BCSC Fundamentals Flashcards
What is the volume of each adult orbit?
30 cc
What are the seven bones of the bony orbit?
Frontal, Zygomatic, Maxilla, Ethmoid, Sphenoid, Lacrimal, Palatine
Which bones form the orbital roof?
Frontal bone and lesser wing of the sphenoid
Which bones form the medial wall of the orbit?
1) Frontal process of maxilla, 2) Lacrimal bone, 3) orbital plate of ethmoid, 4) Leser wing of sphenoid
Which bones form the orbital floor?
1) Maxilla, 2) Palatine, 3) Orbital plate of zygomatic
Which bones form the lateral orbital wall?
1) Zygomatic and 2) Greater wing of the sphenoid
What does the Whitnall tubercle indicate?
The site of attachment of 1) check ligament of LR muscle, 2) suspensory ligament of eyeball, 3) lateral palpebral ligament, 4) levator aponeurosis, 5) Whitnall ligament
What are the orbital foramina?
1) optic, 2) supraorbital, 3) anterior ethmoidal, 4) posterior ethmoidal, 5) zygomatic
Which structures are above the annulus of Zinn in the Superior Orbital Fissure?
lacrimal nerve of V1, frontal nerve of V1, CN IV, sup ophthalmic vein
Which structures are within the annulus of Zinn?
sup and inf divisions of CN III, nasociliary branch of V1, sympathetic roots of ciliary ganglion, CN VI
Which structures pass through the Inferior Orbital Fissure?
Infraorbital and zygomatic branches of V2, an orbital nerve from pterygopalatine ganglion, and inferior ophthalmic vein
What are the four sinuses?
Frontal, ethmoidal, sphenoid, maxillary
Which 3 roots does the ciliary ganglion receive?
1) long sensory root from nasociliary branch of V1, 2) short motor root from inf division of CN III, 3) sympathetic root from plexus around ICA
What is the 7th extraocular muscle?
Levator palpebrae superioris
List the rectus muscles in order of increasing distance of insertion from the limbus
1) MR (5.5), 2) IR (6.5), 3) LR (6.9), 4) SR (7.7)
What is the name for the curve passing through the rectus muscle insertions?
Spiral of Tillaux
Where does the superior oblique insert?
onto the sclera superiorly, under the insertion of the SR, after passing through the trochlea in the superior nasal orbital rim
What does the annulus of Zinn consist of?
The superior and inferior orbital tendons. It is the origin of the four rectus muscles
Where is the origin of the levator muscle?
lesser wing of the sphenoid, at the apex of the orbit, just superior to the annulus of Zinn
Where is the origin of the SO muscle?
periosteum of the body of the sphenoid bone, above and medial to the optic foramen
Where does the IO muscle originate?
from a shallow depression in the orbital plate of the maxillary bone, anteriorly
Which arteries supply the EOMs?
Inf and sup muscular branches of ophthalmic artery, lacrimal artery, and infraorbital artery
Which EOMs are innervated by the superior division of CN III?
levator and SR
Which EOMs are innervated by the inferior division of CN III?
MR, IR, IO
What type of fibers make up the EOMs?
both fast twitch and slow twitch fibers
What is the ratio of nerve fibers to muscle fibers in the EOMs?
1:3 (compared to 1:50 in skeletal muscle)
What is the normal size of the palpebral fissure?
27-30mm long, 8-11mm high
What is the excursion of the upper lid generated by the levator alone?
15mm (extra 2mm if using the frontalis in addition)
What are the segments of the eyelid (from dermal surface inward)?
skin, eyelid margin, subq tissue, orbicularis muscle, orbital septum, levator muscle, muller muscle, tarsus, conjunctiva
Where is the superior eyelid fold located?
at the upper border of the tarsus, at the initial insertion of the levator aponeurosis
What does the gray line of the eyelid margin indicate?
1) the most superficial portion of the orbicularis muscle, 2) the muscle of Riolan, and 3) the avascular plane of the lid
How many rows of eyelashes are there?
2 to 3
What are glands of Zeis?
modified sebaceous glands associated with the cilia
What are glands of Moll?
apocrine sweat glands of skin
Which CN innervates the orbicularis?
VII
Are meibomian orifices and lacrimal punctum anterior or posteiror to the gray line?
posterior
What are the two parts of the orbicularis?
Orbital and palpebral
Does the orbital part of the orbiclularis have involuntary functions?
No, only the palpebral part of the orbicularis does
What is the orbital septum?
a thin sheet of connective tissue that encircles the orbit as an extension of the periosteum of the roof and floor of the orbit
To which surface of the levator muscle does the orbital septum attach?
Anterior surface
How long is the levator muscle and its tendon?
muscle 40mm, muscle + tendon 50-55mm long
Which CN innervates the levator?
CN III
What is the Muller muscle?
A smooth, smypathetically innervated muscle originating from the undersurface of the levator muscle in the upper eyelid
How are the tarsal plates connected to the orbital margins?
by the medial and lateral palpebral ligaments
How much taller is the upper tarsus than the lower tarsus?
3x taller (11mm vs. 4 mm)
How many meibomian orifices are there at the eylid margin?
30 on upper lid, 20 on lower lid
What is distichiasis?
aberrant growth of cilia through the orificies of the meibomian glands
Is the palpebral conjunctival epithelium keratinized?
No
From which systems does the blood supply of the eyelids arise?
Facial (ECA) and Orbital (ICA)
Where does the marginal arterial arcade of the eyelid run?
between orbicularis and tarsus or within tarsus
What are the venous systems draining the eyelids?
Superficial/pretarsal system (IJ/EJ) and Deep/Posttarsal (cavernous sinus)
Are lymphatic vessels present in the eyelids?
Yes, but not in the orbit
Where do the lymphatics of the eyelids drain?
medial group drains to submandibular LNs, lateral group drains to preauricular LNs
Is the plica semilunaris a vestigial structure?
yes, it is analogous to the nictitating membrane of other animals
Are the lacrimal glands endocrine or exocrine?
Exocrine
What are the 2 cell types contained in the lacrimal gland?
1) Acinar cells lining the lumen, 2) Myoepithelial cells
What types of nerve fibers does the lacrimal gland receive?
cholinergic, VIP-ergic, sympathetic, and sensory from V1
What are three divisions of the conjunctiva?
Papebral, Forniceal, and Bulbar
Does the bulbar conjunctiva fuse with the Tenon capsule?
Yes
What is the Tenon capsule?
The Tenon capsule (fascia bulbi) is an envelope of elastic connective tissue that fuses posteriorly with the optic nerve sheath and anteriorly with the intermuscular septum, 3mm posterior to the limbus. The Tenon capsule is the cavity in which the globe moves.
From where do the anterior and posterior ciliary arteries arise?
the ophthalmic artery
What do the posterior ciliary arteries supply?
Whole uveal tract, cilioretinal artery, sclera, margin of cornea, adjacent conjunctiva
What do the anterior ciliary arteries supply?
SR, MR, IR muscles
What are the vortex veins?
Veins draining the choroid. There are usually 4-7 of vortex veins, at least 1 in each quadrant, exiting the eye just posterior to the equator.
What is the shape of the globe?
an oblate spheroid
What is the average transverse diameter of the adult eye?
24mm
What is the average volume of the adult globe?
6.5 to 7 cc
What are three things contained in tears aside from oil, water, and mucus?
immunoglobulins, lysozyme, and lactoferrin
What is the power of the anterior surface of the cornea?
