Cornea and Sclera Flashcards
(193 cards)
0
Q
How much refractive power does the anterior portion of the cornea supply?
A
48 Diopters of plus power
1
Q
Corneal Dimensions
A
H - 12.6mm
V - 11.7mm
2
Q
Radius of curvature of the cornea
A
7.8mm
3
Q
How much of the cornea is spherical/toroidal?
A
Central 1/3rd
4
Q
Corneal Thickness?
A
Central - 0.52mm
Peripheral - 0.65mm
5
Q
How much incident light is transmitted through the cornea?
A
> 99% of light above 400nm
6
Q
Range of radiation that the cornea transmits?
A
310nm in the UV to 2500 in infrared
7
Q
Corneal Layers (Anterior to Posterior)
A
Epithelium Bowman's Layer Stroma Descemet's Membrane Endothelium
8
Q
Define Epithelium
A
Stratified, nonkeratinized, non secretory squamous epithelium
9
Q
3 layers of the epithelium (anterior to posterior)
A
Surface (3-4 cells; sloughing) Wing (1-3 cells; intermediate) Basal Cells (1 cell thick; location of mitosis)
10
Q
Epithelial Turnover
A
7 days
11
Q
Where do basal cells originate from?
A
Stem cells in the basal layer of the limbal epithelium
12
Q
Which layer of the epithelium has high metabolic activity and what does that entail?
A
Basal cell layer
Entails prominent mitochondria, ER and golgi apparatus along with tons of glycogen storage
13
Q
How do stem cells become basal cells?
A
Migrate onto the cornea and differentiate into basal cells thus renewing the supply of basal cells
14
Q
Mitotic rate of epithelium
A
10-15% per day
15
Q
How is the cornea seen when viewed under scanning electron microscopy?
A
As an irregular array of polygonal cells
16
Q
What are smaller, light cells of the cornea viewed under electron microscopy?
A
Younger cells - recently reached the corneae
17
Q
What are larger, dark cells of the cornea when viewed under electron microscopy?
A
Mature cells - will be sloughed
18
Q
What are exfoliation holes of the cornea when viewed under electron microscopy?
A
Breaks in the epithelium - cells in process of peeling off the surface
Superficial cells may be viewable in these holes
19
Q
How do basal cells adhere to the basement membrane and stroma?
A
Hemidesmosomes
20
Q
What are hemidesmosomes linked to in the basement membrane?
A
Anchoring fibrils that pass through Bowman’s layer and into the stroma
21
Q
What should you know about anchoring fibrils?
A
Type VII collagen
Penetrate 2 um into the stroma
End in structures known as anchoring plaques
22
Q
How does photorefractive keratectomy affect the adhesion between basal cells and the stroma?
A
The adhesions are completely destroyed but new ones are reformed post surgery
23
Q
Zonula Occludens
A
Of greatest importance in barrier function
Completely encircle cells - anastimosis of lipid bilayer of the adjoining membranes
Only found between superficial cells of the epithelium
24
What kind of membrane makes up the surface of the cornea?
A highly effective semipermeable membrane
25
Gap junctions
Found in all layers
| More numerous in the basal layers than in the superficial layers
26
Epithelial Ion Transport (Na+ and Cl-)
Na+ is pumped from tears to stroma
Cl- is transported from stroma to tears
Results in a net flux of 0 (balanced)
27
Epithelial Basement Membrane Dystrophy (EBMD) Definition
Basal cells have a decreased number of hemidesmosomes (abnormal adhesion)
28
Result of EBMD
Cornea is susceptible edema and infection resulting in a lot of pain due to recurrent epithelial erosion
29
When does thickening (reduplication) of basement membranes occur?
Aging and diabetic patients
30
How does thickening of basement membranes affect the epithelial layer of the cornea?
Increased risk of epithelial erosion because anchoring fibrils cannot penetrate as deep
31
Where do basal cells of the epithelium rest?
