Cornea

• Describe the cornea

  (what layer, function of pupil?, refractive component)

  It's in the outer fibrous layer of the eye (outer layer)

  It is the transparent part of the eye that covers the iris and pupil (controls and allows light to enter)

  It does majority of the focusing of the light

  Main refractive component (+40D)
• Does the cornea have a bloody supply?

  No, it's avascular

  It gets its oxygen and nutrients from the aqueous humour and air dissolving through.
• Structure of cornea?

  (layers and shape)

  5 layers:

  - Epithelium

  - Bowman's layer

  - Stroma

  - Descemet's membrane

  - Endothelium

  
  

  It isn't a perfect circle or a sphere - the cornea is wider horizontally then vertical (oval shape), and is thicker at the edges and thinner at the centre due to the radii of curvature (which helps focus light).
• What are epithelial cells?

  outer layer of cells (lining) that are fixed to a basement membrane (to keep them stable and in place)
• (epithelial cells structure)

  1. simple (single) layer?

  2. stratified (multiple) layers?


  1. secretion and absorption

  2. protection
• (epithelial cells structure)

  1. squamous suture?

  2. cuboidal structure?

  3. columnar structure?


  1. flat

  2. cube like

  3. tall
• (epithelial cells structure)

  1. keratinised?

  2. non keratinised?


  1. dry (e.g. skin)

  2. moist (e.g. cornea/conjunctiva)
• (Cell junctions):

  1. - Tight junctions (Zonulae Occuldens)?

  2. how do they work?

  3. where are they found?

  4. why do we have them (examples)?

  1. Prevent molecules passing between epithelial cells by acting as a barrier.

  
  

  2. Protein strands between neighbouring cells that fuse together (all along), so the passage is blocked.

  
  

  3. Found in: blood aqueous barrier and blood retinal barrier

  
  

  4. For example, we don't want water getting into the cornea because it can cause swelling and reduce transparency so junctions will stop them getting through.
• (cell junctions)

  1. - Gap junctions?

  2. how do they work?

  3. why do we have them (examples)?

  1. Allow passage of material between cells (cells communicating with each other)

  
  

  2. Proteins in between cell membrane to form channels (gap/tunnel between the two) to allow nutrients and cell components to be passed through.

  
  

  3. Important in smooth muscle (synchronisation). For example, lens and cornea doesn't have a blood supply so we need to be able to get nutrients absorbed in.
• What are desmosomes, how do they work and where are they found?

  they generally hold cells together (mechanical adhesion) by plaques that send out proteins that join together to hold the cell together (base plate)

  filaments extend into the cell to give extra support

  found in tissue subject to mechanical stress e.g. skin
• What do hemidesmosomes do?

  bind epithelial cells to basement membrane
• what are interdigitations?


  cells that don't have smooth round edges in order to interlock with each other.
• What are epithelial cells bound by?

  structure of epithelial cells?

  - basal cells, wing cells, squamous cells?

  - metabolism?


  bound by desmosomes and interdigitations

  non keratinised, stratified, squamous

  - basal cells: sit on basement membranes using desmosomes. They start with mitotic ability but as they migrate towards the surface they loose mitotic ability becoming more flatter and turning into...

  - wing cells: derived from basal cells

  - squamous cells: flat squashed cells, come from wing cells.

  
  

  majority is anaerobic respiration (85%), rest is aerobic (15%-pentose phosphate pathway)
• What are columnar cells?

  they are derived from stem cells from the area around limbus.
• How do squamous cells in the epithelium help hold tears against the eye?

  What do the tight junctions do?

  They have microfilm on top which helps hold the tears against the eye and get nutrients from the eye.

  
  

  Tight junctions prevent fluid uptake (we don't want water getting in).
• What is epithelial regeneration (X,Y,Z theory)?

  
  

  How can wearing contact lenses for too long affect this theory?

  Basal cells work their way up to the surface and start getting replaced by stem cells (columnar cells). Become wing cells which become squamous cells. Loose the squamous cells at the top through exfoliation. For a healthy cornea we need the cells to be replaced (X+Y=Z)

  
  

  Wearing contact lenses for too long reduces the amount of oxygen intake, decreasing the rate of cells dividing and decreasing the rate of which they ingrate up to the surface so reducing the amount of cells getting exfoliated off.

