Topical anesthetic abuse keratopathy: an overlooked occupational eye health concern

Abstract

Background

Topical anesthetic abuse keratopathy is a rare but potentially devastating complication that may lead to irreversible vision loss. In occupational settings, workers who sustain frequent ocular injuries may self-administer topical anesthetics without prior prescription, consequently increasing the risk of severe complications. This study evaluated the clinical findings and visual outcomes of patients with this condition.

Methods

All patients diagnosed with topical anesthetic abuse keratopathy who presented to Khalili Hospital, Shiraz, Iran, from March 2023 to March 2025 were included. Demographics, duration of abuse, risk factors, microbial culture results, treatments, and corrected distance visual acuity (CDVA) at admission and three-month follow-up were analyzed.

Results

Thirteen patients (14 eyes; mean age, 43.15 years; 12 males, 1 female) were included. The median duration of abuse was 8.5 days (IQR = 2). Occupational exposures were the primary risk factors, including welding (5/13, 38.5%), metal grinding (3/13, 23.1%), construction work (2/13, 15.4%), and plumbing (2/13, 15.4%). Additionally, one case (1/13, 7.7%) had a history of drug abuse. Cultures were negative in 7 cases (53.8%); positive results included Staphylococcus aureus (3/13, 23.1%), Staphylococcus epidermidis (3/13, 23.1%), and Streptococcus pneumoniae (1/13, 7.7%). Following topical anesthetic cessation, all patients received supportive therapy with lubricants and broad-spectrum antibiotics. Four patients (30.8%) required hospitalization, and one (7.7%) with a history of drug abuse developed corneal perforation. The proportion of eyes with Snellen visual acuity ≥ 5/10 increased from 2/14 at baseline to 12/14 at follow-up. Median CDVA improved significantly from 0.61 (IQR 0.50) to 0.154 (IQR 0.125) LogMAR at 3 months (p < 0.001).

Conclusions

Topical anesthetic abuse keratopathy is a serious public health concern with potential complications such as infectious keratitis and corneal perforation. Public education, workplace protection, and stricter regulations are essential to reducing the burden of this vision-threatening disorder.

Trial registration

Not applicable.

Introduction

Topical anesthetics are one of the most widely used pharmacologic agents in ophthalmic practice in some regions of the world, with applications ranging from outpatient management of simple corneal abrasions to major surgical procedures, such as cataract surgery under topical anesthesia [1, 2]. The common analgesic agents used in ophthalmological practice include tetracaine, proparacaine, and oxybuprocaine, with concentrations ranging from 0.4% to 0.5% [3]. Topical anesthetic abuse keratopathy is a rare but devastating complication of topical anesthetics abuse that may lead to secondary infectious keratitis, descemetocele, corneal perforation, endophthalmitis, and even irreversible blindness and evisceration [4–6].

It has reported that affected patients typically present with increasing ocular pain, reduced vision, photophobia, and/or tearing [7, 8]. On examination, findings may include corneal epithelial defects, ring-shaped corneal infiltrates, descemet folding, corneal haze, corneal edema, and hypopyon [7, 8]. However, these clinical manifestations mimic other ophthalmic disorders, particularly infectious keratitis such as Acanthamoeba keratitis and herpes simplex virus keratitis [6, 9, 10], which may make accurate and timely diagnosis challenging. Nevertheless, misdiagnosis and delayed cessation of topical anesthetics in affected individuals, may increase the risk of poorer outcomes [6, 7].

Occupational ocular injuries accounts for approximately 3–4% of all occupational injuries [11]. High-risk jobs such as welding and grinding are particularly associated with foreign-body injuries [12]. In response to repeated ocular trauma and following sever ocular pain, workers may self-administer topical anesthetics without prior prescription, which may lead to severe complications such as toxic keratopathy and irreversible visual impairment [8].

Moreover in developing countries, the widespread misuse of topical anesthetics has been attributed to feasible over-the-counter availability, insufficiently of strict regulation, and limited awareness among public and healthcare providers [13].

Given these concerns, and the fact that this condition remains under documented public health issue, further investigation is needed. This study presents a case series of patients with toxic keratopathy following topical anesthetic abuse, highlighting their clinical characteristics, management strategies, and visual outcomes, with the aim of enhancing awareness among healthcare providers, policymakers, and, public to emphasize the urgent need for preventive strategies.

