Chemical injury (alkali burn) is a condition in which the cornea and conjunctiva are damaged by alkaline chemicals entering the eye. It is one of the most urgent ophthalmic emergencies, and immediate response 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 a bimodal peak including 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 often reach Roper-Hall Grade IV severity, and ammonia-related assaults have been reported to result in the worst outcomes 1).
The main causative substances of alkaline materials are shown below. Note that even household products can cause severe eye injury.
| 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 acidic substances, alkalis saponify lipids and cause cell lysis and necrosis. Since they do not form a barrier of coagulated proteins, they have high deep penetration and can reach the anterior chamber, causing iritis, cataract, and glaucoma. Therefore, alkali injuries tend to cause more severe damage overall than acid injuries.
Alkalis saponify cell membrane lipids 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 defects are observed. In severe cases, the entire cornea appears white and opaque, and with conjunctival necrosis, it may appear white and edematous without injection. This finding can appear mild at first glance, so caution is needed.
Evaluation of corneal epithelial defects with fluorescein staining is an essential examination. However, when the corneal and conjunctival epithelium is extensively damaged, the entire area may stain thinly and uniformly, making it appear as if there are no epithelial defects, so caution is needed to avoid underestimation.
Alkali-specific complications include iritis, traumatic cataract, and acute glaucoma due to anterior chamber penetration, which can occur from the acute phase. During the cicatricial phase, the following complications become problematic.
| Stage | Main complications |
|---|---|
| Acute phase | Corneal epithelial defect, corneal stromal edema/opacity, anterior chamber inflammation, elevated intraocular pressure |
| Reparative phase | Persistent corneal epithelial defect, corneal melting |
| Scarring phase | Symblepharon, pseudopterygium, corneal neovascularization, corneal opacity, conjunctival sac shortening |
In severe alkali injury, extensive conjunctival necrosis occurs, and conjunctival vessels are also damaged. The 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, penetrating the corneal stroma instantly and reaching the anterior chamber. Sodium hydroxide (e.g., in mold removers) also reaches the anterior chamber within minutes, damaging the corneal endothelium, iris, and lens.
Risk factors include the following:
Examination after injury proceeds as follows. Eye irrigation takes priority over ophthalmological evaluation.
The Kinoshita classification is a severity classification based on the extent of remaining POV (palisade of Vogt: corneal epithelial stem cell niche at the limbus), allowing prognosis estimation from slit-lamp findings at the initial examination.
| Kinoshita Classification | Findings | Prognosis |
|---|---|---|
| Grade 1 | Conjunctival injection, no corneal epithelial defect | Good |
| Grade 2 | Conjunctival injection, 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 involving more than 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 grades (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 benefit 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 can occur in the acute phase, and intraocular pressure measurement using devices such as iCare® 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 vs. complete loss of POV) 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 grades 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 from injury to initial irrigation significantly affects visual prognosis.
The drug treatment strategy according to 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 or similar 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: Prescribe intravenous hyperosmotic agents, oral carbonic anhydrase inhibitors, and glaucoma eye drops.
Promotion of epithelial regeneration: Use of protective soft contact lenses (SCL), punctal plug insertion
Caution: Do not use NSAID eye drops as they delay epithelial healing
Acute phase (from injury to several weeks):
Necrotic tissue removal 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 trauma2). The postoperative re-epithelialization rate is high, but symblepharon is the most common complication2).
Subacute phase and cicatricial phase (Grade 3a):
If limbal function is preserved, the corneoconjunctival epithelium regenerates, sometimes resolving with residual pseudopterygium or corneal opacity. Amniotic membrane covering may be performed to promote early epithelialization.
Cicatricial phase (Grade 3b and 4):
In severe cases with complete loss of limbal epithelium, limbal function is lost, and conjunctival epithelium invades the cornea. Persistent corneal epithelial defects may lead to corneal melting and perforation. In the cicatricial phase, the following ocular surface reconstruction procedures are considered.
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 if the opacity is limited to the central area and some POV is preserved. If POV is completely lost and the corneal surface is covered by conjunctival tissue, corneal transplantation is performed after reconstructing the ocular surface with KEP, limbal transplantation, or amniotic membrane transplantation. To avoid endothelial rejection, DALK (deep anterior lamellar keratoplasty) may be selected in some cases.
For bilateral severe chemical trauma, a one-stage procedure using femtosecond laser-assisted large-diameter lamellar keratolimbal transplantation for simultaneous transplantation of limbal stem cells and corneal stroma has been reported, achieving good visual improvement3).
At the scene, it is desirable to continue for at least 20 minutes and as long as possible. For severe alkali injuries, irrigation should be continued for 30 minutes or more even after ophthalmological consultation. Tap water is readily available but hypotonic; therefore, isotonic solutions such as normal saline or lactated Ringer’s solution are recommended for irrigation in ophthalmology. Irrigation should take priority over ophthalmological evaluation, and whether sufficient irrigation has been performed before arrival significantly affects the prognosis.
The severity of chemical injury depends on the type of agent, pH, concentration, contact time, and extent of injury.
Alkaline substances saponify the lipids of cell membranes via hydroxyl ions, causing cell lysis and necrosis. They dissolve proteins and reach the deep cornea, causing more severe damage 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 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 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 scarring and permanent visual impairment2).
In difficult cases, ocular surface reconstruction 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 tend to be underestimated by clinical evaluation alone. It also correlates well with final visual prognosis, and integration into existing severity classification systems is anticipated 2).
Femtosecond laser-assisted large-diameter lamellar keratolimbal transplantation is a surgical technique that allows simultaneous transplantation of limbal stem cells and corneal stroma in a single stage for severe bilateral chemical trauma. Compared to conventional manual dissection, it enables uniform lamellar dissection, and good visual improvement has been reported3).
Femtosecond laser applications are limited in the number of cases, and further research is needed to establish long-term efficacy 3). Standardization of AS-OCTA and its incorporation into severity classification systems remain future challenges 2).
