In this section, students will be introduced to those anatomical and physiological concepts that are important to the study of ocular disease. In general, comments on pathophysiology will be covered in lectures dealing with each ocular structure. It will be very important to review the following notes prior to those lectures.
# Orbit
- Cavity that contains eye; cone shaped, with apex posteriorly
# Osteology
Horse, cow: complete bony orbit
Dog, cat: bony orbit is incomplete dorsolaterally; orbital ligament spans from zygomatic process of frontal bone to frontal process of zygomatic arch
Optic foramen: optic nerve, internal ophthalmic artery
Orbital fissure (orbitorotundum in cow): CNs 3,4, &6, ophthalmic br. of CN 5, superior ophthalmic vein.
# Vasculature
- External ethmoidal artery and external ophthalmic artery (branch of maxillary artery) Superior and inferior ophthalmic veins → orbital plexus → cavernous sinus Angular vein medially
# Innervation
Sensory
CN 2 and ophthalmic branch of CN 5
Motor
To extraocular muscles and levator palpebrae
CN 3: dorsal rectus, medial rectus, ventral rectus, ventral oblique, levator palpebrae
CN 4: superior oblique
CN 6: lateral rectus, retractor bulbi
Sympathetic
Ill-defined orbital musculature (sometimes termed “muscularis
orbitalis”), responsible for maintaining orbital tone.
# Extraocular muscles
Originate around orbital fissure; rectus muscles insert approx. 5-7 mm posterior to the limbus, retractor bulbi inserts just behind equator of globe.
Dorsal, medial, ventral and lateral recti turn globe in their respective directions.
Retractor bulbi pulls globe posteriorly
Dorsal oblique causes intorsion (i.e., 12 o’clock position of globe moves medially) via the trochlea, ventral oblique causes extorsion (i.e., 12 o’clock position moves laterally)
# Periorbital fat
- Occupies dead space in and around the muscle cone.
# Periorbita
- Periosteum lining the orbital cavity.
# Tenon’s capsule
- Reflection of periorbita over muscles and globe.
# Retrobulbar area
- Term used to describe area behind posterior to the globe.
# Globe
Three approximately concentric spheres
Fibrous tunic - cornea anteriorly, sclera posteriorly
Vascular tunic - iris anteriorly, ciliary body in middle, choroid posteriorly
Neural tunic - retina
Anterior segment vs. posterior segment
Anterior segment defined as lens and all structures anterior to it;
posterior segment is defined as all structures posterior to the lens.
Fluid chambers of the eye
Anterior chamber - between cornea and iris; contains aqueous humor
Posterior chamber - between ciliary body and iris; also contains aqueous humor
Vitreous chamber - behind lens; contains vitreous humor and constitutes 80% of eye volume.
# Adnexa
Overview * Defined as orbit and contents, eyelids, lacrimal/nasolacrimal structures, conjunctiva, nictitans; the following discussion covers all of the above except orbit (covered previously).
# Eyelids
# Gross anatomy
Palpebral fissure - opening between upper and lower lids.
Medial and lateral canthi - medial and lateral corners of palpebral fissure.
# Histologic anatomy
Muscles
Levator - raises lid; innervated by CN 3; acts in conjunction with dorsal rectus.
Muller’s muscle - sympathetically controlled muscle that provides some tone to upper lid and helps raise upper lid during flight or fight response.
Orbicularis oculi - closes palpebral fissure; innervated by CN 7.
Lateral angular retractor - also called lateral palpebral (canthal) ligament; maintains almond shape to palpebral fissure; important landmark during enucleation.
Medial palpebral (or canthal) ligament - Also helps maintain almond shape to fissure.
Glands
Tarsal (aka Meibomian) - Row of glands just under the conjunctiva approx. 4 mm posterior to the lid margin. Duct goes from gland to pore on eyelid margin. Phospholipid secretion that contributes to the tear film.
Zeis - open into ciliary follicles; sebaceous secretion.
Moll - open onto margin near cilia; modified sweat gland.
Tarsal plate (also called “tarsus”): Fibrous tissue that gives lid form and support; relatively poorly developed in domestic animals.
Nasolacrimal puncta: Upper and lower openings in the conjunctiva near the medial canthus; function to drain tears away from the eye.
Cilia: “Eyelashes” - located on anterior surface of upper lid near the margin in most species; cats lack cilia.
# Physiology
Upper lid more mobile, closes from lateral to medial to spread tears and direct them into the nasolacrimal puncta.
