Cornea Flashcards
What is another name for the surface of the cornea?
air-tissue interface
Which structures of the eye are responsible for most of the refraction of the eye?
the surface of the cornea and associated tear film
What is the most important property of the cornea?
transparency
What is an additional important property of the cornea (as well as transparency)?
presents a tough physical barrier to trauma and infection
What are 4 important factors that are responsible for corneal transparency?
- avascularity
- regularity and smoothness of covering epithelium
- regular arrangment and spacing of the extracellular nad cellular components in the stroma
- the above is dependent on the state of hydration, metabolism and nutrition of the stromal elements
What are the dimensions of the cornea?
smaller in the vertical than in the horizontal
vertical: 10.6mm
horizontal: 11.7mm
(however viewed from behind, the circumference appears circular)
What is the central radius of the cornea?
7.8mm (peripheral corneal curvatuer is less marked)
What is the distribution of the thickness of the cornea like?
it is thicker at the periphery (0.67mm) than in the centre (0.52mm)
How can the shape of the cornea be visualised with imaging methods?
computerised video keratography, as a series of colour-coded topography maps
What condition is computerised video keratography (CVK) frequently used to diagnose?
astigmatism (also early keratoconus)
What do hotter (closer to red) colours represent in CVK?
higher dioptric values
How are images generated from CVK?
projection of over 6000 points of light onto the corneal surface in the form of placido rings. The images are analysed by the computer and complex colour-coded topographical/dioptric maps can be constructed
What is seen on CVK in astigmatism?
multiple higher points of the cornea:
How many layers is the cornea composed of?
5 layers
- corneal epithelium
- anterior limiting lamina: Bowman’s layer
- Substantia propria or corneal stroma
- Posterior limiting lamina (Desçement’s membrane)
- Corneal endothelium
How thick is the corneal epithelium?
50- 60 micrometres thick
What type of epithelium comprises the corneal epithelium?
stratified (5-6 layers), squamous, non-keratinised epithelial cells (superficial cells are flattened, nucleated and non-keratinised)
How do the superificial cells of the corneal epithelium form a barrier?
extensive tight junctions
How are adjacent cells in the corneal epithelium held together? And how are they held to the underlying basal lamina?
adjacent cells: desmosomes
to underlying basal lamina: hemidesmosomes and anchoring filaments
What are 2 features that characterised the anterior surface of the corneal epithelium?
numerous microvilli and microplicae (ridges) whose glycocalyx coat interacts with, and helps stabilise, the precorneal tear film
What is the function of the microvilli and microplicae (ridges) on the anterior surface of the cornea?
glucocalyx coat interacts with and helps stabilise the precorneal tear film
How are new cells in the corneal epithelium derived?
from mitotic activity in the limbal basal cell layer, whcih displace existing cells both superficially and centripetally in an X, Y, X migratory pattern
How does the corneal epithelium respond to repair disruptions in its integrity?
rapidly by amoeboid sliding movements of cells on the wound margin followed by cell replication
What layer do the basal epithelial cells of the corneal epithelium rest on? What 2 sub-layers is this form of?
basal lamina:
lamina lucida, 25nm
lamina densa 50nm
How is corneal epithelial cell adhesion maintained to the basal lamina?
basement membrane complex, which anchors the epithelium to the Bowman’s layer via a complex mesh of anchoring fibrils (type VII collagen) and anchoring plaques (type VI collagen)
these interact with the lamina densa and the collagen fibrils of Vowman’s layer
What are the 2 types of collagen involved in anchoring the corneal epithelium tohe Bowman’s layer?
- anchoring fibrils: type VII
- anchoring plaques: type VI
What type of cells is the cornela epithelium devoid of?
melanocytes
What type of cells are high in numer in the limal and peripheral corneal epithelium?
myeloid-derived major histocompatibility complex (MHC) class II antigen-positive dendritic cells (aka Langerhans cells)
In addition to the limbal and peripheral corneal epithelium, where else are myeloid-derived MHC class II antigen-positive dendritic cells present in low numbers?
in the central cornea (20-25 cells/ square mmm)
What is astigmatism usually the result of?
differences in the radius of curvature in the vertical and horizontal meridians
Are there MHC class-II negative dendritic cells in the corneal epithelium?
some studies have shown them in the mouse central corneal epithelium but these findings are difficult to verify
in vivo confocal microscopy (IVCM) suggests normal human central corneal epithelium contains dendritic cells but immunophenotype can’t be ascertained in the clinic
What are 2 features of the cornea considered crucial to the success of corneal grafting?
