This document discusses the management of ocular chemical injuries. It begins by describing common alkali and acid substances found at home and their sources and properties. It then covers the pathophysiology of chemical injuries, including the role of the corneal epithelium, stroma, polymorphonuclear neutrophils, and conjunctival epithelium in the injury and healing processes. Different classification systems for the severity of ocular chemical burns are also presented. The stages of clinical management, including immediate emergency treatment, early acute phase treatment, and late rehabilitation treatment are summarized.

1. MANAGEMENT OF
OCULAR CHEMICAL
INJURIES
DR. SHRUTI LANJEWAR
M.S (OPHTHAL), FAEH (CORNEA)

2. COMMON ALKALI SUBSTANCE AT HOME
Compound
Common
sources
Comments
Ammonia [NH3] Fertilizers NH4OH fumes
Refrigerants Very rapid penetration
Cleaning agents (7%
solution)
Lye [NaOH] Drain cleaners
Penetrates almost as rapidly
as ammonia
Potassium
hydroxide [KOH]
Caustic potash Severity similar to that of lye
Magnesium
hydroxide
[Mg(OH)2]
Sparklers
Produces combined thermal
and alkali injury
Lime [Ca(OH)2] Plaster
Most common cause in
workplace
Mortar Poor penetration
Cement
Toxicity increased by retained
particulate matter
Whitewash

3. COMMON ACID SUBSTANCE AT HOME
Acid Strength Use
Sulfuric (H2SO4) Strong
Car batteries, fertilizer, making other
acids, explosives, dyes, refining
petroleum
Nitric (HNO3) Strong
Fertilizers, explosives, rocket
propellant, production of nylon
Chromic
(H2CrO4)
Strong
An intermediate in electroplating,
ceramic glazes, wood preservation
Hydrofluoric
(HF)
Weak, but
most reactive
anion
Etching glass, semiconductor
production, rust remover

4. PATHOPHYSIOLOGY OF CHEMICAL INJURIES
ROLE OF CORNEAL EPITHELIUM
 Alkalies saponify and liquefy the lipoidal cell
membranes and junctional complexes.
 Epithelial cytokines stimulate the keratocytes to
produce type I collagenase.
 Epithelial cells themselves can produce a type V
collagenase (gelatinase).
 Epithelial cells release prostaglandins in response
to inflammation.
 Langerhans cells, which appear during local or
remote corneal inflammation..
 Epithelial cells arising from multipotential stem
cells at limbus migrate continuously in a
centripetal fashion toward the corneal center.
Iwata M, Yagihashi A, Roat MI et al: Human leukocyte antigen-class II positive human corneal epithelial cells activate allogeneic T cells. Invest
Ophthalmol Vis Sci 35: 3991, 1994
 Seto SK, Gillette TE, Chandler JW: HLA-DR+ /T6—Langerhans cells of the human cornea. Invest Ophthalmol Vis Sci 28:1719, 1982
Gillette TE, Chandler JW, Greiner JV: Langerhans cells of the ocular surface. Ophthalmology 89:700, 1982
Johnson-Wint B, Bauer EA: Stimulation of collagenase synthesis by a 20,000 dalton epithelial cytokine. J Biol Chem 260:2080, 1985
Fini ME, Girard MT: Expression of collagenolytic/gelatinolytic metalloproteinases by normal cornea. Invest Ophthalmol Vis Sci 31:1779, 1990

5. SOURCE OF REGENERATING CORNEAL EPITHELIUM
1st few hr
• Intact epithelium sends fingerlike extensions forward into the injured zone.
• Fibronectin and other proteins from the tear film are deposited on the bare stroma or intact Bowman's layer.
6th hr
• Basal epithelial cells from the margin of the wound loose their hemidesmosomal attachments, migrate
centripetally.
• At first, individual cells become thin, increasing their surface area to facilitate migration over the defect. Later,
their numbers increase as mitosis occurs a few millimeters behind the advancing edge.
• The healing epithelial cells establish secure attachments to the underlying basement membrane and
extracellular matrix.
• They synthesize the proteins and intercellular bridges that render an intact epithelial surface resistant to
penetration by infectious agents and noxious chemicals.
Thoft RA, Friend J: The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci 24: 1442, 1983
Schultz GS: Modulation of corneal wound healing. In Krachmer JH, Mannis MJ, Holland EJ (eds): Cornea: Fundamentals of Cornea and
External Disease, p 183. St Louis: Mosby, 1997
Kuwabara T, Perkins DG, Cogan DG: Sliding of the epithelium in experimental corneal wounds. Invest Ophthalmol Vis Sci 15:4, 1976
 Dua HS, Forrester JV: Clinical patterns of corneal epithelial wound healing. Am J Ophthalmol 104:481, 1987

