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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
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
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
12/31/2020 3
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
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
12/31/2020 5
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
12/31/2020 6
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
12/31/2020 7
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
12/31/2020 8
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
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
12/31/2020 10
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12/31/2020 12
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
12/31/2020 13
12/31/2020 14
12/31/2020 15
12/31/2020 16
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.
12/31/2020 17
12/31/2020 18
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
12/31/2020 19
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
12/31/2020 20
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
12/31/2020 21
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
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
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
12/31/2020 24
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
12/31/2020 25
Cont.….
Stromal wound healing
• First the proliferating epithelial cell will fill the gap
• Corneal stromal swelling
• Keratocytes start to produce collagen and proteoglycan……scar
12/31/2020 26
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
12/31/2020 27
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
12/31/2020 28
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
12/31/2020 30
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.
12/31/2020 31
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
12/31/2020 32
12/31/2020 33
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
12/31/2020 34
Cont.….
• Parallel lesion
• Wound edges are
approximated
• Epithelium migrate and cover
the wound
• Stroma produce collagen and
ground substance
12/31/2020 35
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
12/31/2020 36
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
12/31/2020 37
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
12/31/2020 38
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
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
12/31/2020 40
12/31/2020 41
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
12/31/2020 42
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
12/31/2020 43
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
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
12/31/2020 45
REFERENCES
BCSC
DUANS CLINICAL OPTHALMOLOGY
BASIC PRINCIPLES OF OPHTHALMIC SURGERY
SCHWARTZ 8TH EDITION
GUYTON 11TH EDITION
THANK YOU
12/31/2020 46

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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 12/31/2020 3
  • 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 12/31/2020 5
  • 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 12/31/2020 6
  • 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 12/31/2020 7
  • 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 12/31/2020 8
  • 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 12/31/2020 10
  • 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 12/31/2020 13
  • 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. 12/31/2020 17
  • 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 12/31/2020 19
  • 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 12/31/2020 20
  • 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 12/31/2020 21
  • 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 12/31/2020 24
  • 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 12/31/2020 25
  • 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 12/31/2020 26
  • 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 12/31/2020 27
  • 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 12/31/2020 28
  • 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. 12/31/2020 31
  • 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 12/31/2020 32
  • 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 12/31/2020 34
  • 35. Cont.…. • Parallel lesion • Wound edges are approximated • Epithelium migrate and cover the wound • Stroma produce collagen and ground substance 12/31/2020 35
  • 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 12/31/2020 36
  • 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 12/31/2020 37
  • 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 12/31/2020 38
  • 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 12/31/2020 40
  • 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 12/31/2020 42
  • 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 12/31/2020 43
  • 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 12/31/2020 45
  • 46. REFERENCES BCSC DUANS CLINICAL OPTHALMOLOGY BASIC PRINCIPLES OF OPHTHALMIC SURGERY SCHWARTZ 8TH EDITION GUYTON 11TH EDITION THANK YOU 12/31/2020 46