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 True ophthalmic emergency
 Irrigation :
 Copious irrigation – pH neutralization
 90 minutes – reduces pH by 1.5
 Neutral irrigation fluid
 ? Amphoteric buffering solution
 Morgan lens
 Removal of retained particles / necrotic material
1. Antibiotic – preservative free :
 Epithelial defect – broad spectrum antibiotic
 Drops / ointment
 Take into account drug toxicity
 Fortified antibiotics if necessary
2. Steroids :
Benefits
Inflammatory cell
suppression
Collagenase inhibition
Risks
Suppress collagen production
and keratocyte migration
Thinning
3. Ascorbate :
 Ascorbic acid supplementation systemically / topically to overcome the scorbutic
state of the aqueous humour( due to damage to the ciliary body ) thus promote
stromal repair .
 15mg /dl
 10 % sodium citrate eye drops every hourly
 1000 mg of oral ascorbic acid 4 times daily
5. Citrate :
 Effective in both preventing and retarding the progression of corneal ulcers.
 Chelates extracellular calcium and diminishes the activity of polymorphonuclear
leukocytes by reducing membrane and intracellular calcium levels.
 Reduces neutrophil infiltration and also has an inhibitory effect on collagenase.
 Topical route is superior
 10% solution of citrate eye drops may be administered hourly
6. Cycloplegic agents
7. Preservative free tear sustitutes
8. Antiglaucoma medication : oral is preferable (avoids drug toxicity )
9. Tetracyclines :
 Reduces collagenase activity and prevents ulceration
 Oral doxy – 100 mg BD
 Topical – 1 % suspension /3 % ointment
10. Serum eye drops
Removal of inflammatory
stimulus
Removal of retained
particles / necrotic tissue
Symblepharon lysis
? Anterior chamber
paracentesis
Aqueous exchange
Facilitation of healing
 Tenon’s advancement :
 Re-establish limbal circulation with the help of vital connective tissue from the
orbit and limit the progression towards necrosis, aseptic ulceration, and scleral
perforation in severe burns
 Initial stabilization of Grade 4 burns
 Tissue adhesives
 Derived from the innermost layer of the human placenta
 3 basic layers :
 Epithelial monolayer
 Thick basement membrane
 Avascular , hypocellular matrix
 Can promote epithelial cell migration , adhesion and differentiation
 Supports the growth of epithelial progenitor cells
Promotes epithelial healing
• Acts as a basement membrane rich in various growth factors
Decreases inflammation
• Physical entrapment of inflammatory mediators and induction
of their apoptosis
Decreases scarring
• Expression of anti inflammatory cytokines
 Fibrous and necrotic tissue meticulously removed
 Symblepharon release
 Hemostasis achieved
 Large sheet of AM devoid of button holes is draped over the ocular surface
 The AM may be anchored to the fornix by 2 sets of double armed chromic catgut
sutures
 The sutures are passed through the AM and then the full thickness of the eyelid
exiting through the skin
 The AM is then fixed by running non absorbable sutures to the limbus or the
corneal periphery
 Multiple interrupted vicryl sutures are placed to anchor the membrane to the
bulbar conjunctiva and the inner lid surface
 Fibrin glue may be used alternatively
 Joseph et al – rapid pain relief and reepithelization in moderate burns but no
definite benefit over medical therapy in severe burns
 Meller et al – performed AMT within 2 weeks of injury and concluded that AMG is
helpful in promoting re epithelization and reducing inflammation in acute stages ,
thereby, preventing scarring in later stages
 Thus , in acute stages AMG helps by reduction of scarring sequelae and optimizes
the ocular surface for future reconstructive procedures
 May alone give satisfactory results in partial LSCD
 Goals :
 Optimization of the ocular surface
 Visual rehabilitation
 Adjunct procedures :
 Reconstruction of fornices
 Correction of eyelid malposition
1. Conjunctival transplantation :
 Contralateral eye
2. Buccal and nasal mucosal transplantation
 symblepharon, trichiasis, entropion, or keratinized conjunctiva at the palpebral
margin.