- paucity of antigen presenting cells such as dendritic cells in the human corneal epithelium
- avascular nature of the cornea
What is the Bowman’s layer (aka anterior limiting lamina)?
lies between corneal epithelium and corneal stroma
is a modified acellular region of the stroma
What is the thickness of the Bowman’s layer?
8 - 12 micrometres thick
What structures form the Bowman’s layer of the cornea?
fine, randomly arranged, collagen fibrils (20-30nm diameter), type I, III, V and VI
What are the 4 types of collagen within the corneal Bowman’s membrane?
- type I
- type III
- type V
- type VI
What separates the Bowman’s layer from the corneal epithelium?
thin basal lamina
the anterior surface of the Bowman’s layer is well delineated
What is the delineation like between the Bowman’s layer and the corneal stroma?
the posterior boundary of the Bowman’s layer merges with the stroma
Where does the edge of the Bowman’s layer terminate?
terminates abruptly at the limbus
What does the image show?
layers of the cornea
What is another name for the corneal stroma?
substantia propria
What is the structure of the corneal stroma?
dense connective tissue of remarkable regularity
2 micrometre thick, flattened, collagenous lamellae (200-250 layers) oriented parallel to the corneal surface and continuous with the sclera at the limbus
Which corneal layer makes up the vast majority of the cornea?
the corneal stroma (substantia propria)
What is the thickness of the collagenous lamellae which form the corneal stroma?
predominantly 2 micrometres thick
How many layers of collagenous lamellae are the in the corneal stroma?
200-250 layers
How does the corneal stroma connect with the sclera at the limbus?
continuous with the sclera at the limbus
How are the collagenous lamellae in the corneal stroma oriented?
parallel to the corneal surface and continuous with the sclera at the limbus
What exists between the collagenous lamellae which form the corneal stroma?
extremely flattened, modified fibroblasts known as keratocytes
What is the shape of the keratocytes within the corneal stroma?
stellate in shape with thin cytoplasmic extensions containing conspicuously few distinctive organelles when viewed in conventional cross-sections
What do frontal sections reveal about keratocytes within the corneal stroma?
an abundance of organelles and a novel network of fenestrations on their surface
What may be the purpose of the fenestrations on the keratocytes within the corneal stroma?
may facilitate the diffusion of metabolites or the mechanical anchoring or attachment of collagen bundles
What is the density of keratocytes int he anterior corneal stroma?
20 000 - 24 000 cells / mm2 (decreases posteriorly before increasing again near Descemet’s membrane)
What is the benefit of in vovo confocal microscopy (IVCM) of the human cornea?
powerful non-invasive instrument used in clinical evaluation of corneal abnormalities and normal structure of the tear film, cornea and conjunctiva
How are IVCM images obtained?
performing optical sections of the cornea using non-coherent white light
cells and matrix components with differing reflective propoerties within the transparent cornea can be imaged
What is the advantage of a confocal approach to imaging the cornea?
only information in a narrow focal plane, approx 4-25µm in thickness, is analysed or collected and scattering of light from structures outside the focal plane is minimised
How do optic allow in vivo confocal microscopy to take place?
optics allow the light beam to be scanned (in the x and y axes) in a narrow area at one focal plane before shifting in depth to another plane of focus (z axis) where the scan is repeated. Thus a series of optical slices of high lateral resolution (1-2µm) can be obtained and cellular detail can be visualised
What is being shown in the IVCM images from A-D?