49D
What structure attaches the basal epithelium of the cornea to the epithelial basement membrane?
hemidesmosomes
What non-epithelial cells are found in the corneal epithelium?
Histiocytes, macrophages, lymphocytes, pigmented melanocytes, and Langerhans cells
Is Bowman layer replaced after injury?
No
How thick is Bowman layer?
8-14 microns thick
What types of collagen are found in the corneal stroma?
Types I, III, V, and VI
What percent of the corneal volume is made up by keratocytes?
5%
Where is the density of keratocytes highest in the corneal stroma?
Anteriorly
What is the Descemet membrane?
The basement membrane of the corneal endothelium.
What are peripheral excrescences in the Descemet membrane called?
Hassal-Henle warts (common in the elderly), as opposed to Guttae (which are central)
Which way does the apical surface of a corneal endothelial cell face?
Toward the anterior chamber
Are desmosomes seen between corneal endothelial cells?
No, but junctional complexes are present between contiguous cells
Where is the sclera the thinnest?
at the insertions of the rectus muscles (0.3mm)
Where is the sclera the thickest?
around the optic nerve head (1mm)
What are included in the corneal limbus?
Conjunctiva and limbal palisades, Tenon capsule, episclera, corneoscleral stroma, aqueous outflow apparatus
What are the two parts of the surgical limbus?
1) anterior bluish gray zone from Bowman termination to Descemet termination, 2) Posterior white zone from Descemet termination (Schwalbe line) to scleral spur
What are conditions that cause an increase in the depth of the anterior chamber?
aphakia, pseudophakia, and myopia
What is the normal volume of the anterior chamber?
200 microliters
What are the two primary means of aqueous drainage?
Schlemm canal and uveoscleral pathway
What is the trabecular meshwork?
a circular spongework of connective tissue lined by trabeculocytes
What are the 3 layers of the TM?
1) Uveal portion, 2) Corneoscleral meshwork, 3) Juxtacanalicular tissue
Which portion of the TM provides the most resistance to outflow?
Juxtacanalicular connective tissue
What are the 3 points of connection of the uvea to the sclera?
1) Scleral spur, 2) Vortex veins, 3) optic nerve
How is aqueous drained via Schlemm canal?
25-30 collector channels arise from the canal and drain into the deep and intrascleral venous plexuses, which in turn drain to the episcleral venous plexus. 8 of the collector channels drain directly to the episcleral venous plexus as “aqueous veins.”
What does eye color correspond to?
The amount of pigment in the anterior border layer and deep stroma of the iris.
What is the orientation of the fibers of the pupillary sphincter muscle?
circular (adjacent to pupillary border)
What is the orientation of the fibers of the iris dilator muscle?
radial (peripheral)
What type of innervation does the iris dilator muscle have?
Both sympathetic and parasympathetic! Cholinergic parasympathetic innervation may inhibit the contraction of the dilator muscle
What is the primary innervation of the iris sphincter muscle?
Parasympathetic innervation from nucleus of CN III. It appears to also have secondary sympathetic innervation that inhibits contraction (and thereby inhibits pupillary constriction).
What are the two primary functions of the ciliary body?
aqueous humor formation and lens accommodation
How far from the corneal limbus is the pars plana of the ciliary body?
3-4mm posterior
Which is more vascular, the pars plana or the pars plicata of the ciliary body?
the pars plicata is richly vascularized
What is the lining of the ciliary body?
2 layers of epithelial cells (non-pigmented and pigmented epithelial layers)
What is the main arterial supply of the ciliary body?
the anterior ciliary arteries and long posterior ciliary arteries
What are the three layers of fibers in the ciliary muscle?
1) longitudinal, 2) radial, 3) circular
What is the primary innervation of the ciliary body?
Parasympathetic fibers from CN III via the short ciliary nerves
What do cholinergic drugs do to the ciliary body muscle?
They cause it to contract, which opens up the TM via its attachments to the sceral spur, thereby increasing aqueous outflow
Where does the perfusion of the choroid come from?
The short posterior ciliary arteries and the perforating anterior ciliary arteries
In to what does blood from the choroid drain?
The vortex veins
What is Bruch membrane?
A PAS-positive layer resuting from the fusion of the basal laminae of the RPE and choriocapillaris
What are the layers of the Bruch membrane?
1) basal lamina of RPE, 2) inner collagenous zone, 3) porous band of elastic fibers, 4) outer collagenous zone, 5) basal lamina of the choriocapillaris
Is Bruch membrane permeable to fluorescein?
Yes
Are the medium and large choroidal vessels permeable to fluorescein?
No, but the choriocapillaris is
On what does the degree of fundus pigmentation viewed ophthalmoscopically depend?
The number of pigmented melanocytes in the choroid
Does the degree of pigmentation of the choroid affect photocoagulation?
Yes
What is the diameter of the lens in the adult?
9-10mm
What is the depth of the lens in the adult?
5-6mm
What is the lens capsule?
A basal lamina put down by the lens epithelial cells, rich in type IV collagen
Does the thickness of the anterior capsule change during life?
Yes, it continues to grow, while the posterior capsule does not
Is lens epithelium present underneath the posterior capsule?
No
What is the germinative zone of the lens?
A set of peripheral meridional rows of cuboidal pre-equatorial lens epithelial cells that undergo mitotic division
Of what material are lens zonules made?
fibrillin
What is the average diameter of the macula?
5-6mm
What is the composition of the RPE?
A monolayer of hexagonal cells
What are the functions of the RPE?
1) Vitamin A metabolism, 2) maintenance of outer blood-retina barrier, 3) phagocytosis of outer segments, 4) absorption of light, 5) heat exchange, 6) formation of basal lamina, 7) production of MPS matrix, 8) active transport into and out of RPE
What is a retinal detachment?
separation of the neurosensory retina from the RPE
From what do lipofuscin granules arise?
the discs of photorecptor outer segments. They represent residual bodies arising from phagosomal activity
What are phagosomes?
membrane-enclosed packets of disc outer segments that have been engulfed by the RPE
What surrounds the photoreceptor outer segments?
An MPS matrix, secreted by the RPE
What types of cells are found in the inner nuclear layer?
Bipolar, Amacrine, and Horizontal cells; (also, Muller-type glial cells)
What types of cells are found in the outer nuclear layer?
Photoreceptor cell bodies
How many rods and cones are there?
120M rods, 6M cones
What is the blood supply of the inner retina?
Branches of the cnetral retinal artery and, in 30% of people, a cilioretinal artery branching from the ciliary circulation
Are retinal arteries permeable to fluorescein?
No, they have tight junctions and maintain the blood-retina barrier
Is the external limiting membrane fenestrated?
Yes
What is the OPL called in the fovea?
the Henle fiber layer
Is the OPL thicker in the macula?
Yes
Of what does the OPL consist?
Photoreceptor axons
Of what does the IPL consist?
axons of bipolar and amacrine cells, as well as the dendrites of ganglion cells
Of what does the NFL consist?
axons of the ganglion cells
Are axons of ganglion cells myelinated?
Not within the eye. They are myelinated only after they pass through the lamina cribrosa
What is the histologic definition of the macula?
The region with more than 1 layer of ganglion cell nuclei (plus the foveola)
What are the two major pigments of the macula?
zeaxanthin (cone-dense areas) and lutein (rod-dense areas)
What is the diameter of the fovea?
1.5mm
What is the diameter of the foveola?
