Corneal and Sclera part 2 Flashcards
what are 2 things that prevent the corneal stroma from swelling
- the barrier function of the endothelium
2. the pump function of the endothelium
what percentage is the water in the corneal stroma maintained at
78%
which contributes more to prevent corneal stroma swelling: the epithelium or endothelium border
the epithelium
what 4 things occur to the corneal stroma is there is edema
displace the fibrils, increase scatter, halos, and bad vision
when the endothelium is disrupted, what is the rate that the cornea swells at
127 microns per hour
what happens when the cornea swells
movement of fluid and solutes from the aqueous humor into the stroma, through the incomplete barrier of the intact cell layer, it reaches the max amount and stops
if the metabolic pump is disrupted, what is the rate the cornea swells at
33 microns per hour
is it normal to have leakage of fluid into the stroma
yes it is a vital function because the cornea is avascular
what does the fluid that leaks into the cornea provide
nutrients (glucose and amino acids)
what is the maintenance of corneal thickness and water content dependent on
temperature (metabolically energy-dependent process)
what happens if the cornea is cooled
it swells
what happens if the cornea has a normal temperature
the cornea has normal thickness
what is the phenomenon called where temperature affects corneal swelling
temperature reversal
how much water is moved by the endothelium from stroma to aqueous humor per hour
6-8 ml
where is the Na+K+ATPase pump located in the corneal endothelium
in the basolateral membrane
how many Na+K+ATPase pumps are there per cell
1.5 x 10^6
what inhibits the N+K+ATPase pumps in the corneal endothelium
Ouabain
how does Ouabain inhibit the pumps in corneal endothelium
it stops sodium transport, causes corneal swelling, prevents temperature reversal and eliminates the transendothelial potential difference
how is the N+K+ATPase pump affected in corneas with Guttata
increase in pump densities per cell and greater capacity for the pump to counteract the leak
what are 2 ocular functions of the Na+K+ATPase pump
- control of corneal hydration
2. production of aqueous humor
why does the corneal stroma readily take up water
to maintain corneal hydration
what happens when the sodium ions are transported into channels between endothelial cells
it creates an osmotic pressure and water follows
how is the N+K+ATPase pump affected in corneas with inflamed edematous
decreased pump site density despite the increased permeability
what 3 things should an ideal intraocular irrigating solution contain
- energy source- glucose
- adequate buffer- bicarbonate
- substrate- calcium, glutathione
what aids the sodium ions in the right direction after being pumped
the density of sodium ions in Descemet’s membrane
what happens in poorly buffered intraocular irrigating solutions
may expose the cornea to pH extremes and cause corneal edema
what does normal saline lack
the components of the aqueous humor
what is the buffers job in a solution
to maintain the pH
what happens with 0.9% NaCl irrigating solution
causes cornea swelling (loss of pump and barrier)
what is an ideal intraocular irrigating solution
Glutathione bicarbonate ringers solution GBR
what happens with 0.9% saline and lactated Ringer’s solution
the cornea is unable to resist the pH change (buffering capacity of the aqueous humor)
what happens when a large defect occurs as a result of surgical insult or a decompensation episode in keratoconus
a more extensive cell migration occurs
what is keratoplasty
a corneal transplant
what are 2 things in the endothelium that are needed for proper corneal function
- adequate endothelial cell density
2. endothelial cells of uniform size and shape
what happens to the cells after a keratoplasty
migration of endothelial cells over the wound edge to the periphery, development of tight junctions, development of pumps
what is polymegathism
a change in cell size
what is pleomorphism
a change in cell shape
what causes both polymegathism and pleomorphism to increase
age
what is CV (coefficient of variation)
the standard deviation of mean cell area
what is normal endothelium CV
about 0.25
what if CV > 0.25 in the endothelium
the cell size is variable and is polymegathism
a healthy cornea has what percentage of hexagonal cells
70-80%
what would indicate endothelial stress and pleomorphism
