpose of Inflammation

• Protects against injury by eliminating its cause, limiting its consequences, and preventing sequelae
• Initiates the healing and regeneration process
• However, excessive inflammation can cause more damage than the initial injury

Clinical Signs of Inflammation

• Signs of acute inflammation include:
  • Rubor (redness)
  • Calor (heat)
  • Tumor (swelling)
  • Dolor (pain)
• Lead to loss of function

Inflammation in the Eye

• Ocular surface allergy (e.g., seasonal allergic conjunctivitis) involves eosinophil cells and serous fluid
• Corneal infection (e.g., bacterial keratitis) involves neutrophil cells and spills off the ocular surface
• Anterior chamber reaction (e.g., anterior uveitis) involves various cells and proteins (e.g., fibrin)
• Chorioretinal inflammation (e.g., posterior uveitis in toxoplasma infection) involves cells and proteins

Ocular Immune Privilege

• Cell and protein response in inflammation inside the eye can reduce vision and lead to permanent visual loss
• The system exists to limit excessive immune response inside the eye
• Evidence for ocular immune privilege includes:
  • Success of corneal transplantation
  • Unrestricted growth of non-self tumor cells inside the eye
  • Aqueous and vitreous fluids inhibit inflammatory cells in vitro
• Signaling protein TGF-β2 is high in the eye, produced by RPE and pigment epithelium of the ciliary body and iris, and "disarms" inflammatory cells

Blood-Ocular Barriers

• Three main sites of blood-ocular barriers:
  • Iris (blood-aqueous barrier)
  • Ciliary body (blood-aqueous barrier)
  • Retina (blood-retina barrier, with two separate locations)
• Blood-ocular barrier in the iris:
  • Dye stays within iris blood vessels
  • Minimal dye detected in aqueous
  • Passage of macromolecules is minimized
  • Capillaries are not fenestrated, and tight junctions form the cell-cell bond
• Blood-ocular barrier in the ciliary body:
  • Dye marker leaks from blood vessels into ciliary body tissue
  • Blood vessels in the ciliary stroma leak, but not outside the ciliary stroma
  • No barrier to macromolecules
• Blood-ocular barrier in the retina:
  • Retinal vessels do not leak marker dye
  • Choroidal vessels freely leak marker dye, but not into the retina
  • Tight junctions in capillary endothelium, and fenestrated blood vessels in the choroid
• Breakdown of blood-ocular barriers in inflammation:
  • Inflammatory cells and proteins mix with aqueous when the iris and ciliary body are inflamed
  • Tight junctions break down, allowing macromolecules to pass through

Inflammation

• Inflammation is the body's immune system response to an irritant, and can be acute or chronic
• Involves cells, proteins, and other mediators from both innate and adaptive immune systems
• Initiated by signals from injured cells or immune system cells
• Causes controlled destabilization of blood vessels and associated exudation of blood contents
• Alters blood flow in the local area

Purpose of Inflammation

• Protects against injury by eliminating its cause, limiting its consequences, and preventing sequelae
• Initiates the healing and regeneration process
• However, excessive inflammation can cause more damage than the initial injury

Clinical Signs of Inflammation

• Signs of acute inflammation include:
  • Rubor (redness)
  • Calor (heat)
  • Tumor (swelling)
  • Dolor (pain)
• Lead to loss of function

Inflammation in the Eye

• Ocular surface allergy (e.g., seasonal allergic conjunctivitis) involves eosinophil cells and serous fluid
• Corneal infection (e.g., bacterial keratitis) involves neutrophil cells and spills off the ocular surface
• Anterior chamber reaction (e.g., anterior uveitis) involves various cells and proteins (e.g., fibrin)
• Chorioretinal inflammation (e.g., posterior uveitis in toxoplasma infection) involves cells and proteins

Ocular Immune Privilege

• Cell and protein response in inflammation inside the eye can reduce vision and lead to permanent visual loss
• The system exists to limit excessive immune response inside the eye
• Evidence for ocular immune privilege includes:
  • Success of corneal transplantation
  • Unrestricted growth of non-self tumor cells inside the eye
  • Aqueous and vitreous fluids inhibit inflammatory cells in vitro
• Signaling protein TGF-β2 is high in the eye, produced by RPE and pigment epithelium of the ciliary body and iris, and "disarms" inflammatory cells

Blood-Ocular Barriers

• Three main sites of blood-ocular barriers:
  • Iris (blood-aqueous barrier)
  • Ciliary body (blood-aqueous barrier)
  • Retina (blood-retina barrier, with two separate locations)
• Blood-ocular barrier in the iris:
  • Dye stays within iris blood vessels
  • Minimal dye detected in aqueous
  • Passage of macromolecules is minimized
  • Capillaries are not fenestrated, and tight junctions form the cell-cell bond
• Blood-ocular barrier in the ciliary body:
  • Dye marker leaks from blood vessels into ciliary body tissue
  • Blood vessels in the ciliary stroma leak, but not outside the ciliary stroma
  • No barrier to macromolecules
• Blood-ocular barrier in the retina:
  • Retinal vessels do not leak marker dye
  • Choroidal vessels freely leak marker dye, but not into the retina
  • Tight junctions in capillary endothelium, and fenestrated blood vessels in the choroid
• Breakdown of blood-ocular barriers in inflammation:
  • Inflammatory cells and proteins mix with aqueous when the iris and ciliary body are inflamed
  • Tight junctions break down, allowing macromolecules to pass through