0.35mm
Which layers are absent in the foveola?
NFL, GCL, IPL, INL
Is the FAZ different from the foveola?
It is roughly the same size and location, but characterized only by its avascularity
What type of photoreceptors are present in the foveola?
ONLY cones
How far from Schwalbe line is the the ora serrata?
5.75mm to 6.5mm
Of what does the vitreous consist?
99% water, plus MPS and hyaluronic acid
What is the path of the fibers forming CN I?
from olfactory receptors in mucous membrane of the nose to the olfactory bulb (where they form the nerve)
What are the 4 topographic areas of the optic nerve?
1) Intraocular region, 2) Intraorbital region, 3) Intracanalicular region, 4) Intracranial region
What is the averatge length of the optic nerve?
40mm (35-55mm)
What is the length of the intraorbital portion of the optic nerve?
25-30mm, via a sinuous course
What is the average size of the optic disc?
1.5mm (horizontal) x 1.75mm vertical
What are the 4 parts of the optic nerve?
1) superficial nerve fiber layer, 2) prelaminar area, 3) laminar area, 4) retrolaminar area
Where within the optic nerve head are fibers from the macula?
Lateral
How do ganglion cell axons pass through the lamina cribrosa?
in fascicles formed by astrocytic glial cells
What leads to enlargement of the optic cup?
Loss of ganglion cell axons and supporting glial elements
How many tissue plates are in the lamina cribrosa?
10
What percent of the optic nerve head volume is made up by astrocytes?
10%
What types of collagen are found in the lamina cribrosa?
Type I and Type III, in addition to elastin, laminin, and fibronectin
What are the functions of the lamina cribrosa?
1) scaffold for optic nerve axons,2) point of fixation for CRA and CRV, 3) reinformcement of posterior segment of globe
What is the diameter of the optic nerve posterior to the lamina cribrosa?
3mm (increases due to myelination of nerve fibers)
What happens to the dural sheath of the optic nerve at the optic canal?
It fuses to the periosteum, completely immobilizing the nerve
What divides the nerve into fascicles?
The pia mater
What is the blood supply of the optic nerve in the optic canal?
Pial vessels from the ophthalmic artery
What is the blood supply of the retrolaminar nerve?
Pial vessels and short posterior ciliary vessels, CRA, and recurrent choroidal arteries
What is the blood supply of the lamina cribrosa?
The short posterior ciliary arteries and branches of the arterial circle of Zinn-Haller
What is the blood supply of the prelaminar nerve?
short posterior ciliary arteries (and cilioretinal artery if present) and possibly recurrent choroidal arteries
What is the blood supply of the NFL?
the CRA
What is the blood supply of the intracanalicular nerve?
ophthalmic artery
What is the blood supply of the intracranial optic nerve?
ICA and ophthalmic artery
What percent of the volume of the optic nerve consists of macular nerve fibers?
80%
Which layers of the LGN receive fibers from the contralateral optic nerve?
1, 4, and 6
What gives rise to the upper homonymous “pie in the sky” defect?
Damage to the optic radiation in the anterior temporal lobe
What is the blood supply of the visual cortex?
The posterior cerebral artery
What does CN III supply?
SR, MR, IR, IO, levator palpebrae, pupillary sphincter, and ciliary muscle
Which nucleus of CN III provides innervation to the ciliary muscle and pupillary sphincter?
The Edinger-Westphal nucleus
Where does CN III divide into superior and inferior divisions?
Usually after passing through the annulus of Zinn in the orbit (sometimes within the cavernous sinus)
What is a sensitive early sign of compression of CN III?
loss of pupillary constriction ability
What is the path of the pupillary light reflex?
light activates photoreceptors –> retinal ganglion cells –> axons cross in the optic chiasm –> in optic tract, pupillary fibers leave visual fibers and go to pretectal nuclei at superior colliculus –> efferents to EW nuclei with partial decussation –> parasympathetic fibers leave from each EW nucleus and join CN III –> fibers join inferior division of CN III –> synapse in ciliary ganglion –> give rise to short ciliary nerves (3%-5% are pupillomotor)
What is the path of the pupillary near reflex?
reflex initiated in occipital association cortex –> relay inpretectal and tegmental areas –> pass to EW nuclei, motor nuclei of MR muscles, and nuclei of CN VI –> efferents to MR, LR, pupillary sphincter, and ciliary muscle
What actions are involved in the near reflex?
1) Accommodation, 2) Pupil constriction, 3) converence
Which CN has the longest intracranial course?
CN IV (75mm)
Which CN is the only CN to be completely decussated?
CN IV
Which CN is the only CN to exit dorsally from the brainstem?
CN IV
Does CN IV enter the orbit through the annulus of Zinn?
No, it enters the orbit through the superior orbital fissure outside the annulus of Zinn
What are the 4 nuclei of the CN V nuclear complex?
1) mesencephalic nucleus, 2) main sensory nucleus, 3) spinal nucleus and tract, 4) motor nucleus (in the pons)
What does the main sensory nucleus of CN V receive?
light touch from the skin and mucous membranes
What does the spinal nucleus of CN V receive?
pain and temperature, as well as cutaneous components of CN VII, IX, and X
What does the mesencephalic nucleus of CN V receive?
prioprioception and deep sensation from masticatory, facial, and extraocular muscles
Which muscles does the motor nucleus of CN V innervate?
muscles of mastication (pterygoid, masseter, temporalis), tensor tympani, tensor veli palatini, mylohyoid, anterior belly of digastric
Where is the trigeminal ganglion located?
in Meckel cave, a recess near the apex of the petrous part of the temporal bone in the middle cranial fossa. It is posterolateral to the cavernous sinus.
What are the 3 branches of V1?
frontal, lacrimal, and nasociliary
What are the two divisons of the frontal branch of V1?
supraorbital nerve and supratrochlear nerve
What does the lacrimal branch of V1 innervate?
lacrimal gland and neighboring conj and skin
What does the nasociliary branch of V1 innervate?
Via nasal branches (anterior ethmoidal nerve): middle and inferior turbinates, septum, lateral nasal wall, tip of nose. Via infratrochlear branch: lacrimal drainage system, conj, skin of medial canthus. Via long ciliary nerves: ciliary body, iris, cornea, sympathetic innervation to iris dilator muscle; Via short ciliary nerves: globe sensation, parasympathetic fibers to pupillary sphincter and ciliary muscle
What are the 5 motor branches of CN VII?
Temporal, zygomatic, buccal, mandibular, cervical
What is the cavernous sinus?
an interconnected series of venous channels located just posterior to the orbital apex and ateral to the sphenoidal (air) sinus and pituitary fossa
What are the structures located within the cavernous sinus?
1) the ICA, 2) sympathetic carotid plexus, 3) CN III, 4) CN IV, 5) ophthalmic and maxillary branches of CN V, 6) CN VI
What are the primary tissues invovled in the process of ocular development?
Head epidermis, neuroectoderm, and mesenchyme
What are three important factors in the development of the eye?
1) growth factors, 2) homeobox genes, 3) neural crest cells
Which growth factors are most important in ocular development?
FGF, TGF-beta 1 and 2, IGF-1
Which homeobox gene is expressed in the area of surface ectoderm destined to form the corneal epithelium?
HOX 8.1
From where do NCCs arise?
From neuroectderm located at the crest of the neural folds at approximately the same time that the folds fuse to form the neural tube.