 Posterior aspect of the upper or lower lip.
 Septum and the lower or medium turbinates
 Secondary LSCD
 One time damage with cicatrizing sequelae
• Absence of the palisades of Vogt
• Dull irregular epithelium
• Superficial vascularization
• Conjunctivalization
• Persistent epithelial defects
 The corneal surface is in a state of constant healing by means of a constant
process of cell renewal and regeneration of the epithelium
 The proliferative potential is limited only to the basal cells
 A vertical, as well as a horizontal, movement of cells characterizes the kinetics of
the maintenance of the corneal epithelial mass- X,Y,Z hypothesis
 Long-lived
 Long cell cycle time
 Increased potential for error-free proliferation
 Poor differentiation
 Asymmetric cell division
 Theoretically it is possible to restore stem cell function by expanding the stem cell
population through modulations in the microenvironment, or inducing transient
amplifying cell mitosis with the use of appropriate factors
 The various limbal transplantation procedures include
 Conjunctival limbal autograft ( CLAU )
 Keratolimbal allograft ( K-LAL )
 Conjunctival limbal allograft (CLAL)
 Cultured corneal epithelial or limbal stem cell transplantation ( LSCT / SLET )
 CLAU:
 Limbal stem cells on a carrier of conjunctiva
 Unilateral / partial LSCD
 Donor – fellow eye
 Careful case selection
 Excision of upto 6 clock hours of conjunctival tissue
 No immunosuppression
 Limbal tissue is primarily transplanted with minimal conjunctival tissue.
 Least risk for rejection
 A 2 × 2 mm area, centered on the superior limbus, is marked.
 Subconjunctival dissection towards the limbus with a shallow area of dissection
1 mm into clear cornea is continued and the limbal tissue excised and placed in
BSS
 Recipient eye - a 360 degree conjunctival peritomy is performed with removal of
any vascular corneal pannus.
 Hemostasis is achieved amniotic membrane is placed over the bare ocular surface
and secured with fibrin tissue glue.
 The donor tissue is cut into 8 to 10 small pieces and placed, epithelial side up, on
the amniotic membrane and distributed in a circular fashion avoiding the visual
axis.
 The transplants are also fixed in place with fibrin glue.
 A soft bandage contact lens is placed
 KLAL / cadaveric KLAL :
 Limbal tissue attached to a corneal carrier is harvested from cadaveric eyes and
transplanted to the recipient eye
 Severe LSCD / one eyed / no living related willing donor
 Works best if conjunctiva is not or minimally scarred and inflammation is quiet
 Combined PKP or conjunctival – KLAL can be considered
 Indefinite immunosuppression
 CLAL :
 One eyed with total LSCD / bilateral LSCD
 Normal limbal tissue on a conjunctival carrier
 Donor – living relative ( best if HLA matched )
 Indefinite immunosuppression
 Better suited for patients with conjunctival loss alongwith LSCD
 Cultured corneal epithelial / limbal stem cell transplantation :
 Stem cells are cultured using a small amount of tissue , proliferated on a
substrate in a tisuue culture medium to form an epithelial tissue .
 Concept was derived from the use of cultured human epidermal cells used in burn
patients in plastic and reconstructive surgery .
 Kenyon and Tseng were the first to apply the limbal stem cell theory clinically in
1989.
