Chemical Injuries to the Eyes

Chemical Injuries to the Eye constitutes an ophthalmic emergency, due to the potential for permanent visual impairment and threat to the structural integrity of the eye. Severe injury may result in widespread damage to the ocular surface epithelium.

Chemical injuries cause tissue destruction created from a wave of strongly dissociated ions flooding the eyelid and/or tear film and reservoir, penetrating the cornea and adjacent tissues, thereby reaching to the aqueous humour. Immediate shrinkage of the collagenous envelope of the eye results in a rapid rise in intraocular pressure, followed by a second rise which lasts longer and is produced by prostaglandin release. At any time, rise in pressure can occur due to clogging of the trabecular meshwork by necrotic debris, and from organisation of inflammatory components, followed by cicatricial closure of the chamber angle, especially inferiorly.

Inflammatory cells, most importantly, neutrophils, pour into the damaged tissue, releasing superoxide radicals and tissue degrading enzymes. There may be development of corneal ulcerations, perforations, and vascularisation.

Responsible chemicals producing injury are numerous and include cleaning agents, fertilisers, refrigerants, cement, preservatives and fireworks. Alkali injuries occur more frequently than acid injuries, due to alkalis being more commonly present in household and industrial products. Ocular burns caused by detergents and thermal agents are less common.

Fortunately, the majority of chemical injuries are classified as mild. Injured patients are usually young, male and exposure most commonly occurs in a variety of agricultural, industrial and domestic settings, or less commonly in association with a criminal assault. Unfortunately, there is a rise in number of patients presenting with chemical eye injuries resulting from assault.

The final visual prognosis is influenced by the nature of the chemical insult, the extent of ocular damage, and the timing and efficacy of treatment.

Regarding terminology, the literature is full with expressions like alkali ‘burns’, potentially confusing the alkali-injury terminology with a, usually non-existent, thermal, or even open flame component. When both chemical and thermal injuries occur simultaneously, the terms ‘alkali-thermal injury’ or ‘thermal-alkali injury’ might be used, with the most prominent injurious agent stated first. Acid injuries should be referred to in a similar way.

 

References:

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Benitez-del-Castillo Jose M. Lemp Michael A. Ocular Surface Disorders. JP Medical Ltd, Victoria Street, London, SW1H 0HW, UK. 2013. P. 149-156.

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Most common immediate symptoms are:

  • Severe pain.
  • Red eyes.
  • Watering or epiphora.
  • Foreign body sensation.
  • Blurring of vision.
  • Reduced visual acuity.
  • Photophobia (increased sensitivity to light).
  • Blepharospasm (sustained involuntary closure of eyelids).

More than 25,000 chemical products with the potential to cause chemical eye injuries have been identified, many of which may be classified as acids or bases, oxidising or reducing agents, or corrosives. Acids and bases are the most frequently implicated chemical agents. The severity of the injury is related to the nature, concentration, quantity and pH of the chemical involved. It also depends upon the duration of contact and surface area of exposure. History of high-velocity (explosive) chemical injury should always raise suspicion of an associated intraocular foreign body.

Causative agents of chemical injury are:

Alkalis:

Most common causes of alkali injury to the eye are lye, potassium hydroxide, magnesium hydroxide, lime, wet/dry cement and ammonia. Most severe injuries are typically caused by ammonia and lye which are both capable of rapid penetration into the eye. The severity of the injury is dependent on the anion concentration, the dissociation of the alkali, and the quantity of fluid. A wave of hydroxyl ions rapidly advances through ocular tissues, causing massive cell death by saponification of cellular membranes and extensive hydrolysis of glycosa-aminoglycans and collagen within the corneal matrix. Damage caused by lime injuries is reduced by the precipitation of calcium soaps that hinders further penetration. Presence of magnesium hydroxide in fireworks results in a combined chemical and thermal injury.

The most important agents causing alkali injuries to the eye are:

