Chemical (Alkali and Acid) Injury of the Conjunctiva and Cornea
Chemical (alkali and acid) injury of the conjunctiva and cornea is a true ocular emergency and requires immediate intervention. Chemical injuries to the eye can produce extensive damage to the ocular surface and anterior segment leading to visual impairment and disfigurement. Early recognition and treatment ensures the best possible outcome for this potentially blinding condition.
- 1 Disease Entity
- 2 Diagnosis
- 3 Management
- 3.1 Irrigation
- 3.2 Medical therapy
- 3.3 Surgical Treatments
- 3.4 Recommended Treatment
- 3.5 Stages of Ocular Recovery
- 3.6 Follow up
- 3.7 Other long term complications
- 4 Additional Resources
- 5 References
Disease Entity[edit | edit source]
International Classification of Diseases[edit | edit source]
ICD-9-CM 940.2 alkaline chemical burn to cornea and conjunctiva, 940.3 acid chemical burn to the cornea and conjunctiva, 372.06 chemical conjunctivitis
ICD-10-CM T26.60XA Corrosion of cornea and conjunctival sac, unspecified eye, initial encounter.
Epidemiology[edit | edit source]
Chemical injuries to the eye represent between 11.5%-22.1% of ocular traumas.About two thirds of these injuries occur in young men. The vast majority occur in the workplace as a result of industrial accidents. A minority of injuries occur in the home or secondary to assault. Alkali materials are found more commonly in building materials and cleaning agents and occur more frequently than acid injuries.
Etiology[edit | edit source]
Pathophysiology[edit | edit source]
Alkali[edit | edit source]
Alkali agents are lipophilic and therefore penetrate tissues more rapidly than acids. They saponify the fatty acids of cell cell membranes, penetrate the corneal stroma and destroy proteoglycan ground substance and collagen bundles. The damaged tissues then secrete proteolytic enzymes, which lead to further damage.
Acids[edit | edit source]
Acids are generally less harmful than alkali substances. They cause damage by denaturing and precipitating proteins in the tissues they contact. The coagulated proteins act as a barrier to prevent further penetration (unlike alkali injuries). The one exception to this is hydrofluoric acid, where the fluoride ion rapidly penetrates the thickness of the cornea and causes significant anterior segment destruction.
Primary prevention[edit | edit source]
Since the majority of injuries occur at work, protective eye shields are mandatory when handling potentially corrosive substances (OSHA regulation, 1910.133). However, even protective goggles are no match for chemicals under high pressure.
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History[edit | edit source]
The severity of ocular injury depends on four factors: the toxicity of the chemical, how long the chemical is in contact with the eye, the depth of penetration, and the area of involvement. It is therefore critical to take a careful history to document these factors. The patient should be asked when the injury occurred, whether they rinsed their eyes afterwards and for how long, the mechanism of injury (was the chemical under high pressure?), the type of chemical that splashed in the eye, and whether or not they were wearing eye protection. If available, it is helpful to obtain the packaging of the chemical. There is often product information on this packaging including chemical composition. If this information is not immediately available, chemical information can be found by contacting the local poison control center at aapcc or 1 800-222-1222.
Physical examination[edit | edit source]
Prior to a full ophthalmic exam, the pH of both eyes should be checked. If the pH is not in physiologic range, then the eye must be irrigated to bring the pH to an appropriate range (between 7 and 7.2). It is recommended to wait at least five minutes after irrigation before checking the pH to ensure that the pH does not rise or fall secondary to retained particulate matter.
The physical exam should be used to assess the extent and depth of injury (see classification schemes below). Specifically, the degree of corneal, conjunctival and limbal involvement should be documented, as it can be used to predict ultimate visual outcome.
The palpebral fissures should be checked and the fornices should be swept during the initial exam. Both the palpebral and bulbar conjunctiva should be examined with fluorescein under a cobalt blue light. As above, retained particulate matter can cause persistent damage, despite irrigation. The intraocular pressure should also be documented, as alkali injuries have been found to both acutely and chronically cause an elevation of IOP.