 Advantages :
 Rejection can be avoided
 Potential damage to the donor eye can be minimized
Tissue
• Limbal biopsy from donor
Medium
• DMEM / Ham’s F12 medium +
• Inactivated 3T3 fibroblasts
• Growth is enzymatically released
• Medium changed every 3 days
Scaffold
• Amniotic membrane / bandage contact
lens / petrolatum gauze/ Fibrin substrate
Transplant
• Airlifting/ transfer to recipient bed
 Pelligrini et al have shown encouraging results in their series with cultured
autologous corneal epithelial stem cells
 Surface was stable and limbal biopsies tested positive for keratin K3
 Sangwan et al , in their series of 18 eyes with severe limbal stem cell deficiency
had a success rate of 94.4 % with cultured autologous limbal and conjunctival
stem cells
 Complications :
 Damage to muscle , bleeding , perforation
 Thick lenticules – improper surfacing of tear – dellen / dislodgement
 Repeated epithelial breakdown due to persistent inflammation
 Allograft rejection – 14 to 74 %
 Infective keratitis
 Glaucoma
 Treatment protocol :
 Antibiotics until epithelization
 Steroids – taper according to inflammation and low maintenance dose
 Lubricants – preservative
 Autologous serum
 Systemic immunosuppression : steroids +
 Rejection : step up steroids / systemic immunosuppressants
 Only after achieving ocular surface stability to provide optimal visual
rehabilitation
•Staged ?
•LSCT may alone suffice
•Wait for atleast 3 months upto
1 year
•DALK may be considered later
•Combined ?
•Optimal visual results
•Theoretical reduction in risk of
rejection
 For severely damaged eyes
 Poor candidates for keratoplasty / surface reconstruction
 Good retention rates in hitherto studies
 Limitations :
 Lifelong antibiotic prophylaxis
 Complications – sterile vitritis , corneal melt , glaucoma , RD , RPM
 Newer technique ?
 Epi-decemetic K-Pro
 Filtration surgery is complicated by extensive scarring of the perilimbal and
bulbar conjunctiva and the shortening of fornices
 Implants – plagued by a high complication rate
 Cyclodiode ablation of the CB may be considered , but eventually leads to phthisis
in a large number of cases
 Painful blind eyes
Comprehensive
Glaucoma
Oculoplasty
Ocular
surface
1. Amniotic membrane transplantation : a review of current indications in the
management of ophthalmic disorders, Virender s sangwan et al
2. Limbal stem cell transplantation , Merle Fernandes et al
3. The Cornea , Mannis
Thank you …..

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Management of chemical injuries

  • 2.  True ophthalmic emergency  Irrigation :  Copious irrigation – pH neutralization  90 minutes – reduces pH by 1.5  Neutral irrigation fluid  ? Amphoteric buffering solution  Morgan lens  Removal of retained particles / necrotic material
  • 3.
  • 4. 1. Antibiotic – preservative free :  Epithelial defect – broad spectrum antibiotic  Drops / ointment  Take into account drug toxicity  Fortified antibiotics if necessary
  • 5. 2. Steroids : Benefits Inflammatory cell suppression Collagenase inhibition Risks Suppress collagen production and keratocyte migration Thinning
  • 6. 3. Ascorbate :  Ascorbic acid supplementation systemically / topically to overcome the scorbutic state of the aqueous humour( due to damage to the ciliary body ) thus promote stromal repair .  15mg /dl  10 % sodium citrate eye drops every hourly  1000 mg of oral ascorbic acid 4 times daily
  • 7. 5. Citrate :  Effective in both preventing and retarding the progression of corneal ulcers.  Chelates extracellular calcium and diminishes the activity of polymorphonuclear leukocytes by reducing membrane and intracellular calcium levels.  Reduces neutrophil infiltration and also has an inhibitory effect on collagenase.  Topical route is superior  10% solution of citrate eye drops may be administered hourly
  • 8. 6. Cycloplegic agents 7. Preservative free tear sustitutes 8. Antiglaucoma medication : oral is preferable (avoids drug toxicity ) 9. Tetracyclines :  Reduces collagenase activity and prevents ulceration  Oral doxy – 100 mg BD  Topical – 1 % suspension /3 % ointment 10. Serum eye drops