  Lead to 'stagnant epithelium' - prone to infection.
• Bowman's layer of cornea (4 features)


  does not regenerate

  provides tight connection between the epithelium and stroma

  a cellular

  collagen fibres
• the stroma?

  - keratocytes

  - metabolic rate, low or high?

  - what's it made of?

  - hydrophobic or hydrophilic, why is that important?


  main body, thickest layer of the cornea

  - karyocytes: linked by gap junctions throughout the cornea. Collagen is being produced by it

  - low metabolic rate, doesn't do much

  - made of collagen fibres that run parallel to the surface and the regularity helps with the transparency of the cornea. Lamellae (layers), un at right angles with each other.

  - hydrophilic causes 'swelling pressure' that generates interfibrillar tension and maintains arrangement of collagen fibrils.
• What are the collagen fibres surrounded by in the stroma of the cornea?

  'ground substance', which is a transparent gel like substance (has a different refractive index to collagen however light still travels in straight line).
• Endothelium of the cornea?

  - structure

  - bound by?

  - what happens if it gets damaged, and reasons for damage?

  flattened, hexagonal cells, single layer

  bound together by interdigitations, gap junctions and tight junctions

  if it gets damaged by diseases, contract lens over where, age, any cells that are lost don't get regenerated.
• what doe the tight junctions do in the endothelium of the cornea?

  limit water leakage from aqueous humour into the stroma but doesn't stop it which is why the endothelium has a high metabolic rate because it has to work in order to keep the balance of water.
• What is the endothelium pump?

  swelling pressure pulls water in, leakage of water across the endothelium from the aqueous humour into the stoma through the gaps. Endothelial cells use ATP to get bicarbonate ions into the aqueous (hydrophilic), and this draws water out of the stroma via osmosis.
• What's the regulated barrier hypothesis?

  might not just be passive. It may regulate the permeability by changing its volume. When changing volume, the gaps between the cells change too.
• Corneal vascularity

  where does it get the nutrients and oxygen from?

  avascular (without blood)

  get nutrients from the aqueous humour and blood vessels (limbal)

  gets oxygen from the air via the tears centrally, in peripherally we get limbus arcades (little blood vessels at the edges).
• Corneal nerves


  sensitive

  long and short ciliary nerves - trigonal nerve for sensation and pain

  fibres become unmyelinated to help with keeping cornea transparent.
• What are plexus and where are they found?

  what are the 2 plexus of nerves?


  Send branches into the stroma and are found around the limbus.

  1. epithelial - no Schwan cell wrapping, 'naked' and sensitive to cold

  2. Stromal - have Schwan cells
• Corneal arcus


  opaque white ring about corneal periphery, seen in many individuals older than 60 years of age. This is due to deposit of lipids in the cornea or to hyaline degeneration. May indicate a lipid disorder, most commonly type II hyperlipidemia if present before the 40 years of age (if seen in younger people, it is called arcus juvenilis).

  
  

  lipid deposits in the stroma near the limbus
• What is corneal acidosis?

  Reduction in pH, increase in acidic content in the cornea.

  The cornea relies on anaerobic respiration however still needs oxygen, if a barrier gets in the way the process of acidosis occurs.
• What is hypoxia?

  O2 deprivation (not enough oxygen) leading to an increase of anaerobic respiration. Waste product is lactic acid, meaning carbon dioxide can't escape.

  
  

  (Cornea uses lactic acid however it is maintained the balance of ph level)
• What is hypercapnia?


  Slowdown of co2 efflux. There's too much carbon dioxide within the cornea and it binds with water in the cornea to produce carbonic acid.

  
  

  (lactic acid and carbonic acid causes decrease in ph level-hypoxia)
• What are the signs and causes of hypoxia and hypercapnia?

  Signs:

  - microcysts within the epithelium and in the endothelium

  - blebs

  - guttae

  - polymegathism (Change in shape of corneal cells)

  
  

  Causes:

  - contact lens wear - it acts as a barrier

  - eye closure (sleep) - not too bad as the blood vessels on the back of the iris in the conjunctiva will help as it it will provide oxygen to the cornea so it's not too bad.
• What is corneal inclusions?

  - reversed illumination, what is it and what's I caused by? And examples

  - unreversed illumination? And examples


  The light is illuminated in reverse to what we would expect (reversed illumination).

