

## Glucose and oxygen metabolism
<ul>
  <li>
    Oxygen is obtained by diffusion through tear film when the eye is open and from the lid
    vasculature and aqueous when closed
  </li>
  <li>Glucose supply to epithelium from tear film and limbal blood vessels</li>
  <li>Glucose supply to endothelium from aqueous</li>
  <li>
    Epithelium and endothelium metabolise glucose via the three main forms of carbohydrate
    catabolism
  </li>
  <ul>
    <li>Citric acid (Kreb&rsquo;s) cycle): 24 molecules of ATP in the presence of oxygen</li>
    <li>Glycolysis: 2 molecules of ATP in the absence of oxygen</li>
    <ul>
      <li>This anaerobic process predominates in the epithelium representing 85% of glucose use</li>
    </ul>
    <li>
      Pentose-phosphate pathway (although keratocytes do not possess 6-phosphogluconate
      dehydrogenase and so cannot use this pathway)
    </li>
  </ul>
  <li>Lactic acid diffuses passively into aqueous</li>
  <ul>
    <li>
      When lactate accumulates (eg. due to overwearing of poorly fitting contact lenses) then only a
      small proportion is lost in tears and more accumulates in the stroma
    </li>
    <ul>
      <li>Leads to corneal oedema by altering osmotic pressures</li>
    </ul>
    <li>
      Lactate is also transported via an H+/lactate pump so increased lactate leads to acidification
      of the cornea and cell shrinkage
    </li>
  </ul>
</ul>

## Electrolyte transport
<ul>
  <li>Cornea is 75-80% water</li>
  <li>Epithelium is relatively impermeable (see above)</li>
  <li>Endothelium is leaky</li>
  <ul>
    <li>At aqueous interface: Na/HCO3 co-transporter and HCO3/Cl exchanger</li>
    <li>At stromal interface: Na/K ATPase and Na/H antiporter</li>
  </ul>
  <li>Sodium passively diffuses into epithelium from tears down concentration gradient</li>
  <li>Na/K ATPase in epithelium pumps sodium into stroma in exchange for potassium</li>
  <li>Epithelium is therefore:</li>
  <ul>
    <li>Low sodium (70 mmol/L)&nbsp;</li>
    <li>High potassium (140 mmol/L)</li>
  </ul>
  <li>Stroma by contrast</li>
  <ul>
    <li>Potassium concentration (20 mmol/L) is seven times lower than epithelium</li>
    <li>But stromal sodium is more than double (170 mmol/L)</li>
    <li>Low chloride concentration in stroma too (110 mmol/L)</li>
    <li>Electroneutrality of the stroma is compensated for by the glycosaminoglycans</li>
  </ul>
  <li>
    Endothelium utilises sodium and bicarbonate ion pumps to maintain hydration levels by causing
    passive secondary movement of water (negative hydrostatic pressure)
  </li>
  <li>
    Tear film tonicity affects corneal hydration, eg. adding glycerin to tear film will draw water
    out of cornea
  </li>
  <li>
    During sleep the cornea thickens due to relative hypoxia: about 4-8% during an average night
  </li>
</ul>

## Corneal transparency
<ul>
  <li>Factors necessary for corneal transparency</li>
  <ul>
    <li>
      Dehydration from: endothelial activity, evaporation of tears and normal intraocular pressure
      (raised pressure leads to hydration)
    </li>
    <li>Acellularity and avascularity</li>
    <li>Regular matrix structure of collagen fibrils with destructive interference</li>
    <li>Consistent refractive index throughout layers</li>
  </ul>
</ul>
<p>Matrix of collagen fibrils</p>
<ul>
  <li>Diameter and spacing of collagen fibrils is remarkably constant</li>
  <ul>
    <li>Collagen fibrils of small and uniform diameter are needed for transparency</li>
    <li>Corneal scars have wider and longer collagen fibrils&nbsp;</li>
  </ul>
  <li>
    Anterior third of stroma: collagen fibrils are oblique, in the posterior two thirds they are
    parallel
  </li>
  <li>High tensile strength between fibrils due to cross-links</li>
  <li>
    Keratan sulphate is the most common corneal proteoglycan (60%) followed by dermatan sulphate
    (40%) and these bind to collagen fibrils, contributing to the regulation of their spacing
  </li>
  <ul>
    <li>
      Adult stroma: keratan sulphate concentrated in posterior stroma and dermatan concentrated in
      anterior stroma
    </li>
    <li>
      The keratan sulphate:dermatan sulphate ratio decreases in corneal scars (ie. loss of keratan
      sulphate leading to irregularly arranged fibrils).
    </li>
  </ul>
  <li>
    Maurice hypothesis: fibril spacing causes destructive interference of the light scattered by
    individual fibrils leading to transparency (light is therefore not scattered at all due to the
    difference between the refractive index of collagen and that of stromal ground matrix).
  </li>
  <li>Endothelial damage leads to the cells becoming fibroblastic</li>
  <ul>
    <li>
      Retrocorneal fibrous membrane (RCFM) develops between Descemet&rsquo;s and endothelium leading
      to loss of VA
    </li>
  </ul>
</ul>
<ul>
  <li>
    MMPs are produced by in-coming inflammatory cells and corneal cells in response to injury:
  </li>
  <ul>
    <li>
      Only MMP-2 (gelatinase) is found in normal cornea but others are produced on injury (including
      MMP-1, MMP-3, MMP-9)
    </li>
    <ul>
      <li>MMP-1: collagenase produced by stroma</li>
      <li>MMP-3: a stromelysin produced by stroma</li>
      <li>MMP-9: a gelatinase produced by epithelium. Involved in corneal remodelling</li>
    </ul>
    <li>
      These are enzymes which destroy the extracellular matrix needed for maintenance and
      remodelling of the cornea after damage
    </li>
    <li>MMPs are pro-angiogenic</li>
  </ul>
</ul>