  • 9. Removal of inflammatory stimulus Removal of retained particles / necrotic tissue Symblepharon lysis ? Anterior chamber paracentesis Aqueous exchange Facilitation of healing
  • 10.  Tenon’s advancement :  Re-establish limbal circulation with the help of vital connective tissue from the orbit and limit the progression towards necrosis, aseptic ulceration, and scleral perforation in severe burns  Initial stabilization of Grade 4 burns  Tissue adhesives
  • 11.  Derived from the innermost layer of the human placenta  3 basic layers :  Epithelial monolayer  Thick basement membrane  Avascular , hypocellular matrix  Can promote epithelial cell migration , adhesion and differentiation  Supports the growth of epithelial progenitor cells
  • 12. Promotes epithelial healing • Acts as a basement membrane rich in various growth factors Decreases inflammation • Physical entrapment of inflammatory mediators and induction of their apoptosis Decreases scarring • Expression of anti inflammatory cytokines
  • 13.  Fibrous and necrotic tissue meticulously removed  Symblepharon release  Hemostasis achieved  Large sheet of AM devoid of button holes is draped over the ocular surface  The AM may be anchored to the fornix by 2 sets of double armed chromic catgut sutures  The sutures are passed through the AM and then the full thickness of the eyelid exiting through the skin  The AM is then fixed by running non absorbable sutures to the limbus or the corneal periphery  Multiple interrupted vicryl sutures are placed to anchor the membrane to the bulbar conjunctiva and the inner lid surface  Fibrin glue may be used alternatively
  • 14.
  • 15.  Joseph et al – rapid pain relief and reepithelization in moderate burns but no definite benefit over medical therapy in severe burns  Meller et al – performed AMT within 2 weeks of injury and concluded that AMG is helpful in promoting re epithelization and reducing inflammation in acute stages , thereby, preventing scarring in later stages  Thus , in acute stages AMG helps by reduction of scarring sequelae and optimizes the ocular surface for future reconstructive procedures  May alone give satisfactory results in partial LSCD
  • 16.  Goals :  Optimization of the ocular surface  Visual rehabilitation  Adjunct procedures :  Reconstruction of fornices  Correction of eyelid malposition
  • 17. 1. Conjunctival transplantation :  Contralateral eye 2. Buccal and nasal mucosal transplantation  symblepharon, trichiasis, entropion, or keratinized conjunctiva at the palpebral margin.  Posterior aspect of the upper or lower lip.  Septum and the lower or medium turbinates
  • 18.  Secondary LSCD  One time damage with cicatrizing sequelae • Absence of the palisades of Vogt • Dull irregular epithelium • Superficial vascularization • Conjunctivalization • Persistent epithelial defects
  • 19.  The corneal surface is in a state of constant healing by means of a constant process of cell renewal and regeneration of the epithelium  The proliferative potential is limited only to the basal cells  A vertical, as well as a horizontal, movement of cells characterizes the kinetics of the maintenance of the corneal epithelial mass- X,Y,Z hypothesis
  • 20.  Long-lived  Long cell cycle time  Increased potential for error-free proliferation  Poor differentiation  Asymmetric cell division
  • 21.
  • 22.  Theoretically it is possible to restore stem cell function by expanding the stem cell population through modulations in the microenvironment, or inducing transient amplifying cell mitosis with the use of appropriate factors
  • 23.
  • 24.  The various limbal transplantation procedures include  Conjunctival limbal autograft ( CLAU )  Keratolimbal allograft ( K-LAL )  Conjunctival limbal allograft (CLAL)  Cultured corneal epithelial or limbal stem cell transplantation ( LSCT / SLET )
  • 25.  CLAU:  Limbal stem cells on a carrier of conjunctiva  Unilateral / partial LSCD  Donor – fellow eye  Careful case selection  Excision of upto 6 clock hours of conjunctival tissue  No immunosuppression
  • 26.