6. ROLE OF THE CORNEAL STROMA
 Corneal stroma consists of appx. 200
layers of mostly type I collagen.
 The stroma itself is relatively acellular,
with only 2% occupied by keratocytes.
 Functions of keratocytes:
 Produce collagen, which accounts for
more than 70% of the stroma by
weight.
 Synthesize glycosaminoglycans.
 Synthesize matrix
metalloproteinases (MMPs) known
as collagenases.
 MMPs are regulated in vivo by tissue
inhibitors of metalloproteinases
(TIMPs) and other inhibitors.
Cameron JD: Corneal reaction to injury. In Krachmer JH, Mannis MJ, Holland EJ (eds): Cornea: Fundamentals of Cornea and External
Disease, p 163. St Louis: Mosby, 1997
Nishida T: Cornea. In Krachmer JH, Mannis MJ, Holland FJ (eds): Cornea: Fundamentals of Cornea and External Disease, p 3. St Louis:
Mosby, 1997
 Woessner JF Jr: The family of matrix metalloproteinases. Ann New York Acad Sci 732:11, 1994

7. ROLE OF THE CORNEAL STROMA
keratocytes increase in number by mitosis, and new ones
migrate into the region of damage.
The energized keratocytes produce new collagen and
proteoglycans
New collagen is type I, the diameter of the resulting fibers is
larger and the spacing is irregular.
proteoglycans bind water more avidly, resulting in excess
hydration of the scar, which further insures irregular spacing
(with lack of transparency) of the new collagen.
stromal keratocytes develop intracytoplasmic contractile
elements that cause contraction of the scar and irregular
astigmatism
Cameron JD: Corneal reaction to injury. In Krachmer JH, Mannis MJ, Holland EJ (eds): Cornea: Fundamentals of Cornea and External Disease, p 163. St
Louis: Mosby, 1997
 Birk DE, Trelstad RL: Extracellular compartments in matrix morphogenesis: Collagen fibril, bundle , lamellar formation by corneal fibroblasts. J Cell Biol 99:24,
1984
Kenyon KR: Morphology and pathologic response of the cornea to disease. In Smolin G, Thoft RA (eds): The Cornea, p 43. Boston: Little Brown, 1987

8. COLLAGENASE
 Collagenases are enzymes which are capable of dissolving insoluble,
undenatured collagen.
 The collagenase produced through the leucocytes and to a much less
degree through keratocytes and this only after a latency period of
seven days.
 Calcium and zinc are necessary for collagenase activity.
COLLAGENASE
True mammalian
collagenase
MMP 1
MMP 8
Bacterial
collagenase

9. ROLE OF THE POLYMORPHONUCLEAR NEUTROPHIL
alkali-
injured
collagen
liberates a
cytokine
stimulating
PMN influx
into the
cornea
PMNs
themselves
release
leukotrienes
resulting in
the
additional
influx of
neutrophils
proteolytic
enzymes, but
also
superoxide
radicals
further
collagen
degradation
and corneal
ulceration
Lazarus GS, Brown RS, Daniels JR et al: Human granulocyte collagenase. Science 159:1483, 1968
Pourmotabbed T, Solomon TL, Hasty KA et al: Characteristics of 92kDa type IV collagenase/gelatinase produced by granulocytic leukemia cells:
Structure, expression of cDNA in E. coli and enzymic properties. Biochim Biophys Acta 1204:97, 1994
 Hasty K, Pourmotabbed TF, Goldberg GI et al: Human neutrophil collagenase. A distinct gene product with homology to other matrix
metalloproteinases. J Biol Chem 265: 11421, 1990
 Matsuda H, Smelser GK: Epithelium and stroma in alkali-burned corneas. Arch Ophthalmol 89:396, 1973

10. BIOCHEMICAL CHANGES
High pH
Hydroxyl anion
Acid glycosidases
Granulocyte protease
Ascorbate
Ascorbate level should
be greater than
15mg/100ml