From which germ layer do the endothelial cells lining blood vessels of the ey arise?
mesoderm
Which eye/orbit tissues derive from surface ectoderm?
Epithelium, glands, and cilia of skin of eyelids and caruncle; conjunctival epithelium, lens, lacrimal gland, lacrimal drainage system, vitreous
Which eye/orbit tissues derive from neuroectoderm?
retina, RPE, pigmented and non-pigmented ciliary epithelium, pigmented iris epithelium, sphincter and ilator muscles of irirs, optic nerve, axons, and glia, vitreous
Which eye/orbit tissues derive from cranial NCCs?
corneal stroma and endothelium, sclera, TM, sheaths and tendons of EOMs, connective tissues of iris, ciliary muscle, choroidal stroma, melanocytes, meningeal sheaths of optic nerve, Schwann cells of ciliary nerves, ciliary ganlgion, cartilage, connective tissue of orbit, muscular layer and connective tissue sheaths of vessels, all midline and inferior orbital bones, parts of orbital roof and lateral rim
Which eye/orbit tissues derive from mesoderm?
fibers of EOMs, endothelium of blood vessels, temporal portion of sclera, vitreous
What are the neurocristopathies?
congenital and developmental anomalies involving NCC-derived tissues, usually deriving from improper migration or differentiation of NCCs
When does the neural tube close?
at the end of the third week of development
What 3 events important to the development of the eye occur as the neural tube closes?
1) optic pits develop from the optic sulci, 2) NCCs begin to migrate, 3) the anterior neural tube flexes ventrally
What are the optic sulci?
small depressions present in the cephalic neuroectocderm
From what do the optic vesicles arise?
The optic pits, as the optic pits deepen
From what does the optic cup arise?
The optic vesicle, as its temporal and lower walls are invaginated
What does the outer layer of the optic cup become?
the RPE
What does the inner layer of the optic cup become?
the retina
What is the embryonic fissure?
The indentation between the folds or margins of the optic cup
At what stage of development does the lens placode form?
28 days
At what stage of development do eyelid folds appear?
2nd month
At what stage of development do axons from ganglion cells migrate to optic nerve?
2nd month
At what stage of development does Bruch membrane appear?
2nd month
At what stage of development do rod and cone precursors differentiate?
3rd month
At what stage of development do the vortex veins pierce the sclera?
3rd month
At what stage of development do the eyelid folds meet and fuse?
3rd month
At what stage of development does Descemet membrane form?
4th month
At what stage of development does Schlemm canal appear?
4th month
At what stage of development does the hyalid system start to regress?
4th month
At what stage of development do the eyelids begin to separate?
5th month
At what stage of development do the photoreceptors develop inner segments?
5th month
At what stage of development does the dilator muscle of the iris form?
6th month
At what stage of development do the photoreceptors develop outer segments?
7th month
At what stage of development do the choroidal melanocytes produce pigment?
7th month
At what stage of development does the lamina cribrosa form?
7th month
At what stage of development does chamber angle formation complete?
8th month
At what stage of development do retinal vessels reach the periphery?
9th month
At what stage of development do fibers of the optic nerve complete myelination to the point of the lamina cribrosa anteriorly?
9th month
At what stage of development does the pupillary membrane disappear?
9th month
At what stage of development does the retina begin to differentiate?
within 1 month
At what stage of development does the hyaloid artery enter the vitreous?
5th week
From which embryonic structure does the optic nerve arise?
the optic stalk
What are the primary functions of the tear film?
1) To provide a smooth optical surface; 2) to serve as a medium for removal of debris; 3) to protect the ocular surface; 4) to supply oxygen, growth factors and other compounds to the epithelium
What are the three parts of the tear film?
1) Tear meniscus, 2) Precorneal tear film, 3) conjunctival tear film
What is the thickness of the precorneal tear film?
3.4 microns
What are the three layers of the tear film?
anterior lipid layer, middle aqueous layer, posterior mucin layer
What portion of the tear film is water?
98.20%
What is the normal rate of tear secretion in the anesthetized and unanesthetized states?
unanesthetized: 3.8 microL/min, anesthetized: 1.8 microL/min by Schirmer method
What are the functions of the lipid layer of the tear film?
1) slow evaporation, 2) contribute to optical properties of tear film, 3) maintain hydrophobic barrier to increase surface tension, 4) prevent damage to lid margin skin by tears
What are the electrolytes found in the tear film?
Na+, K+, Ca2+, Mg,2+ Cl-, HCo3-
What is the predominant innervation of the lacrimal gland?
parasympathetic
Which immunoglobulins are found in the tear film?
IgA, secretory IgA (occasionally IgG in ocular inflammation, IgE in vernal conjunctivitis)
What are the antimicrobial components of the tear film?
lysozyme, lactoferrin, phospholipase A2, lipocalins, defensins, interferon
What are the solutes found in the tear film?
urea, glucose, lactate, citrate, ascorbate, amino acids
What is the function of the aqueous layer of the tear film?
1) supply oxygen to the corneal epithelium, 2) maintain constant electrolyte composition, 3) provide antimicrobial defense, 4) smooth minute irregularities of corneal surface, 5) wash away debris, 6) modulate corneal and conjunctival epithelial cell function
What are the functions of the mucin layer of the tear film?
1) convert the corneal epithelium from a hydrophobic to a hydrophilic layer, 2) interact with tear lipid layer to lower surface tension, 3) trap exfoliated surface cells, foreign particles, and bacteria, 4) lubricate the eyelids as they pass over the globe
What are 2 means of stimulating tear secretion?
1) Nerve stimulation and 2) hormone secretion (alphaMSH, ACTH, VIP)
What are 4 reasons for tear film dysfunction?
1) change in amount of tear film constituents, 2) change in composition of tear film, 3) uneven dispersion of tear film due to corneal surface irregularity, 4) ineffective distribution of tear film by lids
What is the innervation of the cornea?
The long posterior ciliary nerves (branches of V1) penetrate the cornea in 3 planes: scleral, episceral, and conjunctival.
Are corneal nerves myelinated?
No, the corneal nerves lose their myelin sheath 1-2mm from the limbus
Where is the sub-basal plexus located?
Just posterior to Bowman layer (underneath the basal epithelium and Bowman layer). It sends branches anteriorly into the epithelium
From where is oxygen for the cornea derived?
pre-corneal tear film, lid vasculature, aqueous humor
What is the primary metabolic substrate for the cornea?
glucose
How is glucose metabolized by the cornea?
Via all 3 pathways (TCA cycle, anaerobic glycolysis, HMP shunt). TCA cycle more active in endothelium than epithelium.
What is the ideal ionic dissociation characteristic of an organic molecule for penetrating the cornea?
The organic molecule should be able to dissociate into ions at physiologic pH and temperature (i.e., after penetrating the corneal epithelium and entering the stroma)
What happens to Bowman layer in PRK, LASEK, and LASIK?
Bowman layer is lost during PRK and LASEK for myopia correction; Bowman layer is transected but retained in LASIK
How are adjacent lamellae of corneal stroma positioned relative to one another?
approximately orthogonal to one another
What are the GAGs found in the corneal stroma?
1) keratan sulfate, 2) chondroitin sulfate, 3) dermatan sulfate
Which MMP is found in normal healthy cornea?
MMP-2
Which MMPs are found after corneal injury?
MMP-1, MMP-3, and MMP-9
What is the predominant type of collagen in Descemet membrane?
