Download Acute Chemical Injuries

Emergency
OcularOcular
Emergency
Acute Chemical
Injuries
Manpreet Kaur
MD
Manpreet Kaur MD, Rajesh Sinha MD, DNB, Namrata Sharma MD, DNB, MNAMS
Dr. Rajendra Prasad Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences, New Delhi
C
hemical burns account for 11.5-22.1%1 of traumatic
ocular injuries, a majority of which occur in young
males because of exposure to acid or alkali in the setting of
industrial accidents. These injuries also occur frequently as
a result of exposure to chemicals at home and in association
with criminal assaults. Alkali injuries occur more frequently
than acid injuries, with lime (chuna particle) injury being
the commonest2.
Aetiology
Alkali injury is more common than acid injuries, because
of their frequent use in many household cleaning agents
and building materials. A few common acids and alkalis
responsible for acute chemical burns are described below.
Acids
The most common etiological agent responsible for acid
injuries is sulphuric acid, which is commonly used in
invertor batteries. Sulphuric acid is a strong acid used in car
batteries, fertilisers, in the manufacturing of dyes, explosives
and refining petroleum. Nitric acid is also a strong acid
used in manufacturing of fertilisers, rocket propellants and
nylon products. It leads to a yellowish corneal opacity.
Chromic acid is used in electroplating, ceramic glazes and
wood preservation, and causes brownish discoloration of
conjunctiva, often simulating chronic conjunctivitis.
Hydrofluoric acid, though a weak acid in itself, gives
the most reactive anion. It is used in etching glass,
semiconductor production and rust removal. It acts like
alkali to saponify lipids, causing deep rapid penetration,
extensive ischemia and calcific plaques in corneal stroma.
Alkalis
Ammonia is a common cause of alkali injury, and is found in
fertilisers, refrigerants and cleaning solutions. It combines
with water to form ammonium hydroxide with very rapid
penetration in ocular tissues. Lye or sodium hydroxide is
a common constituent of drain cleaners, with almost as
rapid penetration as ammonia. Potassium hydroxide, also
known as caustic potash causes similar injuries as lye.
Magnesium hydroxide is a constituent of sparklers, and
results in combined thermal and chemical injuries. Lime is
the most frequent cause of chemical injury at workplace. It
is a constituent of plaster, mortar, cement and whitewash.
Though it has poor penetration, the toxicity is increased
by retained particulate matter causing prolonged severe
damage.
Pathophysiology
Alkali burns cause corneal damage by three main
mechanisms-
pH changes
The rise in pH leads to saponification of fatty acids of cell
membranes leading to cell destruction. Collagen is more
susceptible to enzymatic degradation by hydrolysis of
protective glycosaminoglycans.
Ulceration and proteolysis
Alkalis cause stromal ulceration at two to three
weeks post injury due to various proteolytic enzymes
(glycosidases, elastases, and catepsins) that are released
by polymorphonuclear leucocytes (PMNL) and epithelial
cells.
Collagen synthesis defects
Alkali burns damage ciliary body to reduce aqueous
ascorbate levels. Ascorbate is necessary for conversion
of proline and lysine to hydroxylysine, and also plays an
important role in the synthesis of glycosaminoglycans.
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Ocular Emergency
Figure 1: Acute chemical injury with
severe limbal ischemia
Table 1: Roper-Hall classification (1965)
Grade Prognosis Cornea
Conjunctiva/
limbus
I
Good
Corneal epithelial
damage
No limbal
ischemia
II
Good
Corneal haze, iris
details visible
<1/3 limbal
ischemia
III
Guarded
Total epithelial loss, 1/3-1/2 limbal
stromal haze, iris
ischemia
details obscured
IV
Poor
Cornea opaque, iris
and pupil obscured
>1/2 limbal
ischemia
Acid burns lead to coagulation and precipitation of proteins.
It reacts with collagen leading to shrinkage of collagen
fibres associated with a rapid rise in intraocular pressure.
No defects in collagen synthesis are usually noted. Severe
acid burns lead to ciliary body damage and decreased
aqueous ascorbate levels.
Classification
Various classification systems have been proposed over the
years, each with its own limitations and advantages.