On the basement membrane/basal lamina
32
How thick is the basal lamina?
~40-60 nm thick
33
What does the basal lamina contain?
```
Type IV collagen
Laminin
The proteoglycan perlecan
Fibronectin
Fibrin
```
34
What happens in corneal epithelial wound response?
Mitosis ceases and the attachment to the basement membrane is lost, cells then enlarge and migrate via ameboid movement to cover the defect, mitosis resumes as soon as the wound closes
35
How long would it take a 6mm diameter epithelial wound to close?
Within 48 hours
| Closes at a rate of 60-80um/hr
36
Does protein synthesis by epithelial cells increase of decrease during cell migration?
Increases
37
Energy use in migrating cells
Glycolytic activity increases resulting in decreased levels of glycogen
38
Do migrating cells use aerobic or anaerobic glycolisis?
Anaerobic, it's a quick and dirty process
39
What glucose transporter mRNA increases in number during epithelial wound healing?
GLUT1
40
How long does GLUT1 remain elevated?
At least 2 weeks
41
What growth factor can be found in tear fluid during healing?
Epidermal Growth Factor (EGF) - expressed by corneal epithelium
42
What do stromal keratocytes synthesize?
Keratocyte and Hepatocyte growth factor (KGF & HGF)
43
How is epithelial wound response different in patients with EBMD, Diabetes, Persistent Epithelial Defects and Severe Injuries?
Healing is delayed and normal epithelial adhesion is not established
44
How is wounding in the limbus and peripheral epithelium different between the central cornea and the peripheral cornea?
Decreased length of cell cycle as there are more nutrients in the periphery
45
How long does it take for normal adhesion complexes to come back after basement membrane is removed during experimental keratectomy?
Delayed for more than 12 months
46
Anatomy of Bowman's Layer
~12um thick
Randomly arranged Type I collagen fibrils
Acellular
Considered a modified superficial layer of the stroma
47
Anatomy of the Stroma
An extracellular matrix of collagen fibrils separated by proteoglycans in a lamellar arrangement parallel to the corneal surface
48
What does the ECM of the stroma produce?
Keratocytes and fibroblasts which also maintain the stroma ECM
49
How many lamellas of collagen fibers can be found in the stroma? How do the run?
200-250; They run limbus to limbus
50
How do lamellae lie in the anterior and posterior stroma?
Anterior - obliquely
| Posterior - orthogonally
51
How do the lamellas of collagen run in the limbus?
Circumferentially forming an annulus 1.5 to 2.0mm wide around the cornea
52
Types of collagen fibers in the corneal stroma?
Mostly Type I but also type V and VI
53
Refractive index of Collagen fibers and extrafibrillar matrix?
Collagen fibers - n=1.411
| Extrafibrillar matrix - n=1.365
54
Percent of light that is scattered traveling through the stroma
10%
55
Define Maurice's Principle
Transparency of the cornea is the result of a lattice arrangement that cancels light scatter via destructive interference
56
Requirements of Maurice's Principle
Fibrils must be of equal diameter and all equidistant (NOT SATIFIED BY THE CORNEA)
57
Scleral collagen arrangement
Fibers of the sclera are large with varying diameters and are not orderly or closely spaced resulting in a great deal of light scatter and nontransparency
58
Collagen arrangement of the Stroma of the cornea
Sizes vary within a small range which is a small fraction of a wavelength of visible light and the distance between fibrils is less than 1/2 the wavelength of visible light.
This creates transparency and weak light scatter
59
What happens to the cornea when damage to the epithelial or endothelial barrier?
The cornea swells (uptakes water) resulting in a loss of corneal transparency
60
What do "lakes" of water in the stroma cause?
Increased divergence of refractive index
Increased distance between collagen fibers
Loss of light transmittance
61
What are "lakes" of water in the stroma?