  • Ammonia (NH3): Ammonia (NH3) is available as a fertiliser and refrigerant, and is used in the manufacture of other chemicals. Ammonium hydroxide ranks high in severity in causing injuries to eyes. It is commonly used as a household cleansing agent. Even 7% solution of ammonia is capable of causing major ocular damage, due to its high solubility and penetrability.
  • Lye: Lye, caustic soda or sodium hydroxide (NaOH), penetrates into the interior of the eye in 3-5 minutes. Solid sodium hydroxide, often used as a drain cleaner, can cause pressure to develop within the drainpipe, resulting in an explosion of lye into the face and eyes. Warmed lye is also commonly used to straighten curly hair. Caustic soda is also used in the manufacture of pulp, paper, textiles and soaps. Due to easy availability in home, it is a common chemical being used by paramours during attack. Lye injuries rank second in severity to those produced by ammonium hydroxide.
  • Potassium hydroxide (KOH): Potassium hydroxide (KOH) or caustic potash penetrates the eye slightly less rapidly than sodium hydroxide. Dissolution of potassium hydroxide in water is strongly exothermic (produces heat) and it is corrosive.
  • Magnesium hydroxide (Mg(OH)2): Magnesium hydroxide(Mg(OH)2) also penetrates the eye slightly less rapidly than sodium hydroxide. Magnesium hydroxide is found in sparklers and flares; the combination of thermal injury and chemical injury accounts for more severe injury than that being produced by either type alone.
  • Lime (Ca(OH)2): Lime, fresh lime or quicklime, calcium hydrate, plaster, cement , mortar and whitewash penetrates the eye less rapidly because it reacts with epithelial cell membranes, forming calcium soaps that precipitate and hinder further penetration. Lime, found in cement and plaster, is the most common cause of alkali injury. Retained particulate matter provides sump for on-going injury. Despite this, these injuries can be quite severe, with the corneal opacity visible before the opacity in case of ammonium or sodium hydroxide.
  • Methyl ethyl ketone peroxide: Methyl ethyl ketone peroxide is a catalyst, and commonly used in various industries. It can cause both immediate and delayed corneal injury. There may be exacerbations and remissions of limbal and corneal disease lasting for more than twenty years.

Acids:

Weak acidic compounds precipitate proteins within the corneal and conjunctival epithelium, thus acting as a partial barrier to further penetration of the chemical. It leaves a greyish white epithelium, which often obscures all tissue underneath it. Stripping off this opacified epithelium often reveals a relatively clear underlying corneal stroma. As long as the corneal stem cells near the limbus are not damaged, epithelial recovery is likely, with little or no stromal cloudiness.

Hydrofluoric, sulphuric, sulphurous, chromic, and hydrochloric acids are the most common causes of acid burns. Strong acids ionise completely in an aqueous solution. The strength of an acid depends on its ability to dissociate and lose a proton. The primary mechanism of damage by acids is due to the action of dissociated proton. Hydrofluoric acid causes most severe acid injury due to its unique properties. Hydrofluoric acid has a unique dissolving action which allows it to quickly penetrate into deeper tissues. Moreover, hydrofluoric acid chelates all calcium and magnesium from cells, thereby halting cellular biochemical activity.

Although alkalis typically cause the most serious chemical injuries, the presence of an acid injury does not preclude an equally severe ocular injury. Very strong acids, however, overcome this precipitated obstacle and progress through tissue, much as alkalis. Indeed, there is no clinically significant difference in course of injury and prognosis between severe acid and alkali burns. The end result of a very severe acid injury is often indistinguishable from that of an alkali injury.

The most important agents causing acid injuries to the eye are:

  • Hydrofluoric acid or hydrogen fluoride (HF): Hydrofluoric acid or hydrogen fluoride (HF) is a weak inorganic acid but a strong solvent, widely used in industries. HF is used in polishing and etching of glass and silicone, in the pickling or chemical milling of metals, and in the refining of uranium, tantalum, and berrylium. In the semiconductor industry it is essential in the manufacture of silicon chips.

HF produces severe ocular injury because of its high degree of activity in dissolving cellular membranes. It chelates calcium/ magnesium ions and penetrates rapidly due to its low molecular weight. It is highly toxic so that as little as 7 ml of HF, or 2.5% burn of the body surface, is sufficient to cause death from uncontrolled hypocalcaemia. 

It is found either in pure form or mixed with agents like nitric acid, ammonium difluoride, and acetic acid.

  • Sulphuric acid (H2SO4): Sulphuric acid is commonly used in batteries and also as industrial chemical. The most common cause of acid burns is sulphuric acid. Sulphuric acid produces injuries varying in degree from mild to very severe. Most of the injuries, especially the more severe ones, occur as a result of battery explosions. Hydrogen and oxygen are produced by electrolysis when sulphuric acid combines with water in the battery. This gaseous mixture explodes on contact with flame. Matches or cigarette lighters used as illumination sources or sparks produced by jumper cables are the most common modes of ignition. Injuries that result from battery explosions are usually combination of acid burn and contusion from particulate matter, but may also show laceration or intraocular foreign body penetration.

Injury with sulphuric acid may be compounded by thermal burns from heat generated by the reaction of acid with water on the corneal tear film. Dissolution of concentrated sulphuric acid in water results in release of heat, which causes tissues charring.

  • Sulphurous acid (H2SO3): Sulphur dioxide (SO2) forms H2SO3 when it combines with water in the eye. It may be present as sulphurous anhydride or sulphurous oxide; a fruit and vegetable preservative, bleach, and refrigerant. Sulphurous acid denatures protein and inactivate various enzymes. Sulphurous acid penetrates the tissue easily, because it is highly soluble in lipid and water.

At first, visual acuity is not severely affected after exposure to sulphurous acid, but it worsens greatly over hours to days as the ocular condition deteriorates.

