Eye and orbit

The eyes are paired, sensory organs that enable vision. Anatomically, the outer portion of the eye is divided into three layers: the fibrous tunic (cornea and sclera), the vascular tunic (choroid, iris, and ciliary body), and the nervous tunic (retina). The eye is further divided into an anterior segment, which contains the lens and structures anterior to it, and a posterior segment, which contains the vitreous humor and the retina. The lens is suspended between the pupil and the vitreous body by ligaments attached to the ciliary body. The anterior eye is subdivided further into two chambers: the posterior chamber (between lens and iris) and the anterior chamber (between iris and cornea), both of which are filled with aqueous humor. Functionally, the eye can be divided into structures that perceive light (components of the visual pathway) and structures that refract light (refractive media). The visual pathway begins with the first-order neurons of the retina, retinal rods and cones, which convert the optical image into neuronal signals, which are transmitted to the brain. The refractive media, comprising the cornea, lens, aqueous humor, and vitreous body, directs and refracts light to the posterior region of the retina. The eye receives its arterial supply from branches of the ophthalmic artery and drains into the ophthalmic vein. Cranial nerves mediate vision (CN II) and eye movement (CN III, IV, VI), while accommodation is mediated by fibers of the autonomic nervous system. The eyeball lies within the bony orbit, which has several openings for the passage of neurovascular structures. Accessory visual structures include the lacrimal gland and the eyelid. The lacrimal gland secretes tear fluid, which reduces friction and cleans the eye, while the eyelid protects the eyeball from excessive light, dryness, and foreign bodies. The development of the eye and accessory visual structures occurs between the 3^rd and 10^th week of embryonic development. Extraocular muscles connect the eyeball to the orbit and control movement of the eyelid as well as the eye.

• Layers
  • Fibrous tunic (external layer): cornea and sclera
  • Vascular tunic/uvea (middle layer): choroid, ciliary body, pigmented epithelium, iris
  • Nervous tunic (innermost layer): retina

• Segments
  • Anterior segment:
    • Cornea: refracts light
    • Iris: regulates the amount of light impinging on the retina
    • Lens: refracts light and focuses it on the retina by accommodating its convexity according to the distance of objects focused on
    • Chambers
      • Anterior chamber: between cornea and iris
      • Posterior chamber: between lens and iris
  • Posterior segment:
    • Vitreous chamber: between lens and retina, contains vitreous humor
    • Retina: pigment cells translate light signals into neuronal signals that travel to the brain via the optic nerve (CN II)
    • Choroid: supplies the retina with nutrients
    • Sclera: protects the eye
• Orbit: bony structure that contains the eyeball and several openings for the passage of nerves, vessels, and lymphatics
• Vasculature: primarily derived from the ophthalmic artery
• Innervation: Cranial nerves mediate vision (CN II) and eye movement (CN III, IV, VI), accommodation is mediated by fibers of the autonomic nervous system.
• Accessory visual structures
  • Eyelids: protect the eyes from excessive light, dryness, and foreign bodies
  • Lacrimal apparatus: supplies tear fluid for the surface of the eyeball and the eyelid, minimizing friction and cleaning the eye (tear film)
  • Extraocular muscles: control eye movement and elevation of the eyelid

Fibrous tunic (external layer)

The outer, fibrous coat of the eyeball is composed of the transparent cornea and the opaque sclera. Together, they form a protective capsule and maintain the eye's spherical shape. The cornea allows light to enter and is the major refractive surface of the eye, while the sclera provides attachment to the extraocular muscles.

Vascular tunic (middle layer): the uvea

The pigmented, vascular tunic of the eye consists of the iris, the ciliary body, and the choroid.

Innermost layer: the retina (nervous tunic)

On the gross anatomical level, the retina's most important features are the optic disc and the macula. On a microanatomical level (see “Microscopic anatomy” below), it consists of neural cells that register light signals and translate them into neuronal signals that are transmitted to the brain.

