<ul>
 <li>5 layered structure</li>
 <li>Horizontal diameter (11.7mm) greater than vertical (10.6mm)</li>
 <ul>
 <li>
 And vertical meridian typically shorter radius of curvature than horizontal (more curved
 vertically)
 </li>
 </ul>
 <li>Thinnest centrally (0.5mm) then peripherally at limbus (1.1mm)</li>
 <ul>
 <li>In most people, the thinnest part is inferotemporal to the centre</li>
 </ul>
 <li>Curvature steepest centrally and flattened peripherally</li>
 <ul>
 <li>The radius of curvature is greater anteriorly than posteriorly</li>
 </ul>
 <li>Refractive index 1.376 (cp 1.336 for aqueous)</li>
 <li>
 Refractive power: 48.8 dioptres on anterior surface (RoC 7.7mm) and -5.8 dioptres on posterior
 surface (RoC 6.8mm): total is 43 dioptres
 </li>
 <ul>
 <li>Provides 70% of eye&rsquo;s refractive power</li>
 </ul>
</ul>
<ClinicalCorrelate>
 Cornea plana: rare anomaly of flat central cornea with power less than 43 dioptres. Associated with colobomas, Ehlers-Danlos, Finnish ancestry. The adjacent sclera has the same curvature.
</ClinicalCorrelate>
<ul>
 <li>Anatomical limbus: Schwalbe&rsquo;s line and the corneoscleral junction</li>
 <li>Surgical limbus:&nbsp;</li>
 <ul>
 <li>
 Anterior to anatomical, a blueish transition zone. It lies between the anatomical limbus
 (Schwalbe&rsquo;s line aka the termination of Descemet&rsquo;s membrane) and and termination
 of Bowman&rsquo;s layer (which is more anterior)
 </li>
 <li>
 The white zone posterior to Schwalbe&rsquo;s line extending to the scleral spur is the area
 overlying the trabecular meshwork
 </li>
 </ul>
 <li>Conjunctival limbus: 1mm anterior to anatomical limbus</li>
 <li>Collagen comprises 70% of dry weight</li>
 <li>Proteoglycans comprise 10% of dry weight</li>
</ul>

## Embryology
<ul>
 <li>Development begins at day 33</li>
 <li>Epithelium and Bowman&rsquo;s: surface ectoderm</li>
 <li>Stroma: mesenchymal neural crest</li>
 <li>Lamina propria (fibroblasts forming) and endothelium: neural crest (mesoderm)</li>
 <li>Descemet&rsquo;s: mesodermal and formed by endothelium</li>
 <li>Corneal development induced by lens formation</li>
 <li>Diameter determined by size of optic cup</li>
 <li>Steps:</li>
 <ul>
 <li>1. Bilayered epithelium formed from surface ectoderm</li>
 <li>2. Waves of mesenchymal cells (from neural crest) pass over optic cup</li>
 <li>3. Day 33: first wave forms double-layered endothelium</li>
 <li>4. Day 49: second wave forms substantia propria/stroma</li>
 <li>5. Weeks 9-10: epithelium stratifies to 3-4 layers and the eyelids form</li>
 <li>6. Stroma infiltrated by fibroblasts (which become keratoblasts)</li>
 <li>7. Endothelium synthesises DM</li>
 <li>8. 5 months: Bowman&rsquo;s is last to form</li>
 <li>9. 5 months: corneal nerves reach epithelium</li>
 <li>10. Adult form by 7 months (maturation progresses from deep to superficial)</li>
 </ul>
</ul>
<ul>
 <li>
 Fetal cornea is opaque due to high hydration but transparency occurs before birth once the
 lamellae mature and the endothelial cells activity begins
 </li>
</ul>
<ClinicalCorrelate>
 <ul>
 <li>Corneal opacification: failure of lamellar array of collagen (scleralisation of cornea)</li>
 <li>
 Peter&rsquo;s anomaly: posterior axial stromal defect with incarceration of pupillary iris.
 FOXE3 gene involved and PAX6 also implicated
 </li>
 <li>Embryotoxon: displacement of Schwalbe's anterior to the limbus</li>
 <li>Axenfeld&rsquo;s anomaly: iridocorneal strands localised to Schwalbe&rsquo;s line</li>
 <ul>
 <li>
 Axenfeld-Rieger&rsquo;s anomaly: the addition of iris hypoplasia, associated with juvenile
 glaucoma. PITX2 and FOXC1 genes involved
 </li>
 </ul>
 <li>Neonatal cloudy cornea (STUMPED)</li>
 <ul>
 <li>Sclerocornea: cornea is clear centrally (cp. Peters) and flatter than normal</li>
 <li>Trauma or tears in Descemet&rsquo;s</li>
 <li>Ulcers</li>
 <li>Metabolic disorder</li>
 <li>
 Peters&rsquo; anomaly (dysgenesis of the anterior segment): cornea is opaque centrally (cp.
 sclerocornea)
 </li>
 <li>Endothelial dystrophy</li>
 <li>Dermoid&nbsp;</li>
 </ul>
 </ul>
</ClinicalCorrelate>