  • Hydrochloric acid (HCl): Hydrochloric acid (present in gastric juices as well) is used in household cleaning and in production of plastics. Fumes of hydrogen chloride gas, act as irritant to the eye and produce profuse tearing which serves to limit ocular damage. At high concentrations and with prolonged exposure, liquid HCl produces severe ocular damage.
  • Nitric acid (HNO3): Injuries produced by nitric acid (HNO3) are similar to those produced by HCl, except that the opacity in epithelium produced by nitric acid is yellowish rather than white, as it is in other types of acid burns.
  • Chromic acid: Chromic acid is a strong agent derived from chromic oxide and chromium trioxide. Ocular injuries caused by chromic acid result from exposure to droplets of the acid in the chrome-plating industry. It produces chronic conjunctival inflammation and a brown discolouration of the epithelium, in the exposed interpalpebral fissure.
  • Acetic acid (CH3COOH): Acetic acid (CH3COOH) is a relatively weak organic acid, and is also known as vinegar and glacial acetic acid. The various forms of acetic acid, especially vinegar, typically produce only minor ocular damage, unless exposure is prolonged. Exposure to a solution in strength more than10% produces severe injury due to corrosive action, unless the time of exposure is exceedingly short. ‘Essence of vinegar’ (80% acetic acid) and glacial acetic acid (90%) are the most concentrated forms of acetic acid, and most likely to produce severe ocular injury.

Other toxic chemicals:

Other types of ocular chemical injuries are usually less severe than alkali and acid injuries.

Lacrimatory agents: Lacrimatory agents are aerosol dispersed chemicals which produce ocular irritation.

Common lacrimatory agents are:

  • Tear gas: Common agents used in tear gas are chloroacetophenone, chlorobenzylidene nalononitrile or dibenzoxazepine. Tear gas is used in riot control. Exposure to these chemicals causes ocular stinging, pain, excessive watering and inability to open eyes.

    Chemical Mace (nonlethal spray containing purified tear gas and chemical solvent): Chemical Mace and similar compounds can cause minor to severe ocular injury, depending on a number of factors. The ocular injury associated with the original Chemical Mace is caused by the lacrimator chloroacetophenone.Degree of severity depends upon proximity of spray can to the eye, quantity of chemical entering the eye, duration of exposure, state of normal reflex mechanisms, and the mechanism of propelling the chemical.Extensive exposure leads to damage including loss of ocular surface epithelium, severe persistent stromal oedema, presumably secondary to endothelial damage, stromal clouding, and corneal neovascularisation.
     
  • Pepper spray (Oleoresin capsicum): Pepper spray (Oleoresin capsicum) is used for riot control or self defence. Exposure to these chemicals causes ocular stinging, pain, excessive watering and inability to open eyes.
  • Mustard gas (Dichlorodiethyl sulphide): Mustard gas (Dichlorodiethyl sulphide) is a poisonous agent used as a chemical warfare agent. It causes irritation of conjunctiva and sore sticky eyes on exposure or a chronic and delayed mustard gas keratitis manifesting as recurrent corneal erosions.

Chemicals and Festivals in India:

Holi: The colourful festival of Holi is celebrated in Phalgun month of Indian calendar, which falls in February end or month of March, every year. It is also known as festival of colours. Instead of using natural colours, people mix harmful chemicals in colours. Most of these chemical colours are oxidised metals or industrial dyes mixed with inferior quality oil e.g. engine oil. Many water colours have an alkaline base which is harmful.

Chemicals used to impart different colours may be:

  • Copper sulphate: It imparts green colour.
  • Chromium iodide: It imparts purple colour.
  • Aluminium bromide: It produces white to yellowish red shade to the colour.
  • Mercury sulphide: Mercury sulphide gives red colour.
  • Powdered glass: Powdered glass is used to produce shiny colour.

Diwali (Deepavali): Diwali is an important Indian festival celebrated by lighting lamps and bursting crackers. Diwali festival also marks end of Ashwin and beginning of Kartik month of Indian calendar and it falls in the month of October or November. The chemicals released by the firecrackers are harmful.

Chemical in firework includes:

  • Sulphur dioxide.
  • Cadmium.
  • Copper.
  • Lead.
  • Magnesium.
  • Nitrate.
  • Nitrite.

Magnesium hydroxide is found in sparklers and flares. The combination of thermal and chemical injury accounts for more severe injury.

Firecrackers release chemical pollutants such as carbon dioxide and carbon monoxide.

 

Pathophysiology:

Alkalis:

The severity of an ocular chemical injury is determined by the ability of the chemical to penetrate the eye. Alkalis, characteristically, penetrate the eye more rapidly than acids.

The hydroxyl anion (OH) saponifies plasma membranes, resulting in cell disruption and death, while the cation is responsible for the penetration by the alkali. Stronger alkalis are associated with more rapid penetration and the penetration rate increases in ascending order from calcium hydroxide, Potassium hydroxide, sodium hydroxide to ammonium hydroxide. Changes in aqueous humour pH are observed within a few seconds of contact with ammonium hydroxide and within 3-5 minutes after sodium hydroxide injury. Irreversible tissue damage occurs when the pH rises above 11.5.