Segments of the eye

Chambers of the eye

Pathway of aqueous humor outflow

• Trabecular outflow (∼ 85%) ^[1]
  • Ciliary body (nonpigmented epithelium) → posterior chamber → through the pupil → anterior chamber → trabecular meshwork with spaces of Fontana (in the iridocorneal angle) → canal of Schlemm → episcleral vessels
  • Increased by muscarinic (M₃) receptor agonists (e.g., pilocarpine and carbachol)
• Uveoscleral outflow (∼ 15%)
  • Ciliary body (nonpigmented epithelium) → posterior chamber → through the pupil → anterior chamber → direct drainage into uvea and sclera
  • Increased by prostaglandin agonists (e.g., latanoprost and bimatoprost)
• Aqueous humor production is decreased by carbonic anhydrase inhibitors (e.g., acetazolamide), α2 agonists (e.g., clonidine, brimonidine), and beta blockers (e.g., timolol)

Arteries

The blood supply to the eye is primarily derived from the ophthalmic artery, a branch of the internal carotid artery that reaches the eye via the optic canal. The arteries listed below are all branches of the ophthalmic artery.

• Central artery of the retina
  • Main branch of the ophthalmic artery
  • Supplies the retina and parts of the optic nerve
  • A terminal artery (no anastomosis)
  • Travels in the optic nerve
  • Divides into superior, inferior, nasal, and temporal branches
• Medial palpebral arteries: anastomoses with the lateral palpebral arteries to supply the eyelid
• Long posterior ciliary arteries: supply the iris and ciliary body
• Short posterior ciliary arteries: supply the choroid
• Muscular branches
  • Supply the extraorbital muscles
  • Branch into the anterior ciliary arteries that supply the iris
• Supraorbital artery
  • Supplies part of the orbit, the forehead, and the scalp
  • Passes through the supraorbital foramen
• Frontal artery: supplies the forehead and the scalp
• Lacrimal artery
  • Supplies the lacrimal gland, eyelid, and conjunctiva
  • Branches into the lateral palpebral arteries
• Dorsal nasal artery: supplies the lacrimal sac

Veins

• Ophthalmic veins
  • Superior ophthalmic vein: travels parallel to the ophthalmic artery
  • Inferior ophthalmic vein: may divide into two branches
    • One branch passes through the inferior orbital fissure
    • The other branch passes through the superior orbital fissure
  • Drain into the cavernous sinus
• Central vein of the retina
  • Main pathway of retinal venous drainage
  • Travels in the optic nerve
  • Drains blood from the capillaries of the retina
  • Drains into either superior ophthalmic vein or into the cavernous sinus directly
  • Occlusion → restriction in blood supply (ischemia) and/or swelling (edema) → severe damage to the retina or blindness

The angular vein forms an anastomosis from the superficial facial veins to the intracranial veins. Infections from the midface can spread via the angular vein to the cavernous sinus and sinus veins, potentially causing cavernous sinus thrombosis with life-threatening complications.

Cavernous sinus thrombosis is one of the possible causes of cavernous sinus syndrome, which is characterized by a partial or complete loss of function of the cranial nerves passing through (i.e., CN III, CN IV, CN V₁, and CN V₂).

Nerves

• Ophthalmic nerve (CN V₁)
  • Part of the trigeminal nerve arising from the trigeminal ganglion
  • Supplies sensation to the forehead, anterior scalp, lacrimal gland, upper eyelid, and eyeball
  • Receives sympathetic and parasympathetic nerve fibers that facilitate pupil dilation and innervate the ciliary body, iris, lacrimal gland, conjunctiva, and cornea
  • Enters the orbit through the superior orbital fissure where it divides into its branches
• Branches of the ophthalmic nerve
  • Lacrimal nerve
    • Enters the orbit through the superior orbital fissure
    • Innervates the lacrimal gland, the skin of the upper eyelid, and the conjunctiva
    • Communicates with the zygomatic branch of the maxillary nerve (CN V₂), which may carry postganglionic parasympathetic fibers to the lacrimal gland
  • Frontal nerve: enters the orbit through the superior orbital fissure and divides into
    • Supratrochlear nerve: innervates the forehead, scalp, and upper eyelid
    • Supraorbital nerve: innervates the frontal sinus, conjunctiva, scalp, forehead, and upper eyelid
  • Nasociliary nerve
    • Sensory limb (afferent limb) of the corneal reflex
    • Enters the orbit through the superior orbital fissure and divides into
      • Infratrochlear nerve
      • Posterior ethmoidal nerve
      • Anterior ethmoidal nerve
      • Long ciliary nerves
        • Supply iris, ciliary body, and cornea
        • Postganglionic sympathetic fibers to the iris dilator muscle derived from the superior cervical ganglion
        • Sympathetic fibers to facial sweat glands and smooth eyelid muscle
      • Communicating branch to the ciliary ganglion