Two major classification schemes for corneal burns are the Roper-Hall (modified Hughes) classification and the Dua classification. The Roper-Hall classification is based on the degree of corneal involvement and limbal ischemia. The Dua classification is based on an estimate of limbal involvement (in clock hours) and the percentage of conjunctival involvement. In a randomized controlled trial of acute burns, the Dua classification was found to be superior to the Roper-Hall in predicting outcome in severe burns. However, both classification schemes are commonly employed in daily practice.
Symptoms[edit | edit source]
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Irrigation[edit | edit source]Morgan Lens® (MorTan, Missoula MT) can be used to keep the eye open, while the irrigating solution is delivered through IV tubing. There has been some debate on the most effective irrigating solutions. A study by Herr et al. compared Normal Saline (NS), Normal Saline with Bicarbonate (NS + Bicarb), Lactated Ringer’s solution (LR), and Balanced Saline Solution Plus (BSS Plus, Alcon Laboratories, Fort Worth, TX) irrigating solutions to investigate which solution optimized patient comfort. They found that patients tolerated and preferred BSS irrigation compared to NS, NS + Bicarb, and LR. In experiments in rabbit eyes following sodium hydroxide injury, a borate buffer solution called Cedderroth eye wash (Cedderroth Industrial Products, Upplands Vaasby Sweden) and a Diphthorine and Previn solution (Prevor, Cologne Germany) more efficiently normalized the pH compared to saline and phosphate buffer solutions. Of course, early irrigation is paramount to limiting the duration of chemical exposure. If clean water is available at the site of injury and a standard irrigating solution is not, then the eyes should immediately be washed out with water.
Medical therapy[edit | edit source]
Patients with mild to moderate injury (Grade I and II) have a good prognosis and can often be treated successfully with medical treatment alone. The aims of medical treatment are to enhance recovery of the corneal epithelium and augment collagen synthesis, while also minimizing collagen breakdown and controlling inflammation.
Standard Treatments[edit | edit source]
Antibiotics- A topical antibiotic ointment like erythromycin ointment four times daily can be used to provide ocular lubrication and prevent superinfection. Stronger antibiotics (e.g. a topical fluoroquinolone) are employed for more severe injuries (e.g. Grade II and above).
Cycloplegic agents such as atropine or cyclopentolate can help with comfort.
Artificial tears- and other lubricating eye drops, preferably preservative free, should be used generously for comfort.
Steroid drops- In the first week following injury, topical steroids can help calm inflammation and prevent further corneal breakdown. In mild injuries, topical prednisolone (Predforte) can be employed four times daily. In more severe injuries, prednisolone can be used every hour. After about one week of intensive steroid use, the steroids should be tapered because the balance of collagen synthesis vs. collagen breakdown may tip unfavorably toward collagen breakdown.
Other Treatments:[edit | edit source]
Ascorbic acid- is a cofactor in collagen synthesis and may be depleted following chemical injury. Ascorbic acid can be used as a topical drop (10% every hour) or orally (two grams, four times daily in adults). In one study, severe alkali burns in rabbit eyes were associated with reduced ascorbic acid levels in the aqueous humor. This reduction correlated with corneal stromal ulceration and perforation. Systemic administration of Vitamin C helped promote collagen synthesis and reduce the level of ulceration.Care must be taken in patients with compromised renal function because high levels of Vitamin C are potentially toxic to the kidneys.
Doxycycline- acts independently of its antimicrobial properties to reduce the effects of matrix metalloproteinases (MMPs), which can degrade type I collagen. The tetracycline class inhibits MMPs by restriction of the gene expression of neutrophil collagenase and epithelial gelatinase, suppression of alpha 1 antitrypsin degradation and scavenging reactive oxygen species, thereby reducing ocular surface inflammation.
Citrate drops- histological sections of cornea from alkali burns reveal an intense polymorphonuclear infiltrate (PMN). PMNs provide a major source of proteolytic enzymes, which can dissolve the corneal stromal collagen. Deficiency in calcium inhibits the PMNs from granulating and releasing proteolytic enzymes. Citrate is a potent chelator and can therefore decrease proteolytic activity. Citrate also appears to inhibit collagenases.