- A: epithelium
- B: sub-basal nerve plexus and dendriform cells which may represent Langerhans cells
- C: keratocytes in the posterior stroma
- D: corneal endothelial cells
What is shown in the image?
electron micrograph of the corneal epihtelium (including basal cell layer B, Bowman’s layer BL, Descemet’s membrane DM, endothelium E, epithelium S, substantia proporia SS, W wing ells)
What is shown in the image?
diagram showing arrangement of the collagenous lamellae (CL) and interposed keratocytes (K) in the corneal stroma
What is shown in the image?
keratocyte K among regularly spaces collagenous lamella
How a keratocytes within the corneal stroma connected to their neighbouring cells?
by gap junctions
How are keratocytes arranged in the corneal stroma?
in a corkscrew pattern spiralling from the epithelium to the endothelium
What is the orientation of the collagenous lamellae in the corneal stroma in relation to each other?
highly organised orthagonal ply, adjacent lamellae being orientated at right angles, with the exception of the anterior third in which they show a more oblique orientation
What is the predominant type of collagen fibres in the corneal stroma? What are their dimensions?
type I: 30nm diameter, 64-70nm banding
What features of the collagen fibres in the corneal stroma is its transparency dependent on? 2 things
- regular diameter of collagen fibres (influenced by presence of type V collagen)
- spacing of collagen fibres (interfibrillary distance) (influenced by negatively charged glycosaminoglycans and proteoglycans)
What helps to influence the regular diameter of collagen fibres in the corneal stroma to ensure transparency?
presence of type V collagen
What regulates interfibrillary distance (spacing) of collagen fibres in the corneal stroma ensuring transparency?
negatively charged glycosaminoglycans (GAG) and proteoglycans forming bridges between the collagen fibrils
What are the glycosaminoglycans that are predominant in the human cornea? 2 kinds
- keratan sulphate
- chondroitin (dermatan) sulphates
(it is unusual in that there is NO hyaluronate)
What sensory nerve fibres are present int he anterior layers of the corneal stroma?
nerve fibres en route to the corneal epithelium
What type of cells have mouse studies revelaed may be present in the corneal stroma?
macrophages, some of which communicate via novel cell-cell membrane nanotubes
What is another name for Desçemet membrane?
posterior limiting lamina
What is the structure of Desçemet’s membrane?
thin, homogeneous, discrete, periodic acid-Schiff-positive layer between the psoterior stroma and the endothelium
What is the thickness of Desçemet’s membrane?
8-12 µm
What does Desçemet’s membrane represent in relation ot the corneal endothelium?
modified basement membrane of the corneal endothelium
What are the 2 parts the Desçemet’s membrane is divided into?
- anterior third that is banded
- posterior two-thirds that are non-banded (aka homogeneous)
What 3 things is Desçemet’s membrane rich in?
- basement membrane glycoproteins
- laminin
- type IV collagen
What type of collagen is Descemet’s membrane rich in?
type IV collagen
In addition to type IV collagen in Desçemet’s membrane, what other 3 types of collagen are present and what are their roles?
- type VIII collagen: in anterior banded region
- type V: involved in maintaining adherence at interface of Desçemet’s membrane with most posterior lamellae of stroma
- type VI: as for type V
How does Desçemet’s membrane relate to the surrounding structures peripherally?
it is continuous peripherally with the cortical zone of the trabeculae in the trabecular meshwork
What structures apart to appear in the periphery of Desçemet’s membrane with age?
microscopic wart-like protuberances (Hassall-Henle bodies) containing long-banded (100nm) depositis of unknown nature
What is the name of the peripheral termination of the Desçemet’s membrane which is frequently thickened?
Schwalbe line, the anterior limit of the trabecular meshwork
What tends to happen if Desçemet’s membrane is disrupted?
if tends to curl inwards towards the anterior chamber
What type of cells make up the corneal endothelium?
simple squamous epithelium on the posterior surface of the cornea
What is an important role of the corneal endothelium?
maintaning corneal hydration and thus transparency
How is fluid frequently lost at the ocular surface?
by evaporation
What facts demonstrate the fact that fluid is contantly being lost via evaporation at the ocular surface?
increased corneal thickness after a night of lid closure and when an impermeable contact lens is placed over the epithelium
What is the struture of the corneal endothelium?
rests on Descemet’s membrane and forms an uninterrupted polygonal or hexagonal array, or mosaic
What are 2 techniques that allow polgyonal/hexagonal mosaic formation of the corneal endothelium to be seen?
- in vivo specular microscopy
- in vivo confocal microscopy
What is the height and diameter of the cells in the corneal endothelium?
5-6 µm in height and 18-20 µm in diameter
What are 3 features of epithelial cells within the corneal endothelium indicative of their crucial role in active transport of bicarbonate and sodium?