• Optic nerve (CN II)
  • Leaves the orbit through the optic canal
  • The crossing of the two optic nerves, one from each eye, forms the optic chiasm.
• Maxillary nerve (CN V₂)
  • Second branch of the trigeminal nerve
  • Sensory innervation of the lower eyelid
• Ciliary ganglion
  • Parasympathetic ganglion
  • Located behind the eyeball, between the lateral rectus muscle and the optic nerve
  • Short ciliary nerves arise from the ciliary ganglion
    • Postganglionic parasympathetic fibers that innervate the ciliary muscle and the iris sphincter muscle
    • Sympathetic postganglionic fibers (derived from the superior cervical ganglion) to the iris dilator muscle

Long ciliary nerves: long pupil diameter (mydriasis). Short ciliary nerves: short pupil diameter (miosis).

The orbit is a bony structure formed by the frontal, maxillary, ethmoid, sphenoid, lacrimal, and zygomatic bones. It contains the eyeball and openings for the passage of the optic nerve (CN II), vessels, and lymphatics.

Walls of the orbit

• Superior (roof): lesser wing of the sphenoid bone and orbital portion of the frontal bone
• Inferior (floor): orbital surfaces of the maxilla, zygomatic, and palatine bones
• Medial: orbital plate of the ethmoid bone, body of the sphenoid bone, frontal bone, lacrimal bone, and the maxilla
• Lateral: greater wing of the sphenoid, orbital plate of the frontal bone, and the frontal process of the zygomatic bone

Openings of the orbit

The eyelid protects the eyeball from excessive light, dryness, and foreign bodies. It receives sensory innervation from branches of the trigeminal nerve (CN V): the ophthalmic nerve (CN V₁) innervates the upper eyelid, while the lower eyelid receives sensory innervation from the maxillary nerve (CN V₂). The palpebral fissure (aperture) is formed by the upper and lower eyelid, which meet in the lateral and medial canthi. The following structures form the eyelid:

• Skin and subcutaneous tissue
  • Thinnest skin of the body
  • Very small amount of fatty tissue
  • No subcutaneous tissue over the lateral and medial palpebral ligaments
• Orbicularis oculi muscle
  • Innervated by the facial nerve (CN VII)
  • Closes the eye
• Orbital septum
  • Connective tissue that forms the anterior boundary of the orbit
  • Runs from the margin of the eyelids to the periosteum of the orbital margin
  • Within the eyelid, the orbital septum thickens and forms the tarsal plates, which provide stability to the eyelid.
  • Landmark to differentiate between preseptal cellulitis and orbital cellulitis
• Tarsal plates
  • Thickened extensions of the orbital septum composed of dense connective tissue
  • Contain tarsal glands
  • Superior tarsal plate: insertion site of the superior tarsal muscle
  • Inferior tarsal plate: smaller, elliptical form
• Levator palpebrae superioris
  • Originates from the roof of the orbit and inserts into the upper eyelid on the superior border of the tarsal plate
  • Site of origin of the superior tarsal muscle (its primary function is to raise the eyelid and the levator palpebrae superioris)
  • Innervated by the oculomotor nerve (CN III)
  • Elevates the upper eyelid (opens the eye)
• Conjunctiva
  • Highly vascularized mucus membrane that lines the inside of the eyelids and the sclera
  • Divided into two distinct layers
    • Palpebral (tarsal) conjunctiva: lines the inner surface of the eyelid
    • Bulbar conjunctiva: lines the anterior surface of the eyeball
    • The palpebral conjunctiva transitions to bulbar conjunctiva in the superior and inferior fornices
  • Accessory glands in the conjunctiva produce tear fluid (smaller volume than the lacrimal apparatus)

Lacrimal apparatus

The lacrimal apparatus supplies tear fluid to the surface of the eyeball and the eyelid, minimizing friction and cleaning the eye (tear film).

