

## Full thickness skin laceration healing
<ul>
  <li>Initial inflammatory response</li>
  <li>Epidermis epithelialisation:</li>
  <ul>
    <li>Cell migration stimulated by fibronectin</li>
    <li>Cell proliferation (inhibited by chalones)</li>
    <li>Cell differentiation&nbsp;</li>
  </ul>
  <li>Vascularisation</li>
  <ul>
    <li>Intact capillaries at wound edges send out buds of endothelial cells</li>
    <li>New vessels appear within first week</li>
  </ul>
  <li>Wound closure</li>
  <ul>
    <li>Macrophages and fibroblasts migrate into wound</li>
    <li>Macrophages: clot removal</li>
    <li>Fibroblasts: collagen and GAG production</li>
    <li>Myofibroblasts can cause wound contraction</li>
    <li>Scarring may affect function of the structure</li>
    <li>Matrix metalloproteinases produce collagen degradation</li>
  </ul>
</ul>

## Full thickness corneal laceration
<ul>
  <li>Immediate phase:</li>
  <ul>
    <li>
      Descemet&rsquo;s membrane and stromal collagen retract causing anterior and posterior gaping
    </li>
    <li>Fibrin plug forms from aqueous fibrinogen</li>
    <li>Stromal oedema</li>
  </ul>
  <li>Leukocytic phase (within 30 minutes):</li>
  <ul>
    <li>PMLs invade wound from conjunctival vessels and aqueous</li>
  </ul>
  <li>
    Epithelial phase (1 hour): epithelial ingrowth. Contact inhibition by healthy endothelium
    prevents full thickness ingrowth
  </li>
</ul>
<ClinicalCorrelate>
  <p>
    Epithelial downgrowth syndrome can occur after endothelial damage, lens remnants in wound,
    vitreous in wound
  </p>
</ClinicalCorrelate>
<ul>
  <li>Fibroblastic phase:</li>
  <ul>
    <li>
      Fibroblasts are derived from invading leukocytes and stromal keratocytes in central wounds
    </li>
    <li>Produce collagen and mucopolysaccharides into matrix</li>
    <li>As this occurs, the epithelium retreats anteriorly</li>
  </ul>
  <li>Endothelial phase (after 24 hours):</li>
  <ul>
    <li>
      Endothelial sliding and mitotic/amitotic multiplication to cover the posterior aspect of the
      wound: filling in gaps in DM and endothelium
    </li>
  </ul>
  <li>Late phase (after 1 week):</li>
  <ul>
    <li>Cellular infiltrate diminishes</li>
    <li>Collagen fibres uniformly arranged</li>
    <li>Stroma and Bowman&rsquo;s are replaced by scar tissue (cannot regenerate)</li>
    <li>
      Descemet&rsquo;s membrane cannot regenerate either but during endothelial sliding, cells
      deposit secondary layers in DM
    </li>
  </ul>
</ul>

## Fibroblast growth factor (FGF)
<ul>
  <li>Important role in healing</li>
  <li>Remodels connective tissue</li>
  <li>Collagenisation/wound strength</li>
  <li>
    Monocyte chemotaxis, fibroblast migration and proliferation, angiogenesis, collagenase secretion
  </li>
</ul>
<ul>
  <li>
    Conjunctival healing is similar to corneal healing (with cell sliding and proliferation) however
    granulation tissue can be formed due to the vasculature and lymphatics
  </li>
  <li>
    Sclera does not actively heal: wounds are closed by granulation tissue from the episclera and
    underlying uvea
  </li>
  <li>Iris can only heal if wound edges are directly apposed</li>
  <ul>
    <li>Hence PIs/iridectomies remain patent</li>
  </ul>
  <li>Ciliary body and choroid heal with granulation tissue and are replaced by scar tissue</li>
  <li>Lens: does not truly heal but responds to trauma with cataract formation</li>
  <li>
    Retinal healing is by gliosis (replacement of nerve cells by glial cells) principally by
    astrocytes and by Muller cells (fibroblasts are not native to the normal retina)
  </li>
  <ul>
    <li>RPE undergoes metaplasia and proliferation to form fibrous tissue</li>
    <li>In retinal detachment, extensive gliosis/fibrosis leads to PVR</li>
  </ul>
</ul>
<HotTopic>
  <>
    <p>Anti-proliferative agents</p>
    <ul>
      <li>5-FU: converted intracellularly to active form (FdUMP)</li>
      <ul>
        <li>
          Competitively inhibits thymidylate synthetase in S phase cells so impedes DNA synthesis
        </li>
        <li>
          Metabolites are also incorporated into DNA to render it unstable and interfere with RNA
          processing
        </li>
        <li>Adverse effect: corneal epithelial toxicity</li>
        <li>
          Inhibits fibroblast proliferation for 4-6 weeks when given during glaucoma filtration
          surgery
        </li>
      </ul>
      <li>
        Mitomycin-C: alkylating agent with antibiotic and antineoplastic properties derived from
        Streptomyces caespitosus
      </li>
      <ul>
        <li>
          Antiproliferative on cells at any stage of the cell cycle but maximal in G and S phases
        </li>
        <li>
          100 times more potent than 5FU on fibroblasts and permanently inhibits their proliferation
          (but does not inhibit their migration)
        </li>
        <li>Not usually associated with epithelial toxicity</li>
      </ul>
    </ul>
  </>
</HotTopic>


Pathology

Wound Healing

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

Cornea

Corneal Structure And Development

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

Collagen

Tissue Damage

Inflammation

Disease Entities

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