CHEMICAL INJURIESSIVATEJA CHALLA

• INTRODUCTION• EPIDEMIOLOGY• ETIOLOGY• PATHOGENESIS• CLASSIFICATION/GRADING• CLINICAL COURSE• CLINICAL FEATURES• MANAGEMENT

CHEMICAL INJURIES• One of the true ophthalmic emergencies

• Often result in significant ocular morbidity and generally strike young adults in the prime of life.

• Alkali injuries are more common and can be more deleterious

EPIDEMIOLOGY • 2/3rd in young males.• 2/3rd at Workplace vs home• 2/3rd by Alkali vs acid• 2/3rd are minor (gr. I & II) injuries• In India common d/t fire cracker injuries,lime or after

accidental injury with holi colours

ETIOLOGY• Alkalic agents• Acidic agents

COMMON ALKALI SUBSTANCE at homeCompound 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  

COMMON ACID SUBSTANCE home

Acid Strength Use

Sulfuric (H2SO4) StrongCar 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

PATHOPHYSIOLOGY• The severity of this injury is related to type, volume,

concentration, duration of exposure, and degree of penetration of the chemical

• The mechanism of injury differs slightly between acids and alkali.

Acid injury • Acids dissociate into hydrogen ions and anions in the

cornea, e.g.: HCl= H++Cl-

• The hydrogen molecule damages the ocular surface by altering the pH, while the anion causes protein denaturation, precipitation, and coagulation .

• Protein coagulation generally prevents deeper penetration of acids.

Alkali injury • Alkaline substances dissociate into a hydroxyl ion and a

cation in the ocular surface. e.g.: NaOH= Na+ + OH-

• The hydroxyl ion saponifies cell membrane fatty acids, while the cation interacts with stromal collagen and glycosaminoglycans.

• This interaction facilitates deeper penetration into and through the cornea and into the anterior segment

CLASSIFICATION OF CHEMICAL INJURIES

• Hughes classification.• Modified Hughes/Roper Hall classification.• Duas clasification.

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 pathological course. Arch Ophthalmol 36:189, 1946

• Roper-Hall/ modified Hughes classification• Degree of corneal involvement• Limbal ischemia.

• Dua classification • Limbal involvement (in clock hours) • Percentage of conjunctival involvement.

• In a randomized controlled trial of acute burns, the Dua classification was found to be superior to the Roper-Hall in predicting outcome in severe burns. However, both classification schemes are commonly employed in daily practice.

Roper Hall classification.

Roper-Hall MJ. Thermal and chemical burns. Trans Ophthalmol Soc UK, 1965;85:631–53.

DUAS CLASSIFICATIONburnsGr Prognosis Clinical findings(clock

hrs of limbal involvementConjunctival involvelment

Analogue scale

I Very good 0 clock hours 0% 0.0%

II Good ⩽3 clock hours ⩽30% 0.1-3/1-30%

III Good >3–6 clock hours >30–50% 3.1-6/31-50%

IV Good to guarded >6–9 clock hours >50–75% 6.1-9/51-755

V Guarded to poor >9–<12 Clock hours >75–<100% 9.1-11.9/75.1-99.9%

VI Very poor 12 clock hours involved Total conjunctiva (100%) involved

12/100%

A new classification of ocular surface burns: Harminder S Dua, Anthony J King, Annie Joseph, Br J Ophthalmol 2001;85:1379–1383.

Dua’s classification

CLINICAL COURSEMc Culley four phases

• Immediate (day 0) • Acute( day 0-day 7 )• Early repair (day 7 – day 21)• Late repair ( after 21 days )

Multiple events• Epithelial regrowth and migration• Collagen synthesis and degradation• Activation and migration of keratocytes

19

PATHOPHYSIOLOGY OF OCULAR INJURES

Necrosis of the conjunctival and corneal epithelium

Disruption and occlusion of the limbal vasculature.