11. THE CONJUNCTIVAL EPITHELIUM
 Functions:
 Establishes a relative
barrier to the passage of
microorganisms and
noxious chemical agents
 It is active in local immune
reactions.
 Its goblet cells produce
mucin, which adsorbs to
the glycoproteins coating
the microvilli of corneal and
conjunctival epithelial cells.
Montan PG, Biberfeld PJ, Scheynius A: IgE, IgE receptors, and other immunocytochemical markers in atopic and nonatopic patients with
vernal keratoconjunctivitis. Ophthalmology 102:725, 1995
Shapiro MS, Friend J, Thoft RA: Corneal re-epithelialization from conjunctiva. Invest Ophthalmol Vis Sci 21:135, 1981
 Danjo S, Friend J, Thoft RA: Conjunctival epithelium in healing of corneal epithelial wounds. Invest Ophthalmol Vis Sci 28:1445, 1987

12. HUGHES CLASSIFICATION
 Mild
 Erosion of corneal epithelium.
 Faint haziness of cornea.
 No ischemic necrosis of conjunctiva or sclera
 Moderately severe.
 Corneal opacity blurring iris details.
 Minimal ischemic necrosis of conjunctiva and
sclera
 Very severe
 Blurring of pupillary outline
 Blanching of conjunctival and scleral vessels
 Hughes WF Jr: Alkali burns of the eye. I. Review of the
literature and summary of present knowledge. Arch Ophthalmol
35:423, 1946

13. CLASSIFICATION OF OCULAR SURFACE BURN
Roper-Hall MJ. Thermal and chemical burns. Trans Ophthalmol Soc UK,
1965;85:631–53.

14. NEED FOR NEW CLASSIFICATION
Change in the knowledge & understanding of
ocular surface healing
Changed approach to surgical management
Concept of stem cells

15. NEW CLASSIFICATION OF OCULAR SURFACE BURNS
Grade Prognosis Clinical findings Conjunctival
involvelment
I Very good 0 clock hours of limbal
involvement
0%
II Good ⩽3 clock hours of limbal
involvement
⩽30%
III Good >3–6 clock hours of limbal
involvement
>30–50%
IV Good to guarded >6–9 clock hours of limbal
involvement
>50–75%
V Guarded to poor >9–<12 clock hours of limbal
involvement
>75–<100%
VI Very poor Total limbus (12 clock hours)
involved
Total
conjunctiva
(100%)
involved
A new classification of ocular surface burns: Harminder S Dua, Anthony J King,
Annie Joseph, Br J Ophthalmol 2001;85:1379–1383.

16. NEW CLASSIFICATION OF OCULAR SURFACE BURNS

17. CLINICAL STAGES:
ACUTE STAGE (IMMEDIATE TO 1 WEEK) -
 In mild burns, the corneal and conjunctival epithelium have
defects with sparing of limbal blood vessels.
 In severe burns the epithelium of cornea and conjunctiva is
destroyed and there is immediate limbal ischaemia as a result of
damage to blood vessels and thrombosis.
 There is an increase in pH of the aqueous humor along with
decrease in glucose and ascorbate levels.

 An initial peak of increased intraocular pressure is due to
compression of the globe as a result of hydration and longitudinal
shortening of collagen fibrils. The second peak of raised
intraocular pressure occurs due to impedence of aqueous humor
outflow.

18. EARLY REPARATIVE STAGE (1-3WEEK):
 In grade I and II chemical burns, there is regeneration of epithelium,
neovascularization of cornea, clearing of stroma and beginning of
synthesis of collagen glycosaminoglycans.
 In grade III and IV chemical burns, regeneration of epithelium may not
start, stroma remains hazy, and endothelium may be replaced by a
retrocorneal membrane. It is during this stage, corneal ulceration tends
to occur, attributed to the action of digestive enzymes such as
collagenase, metalloprotinase, and other proteases released from
regenerating corneal epithelium and polymorphonuclear leukocytes.

19. LATE REPARATIVE STAGE AND SEQUELE
( 3 WEEKS AND LONGER ):
 This stage is characterized by completion of
healing with a good prognosis (grade I and II) and
complication in those with a guarded visual
prognosis (grade III and IV).
 The late complications of chemical burns include
poor vision, corneal scarring, xerophthalmia, dry
eyes, symblepharon, ankyloblepharon, glaucoma,
uveitis, cataract, adnexal abnormalities such as
lagophthalmos, entropion, ectropion, and trichiasis.

