

## 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>


Full thickness skin laceration healing Initial inflammatory response Epidermis epithelialisation: Cell migration stimulated by fibronectin Cell…

Pathology

Wound Healing

Intro

FRCOphth Part 1 Study Notes

Orbit and ocular adnexae

Orbit

Extraocular Muscles

Orbital Blood Vessels

Paranasal Sinuses

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Tear Film

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Anterior segment - ocular surface

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Corneal Physiology

AC to Lens

Angle

Ciliary Body

Aqueous Humour Dynamics

Iris

Pupil

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Vitreous

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