a decrease in hexagons with an increase in cells with more than or fewer than 6 sides
what is the range of myopia that LASIK has no significant effect on endothelial cell density or percent of hexagonal cells
2.25 to 14.5 D
what does the residual stroma post-LASIK need to be in order to maintain and protect the corneal endothelial structure and barrier function
200 microns
how many years does it take for the CV of cell sizes to improve after LASIK if the patient previously wore CL
3 years
what part of the cornea does LASIK affect
corneal stroma not endothelium (about 12-15 microns per diopter)
will cataract surgery cause endothelial cell loss in the cornea
yes - study saw mean loss of 8.5% after 12 months
what two diseases can cause a decrease in cell density
type 1 diabetes and glaucoma
what would cause corneal endothelium to remodel
stress (KCN) and excessive glucose (diabetes type 2)
what happens to the endothelial corneal cells in keratoconus (KCN) and Type 2 diabetes
morphology changes, no decrease in cell density, increase of cell size and decrease of hexagonal cells
what happens to the corneal endothelium in glaucoma suspects with elevated IOP (ocular hypertension)
after 40 y/o there is a decrease in endothelial cell density
what happens to endothelial cells in long-term use of rigid polymethylmethacrylate lenses and daily/extended wear CL’s
polymegathism
why would you need to take special care when doing cataract surgery on those with glaucoma or diabetes
they have a decreased endothelial cell density
what is responsible for the change in endothelial morphology in CL’s
CL induced hypoxia- CLUE syndrome (contact lens use endotheliopathy)
does the cornea have nerves
yes- richly supplied with sensory nerves
what is the source of innervation for the cornea
ophthalmic division of the Trigeminal nerve (CN5) via anterior ciliary nerves
which parts of the cornea are not innervated
Descemet’s membrane and endothelium
what type of nerve classification are most corneal receptors
nociceptors
what are nociceptors
stimulation results in the perception of pain
why are corneal abrasions, ulcers and bullous keratopathy extremely painful conditions
the cornea has nociceptors which have the lowest threshold for mechanical stimulation
what 3 conditions result in corneal sensory denervation
stroke, diabetic retinopathy, and herpes simplex
what does sensory denervation cause in the cornea
high incidence of epithelial erosions and neurotrophic ulcers
what would result from the loss of foreign body sensations on the cornea
mechanical cornea damage
what happens to corneal sensitivity after LASIK
causes a decrease in corneal and conjunctival sensitivity up to 16 months
do both soft and rigid gas-perm CL reduce corneal sensitivity
yes- or you would be aware of the CL on the eye
corneal metabolism depends on oxygen from what 3 things
atmosphere, aqueous humor, and limbal vasculature
what is the largest source of oxygen for the cornea
atmosphere
what is the normal amount of oxygen in aqueous humor compared to tears
40mm Hg in aqueous humor and 155mm Hg in tears
how much more oxygen does the epithelium consume compared to the stroma
10 times more
when the eye is closed, how is oxygen delivered to the cornea
by the vascularized superior palpebral conjunctiva
what are the percentages of oxygen delivered to the cornea for the eyelid open and eyelid closed
21% for open and 8% closed
what happens to oxygen tension following cataract surgery
it may increase in the aqueous humor as a result of decreased oxygen metabolism by the crystalline lens
why would the cornea have a greater tolerance for hypoxic stress following cataract surgery
the oxygen in the aqueous supplements that in the tears
what delivers the nutrients to the cornea
the aqueous humor via the ciliary body (lesser amounts by the tears and limbal vessels)
how does the cornea receive glucose
from the glycogen stores in the corneal epithelium
why does wearing CL cause edema
decreases available oxygen to the corneal epithelium, resulting in corneal edema (20% increase in corneal thickness)
how much oxygen reserve do hard CL use in 8 hours of wear
80%
what is the glucose from the aqueous humor or glycogen stores converted to
pyruvate by the Embden-Meyerhof pathway (glycolysis)
what is the product from the conversion of glucose to pyruvate
two molecules of adenosine triphosphate (ATP) per glucose molecule