20. MANAGEMENT
 Treatment of chemical injuries to the eye requires medical and surgical intervention,
both acutely and in the long term, for maximal visual rehabilitation.
 Common goals of management include the following:
 Removing the offending agent
 Promoting ocular surface healing
 Controlling inflammation
 Support of reparative processes
 Prevention of complications
 Management of the chemical burns cases can be divided
into:
 Immediate / Emergency treatment
 Early acute phase treatment
 Intermediate term treatment
 Late rehabilitation treatment

21. IMMEDIATE / EMERGENCY TREATMENT
REMOVE INCITING CHEMICAL BY IRRIGATION
Copious irrigation should begin immediately
at the scene of the accident with any non-
toxic liquid which is continued during rapid
transport to a medical care facility.
Burns FR, Paterson CA Prompt irrigation of chemical eye injuries may avert severe damage
Occup Health Saf 1989 Apr;58(4):33-6.
These solutions, with their varying osmolarities
are:
Water
Normal saline solution
Ringer's lactated solution
Balanced salt solution(BSS)
Phosphate buffers
Diphoterine, Previn and Cederroth Eye Wash
Solution
90 minutes of external irrigation shows 1.5
unit reduction of the elevated pH.
Paterson CA, Pfister RR, Levinson RA: Aqueous humor pH changes after
experimental alkali burns. Am J Ophthalmol 1975; 79:414-419.

22. WATER
 The Benefits of Rinsing with Water :
 Rinsing with water was the first protocol used
for chemical decontamination because
 Non-toxic character
 Easy availability
 It allows the chemical agent to be carried away by a
mechanical effect, independent of its nature and
concentration.
 Limitations of Rinsing with Water :
 More cellular damage is produced due to
hypotonicity of water.
 It does not act on the potentially irritating or
corrosive nature of the chemical agent,
 Water favors the chemical agent's penetration of the
tissue
 Professor Schrage (link with the publication
Schrage, Klin Monastbl Augenheilkd, 2004),

23. BALANCED SALT SOLUTION
 Advantages:
 More physiological osmolality and pH.
 Enhanced buffering capacity.
 Prevents the swelling of the cornea
under healthy conditions,
 Protects the endothelium.
 Moreover, it includes citrates.
 Drawbacks:
 High cost.
 Need to reconstitute fresh solutions.
 McDermott MI, Edelhauser HF, Hack HM et al (1998)
Ophthalmic irrigants. A current review and update.
Ophthalmic Surg 19:724–733

24. PHOSPHATE BUFFER
 Inappropriate application of
phosphate leads to uncontrolled
calcifications of the cornea after
severe burns to the eye.
 Huige WMM, Beekhuis WH, Rijnefeld WJ, Schrage N,
Remeijer L. Deposits in the superficial corneal stroma after
combined topical corticosteroid and beta-blocking
medication. Eur J Ophthalmol1991;1(4):198–9.
 Schrage NF, Schloßmacher B, Aschenbrenner W,
Langefeld S. Phosphate buffer in alkali eye burns as an
incuder of experimental corneal calcification. Burns
2001;27:459–64.

25. DIPHOTERINE
 Diphoterine® Solution is highly effective against all kinds of corrosive
and irritant chemicals.
 It is an amphoteric, chelating molecule with at least one site able to
rapidly and effectively absorb and neutralise the aggressive chemical
molecule
 It has two different groups of pK in the acid and alkali region with a pK1
= 5.1 and a pK2 = 9.3.
Norbert Franz Schrage∗, Sirpa Kompa, Wolfram Haller, Stéphanie Langefeld Department of Ophthalmology, Eye-Clinic RWTH
Aachen, Pauwelstraße 30, D-52057 Aachen, Germany: Use of an amphoteric lavage solution for emergency treatment of eye
burns; First animal type experimental clinical considerations; Accepted 2 August 2002

26. DIPHOTERINE : ADVANTAGES
 It stops the chemical agent penetration of the tissues and
carries the chemical away from the interior to the exterior of the
tissue, thanks to its hypertonicity.
 Absorption and neutralization of the aggressive chemical
molecule remaining on the tissue surface.
 It allows a rapid return to a pH level between 5.5 to 9.
 Absence of after-effects.