1% Medroxyprogesterone- is a progestational steroid and has less anti-inflammatory potency than corticosteroids, but has a minimum effect on stromal repair. Medroxyprogesterone can therefore be substituted for cortical steroids after 10-14 days of steroid treatment.
Platelet rich plasma eye drops- have been found to be rich in growth factors and platelet rich plasma eye drops can lead to faster epithelialization for certain classes of burns.
Surgical Treatments[edit | edit source]Debridement of necrotic epithelium- should be performed as early as possible because necrotic tissue serves as a source of inflammation and can inhibit epithelialization.
Conjunctival/Tenon’s transposition (Tenonplasty)- in Grade IV burns, anterior segment necrosis can result from loss of limbal vascular blood supply. In severe limbal ischemia, a sterile corneal ulceration can ensue. After removal of necrotic tissue, a tenonplasty (advancement of the conjunctiva and Tenon’s to the limbus) can be employed to reestablish limbal vascularity and facilitate re-epithelialization.
Amniotic membrane transplantation (AMT)- the purpose of AMT is to rapidly restore the conjunctival surface and to reduce limbal and stromal inflammation. The benefits are thought to be two fold: physical and biological. Physically, AMT has been shown to improve patient comfort by reduction of eyelid friction. Numerous studies have found a reduction in pain following AMT for moderate to severe burns. Through its physical actions, AMT may also prevent symblepharon formation. Amniotic membrane is also felt to have biologic effects. It expresses TGFB1 and epidermal growth factor, which have roles in wound healing. It has also been found to have anti-inflammatory properties. Taken together, these biological effects may dampen inflammation, promote epithelial growth, prevent scarring and prevent neovascularization. New delivery devices like ProKera® (Bio-Tissue, Miami, Florida), which consists of a piece of cryopreserved amniotic membrane clipped into a dual ring system, like a symblepharon ring, allows rapid and sutureless placement of amniotic membrane. A recent Cochrane review found only one randomized controlled trial of amniotic membrane for treatment of chemical ocular burn in the first seven days following injury. Patients with moderate burns were found to have a significantly better visual acuity following AMT compared to medical therapy alone. However, this was an unmasked trial and there were uneven baseline characteristics of the control and treatment eyes. While case series and reviews show great promise of AMT in the treatment of chemical burns, conclusive evidence is still lacking.
Limbal stem cell transplant- Much of the damage following chemical injuries results from limbal ischemia and the subsequent loss of stem cells capable of repopulating the corneal epithelium. Limbal stem cell transplants have been employed to replace this critical group of cells. Limbal stem cells are located at the base of the limbal epithelium and are responsible for repopulation of cells in the corneal epithelium and inhibition of conjunctival growth over the cornea. Limbal autografts can be used from the healthy contralateral eye if only one eye is injured in a chemical burn. When both eyes are injured, transplants have been attempted from living related donors. In a recent study from China, a portion of the limbus of HLA matched living related donors (allograft) was transplanted following chemical injury. Patients experienced a reduction in vascularity, improved corneal opacity and corneal epithelialization without the need for systemic immunosuppression. Another option is to use cadaveric donors. This requires systemic immunosuppression. When possible, limbal stem cell transplantation should be delayed until ocular surface inflammation has quieted.
Cultivated oral mucosal epithelial transplantation (COMET)- can also be used to promote re-epithelialization and reduce inflammation in corneal burns. The cells are harvested from the patient’s own buccal mucosa so that systemic immunosuppression is not necessary.
Boston Keratoprosthesis- Severe chemical injury leads to chronic inflammation and scarring, making visual recovery challenging. In cases with severe inflammation, limbal stem cell transplants and corneal transplants do not survive. In these most difficult cases, the Boston Keratoprosthesis can be used. Because it is independent of stem cell function, it does not require systemic immunosuppression.
