Topical anesthetic abuse keratopathy is a corneal disorder caused by repeated self-administration of topical anesthetics such as tetracaine, proparacaine, oxybuprocaine, and lidocaine 1. It is one of the most destructive forms of self-inflicted ocular injury and can lead to corneal perforation and vision loss 2,6.
In 1884, Carl Koller developed topical anesthesia using an aqueous solution of cocaine. Based on inspiration from Sigmund Freud’s paper “Ueber Coca,” he first tested it on animal corneas, then on himself and a friend, marking the beginning.
Patients with addictive behaviors, healthcare workers with easy access to the drug, and those with comorbid psychiatric disorders are risk factors 3. Abuse of topical anesthetics prescribed for pain management after refractive surgery has also been reported 6. In regions where these drugs are available over the counter, cases of abuse triggered by occupational exposure, such as in welders or workers after metallic foreign body injury, are common, further increasing the risk 1,2.
After refractive surgery (such as LASIK), corneal nerves are severed, causing temporary pain. Topical anesthetics may be prescribed for postoperative pain management, and their rapid analgesic effect can lead to dependence. The frequency of use increases to reduce pain, creating a vicious cycle where corneal epithelial damage causes further pain. Inappropriate prescribing by primary care physicians or emergency doctors is also an iatrogenic factor.
Topical anesthetics are classified into amide-type or ester-type. Both block sodium channels in nerve cells, preventing the generation of action potentials and thereby stopping nerve conduction 6.
The toxic mechanism on the corneal surface involves damage to vinculin and actin filaments via a calmodulin-mediated pathway, inhibiting the migration and division of corneal epithelial cells 6.
Under electron microscopy, loss of microvilli, deposition of anesthetic on cell membranes, and increased desquamation are observed. The number of desmosomes decreases, and the tendency for cell rupture increases. Similar morphological changes have been reported in the corneal stroma and endothelium.
Preservatives such as benzalkonium chloride contained in topical anesthetics may also contribute to ocular surface toxicity.
Clinical Diagnosis
History taking: Carefully inquire about the use of topical anesthetics. Since patients often conceal use, a high index of suspicion is important.
Slit-lamp examination: Check for epithelial defects, ring-shaped stromal infiltrates, stromal edema, Descemet’s membrane folds, and hypopyon.
Corneal scraping and culture: Perform corneal scraping and culture to rule out infectious keratitis, as infiltrates and intraocular inflammation are present.
Key Points for Differential Diagnosis
Similarity to Acanthamoeba keratitis: Both conditions present with severe pain disproportionate to clinical findings, ring-shaped infiltrates, and lack of response to antibiotics. Topical anesthetic abuse keratopathy is often misdiagnosed as Acanthamoeba keratitis 3,5. The differential diagnosis of ring-shaped infiltrates is broad, including infectious (bacterial, fungal, viral), immunological mechanisms, drug toxicity, and contact lens wear 5.
Exclusion of infectious keratitis: Differentiate from bacterial, fungal, and herpetic keratitis. Negative culture and lack of response to antibiotics are diagnostic clues.
| Differential Diagnosis | Key Points for Differentiation |
|---|---|
| Acanthamoeba keratitis | Differentiate by culture/PCR, inquire about contact lens use history |
| Bacterial keratitis | Positive culture, responds to antibiotics |
| Herpetic keratitis | Dendritic ulcer, often unilateral |
Both diseases are difficult to differentiate due to similar clinical presentations. Both show severe pain disproportionate to findings, ring infiltrates, and non-responsiveness to antibiotics. Detailed inquiry about topical anesthetic use history is most important for differentiation. If Acanthamoeba is not detected by corneal scraping/culture, anesthetic abuse is strongly suspected. Being a healthcare worker, history of refractive surgery, and comorbid psychiatric disorders are also risk factors to confirm. Improvement after discontinuation of topical anesthetics serves as diagnostic treatment.
Immediate discontinuation of topical anesthetics is most important1,3. Other eye drops should also be discontinued as much as possible to remove toxicity from the ocular surface.
For pain after discontinuation of topical anesthetics, oral analgesics are used. If pain is severe, consider peribulbar, retrobulbar, or sub-Tenon’s local anesthesia.
Consider inpatient management to ensure discontinuation of drug use1. If there is underlying addictive behavior or psychiatric illness, arrange a psychiatric consultation. Katsimpris et al. reported that all 5 abuse cases had comorbid psychiatric disorders or substance abuse, making psychiatric evaluation essential3. In a study of 10 cases by Yalcin Tok et al., all patients had depression or personality disorders4.
Rule out concurrent infectious keratitis. For epithelial defects, provide epithelial protection with artificial tears or eye ointments. Steroid eye drops are usually avoided as they may promote corneal thinning.
For persistent epithelial defects or ring ulcers, amniotic membrane transplantation (AMT) has been reported to be useful for early pain relief and epithelial healing. Yalcin Tok et al. reported that AMT in 15 eyes significantly improved pain scores and mean corrected visual acuity from 0.069 to 0.334. However, many cases still have residual corneal opacity and visual loss; in a study of 31 eyes by Sharifi et al., 51.6% had visual loss, 45.2% had corneal opacity, and one eye developed corneal perforation and phthisis bulbi2. In cases of severe and irreversible corneal damage, corneal transplantation may be indicated, but visual prognosis may be poor.
Topical anesthetics damage vinculin and actin filaments via a calmodulin-mediated mechanism. This impairs the migration and division ability of corneal epithelial cells, disrupting epithelial repair mechanisms6. Normal corneal epithelial turnover cannot be maintained, leading to persistent epithelial defects.
The number of desmosomes decreases, weakening intercellular adhesion. Loss of microvilli impairs interaction with the tear film, disrupting ocular surface homeostasis.
Morphological changes also occur in the corneal stroma, causing stromal edema and ring infiltrates. Endothelial damage is clinically observed as Descemet’s membrane folds.
Corneal damage due to drug toxicity begins with punctate keratopathy and progresses stepwise to vortex keratopathy (hurricane keratopathy), epithelial crack lines, and persistent corneal epithelial defects. When limbal stem cell deficiency occurs, prognosis becomes poor due to exhaustion of corneal epithelial stem cells.
Topical anesthetics directly inhibit the migration and division of corneal epithelial cells, so repeated use disrupts the corneal epithelial repair mechanism. Because they provide rapid pain relief, dependence easily develops, leading to a vicious cycle of pain → use → epithelial damage → further pain. Severe cases present with ring infiltrates, stromal edema, and hypopyon, sometimes requiring corneal transplantation. Since they worsen corneal epithelial damage, oral analgesics should be used for pain management.