Type IV collagen
From which germ layer is the smooth muscle of the iris and ciliary body derived?
Neuroectoderm (unlike smooth muscle elsewhere in the body, which is derived from mesoderm)
What types of receptors are expressed by the iris-ciliary body complex?
adrenergic, muscarinic cholinergic, peptidergic, prostaglandin, serotonin, platelet activating factor, growth factor receptors
Compared to plasma, how much protein is there in aqueous humor?
aqueous has 1/500th of the amount of protein found in plasma
What are the two means by which aqueous is produced?
1) passive (diffusion and ultrafiltration), 2) active (energy-dependent secretion, including carbonic anhydrase II activity)
What is ultrafiltration (with regard to aqueous production)?
the nonenzymatic component of aqueous formation, dependent upon IOP, blood pressure, and blood osmotic pressure in the ciliary body
What is the mechanism of action of PG analogues on IOP?
enhancement of aqueous outflow
What do PGs of type E and F do when used topically at high concentrations?
They cause miosis, elevation of IOP, increase in aqueous protein content, and entry of WBCs into aqueous and tear fluid.
What are the primary receptors found on the ciliary muscle and iris sphincter?
muscarinic cholinergic receptors
What are the primary receptors found on the iris dilator muscle?
alpha-adrenergic receptors
Which neurotransmitters are used by the sensory nerves of the iris muscles?
substance P and CGRP
By what mechanisms do miotic agents act?
1) stimulate the iris sphincter muscle (cholinergic agonist) or 2) block the iris dilator muscle (alpha-adrenergic blockade)
What are the mechanisms by which cholinergic agonist miotics act?
1) Direct agonism through ACh, carbachol, or pilocarpine or 2) Accumulation of ACh via AChE blocker (reversible or irreversible)
Which AChE blockers are reversible?
physostigmine and neostigmine
Which AChE blockers are irreversible?
diisopropyl fluorophosphate (DFP) and echothiophate iodide
What are the two mechanisms for the of dilator blocking miotics?
1) inhibition of NE release by depletion of NE stores (guanethidine), 2) blockage of alpha1-adrenergic receptors of dilator muscle (thymoxamine, dapiprazole, phenoxybenzamine, dibenamine, phentolamine)
What are the two mechanisms of mydriatic agents?
1) stimulating the dilator muscle (alpha adrenergic agonists) or 2) blocking the iris sphincter muscle (cholinergic blockade)
What are the three mechanisms of adrenergic agonist mydriatics?
1) increasing NE release (hydroxyamphetamine), 2) blocking NE reuptake (cocaine), 3) directly stimulating alpha1 receptors of dilator muscle (phenylephrine)
Why is an anticholinergic agent both mydriatic and cycloplegic, while an adrenergic agent is only mydriatic?
The ciliary body has cholinergic innervation, and thus, paralysis of the ciliary body (i.e. cycloplegia) requires an anticholinergic.
What are common cycloplegic agents?
atropine, cyclopentolate, and tropicamide (in order of decreasing duration of action)
Which types of drugs decrease aqueous humor production?
beta-antagonists and alpha2 agonists
Which types of drugs increase trabecular outflow?
miotics (alpha1 agonists and anticholinergic) and adrenergic agonists
Which types of drugs increase uveoscleral outflow?
1) prostaglandins and 2) alpha agonists
What is the rate of secretion of aqueous humor by the ciliary epithelium?
2-3 microL/min
What are the two types of ciliary epithelium and in which direction does each face?
1) Non-pigmented epithelium –> aqueous humor, 2) pigmented epithelium –> stroma
What are the 3 steps in the formation of aqueous?
1) uptake of solute and water by surface PE cells, 2) transfer from PE to NPE cells through gap junctions, 3) transfer of solute and water by NPE cells into the posterior chamber
What is contained in the aqueous humor other than water?
1) inorganic ions and organic anions, 2) carbohydrates, 3) glutathione and urea, 4) proteins, 5) growth-modulatory factors, 6) oxygen and CO2
What is the ratio of plasma calcium to aqueous calcium?
2 to 1
What are the commonly found organic anions in aqueous?
1) Lactate most abundant, 2) ascorbate (vit C) 10x greater than plasma
What is the glucose concentration in aqueous relative to plasma?
70% of plasma glucose concentration
What are the growth-modulatory factors found in aqueous?
1) TGF-beta1 and beta2, 2) aFGF, bFGF, 3) IGF-I, 4) IGFBPs, 5) VEGF, 6) transferrin
What are the 3 VEGF receptors?
1) VEGFR1 – both positive and negative angiogenic effects, 2) VEGFR2 – primary mediator of mitogenic, angiogenic, and vascular permeability effects of VEGF-A, 3) VEGFR3 – mediates angiogenic effects on lymphatic vessels
Which is the only member of the VEGF family that is induced by hypoxia?
VEGF-A. It is a critical regulator of angiogenesis and a potent inducer of vascular permeability.
What is the partial pressure of oxygen in the aqueous?
55mmHg
What is the partial pressure of CO2 in aqueous?
40-60mmHg
What contributes to the high refractive index of the lens?
soluble proteins called crystallins
What type of collagen makes up the lens capsule?
Type IV collagen
Where do the zonular fibers insert on the lens capsule?
anteriorly and posteriorly near the lens equator
How many cells deep is the anterior lens epithelium?
1 cell deep anteriorly; germinative zone is near equator
What are the two proteins expressed in large amounts by elongating lens fibers?
Crystallins and Major intrinsic protein (MIP, an aquaporin)
Do terminally differentiated lens fibers have nuclei, mitochondria, or other organelles?
No, they disintegrate
What are the two portions of the lens fiber mass?
The cortex (laid down after age 20) and the nucleus (laid down from embryogenesis to age 20)
What compound is lost in the lens with age, particularly in the nucleus?
phospholipid
What are lens crystallins?
A diverse group of proteins expressed in high abundance in the lens fiber cells and throught to provide transparency and refractile properties to the lens. They make up 90% of the total lens protein.
What are the two groups of crystallin proteins?
alpha-crystallin family and beta,gamma cyrstallin family
Is alpha-crystallin a member of the heat-shock protein family?
Yes, it is inducible by heat and other stresses.
What is the chaperone-like activity of alpha crystallins?
they bind proteins that are beginning to denature and prevent further denaturation and aggregation
Where are the gamma crystallins found?
In the nuclus, as they are mostly expressed in early development
Where are the longest-lived proteins in the body found?
in the lens (at the center of the nucleus) – synthesized before birth
Is the oxygen tension in the lens higher or lower than that of other tissues?
Lower, it is avascular and relies on the diffusion from the aqueous
What is a critical factor in the cascade leading to hyperglycemic cataracts in animal models?
aldose reductase
What is the function of the vitreous?
act as a conduit for nutrients and other solutes to and from the lens, occupy the major volume of the globe
What is the physical structure of the vitreous?
a gel composed of a collagen framework interspersed with hydrated hyaluronan molecules
What determines whether the vitreous is liquid or gel?
the amount of collagen (more collagen –> more gel-like)
What is the function of the collagen in the vitreous?
The collagen fibrils supply resistance to tensile forces and give plasticity to the vitreous
What is the function of the hyaluronan in the vitreous?
it resists compression and confers viscoelastic properties
What is the composition of the vitreous?
98% water, 0.15% macromolecules (collagen, hyaluronan, soluble proteins, the rest is ions/solutes
What are two important enzymes found in vitreous?
hyaluronidase and MMP-2
What are the 3 types of collagen comprising collagen fibrils in the vitreous?