Loss of limbal stem cells

Conjunctivilisation and vascularization of the corneal surface

Persistent corneal epithelial defects with sterile corneal ulceration

1.Corneal Damage by severe chemical injuries occurs in the following order:

20

2- Healing of the corneal epithelium and stroma as follows:

THE EPITHELIUM Centripetal movement of cells from the peripheral cornea, limbus,

or conjunctiva is responsible for normal and posttraumatic replacement of corneal epithelium.

Only partial transdifferentiation of conjunctival epithelium to corneal epithelium is possible but conjunctiva-derived epithelium never fully expresses corneal epithelial phenotypic features.

Limbal stem cells are the cells most qualified to restore the functional competence of the corneal epithelial surface after injury

21

Damaged STROMAL COLLAGEN

The maintenance and regeneration of the corneal stroma -responsibility of the pluripotent cells- keratocyte.

Keratocyte Function:Phagocytosis of collagen fibrilsSynthesis and secretion of collagen glycosaminoglycan

ground substance, collagenase, and collagenase inhibitors.Modulated by cytokines from the epithelium, inflammatory cells,

and other keratocytes.

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 is destroyed and there is immediate limbal ischaemia due to damage to blood vessels.

• Rise in intraocular pressure in a bimodal manner

• An initial peak is due to compression of the globe as a result of hydration and longitudinal shortening of collagen fibrils.

• The second peak due to impedence of aqueous humor outflow

EARLY REPAIR STAGE (1-3WEEK)• This stage is characterized by replacement of

destroyed cells and extracellular matrix.GRADE 1 AND GRADE 2 BURNS GRADE 3 AND GRADE 4 BURNSregeneration of epithelium regeneration of epithelium may not

start and progressneovascularization of cornea limited

clearing of stroma stroma remains hazy

beginning of synthesis of collagen glycosaminoglycans

endothelium replaced by a retrocorneal membrane

In stage 3 and 4, corneal ulceration tends to occur.

Stromal ulceration is due to action of digestive enzymes such as collagenase, metalloprotinase

LATE REPAIR STAGE AND SEQUELE( 3 WEEKS AND LONGER )

• This stage is characterized by completion of healing

• Corneal inflammation,collagen synthesis, and collagenase activity are peaking.

TYPE

TYPE 1 Corresponds to gr 1 injury COMPLETE RE EPITHELIALIZATION occurs Corneal phenotypically normal

TYPE 2 Gr 2 injury Sectorial corneal epithelial defect in the quadrant

corresponding to LSCD Delayed epithelialization SUPERFICIAL VASCULAR PANNUS

HEALING PATTRENS

TYPE

TYPE 3 gr 3 injury No re epithelialisation,FIBROVASCULAR PANNUS formed Conjunctivalization of cornea occurs ultimate outcome is a tectonically stable but scarred and

vascularized corneaTYPE 4 Gr 4 injurySTERILE ULCERATION

No conj and corneal epithelium d/t complete limbal ischemia and conj necrosis

Sterile ulceration,AS necrosis, PAS, cataract, glaucoma, hypotony and pthisis bulbi

HEALING PATTRENS

CLINICAL FEATURES

SYMPTOMS

- Pain- Lacrimation- Photophobia- Blepharospasm- Diminution of vision

SIGNS

- Eye lid edema,- Chemosis,- Corneal abrasions

Effects of Ocular Surface Burn

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

IMMEDIATE MANAGEMENT

ACUTE MANAGEMENTMEDICAL MANAGEMENT1.Copious irrigation with isotonic saline/clean liquid

2.Remove chemical completely from conjunctival surface,cornea and fornices

3.Topical corticosteroids prednisolone 1% 4-6 times in gr1-2 2nd hrly in gr3-4,hrly in gr 5-6 taper when epithelial healing occurs stop if corneal thinning or melting seen

4.Topical citrate 10% 2nd hrly

5.Topical ascorbate 2nd hrly

6.Tab doxy 100mg bd for 2 wks

7.Moxifloxacin e/d qid

8.AGM if required

9.Cycloplegics –homatropine 2%qid

SURGICAL THERAPY1.Debridement

2.Amniotic membrane transplantation

3.Tissue adhesives,tectonic keratoplasty

IRRIGATIONCopious 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

These solutions, with their varying osmolarities are:>Normal saline solution >Ringer's lactated solution>any clean fluid>water

90 minutes of external irrigation shows 1.5 unit reduction of the elevated pH.