Roper-Hall classification3 originally described in 1965 has
been the most widely used classification system (Table 1). It
is a modification of the Ballen classification4 (1964), which
is based on the original Hughes classification5 (1946). It
classifies all burns with more than 50% limbal ischemia
as grade IV burns However, the prognosis of burns with
just over 50% limbal ischemia is much better than those
with total limbal ischemia, warranting the need for a better
classification.
42 l DOS Times - Vol. 19, No. 9 March, 2014
Figure 2: Acute chemical injury with epithelial
defect, stromal haze and limbal ischemia
Dua6 in 2001 gave a new classification for ocular burns,
based on the clock hours of conjunctival and limbal
involvement (Table 2). It also prognosticated each grade
of injury. This classification has the added advantage that
it can be presented in an analogue manner rather in the
stepped progression of a graded classification.
Clinical course
The clinical course following an acute chemical injury can
be characterised in three stages-
Acute stage (immediate to one week)
In mild burns, corneal and conjunctival epithelial defects
with sparing of limbal blood vessels are found. In severe
burns, destruction of corneal and conjunctival epithelium
with immediate limbal ischemia (Figure1,2) is observed.
Increase in pH of aqueous humor with decreased glucose
and ascorbate levels further aggravates ischemia, and leads
to alteration of nutrients and cell death. A bimodal rise
in intraocular pressure is observed, with the initial peak
due to compression of globe because of hydration and
longitudinal shortening of collagen fibrils. The second peak
is a result of impedance of aqueous humor outflow.
Early reparative stage (one to three weeks)
It is characterised by the replacement of destroyed
cells and extracellular matrix. In grade I/II burns,
epithelium regeneration begins, along with corneal
neovascularisation, clearing of stroma and synthesis
of collagen glycosaminoglycans. In grade III/IV burns,
epithelium regeneration may not start and progress. Stroma
remains hazy, and endothelium may be replaced by retro
corneal membranes. Stromal ulceration takes place due to
action of digestive enzymes such as collagenases, Matrix
Ocular Emergency
Table 2: Dua classification of ocular surface burns (2001)
Grade Prognosis
Clinical findings
Conjunctival
involvement
Analogue scale
I
Very good
0 clock hours limbal involvement
0%
0/0%
II
Good
≤3 clock hours limbal involvement
≤30%
0.1-3/ 1-29.9%
III
Good
>3-6 clock hours limbal involvement
>30-50%
3.1-6/ 31-50%
IV
Good to guarded
>6-9 clock hours limbal involvement
>50-75%
6.1-9/ 51-75%
V
Guarded to poor
>9-<12 clock hours limbal involvement >75-<100%
9.1-11.9/ 75.1-99.9%
VI
Very poor
Total (12 clock hours) limbal involvement 100%
12/100%
Figure 3: Post chemical injury symblepharon
with vascularised LCO
Figure 4: Irrigation of the eye
with i.v. tubing
metalloproteinases (MMP) and other proteases released
from regenerating corneal epithelium and PMNLs.
possible, within first few minutes of injury. Immediate
irrigation (Figure 4) of the eye with any non toxic liquid
for a minimum of thirty minutes is recommended. pH
should be measured from the cul-de-sac 5-10 minutes after
completion of irrigation, and further irrigation should be
carried out if pH is less than 7, till pH approaches normal
level. Eyelid speculum or Morgan lens (sclera irrigating
lens) may be used to keep the eye open while irrigating
solution is delivered through i.v. tubing.
Late reparative stage and sequelae (≥ three weeks)
Grade I/II burns achieve completion of the healing process
usually, with good prognosis. Grade III/IV burns usually
have a variety of complications (Figure 3) such as corneal
scarring, xerophthalmia, symblepharon , ankyloblepharon,
glaucoma, uveitis, cataract, lagopthalmos, cicatricial
entropion or ectropion, trichiasis, dry eye etc.