Swelling of the cornea where there aren't collagen fibers
62
How does fibril diameter of the anterior and posterior cornea compare to each other?
Anterior > Posterior
63
How does the density of fibrils compare between the anterior and posterior cornea?
Anterior < Posterior
64
Does the anterior or posterior cornea scatter more light and by how much?
The anterior has a two-fold increase in light scatter when compared to the posterior
65
Rate of tear film evaporation of the cornea
2.5 uL/cm^2/hr
66
By how much does the cornea thin during the day in comparison to the night?
5%
67
Patients with comprised endothelial metabolic pump function (Fuch's endothelial dystrophy) experience what in the morning?
Increased edema due to lack of evaporation of tear film at night when eyes are closed
68
Define Dellen
Localized area of corneal drying and evaporation
69
What happens when Dellen persists?
Decreased stromal fluid flow when stroma hydration is abnormal
in addition to
Minimal lateral flow of water in the cornea
70
What is normal IOP?
Less than 50 mmHg
71
What happens if IOP rises above 50 mmHg?
Epithelial edema occurs as well as increased stromal thickness
72
How is stromal swelling pressure affected by increased corneal thickness?
Pressure of stromal swelling decreases
73
What can mild corneal edema with elevated pressure lead to?
High imbibition (fluid replacement) pressure and subsequent epithelial edema and bullae (fluid filled blisters on the surface of the cornea)
74
How to restore tensile strength to the stroma after damage?
Resynthsize and cross-link collagen
Alter proteoglycan synthesis
Gradual wound remodeling
75
What happens around areas of cellular necrosis in the stroma?
Polymorphonuclear (granulocytes) cells appear which are then followed by monocytes (WBC)
76
How long after an operation does tensile strength take to fully return?
Gradually up to the 4th year
77
Descemet's Membrane Anatomy
Basement membrane the corneal endothelium rests on
10-15 um thick (increases with age)
Composed of Type IV collagen, laminin and fibronectin
78
Descementocele
Descemet's membrane remains intact in some cases following severe corneal ulceration; shows that the membrane is resistant to proteolytic enzymes
Bulges out because no longer supported by stroma
79
Fuch's Dystrophy
Disease of the endothelial cells in which descemet's membrane is abnormally secreted
80
What happen's as Fuch's Dystrophy progresses?
Decreased endothelial cell function resulting in cell loss and corneal decompensation
81
Define guttata
Wartlike excrescences of collagenous material on the posterior surface of descemet's membrane
82
What do guttata cause?
Enlargment of overlying endothelial cells
83
Endothelial Anatomy
A single layer of polygonal cells covering the posterior surface of the cornea
Cell density increases with age
84
Newborn endothelial cell density
> 5500 cells/mm^2
85
Adult endothelial cell density
2500 - 3000 cells/mm^2
86
Minimum endothelial cell density
400-700 cells/mm^2
87
Function of endothelial cells
Metabollically active in transport, synthesis and secretory functions
88
What do endothelial cells contain?
Large nucleus
Numerous mitochondria
Prominent ER
Golgi apparatuss
89
Endothelial Tight Junctions (Macula Occludens)
Create a leaky barrier between aqueous and stroma
90
Gap junctions in the endothelium
Mainly in lateral membranes for intercellular communication
| Do not contribute to the endothelial barrier
91
How much water is maintained in the stroma?
78%
92
If the endothelium is disrupted at what rate does the cornea swell?
127 um/hr
93
At what rate does the cornea swell when just the metabolic pump is disrupted?
33 um/hr
94
What does normal leakage in the corneal stroma supply?
glucose and amino acids
95
What happens to the cornea if it is cooled? And what is this process called?
The cornea swells; this is called temperature reversal
The cornea will return to normal thickness if the temperature returns to normal
96
Where are the Na+K+ATPase pumps located in the endothelium?
In the basolateral membrane
97
Approximately how many Na+K+ATPase pumps are there per cell?