what increases under hypoxic conditions that causes corneal edema
increase in lactate production (pyruvate is converted by lactate dehyrogenase to lactate)
what are 3 symptoms of epithelial edema
halo and rainbow formation, increased glare sensitivity (light scattering) and decreased contrast sensitivity
which direction does stromal edema manifest
posterior direction (because the anterior surface of the cornea is structurally fixed by Bowmans layer and the anterior stroma)
what causes vertical striae in the cornea
buckling of the stroma and Descemet’s membrane
what percentage of edema do vertical striae become visible
8%
how does increased amounts of lactate lead to corneal edema
the lactate diffuses from the epithelium into the stroma osmotically, inducing epithelial and stromal edema
at what oxygen level can corneal deturgescent (clarity) be maintained
as low as 25mm Hg
what is a disadvantage of wearing a hard CL versus a soft lens
impermeable to oxygen (soft has oxygen permeability)
what is an advantage of having a small diameter of a hard CL
good movement needed for tear exchange
what is the underlying mechanism of polymegathism
certain byproducts of long term hypoxia and stress (12HETE) has the ability to inhibit the Na+K+ATPase of the endothelial metabolic pump
what is a disadvantage of have a large diameter of a soft CL
moves minimally on the eye- bad for tear exchange
what does CL wear stimulate in polymegathism
the arachadonic acid cascade in corneal epithelium from the lenses and the protein they absorb from water
what causes volume-regulated stress of the cornea
long term CL (10 years) and diabetic patients
extended wear CL have been associated with what 3 things
decreased rate of mitosis (rubs on the stem cell layer), reduced oxygen uptake and glucose utilization, and smaller numbers of intercellular desmosomes
what condition can occur due to the compromised epithelial barrier in EW CL
increased likelihood of ulcerative microbial keratitis
why is the epithelial barrier compromised in extended wear CL
there is reduced metabolic activity
what does a lack of vitamin A cause
Xerophthalmia (occurs late in the progression of a vitamin A deficiency)
what happens with Xerophthalmia
keratinization of the epithelium (becomes opaque)
what are the symptoms of Xerophthalmia
keratinization (opaque), decreased mucin production, dry spots on cornea, night blindness (prior to xerophthalmia)
what requires vitamin A
mucin production
what is the volume of a normal adult tear film
7-9 microliters
what is the maximum amount of fluid that the cul-de-sac can contain
20-30 microliters
what is the amount of the average drop of topical medication
50 microliters
what would cause tear dilution or a change in tear pH levels
reflex tearing caused by irritating or hypertonic solutions
what might decrease the bioavalability of drugs
increased protein concentration in tears bathing inflamed or infected eyes
what is the initial barrier for drug penetration
the epithelium (tight junctions)
how is the epithelium a barrier for drugs
they limit the absorption of hydrophilic, ionized substances and favor penetration of lipid-soluble hydrophobic compounds
what does the loss of corneal epithelium greatly enhance when instilling drugs
penetration of hydrophilic water-soluble pharmacologic agents (such as gentamicin)
in clinic, how can you disrupt the corneal epithelium to make drug delivery easier
anesthetic causes a few spots of epithelial damage
how is the corneal stroma a drug barrier
the hydrophilic nature results in a barrier to lipid based drugs
how is the corneal endothelium a drug barrier
drug penetration is determined by the molecular size
how can you increase drug penetration
by increasing duration of the contact of the drug with the ocular surface
what are examples of mechanical means to increase drug penetraion
press on lacrimal sac, use viscous drops, suspensions or ointments
why would you want to block a beta blocker from entering the body
because it will lower the heart rate (press on lacrimal sac to prevent)
what are examples of slow release delivery systems to increase drug penetration
contact lenses, porcine collagen corneal shields and punctal plugs
what are 4 types of preservatives used in eye drops
BAK (benzalkonium chloride), chlorhexidine digluconate, polyquarternium-1, and thimerosal
what is the most common type of drug preservative
