This document provides an overview of ocular wound healing. It begins with an introduction and history of wound healing concepts. It then describes the typical phases of wound healing (hemostasis, proliferation, and maturation) and how they apply to specific ocular tissues like the cornea, conjunctiva, sclera, iris and retina. Factors that can modify wound healing like suture choice, anti-inflammatories and anti-proliferative agents are also discussed. The presentation aims to explain the summation of processes involved in ocular healing and how they may differ based on the injured tissue.
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Ocular Wound Healing Phases and Structures
1. OCULAR WOUND
HEALING
PRESENTER – BEMNET T.(R2)
MODERATOR – DR.YARED A.
(MD ,MPH, ASSOCIATE PROFESSOR OF OPHTHALMOLOGY,
SUBSPECIALTY IN ANTERIOR SEGMENT AND CORNEAL DISEASE)
DR.YORDANOS T.(SENIOR RESIDENT)
12/31/2020
1
2. OUTLINE
Introduction
History of wound healing
Types of wound healing
Phases of wound healing
Specific ocular structure wound healing
Dermal/conjunctival
Corneal
Scleral
Uveal
Modifying wound healing 12/31/2020 2
3. INTRODUCTION
In human regeneration is limited to epithelium and the liver; most tissues
heal by repair resulting in scarring.
Wound healing is the summation of a number of processes that follow injury
Healing in ophthalmic surgery involve different tissue with different
characteristics
Even if almost all tissues have common feature they vary accordingly
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4. HISTORY OF WOUND HEALING
Sumerians – were the earliest to be accounted for wound healing around
2000 B.C
Egyptians - were the first to differentiate between infected and noninfected
wounds
The Greeks – classify wounds as acute and chronic
Galen of Pergamum – emphasized on maintaining moist env’t to fasten
wound healing 12/31/2020 4
5. Louis Pasteur (1822–1895) - proving that germs were always introduced
into the wound from the environment
Joseph Lister – began soaking his instruments in phenol and spraying the
operating rooms
Robert Wood Johnson – produce antiseptic dressing in the form of cotton
gauze impregnated with iodoform
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6. TYPES OF WOUND HEALING
Traditionally there are three types of wound healing. These are:
1. Healing by first intention/ primary closure
Wound will be approximated or closed using sutures, strips, graft or
flaps
Minimal basement membrane interruption , tissue loss, and cellular
damage
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7. Cont.…
2. Healing by secondary/spontaneous intention
No active intent to seal the wound
Contaminated and wounds that have extensive tissue loss
Closure is by re- epitelazation ….. Wound contracture
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8. Cont.…
3. Tertiary intention /delayed primary closure
Contaminated wound will be treated using repeated debridement , ABX and
negative pressure
Close the wound using primary methods once the wound is ready
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9. PHASES OF WOUND HEALING
• Classically its divided into three continues and overlapping phases
• Are differentiated depending on the type of cells and chemicals involved
12/31/2020 9
10. Cont.….
1. Hemostasis and inflammatory phase
Represents an attempt to limit damage by stopping the bleeding, sealing
the surface of the wound, and removing any necrotic tissue, foreign
debris, or bacteria present
First hemostasis ensue
• Vascular Constriction – local myogenic constriction, platelet derived
autacoids and nervous reflex
• Formation of the Platelet Plug
• Formation of blood clot
• Growth of fibrous tissue
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13. Cont.…
PMN are the first to infiltrate the wound site
Infiltration of neutrophil…….phagocytosis and debride necrotic tissue
Infiltration of macrophages….. Debridement of necrotic tissue ,
microbial stasis and also activate and recruit other cell
Macrophages also involve in proliferation, matrix synthesis, and
angiogenesis
T lymphocytes – are bridge the transition from the inflammatory to the
proliferative phase
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17. Cont.….