In injuries with alkalis, cations react with the carboxyl (COOH) groups of stromal collagen and glycosa-aminoglycans. Hydration of glycosa-aminoglycans results in loss of clarity of the stroma, whereas, hydration of collagen fibrils causes distortion of trabecular meshwork and the release of prostaglandins, these sequelae combine to produce rise in intraocular pressure (IOP).

Acids:

In general, acids penetrate the corneal stroma much less readily than alkalis. The hydrogen ion mediates damage due to pH alteration, while the anion causes precipitation and denaturation of proteins in the corneal epithelium and anterior stroma. Precipitation of the epithelial proteins produces a degree of protection by providing a physical barrier against further penetration. However, when an acid penetrates the stroma, the damage to ocular structures is similar to that observed in alkali injury.

Acid injury produces:

  • Precipitation of extracellular glycosa-aminoglycans.
  • Corneal opacification.
  • Distortion of the trabecular meshwork.
  • Changes in anterior chamber pH.
  • Damage to anterior chamber structures.
  • Reduced aqueous ascorbate levels.
  • Vascular damage resulting in ischaemic injury.

Both acids and bases may mediate osmolar damage to the cornea. Chemical damage may initiate large changes in osmolarity, which gives rise to cellular dysfunction and destruction. There is little protection against a variety of chemical and toxic insults due to limited buffering capacity of the cornea. In the event that the buffering capacity is exceeded, there is an immediate cessation of biochemical activity e.g. protein synthesis.

Injury, repair and differentiation:

Ocular surface:

Following injury, recovery is dependent upon centripetal migration of cells from the most proximal region of viable epithelium. The extent of the injury determines the source of regenerating epithelium. Epithelial defect involving small area, or the entirety of cornea are replenished by adjacent corneal epithelium and limbus, respectively. In the event of complete corneal and limbal epithelial loss, the conjunctiva is the only source of regenerating epithelium. The source of regenerating epithelium influences the rate of re-epithelialisation and the type of restored epithelium.

Factors retarding rate of re-epithelialisation, following chemical injury:

  • Robust and persistent inflammatory response.
  • Structural damage to the epithelial basement membrane.

Non-healing corneal epithelial wounds pose a significant risk as they expose the cornea to potential microbial infection.

Stroma:

Severe chemical injuries deplete stromal keratocytes, and initiate collagenolytic process which degrade collagen fibrils. These processes disrupt structural integrity and may result in corneal ulceration and perforation. Keratocytes are important for maintenance and regeneration of the corneal stroma. Following corneal injury, keratocytes migrate into areas of damaged stroma from adjacent tissue. Keratocytes are responsible for collagen synthesis. Collagen production is maximal between days 7 and 56, with a peak at about day 21 after injury. Collagen synthesis requires ascorbate and thus, may be significantly impaired following severe chemical injury.

Inflammation:

Chemical injury to the eye is associated with release of inflammatory mediators and the infiltration of inflammatory cells into injured tissue. Regulation of this inflammatory response is crucial, since a robust and prolonged inflammatory response may affect wound healing.

Severe chemical injuries are characterised by two waves of inflammation; the first wave occurs in the first 24 hours and the second wave begins at approximately 7 days and peaks 2 to 3 weeks after injury. The intensity of the first wave may be critical for the recruitment of the second wave. The second wave of inflammation coincides with the period of maximal corneal degradation and repair, and may facilitate sterile enzymatic digestion of the corneal stroma. Sterile ulceration is associated with the infiltration of polymorphonuclear leucocytes. The exclusion of inflammatory cells from the corneal stroma is associated with cessation of sterile ulceration.

The severity of eye injury depends upon:

  • Toxicity of the Chemical.
  • Duration contact of chemical with eye.
  • Depth of penetration.
  • Area of involvement.

Diagnosis requires:

Clinical history: Patient should be asked for:

  • When the injury occurred.
  • Whether the eye was rinsed and for how long.
  • Mechanism of injury (was the chemical under pressure).
  • The nature of chemical.
  • Whether there was any eye protection or not.

Clinical Examination:

Prior to clinical eye examination, pH of both the eyes should be checked. Eye must be irrigated to bring the pH to a safer range between 7 and 7.2.

Early assessment includes careful documentation of the extent and severity of limbal, corneal and bulbar/ palpebral conjunctival involvement, since it provides baseline reference in subsequent evaluation and treatment.

Palpebral fissures should be examined and fornices should be swept to remove a retained particulate matter, which can cause persistent damage. Eye should be examined under fluorescein dye. Intraocular pressure should be documented as well to exclude any rise.

Emergency treatment of the chemically injured eye must precede any attempt at classification. Once the condition has been stabilised, determine the anticipated course of the chemical injury by examining the critical features. Understanding and documenting the salient features of an alkali injury of the eye permits proper classification so that appropriate treatment can be initiated and accurate prognosis deduced. Photographic documentation may be obtained, if possible.

