Chemical injury (alkali burn) is a condition in which the cornea and conjunctiva are damaged by the entry of alkaline chemicals into the eye. It is one of the most urgent ophthalmic emergencies, and immediate management determines the prognosis.
The incidence of ocular chemical injury is estimated at 65–78 per 100,000 population 1). The mean age is 48 years, but there is also a bimodal peak in those under 1 year of age 1). Alkali injuries are more common than acid injuries 1). Workplace injuries are the most frequent, and among occupational eye injuries, they are the second most common after metallic foreign bodies 1). Alkali injuries due to assault are often severe, reaching Roper-Hall Grade IV, and ammonia-related assaults have been reported to have the worst outcomes 1).
The main causative substances of alkaline materials are shown below. Note that even household products can cause severe eye injuries.
| Causative substance | Examples of products containing it | Characteristics |
|---|---|---|
| Sodium hydroxide | Mold remover, drain cleaner | Reaches anterior chamber within minutes |
| Ammonia | Hair dye, industrial cleaner | Penetrates cornea instantly |
| Potassium hydroxide | Industrial cleaner | High tissue penetration |
| Lime/cement | Construction materials (slaked lime, quicklime) | Common in occupational injuries |
| Quicklime (calcium oxide) | Desiccant, building materials | Accompanied by exothermic reaction |
Compared to acids, alkalis saponify lipids and cause cell lysis and necrosis. Since they do not form a barrier of coagulated proteins, they have high deep penetration, reaching the anterior chamber and causing iritis, cataracts, and glaucoma. Therefore, alkali injuries tend to cause more severe damage overall than acid injuries.
Alkalis saponify the lipids of cell membranes via hydroxide ions, causing lysis and necrosis. While acids form a barrier of coagulated proteins that limits damage to the surface (except for strong acids and hydrofluoric acid), alkalis do not form such a barrier and penetrate deep into the cornea and anterior chamber within a short time. Ammonia penetrates the cornea instantly, and sodium hydroxide reaches the anterior chamber within minutes, causing iritis, traumatic cataract, and secondary glaucoma.
In mild cases, conjunctival injection and partial corneal epithelial defect are observed. In severe cases, the entire cornea becomes white and opaque, and if conjunctival necrosis is present, it appears white and edematous without injection. This finding may appear mild at first glance, so caution is needed.
Evaluation of corneal epithelial defect with fluorescein staining is an essential test. However, if the corneal and conjunctival epithelium is extensively damaged, the entire area may stain uniformly and faintly, making it appear as if there is no epithelial defect, so caution is needed to avoid underestimation.
As complications specific to alkali, iritis, traumatic cataract, and acute glaucoma due to anterior chamber penetration can occur from the acute phase. In the cicatricial phase, the following complications become problematic.
| Phase | Main Complications |
|---|---|
| Acute phase | Corneal epithelial defect, corneal stromal edema/opacity, anterior chamber inflammation, high intraocular pressure |
| Reparative phase | Persistent corneal epithelial defect, corneal melting |
| Scarring phase | Symblepharon, pseudopterygium, corneal neovascularization, corneal opacity, conjunctival fornix shortening |
In severe alkali injury, extensive necrosis of the conjunctiva occurs, and conjunctival vessels are also damaged. Necrotic tissue appears white and edematous, presenting a white appearance without hyperemia. This can easily lead to a misjudgment that “no hyperemia = mild case.” In reality, it indicates extensive ischemia including limbal vessels, suggesting a poor prognosis.
The degree of penetration of alkaline substances depends on the type of agent, pH, concentration, contact time, and area of injury.
Ammonia has particularly high tissue permeability, instantly penetrating the corneal stroma and reaching the anterior chamber. Sodium hydroxide (e.g., mold remover) also reaches the anterior chamber within minutes, damaging the corneal endothelium, iris, and lens.
Risk factors include the following:
Examination after injury proceeds according to the following flow. Eye rinsing takes priority over ophthalmological evaluation.
The Kinoshita classification is a severity classification based on the extent of residual POV (palisade of Vogt: corneal epithelial stem cell niche at the limbus), allowing prognosis estimation from slit-lamp findings at the initial visit.
| Kinoshita Classification | Findings | Prognosis |
|---|---|---|
| Grade 1 | Conjunctival hyperemia, no corneal epithelial defect | Good |
| Grade 2 | Conjunctival hyperemia, partial corneal epithelial defect | Good |
| Grade 3a | Partial conjunctival necrosis, total corneal epithelial defect, partial POV remaining | Relatively good |
| Grade 3b | Partial conjunctival necrosis, total corneal epithelial defect, complete loss of POV | Poor |
| Grade 4 | Limbal conjunctival necrosis over half the circumference, total corneal epithelial defect, complete loss of POV | Poor |
The Roper-Hall classification is a 4-grade system based on the degree of corneal opacity and the extent of limbal ischemia 1). The Dua classification further subdivides Roper-Hall Grade IV into three stages (Dua grade IV: limbal involvement 50–75%, grade V: 75–100%, grade VI: 100%) 1). Early amniotic membrane transplantation is effective in Dua grades IV and V, but its effect is limited in grade VI 1).
AS-OCTA (anterior segment optical coherence tomography angiography) is useful for evaluating limbal ischemia. Clinical assessment alone tends to underestimate the extent of limbal ischemia, and objective evaluation with AS-OCTA improves the accuracy of prognosis prediction 2).
Severe intraocular pressure elevation may occur in the acute phase, and intraocular pressure measurement using iCare® or similar devices is necessary. If solid foreign body entry is suspected, dilated examination should be performed to check for traumatic cataract, hyphema, and retinal detachment.