2. Proliferation phase
Consists of re-epithelialization, matrix synthesis, and
neovascularization
Tissue re-continuity established
Cells that are involved in this phase are:
Fibroblasts …….secret connective tissue proteins (collagen type 1,111
and proteoglycan)
Vascular endothelial cells…….initiate the process of angiogenesis.
Epithelial cells………migrate over the wound surface
Myofibroblasts……….contract the wound and facilitate wound closure.
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19. Cont.….
3. Maturation and remodeling
Characterized by a reorganization of previously synthesized collagen to re-
establishment of extracellular matrix
Fibroblasts ……….continue to secrete the structural proteins and protease
MMP is the major enzyme that involve in this phase
Net wound collagen ….result of a balance between collagenolysis and
collagen synthesis
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20. Cont.…..
Wound strength and mechanical integrity……. quantity and quality of the
newly deposited collagen
The deposition of matrix at the wound site follows a characteristic
pattern:
Fibronectin and collagen type III
Glycosaminoglycan's and proteoglycans and
Collagen type I is the final matrix
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21. Cont.…..
By several weeks postinjury the amount of collagen in the wound
reaches a plateau
The tensile strength continues to increase for several more months
The mechanical strength of the scar never achieves that of the uninjured
tissue
Re-epithelialization………by rapid mitotic activity of migrating epithelial
cells
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22. Cont.….
Factors affecting the wound healing processes are :
Age
Medical conditions
Medications
Vascularity
Availability of chemoattractant factors and
Cellular proliferation rates
Heritable Diseases of Connective Tissue
Ehlers-Danlos syndrome,
Marfan syndrome,
Osteogenesis imperfecta,
Epidermolysis bullosa, and acrodermatitis enteropathica 12/31/2020 22
23. Ocular wound healing
CONJUNCTIVAL WOUND HEALING
• Is highly vascularized structure
• Have similarity in wound healing with skin
• Healing could be accomplished in both primary and secondary
intension
• In general primary wound healing is preferable
• Re-epitelazation will be achieved with in days
• It depend on:
• Type of suture material – Vicryl or gut sutures.
• Type of suture placed.
12/31/2020 23
24. Cont.….
Corneal wound healing
• Has no vascular stage
• No granulation tissue rather there is fibroblastic tissue
• Healing differ in each layer
Epithelial wound/ abrasions healing
• Migration of epithelial cells from wound margin ….. 1hr post injury
at 60 to 80um per hr.
• If entire cornea is injured ….source of epithelial cells is limbal
stem cell and will take 48 to 72 hr
• Epithelial mitotic division and stratification ……re-establish corneal
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25. Cont.….
Wound involving bowman layer and superficial stroma
• Do not heal by fibrous proliferation of the stroma
• The gap will be filled by the proliferating epithelial cells ……Epithelial
facet
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26. Cont.….
Stromal wound healing
• First the proliferating epithelial cell will fill the gap
• Corneal stromal swelling
• Keratocytes start to produce collagen and proteoglycan……scar
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27. Cont.….
Full thickness corneal wound healing
• Proteinaceous coagulum(fibrin and fibronectin) will seal the posterior gap
• Migration of endothelial cells
• Polymegatism and polymorphisim
• In young individual there could be a mitotic activity
• Descemet will be produced by endothelial cells
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28. Cont.….
Practical consideration
• Partial and full thickness corneal wounds have to be heal by primary
intention
• Epithelial wounds will be left to heal by secondary intention
• The two factors that affect corneal wound healing are:
• Type of suture……. nylon monofilaments
• Technique ………. Interrupted sutures
• Topical steroid ……retard cellular response and scar formation
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29. Cont.….
Scleral wound healing
• The healing is by granulation formation
Partial wound healing
• External….. Tissues for granulation are derived from episclera
• Internal ….. Tissues are derived from uveal tissue
Full thickness wound healing
• Granulation tissue will originate from both episclera tissue and uveal tract
12/31/2020 29
31. Cont.….
Practical consideration
• Healing by primary intention is important
• Prevention of scar formation is less important
• Choice of suturing material depends size and anatomic location of the wound
• Small and/or anterior wounds……absorbable sutures
• Large and/or posterior wounds……non absorbable nylon monofilaments.