 

Clinical grading of chemical Injuries:

Epithelial defect: Measure the size and draw the shape of the defect after instilling 2% fluorescein dye. Include any conjunctival epithelial defects as well, particularly concerning the palisades of Vogt (limbal stem cells). Document all epithelial defects, including those extending into the fornices of the eye.

Corneal stromal opacity: Grade corneal stromal opacity on the basis of penlight examination:

  • Grade 0: Grade 0 is clear cornea.
  • Grade 1: Grade 1 has mild corneal haze.
  • Grade 2: Grade 2 represents mild to moderate opacity.
  • Grade 3: Grade 3 has moderate opacity.
  • Grade 4: Grade 4 represents moderate to severe opacity. Details of iris trabeculae can be seen and pupils are visible.
  • Grade 5: Grade 5 severe corneal opacity, pupils are not visible with penlight.

Perilimbal ischaemia: To document perilimbal ischaemia, note the clock hours where the conjunctiva is whitened. The conjunctiva and episclera are devoid of blood vessels in these areas. This whitening should not be confused with less severe injury, where there is chemosis and thrombosed blood vessels, but some of the conjunctiva is still viable. Perilimbal whitening is a useful parameter by which the extent of corneal stem cell damage, and indirectly, injury of the underlying ciliary body and trabecular meshwork, may be judged. Documentation of these findings allows for more accurate determination of the necessity for corneal stem cell transplantation.

Adnexa: Measure and document the blinking pattern, corneal exposure, and/or lagophthalmos.

These measurements and findings can be applied to the classification of alkali injuries as described by Hughes, and later modified by Ballen (1963), Roper- Hall (1965) and Pfister et al (1982). This classification, with accompanying drawings and photographs, represents the span of damage encountered after alkali injury. The accuracy of early assessment becomes important in prognostication and treatment plans.

 

Classification of chemical injury to the eye:

Dua (2001) provides a classification of ocular surface burns giving prognosis based on corneal appearance, conjunctival involvement and analogue scale recording the amount of limbal involvement in clock hours of affected limbus/ percentage of conjunctival involvement. The conjunctival involvement should be calculated only for the bulbar conjunctiva, up to and including the conjunctival fornices.

  • Grade I: In Grade I, there is 0 clock hours of limbal involvement, 0% of conjunctival involvement, analogue scale reading of 0/0%, and the prognosis is very good.
  • Grade II: In Grade II, there is less than 3 clock hours of limbal involvement, less than 30% of conjunctival involvement, analogue scale reading of 0.1- 3/ 1- 29.9%, and the prognosis is good.
  • Grade III: In Grade III, there is between 3- 6 clock hours of limbal involvement, 30- 50% of conjunctival involvement, analogue scale reading of 3.1- 6/ 31- 50%, and the prognosis is good.
  • Grade IV: In Grade IV, there is between 6- 9 clock hours of limbal involvement, 50- 75% of conjunctival involvement, analogue scale reading of 6.1- 9/ 51- 75%, and the prognosis is good to guarded.
  • Grade V: In Grade V, there is between 9- 12 clock hours of limbal involvement, 75- 100% of conjunctival involvement, analogue scale reading of 9.1- 11.9/ 75- 100%, and the prognosis is guarded to poor.
  • Grade VI: In Grade VI, there is total limbal (12 clock hours) involvement, total conjunctival (100%) involvement, analogue scale reading of 12/ 100%, and the prognosis is very poor.

McCulley (1987) has divided the clinical course of chemical injury in four distinct phases:

  • Immediate.
  • Acute phase (0- 7 days).
  • Early reparative phase (7- 21 days).
  • Late reparative phase (after 21 days).

The clinical findings immediately following chemical exposure may be used to assess the severity and prognosis of the injury.

Hughes (1946) classification (modified by Ballen in 1963, Roper- Hall in 1965 and Pfister et al in 1982) provides a prognostic guideline based on corneal appearance and extent of limbal ischaemia. The Roper-hall classification system was introduced in the mid-1960s and is the most established and commonly applied system.

  • Grade I injury: In Grade I injury, there is corneal epithelial damage, no corneal opacity, no limbal ischaemia, and the prognosis is good.
  • Grade II injury: In Grade II injury, the cornea is hazy but the iris details are visible. There is also ishaemia involving less than one third of the limbus and the prognosis is good.
  • Grade III injury: In Grade III injury, there is total epithelial loss, stromal haze with obscuration of iris details, ischaemia of one third to one half of the limbus, and the prognosis is guarded.
  • Grade IV injury: In Grade IV injury, the cornea is opaque with no view of the iris or pupil, the ischaemia is greater than one half of the limbus, and the prognosis is poor.

In the acute phase (during first week), Grade I injuries heal while Grade II injuries slowly recover with corneal clarity. Grade III and Grade IV injuries have little or no epithelialisation, with no collagenolysis or vascularisation. Intraocular pressure may be elevated due to inflammation or decreased due to damage to ciliary body.