1) Type II (major component), 2) Type IX (on surface of fibrils), 3) Type V/XI (projects from surface of fibril)
What are two glycoproteins thought to be important in the structure of the collagen fibril?
opticin and VIT1
What percent of the vitreous is typically liquid by age 80?
50%
What occurs to collagen fibrils in the process of vitreous liquefaction?
breakdown of thin collagen fibrils into smaller fragments, thought to be due to loss of Type IX collagen shielding of the fibrils with age
What are 2 major physical changes in ocular characteristics after vitrectomy?
1) 300x to 2000x reduction in viscosity and 2) marked increase in oxygen tension at the retina (due to rapid diffusion from anterior to posterior segment)
What happens to vitreous in an area of hemorrhage?
The vitreous becomes liquified in response to phagocytic inflammatory reaction (if not already liquefied)
What are the types of neural retinal cells?
1) photoreceptors (rods and 3 cone types), 2) bipolar cells (rod on- and cone on- and off- bipolars), 3) interneurons (horizontal and amacrine cells), 4) ganglion cells, 5) supporting cells (astroglia, oligodendroglia, Schwann cells, microglia, vascular endothelium, pericytes)
What part of the photoreceptor is involved directly in phototransduction?
the outer segment
What is the composition of the rod outer segment?
1000 sacs/discs containing 1M rhodopsin molecules each
What amount of light is required to active a rhodopsin molecule
a single photon is sufficient
At what wavelength does rhodopsin best absorb light?
510nm
What neurotransmitter is released from the synaptic terminal upon depolarization of a rod?
glutamate
Does the rod outer segment contain mitochondria?
No, only the inner segment does. The outer segment performs glycolysis, but not oxidative metabolism.
What is the flicker fusion frequency in cones?
100Hz in cones (30Hz in rods)
How many spectral classes of cones are required to see color?
at least 2 classes
What are the 3 types of cones in the human?
S, M, and L
What is Nougaret disease?
the oldest known form of AD stationary nyctalopia, caused by a G38D mutation in rod transducin
What causes Leber congenital amaurosis?
LCA (a childhood AR form of retinitis pigmentosa) is caused by null mutations of guanylate cyclase or homozygous defects of RPE 65
What cuases gyrate atrophy?
homozygous defects of OAT (ornithine aminotransferase)
What are the cells of the inner nuclear layer (INL)?
3 neuron types (bipolar, amacrine, horizontal) and 1 glial type (Muller cell)
Do rods and cones share the same type of bipolar cells?
No, rods and cones have separate types of bipolar cells. Furthermore, there are cone on-bipolars and cone off-bipolars (for L and M cones), while there are only rod on-bipolars.
What are the horizontal cells?
they are antagonistic interneurons that inhibit photoreceptors by releasing GABA when depolarized.
What do amacrine cells do?
They mediate antagonistic interactions among on-bipolars, off-bipolars, and ganglion cells.
What are the 2 main types of retinal ganglion cells?
On-center and off-center ganglion cells (based on their receptive fields)
What are the 3 subgroups of retinal ganglion cells?
1) Tonic cells driven by L or M cones (project to parvocellular layers of LGN), 2) tonic cells driven by S cones, and 3) phasic cells (project to magnocellular layers of LGN)
What makes up the ILM?
the end-feet of Muller (glial cells) of the retina (extend from photoreceptor inner segments to ILM)
What is the RPE?
It is a single layer of cuboidal epithelial cells that constitutes the outermost layer of the retina
Does the RPE contribute to the blood-retina barrier?
Yes, RPE cells are joind by tight junctions near their apical side (adjacent to the neurosensory retina)
What are the physiologic roles of the RPE?
1) visual pigment regeneration, 2) phagocytosis of shed photoreceptor outer segment discs, 3) transport of necessary nutrients and ions to photoreceptor cells and removal of waste products from photoreceptors, 4) absorption of scattered and out of focus light via pigmentation, 5) adhesion of the retina
What compound used in the formation of rhodopsin is generated by the RPE?
11-cis-retinaldehyde
What are the 3 ways in which the RPE acquires vitamin A?
1) through release during bleaching of rhodopsin, 2) from circulation, 3) via phagocystosis of shed photoreceptor outer-segment discs
How many outer-segment discs are shed per day by each photoreceptor?
100/day
When does photoreceptor outer-segment disc shedding occur?
within 2 hrs of light onset for rods; at the onset of darkness for cones
Is the fundus of an old person more or less pigmented than that of a young person?
The older person’s fundus is expected to be less pigmented, if everything else is held equal
What factors contribute to the adhesion of the neurosensory retina to the RPE?
1) passive hydrostatic forces, 2) interdigitation of the outersegments and RPE microvilli, 3) active transport of subretinal fluid, 4) complex structure and binding properties of the interphotoreceptor matrix
What are two old medication preservatives frequently implicated in ocular toxicity?
Thimerosal and benzalkonium chloride (BAK)
What are two (currently) new medication preservatives that break down upon contact with the tear film to reduce corneal toxicity?
Oxychloro complex (Purite) – breaks down in presence of NaCl and H2O; Sodium perborate – breaks down in presence of hydrogen peroxide
What percent of an eyedrop (50 microL) is actually retained in the tear lake of a patient?
at most 20% (10 microL)
What is the half-life for tear lake turnover for an eye?
4 minutes (derived from rate of 16% turnover per minute)
What factors affect the amount of a topically administered drug available for absorption?
1) Limited capacity of tear lake, 2) rate of tear lake turnover, 3) reflex tearing upon drug administration, 4) timing of subsequent med administration
What is the “residence time” of a medication?
The amount of time that a drug remains in the tear reservoir and tear film
What two patient actions can improve the delivery of a topical medication?
1) wait at least 5 minutes between administration of topical drops, 2) avoid blinking (to reduce the nasolacrimal pump mechanism) or apply punctal pressure for 5 minutes after administration
How does systemic toxicity occur with topical medications?
Medication drains into the nasolacrimal duct and enters the nasopharynx, allowing absorption into systemic circulation via nasal mucosa
What is a quick way to convert drug percentatge to mg/mL?
Add a power of ten (i.e., add a 0) to the drug percent (e.g. 1% –> 10 mg/mL)
What is the permeability of the conj relative to the cornea for small water-soluble molecules?
20x that of the cornea
What are the three stages that a medication needs to pass through to enter the AC through the cornea?
1) hydrophobic (epithelium cell membranes), 2) hydrophilic (stroma), 3) hydrophobic (endothelial cell membranes)
What drug factors affect corneal penetration?
1) concentration, 2) solubility in delivery vehicle, 3) viscosity, 4) lipid solubility, 5) drug’s pH, ionic and steric form, 6) molecular size, 7) chemical structure and configuration, 8) vehicle, 9) surfactants, 10) amount of reflex tearing induced, 11) amount of binding to non-target tissue
For what type of medications are subconjunctival, sub-Tenon, and retrobulbar injections particularly helpful?
For drugs with low lipid solubility (e.g. penicillin). These drugs would not penetrate the eye if given topically.
Where are ACh receptors found in the somatic and autnomic nervous systems?
1) motor end plates of EOMs, levator, 2) superior cervical ganglion and ciliary and sphenopalatine ganlgia, 3) parasympathetic effector sites in iris sphincter and ciliary body, lacrimal, accessorry lacrimal, and meibomian glands
What are the two subtypes of AChR?