~1.5 x 10^6
98
What does ouabain do to the Na+K+ATPase pump
It stops sodium transport resulting in corneal swelling and preventing temperature reversal. It eliminates the transendothelial potential difference.
99
How do guttata affect Na+K+ATPase pumps?
Increased pump site density allowing for greater capacity for the pump to counteract leaks
100
What does Inflamed, edematous cornea do to the sodium pump?
Decreased pump site density despite increased permeability
101
Function of Sodium Potassium-ATPase
Enzyme located on the plasma membrane of cells
Control corneal hydration
Involved in production of aqueous humor
102
How do the Na+ ions being pushed out result in decreased pressure?
They generate osmotic pressure that water then follows to reduce the created osmotic pressure
103
What does the ideal irrigating solution contain?
```
Energy source (glucose)
Adequate buffer (bicarbonate)
Substrate (calcium)
```
104
How do poorly buffered irrigating solutions affect the cornea?
They may expose the cornea to pH extremes and cause corneal edema
105
What does the irrigating solution consisting of 0.9% saline and lactated Ringer's colution do?
Overcomes the buffering capacity of the aqueous humor (moderate corneal thickening)
106
What does 0.9% NaCl do to the cornea?
Causes corneal swelling (loss of pump barrier)
High corneal swelling
107
What is GBR?
Glutathione bicarbonate ringers solution
Low corneal swelling
108
How are defects in the endothelium healed?
Endothelial cells do not regenerate so cells spread out to cover adjacent areas
109
How does then endothelium heal after keratoplasty?
Migration of endothelial cells over the wound edge to the periphery and tight junctions are developed to establish the endothelial barrier
110
Define Polymegathism
A change in cell size
111
Define pleomorphism
A change in cell shape
112
Do polymegathism and pleomorphism increase or decreasen with age?
They increase significantly with age
113
Define coefficient of variation (CV)
Standard deviation of mean cell area / mean cell area
114
What is normal endothelium CV?
~0.25
115
What does CV > 0.25 mean?
The cell size is variable = polymegathism
116
What percent of a healthy cornea has hexagonal cells?
70-80%
117
A decrease in hexagonal cells with an increase in cells with less than 6 sides shows what?
Endothelial stress = pleomorphism
118
What range of myopia can LASIK treat?
2.25 to 14.5 Diopters
119
Does LASIK have any effect on endothelial cells density of percent of hexagonal cells?
No it does not
120
How much residual stroma must be left above the corneal endothelium after LASIK in order to maintain and protect the corneal endothelial structure and barrier function?
200 um
121
Does the CV of cell size improve or diminish 3 years LASIK and why?
Improves significantly but is most likely due to the removal of contact lenses
122
How does a PK (pentrating keratoplasty) corneal transplant affect cell counts and cell loss rate?
Cell Counts: 575 - 1243 cells/mm^2 with long term follow up
| Cell Loss Rate: 7.8% per year (3-5 years after PK)
123
How much greater is the cell loss rate in a PK cornea than that of a normal cornea?
13X the normal rate
124
How does IOL surgery affect the endothelium?
Mean overall endothelial cell loss rate = 8.5% after 12 months
125
How does Keratoconus (KCN) and Type 2 Diabetes affect endothelium?
Increased CV of cell size and decreased percent of hexagonal cells (50%)
126
After 40 years of age how does Glaucoma with increased IOP affect endothelial cell density? What must one do if the Glaucoma patient also has cataracts?
Decreased; must take special care when performing cataract surgery on a glaucoma patient
127
Contact Lens Use Endotheliopathy Syndrome (CLUE Syndrome)
Polymegathism reported with long-term use of rigid polymethylmethacrylate lenses which is probably secondary to contact lens induced hypoxia
128
What is the cornea innervated by?
The ophthalmic division of the trigeminal nerve via ciliary nerves
129
Which parts of the cornea are not innervated in humans?