Limits entry of light into the eye.
Protection of globe via palpebral reflex and menace response.
# Lacrimal/Nasolacrimal system
# Pre-corneal tear film - 3 layers
Lipid layer: Most anterior of the 3 layers of the tear film Prevents evaporation of aqueous portion of tear film. Produced by the tarsal (Meibomian) glands
Aqueous layer: Middle layer, comprises majority of tear film. Produced by main lacrimal gland (50%) and nictitating membrane gland (50%)
Mucoid layer: Inner layer, acts as surfactant to help spread tear film across cornea. Produced by conjunctival goblet cells.
# Tear production
Main lacrimal gland - on dorsolateral surface of globe.
Gland of the nictitans - on ventroposterior aspect of nictitans.
# Tear drainage
- Upper and lower nasolacrimal puncta → upper and lower canaliculi → both canaliculi join at the nasolacrimal sac → nasolacrimal duct → nasal cavity.
# Functions of tears
Corneal nourishment
Medium for sweeping debris from corneal surface
Lubricate corneal surface to facilitate movement of lids and nictitans Refractive surface
# Conjunctiva
# Overview/ Gross anatomy
Mucous covering the inner of the lids and the anterior portion of the globe.
Bulbar conjunctiva - portion covering globe.
Palpebral conjunctiva - portion covering inner surface of the lids
Fornix (or cul-de-sac) - portion where bulbar and palpebral portions come together.
# Histologic anatomy
Stratified squamous epithelium with microvilli, coated with mucopolysaccharides to help stabilize tear film.
Goblet cells - located primarily in palpebral conjunctiva and fornix, secrete mucin layer of tear film. Conjunctiva associated lymphoid tissue (CALT)
# Functions of conjunctiva
Prevents corneal desiccation via secretions of goblet cells and blinking.
Prevents microbe invasion via CALT and Ab secretion (the conjunctiva of most domestic species normally contains high numbers of potential pathogens).
# Nictitating Membrane (aka third eyelid)
# Overview/ Gross anatomy
Located in ventromedial conjunctival sac.
Sweeps across cornea in a dorsolateral direction; movement is passive, occurring when the animal retracts the globe into to orbital cavity.
Avian - located dorsomedially; movement is active and in a ventrolateral direction
# Histologic anatomy
T-shaped cartilage gives support to NM.
NM gland on ventroposterior aspect of nictitans, surrounds shaft of T-cartilage.
Anterior and posterior surfaces (also called palpebral and bulbar surfaces, respectively) of NM covered with conjunctiva.
Numerous lymphoid follicles located on bulbar surface.
Muscle not found in NM of most species; cat has some smooth muscle, the function of which is not clear.
# Functions of NM
Secretion of tears.
Protection of globe.
# Cornea and Sclera
# Cornea
# Overview/ Gross anatomy
Comprises anterior 1/5 of fibrous tunic
Approximately 0.5-0.6 mm thick
Joins sclera in transitional zone called “limbus”
# Histologic anatomy
# Epithelium
Anterior most layer of cornea
Constantly replenishing tissue (turnover approx. 7 days)
Divided into 3 layers
Basal cells: Caudal layer; single cell thickness; attached to basement membrane via hemidesmosomes. Only epithelial layer to undergo mitosis
Wing cells: Middle transitional layer between basal cells and squamous cells. 2-3 cells thick in dog
Squamous cells: Anterior layer, 2-3 cells thick in dog.
Microplicae and microvilli on surface help stabilize tear film
Tight junctions between squamous cells limit permeability Nonkeratinized
# Bowman’s layer
Condensation of anterior stroma just beneath basal epithelium
Present in primates
Absent in most domestic species (equivocal in cows)
# Stroma
90% of corneal thickness
Collagen and GAGs; low cellularity
Collagen in lamellae that span corneal diameter
Keratocytes - cells that are responsible for maintenance of collagen, can transform into fibroblasts to form scar tissue
# Descemet’s membrane
- Basement membrane of endothelium
# Endothelium
Single layer of hexagonal cells Posterior-most layer
Important in maintaining state of relative dehydration of cornea
# Physiology
# Corneal transparency
Devoid of blood vessels (except at limbus)
Nonpigmented (except at limbus)
Nonkeratinized surface epithelium
Size and organization of stromal collagen fibrils (bundles spaced at regular intervals)
Relative state of dehydration (NaKATPase pump in endothelium pumps water out of stroma into anterior chamber).