  • 27.  Limbal tissue is primarily transplanted with minimal conjunctival tissue.  Least risk for rejection  A 2 × 2 mm area, centered on the superior limbus, is marked.  Subconjunctival dissection towards the limbus with a shallow area of dissection 1 mm into clear cornea is continued and the limbal tissue excised and placed in BSS  Recipient eye - a 360 degree conjunctival peritomy is performed with removal of any vascular corneal pannus.  Hemostasis is achieved amniotic membrane is placed over the bare ocular surface and secured with fibrin tissue glue.  The donor tissue is cut into 8 to 10 small pieces and placed, epithelial side up, on the amniotic membrane and distributed in a circular fashion avoiding the visual axis.  The transplants are also fixed in place with fibrin glue.  A soft bandage contact lens is placed
  • 28.  KLAL / cadaveric KLAL :  Limbal tissue attached to a corneal carrier is harvested from cadaveric eyes and transplanted to the recipient eye  Severe LSCD / one eyed / no living related willing donor  Works best if conjunctiva is not or minimally scarred and inflammation is quiet  Combined PKP or conjunctival – KLAL can be considered  Indefinite immunosuppression
  • 29.
  • 30.  CLAL :  One eyed with total LSCD / bilateral LSCD  Normal limbal tissue on a conjunctival carrier  Donor – living relative ( best if HLA matched )  Indefinite immunosuppression  Better suited for patients with conjunctival loss alongwith LSCD
  • 31.  Cultured corneal epithelial / limbal stem cell transplantation :  Stem cells are cultured using a small amount of tissue , proliferated on a substrate in a tisuue culture medium to form an epithelial tissue .  Concept was derived from the use of cultured human epidermal cells used in burn patients in plastic and reconstructive surgery .  Kenyon and Tseng were the first to apply the limbal stem cell theory clinically in 1989.  Advantages :  Rejection can be avoided  Potential damage to the donor eye can be minimized
  • 32. Tissue • Limbal biopsy from donor Medium • DMEM / Ham’s F12 medium + • Inactivated 3T3 fibroblasts • Growth is enzymatically released • Medium changed every 3 days Scaffold • Amniotic membrane / bandage contact lens / petrolatum gauze/ Fibrin substrate Transplant • Airlifting/ transfer to recipient bed
  • 33.  Pelligrini et al have shown encouraging results in their series with cultured autologous corneal epithelial stem cells  Surface was stable and limbal biopsies tested positive for keratin K3  Sangwan et al , in their series of 18 eyes with severe limbal stem cell deficiency had a success rate of 94.4 % with cultured autologous limbal and conjunctival stem cells
  • 34.  Complications :  Damage to muscle , bleeding , perforation  Thick lenticules – improper surfacing of tear – dellen / dislodgement  Repeated epithelial breakdown due to persistent inflammation  Allograft rejection – 14 to 74 %  Infective keratitis  Glaucoma
  • 35.  Treatment protocol :  Antibiotics until epithelization  Steroids – taper according to inflammation and low maintenance dose  Lubricants – preservative  Autologous serum  Systemic immunosuppression : steroids +  Rejection : step up steroids / systemic immunosuppressants
  • 36.