  This is due to the material in the inclusion having a higher refractive index then the surrounding tissues, meaning the light rays bend towards each other and cross over and bend.

  Examples: epithelial microcysts and endothelial bedewing

  
  

  unreversed: refractive index within the inclusion has a lower refractive index then the surrounding tissue so the light rays DON'T bend towards each other and they remain uncrossed.

  Examples: epithelial vacuoles, useful to medication and something secondary to inflammation in the cornea.
• Punctate erosion?

  -caused by

  -how is it viewed

  - what can you see and why

  Caused by damage to the cornea, dryness or allergic reaction

  seen with fluroscein dye viewed with blue light and yellow filter on the slit lamp.

  Shows up as bright green and it stains areas of missing epithelial (erosion of the epethilial cells). Corneal staining.
• Epithelial signs: Filaments

  -dry eyes

  -recurrent epithelial erosion


  grey strands on the surface that are made up of mucus and epithelial cells.

  Causes:

  - dry eyes: oil layer in front, then water layer then mucus layer at back nearest to the cornea. The oil layer isn't being formed properly so the water can evaporate more rapidly and the eye would dry out. The mucus layer would stay the same and as we constantly blink, the mucus layer status to dry out and it rolls into little filaments and collects some of the epithelial cells that we naturally loose. The little areas where the epithelial is getting damaged it acts like an anchor point for the strands on the mucus, they stick on and it gives pain and foreign body sensations.

  
  

  - recurrent epithelial erosion: scratch not he cornea or surface damage to the epithelial. It heals and we get hemidesmosomes, but the adhesion between the cells and cells at the basement membrane are quite weak so it doesn't take much for damage to occur.
• Epithelial signs: microcysts

  - caused and signs?

  -'reversed' illumination

  -contain fluid and cell debris

  -caused by acidosis

  -sign of chronic metabolic stress and altered cellular growth patterns

  
  

  main cause is extended wear of contact lens and overnight wear. Unable of blood flow inside of the eyelids that would help to get oxygen to the cornea overnight. The hypoxia changes the way the cornea can be respirated. This changes how the corneal metabolism works.
• Epithelial signs: vortex keratopathy

  Fine lines heading from the outside towards the limbus towards the centre of the cornea.

  -epithelial deposits of basal cells (pattern of cell migration)

  -drug induced:

  -chloroquine (antimalarial)

  -amiodarone (cardiac arrhythmia) for irregular heartbeat

  
  

  fabry disease: genetic disease and is x linked. Corneal changes at an earlier age because the patient can't breakdown lipids. (Early teens).
• Stromal signs: oedema

  -signs and occurrence

  -accumulation of fluid in stroma causing swelling

  signs:

  -striae - fine lines caused by fluid getting into stroma and separating collagen fibres, often oblique angle.

  -folds - buckling of stroma (>8% oedema). DM folds, reduced transparency and vision is affected.

  -reduced transparency (>15% oedema)

  
  

  Occurrence:

  - sleep causes hypoxia and causes swelling (3%).

  - contact lens wear due to hypoxia: the endothelium can't work as well and the endothelium pump isn't working effectively so water isn't going out, only coming in.

  - acute glaucoma: increase of pressure in the eye. Stress at the back of the eye killing of nerve fibres, loosing peripheral vision. Rapid increase in pressure in the eye so the aqueous humour is being forced through the endothelium and into the stroma.
• Stromal signs of Neovascularisation

  caused by?

  -new blood vessels

  caused by:

  -inflammations

  -Infections

  -hypoxia (contact lenses). If we deprive oxygen in the eye, new blood vessels are grown to get oxygen into the eye that are starved of it.
• Stromal infiltrates

  caused by?

  When we have infection and inflammation, we get white blood cells migrating to area when there is a problem.

  Round grey spots is where we have a collection of leucocytes and cellular debris and inflammatory cells.

  Caused by:

  - contact lens wear - poor fit and hygiene (experienced as irritation)

  - infection (experience pain and bluriness, discharge from the eye and red eye).
• Endothelial signs: polymegathism


  Variation in the cell shape and size.

  
  

  Caused by:

  -chronic response to acidosis

  -variation cell shape that appears as size variations

  -age: as we get older, we loos cells matrix, more fluid coming in so cell adjust size and shape to plug in gaps.