# Sclera
# Overview/ Gross anatomy Posterior 4/5 of fibrous tunic
- Composition similar to cornea, but not transparent
# Histologic anatomy
# Intrascleral venous plexus
Anterior stromal veins
Collect aqueous from iridocorneal angle, transfers to systemic circulation Circumferentially oriented in dogs, cats; 4-5 mm posterior to limbus Radially oriented in horses
# Lamina cribrosa
Circular area of sclera at posterior pole
Contains small perforations through which optic nerve axon bundles exit eye.
# Uveal Tract
# Overview
Anterior uvea: iris and ciliary body
Posterior uvea: choroid
Very vascular, darkly pigmented
# Iris
# Gross anatomy
Ciliary zone - peripheral half of iris
Pupillary zone - central half
Collarette - line of demarcation between pupillary and ciliary zones
Iris rests against anterior surface of lens
# Histologic anatomy - divided into 4 layers:
Anterior border layer
Stroma: Loose collagenous fibers. Contains pupillary sphincter muscle.
Dilator muscle layer: Myoepithelial; not as strong as sphincter muscle
Posterior epithelium: Sometimes extends axially into pupil as “pupillary ruff”
# Pupil
Hole in center of iris
Round in dog, vertical slit in cat, horizontal oval in horse, cow
Corpora nigrum (or granula iridica): spherical protuberances of anterior and posterior epithelial layers that extend into the pupil; present in ungulates.
# Vascular supply
Long posterior ciliary arteries: Enter iris at 3 and 9 o’clock positions, each then divides into dorsal and ventral branches
Major arterial circle: Formed by dorsal and ventral branches of l.p.c.a., located in peripheral iris
Radial arteries: From major arterial circle toward pupil
# Innervation
Sensory: Long posterior ciliary nerves (ultimately from ophthalmic br. of CN5)
Pupillary sphincter: Parasympathetically innervated
Dilator: Sympathetically innervated
# Physiology
Interendothelial tight junctions of iridal vasculature prevent macromolecules from entering aqueous humor (therefore contributes to “blood aqueous barrier”)
Iris muscles controlled by autonomic nervous system
Pupil size controls amount of light entering eye
# Ciliary body
# Gross anatomy
Circumferential structure (i.e., doughnut shaped) posterior to iris Pars plana - posterior half of doughnut; flat
Pars plicata - anterior half of doughnut; thrown into 75-100 folds called ciliary processes
Zonules extend from processes and valleys between them to lens equator
# Histologic anatomy - divided into 3 layers:
Stroma: Adjoins sclera
- Three muscles: longitudinal, radial and circumferential; longitudinal inserts anteriorly on trabecular meshwork of iridocorneal angle
Pigmented epithelium: Overlays stroma. Continuous with dilator muscle layer of iris
Nonpigmented epithelium Overlays pigmented epithelium: Continuous with posterior epithelium of iris Secretes aqueous humor
# Vascular supply
Long posterior ciliary arteries: Branches sent posteriorly to ciliary body just before entering iris
Anterior ciliary arteries: Travel anteriorly with rectus muscles, pierce sclera just posterior to limbus
# Innervation
Sensory: Long posterior ciliary nerves
Ciliary muscles: Parasympathetic innervation via short posterior ciliary nerves
Ciliary epithelium: Contains sympathetic innervation, the function of which is unknown
# Physiology
Accommodation: Thickening of lens in anterior-posterior dimension for focusing on near objects Accomplished via contraction of longitudinal ciliary muscle
Trabecular meshwork: Iridocorneal angle structure through which aqueous drains. Contains small pores which enlarge when longitudinal ciliary muscle contracts
Production of aqueous humor:
Diffusion
Active transport
Most important process in aqueous production
NaKATPase located between NPE cells; Na+ pumped into posterior chamber, water follows
Carbonic anhydrase - enzyme in NPE; necessary for aqueous production
Ultrafiltration
- Movement of fluid in accordance with hydrostatic forces
Blood-aqueous barrier
Interendothelial junctions of iris vasculature Interepithelial junctions of NPE
Restricts entry of macromolecules (proteins, especially fibrinogenic proteins) into aqueous humor
# Iridocorneal angle
# Overview
- Area where iris meets cornea Aqueous humor drainage
# Structures comprising the iridocorneal angle
Pectinate ligaments
- Collagenous beams spanning from peripheral anterior iris to corneal endothelium Large pores