  • 37.  Only after achieving ocular surface stability to provide optimal visual rehabilitation •Staged ? •LSCT may alone suffice •Wait for atleast 3 months upto 1 year •DALK may be considered later •Combined ? •Optimal visual results •Theoretical reduction in risk of rejection
  • 38.  For severely damaged eyes  Poor candidates for keratoplasty / surface reconstruction  Good retention rates in hitherto studies  Limitations :  Lifelong antibiotic prophylaxis  Complications – sterile vitritis , corneal melt , glaucoma , RD , RPM  Newer technique ?  Epi-decemetic K-Pro
  • 39.  Filtration surgery is complicated by extensive scarring of the perilimbal and bulbar conjunctiva and the shortening of fornices  Implants – plagued by a high complication rate  Cyclodiode ablation of the CB may be considered , but eventually leads to phthisis in a large number of cases
  • 42. 1. Amniotic membrane transplantation : a review of current indications in the management of ophthalmic disorders, Virender s sangwan et al 2. Limbal stem cell transplantation , Merle Fernandes et al 3. The Cornea , Mannis

Editor's Notes

  1. pH of both eyes to be tested / anaesthetic drops to enhance comfort
  2. Sterile ulceration occurs when there is an imbalance between collagen synthesis and proteolytic degradationthe, risk of sterile ulceration in the first week following a chemical injury is relatively modest but increases as the corneal repair process becomes established around day 14 post injury
  3. Early administration is crucial as once the ulceration is established ascorbate is not very beneficial / topical admin may be superior to oral as the CB is unable to concentrate ascorbate
  4. Promote re-epithelialization by washing out inflammatory cells and hydrating the ocular surface. Temporary or permanent punctal occlusion
  5. Symblepharon lysis can be done with a glass rod / fornices should be maintained with the help of an early AMT / to line the eyelids and conjunctiva Paracentesis not tried in humans but favourable results in animal models
  6. The structural integrity , transparency and elasticity make the AM most suitable for ocular surface reconstruction
  7. Growth factors – TGF/ HEPATOCYTE GROWTH FACTOR/ EPIDERMAL GROWTH FACTOR
  8. Amg orientation ? Stromal side – vitreous like strands when lifted with a cellulose sponge / lissamine green staining – helps in identification of graft wrinkles and folds
  9. Conj . Transplantation can be done from the contralateral eye in unilateral injury cases / a small sample of the upper bulbar conjunctiva can be taken without compromising the limbus . The advantage is that we can use compatible tissue alongwith mucous cells and it gives good results in cases of forniceal foreshortening and fibrosis Nasal mucosal –large sized grafts and transplantation of intraepithelial mucous cells
  10. Hallmark of LSCD – conjunctivalisation , vascularization and inflammation features - recurrent and persistent epithelial defects, superficial vascularisation, scarring, thick fibrovascular pannus, ulceration, melting and perforation/ diagnosis can be made by impression cytology, histopathology and fluorophotometry
  11. Cells in the uppermost layer of the corneal epithelium are continuously desquamated from the surface and must be replaced by cell proliferation
  12. Allows one of the daughter cells to remain a stem cell while the other differentiates to become a transient amplifying cell. TACs then differentiate into postmitotic cells, and finally to terminally differentiated cells (TDCs).
  13. The decision to undertake a LSCT depends on the laterality and severity of the disease
  14. The limbal stem cells may be drawn either from the fellow eye (autograft), a cadaver (allograft) or a living relative (allograft). The limbal stem cells are harvested with a carrier which may be either the conjunctiva (conjunctival-limbal auto- or allograft) or cornea (kerato-limbal allograft).
  15. CLAU – large tumours / pterygium / contact lens induced keratopathy
  16. A 360° limbal peritomy is performed with removal of 2–3 mm of bulbar conjunctiva and additional resection at the 12 and 6 o'clock meridians. (B) Abnormal corneal epithelium and fibrovascular pannus are removed by superficial dissection using the necessary techniques (peeling, blunt dissection, sharp dissection). (C) Donor tissue harvesting. Conjunctival dimensions of the grafts are marked with a gentian violet marking pen. Inset: dissection of limbus is carried onto peripheral cornea beyond the vascular arcades. Harvesting begins with the bulbar conjunctival portion and proceeds anteriorly. (D) The conjunctival limbal grafts are transferred to their corresponding anatomic positions on the recipient eye and secured with multiple interrupted 10/0 nylon sutures.
  17. Indications and CI are similar to CLAU
  18. Limbal tissue from almost one and half cadaver eyes is transplanted hence a large no of stem cells are transplanted
  19. Since only epithelial cells without blood vessels and Langerhans cells are transplanted
  20. Culture system is maintained for 14-28 days / Airlifting to promote epithelial tight junction formation / the cultured SC and their carrier is anchored to the limbus via 10-o nylon sutures and to the conjunctiva by 8-0 vicryl / BCL placed
  21. Last resort /… only hope of restoring vision in a end stage eye
  22. Goes hand in hand with chemical burns / manifests within 1 week of presentation / Surgical therapy may be required for glaucoma recalcitrant to MMT