• Irrigation for a minimum of 30 min and checking the pH of tears for evidence neutrality is recommended.

• Initial PH testing should involve both eyes even if pt says uniocular pain, C/L eye should not be neglected

• Failure to achieve neutrality often is evidence of a retained reservoir of chemical in the eye.

• This is particularly true in plaster injuries, in which particles embedded in the upper tarsal conjunctiva can provide continued slow release of alkali into the tear film.

MEDICAL THERAPY1.Control inflammationCorticosteroids mainstay for infl control in initial periodCorticosteroids have no adverse effect on the rate of epithelial wound healinginterfere with stromal repair by impairing both keratocyte migration and collagen synthesis. the deleterious do not become apparent until the early repair phaseThe key to successful use is to maximize the antiinflammatory effect during the ‘window of opportunity’ in the first 7–10 days, when there is little risk associated with corticosteroid use.

Progestational steroids• If there is no ep healing and early signs of stromal

melting noted stop steroids.

• Progestational steroids have less antiinflammatory potency than do corticosteroids but have only a minimal effect on stromal repair and collagen synthesis.

• Medroxyprogesterone 1% to inhibit collagenase and reduce ulceration after chemical injury.

• Progestational steroids may be substituted for corticosteroids after 10–14 days, when suppression of inflammation still is required but interference with stromal repair is undesirable.

Citrate• Citrate is a calcium chelator that decreases the

membrane and intracellular levels of calcium, resulting in impaired chemotaxis, phagocytosis, and release of lysosomal enzymes of polymorphonuclear leukocytes.

• It significantly reduces the incidence of corneal ulceration.

2.Promotion of epithelialization

The use of topical Tear Substitutes may be useful in facilitating corneal epithelial migration ingrade I and II injuries and in minimizing conjunctival scarring and symblepharon formation after grade III and IV injuries.

Role of fibronectin,epidermal growth factor,retinoic acid,sodium hyaluronate needs to be established

3. SUPPORT REPAIR AND MINIMIZE ULCERATIONAscorbate • It is a cofactor in the RLS of collagen formation.

• Damage to the cilliary body epithelium by intraocular chemical injury results in decreased secretion of ascorbate and a reduction in its concentration in the anterior chamber.

• Both topical and systemic ascorbate have been shown to decrease the incidence of sterile corneal ulceration after chemical injury.

Tetracyclins

• Tetracycline derivatives are efficacious in reducing collagenase activity.

• It is due to chelation of zinc at the active site of the collagenase enyzme.

• Doxycycline is the most potent tetracycline collagenase inhibitor

• Can be given 100mg bd for 2 wks

4.Adjuvant therapya.broad spectrum antibiotic drops like moxy QIDb.If glaucoma,give tab acetazolamide BDc.Cycloplegics like homatropine 2% QID

SURGICAL THERAPYDebridement

• Débridement of necrotic corneal epithelium is necessary to allow proper reepithelialization, irrespective of the severity of the injury.

• It is important to débride necrotic conjunctival tissue because this tissue has been shown to be a nidus of continued inflammation from retained caustic materials.

• The end point in removal of dead or necrotic tissue is induction of bleeding especially in gr4-6 injuries

AMNIOTIC MEMBRANE TRANSPLANTATIONAM Action Mechanisms• Provides a new basement membrane• Provides a new stroma that exerts Anti inflammatory action Antiscarring action Antiangiogenic action

It consists of an avascular stromal matrix a thick basement memb an epithelial monolayer.