Descemet's Membrane and the Endothelium
130
Which corneal receptors are the most prominent?
Nociceptors (pain) - why abrasions, ulcers and bullous keratopathy are all extremely painful
131
What can cause sensory denervation of the Cornea?
Stroke, diabetic neuropathy and herpes simplex
132
What does Sensory Denervation cause?
High incidence of epithelial erosions and neurotrophic ulcers
Loss of foreign body sensations resulting in mechanical corneal damage
133
How does LASIK affect corneal and conjunctival sensitivity?
Decreased for up to 16 months
134
How do CL's affect corneal sensitivity?
Decrease sensitivity in both soft and rigid
135
Where does the cornea get its oxygen from?
Atmosphere (most)
Aqueous Humor
Limbal Vasculature
136
How does aqueous humor O2 levels in aqueous humor compare to that of tears?
Lower
137
How much more oxygen does the epithelium consume than the stroma?
10X
138
How is oxygen delivered to the cornea during sleep?
Via vascularized superior palpebral conjunctiva
139
What percent of oxygen is delivered to the cornea when the eyes are opened and closed?
```
Opened = 21%
Closed = 8%
```
140
What is aphakia?
Cataract removal
141
How does aphakia affect the O2 demands of the cornea?
There may be an increase in aqueous humor oxygen thus giving greater tolerance to hypoxic stress (CL use)
142
Where do nutrients for the cornea come from?
Mostly the aqueous humor
Lesser amounts in tears and limbal vessels
Glucose from glycogen stores in corneal epithelium
143
How much of the cornea's oxygen reserve is used up after 8 hours of wearing hard contact lenses? What are the results of this?
80% is used up
Results in a 20% increase in corneal thickness (edema)
Not much better in soft lenses
144
Embden-Meyerhof Pathway
How glucose stores from the aqueous humor or glycogen stores are converted to pyruvate in the cornea
145
Symptoms of epithelial edema
Halo and rainbow formation
Increased glare sensitivity
Decreased contrast sensitivity
146
In which direction does stromal edema manifest?
Posteriorly - buckling of the stroma and descemet's membrane causes vertical striae
147
At what oxygen level can detergesence (decrease in swelling) be maintained?
As low as 25 mmHg
| Any lower results in corneal hardening
148
Oxygen exchange and small diameter hard lenses
Impermeable to oxygen
| Good movement needed for tear exchange
149
Oxygen exchange in large diameter soft lenses
Oxygen permeability needed for diffusion through the lens itself
Tear pump exchange (lesser)
150
Underlying mechanism of Polymegathism
Byproducts of long term hypoxia and stress (12HETE) inhibit the Na+K+ATPase of the endothelial metabolic pump
151
When does polymegathism occur?
Only after long term volume regulation stress (CL wear) and in cornea's of diabetic patients
152
Effects of extended wear CL's on metabolism
Decreased rate of mitosis
Decreased oxygen uptake and glucose utilization
Decreased intercellular desmosomes
153
Consequences of EW CL effects on metabolism
Compromised epithlial barrier function
| Increased likelyhood of ulcerative microbial keratitis
154
What is Xerophthalmia and what causes it?
Keraitnization of the epithelium; caused by a lack of vitamin A which is required for mucin production (usually found in developing countries)
155
What are Bitot's Spots?
Triangular foamy lesions seen in the conjunctiva
156
What is the initial barrier to drug penetration and what does it allow through?
Epithelium (tight junctions)
Favors lipid-soluble hydrophobic compounds
Limits adsorption of hydrophilic, ionized substances
157
How does the stroma affect drug penetration?
Barrier to lipid-based drugs
158
How does the endothelium affect drug penetration?
Mostly depends on size of the molecule
159
Ways to increase drug penetration
```
Press on lacrimal sac
Use viscous drops, suspensions and ointments
Slow release delivery systems
Contact lenses
Porcine collagen corneal shields
```
160
What is the action of the preservative BAK?