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32. Cont.….
Surgical limbus healing
• Involve features of corneal, conjunctival and scleral wound healing
• Conjunctival epithelium will seal the wound by granulation tissue
derived from conjunctiva and episclera
• The rest healing processes is similar to external scleral wound
healing
• Internally there is no granulation tissue due to no involvement of uveal
tract
• Internal wound will be sealed by migration of endothelial cells and
reformation of descemet
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34. Cont.….
Uveal wound healing
• Posterior uveal tract heal by granulation and subsequent scar formation
• Iris wound healing is different and depend on the anatomy of the lesion
• Perpendicular lesions
• Allows the radial muscle to pull the wound edges apart……gaping
the wound
• Wound healing does not extend across the gap
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35. Cont.….
• Parallel lesion
• Wound edges are
approximated
• Epithelium migrate and cover
the wound
• Stroma produce collagen and
ground substance
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36. Cont.….
Lens healing
• Proliferation and fibrous metaplasia of epithelium will close small capsular
defects
• Most wounds to the lens, small and large, result in cataracts.
Injury fibromyoblastic transformation of the epithelium
Transformed epithelium produce type I and type III collagen and GAG……
opacities
Eg. PCO after ECCE and pheco
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37. Cont.….
Retinal healing
• Wound healing of the neurosensory retina follows the principles of wound
healing.
• Removal of necrotic tissue
• Migration and proliferation
• Astrocytes will migrate from periphery to wound site and
proliferate down to subretinal space
• RPE will migrate from periphery to wound site and proliferate up
to subretinal space
• When the two proliferating cell types unite, a tight chorioretinal bond
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38. Cont.….
Vitreous healing
• Vitreous has few cells and no blood vessels.
• However it contain large amount of collagen fibrils
• This collagens act as a scaffold for glial and fibro vascular tissue from the
retina and uveal tract to grow and extend into the vitreous to proliferate as
membranes
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39. Modifying wound healing
• Scarring of any ocular tissue can result in decreased vision and
increase morbidity.
• Methods of modifying wound healing are:
Suture Materials
• Is a simply way of modifying wound healing
• If rapid healing is desired …. Use sutures capable of inducing
inflammatory response
• This include Vicryl , gut, and silk.
12/31/2020 39
40. Cont.….
• If inflammation is not desired ….use monofilament
sutures such as Prolene and nylon
• In some surgeries we can use both sutures
Eg. Limbal based trabeculectomy
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42. Cont.….
Anti- inflammatory
• Corticosteroid affect all stages of wound healing
• In acute stage affect neutrophil adherence and migration
• In late stages it affect production of plasmin no degradation of fibrin
• NSAIDs
• In early stage affect some cell adhesion interaction and migration
• It also non specifically inhibit COX affect production of PG Affect
leucocyte migration
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43. Cont.….
Anti - proliferative agents
The two most common anti- proliferative agents that is used are:
Fluorouracil (5-FU)
• Fluorinated pyrimidine nucleoside analogue that blocks production of
thymidylate synthase
• Interrupts normal cellular DNA and RNA synthesis
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44. Cont.…..
• Cause cellular thymine deficiency and resultant cell death.
• The effect is most pronounced on rapidly growing cells
• Used postoperatively as a sub conjunctival injection and
intraoperatively as a topical application to the trabeculectomy site
12/31/2020 44
45. Cont.….
Mitomycin C
• Compound isolated from the fungus streptomyces caespitosus
• Becomes a bifunctional alkylating agent after enzymatic alteration within
the cell
• Inhibits DNA synthesis by DNA cross-linkage
• Weak immunosuppressive but a potent inhibitor of fibroblast proliferation
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