MANAGEMENT OF

OCULAR CHEMICAL

INJURIES

DR. SHRUTI LANJEWAR

M.S (OPHTHAL), FAEH (CORNEA)

COMMON ALKALI SUBSTANCE AT HOME

CompoundCommon

sourcesComments

Ammonia [NH3] Fertilizers NH4OH fumes

Refrigerants Very rapid penetration

Cleaning agents (7%

solution)

Lye [NaOH] Drain cleanersPenetrates almost as rapidly

as ammonia

Potassium

hydroxide [KOH]Caustic potash Severity similar to that of lye

Magnesium

hydroxide

[Mg(OH)2]

SparklersProduces combined thermal

and alkali injury

Lime [Ca(OH)2] PlasterMost common cause in

workplace

Mortar Poor penetration

CementToxicity increased by retained

particulate matter

Whitewash

COMMON ACID SUBSTANCE AT HOME

Acid Strength Use

Sulfuric (H2SO4) Strong

Car batteries, fertilizer, making other

acids, explosives, dyes, refining

petroleum

Nitric (HNO3) StrongFertilizers, 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

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

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

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

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

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

ROLE OF THE POLYMORPHONUCLEAR NEUTROPHIL

alkali-injured collagen liberates a cytokine

stimulating PMN influx into the cornea

PMNs themselves release leukotrienesresulting in the additional influx of neutrophils

proteolyticenzymes, 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

BIOCHEMICAL CHANGES

High pH

Hydroxyl anion

Acid glycosidases

Granulocyte protease

Ascorbate

Ascorbate level should be greater than

15mg/100ml

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

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

Hughes WF Jr: Alkali burns of the eye. II. Clinical and

CLASSIFICATION OF OCULAR SURFACE BURN

Roper-Hall MJ. Thermal and chemical burns. Trans Ophthalmol Soc UK,

1965;85:631–53.

NEED FOR NEW CLASSIFICATION

Change in the knowledge & understanding of

ocular surface healing

Changed approach to surgical management

Concept of stem cells

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.

NEW CLASSIFICATION OF OCULAR SURFACE BURNS

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.

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.

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.

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

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 osmolaritiesare:Water Normal saline solution Ringer's lactated solution Balanced salt solution(BSS) Phosphate buffersDiphoterine, 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.

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),

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

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.

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

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.

WHICH RINSING SOLUTION SHOULD WE CHOOSE?

A prompt rinsing with agents of high neutralizing capacity such as Diphoterine, Previn and CederrothEye 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.

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.

NASAL CANNULA

OTHER TECHNIQUES

There is also a perforated silicone tube (Oklahoma Eye Irrigating Tube) shaped to fit the conjunctival fornicesand adaptable to an intravenous delivery system.

Ralph RA, Slansky HH: Therapy of chemical burns. IntOphthalmol Clin 14:171, 1974

Tan BG: Oklahoma eye irrigating tube. Trans Am AcadOphthalmol Otolaryngol 74:435, 1970

For prolonged continuous perfusion, a thin (PE 20) polyethylene tube inserted percutaneously into the conjunctivalfornix 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 Ophthalmol93:1039, 1975

Doane MG: Mechanical devices. Int Ophthalmol Clin13:239, 1973

LITMUS PAPER TEST

Litmus paper is a readily available test of tear film pH.

It is composed of dyes extracted from lichens, which exhibit colourchanges under differing pH conditions.

Advantages: easy to perform, quick, cheap and requires only a small sample size

Disadvantages: inaccurate and errors in pH measurement.

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 colourpigment 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’’

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.

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

CASE 1

14 yr, male child, RE lime injury

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 : Intracameralphosphate buffer in alkali burns. Can J Ophthalmol 13: 93,1978.

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

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 OculPharmacol.1990 Summer;6(2):101-12.

Miotics are contraindicated because they cause increase inflammation and contribute to posterior synaechiae that culminate in pupillary block.

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

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.

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.

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 collagenaseproduction.

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

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. CurrOpin 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

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.

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.

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.

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 .

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.

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

Symblepharonrings

Glass rod

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

EPITHELIAL REGENERATION:

MEDICAL MANAGEMENT

Refitting a therapeutic soft contact lens.

Artificial equivalent of acetylcholine (phospholineiodide, 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

SURGICAL MANAGEMENT

Tarsorrhaphy

Symblepharon release

Scleral lens

Conjunctival flap

Mucous membrane graft

Perforation: N butyl cyanoacrylate or patch graft

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.

AMNIOTIC MEMBRANE TRANSPLANTATION

Mechanism of action:

AM possesses a direct anti-inflammatory action.

Expression of such inflammatory chemokinesas 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).

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 Sci40(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 limbalepithelial stem cells.

When there is deep stromal ischemia, AMT alone does not work

CASE 2

25 yr male, RE lime injury

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.

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.

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 limbalstem 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.