27. WHICH RINSING SOLUTION SHOULD WE CHOOSE?
 A prompt rinsing with agents of high neutralizing
capacity such as Diphoterine, Previn and Cederroth
Eye Wash Solution. Rinsing with tap water had an
intermediate position on the scale of efficiency, but
was much less effective in this experiment than the
amphoteric or buffering solutions.
 S. Rihawi, M. Frentz, N. F. Schrage: Graefe’s Arch
Clin Exp Ophthalmoly; (2006) 244: 845–854.
 The hypo-osmolarity of tap water led to remarkable
corneal oedema. Enlargement of the diffusion
barrier and intracorneal dilution inhibit elevated
intracameral pH levels. Therefore, the use of iso-
osmolar saline solution proves to be less efficacious
than tap water as an irrigation agent for ocular
burns.
 Sirpa Kompa, Claudia Redbrake, Christoph Hilgers,
Henrike Wu¨ stemeyer, Norbert Schrage and
Andreas Remky: ACTA OPHTHALMOLOGICA
SCANDINAVICA 2005.

28. MORGAN LENS
 An irrigating, polymethylmethacrylate scleral lens with an attached
perfusion tube (Morgan therapeutic lens or Mor-FLEX® Lens (MT2000),
Mor-Tan Inc, Missoula, MT 59807).
 The irrigating lens should be inserted into the fornices.

29. NASAL CANNULA

30. OTHER TECHNIQUES
 There is also a perforated silicone
tube (Oklahoma Eye Irrigating Tube)
shaped to fit the conjunctival fornices
and adaptable to an intravenous
delivery system.
 Ralph RA, Slansky HH: Therapy of chemical burns. Int
Ophthalmol Clin 14:171, 1974
 Tan BG: Oklahoma eye irrigating tube. Trans Am Acad
Ophthalmol Otolaryngol 74:435, 1970
 For prolonged continuous perfusion, a
thin (PE 20) polyethylene tube inserted
percutaneously into the conjunctival
fornix and attached to either an
intravenous drip apparatus or a mobile
ocular perfusion pump.
 Ralph RA, Doane MG, Dohlman CH: Clinical experience
with a mobile ocular perfusion pump. Arch Ophthalmol
93:1039, 1975
 Doane MG: Mechanical devices. Int Ophthalmol Clin
13:239, 1973

31. LITMUS PAPER TEST
 Litmus paper is a readily
available test of tear film pH.
 It is composed of dyes extracted
from lichens, which exhibit colour
changes under differing pH
conditions.
 Advantages: easy to perform,
quick, cheap and requires only a
small sample size
 Disadvantages: inaccurate and
errors in pH measurement.

32. CAUSES OF PH MEASUREMENT ERRORS
 The mean pH of tears is 7.6, and scales often show only show 7
or 8.
 The scale is made from of a different material than litmus paper.
 Allowing drying of the paper, which creates a darker colour
 Excessive wetting of the paper, washing washes away colour
pigment away
 Too small a sample size to wet the paper
 Too quickly measuring the pH after irrigation (thus measuring the
pH of irrigating fluid)
 Use of an incorrectly matched scale for that particular litmus
paper
 Use of litmus paper past its ‘‘use -by date’’

33. CONTROL TEST TO AID PH ASSESSMENT
 Use of a litmus paper control test allows direct
comparison of colour given by the normal tear film.
 It reduces the difficulty in comparison of colours on
different materials.
 It would aid in the detection of small differences in
pH.
 It also would highlight faults caused by use of out-
of-date materials or use of incorrect pH scale.
 A J Connor, P Severn: Use of a control test to aid pH assessment of chemical
eye injuries; Emerg Med J 2009;26:811–812.

34. RETAINED PARTICULATE MATTER
 The pultaceous character of lime
particles clings in fornices.
 It can be removed with a cotton-
tipped applicator.
 It can be loosened and removed
with greater ease by irrigation
(EDTA 0.01 M).
 Debridement: removing of the
necrotic tissue with foreign
debris.
Pfister RR, et al: Identification and synthesis of chemotactic
tripeptides from alkali-degraded whole cornea: a study of N-
acetyl-Proline-Glycine-Proline and N-methyl-Proline-Glycine-
Proline. Invest Ophthalmol Vis Sci 1995; 36:1306-1316

35. CASE 1
14 yr, male child, RE lime injury

36. PARACENTESIS
 A further decrease in pH by 1.5 units can be
achieved by removing aqueous by
paracentesis.

 If buffered phosphate solution is then used
to refill the anterior chamber, a greater
reduction in pH (another 1.5 units) is
possible.
 Severe alkali burns of the eye should be
treated by paracentesis and if possible with
anterior chamber reformation with a sterile
solution.
 Paterson CA, Pfister RR, Levinson RA: Aqueous humor
pH changes after experimental alkali burns. Am J
Ophthalmol 79:414, 1975
 Bennett TO, Peyman GA, Rutgard J : Intracameral
phosphate buffer in alkali burns. Can J Ophthalmol 13:
93,1978.