• When used with the basement membrane oriented downward, the amniotic membrane acts like a biologic bandage contact lens or an ‘onlay’ (patch) graft, promoting epithelialization beneath the membrane.

• When used with basement membrane oriented upward it acts like an ‘inlay’ graft, which promotes epithelialization over its surface.

• Irrespective of the transplantation technique, amniotic tissue facilitate reepithelialization if complete or partial limbalstem-cell function is present.

TENOPLASTY• The use of conjunctival and Tenon’s advancement, or

tenoplasty, is based on the principle of using vital connective tissue within the orbit to reestablish limbal vascularity and to facilitate corneal reepithelialization with conjunctival epithelium.

• This technique is recommended to facilitate initial stabilization of a grade IV injury.

TISSUE ADHESIVESCan be done in cases of impending or frank perforation < 1mm in size

STEPS OF APPLICATION OF CYANOACRYLATE GLUE1. Area surrounding the perforation is cleaned,any mucous necrotic

tissue surrounding 1-2 mm of epithelium is removed

2. Corneal surface is kept dry

3. If AC flat/iris prolapse,paracentesis Done and BSS is injected in to AC

4. cyano acrylate glue drawn in to 1ml syringe attached to 30g needle

5. Small amount glue placed directly on perforation site

6. Site of perforation is inspected for leak

7. BCL placed over the cornea,topical antibiotics instilled at the end

Can be left in place until it loosens spontaneously and reepitheliasiation occurs

Tectonic keratoplasty Size of perforation large Difficult d/t corneal thinning,passage of sutures becomes

worse But helps in visual rehabilitation in later stages

CHRONIC CHEMICAL BURNSMANAGEMENT

1.Surface stabilisation2.Ocular surface transplantation3.Keratoplasty

1.SURFACE STABILISATIONA. Surgery of the lids to address entropion,ectropion,trichiasis

B. Management of persistent epithelial defect 1.frequent use of preservative free lubricants 2.use of preservative free antibiotics 3.Over night patching 4.autologous serum may be given 2nd hrly.umbilical cord serum has better results 5.tarsorrhaphy if PED not healing on medical therapy

C.Symblepharon release with amniotic membrane transplantation in some cases

2.Ocular surface trasplantation Corneal transplantation alone is not sufficient as

functional epithelial stem cells cannot be supplemented by corneal transplant alone

Hence some form of stem cell transpalntation is required to stabilise ocular surface

Proposed classification

Management of LSCD

CONJUNCTIVAL LIMBAL GRAFT

• Auto limbal transplantation – donor fellow eye– Unilateral LSD

• Allo limbal transplantation– Live related donor– Cadaveric donor– Bilateral LSD

Autolimbal transplantation

• Partial removal of the limbus from the fellow eye

• Unilateral LSCD

• Less than four to six clock hours of limbal tissue and a moderate amount of conjunctiva

• > 6 clock hours – Donor eye LSCD

Technique

DONOR EYE • Conjunctival corneal

specimens • Two explants – each 2

clock hrs• Superior and inferior• 150 micron thick• 2 mm of conjunctiva

+1mm of limbus + 2mm peripheral cornea

RECIPIENT EYE• Recepient bed • Same demention• 100 micron depth• Same clock hours• Sutured with 10 nylon

Technique

Advantageso Fresh tissue-more viable cellso Technically easiero No antigenic loado No rejection

Disadvantageso Risk of iatrogenic LSD in fellow eye

Allo limbal transplants• Bilateral total ocular surface disease• Living relatives are potential donors • Cadaver donor - "fresh" eyes• HLA-matched tissue is preferred• High rate of immune reactions – rejection• Immuno suppressants for 12 months