## Epithelium
<ul>
 <li>Multilayered epithelium: 5 layers centrally, 10 peripherally</li>
 <li>Squamous superficially and columnar in deeper layers</li>
 <li>Microvilli on outer surface</li>
 <li>
 Desmosomes between cells: tight junctions prevent access of tear electrolytes, therefore the
 epithelium is relatively impermeable
 </li>
 <ul>
 <li>
 Zonulae adherens are a form of &ldquo;belt&rdquo; desmosome forming a ring around the cell
 apex
 </li>
 <li>Desmosomal junctions are approx 20 nm in width</li>
 </ul>
 <li>Hemidesmosomes with Bowman&rsquo;s layer</li>
 <ul>
 <li>Type VII (and type VI) collagen is an important part of hemidesmosomes</li>
 </ul>
</ul>
Note: desmosomes link cells together; hemidesmosomes link cells to the extracellular matrix.&nbsp
<ul>
 <li>Regenerates via mitosis at the limbus</li>
 <li>
 Subepithelial connective tissue creates folds (palisades of Vogt) at limbus to increase surface
 area
 </li>
 <li>Glycocalyx coat contributes to mucin layer of tear film</li>
 <li>Continuous with conjunctiva peripherally</li>
</ul>

## Bowman&rsquo;s membrane
<ul>
 <li>Acellular&nbsp;</li>
 <li>Not a true basement membrane</li>
 <li>10 microns thick</li>
 <li>Consists of randomly arranged collagen fibrils</li>
 <li>Posterior surface merges with stroma</li>
</ul>
<HotTopic>
 Bowman&rsquo;s membrane is not capable of regeneration: eg. corneal haze following PRK and LASEK
</HotTopic>

## Stroma
<ul>
 <li>90% of corneal thickness</li>
 <li>Organised lamellae obliquely li in the anterior 1/3rd and at right angles in the posterior 2/3rds</li>
 <li>Principally type 1 collagen (50%)</li>
 <li>Keratocytes arranged in corkscrew pattern</li>
 <ul>
 <li>
 Produce GAGs: primarily keratan sulphate, chondroitin sulphate and dermatan sulphate (Note:
 not hyaluronic acid)&nbsp;
 </li>
 <li>Gap junctions between cells</li>
 </ul>
</ul>

## Descemet&rsquo;s membrane
<ul>
 <li>Basement membrane of endothelium (a true basement membrane, cp Bowman&rsquo;s)</li>
 <li>10 microns thick in adulthood (3-4 at birth)</li>
 <li>Collagen fibres (type IV mostly) arranged in hexagonal pattern</li>
 <li>Acid-schiff positive</li>
 <li>&lsquo;Banded&rsquo; anterior third and &lsquo;non-banded&rsquo; posterior two-thirds</li>
 <ul>
 <li>Anterior &ldquo;fibrillar&rdquo; layer is present at birth</li>
 <li>
 Posterior layer is deposited after birth by the endothelium (as its BM) and thickens with age
 </li>
 </ul>
 <li>
 Peripheral termination of DM is Schwalbe&rsquo;s line (the anterior edge of the trabecular
 meshwork and the anatomical limbus)
 </li>
 <li>
 Able to regenerate
 </li>
 <li>More resistant to the flow of solvent than Bowman&rsquo;s layer</li>
</ul>
<ClinicalCorrelate>
 <>
 Breaks in infant Descemet&rsquo;s&nbsp;
 <ul>
 <li>Birth trauma: typically vertical with normal IOP</li>
 <li>Congenital glaucoma: typically horizontal (Haab&rsquo;s striae) with raised IOP</li>
 </ul>
 </>
</ClinicalCorrelate>


## Endothelium
<ul>
 <li>Single layer of cuboidal endothelium</li>
 <li>Microvilli extend into the aqueous humour</li>
 <li>Lots of mitochondria:&nbsp;</li>
 <ul>
 <li>Maintains corneal transparency by pumping water out into aqueous (active transport)</li>
 <li>5 times as metabolically active as epithelium</li>
 </ul>
 <li>Hexagonal array of cells resting on DM</li>
 <li>Interdigitations between cells with tight junctions (ensure corneal hydration)</li>
 <ul>
 <li>
 Endothelium is therefore relatively permeable
 </li>
 </ul>
 <li>No regenerative capacity: defects closed by spreading of remaining cells</li>
 <li>Number of endothelial cells decreases with age</li>
 <li>Continuous with the passageways of the trabecular meshwork</li>
 <li>Synthesises type VIII and type IV collagens</li>
 <ul>
 <li>After injury, converts to fibroblast-type cells producing mainly type I collagen</li>
 </ul>
 <li>Density is around 2500 cells/mm2 in healthy adults (3000-4000 cm/mm2 in children)</li>
</ul>
<ClinicalCorrelate>
 <>
 Age-related changes to cornea
 <ul>
 <li>Decreased translucency</li>
 <li>Increased thickness of Bowman&rsquo;s membrane</li>
 <li>Increased thickness of Descemet&rsquo;s membrane</li>
 <li>Reduced endothelial density: compensated by cell enlargement (polymegathism)</li>
 </ul>
 </>
</ClinicalCorrelate>