37. EARLY (ACUTE) PHASE TREATMENT
 Topical antibiotics
 Mydriatics/ cycloplegics
 The mydriatic agent phenylephrine, which is also a
vasoconstrictor, should be avoided in cases in which perilimbal
ischemia is already a prominent factor.
 Paterson CA, Pfister RR, Levinson RA: Aqueous humor pH changes after experimental alkali
burns. Am J Ophthalmol 79:414, 1975

38. ANTIGLAUCOMA TREATMENT
 Carbonic anhydrase inhibitors and
hyperosmotic agent should be
administered.
 Systemic medications are preferred as
reepithelization may be prevented by topical
drops.
 Topically timolol maleate eyedrops can be
effective but beta blockers inhibit corneal re-
epithelialization.
 Liu GS, Trope GE, Basu PK. Beta adrenoceptors and
regenerating corneal epithelium. J Ocul
Pharmacol.1990 Summer;6(2):101-12.
 Miotics are contraindicated because they
cause increase inflammation and contribute
to posterior synaechiae that culminate in
pupillary block.

39. TOPICAL CORTICOSTEROIDS
 Mechanism of action:
 Topical steroids are indicated to reduce the number of inflammatory cells
infiltrating the corneal stroma.
 It assist in the process of corneal reepithelialization.
 They inhibit collagenase production in tissue cultures of human skin, but
it also predisposed to perforation of the alkali-burned rabbit cornea,
possibly by inhibition of repair processes and decrease in collagen
synthesis.
 Koob TJ, Jeffrey JJ, Eisen AZ: Regulation of human skin collagenase activity by
hydrocortisone and dexamethasone in organ culture. Biochem Biophys Res
Commun 61: 1083, 1974
 François J, Feher J: Collagenolysis and regeneration in corneal burnings.
Ophthalmologica 165:137, 1972

40. TOPICAL CORTICOSTEROIDS
 During first 10 days after an alkali burn even if epithelium
is not intact.
 At end of 10 days:
 If epithelium is intact- topical steroid may be continued
with relative safety.
 If epithelium is not intact- topical steroid must be tapered
rapidly and stopped.
 Prolonged treatment with topical steroids when used in
conjunction with topical vitamin C is not associated with
corneoscleral melting.
 A R Davis, Q H Ali,W A Aclimandos, P A Hunter; Topical steroid use in the treatment
of ocular alkali burns; British Journal of Ophthalmology 1997;81:732–734.

41. COLLAGENASE INHIBITORS
 0.2 M Disodium EDTA: Due to its
chelation of the essential calcium and is
completely reversible when more
calcium was added to the system or
when the free EDTA calcium complexes
were dialyzed
 0.2 M Cysteine : chelating the divalent
ions and disrupting the dislfide bond,
irreversible inhibition.
 10% and 20% N acetyl cystein
(Mucomyst eyedrop).
 Penicillamine: chelating the divalent
ions and disrupting the dislfide bond.
Inhibits the inflammatory cells into
stroma.

42. COLLAGENASE INHIBITORS
 Medroxyprogesterone: Topical instillation of a 0.5% suspension of
medroxyprogesterone in 1% aqueous methylcellulose twice daily, s/c
injection of 10 mg of depo medroxyprogesterone weekly, or an IM
injection of depo medroxyprogesterone all inhibits collagenase
production.
 cAMP
 SYNTHETIC INHIBITORS OF COLLAGENASE:
 Hydroxymate -containing dipeptide, Galardin
 Mercaptan (thiol)-containing compounds
 Synthetic metalloproteinase inhibitors (SIMP)Gray RD, Paterson CA: Application of peptide-based matrix metalloproteinase inhibitors in corneal
ulceration. Ann NY Acad Sci 732:206, 1994
Burns FR, Stack MS, Gray RD et al: Inhibition of purified collagenase from alkali-burned corneas. Invest
Ophthalmol Vis Sci 30:1569, 1989
Burns FR, Gray RD, Paterson CA: Inhibition of alkali-induced corneal ulceration and perforation by a thiol
peptide. Invest Ophthalmol Vis Sci 31:107, 1990