During early reparative phase (7- 21 days), in Grade II injuries, re- epithelialisation is completed with clearing of opacification. In more severe cases, there may not be a change in clinical appearance and there may be delayed or arrested re- epithelialisation. Keratocyte proliferation occurs with production of collagen and collagenase, resulting in progressive thinning with potential of perforation.

In late reparative phase, re- epithelialisation patterns divide injured eyes into two groups:

  • First group: In the first group, epithelialisation is complete or is nearly complete with sparing of limbal stem cells. Corneal anaesthesia, goblet cell/ mucinous abnormalities, and irregular epithelial basement membrane regeneration may persist.
  • Second group: In the second group, limbal stem cell damage results in corneal re- epithelialisation from conjunctival epithelium. This group has the worst prognosis with severe ocular surface damage characterised by vascularisation and scarring, goblet cell/ mucinous deficiency, and recurrent and persistent erosions. There may be cicatricial entropion (inward turning of eyelid), trichiasis (misdirected eyelashes), and symblepharon (adhesion between palpebral and bulbar conjunctiva) formation. A fibro-vascular pannus may form if there is no ulceration, and it compromises visual rehabilitation.

Differential diagnosis:

  • Thermal burns to the eyes.
  • Ultraviolet radiation keratitis.
  • Other causes of corneal opacification.
  • Ocular cicatricial pemphigoid.

Management should be carried out under medical supervision.

Preparation for vision restoration: Preparation for vision restoration must begin immediately after the injury. Deliberate and timely treatment determines successful outcomes in the rehabilitative process.

In succession, management consists of emergency treatment, pressure control, suppression of inflammation, enhancing stromal repair, and establishing eyelid-globe congruity during the early days, weeks, and months after the injury.

Topical or oral carbonic anhydrase inhibitors and topical beta blockers continue to form the mainstay of intraocular pressure control. Fibroblast inhibiting mitomycin C may improve the success of filtration surgery for glaucoma. Drainage procedures may be done if one or more filtration surgeries fail.

Operative procedures include amniotic membrane transplant, corneal epithelial stem cell transplants, keratoplasty, large-diameter lamellar keratoplasty, and keratoprosthesis.

Medical therapy:

Emergency management:

  • Irrigation of eyes: Emergency management requires prompt irrigation and the removal of residual chemical debris from the eye. The objectives are to minimise penetration of the chemical into the anterior chamber, and to remove a potential reservoir for ongoing injury. Immediate copious irrigation should begin at the scene of the incident and this is an important intervention. Irrigation with the lids kept open should be initiated and maintained at least for 30 minutes, which may require 1- 2 liters of solution. Irrigation should be continued until pH neutralisation is achieved. Patients with immediate copious irrigation have less severe injury, as compared to eyes which are not irrigated. Although there may be an advantage in the use of amphoteric buffering solution, any available neutral irrigation solution may be used in emergency. Solutions available for irrigation include normal saline, normal saline with bicarbonate, Ringer’s lactate, balanced salt solution (BSS), and BSS- plus. No therapeutic differences have been noted among these solutions. After copious irrigation, necrotic corneal epithelium should be débrided to promote re-epithelialisation.

    Where possible, topical anaesthetic drops should be instilled to reduce pain and blepharospasm, thereby facilitating irrigation. Remove all particulate matter, and this may require eyelid eversion (double eversion may be necessary) and cleaning of the fornices. Lime particles should be removed with forceps and a cotton-tipped applicator soaked in ethylenediaminetetraacetic acid (EDTA) may help with the removal of stubborn particles. Few patients may require general anaesthetic or sedation to effectively remove particulate matter.
  • Aqueous humour replacement: External irrigation is of limited value in eliminating chemicals once they have reached the anterior chamber. Role of paracentesis (removal of aqueous from anterior chamber) and irrigation of the anterior chamber is controversial. Nonetheless, it may be reasonable to consider aqueous humour replacement in patients with severe injuries presenting within first two hours following exposure.

Acute and Reparative phases:

After irrigation, better outcomes may be expected with prompt re-epithelialisation, while delayed or absent re-epithelialisation may require surgical intervention.

  • Corticosteroid therapy: Intensive corticosteroid therapy during first two weeks decreases the inflammatory response (which can delay epithelial migration), and thus enhances re-epithelialisation. Corticosteroids use during first 10 days of injury has no adverse effect on outcome. Prolonged use of corticosteroids beyond two weeks may lead to stromal ulceration, since steroids blunt stromal wound repair by decreasing keratocyte migration and collagen synthesis.
  • Medroxyprogesterone: Medroxyprogesterone is a pogestational steroid that has weak anti- inflammatory activity as compared to corticosteroids. Medroxyprogesterone inhibits collagenase but, unlike corticosteroids, minimally suppresses stromal wound repair. Medroxyprogesterone may be substituted for corticosteroid after two weeks if worsening corneal ulceration is of concern.
  • Topical and systemic sodium ascorbate (10%): Topical and systemic sodium ascorbate (10%) replenish depleted levels from the aqueous humour, following injury with alkali. Ascorbate is a cofactor in the rate- limiting step of collagen synthesis, and thus decreases the incidence of stromal ulceration. The molecular events responsible for the failure of collagen to assemble properly occur because of the deficiency of the reducing agent ascorbate.
  • Topical Citrate (10%): Topical buffered citrate is a calcium chelator that decreases intracellular levels of calcium in neutrophils and thus impairs chemotaxis, phagocytosis, and release of lysosomal enzymes. Topical citrate also reduces corneal ulceration and perforation of eye.
  • Oral tetracyclines: Oral tetracyclines offer protection against collagenolytic degradation.