Muscarinic and nicotinic
What are the 3 types of action of cholinergic agents?
agonist, antagonist, and indirect agonist
What are the 3 actions of topical direct cholinergic agonists?
1) miosis, 2) accommodation, 3) relative opening of TM, facilitating aq outflow
What are the cholinergic agonists available?
1) Acetylcholine, 2) bethanechol, 3, carbachol, 4) pilocarpine
What are the available reversible AChAse inhibitors?
1) Physostigmine, 2) neostigmine, 3) edrophonium
What is the available irreversible AChAse inhibitors?
isoflurophate
Does acetylcholine penetrate the cornea well?
No, it is usually given intracamerally
What are side effects of muscarinic therapy?
1) miosis, 2) cataractogenesis, 3) induced myopia
Is pralidoxime useful in ofrms of acetylcholinesterase inhibition caused by drugs other than organophosphates?
No, pralidoxime is only useful in organophosphate poisoning
What are the actions of muscarinic antagonists?
1) paralysis of iris sphincter –> mydriasis, 2) cycloplegia (lack of accommodation), 3) reduction in iris-anterior capsule contact
What is the oculocardiac reflex?
a reflex bradycardia elictied by manipulation of the conjunctiva, globe, or EOMs. Can be blocked by systemic administration of atropine or retrobulbar anesthesia.
What are the systemic side effects of muscarinic antagonists?
flushing, fever, tachycardia, delirium
What is the mechanism of action of edrophonium?
competitive inhibitor of acetylcholinesterase (reversibly binds to active site of AChAse)
What is the effect of edrophonium in myasthenia gravis?
The inhibition of AChAse by edrophonium allows acetylcholine released into the synamptic cleft to accumulate to levels adequate to act through the reduced number of acetylcholine receptors.
What can be co-administered with edrophonium to reduce side effects?
atropine 0.4-0.6mg IV, to reduce muscarinic receptor activation and leave only nicotinic receptor activation
What are side effects of muscarinic antagonists?
blurred vision, confusion, mydriasis, constipation, urinary retention
What are the two types of anti-nicotinic agents?
non-depolarizing and depolarizing agents
Why should depolarizing nicotinic cholinergic receptor blockers be avoided in avoided in operatinos on lacerated eyes?
Depolarizing agents cause an initial depolarization and contraction that is temporary in most muscles. However, in the multiply innervated fibers of the EOMs (1/5 of fibers in EOMs), the depolarization and contraction is sustained. Contraction of the EOMs –> IOP increase –> expulsion of intraocular contents.
Where are adrenergic receptors found in visual system?
1) cell membranes of iris dilator muscle, 2) Muller muscle, 3) ciliary epithelium and processes, 4) TM, smooth muscle of ocular blood vessels, 5) presynaptic terminals of some sympathetic and parasympathetic nerves
What is the transmitter of most sympathetic postganglionic fibers?
norepinephrine
What is the primary clinical use of direct-acting alpha-1 adrenergic agonists?
stimulation of iris dilator muscle to produce mydriasis
In which patients is the elevatino in blood pressure due to alpha-1 agonists particularly significant?
patients with orthostatic hypotension and patients using drugs that accentuate adrenergic effects (reserpine, TCAs, cocaine, MAO inhibitors)
What is the process by which testing to confirm and localize a sympathetic lesion affecting innervation of the iris dilator muscle is performed?
1) cocaine 4% given, pupil measured at 1 hr –> injured side has less accumulation of norepi, less dlation; 2) give hydroxyamphetamine (releases stored norepi), dilation => preganglionic, no dilation => postganglionic
What is the mechanism of action of apraclinidine?
it is an alpha-2 agonist that prevents release of norepi at nerve terminals
;What are the peak and trough IOP reduction of brimonidine tartrate?
26% and 14%, trough is less than that of nonselective beta blockers
How do beta-2 agonists lower IOP?
reducing aqueous production, improving trabecular outflow, and increasing uveoscleral outflow
How do beta antagonists lower IOP?
by reducing aqueous production by as much as 50%
What are the 6 beta antagonists approved for the treatment of glaucoma?
1) betaxolol, 2) carteolol, 3) levobunolol, 4) metipranolol, 5) timolol maleate, 6) timolol hemihydrate
Is the beta-1 selectivity in betaxolol absolute?
No, it is releative, and some beta-2 effect can remain
What is a paradox associated with beta agonists and antagonists with regard to IOP?
Both beta agonists (e.g. dipivefrin) and beta antagonists can lower IOP. Furthermore, beta agonists and beta antagonists have slightly additive effects in lowering iOP
Which part of the ciliary body secretes aqueous?
The nonpigmented epithelium of the ciliary processes
On what physiologic function does ciliary body production of aqueous depend?
Na+ transport via Na/K/ATPase, which appears to be linked to HCO3 formation in the ciliary body
What are the two portions of Na+ transport related to ciliary body production of aqueous?
Cl- related portion (60%) and HCO3- related portion (40%)
What would potentially serve as a new class of aqueous production reducing drugs?
Drugs inhibiting the Cl- related portion of Na+ transport in the ciliary body
How many times more carbonic anhydrase is present in the ciliary body and kidney than needed?
100x in the ciliary body and 1000x in the kidney
What is a side effect of carbonic anhydrase inhibitors (and particularly acetazolamide, which is actively secreted into the renal tubules)?
metabolic acidosis
Which CAIs are available in topical formulations?
dorzolamide (Trusopt) and brinzolamide (Azopt)
What is the frequency of dosing of prostaglandin analogues?
qhs
What are the side effects associated with prostaglandin analogues?
darkening of the iris and periocular skin (extent is positively correlated with degree baseline pigmentation), conjunctival hyperemai, hypertrhicosis or eyelashes, CME, uveitis
What is an FDA restriction on combination medications?
That the combination be more efficacious than either component drug alone
What are the two most common combination medications for IOP reduction?
Cosopt (timolol/dorzolamide) and Combigan (timolol/brimonidine)
How do osmotic agents affect IOP?
Osmotic agents increase serum osmolarity –> fluid drawn out of eye across vascular barriers into vasculature –> IOP and vitreous volume decrease
What are two uses of osmotic agents?
management of acute glaucoma, reduction of vitreous volume prior to cataract surgery
Which osmotic agents are currently available for ophthalmic use in the US?
1) glycerin, 2) mannitol, 3) urea
Why is urea rarely used as an osmotic agent?
It causes rebound elevation in IOP/vitreous volume, can cause tissue necrosis if it extravasates during administration
What is a serious complication of mannitol and urea use as osmotic agents?
subarachnoid hemorrhage due to brain shrinkage and traction on subarachnoid vessels. The elderly are at increased risk for this complication
What are the classes of ocular anti-inflammatory agents?
1) glucocorticoids, 2) NSAIDs, 3) mast-cell stabilizers, 4) antihistamines, 5) antifibrotics
What are the effects of glucocorticoids at a tissue level?
suppress 1) local hyperthermia, 2) vascular congestion, 3) edema, 4) pain of inflammatory responses, 5) inflamatory tissue remodeling (capillary proliferation, fibroblast proliferation, colagen deposition, and scarring)
Do glucocorticoids affect the afferent limb of immune response?
No, they primarily affect the efferent limb of immune response
What are adverse effects of steroids in the eye?