Glucose and oxygen metabolism Oxygen is obtained by diffusion through tear film when the eye is open and from the lid vasculature and aqueous when closed…

Cornea

Corneal Physiology

Intro

FRCOphth Part 2 Study Notes

Tumours, masses and neoplasia

Tumours overview

Uveitis

Uveitis background

Anterior uveitis

Intermediate uveitis

Uveitis in JIA

Uveitis with JIA

Retinal vasculitis

Sarcoidosis

Behcet's disease

Toxoplasmosis

Viral uveitis

Strabismus

Overview

Esotropia

Fungal uveitis

Mycobacterial uveitis

Adnexal masses

Spirochaetal uveitis (including Syphilis)

Exotropia

Melanoma

Nematode uveitis

Retinoblastoma

Retinoblastoma (for Part 2)

Incomitent

Voyt-Koyanagi-Harada syndrome

Conjunctival intraepithelial neoplasia

Vertical deviations

Sympathetic ophthalmia

Orbit and ocular adnexae

Orbit

AV Malformations and hamartomas

Arteriovenous malformations and hamartomas

Restriction syndromes

Paediatrics

Leucocoria

Congenital Cataract

Paediatric Glaucoma

Retinopathy of prematurity

Retinopathy of Prematurity

ROP-like disorders

Congenital nasolacrimal duct obstruction

White dot syndromes

Aniridia: Short Arm 11 Deletion (11p13)

Choristomas

Management Of Amblyopia

Alphabet patterns

Scleritis

Iris Nodules

Meningioma

Strabismus surgery

Optic nerve glioma

Lymphoma

Extraocular Muscles

Rhabdomyosarcoma

Idiopathic orbital inflammation

Orbital neuroblastoma

Anterior Persistent Foetal Vasculature

Lacrimal system

Metastatic lesions

Surgical Retina

Retinal Detachment

Vitreoretinal Interface And Macular Hole

Epiretinal Membrane

Medical Retina

Diabetic Eye Disease

Orbital Blood Vessels

Retinal Vascular Disease

Macular Degeneration

Central Serous Chorioretinopathy (CSCR)

Sickle Cell Retinopathy

Retinitis Pigmentosa

Albinism

Retinal Telangiectasias

Miscellaneous Retinopathies

Atropine And Myopia Progression

Pharmacology

Side Effects Of Systemic Drugs

Foetal Alcohol Syndrome

Neuro-ophthalmology

Optic Neuropathy

Papilloedema

Idiopathic Intracranial Hypertension

Chiasmal Disorders

Retrochiasmal Disorders

Migraine

Paranasal Sinuses

Supranuclear Motility Disorders

Third Nerve Palsies

Fourth Nerve Palsies

Sixth Nerve Palsies

Seventh Nerve Palsies

Anisocoria

Myasthenia Gravis

Myopathies

Blepharospasm

Functional Visual Loss

Lacrimal Glands

Phakomatoses

Developmental diseases

Tear Film

Eyelids

Blinking

Lid Malpositions

Anterior segment - ocular surface

Conjunctiva

Conjunctivitis

Sclera

Pigmented Conjunctival Lesions

Squamous Cell Carcinoma Of The Conjunctiva

Ocular Cicatricial Pemphigoid

Corneal Structure And Development