Keratolimbal allograft

• Cadaveric donor• Technique is not routinely used• Bilateral cases, unilateral cases unwilling• AdvantagesReadily available360 coverage possibleNormal eye spared

• DisadvantagesFresh tissueImmediate sx preferredRejection more,immunosuppressives post opTechnically difficult

Cultured limbal stem cell transplantation

• Promising technique in limbal transplantation• Procedure of Choice• Stem cells cultured using a small amount of tissue• Minimizes the damage to donor tissue• Avoids risk donor eye LSD

• Incidence of rejection reduced• Donor tissue - other healthy eye (autograft)• donor material – live related individual (allograft)• Ex-vivo expansion of limbal epithelial cells on amniotic

membrane

1. 2*2 mm piece of conj epithelium with 1mm in to clear corneal stroma at limbus dissected and excised

2. Transported to lab in HCE(human corneal epithelium) medium

3. In lab donor limbal tissue shreded in to small bits

4. 3*4 aminiotic membrane sheet is deepithelialized and bits of limbal tissue explanted over it with BM side up

5. Incubated at 37’ with 5% co2 and 95% air

6. Culture completes when monolayer of cells growing from small bits merge will take 10-14 days

Simple limbal epithelial transpalntation

Cultivated oral mucosa epithelium transplantation (COMET)

• In bilateral cases, mucosal membrane grafts are used to reconstruct the fornix and restore normal lid–globe relations.

• Since autologous no immunological rxn

• Disadvantage is they maintain original phenotype ,invite vascularisation and provide poor visual outcome

CONCLUSIONS• Unilateral cases – autologous cultured stem cell

transplantation good option

• Bilateral cases cultured limbal stemcells from live related HLA matched donors better than Keratolimbal graft

• Limbal stem cell transplantation followed by PK/LKP better than combined surgery

3.keratoplasty

• Penetrating/lamellar• Can be done simultaneously with LSCT• Or 2 staged procedure,6 wks following

limbal transplant

69

Penetrating Keratoplasty

Removing the affected corneal button measuring 7mm in diameter .

After removal of the corneal button. An intraocular lens can be seen centrally.

Interrupted corneal sutures (10/0 nylon) were used to suture the donor cornea to the recipient's.

Clear graft after penetrating keratoplasty utilizing and showing a continuous (running) 24-bite suture.

KERATOPROSTHESIS

SPECIFIC THERAPYACUTE PHASE1. Topical corticosteroids every 1–2 h.2. Topical sodium ascorbate 10% every 2 h.3. Topical sodium citrate 10% every 2 h.4. Topical tetracycline 1% ointment four times a day.5. Topical cycloplegics as needed.6. Topical antiglaucoma medications as needed.7. Systemic sodium ascorbate 2 g orally four times a day.8. Systemic doxycycline 100 mg orally twice a day.9. Consider amniotic membrane transplantation. (grade II

and III)10. Consider conjunctival and Tenon’s advancement. (grade IV)

EARLY REPAIR PHASE

1. Discontinue or taper (with close observation) topical corticosteroids.

2. Begin progestational steroids (Provera 1%), NSAIDs, or both, topically every 1-2 hr.

3.Continue topical and systemic sodium ascorbate.

4. Continue topical sodium citrate.

5. Continue topical tetracycline and systemic doxycycline.

LATE REPAIR PHASE

1. Taper medical therapy after reepithelialization is complete(grade I or II).

2. Limbal stem-cell transplantation +/– amniotic membrane transplantation (for grade III or IV injuries).

3. Tectonic procedures (tissue adhesive, small- or largediameter keratoplasty), if necessary.

Late Rehabilitation1. Ocular surface reconstruction (amniotic membrane

transplantation, conjunctival transplantation, mucous membrane transplantation).

2. Limbal stem-cell transplantation.

3. Penetrating keratoplasty.

4. Keratoprosthesis.

BEWARE OF !!!