There are 3 main goals in managing a chemical injury: enhance recovery of the corneal epithelium; augment collagen synthesis while minimizing collagen breakdown and sterile ulceration; and control inflammation. In severe cases, surgical treatment may be indicated. Table 2 summarizes initial treatments based on the grade of the injury.
Initial management of an acute chemical injury is relatively straightforward. The severity of a chemical burn is a function of both the toxicity of the agent involved and the duration of exposure. Time is of the essence, since chemical burns are one of the only true ophthalmic emergencies. The eye should be copiously irrigated as quickly as possible after the exposure with whatever clean fluid is available. Irrigation should be repeated upon arrival to the hospital, since irrigation at the location of the injury or in the ambulance is often insufficient to entirely remove the offending agent. Once irrigation is complete, the pH of the ocular surface is checked with expanded range pH paper. If the pH has normalized (7.0 to 7.2), then the rest of the history can be taken and the eye examined. If the pH is still abnormal, then irrigation should be continued and the pH measurement repeated. The pH should be rechecked every 15 to 30 minutes to ensure that it remains normal. A pH that rises after initial normalization suggests that trapped particulate matter (for example, particles of plaster) is continuing to leach chemical onto the surface of the eye.
A complete ophthalmic exam is performed, including inspection and sweeping of the inferior and superior fornix to remove trapped particles. Intraocular pressure is checked, since chemical injuries may cause an acute pressure increase. The injury is graded based upon the extent of damage to the cornea, limbus, and conjunctiva. In an acute chemical injury, a white “porcelainized” eye typically denotes extensive limbal ischemia, representing severe damage. This is occasionally misinterpreted as a mild injury by an inexperienced observer. Similarly, a cornea that is completely denuded of epithelium will take up fluorescein stain poorly, leading the examiner to underestimate the initial extent of the damage. One should also inspect the chemical safety sheet for the agent in question. Certain agents such as hydrofluoric acid can cause life-threatening metabolic imbalances; patients injured by this agent need concurrent medical evaluation.
During the acute phase of recovery (first week after the injury), the goal is to encourage epithelial healing while controlling inflammation and preventing superinfection. Patients with mild injuries (grade I) can be placed on a topical antibiotic ointment such as erythromycin 4 times a day. A cycloplegic agent can be given to help with comfort (cyclopentolate 2 to 3 times daily or a single dose of scopolamine given by the examiner). Preservative-free artificial tears can also provide comfort following a chemical injury. Even mild chemical injuries have significant associated inflammation, and we would typically give topical corticosteroids, usually prednisolone acetate 1% 4 times a day, with a rapid taper to off once the corneal epithelium is healed. Patients with mild chemical injuries are followed every 1 to 2 days until the ocular surface is stable. Patients may experience ocular discomfort even months after a relatively minor chemical injury. Supportive measures such as lubrication and treatment of any associated meibomian gland dysfunction or dry eye will help return the ocular surface to its pre-injury state.
For burns of grade II and above, the importance of intensive topical corticosteroids in the acute phase cannot be overemphasized. There is concern that topical corticosteroids can exacerbate corneal melting. While this is true in the later stages of chemical injury management, in the acute stage topical corticosteroids are very beneficial for controlling the severe inflammatory sequelae and should be used in an appropriately aggressive fashion. Corneal melting from activation of corneal collagenases typically does not begin before 10 to 14 days after the injury. Therefore, the first week represents a window in which corticosteroids can and should be used to quell the raging inflammation and give the ocular surface a chance to heal. For grade II burns and above, we typically use prednisolone acetate 1% hourly while the patient is awake.
Additional considerations include the following:
Monitoring and Follow-Up
- Long-acting cycloplegia (ie, atropine sulfate 2 times daily) is beneficial.
- Oral narcotics are often required for pain control.
- A stronger topical antibiotic (such as a fluoroquinolone) is given at least 4 times daily to reduce the risk of bacterial superinfection.
- Topical sodium ascorbate (10%) and oral vitamin C supplementation are given to promote collagen synthesis. Ascorbate, a cofactor in the rate-limiting step of collagen synthesis, may be depleted following a chemical injury. Animal data suggests that ascorbate administration may reduce corneal ulceration.
- Oral tetracycline derivatives are given to reduce the risk of ulceration due to their inhibitory effects on corneal matrix metalloproteinases. They may also help to reduce ocular surface inflammation.
- Preservative-free tear supplements may be administered as needed.
- Glaucoma medications (topical or oral) are prescribed if the intraocular pressure is elevated.
- There is little role for topical nonsteroidal agents in a severe chemical injury. Their anti-inflammatory power is dwarfed by that of the recommended topical corticosteroids and they have the potential to cause issues with epithelial healing.
- Similarly, bandage contact lenses are of marginal utility in the acute management of chemical burns, as the eye is usually too inflamed to tolerate a foreign body on its surface.
Patients with severe chemical injuries (grade II and above) should be followed daily initially. If there is a concern about compliance, consideration should be given to inpatient admission. Once epithelial healing is progressing, then follow-up visits can be reduced accordingly. However, it is important to maintain close observation while patients remain on topical corticosteroids.
The real “art” of managing chemical burns comes after the first week. For milder injuries (grade I and less severe grade II), epithelial regrowth within the first 7 to 10 days is typical. Once epithelial regrowth is progressing, topical corticosteroids can be tapered, with cessation of therapy once the epithelium is completely intact and the eye is quiet. Lubrication and management of co-existing dry eye and meibomian gland dysfunction will help with post-injury discomfort.