Trabecular meshwork
- Smaller pores, offers some resistance to aqueous outflow
Ciliary cleft
- Depression in anterior ciliary body where trabecular meshwork is located
Intrascleral venous plexus
- Shunts aqueous from angle to systemic circulation
# Aqueous Humor Dynamics
# Why have aqueous?
- Nourishment of avascular anterior segment structures
# Aqueous flow
- NPE of ciliary body → posterior chamber → pupil → anterior chamber → between pectinate ligaments → through trabecular meshwork → into intrascleral venous plexus → into systemic circulation
# Aqueous production
- See “Ciliary Body - Physiology”
# Aqueous drainage
Facility of outflow
- Ease with which aqueous humor escapes
Conventional outflow
- Outflow via trabecular meshwork and intrascleral venous plexus described above
Unconventional (aka uveoscleral) outflow
- Some fluid will bypass meshwork to be absorbed directly into anterior ciliary body → supraciliary space → systemic circulation. Minor pathway in dog, cat, major pathway in horse
# Establishment and maintenance of intraocular pressure
Outflow resistance
- Primarily at trabecular meshwork and intrascleral venous plexus
Maintaining “normal” IOP
- Balance between production and drainage of aqueous humor
# Choroid
# Gross anatomy
Posterior 2/3 of uvea
Anterior choroidal margin meets posterior aspect of ciliary body stroma Very vascular, darkly pigmented
# Histologic anatomy - divided into 3 layers:
Suprachoroidea
- Potential space between choroidal stroma and sclera Long posterior ciliary arteries and nerves reside here Site of unconventional aqueous humor outflow
Stroma
Large vessel layer (posterior)
Intermediate vessel layer (anterior)
- Tapetum: Highly reflective layer to aid nocturnal vision. Triangular on frontal view, located dorsally.
Choriocapillaris
- Single layer of capillaries between anterior stroma and retinal pigmented epithelium
# Physiology
- Choriocapillaris supplies nutrition to outer half of retina
# Lens
# Overview
- Accommodation in near vision (relatively poorly developed in domestic species)
# Gross anatomy
Anterior and posterior poles
Equator
Ciliary zonules (suspensory ligaments) from equator to ciliary body
# Histologic anatomy
# Capsules
Anterior and posterior; basement membrane of epithelium
Posterior epithelium only present in utero, so posterior capsule very thin; anterior capsule thickens throughout life
# Epithelium
- Postnatally only present anteriorly and at equator Equatorial epithelial cells elongate to form lens fibers
# Cortex Outermost fibers
- Y-sutures; visible lines where lens fibers come together
# Nucleus Innermost fibers
- Subdivided into embryonal, fetal and adult nuclei
# “Geographic anatomy”
Axial (aka polar) vs. equatorial
Terms used to describe location of lens opacities
# Physiology
# Protein content
- Highest concentration of protein in body (approx. 35%)
# Na+ pump
- Found in lens fiber membranes and epithelium Maintains low intralenticular water content
# Glucose metabolism - glucose readily enters lens
Glycolysis
Responsible for 80% of glucose metabolism
Initial enzyme: hexokinase; saturated at glucose concentration of 200 mg/dl
TCA cycle
- 5%
Pentose monophosphate shunt
- 15%
Sorbitol pathway
Usually negligible, utilization increases when hexokinase saturated
End product is fructose, which can’t escape lens
# Glutathione and sulfhydryl proteins
- Maintained in reduced form - prevents abnormal cross linking of proteins and subsequent opacification
# Production of lens fibers
Equatorial epithelial cells
Fibers meet in Y-sutures
# Accommodation
- Contraction of ciliary body muscles → loosening of ciliary zonules → lens assumes more spherical shape (i.e., thickens in anterior-posterior dimension) → brings near objects into focus.