Management
The primary goals of treatment are
•
Restoration of intact epithelium
•
Control of acute inflammatory reaction
•
Support of reparative process
•
Prevention of complications
Management can be divided into four stages
Immediate emergency treatment
Immediate treatment should be instituted as soon as
Various solutions may be used for irrigation, including
tap water, normal saline, ringer’s lactate, balanced salt
solution, Cedderoth eye wash (borate buffer solution) or
diphoterine (high buffer capacity amphoteric hypertonic
polyvalent compound). No therapeutic differences have
been identified between normal saline, normal saline with
bicarbonate, lactated Ringer’s, and balanced salt solution
(BSS), or BSS Plus7. Use of acidic solution to neutralise
alkali is dangerous and NOT recommended.
After irrigation, a thorough examination should be carried
out by double eversion of lids to examine the fornices
under proper ocular anaesthesia (Figure 5). Any embedded
particulate matter should be removed. Chuna particles
should be removed with cotton tipped applicator.
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Ocular Emergency
phosphate solution or balanced salt solution may
be used for anterior chamber reformation.
•
Support repair and minimize ulceration
a)Ascorbate
Dose: oral ascorbate 2g/day (500 mg QID), topical
10% solution in artificial tears administered hourly
A decreased incidence of corneal ulceration and
perforation has been observed in rabbit studies
when aqueous ascorbate levels are >15mg/dl. It
acts by replenishing ascorbic acid to the scorbutic
fibroblasts of cornea.
b)Tetracycline
Figure 5: Examination under anaesthesia- double
eversion of lids
Early acute phase treatment
•
Treatment with broad spectrum antibiotics to prevent
secondary bacterial infection and cycloplegics to relieve
ciliary spasm should be instituted. Antiglaucoma drugs,
both topical and systemic may be needed to control
IOP spikes. Further drugs are added to-
•
Control of inflammation
a) Topical corticosteroids
Topical steroids used in the initial ten days after
injury have been shown to reduce inflammatory
cells infiltrating the corneal stroma, which are a
source of proteolytic enzymes responsible for
corneal ulceration. Steroids should be rapidly
tapered after ten days if the epithelium is not intact,
as it slows repair process.
b) Progestational steroids
Medroxyprogesterone acetate 1% inhibits
collagenase and ulceration, and suppresses corneal
neovascularisation with minimal suppression of
stromal wound repair10. It can be used 10-14 days
post injury instead of corticosteroids.
c) Topical nonsteroidal anti-inflammatory drugs
should be used cautiously due to the possibility
of corneal melting in conjunction with epithelial
defects.
A simple sweeping of the glass fornices daily
with ointment coated glass rod may go a long
way in prevention of symblepharon formation.
Additionally, scleral lenses and symblepharon rings
may be used, to aid symblepharon prevention.
The benefit of paracentesis and irrigation of the
anterior chamber following a severe chemical
injury is uncertain. It may be therapeutic by
allowing rapid normalization of pH, and buffered
44 l DOS Times - Vol. 19, No. 9 March, 2014
Doxycycline 100 mg BD inhibits MMP through
restriction of gene expression of neutrophil
collagenase and epithelial gelatinase. It suppresses
alpha-1
antitrypsin
mediated
degradation
and causes scavenging of reactive oxygen
intermediates.
c) Collagenase inhibitors
10% sodium citrate drops made in artificial tears,
instilled hourly also play a role in supporting
repair9. Other collagenase inhibitors include
cysteine, acetylcysteine, EDTA and penicillamine.
•
Promote re-epithelialization and transdifferentiation
a) Tear substitutes- they promote re-epithelialization,
ameliorate persistent epitheliopathy, decrease
risk of recurrent erosions and accelerate visual
rehabilitation
b) Autologous serum eye drops 20-40% contain
growth factors that may aid in establishing
epithelial integrity.
c) Bandage contact lens prevents the ocular surface
from windshield-wiper effect of the eyelids. The
promote basement membrane regeneration.
d)Fibronectin8 has shown a favourable effect in
animal models. It is still under investigation.
e) Epidermal growth factor favourably influences
epithelial migration in human studies. However
recurrent erosions have been seen after
discontinuation.
f) Retinoic acid is theoretically useful in promoting
goblet cell recovery, tear film stabilisation and
improved ocular surface wetting.
Intermediate term treatment
a)Debridement
A careful excision of all necrotic tissues should be
carried out, as necrotic tissue acts as a store for
inflammatory mediators that elicit a PMNL response
and further hasten ulceration.