The Kinoshita classification focuses on the presence or absence of residual POV (corneal epithelial stem cell niche) and directly reflects the potential for epithelial regeneration, making it superior for prognosis prediction. The distinction between Grade 3a and 3b (residual POV vs. complete loss) greatly influences treatment strategy. The Roper-Hall classification is an international 4-grade system combining the degree of corneal opacity and the extent of limbal ischemia, while the Dua classification further subdivides Roper-Hall Grade IV into three severity levels to aid in determining surgical treatment indications 1).
The severity and healing time of alkali burns can be reduced by immediate copious irrigation. The time to initial irrigation significantly affects visual prognosis.
The treatment strategy based on severity is shown below.
Grade 1–2 (Mild to Moderate)
Antibiotic eye drops: Use new quinolone eye drops to prevent infection.
Steroid eye drops: Topical administration of 0.1% betamethasone etc. to suppress inflammation.
Mydriatics: Atropine sulfate eye drops to prevent iritis and reduce pain.
Prognosis: In most cases, healing occurs with topical medications alone, and the prognosis is good.
Grade 3b–4 (Severe)
Systemic steroids: Administer intensively for about 1 week, then taper.
Management of elevated intraocular pressure: Intravenous hyperosmotic agents, oral carbonic anhydrase inhibitors, and glaucoma eye drops.
Promotion of epithelial regeneration: Use of protective soft contact lenses (SCL), insertion of punctal plugs
Caution: Do not use NSAID eye drops as they delay epithelial repair
Acute phase (from injury to several weeks):
Removal of necrotic tissue and amniotic membrane transplantation (to reduce inflammation and promote epithelialization) are performed. Tenonplasty is a procedure that advances Tenon’s capsule to the limbus to restore vascular supply in cases of limbal and scleral ischemia, and is useful as an eye-preserving surgery in severe chemical trauma 2). The postoperative re-epithelialization rate is high, but symblepharon is the most common complication 2).
Subacute phase / Scarring phase (Grade 3a):
If limbal function is preserved, the corneal and conjunctival epithelium regenerates, sometimes with resolution leaving pseudopterygium or corneal opacity. Amniotic membrane covering may be performed to promote early epithelialization.
Scarring phase (Grade 3b and 4):
In severe cases with complete loss of limbal epithelium, limbal function disappears and conjunctival epithelium invades the cornea. Persistent corneal epithelial defects may lead to corneal melting and perforation. The following ocular surface reconstruction procedures are required.
Chronic phase (persistent epithelial defect for more than 1 month after injury):
If corneal opacity remains in the cicatricial stage, superficial or full-thickness corneal transplantation is performed when the opacity is limited to the central area and the POV is partially preserved. If the POV has completely disappeared and the corneal surface is covered by conjunctival tissue, the ocular surface is reconstructed with KEP, limbal transplantation, and amniotic membrane transplantation before corneal transplantation. To avoid endothelial rejection, DALK (deep anterior lamellar keratoplasty) is recommended whenever possible.
For bilateral severe chemical trauma, a one-stage surgery using femtosecond laser-assisted large-diameter lamellar keratolimbal transplantation, which simultaneously transplants limbal stem cells and corneal stroma, has been reported, achieving good visual improvement 3).
At the scene, irrigation should continue for at least 20 minutes, and as long as possible is desirable. For severe alkali trauma, irrigation for 30 minutes or more is performed even after ophthalmological consultation. Tap water is readily available but hypotonic; therefore, isotonic solutions such as saline or lactated Ringer’s solution are recommended for irrigation in ophthalmology. Irrigation is a priority over ophthalmological evaluation, and whether sufficient irrigation has been performed before arrival significantly affects the prognosis.
The severity of chemical trauma depends on the type of agent, pH, concentration, contact time, and area of injury.
Alkaline substances saponify the lipids of cell membranes via hydroxide ions, causing cell lysis and necrosis. They dissolve proteins and reach deep into the cornea, thus causing damage deeper than acids. Since they do not form a barrier of coagulated proteins, they penetrate deep into the corneal stroma and anterior chamber within a short time.
Alkali that penetrates into the anterior chamber causes iritis, traumatic cataract, and acute glaucoma (severe intraocular pressure elevation in the acute phase). Ammonia is particularly permeable and penetrates the cornea instantly, while sodium hydroxide reaches the anterior chamber within minutes.
The degree of damage to the corneal epithelial stem cells located in the palisades of Vogt (POV) of the limbus determines the prognosis.
As conjunctivalization progresses, mucin deficiency due to goblet cell damage, tear film instability, symblepharon, and conjunctival sac shortening further worsen the ocular surface environment. Limbal ischemia increases the risk of limbal stem cell deficiency (LSCD), leading to corneal scar formation and permanent visual impairment 2).
In difficult cases, even ocular surface reconstruction surgery is often challenging, and immediate irrigation after injury followed by appropriate treatment are key factors determining the prognosis of the ocular surface.
AS-OCTA objectively quantifies limbal ischemia in the acute phase of chemical injury, allowing more accurate assessment of ischemic areas that are often underestimated by clinical evaluation alone. It correlates well with final visual prognosis, and integration into existing severity classification systems is expected2).
Femtosecond laser-assisted large-diameter lamellar corneal limbal transplantation is a procedure that can transplant limbal stem cells and corneal stroma in one step for severe bilateral chemical injuries. Compared with conventional manual dissection, it enables uniform lamellar dissection, and good visual improvement has been reported3).
The application of femtosecond laser is limited in case numbers, and further research is needed to establish long-term efficacy3). Standardization of AS-OCTA and its incorporation into severity classification systems remain future challenges2).