For more severe grade II injuries and all grade III injuries, complete epithelial healing usually takes longer than 10 days. At this point, the risk of corneal melting increases due to the shift towards collagen breakdown at the expense of collagen synthesis. Topical corticosteroids must be tapered if the epithelium is not intact. Low-dose corticosteroids (prednisolone acetate 1% once or twice daily) may be continued if the patient is followed closely, because corneal melting can occur precipitously in these patients. In place of corticosteroids, topical progestational steroids such as 1% medroxyprogesterone can be started to provide some anti-inflammatory effect without inducing corneal melting. Other medicines are continued. If epithelial healing falters or comes to a complete halt or progressive corneal melting occurs, then one must resort to the surgical maneuvers described in the next section.
In grade IV injuries, medical therapy alone will not restore the epithelial integrity of the eye, and surgery is virtually always required. One may begin medical management initially to quiet the eye, but with the knowledge that this is purely a temporizing measure.
Role and Timing of Surgical Treatment Following Chemical Injury
Mild chemical injuries rarely require surgery for management. More severe grade II injuries may require focal debridement of necrotic corneal or conjunctival epithelium. This should be done as early as possible, because the necrotic tissue serves as a source of inflammatory mediators that can inhibit re-epithelialization. Necrotic corneal epithelium can be removed at the slit lamp with surgical sponges. Extensive necrotic conjunctiva can be excised with scissors using topical anesthesia with the aid of a slit lamp or under an operating microscope. Occasionally grade II injuries show focal corneal melting that can usually be managed with the application of cyanoacrylate tissue adhesive covered with a bandage contact lens.
Grade III injuries often require surgery for both acute and long-term management. In the acute phase, necrotic tissue should be debrided whenever needed, for the reasons detailed above.
Restoration of the Corneal Surface
If epithelium (either corneal or conjunctival) does not begin to grow in to cover the cornea or if regrowth begins but then fails to progress, placement of an amniotic membrane within the first several weeks after the injury may be useful. Amniotic membrane has anti-inflammatory properties and can provide a scaffold for the regrowth of epithelium. It can be sutured (using either 10.0 Vicryl or 10.0 nylon) or glued (using Tisseel fibrin glue) into place. Amniotic membrane on a conformer ring (ProKera, Bio-Tissue, Miami, FL) can also be used in this setting, often with a tarsorrhaphy to prevent dislocation of the membrane. However, despite the useful properties of amniotic membrane in this setting, it does not replace limbal stem cells, but may allow conjunctival epithelium to grow in to cover the cornea. In severe injuries, one often must be satisfied, in the short-term at least, with an eye that is resurfaced by vascularized, conjunctival epithelium. While this is not compatible with good vision, at least this restores tectonic stability to the eye and eliminates the risk of progressive corneal melting.
Amniotic Membrane in Acute Chemical Burn
Use of Sutureless Amniotic Membrane
Some clinicians advocate the use of amniotic membrane transplantation acutely in all serious chemical injuries (grade II and above). In our hospital, we generally reserve amniotic membrane for chemical injuries that do not respond to initial medical management. Amniotic membrane is a useful adjunct, but it is quite expensive and not covered by some insurers in our area, so we prefer to limit its use to situations in which we know it is required.
The same management strategies can be used in grade IV injuries, although the complete destruction of the limbal stem cell population and limbal conjunctiva makes it unlikely that they will be successful. Mobilization and advancement of more posterior conjunctiva and Tenon’s capsule can be used to bring healthy tissue into the damaged area and may increase the likelihood of initial stabilization of these badly damaged globes.
Eyelid issues such as malpositions or trichiasis may accompany severe chemical injuries and need to be addressed to prevent further damage to the cornea and inhibition of epithelial healing.
Ongoing Suppression of Inflammation
Once the corneal surface has been restored, either with corneal epithelium in less severe burns, or with conjunctival epithelium in more severe burns, the frequency of follow-up can be reduced. Severely burned eyes will benefit from ongoing suppression of inflammation with low-dose corticosteroids or topical cyclosporine. Bland ophthalmic ointment and preservative-free artificial tears will help improve ocular comfort.
Stem Cell Transplantation
Following a severe unilateral chemical injury in which there has been loss of most or all of the limbal stem cell population, one can consider an autologous limbal stem cell transplant from the patient’s other eye, described in detail by Nordlund et al. Caution should be exercised if the other eye was damaged as well, since even mild injuries can deplete the stem cell reserve to the point that harvesting some of the stem cells may lead to the surface epitheliopathy in the good eye.
If the original injury was bilateral or there is concern about the viability of the stem cell population in the good eye, then there are several options. One can consider a living-related stem cell graft from a family member or a cadaveric donor. Both of these require systemic immunosuppression, which adds to the complexity of postoperative management. Cultured buccal mucosa has shown some utility in this situation, although again, like amniotic membrane alone, buccal mucosa does not contain limbal stem cells. A novel approach involves the use of the patient’s own limbal stem cells that have been expanded in culture in vitro and then transplanted back on to the injured eye. This allows harvesting of a much smaller amount of limbal stem cells, which can be useful when one is unsure of the status of the stem cell population in the good eye.
Additional Measures and Follow-Up
Once the health of the ocular surface has been restored, then a corneal transplant can be considered if needed. Supportive measures including concurrent amniotic membrane transplantation and suture tarsorrhaphy may also be performed to promote epithelial healing of the corneal transplant. The graft should be secured with interrupted sutures (rather than with a running suture) to allow selective suture removal if corneal neovascularization ensues. Postoperative management includes topical steroids, antibiotics and possibly cyclosporine. Occasionally restoration of the ocular surface is enough to allow acceptable vision, however, and a penetrating keratoplasty is not required (see below).
Permanent Boston keratoprostheses have been used in chemical burn patients with reasonable success. This type of device is especially useful in bilateral severe burns, because its success is not dependent upon limbal stem cell function and it does not require the use of systemic immunosuppression.