- highly interdigitated lateral surfaces
- lateral surfaces possess apical junctional complexes
- abundant cytoplasmic organelles (including mitochrondria)
Why is the role of the epithelial cells of the corneal endothelium in active transport of sodium and bicarbonate important?
controls transport of fluid from the stroma into the aqueous humour
What is the regenerative capacity of corneal endothelial cells and what happens when endothelial cells are lost?
low regenerative capacity
cells quickly replaced by spreading of adjacent cells when lost
What does some evidence suggest is the location of putative endothelial stem cells?
in centripetally arranged ‘niches’ ro columns in the extreme peripheral cornea
What is the result of damage to corneal endothelial cells and density below 800 cells/ mm2?
rapid oedema and swelling of the stroma, with resultant loss of transparency of the cornea
What happens to the density of corneal endothelial cells with age?
the density decreases with age
What density of endothelial cells in the corneal endothelium is considered unsuitable for transplantation?
lower than 1500/cells / mm2
How many corneal endothleial cells are there in total at birth? How does this change in middle age and old age?
350 000 (3000-4000 / mm2) falls to 2500/mm2 in middle age and 2000 in old age
What happens to the dense, regular hexagonal arrangement of endothelial cells in the cornea with age?
repalced by fewer cells of more heterogeneous size and shape
What is the major nerve supply of the cornea?
supplied by senosry fibres derived from the ophthalmic division of the trigeminal nerve - mainily via the long ciliary nerves
What nervous supply does the inferior cornea sometimes receive?
some branches from the maxillary division of the trigeminal
How do nerve bundles enter the cornea?
in a radial manner
What happens to nerve bundles entering the cornea as they travel more centrally?
as they go centrally within the anterior one third of the stroma and approx 1mm from the limbus they lose their perineurium and myelin sheaths
What is the alteration in the myelination of nerve bundles travelling centrally within the cornea thought to be due to?
thought to be related to the importance for transparency
What happens after demyelination of nerve bundles as they travel more centrally within the cornea?
they divide into smaller branches and begin to change direction towards the epithelium where they pierce Bowman’s layer
What happens once nerve bundles in the cornea reach Bowman’s layer?
they further divide into smaller bundles to form the subepithelial or sub basal plexus in the interface between Bowman’s layer and the basal aspect of the corneal epithleium
What exists at the terminal axons of nerve bundles in the cornea once they’ve reached the interface between Bowman’s layer and the basal aspect of the epithelium?
no specialised end organs
What is the size range of terminal axons of nerve bundles in the cornea?
0.1 - 0.5 µm
What type of neurons are the terminal axons of nerve bundles in the cornea consistent with?
A-delta and C fibres - which function to transmit sensory modalities of pain and temperature
How do nerve bundles penetrate the corneal epithelium?
individual beaded fibres penetrate the epithelial layers and temrinate in the superifical layers in the form of an intraepithelial plexus
How many nociceptors per mm2 exist in the human corneal epithelium?
7000 (render it exquisitely sensitive)
Why are the sensory nerves in the corneal epithlieum of great interest to researchers? 3 key things
- can be readily viewed non-invasively using IVCM
- act as conduits for the spread of herpes simplex virus to the cornea
- indicate presence of range of ophthalmic and systemic disease including dry eye disease and diabetes
How can larger myelinated nerve fibres often be seen in slit-lamp examination in the cornea?
as fine whitish fibres radiating into the cornea from the limbus
What is the risk of corneal nerves’ position in the anterior stroma and their radial arrangement?
at risk of damage during refractive procedures such as LASIK (Excimer laser in situ keratomileusis)
What can damage to the corneal epithleium and intraepithleial nerve terminals lead to?
great deal of pain
What are 4 things that can damage nerve terminals in the cornea and what can this damage lead to?
- cold
- exposure to UV light
- trauma
- corticosteroids
→can cause reactivation of latent herpes simplex virus in the trigeminal ganglion
What happens to the cornea once latest herpes simplex virus in the trigeminal ganglion is reactivated?
the virus is transmitted to the cornea along senosry nerve branches, leading to recurrent herpes simplex keratitis and superficial corneal ulceration
Which glycosaminoglycan is predominant in the cornea?
keratan sulphate