• Composition of tear fluid: consists of three layers
  • Mucous layer (innermost layer)
    • Mucins produced by goblet cells on the inside of the conjunctiva
    • Hydrophilic layer that ensures stability and even distribution of the tear film
  • Aqueous layer (middle layer)
    • Isotonic fluid composed mainly of water, electrolytes (Na⁺, K⁺, Cl^-, HCO₃^-), proteins (lysozyme, lactoferrin, defensins), EGF, IgA secreted by the lacrimal gland
    • Supplies the eye with nutrients
    • Disposes of waste products
    • Hydrates the cornea and lubricates the eye
  • Lipid layer (outermost layer)
    • Oils produced by Meibomian glands
    • Prevents drying and cooling of the eye
• Lacrimal gland
  • Located on the upper lateral part of the orbit, on the surface of the levator palpebrae superioris and the lateral rectus muscle
  • Serous gland with tubuloalveolar secretory elements that secretes the watery fluid that makes up the aqueous layer of the tear fluid
  • Drains via the 12 lacrimal ducts into the superior conjunctival fornix
  • Innervated by parasympathetic fibers of the facial nerve (CN VII) via the pterygopalatine ganglion
• Tarsal glands (Meibomian glands)
  • Sebaceous glands
  • Located within the tarsal plate with orifices at the rim of the marginal zone of the conjunctiva
  • Produce the oils that make the lipid layer of the tear film
• Lacrimal sac
  • Dilated portion of the nasolacrimal duct
  • Gathers tear fluid
• Nasolacrimal duct: drains into the inferior meatus of the nose
• Lacrimal punctum: an opening near the medial eyelid that collects tears produced by the associated lacrimal gland

Pathway of tears

• Produced in the lacrimal gland (below lateral eyebrow) → lacrimal ducts → superior conjunctival fornix → anterior eyeball → lacus lacrimalis → lacrimal canaliculi (at the inner canthus) → lacrimal sac → nasolacrimal duct → inferior nasal meatus

Layers of the cornea

The cornea consists of five layers (from anterior to posterior)

• Corneal epithelium: stratified squamous, nonkeratinizing epithelium
• Bowman membrane: collagen fibrils, no cells
• Substantia propria: collagen fibers, fibroblasts, proteoglycans, water
• Dua layer: thin, collagen fibers
• Descemet membrane: the basement membrane of the corneal endothelium (located between the stromal tissue of the cornea and the corneal endothelium)
• Endothelium: single layer of squamous cells

Layers of the iris

The color of the iris (eye color) is determined primarily by melanocyte concentration in the anterior border and, to a lesser extent, in the iris stroma.

• Anterior border layer: network of fibroblasts with an underlying layer of melanocytes (modified layer of the iris stroma)
• Iris stroma: scattered fibroblasts and melanocytes in a collagenous matrix
• Posterior border layer: opaque pigmented epithelium (a continuation of the bilaminar ciliary epithelium)

Layers of the sclera

The sclera consists of four layers (from outer to innermost)

• Episclera: thin layer of dense, fibrous tissue
• Stroma: collagen fibers that are orientated in different directions , fibroblasts, elastic fibers, proteoglycans
• Lamina fusca: pigmented cells and collagen fibers
• Endothelium: single layer of endothelial cells

Layers of the retina (from choroid to vitreous body)

The retina consists of ten retinal layers. The outermost layer is the retinal pigment epithelium; the other nine layers (neural retina) consist of three types of neural cells: photoreceptor cells (retinal rods and cones), bipolar cells, and ganglion cells. These cells register light and translate this into neuronal signals that travel to the brain via the optic nerve (CN II).