BAK (benzalkonium chloride)
which preservative has been discontinued because of allergic reactions
Thimerosal
what is the antibacterial action of BAK based on
the detergent property of the compound
what does the detergent property of BAK do to bacterial cells
breaks down bacterial walls (or other walls) that it is exposed to. It also damages epithelium and endothelium cell walls
what happens when one drop of 0.01% of BAK is used
it increases the permeability of the cornea to fluorescein
what type of healing does BAK inhibit
epithelial wound healing
which patients have an increased fluorescein permeability secondary to the compromised epithelial barrier
severe dry eye patients
what is the down side of using EDTA to counteract BAK
it chelates calcium, which is required for maintenance of tight junctions
what is ethylenediaminetetraacetic acid (EDTA)
used to stabilize BAK-containing formulations
should ophthalmic products contain EDTA
no, formulations with EDTA should be avoided by patients with dry eyes (EDTA may increase corneal permeability)
what is the sclera made of
connective tissue containing fibroblasts, collagen, and proteoglycans
how much of the sclera is water
70%
how much of the sclera is dry weight
30%
what percentage of the dry weight of the sclera is collagen fibers
75%
the sclera is essentially avascular, what are the 2 sources for the exceptions
superficial vessels of the episclera and intrascleral vascular plexus
what type of collagen is in the sclera
type 1: resists tension
what is located at the posterior sclera
scleral canal and the lamina cribrosa
which arteries, veins, and nerves go through sites of perforation at the posterior sclera
long and short posterior ciliary arteries, short ciliary veins, ciliary nerves and the vortex veins
where do the tendons of the recti muscles insert
into the superficial sclera collagen
how much of the total globe is the sclera
95%
where does the scleral thickness decrease
towards the equator and right before the recti muscles insert
where is the sclera the thickest
near the optic nerve
what is the scleral fiber in diameter
25-230nm
how are the scleral fibers arranged
randomly
what is the diameter of the corneal fibers
25nm
what are the 3 distinct fibers in the sclera
elastic, elaunin, and oxytalan
why would infants have a bluish tint in their sclera
the sclera is still developing and the choroid is visible
what does form vision deprivation result in
axial elongation of the ocular globe causing myopia
how do changes in the rate of proteoglycan synthesis cause myopia
it accumulates in the sclera causing axial elongation
does the stroma increase or decrease in tissue density as we age
increase
what 4 things happen to the sclera as age increases
progressive degeneration of collagen and elastic fibers, loss of GAGs, scleral dehydration, and accumulation of lipids and calcium salts
what happens to the prostaglandins as it enters the eye
the drug gets into the eye in a readily absorbed form and changes the structure into the active compound and get absorbed in the sclera through the ciliary base
what color does the sclera turn as we age
yellow and it thins
is the sclera more or less rigid as we age
more rigid- decreased scleral elasticity
is the sclera innervated
no but is allows passage of nerves
what is the primary mechanism of drug permeation across the sclera
passive solute diffusion through an aqueous pathway
what are 3 factors that control diffusion rates of drugs across the sclera
tissue hydration, tissue thickness, and size and volume fraction of proteoglycans present
what is the pH level the sclera can swell to
near a pH of 4
what 3 things do not alter scleral permeability
age, cryotherapy and diode laser treatments
does surgical thinning increase or decrease scleral permeability
increases
does scleral permeability increase or decrease with increased molecular weight and radius
decreases
what IOP can decrease sclera permeability to small molecules by half
15-60 mmHg
if the sclera is exposed to various prostaglandins in organ culture, is there an increase or decrease in pemeability
increase
what causes an increase in expression of matrix metalloproteinases
when the sclera is exposed to various prostaglandins
if you have a large molecule, how can transscleral delivery be improved
taking advantage of thinner regions of tissue, increasing scleral hydration, and transient modification of sclera ECM