## Specular microscopy
<ul>
 <li>Reflections from the corneal endothelium can be viewed to assess its health</li>
 <li>Coefficient of variation: how variable endothelial cell size is</li>
 <ul>
 <li>Polymegathism: increased variation with higher risk of post-operative oedema</li>
 </ul>
 <li>
 Hexagonality: lower percentages of hexagonal cells (pleomorphism) are associated with poor
 endothelial health and increased risk of post-operative oedema
 </li>
</ul>

## Nerve supply
<ul>
 <li>Long ciliary nerves: branches of ophthalmic division of trigeminal</li>
 <li>Course</li>
 <ul>
 <li>1 Annular plexus of myelinated fibres form in stroma at limbus.</li>
 <ul>
 <li>There are 50-90 main stromal nerve fibres at the limbus</li>
 </ul>
 <li>
 2 Subepithelial plexus forms and fibres lose myelin approx 1-2mm from the limbus to preserve
 clarity
 </li>
 <ul>
 <li>
 These axons travel in the anterior half of the stroma and from a mid-stromal plexus. This is
 densest at the periphery
 </li>
 </ul>
 <li>
 3 Most mid-stromal fibres pass forward and form a subepithelial plexus beneath Bowman&rsquo;s
 layer
 </li>
 <li>4 Axons pierce Bowman&rsquo;s layer&nbsp;</li>
 <li>5 Intraepithelial plexus forms and sensory nerve endings supply the corneal surface</li>
 </ul>
</ul>
<HotTopic>
 There are more sensory nerve endings per unit area than anywhere in the body
</HotTopic>
<ul>
 <li>Cornea is sensitive to pain and cold only</li>
 <li>Sympathetic supply too</li>
</ul>
<ClinicalCorrelate>
 <>
 Enlarged corneal nerves
 <ul>
 <li>Multiple endocrine neoplasia type 2b (MEN)</li>
 <li>Leprosy</li>
 <li>Neurofibromatosis</li>
 <li>Acanthamoeba perineuritis</li>
 </ul>
 </>
</ClinicalCorrelate>

Cornea

Corneal Structure And Development

Intro

FRCOphth Part 1 Study Notes

Orbit and ocular adnexae

Orbit

Extraocular Muscles

Orbital Blood Vessels

Paranasal Sinuses

Lacrimal Glands

Tear Film

Eyelids

Blinking

Anterior segment - ocular surface

Conjunctiva

Conjunctivitis

Sclera

Corneal Physiology

AC to Lens

Angle

Ciliary Body

Aqueous Humour Dynamics

Iris

Pupil

Lens

Posterior segment

Choroid

Vitreous

Retinal Macrostructure

Neurosensory Retina

Retinal Pigment Epithelium

Neuroanatomy

Venous Sinuses

Cerebral Ventricles

Cerebral Blood Supply

Supranuclear Gaze Pathways

Head And Neck Autonomic Nervous Supply

Head And Neck Glands

Osteology

Nerves

Muscles And Pharyngeal Arches

Extraocular Nerves

Sensory Nerves

Physiology

Physics Of Blood Flow

Neuronal Control Of Blood Vessels

Oxygen-Haemoglobin Dissociation Curve

Cytochrome p450

Pituitary Gland

Thyroid Hormone Production

Insulin

Glucagon

Parathyroid Hormone

Corticosteroids

Catecholamines

Cardiac Cycle

Renal Physiology

Fluid Balance

Acid-Base Balance

Muscle Physiology

Sensory Fibres

Cutaneous Receptors

Endocytosis

Glycosaminoglycans

Condensed Ocular Biochemistry

Eye Movements

Accomodation

Vision

Visual Cycle And Phototransuction

Visual Pathway

Visual Acuity

Colour Vision

Binocular Vision

Pathology

Collagen

Tissue Damage

Inflammation

Disease Entities

Wound Healing

Thrombosis / Atherosclerosis

Cell Growth

Neoplasia

Histopathology

Nystagmus

Free Radicals And Antioxidants

Immunology

Ocular Immunology

Microbiology

Viral Infections

Bacterial Infections

Fungal Infections

Protozoa

Nematodes

Antimicrobials

Genetics

Chromosomes

Mitosis

Meiosis

Genes

Polypeptide Synthesis

Histones

MicroRNA

Hardy-Weinberg Equilibrium

Mutations

Chromosome Defects

Autosomal Inheritance

X-Linked Inheritance

Mitochondrial Inheritance

Multifactorial Inheritance