It is a detergent (breaks down bacterial cell walls)
May also make the endo and epithelium susceptible to damage
161
Effects of BAK
One drop of 0.01% BAK increases corneal permeability to fluorescein
Inhibits epithelial wound healing
162
How may BAK affect severe dry eye patients?
May risk further damage as they are already more permeably to fluorescein due to their compromised epithelial barrier
163
EDTA
Used to stabilize BAK containing formulations by chelating calcium (breaks up tight junctions)
Try not to use especially in dry eye patients
164
Scleral Anatomy
Connective tissue consisting of fibroblasts, collagen (Type I) and proteoglycans
70% water
30% dry weight; 75% of which is collagen fiber
165
What overlies the sclera?
Episclera
166
Is the sclera vascular?
No, it is mostly avascular with exceptions including superficial vessels of the episclera and the intrascleral vascular plexus
167
Features of the posterior sclera
Contains scleral canal and lamina cribrosa (optic nerve passage)
Perforation site for arteries, veins and nerves
Tendon's of recti muscles insert into superficial sclera collagen
168
How much of the total surface area of the globe is sclera?
95%; thickness decreases at the equator and increases near the optic nerve
169
Arrangement and diameter of scleral collagen fibers
Diameter ranges from 25 - 230nm
| Arranged in bundles
170
Connections between the sclera and myopia
Form vision deprivation results in axial elongation
| Changes in rate of proteoglycan synthesis and accumulation within the sclera also results in axial elongation
171
Aging effects on sclera
Degeneration of collagen and elastic fibers
Loss of GAG's*
Scleral Dehydration*
Accumulation of lipids and calcium salts (yellow sclera)
172
Aging effects on sclera cause?
Increased tissue density
Scleral thinning and yellowing
Decreased scleral elasticity
Sclera and Cornea get tougher
173
Is the sclera innervated?
The stroma of the sclera is devoid of innervation but does allow passage of nerves
Axons of parasympathetic origin present at scleral spur
174
Primary Mechanism of Transscleral Delivery of Drugs
Diffusion through aqueous pathway
*Possibly treat posterior segment disease*
175
Factors controlling diffusion rates in the sclera.
Tissue Hydration
Tissue Thickness
Size and Volume fraction of proteoglycans present
176
At what pH does the sclera swell the least?
pH 4
177
What is the only treatment that can alter scleral permeability?
Surgical thinning which increases permeability
178
How does increased pressure affect scleral permeability?
Decreases permeability to small molecules by half
179
What is a strong function of permeability?
Molecular weight
180
How do prostaglandins affect permeability? And what does this result cause?
They increase permeability which causes and increased expression of matrix metalloproteinases
181
How to increase Transscleral delivery for large molecules?
Take advantage of thinner regions of tissue
Increase scleral hydration
Modification of scleral ECM
183
The horizontal and vertical diameters of the cornea?
H - 12.6 mm V - 11.7 mm
184
Three layers of cells in the epithelium of the cornea
1. Surface cells (3-4 cells thick)2. Wing cells (1-3 cells thick) 3. Basal cells (1 cell thick)
185
What is the turnover rate of the epithelium?
7 days
186
Basal cells have a ____ metabolilic activity
high
187
What is the mitotic rate of epithelium?
10-15 % per day
188
Anchoring fibrils are a type ____ collagen and penetrate _____ into the stroma
Type VII collagen 2 um
189
The adhesion complex is ______ _______ after surgery
completely destroyed
190
Where are zonula occludens found?
Only found between the superdicial cells of the epithelium
191
How thick is Descemet's Membrane?
10-15 um
192
What is deturgescence?
relative dehydration maintained by the normal cornea that is necessary for transparancy
193
What is the lowest oxygen level that must be sustained to maintain corneal transparency (deturgescence)?
25 mm Hg