• Bruch membrane
  • The innermost layer of the choroid
  • Lies adjacent to the pigment epithelium layer
  • Site of drusen deposits in the dry (nonexudative) form of age-related macular degeneration.
• Pigment epithelium
  • Outermost layer of the retina, adjacent to the Bruch membrane
  • Contains melanin granules
  • Aids in the formation of rhodopsin and storage of vitamin A
  • Provides nutrition to photoreceptors
  • Absorbs light and prevents reflection
  • Separates easily from the neural retina in the event of trauma or disease due to a lack of junctional complexes connecting the two layers (retinal detachment).
  • Not connected to the neural retina by junctional complexes → can easily be parted (retinal detachment)
• Layer of rods and cones
  • Retinal rods: first-order receptors of slender, and cylindrical cells
    • Primarily located around the fovea centralis
    • Achromatic: photoreceptors specialized for night vision (dim light) and motion
    • Contain rhodopsin: visual pigment and G-protein-coupled receptor that is activated by light (phototransduction)
  • Retinal cones: first-order receptors of flask-shaped cells
    • Primarily located within the fovea centralis
    • Chromatic (contain pigments for blue, red, and green light): photoreceptors specialized for color vision, bright light, and visual acuity
    • Contain several types of visual pigments with different spectral sensitivities (enabling the distinction of colors)
  • Rods and cones convert the optical image into neural activity, both using glutamate as a neurotransmitter
• External limiting membrane: supports photoreceptor cells
• Outer nuclear membrane: contains the nuclei of rods and cones
• External plexiform layer: contains synapses between bipolar and horizontal cells and synapses between the photoreceptor cells
• Inner nuclear layer
  • Contains Müller cells (supporting glial cells), which extend from the inner limiting layer to the outer limiting layer
  • Contains the cell bodies of bipolar neurons (second-order neurons) which transmit information from cones and rods to ganglion cells
• Internal plexiform layer: contains the synapses between ganglionic cells and bipolar neurons
• Ganglion cell layer: contain neuroglia and nuclei and cell bodies of ganglion cells
  • Project to the hypothalamus, pretectal nucleus, lateral geniculate body, and superior colliculus
  • Third-order neurons whose axons form the optic nerve (CN II)
• Optic nerve fibers: formed by axons of ganglion cells
• Internal limiting membrane: innermost layer; adjacent to the vitreous humor

The fovea Centralis contains mainly Cones, whereas the peripheral Retina contains mainly Rods.

The eyes are sensory organs that enable vision by translating light signals into neuronal signals, which travel via the optic nerve (CN II) to the visual cortex (visual pathway). The eye can adjust its refractory power (accommodation) to adjust focus according to the distance of an object perceived. Pupillary size is mediated by autonomic fibers and depends mainly on the intensity of incoming light. For more information on accommodation and pupillary control, see “Physiology and abnormalities of the pupil.” Eye motility is discussed under “Extraocular muscles” below.

Visual pathway

1. Retina: rods and cones (first-order neurons) → bipolar cells (second-order neurons) → ganglion cells (third-order neurons)
2. Optic nerves
   • The axons of ganglion cells merge to form the optic nerve
   • Each optic nerve carries the nasal and temporal fibers of the ipsilateral retina
3. Optic chiasm
   • Site where the optic nerves from each eye cross
   • Nasal fibers of the retina cross over to the contralateral side while temporal fibers remain uncrossed.
4. Optic tracts: Each optic tract carries contralateral nasal fibers and ipsilateral temporal fibers.
5. Lateral geniculate nucleus (LGN): The optic tracts terminate in the ipsilateral LGN.
6. Optic radiation: consists of neurons that carry visual information from the ipsilateral LGN to the ipsilateral primary visual cortex
7. Primary visual cortex
   • Processes visual information
   • Located at the posterior aspect of the occipital lobe
   • Each visual cortex receives visual information from the ipsilateral nasal field and the contralateral temporal field of vision.

Emmetropia

Emmetropia is the physiologic state of vision in which the eye is in a relaxed state and rays of light are relayed to the retina with physiologic refraction

• Refractory media
  • Comprise the cornea, lens, aqueous humor, and vitreous body
  • Direct and refract light to the posterior region of the retina
  • Alterations in the structure of the refractory media can lead to impairment of vision (e.g., cataract).
  • Minor deviations in eye anatomy that affects refractory media (e.g., axial eye length, cornea curvature) can result in the development of refractive errors (see “Refractive errors” below).

The orbit contains 6 muscles that are attached to the eyeball. There is an additional muscle in the orbit that attaches to the upper eyelid, the levator palpebrae superioris, which is responsible for eyelid elevation.

Development of the eye

The development of the eye takes place between the 3^rd and 10^th week of embryonic development.

