Introduction

It is very frequent to encounter chemical injury in our routine ophthalmic practice. Most of the chemical injuries are minor, which heal without any squeal. Most are acids and alkalis. Alkali injuries are more common (nearly twice) than acids and are more severe in nature. It is of utmost importance to recognize the nature of chemicals for treating such patients. Here, we review the chemical injuries of the eye with their recent management update.

Epidemiology

Chemical burn

• 7.9-9% of all reported ocular burns.
• 23 -42% are bilateral.
• Young males are affected mostly.
• Most are industrial accidents (at workplace 60-70%, at homes 25-30%, criminal assault, and others comprise 2-3%)

Sources of common chemicals

Alkalis

Ammonium hydroxide and Ammonia- They are the most severe alkalis known so far, as they are both water and lipid-soluble, hence faster penetrability within the cornea. They reach within the anterior chamber after one minute of exposure. Sodium hydroxide (NaOH/Lye/caustic soda)- the time of penetration within the cornea is three minutes. Calcium hydroxide (CAOH/Lime/quick lime)-This is the most common alkali causing chemical injury in clinical practice.

Acids

They usually cause minor injuries and heal with little or no damage.

Sulphuric acid (H₂SO₄) is the most commonly responsible for acid injury. Exothermic injury (H₂SO₄ > H₂O > heat) is associated, hence it causes severe injury.

Sulphurous acid - more penetrable.

Hydroflouric acid – weak acid. Ulceration is less common.

Hydrochloric acid (HCL) and Nitric acid (HNO₃)- more lipid-soluble thus causing more severe injury in high concentrations.HCL acid releases HCL gas which is irritating to eyes.

Mechanism of Injury

Chemical injury to eyes leads to typical sequential damage, as follows-

Acute inflammatory response→ Ocular surface damage→ Stromal collagen lysis.

But, before the onset of inflammatory damage, both Alkali and Acid individually follow their own way of Initiating destructive process.

Alkali

Anionhydroxyl ion (OH^-) damage initiated by all alkalis is the same. They saponify the fatty acids of cell membrane → cell death→ epithelial damage i.e. barrier breakdown→ deeper penetration of alkali into the stroma.

Cation It determines the severity of damage i.e. toxicity. It reacts with carboxyl (COOH^-) in the collagen and the stromal glycosaminoglycan(GAG) → increase of intraocular pressure and increased susceptibility to collagen degrading enzymes.

AcidThey lack corneal permeability due to protein denaturation and precipitation, and also due to coagulative necrosis of the corneal epithelium. This forms a protective barrier to further penetration of acids and this gives a “ground glass” appearance of the cornea. But strong acids in higher concentration can cause devastating ocular injury, as acid’s ability to penetrate deeper tissues is affected by its lipid solubility. Stromal penetration→ extracellular GAG precipitation and coagulation of epithelial cells → corneal opacity (due to collagen fibrils shortening and edema). The increase in IOP is due to collagen shrinkage and trabecular meshwork-distortion. Ascorbate content is decreased just like Alkali.

Inflammation Epithelial damage/defect leads to the infiltration of polymorphic neutrophil (PMN) and leucocytes within 24 hrs. They are also attracted by toxins and extracellular proteins (chemotaxis).Type 1 collagenase released by PMN and superoxide free radical leads to further tissue damage.

Ocular surface damage Epithelial damage is repaired by the centripetal movement of the proximal epithelium, but complete defect to be repaired by Limbal stem cells(LSC). If LSC is not available, then conjunctiva must reepithelialise the denuded epithelium, but this process is slower than the normal and does not produce a normal phenotypic corneal epithelium.

Stromal ulceration- Factors are corneal epithelial defect, the release of proteolytic enzymes, anesthesia, tear deficiency, and impaired collagen synthesis. Decreased ascorbate and increased type-1 collagenase from PMN and keratocytes are the causes of impaired collagen synthesis.Type-1 collagenase is earliest detected by 9 hours and peaks by 2-3 weeks after the insult. Epithelial cytokines normally inhibit type-1 collagenase, leading to stromal melting. Stromal edema and keratocyte loss, are responsible for haze. Immature fibroblasts that repair stromal damage are new and collagen produced by these are underhydroxylated, lacking typical triple helical structure, which is vulnerable to enzymatic lysis.