43. TETRACYCLINE
 Tetracyclines exhibit antiinflammatory and
anticollagenolytic activity independent of their
antimicrobial properties.
 Golub LM, Suomalainen K, Sorsa T: Host modulation with
tetracyclines and their chemically modified analogues. Curr
Opin Dent 2:80, 1992.
 Tetracycline binds to collagenase by a calcium
bridge, inactivating the enzyme unless additional
calcium is added.
 Perry HD, Kenyon KR, Lamberts DW et al: Systemic
tetracycline hydrochloride as adjunctive therapy in the
treatment of persistent epithelial defects. Ophthalmology
93:1320, 1986
 Tetracycline decreases ascorbic acid levels in
PMNs and by decreasing collagenlysis, the
products of which are chemotactic for PMNs.
 Windsor ACM, Hobbs CB, Treby DA et al: Effect of
tetracycline on leukocyte ascorbic acid levels. Br Med J
1:214, 1972

44. ROLES OF ASCORBIC ACID
Mechanism of action:
 Ascorbic acid is required for hydroxylation
of the proline and lysine.
 After severe ocular chemical burns,
aqueous ascorbic acid concentrations drop
markedly.
 When the aqueous ascorbic acid level is
artificially maintained at a level greater than
15 mg/dl, corneal ulceration can be
prevented or significantly reduced.
 Pfister RR, Paterson CA: Additional clinical and morphological
observations on the favorable effect of ascorbate in experimental
ocular alkali burns. Invest Ophthalmol Vis Sci 16:478, 1977
 Dosage:
 Oral ascorbate 2 gm/day
 Topical 10% ascorbic acid solution
formulated in artificial tears every hour.

45. SODIUM CITRATE
 10% solution of sodium citrate made up in
artificial tears and applied topically .
 Acts through citrate chelation of
extracellular calcium, decreasing the
availability of calcium which acts as an
intracellular second messenger in PMNs.
 Paterson CA, Williams RN, Parker AV
Characteristics of polymorphonuclear leukocyte
infiltration into the alkali burned eye and the
influence of sodium citrate. Exp Eye Res. 1984
Dec;39(6):701-8.
 Prevents activities like locomotion,
phagocytosis, degranlation and enzyme
release .
 Plister RR: The effect of chemical injury on ocular
surface. Ophthalmology 90: 601, 1983.

46. AUTOLOGOUS SERUM EYEDROPS
 Promote the epithelial healing
process in corneal alkali wounds.
 Serum contains various factors
including Vitamin A, Epidermal
growth factor, transforming growth
factor beta, basic fibroblast growth
factor, Insulin like growth factor,
Substance P as well as proteins
such as lactoferrin and lysozyme.
 Alkali -injured corneal epithelial
wounds heal faster when treated
with amniotic membrane suspension
than with autologous serum or
preservative-free artificial tears.

47. OTHERS
 Aprotonin:
 Inhibitor of plasmin and other serine proteinases, decreases tear
plasmin and proteinase concentration and prevent corneal ulceration.
 Topical fibronectin:
 Increase corneal epithelium healing and decreases corneal ulceration.
 Heparin
 Subconjunctival injection may promote neovascularization. S.c injection
of 0.75 ml of heparin (750 units) mixed with 0.2 ml of lidocaine 2% and
0.35 ml of sodium chloride is given every other day. Atleast 10 inj are
given.
 Se of this treatment modality is limited in whom patients with intact
bulbar conjunctiva .

48. HYDROPHILIC AND COLLAGEN BANDAGE LENSES
 Facilitate corneal epithelial regeneration
and prevent symblepharon formation.
 It should be fitted as soon as possible.
 Lens with greatest oxygen permeability is
preferred.
 Placed for 6-8 weeks.
 Antibiotic coverage and close
observation are necessary.
 In alkali-burned rabbit eyes, corneas
treated with collagen shields ulcerated
earlier than those of the control eyes
because they trap PMNs which secrete
stromal digesting protease.