Topical antibiotics may be required to prevent superadded infections. Cycloplegics provide comfort to the eye. Artificial tears, preferably preservative free, may provide general lubrication for ocular comfort.

 

Surgical therapy:

Surgical intervention that may help stabilising the ocular surface in severe chemical injury includes:

  • Tenonplasty: Tenonplasty attempts to re-establish limbal vascularity in severe injuries and to promote re- epithelialisation. In this, all necrotic conjunctival and episcleral tissues are excised. Tenon’s capsule is dissected with blunt instrument, and the resultant flap with its preserved blood supply is advanced to the limbus.
  • Tissue adhesives (tissue glue): Tissue adhesives preserve integrity in the event of corneal thinning with impending or actual perforation of the globe. This is usually accompanied by the application of a soft bandage contact lens, which prevents glue dislodgement. Tissue glue can stop further melting by excluding inflammatory cells and their mediators. Tissue adhesives also provide a means of delaying penetrating keratoplasty.
  • Amniotic membrane transplantation: Amniotic membrane transplantation may be used as supplement to surgical procedures where coverage of raw surfaces or suppression of inflammation is required. Amniotic membrane has anti-angiogenic (inhibitors of blood vessels growth) and anti-inflammatory proteins capable of suppressing the inflammatory response. Amniotic membrane can create a new basement membrane and promote epithelial healing. Amniotic membrane might be applied very early after a chemical injury following emergency services, usually weeks later. Despite benefits, amniotic membrane cannot replace the need for corneal stem cells.
  • Corneal stem cell transplantation: Replacement of the corneal stem cells lost due to injury is important in the restoration of an intact and normal corneal epithelial cell layer. These primitive, slow-cycling stem cells are located in the limbal area.  

Monocular injuries allow for procurement of stem cells from the uninjured eye. When the injury is bilateral, Pfister (1993) showed that allografted limbal tissue was capable of restoring the stem cell population from an unrelated donor. Allografted corneal stem cells must be protected from the recipient immune process by systemic immune-suppression e.g. cyclosporine.

  • Corneal transplantation (Keratoplasty):

                Success in restorative corneal surgery is governed by:

-  Lid-globe congruity with normal blinking and the absence of corneal exposure. Preparatory procedures to lyse symblepharon, expand cul-de-sacs, and to eliminate lagophthalmos are often required to re-establish normal lid functioning.

-  Quality and quantity of tear film.

-  The presence of epithelial stem cells phenotypic for cornea.

-  The absence of any current ulceration, inflammation, and/or uncontrolled glaucoma. Secondary glaucoma must also be controlled with medications or filtration surgery.

-  Flawless surgical technique.

-  Fresh corneal transplant tissue.

The value of preoperative use of LASER for blood vessels at the limbus in high-risk patients is controversial, but at least it reduces bleeding at the time of surgery.

If corneal surgery is delayed 18 months to 2 years after a chemical burn, it increases the chances of success, especially without pre-existing ulceration, perforation, or glaucoma.

Penetrating keratoplasty: Penetrating keratoplasty refers to the full- thickness replacement of the affected cornea with a healthy donor. Penetrating keratoplasty may be used to provide tectonic support (such as in corneal thinning and perforation), and to improve visual outcome (such as in the replacement of corneal scarring).

Large-diameter penetrating keratoplasty: Replacement of the entire cornea and adjacent stem cells by large-diameter penetrating keratoplasty may be performed. One potential danger might be that such large transplants might interfere with the trabecular outflow channels and hence increase the likelihood of glaucoma. Proximity to the limbal blood vessels makes an immune rejection more likely.

Large-diameter lamellar keratoplasty: A very promising technique in corneal transplantation for chemical injuries includes the use of 12 or 13 mm lamellar corneal transplants, along with the limbal epithelial stem cell population. Smaller lamellar transplants are useful to fill in deep corneal ulcerations, descemetoceles, or frank corneal perforations.

  • Keratoprosthesis (Artificial cornea): In the most severe cases, implantation of a keratoprosthesis might afford the only means by which vision can be restored.

Indications for keratoprosthesis are:

-  Corneas exhibiting exuberant vascularity.

-  Repeated failures of fresh transplanted corneal tissue.

-  Chronic limbal stem cell deficiency.