• Optic grooves arise from the neural fold bilaterally and develop into optic vesicles after closure of the neural tube.
• Optic vesicles induce changes in the surface ectoderm and begin to form the lens placode.
• The lens placode invaginates, giving rise to the lens pit.
• Simultaneously, optic vesicles begin to invaginate and form the optic cup.
• The optic cup has a central groove (choroidal fissure), which allows entrance of the blood vessels that supply the eye (hyaloid vessels).
• Failure to close the choroidal fissure by the 7^th week of development results in coloboma, a unilateral or bilateral defect in a structure of the eye (e.g., retina, optic disc, iris) that typically manifests as a keyhole-shaped defect of the iris

Important structures and their derivatives

• Neuroectoderm: retina, optic nerve, ciliary body, iris
• Surface ectoderm: lens, cornea (epithelium), lacrimal apparatus, skin of the eyelids
• Neural crest cells or mesoderm: cornea (endothelium, Descemet membrane), sclera, ciliary muscle, extraocular muscles, vitreous humor

• Cornea
  • Astigmatism
  • Cataract
  • Keratitis
  • Hurler syndrome (corneal clouding)
  • Familial hypercholesterolemia (corneal arcus)
  • Wilson disease (accumulation of copper in the cornea)
• Sclera
  • Scleritis
  • Osteogenesis imperfecta (blue sclera)
  • Hyperbilirubinemia (yellow sclera)
  • Alkaptonuria (bluish-black sclera)
• Episclera
  • Episcleritis
  • Episcleral hemangioma in Sturge-Weber syndrome
• Uvea
  • Uveitis
  • Age-related macular degeneration
  • Lisch nodules in neurofibromatosis type 1
  • See “Physiology and abnormalities of the pupil.”
  • See “Diseases of the uvea.”
• Retina
  • Retinal detachment
  • Retinal vessel occlusion
  • Diabetes mellitus (diabetic retinopathy)
  • Hypertensive retinopathy
  • Papilledema
  • Retinoblastoma
  • Giant cell arteritis
  • Retinitis pigmentosa
  • See “Diseases of the retina.”
• Iris: coloboma
• Lacrimal system
  • Sjogren syndrome
  • See “Diseases of the lacrimal apparatus.”
• Eyelid
  • Conjunctivitis
  • Horner syndrome (due to sympathetic denervation of the superior tarsal muscle, causing ptosis)
  • Inflammation of the eyelids
    • Preseptal cellulitis (infection of the eyelid and periorbital soft tissues anterior to the orbital septum)
    • Orbital cellulitis (infection of the orbital contents posterior to the orbital septum)
• Extraocular muscles
  • See “Cranial nerve examination” in “Neurological examination” and “Ocular motility disorders and strabismus.”
  • See “Oculomotor nerve lesion,” “Trochlear nerve palsy,” and “Abducens nerve palsy” in “Cranial nerve palsies.”
• Orbita
  • Orbital disorders
  • Traumatic eye injuries
• Aqueous humor: Glaucoma
• Vitreous humor: Endophthalmitis
• Visual pathway: See “Disorders of the visual pathway.”
• Cavernous sinus
  • Cavernous sinus syndrome
  • Cavernous sinus thrombosis

Myopia (short-sightedness)

• Pathophysiology: abnormally increased axial length of the eye or, less commonly, increased refraction → focal point anterior to the retina
• Clinical features: clear near vision, blurred far vision
• Treatment: glasses with concave (diverging) lenses or refractive surgery
• Complications: retinal detachment, macular degeneration

Hyperopia (far-sightedness)

• Pathophysiology: abnormally decreased axial length of the eye → focal point posterior to the retina
• Clinical features: blurred near vision, clear far vision
• Treatment: glasses with convex (converging) lenses or refractive surgery
• Complications: increased risk for closed-angle glaucoma

Presbyopia

• Pathophysiology: age-related decrease in lens elasticity, strength of ciliary muscle, and lens curvature → decreased lens accommodation (focusing on an object up close)
• Clinical features
  • Similar to hyperopia
  • Preexisting myopia may temporarily compensate presbyopia, leading to better near vision (second sight)
• Treatment: reading glasses with convex lenses or refractive surgery

Astigmatism

• Pathophysiology: abnormal curvature of the cornea → refractive error hinders even refraction → two or more focal points, which can be anterior and/or posterior to the retina, depending on the curvature
• Clinical features: blurred vision at all distances
• Treatment
  • Regular astigmatism: cylindrical lenses
  • Irregular astigmatism: corrective contact lenses and refractive surgery
• Complications: early onset increases risk for amblyopia