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.
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Most common immediate symptoms are:
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:
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:
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:
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.
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.
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.
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:
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:
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:
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.
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).
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:
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:
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:
Non-healing corneal epithelial wounds pose a significant risk as they expose the cornea to potential microbial infection.
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.
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:
Clinical history: Patient should be asked for:
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:
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.
McCulley (1987) has divided the clinical course of chemical injury in four distinct phases:
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.
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:
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.
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.
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 intervention that may help stabilising the ocular surface in severe chemical injury includes:
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.
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.
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.
Stages of ocular recovery following chemical injury (Colby, 2010):
Management of exposure to lacrimatory agents:
Exposure to chemicals used for festivals in India also requires thorough rinsing/ irrigation with running water or normal saline for relief.
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:
Potential complications and sequelae of chemical injuries to the eye are:
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.