49. GLUED-ON CONTACT LENS
 Mechanism: to protect the
denuded stroma from
collagenase-containing
epithelium, PMNs, and tears.
 The glued-on contact lens is a
long-term commitment of at least
a year.
 Its removal while inflammation
remains active is likely to promote
collagenolysis of the stroma

50.  Symblepharon
rings
 Glass rod

51. INTERMEDIATE PHASE TREATMENT
 Major problems during this
period:
 Persistance of epithelial defect
due to eyelid incongruities,
incomplete blinking, toxicity of
preservatives in eyedrops, tear
film deficiencies, or other
factors influencing the vitality
of the corneal epithelium.
 Stromal ulceration

52. EPITHELIAL REGENERATION:
MEDICAL MANAGEMENT
 Refitting a therapeutic soft contact lens.
 Artificial equivalent of acetylcholine (phospholine
iodide, carbochol). They stimulate an increase of
intracellular cGMP, reslting in stimulation of mitosis.
 Cavanagh HD: Herpetic ocular disease: therapy of persistance epithelial defect.
Int Ophthalmol Clin 15:67,1975.
 Mucomimetic tear substitutes.
 Autologous serum eyedrops

53. SURGICAL MANAGEMENT
 Tarsorrhaphy
 Symblepharon release
 Scleral lens
 Conjunctival flap
 Mucous membrane graft
 Perforation: N butyl cyanoacrylate or patch graft

54. TENON-PLASTY
 To improve vascular support.
 In severe ischemia in acute stages,
tenoplasty and glued-on contact lenses
are important measures for preventing
scleral and corneal melt.
 Reim M, Overkamping B, Kuckelkorn R: 2
years experience with
tenoplasty. Ophthalmologe 1992; 89:524-
530.

55. AMNIOTIC MEMBRANE TRANSPLANTATION
 Mechanism of action:
 AM possesses a direct anti-inflammatory
action.
 Expression of such inflammatory chemokines
as IL-8, Gro-alpha and ENA by keratocytes is
downregulated when cultured on AM
 The stromal matrix of AM is capable of
excluding inflammatory cells
 AM also has a direct effect of preventing
scarring.
 (Lee et al. Invest Ophthalmol Vis Sci 40(Suppl):334,
1999).

56. AMNIOTIC MEMBRANE TRANSPLANTATION
 Advantages:
 Promote epithelialization and restore normal
epithelial phenotype
 Promotes proliferation and differentiation of
conjunctival and limbal epithelial stem cells in vivo
and in vitro
(Meller et al. Invest Ophthalmol Vis Sci
40(Suppl):329, 1999).47,48
 Help preserve and expand the slow-cycling property
of the epithelial stem cells (Meller et al. Invest
Ophthalmol Vis Sci 40(Suppl):329, 1999).
 Limitations:
 The use of AMT for severe (grade IV) burns is
limited. The limbal stem cell deficiency requires
transplantation of autologous or heterologous limbal
epithelial stem cells.
 When there is deep stromal ischemia, AMT alone
does not work

57. CASE 2
25 yr male, RE lime injury

58. LATE REHABILIATION TREATMENT
 A patient of partial limbal stem cell deficiency
with a clear visual axis can be followed up for
any progression / encroachment onto the
visual axis.
 In case of diffuse limbal stem cell deficiency
the following procedures have been tried.

59.  Keratolimbal allograft
 A kerato limbal allograft from a cadaveric donor tissue may be harvested and
transplanted onto the burned cornea under the cover of oral
immunosuppression.
 Conjunctival limbal autograft
 A conjunctival limbus autograft may be taken from contralateral uninvolved eye
in a case of unilateral involvement or from a living related donor in cases of
bilateral involvement.
 Cultured limbal stem cells
 Limbal stem cell grafting is a newer modality of treatment for treatment of alkali
burns. The stem cells can be taken either from the ipsilateral, contralateral or
related donor eye. It is said to help in corneal re-epithelization, achieves stable
ocular surface and prevent recurrent corneal erosions and corneal scarring. A
new concept of ex-vivo expansion of limbal stem cells and its transplantation has
also evolved.

60.  Large diameter therapeutic penetrating keratoplasty
 There have been encouraging reports with use of large diameter
PK (1 1mm-12mm) in management of severe chemical burns. By
transferring not only corneal tissue for tectonic support, this
procedure also gives early visual rehablitation by providing limbal
stem cells.
 The penetrating keratoplasty should be delayed forone year
after the active process has become quiescent. This delay allows
the inflammatory process to subside completely and permits the
injured tissue to return to the maximum degree of structural and
biochemical normalcy.
 After the inflammation subsides, Keratoprosthesis for visual
rehabilitation is also an option.