Ocular Emergency
Figure 6: Amniotic membrane transplantation
in acute chemical burn
b) Conjunctival/ tenon advancement (tenoplasty) can
be undertaken to improve the vascular supply of the
anterior segment11. It involves excision of the necrotic
conjunctiva and cornea, followed by the advancement
of Tenon’s over the cornea employing careful
dissection to preserve the vascular supply of capsule
located posteriorly.
c) Tissue adhesives such as cyanoacrylate glue may be
used in conjunction with a bandage contact lens, in the
eventuality of a small corneal perforation.
d) Large perforations may need emergency patch graft or
therapeutic penetrating keratoplasty, depending on the
size of the perforation.
e) Amniotic membrane transplantation (Figure 6) has seen
a revival of interest for use in acute chemical injuries,
with several studies showing a beneficial effect in grade
II-III chemical burns12. Amniotic membrane facilitates
epithelialisation, reduces inflammation, and prevents
symblepharon formation, vascularisation and scarring.
It also provides a fast and dramatic relief from pain and
photophobia.
Late rehabilitation treatment
a) Ocular surface rehabilitation
Symblepharon lysis, fornix formation, entropion or
ectropion surgery may be needed.
b) Limbal stem cell deficiency (Figure 7).
Limbal stem cell transplantation may be needed,
especially in high grade chemical injuries with
extensive perilimbal ischemia. Sources for limbal
stem cell transplants range from conjunctival limbal
autografts, living related and cadaveric donors, to
ex-vivo culture expanded limbal epithelium. Large
diameter lamellar keratoplasty provides corneal tissue
for tectonic support in addition to limbal stem cells.
Figure 7: limbal stem cell deficiency post
chemical injury
c) Visual rehabilitation
Penetrating keratoplasty, if needed, should be delayed
for 18 months-2 years, as keratoplasty in acute
inflammatory stage is fraught with a high failure rate.
The ocular surface problems that arise as sequelae of
chemical injury may be a potential contraindication
for keratoplasty, and may necessitate the need for a
keratoprosthesis.
d) Glaucoma is a frequent complication, and should be
appropriately managed.
References
1. Clare, G. et al., Amniotic membrane transplantation for acute
ocular burns. Cochrane database of systematic reviews, 2012. 9: p.
CD009379.
2. Morgan SJ: Chemical burns of the eye: causes and management. Br
J Ophthalmol 1987; 71:854-857.
3. Roper-Hall MJ. Themal and chemical burns. Trans Ophthalmol Soc
UK 1965;85:631–53.
4. Ballen PH, Hemstead NY. Treatment of chemical burns of the eye.
Eye, Ear, Nose and Throat Monthly1964;43:57–61.
5. Hughes Jr WF. Alkali burns of the cornea. I. Review of the litera. &
summary of present knowledge. Arch Ophthal. 1946; 35: 423–449.
6. Dua HS, King AJ, Joseph A. A new classification of ocular surface
burns. Br J Ophthalmol 2001;85:1379–83.
7. Herr RD, White GL Jr, Bernhisel K, et al: Clinical comparison of
ocular irrigation fluids following chemical injury. Am J Emerg Med
199l; 9:228-231
8. Nishida T, Nakagawa S, Nishibiyashi C. et al: Fibronectin
enhancement of corneal epithelial wound healing of rabbits in vivo.
Arch Ophthalmol 1984; 102:455-456.
9. Haddox IL. Pfister RR, Yuille-Barr D: The efficacy of topical
citrate after alkali injury is dependent on the period of time it is
administered. Invest Ophthalmol Vis Sci 1989; 30: 1062-1068.
10. Gross J, Azizkhan RG, Biswas C. et al: Inhibition of tumor growth,
vascularization, and collagenolysis in the rabbit cornea by
medroxyprogesterone. Proc Nat1 Acad Sci USA I981; 78:117&1180.
11. Teping C, Reim M: Tenoplasty as a new surgical principle in the
early treatment of the most severe chemical eye burns. Klin Monatsbl
Augenheilkd 1989; 194:1-5.
12. Meller D, Pires RTF, Mack RJS, Figueiredo F, Heiligenhaus A, Park
WC et al. Amniotic membrane transplantation for acute chemical or
thermal burns.Ophthalmology 2000
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