1) glaucoma, 2) PSC cataracts, 3) exacerbation of infections, 4) ptosis, 5) mydriasis, 6) scleral melting, 7) eyelid skin atrophy
Is ocular hypertension in response to steroids usually reproducible?
Yes
What is the duration of steroid therapy required to develop steroid induced IOP elevation?
> 2 weeks
What duration of steroid therapy can result in permanent elevations of IOP?
> 1 year
Which two steroids have been developed to minimize IOP elevations?
1) rimexolone, 2) loteprednol etabonate
What are the classes of NSAIDs?
1) salicylates, 2) indoles, 3) phenylalkanoic acids, 4) pyrazolones
How is the anti-coagulative effect of aspirin mediated?
Irreversible inhibition of cycloxygenase, which prevents thromboxane formation in anucleate platelets
What is the half-life of platelets and what is the duration of the anticoagulative effect of aspirin?
8-12 day half-life, 7-10 day duration of anti-coagulative effect of aspirin
What is the frequency of dosing of ketorolac?
1 drop qid
What are the corneal complications of topical NSAIDs?
corneal melting, corneal perforation
How many mast cells are contained in the human eye?
50 million
What is the mechanism of allergic conjunctivitis?
triggering antigens couple to reaginic antibodies (IgE on the cell surface of mast cells and basophils, leading to the release of histamine, PG, leukotrienes, and chemotactic factors from secretory granules
What are the actions of histamine?
capillary dilation, increase in capillary permeability, nerve ending stimulation –> pain and itching
Is lodoxamide superior to cromolyn sodium in treating vernal keratoconjunctivitis?
Yes
What is a drawback of traditional mast cell stabilizers?
they take weeks to reach peak efficacy
What is a dosing advantage of mitomycin C over 5-FU?
5-FU requires repeated postoperative injections when used in glaucoma filtering surgery, while mitomycin C requires only a single intraoperative application
What are complications of mitomycin C application during glaucoma filtering surgery?
wound leakage, hypotony, localized sclearal melting
What are the 5 classes of penicillins?
1) penicillin and phenethicillin, 2) PRSPs, 3) broad-spectrum penicillins (e.g. ampicillin, amoxicillin), 4) carbenicillin and ticarcillin (cover pseudomonas and enterobacter), 5) piperacillin, mezlocillin, and azlocillin (cover pseudomonas and klebsiella)
How do 2nd generation cephalosporins differ from 1st generation cephalosporins?
The 2nd generation expand the activity against gram-negative organisms
How do 3rd generation cephalosporins differ from 1st generation cephalosporins?
3rd generation cephalosporins provide expanded gram-negative coverage, but diminished gram-positive coverage. They do provide improved gram-positive coverage compared to 2nd generation cephalosporins, however.
How do 4th generation cephalosporins differ from 3rd generation cephalosporins?
4th gen provide similar gram-negative coverage to 3rd gen (improved over 1st gen) and add anaerobic coverages
What bacteria do all cephalosporins NOT cover?
enterococci, Listeria, Legionella, MRSA
What are the commonly used ophthalmic fluoroquinolones?
ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, ofloxacin
What is the mechanism of action of fluoroquinolones?
Inhibition of DNA gyrase and topoisomerase IV
How are sulfonamides specific to bacteria?
They affect the production of folic acid, which affects only those bacteria that must synthesize their own folic acid
What is the overall incidence of adverse reactions to all sulfonamides?
5%
What is the mechanism of action of tetracyclines?
inhibition of the 30S ribosomal subunit, preventing access of aminoacyl tRNA to the acceptor site on the mRNA-ribosome complex
What is the mechanism of action of aminoglycosides?
binding to the 30S and 50S ribosomal subunits, interfering with initiation of protein synthesis
What is the mechanism of action of vancomycin?
inhibition of glycopeptide polymerization in the cell wall
Have topical or intraocular vancomycin been associated with ototoxicity or nephrotoxicity?
No, unlike systemic vancomycin
What is the mechanism of action of macrolides?
binding to 50S subunit of bacterial ribosomes to interfere with protein synthesis
What are the classes of antifungals?
1) polyenes (amphotericin, natamycin), 2) imidazoles (ketoconazole, miconazole), 3) triazoles (fluconazole and itraconazole), and 4) fluorinated pyrimidine (flucytosine)
How is flucytosine primarily used?
as a PO adjunct to systemic amphotericin B therapy
What are the 3 topical nucleotide analogues used to treat HSV keratitis?
idoxuridine, trifluidine, and vidarabine
Is acyclovir available in the US as a topical formulation?
No, only IV and PO formulations are available in the US
What are the 3 mechanisms by which acyclovir triphosphate (activated acyclovir) inhibits viral growth?
1) competitive inhibitor of DNA polymerase, 2) DNA chain terminator, 3) irreversible binding between viral DNA polymerase and interrupted chain, causing permanent inactivation of viral DNA polymerase
Which medications can be used in thymidine kinase mutants?
vidarabine and foscarnet
What are adverse effects of parenteral acyclovir?
renal toxicity (cyrstalline nephropathy) and neurotoxicity
What is the recommended dosage of valacyclovir for HSV infections in immunocompetent individuals?
1g tid x7-14 days
What is the mechanism of action of foscarnet?
inhibition of DNA polymerases, RNA polymerases, and reverse transcriptases
What are the ocular side effects of cidofovir?
uveitis and hypotony
In what form do the species of acanthamoeba involved in corneal infections exist?
as trophozoites or as double-walled cysts
What is the first-line agent in the treatment of acanthamoeba keratitis?
polyhexamethylene biguanide (PHMB)
What is the chemical form of local anesthetic agents used in ophthalmology?
tertiary amines linked by either 1) ester or 2) amide bonds to an aromatic residue
Why are local anesthetics provided in the form of hycrochloride (HCl) salts?
the protonated forms of ophthalmic local anesthetics are more soluble and undergo hydrolysis more slowly in acidic solutions
Why are unmyelinated fibers anesthetized more easily than myelinated fibers?
Only a small segment of an unmyelinated fiber must have sodium channels blocked to become anesthetized, as opposed to blocking sodium channels in multiple (separated) nodes in myelinated fibers
Which type of local anesthetic (amide or ester) is preferred for retrobulbar blocks?
amide, due to their longer duration of action and lower systemic toxicity
Is licodaine an amide or an ester?
amide
What are the onset and duration of action for lidocaine as a retrobulbar or eyelid block?
5-minute onset, 1-2 hour duration of action
Which nerves are the target of topical anesthetics for anterior segment surgery?
long and short ciliary, nasociliary, and lacrimal nerves
What is the mechanism of action of botulinum toxin?
inhibition of release of acetylcholine at motor nerve terminals
What are the active ingredients in artificial tear preparations?
polyvinyl alcohol, cellulose, methylcellulose, and their derivatives
What is the frequency of dosing for topical cyclosporine (Restasis) for dry eye?
bid
For what purpose are topical hyperosmolar agents used?
The treatment of corneal edema
What does rose bengal highlight, and how does this differ from fluorescein?
Rose bengal highlights devitalized epithelial cells, while fluorescein outlines defects of the corneal or conjunctival epithelium
For what uses has tPA been successfully applied in ophthalmology?
The resolution of fibrin clots after vitrectomy, keratoplasty, and glaucoma filtering procedures
What drugs can be used to treat hemorrhage secondary to excessive fibrinolysis and to prevent recurrence of hyphema?
aminocaproic acid and tranexamic acid