# Maintenance of transparency
High concentration of crystalline proteins
Few intracellular organelles
Very little interfibrillar water
Fibers densely packed
Avascular
Nonpigmented
# Vitreous
# Overview/ Gross anatomy
Occupies 75-80% of volume of eye
Transparent, avascular, low cellularity Gel-like consistency
# Histologic anatomy
Cloquet’s canal: Remnant following regression of hyaloid artery (H. artery regresses within a few weeks of birth in most species)
Primary vitreous: Immediately surrounding Cloquet’s canal Secondary vitreous: Majority of vitreous body
Tertiary vitreous: Synonymous with ciliary zonules
# Physiology
98% water suspended in hyaluronic acid and collagen matrix
Often liquefies in response to posterior segment disease
# Retina
# Overview
- Purpose: Transforms electromagnetic radiation (i.e., visible light) into an electrochemical signal that can be interpreted by the brain
# Gross anatomy
Ora Ciliaris Retinae (ora serrata in primates)
Junction of anterior retina and posterior ciliary body
Neurosensory retina
Innermost 90% of retina
Peripherally, continues anteriorly as nonpigmented ciliary body epithelium
Retinal pigmented epithelium
- Peripherally, continues anteriorly as pigmented ciliary body epithelium
Area centralis
Central visual area
# Histologic anatomy
# Classically divided into 10 layers (see Fig 15-1, p. 415 in Severin ).
Retinal pigmented epithelium
Photoreceptors
External limiting membrane
Outer nuclear layer
Outer plexiform layer
Inner nuclear layer (includes bipolar cells)
Inner plexiform layer
Ganglion cell layer
Nerve fiber layer
Internal limiting membrane
# Three neuron chain in neurosensory retina transduces photic signal into electrochemical signal and sends to brain
Photoreceptors
Rods - very sensitive; dim light vision
Cones - bright light vision, color vision, most acute vision
Rod outer segment: Thousands of membranous discs stacked like pancakes; rhodopsin embedded in membranes
Rods out number cones 100:1 in peripheral retina, 10:1 in area centralis
Bipolar cell
- Transfers potential generated in photoreceptor to ganglion cell
Ganglion cell
Axons of ganglion cells make up optic nerve
Transfers potential from bipolar cells to midbrain (for pupillary light responses) and visual cortex
# RPE
Single cell layer between neurosensory retina and choriocapillaris
Important supporting role for photoreceptors
Nonpigmented dorsally to expose tapetum
# Müeller cell
- Retinal “support” cell that spans from RPE to internal limiting membrane
# Vascular supply
Inner half of retina
Retinal vessels located in nerve fiber layer
Outer half of retina
Choriocapillaris
Short posterior ciliary arteries
9-12 arteries that pierce the sclera around the optic nerve to become
retinal vessels
# Various vascular patterns seen in domestic animals:
Holangiotic - all quadrants, from peripapillary to periphery, supplied with retinal vessels (dog, cat)
Merangiotic - only selected sectors of retina supplied with vessels (rabbit)
Paurangiotic - vessels in all quadrants, but only in vicinity of optic disc (horse)
Anangiotic - no retinal vessels (avian)
# Physiology of neurosensory retina (will use rod as example)
Similarity to other sensory systems
Receptor cell, 3 neuron chain to brain
Electrical state of PR cell in dark
Relatively depolarized (approximately - 30 mV, vs. - 70 mV found in most excitable cells) due to outer segment permeability to Na+
Inner segment NaKATPase pump removes Na+ from cell
Inhibitory neurotransmitter between photoreceptor and bipolar cell continuously released in dark
# Transduction
Rhodopsin
Photopigment composed of the protein opsin and 11-cis retinal
Photon causes configurational change that results in closure of outer segment Na+
channels and, therefore, hyperpolarization
Hyperpolarization
- Causes cessation of release of inhibitory neurotransmitter Bipolar cell therefore “switched on”
# PR-bipolar interaction
- Removal of inhibitory neurotransmitter creates typical depolarizing potential in bipolar cell
# Bipolar-ganglion cell interaction
- Typical depolarization
# Optic Nerve
Collection of axons of ganglion cells
Lamina cribrosa - Scleral structure through which axons exit the globe
Optic disc (aka papilla)
# Location in fundus
Just ventral to geometric axis in most species
Dog: may be in tapetal area, in non-tapetal area, or at tapetal/non-tapetal junction, depending on size of tapetum
# Myelination
Dog: myelination of ganglion cell axons extends for 1-2 mm into retina (i.e., disc is myelinated)
Other species: disc not myelinated.
# Physiologic cup or pit
- Small depression in center of canine disc Represents posterior turn of ganglion cell axons
# Optic chiasm
- Crossing of optic nerves to contralateral sides
# Degree of decussation in different species
Primates: 50%
Horse: 80%
Cat: 60%
Avian: 100%
Dog: 70%
# Optic tracts
- Between chiasm and brain
# Destinations of optic nerve
Midbrain - for pupillary light responses
Lateral geniculate nucleus - to be transferred to visual cortex