Recommended Treatment[edit | edit source]
While there is variability in treatment strategies of chemical burns, most authors recommended a graded approach depending on the severity of injury. Mild burns (Roper-Hall grade I) respond well to medical treatments and lubrication, while more severe burns necessitate more intensive medical therapies and surgery. Below is a paradigm for the initial treatment of chemical injury based on the Roper-Hall grade of injury.
Grade I[edit | edit source]
- Topical antibiotic ointment (erythromycin ointment or similar) four times a day
- Prednisolone acetate 1% four times a day
- Preservative free artificial tears as needed
- If there is pain, consider a short acting cycloplegic like cyclopentolate three times a day
Grade II[edit | edit source]
- Topical antibiotic drop like fluoroquinolone four times daily
- Prednisolone acetate 1% hourly while awake for the first 7-10 days. Consider tapering the steroid if the epithelium has not healed by day 10-14. If an epithelial defect persists after day 10, consider progestational steroids (1% medroxyprogesterone four times daily)
- Long acting cycloplegic like atropine
- Oral Vitamin C, 2 grams four times a day
- Doxycycline, 100 mg twice a day (avoid in children)
- Sodium ascorbate drops (10%) hourly while awake
- Preservative free artificial tears as needed
- Debridement of necrotic epithelium and application of tissue adhesive as needed
Grade III[edit | edit source]
- As for Grade II
- Consider amniotic membrane transplant/Prokera placement. This should ideally be performed in the first week of injury. Experienced surgeons have emphasized placement of the amniotic membrane to cover the palpebral conjunctiva by suturing to the lids in the operating room, not just covering the cornea and bulbar conjunctiva.
Grade IV[edit | edit source]
- As for Grade II/III
- Early surgery is usually necessary. For significant necrosis, a Tenonplasty can help reestablish limbal vascularity. An amniotic membrane transplant is often necessary due to the severity of the ocular surface damage.
Stages of Ocular Recovery[edit | edit source]
Figure E Figure F
*Images courtesy of Dr. Kathryn Colby (Massachusetts Eye and Ear Infirmary)
Follow up[edit | edit source]
With severe chemical burns, patients should initially be followed daily. If there is concern for compliance with medication or if the patient is a child, one should consider inpatient admission. Once the health of the ocular surface has been restored, follow up can be spread apart. However, even in the healthiest appearing eyes, patients need long term monitoring for glaucoma and dry eye as below.
Other long term complications[edit | edit source]
Glaucoma[edit | edit source]
Glaucoma is quite common following ocular injury, ranging in frequency from 15%-55% in patients with severe burns. The mechanism of glaucoma is multifactorial and includes contraction of the anterior structures of the globe secondary to chemical and inflammatory damage, inflammatory debris in the trabecular meshwork, and damage to the trabecular meshwork itself. More severe burns (Roper-Hall Grade III or IV) have been found to have significantly higher intraocular pressure at presentation and were more likely to require long term glaucoma medication and undergo glaucoma surgery than grade I or II injuries. Glaucoma medications should be prescribed as necessary to maintain normal intraocular pressure
Dry eye[edit | edit source]
Chemical injury can destroy conjunctival goblet cells, leading to a reduction or even absence of mucus in the tear film, and compromising the proper dispersion of the precorneal tear film. This mucus deficiency results in keratoconjunctivitis sicca (dry eye). Even in well-healed eyes, chronic dry eye can cause significant morbidity because of discomfort, visual disturbance, and potential for damage of the ocular surface.
Damage to the eyelids or palpebral conjunctiva[edit | edit source]
Direct chemical damage to the conjunctiva can lead to scarring, forniceal shortening, symblepharon formation and ciccatricial entropion or ectropion. These entities are encountered weeks to months after injury and can be treated by suppressing inflammation and with early amniotic membrane transplantation or oral mucosal graft.
Additional Resources[edit | edit source]
American Academy of Ophthalmology: http://www.aao.org
American Association of Poison Control Centers: http://www.aapcc.org (1-800-222-1222)
Iowa State University’s Chemistry Material Safety Data Sheets: http://avogadro.chem.iastate.edu/MSDS/
Occupational Safety and Health Administration requirement for eye protection at work:
Amniograft & Prokera: http://www.biotissue.com/
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