Severity :

It depends on the penetration power of the chemical. Alkali > Acids.

• Concentration/ amount of chemical compound.
• The surfacearea of contact.
• Duration of contact (i.e. the lag time before cleaning/irrigation)

Classification and Clinical manifestation:

HUGHS-ROPER HALL Classificationbased on the extent of epithelial damage, the extent of stromal edema, degree of corneal involvement, and degree of limbal ischemia.

Evidence of intraocular injury and perilimbal ischemia- important prognostic factors.

H S DUA’s Classification It is a more complete classification which is mostly followed worldwide nowadays. This is based on surface staining and includes limbal involvement (not only ischemia), conjunctival involvement, and analog scale (rather than grading).

* analog scale indicates- limbal involvement in clock hours/% of conjunctival involvement

Clinical Feature

It varies depending upon the severity of the injury.

Acute phase manifestation the whole of the ocular surface is involved immediately and simultaneously. Conjunctiva may be injected, chemotic, and necrotic. There may be a corneal or conjunctival, partial, or total epithelial defect. Perilimbal ischemia occurs due to vascular endothelial damage. In grade-4 injury anterior segment necrosis takes place. Corneal stroma may be clear or completely opacified depending upon severity. The inflammatory membrane in AC may be triggered by phospholipids breakdown leading to the enormous liberation of prostaglandins. The increase of IOP usually takes place within a few hours, due to peripheral corneal edema and TM blockage. Later, ciliary body may shut down, which may lead to hypotony. Burns to periocular areas (skin, eyelids) may show laceration or contusion. Cataract (lens epithelial damage), sclera thinning and necrosis, are the other common associated findings.

Early repair phase In grade 1 and 2 injuries, epithelial migration followed by regeneration and healing of cornea takes Place. In early grades and in milder cases, stroma gradually becomes clear due to keratocyte proliferation, collagen synthesis, and collagenase synthesis. In grade 3 and 4 injury, retardation of epithelialization occurs due to limbal stem cell deficiency (LSCD), followed by fibrovascular pannus and/or corneal conjunctivitilisation along with symblephara between the denuded surface of the palpebral and bulbar conjunctiva. Stromal ulceration typically occurs between the 2^nd and 3^rd weeks.

Late repair phaseconjunctival scarring, trichiasis, cicatricial entropion, the progression of corneal scar, dry eye, decreased corneal sensation, fluctuation (↓↑ ) of IOP.

Treatment

Aim of the treatment

• Acute phase- to promote healing, to reduce severity- treatment is mostly medical.
• Chronic phase- to restore the normal ocular surface and corneal clarity-mostly surgical.

Acute Phase Treatment

For both Acids and Alkali, management is almost the same.

The first aid basic treatment should be always IRRIGATION-IRRIGATION-AND IRRIGATION. It should occur prior to taking a detailed history and examination. Any isotonic nontoxic solution (e.g. NS or RL) is preferable. Use the continuous flow of this solution in IV-tubing with the application of lid speculum, for at least 30 minutes or until the P_H of lower fornix becomes neutral (checked by Litmus paper). It is to be noteworthy, either irrigation for 90mins or aqueous paracentesis decreases aqueous P_H by 1.5units.

For Acids injury irrigation should never be performed with base, →exothermic damage. We should always double evert the eyelids with Desmarre lid retractor, and to take out all the embedded foreign particulate matter with forceps. Any necrotic tissue is debrided.

If CaOH is the reason, EDTA 0.01M can be used to chelate CaOH. Then, a detailed history is taken (mechanism of injury, the chemical involved, whether eye protection was used or not) and then a thorough ocular examination under slit lamp is done.

Minimum medications are used to prevent toxicity.