-  Inability to restore normal lid anatomy.

The operation is usually advised in patients with severe bilateral injuries where serviceable vision is not present in either eye. A surprising degree of success may be achieved with keratoprosthesis. Critical to the visual outcome of a keratoprosthesis is the control of intraocular pressure at all times after the chemical injury.

  • Conjunctival transplantation: Conjunctival transplantation is a means of restoring conjunctival fornices following fibrosis. This provides compatible tissue with a basement membrane, unlike other mucosal replacements. The procedure involves taking a sample of upper bulbar conjunctiva from the contralateral (other uninvolved) eye.
  • Buccal and Nasal mucosa transplant: Buccal mucosa grafts may be used to treat symblepharon (adhesion between bulbar and palpebral conjunctiva), trichiasis (misdirected eyelashes), distichiasis (partial or complete second row of eyelashes), or entropion. The graft is usually obtained from the posterior aspect of the upper or lower lip. The advantage of nasal mucosal grafts lies in the ability to obtain large sized grafts.

 

Stages of ocular recovery following chemical injury (Colby, 2010):

  • Initial phase (day 0): Clinical findings relate to the severity of injury and can be graded according to degree of limbal, corneal and conjunctival involvement.
  • Acute phase (day 0- 7): Epithelial re-growth begins to occur if there is sufficient amount of undamaged limbal stem cells. Treatment should be directed at encouraging growth while suppressing inflammation.
  • Phase of early repair (days 7- 21): Corneal/ conjunctival epithelium and keratocytes proliferate during this stage. Mild injuries show complete re-epithelialisation while more severe injuries can have persistent epithelial defects. Activity of collagenases peaks by day 14- 21 while collagen synthesis continues. Treatment should attempt to maximise collagen synthesis while minimising collagenase activity.
  • Phase of late repair (after day 21): In mild injuries, where the limbal stem cell population is intact, repair is completed. In injuries, where there is focal stem cell loss, there may be a focal growth of conjunctiva on the cornea. In more severe injuries, there is delayed re-epithelialisation of the cornea, ultimately leading to either repopulation by conjunctival epithelium or stromal ulceration and permanent scarring. In cases of severe limbal damage, despite optimal management, the eye cannot be salvaged.

 

Management of exposure to lacrimatory agents:

  • Tear gas and Chemical Mace: Following exposure to tear gas and Chemical Mace, thorough rinsing/ irrigation provides immense relief.
  • Pepper spray (Oleoresin capsicum): Irrigation with fresh water, although recommended, has little effect as capsicin is not soluble in water. Flushing the eye with a solution containing half liquid antacid (of aluminium or magnesium hydroxide base) and half water (LAW) is more effective.
  • Mustard gas (Dichlorodiethyl sulphide): Prompt irrigation of eyes with running water or normal saline is useful. Topical antibiotic, cycloplegic and lubricant may be used for associated corneal erosions.

Exposure to chemicals used for festivals in India also requires thorough rinsing/ irrigation with running water or normal saline for relief.

 

Prognosis:

The prognosis for severe injury is typically poor and may result in widespread damage to the ocular surface epithelium, cornea and anterior segment. However, in recent years, the prognosis of severe ocular burns has improved, with advances in the understanding of the physiology of the cornea and the resultant development of enhanced medical and surgical treatments. The final visual prognosis is influenced by:

  • The nature of the chemical insult.
  • The extent of ocular damage.
  • The timing and efficacy of treatment.

Potential complications and sequelae of chemical injuries to the eye are:

Lids:

  • Posterior displacement of meibomian orifices.
  • Trichiasis.
  • Cicatricial ectropion.
  • Cicatricial entropion.
  • Lagophthalmos (inability to close the eyelids completely).
  • Ankyloblepharon (adhesion of eyelids to each other).

Ocular surface:

  • Dry eye.
  • Loss of goblet cells.
  • Damage to lacrimal system.
  • Corneal scarring.
  • Corneal neovascularisation.
  • Limbal stem cell deficiency.
  • Symblepharon.
  • Corneal melt.
  • Corneal opacity.
  • Intraocular inflammation.
  • Recurrent corneal erosions.
  • Non healing epithelial defects.
  • Microbial keratitis.

Elevated IOP:

  • Secondary glaucoma.

Intraocular structures:

  • Fixed dilated pupil.
  • Iris ischaemia.
  • Ciliary body shut down with secondary hypotony (reduced intraocular pressure).
  • Cataract.
  • Retinal detachment.
  • Phthisis bulbi (shrunken globe).

Education and training regarding prevention of chemical exposures in the workplace can help in preventing chemical injuries to the eye.

For general prevention, safety glasses may be used to safeguard eyes. Even these measures may not suffice in high-velocity (explosive) chemical injury.

  • PUBLISHED DATE : Jun 23, 2016
  • PUBLISHED BY : NHP Admin
  • CREATED / VALIDATED BY : Dr. S. C. Gupta
  • LAST UPDATED ON : Jun 23, 2016

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