Cycloplegics provides comfort. Phenylephrine should be avoided, as it increases limbal ischemia. Topical broad-spectrum antibiotics, IOP reducing drugs, lubricants (helps reepithelialisation ) should be started.

Steroids decrease cellular infiltration and fibrosis, but there is a risk of corneal melting and ulceration after its use for more than 7 days( by decreasing collagen synthesis affecting on collagenase activity), hence it is better to convert to topical NSAID’s (eg, Ketorolac) after 7 days.

Hydrophilic BCLThe role is still controversial. In one hand, it helps prevent symblephara and increases reepithelialization, in other way it increases the risk of infection.

Close follow up is mandatory while using BCL. Lower fornix sweeping (e.g. by glass rod) prevents fibrin adhesion, hence pseudopterigia and symblephara.

Oral vitamin C, 2gm BID or topical Ascorbic acid 10%-achieves therapeutic level concentration (15mg/ml) in aqueous. They promote mature collagen synthesis.

Newer drugs, to promote stromal healing have emerged up nowadays, which can be used for stromal ulcer prophylaxis also.

Anticollagenase:

Medroxyprogesterone acetate 1% (PROVERA)- topical/oral/subconjunctival

Acetylcysteine 10% (MUCOMYST)-topical

Sodium citrate 10%- topical (chelates calcium which is necessary for collagenase. Also stabilize PMN,↓leucocyte adherence and phagocytosis,↓lysozyme enzyme releases)

Sodium EDTA 0.2M solution-topical (calcium chelator)

Doxycycline, Tetracycline (chelates Zinc which is necessary for collagenase)

Oral

Vitamin A-analogue (Retinoic Acid) and fibronectin-topical. Latter promote cell to cell adhesion also.

Autologous serum-topical(also provides growth factors for epithelial healing)

Thiol peptides, recombinant metalloproteinase tissue inhibitor-presently not available for therapeutic use.

Antiprotease- Aprotinin

Epidermal growth factor, 0.05% in phosphate buffer solution (stimulates RNA, DNA and thus protein synthesis)

If healing fails, then eye patching, tarsorrhaphy or amniotic membrane graft (AMG: biological BCL) anyone can be useful. But, nowadays a trend is going toward straightforward AMG in grade2and 3 acute injury. If there is descematocele or small perforation (for <2mm size), Isobutyl- Cyanoacrylate or fibrin glue can be applied. Tectonic penetrating keratoplasty is indicated for globe threatening perforations that are too large to be managed by glue application alone.

Chronic Phase Treatment:

Conjunctiva and Tenon advancement procedure/tenoplasty- This to be done after excising all the necrotic and ischemic tissue from the limbal area.Tenon’s and limbal vascular supply can be achieved in a good number of cases.

AMG- reconstructs corneal epithelium and suppresses fibrovascular membrane formation, esp in extreme conjunctival damage.

AMG + LSCT (Limbal stem cell transplantation)-successful result with dramatic visual impairment.

In severe grade 4 injury, the following can be done.

Conjunctival autograft or conjunctivolimbal autograft. Especially done when AM availability is a problem.

Live related Conjunctival Allograft or Live related conjunctivolimbal allograft. It is especially useful for bilateral involvement.

Keratolimbal allograft for bilateral LSCD, one-eyed patient with total LSCD, total LSCD without the availability of donor or culturing technique.

Optical Penetrating keratoplasty should be delayed for at least 1 year, when all corneal repair process and inflammation have become inactive. Fornix shortening, cicatricial entropion, symblepharon, scarring and keratinization, etc should always be corrected before PK. LSCT followed by optical PK with a gap of atleast 3 months gives good results.

Keratoprosthesis- is the last resort for visual rehabilitation. The only indication nowadays is repeated graft failure.

Some surgical procedures, which are still in experimental stage-Cultured or harvested human LSCT on AMG(most recent and most promising technique, esp. for grade 4 and bilateral cases), Cultivated oral mucosal epithelium transplantation, Co-cultivated limbal and conjunctival epithelium transplant, Limbal transplants combined with large aperture excimer Laser photoablation, Limbal transplants from a heterologous donor.

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