Methods

This study adhered to the principles of the Declaration of Helsinki, and its protocol was approved by the Ethics Committee of Shiraz University of Medical Sciences, Shiraz, Iran. Written informed consent was obtained from all participants prior to the study.

This retrospective case series study included all patients with a confirmed diagnosis of toxic keratopathy after topical anesthetic abuse who were treated in the ophthalmology department of the Khalili hospital, Shiraz, Iran between March 2023 to March 2025 and had a minimum of 3 months of documented follow-up findings. The exclusion criteria included patients without history of topical anesthetic abuse, with history of hereditary corneal disorders and those with less than three months of follow-up results.

We investigated the clinical characteristics and visual outcomes of post topical anesthetic abuse keratopathy. The following data were retrieved from the health information system of our center and reviewed and analyzed: patient age, gender, affected eye, topical anesthetic abuse time, the microbial culture results, treatments, and corrected distance visual acuity (CDVA) at presentation, and 3 months follow-up.

The diagnosis of topical anesthetic abuse induced was defined as a history of repeated or prolonged self-administration of topical anesthetic eye drops, together with slit-lamp evidence of a persistent epithelial defect and/or stromal infiltration or thinning. Typical features included ring-shaped infiltrates, paracentral thinning with a central clear zone, markedly reduced corneal sensation, and, as a supportive finding, lack of epithelial healing during continued anesthetic use with improvement after withdrawal. Moreover, all cases underwent corneal cultures, with primary culture panels such as Sabouraud agar, Blood agar plates, and Chocolate agar.

In our center, management for these patients included prompt discontinuation of the topical anesthetic, broad-spectrum topical antibiotic therapy, and supportive treatment with frequent preservative-free artificial tears.

CDVA was measured using the Snellen chart and subsequently converted to logMAR values for statistical analysis. Visual acuity levels of count fingers (CF), hand motion (HM), light perception (LP), and no light perception (NLP) were assigned logMAR equivalents of 1.8, 2.3, 2.8, and 3.0, respectively.

Descriptive statistics were applied to summarize demographic, clinical, and management data. The Wilcoxon signed-rank test was employed to compare CDVA before and after treatment. All analyses were conducted using SPSS software (Version 21).

Results

Fourteen eyes from 13 patients with diagnosis of topical anesthetic abuse keratopathy included in this study (Table 1).

Table 1.

Demographics and clinical features of patients

sex	age	eye	VA initial		VA follow-up		Topical anesthetic use duration (day)	smear/culture result	Hospitalization	Treatment	risk factor
			Snellen	Logmar	Snellen	Logmar
m	42	os	0.1	1	0.7	0.154	7	staph epidermis	no	levofloxacin	Welder
m	48	od	0.3	0.522	0.8	0.096	8	neg	no	ofloxacin	Mason
m	51	od	0.4	0.397	0.8	0.096	9	neg	no	ofloxacin	Machinist
f	36	os	0.2	0.698	0.6	0.221	6	staph epidermis	yes	ceftazdidime/vancomycin	Welder
m	43	os	0.2	0.698	0.6	0.221	10	staph aureus	no	levofloxacin	Welder
m	39	od	0.3	0.522	0.7	0.154	9	staph aureus	no	levofloxacin	Machinist
m	56	od os	CF	1.8	0.1	1	8	neg	yes	ceftazdidime/vancomycin	Welder
			0.3	0.522	0.8	0.096		neg
m	37	os	0.2	0.698	0.6	0.221	8	strep pneumonia	yes	ceftazdidime/vancomycin	Mason
m	47	od	0.4	0.397	0.8	0.096	7	staph aureus	no	ofloxacin	Machinist
m	38	od	0.1	1	0.7	0.154	9	neg	no	ofloxacin	Plumber
m	40	os	0.5	0.301	1	0	10	neg	no	levofloxacin	Plumber
m	52	os	0.5	0.301	0.9	0.0457	12	staph epidermis	no	levofloxacin	Welder
m	32	od	HM	2.3	CF	1.8	10	neg	yes	ceftazdidime/vancomycin	Coexistent illicit drug misuse

CF: count fingers, HM: hand motion

Males were disproportionately represented (92.3%, 12/13) with only one patient (7.7%, 1/13) female. The mean age was 43.15 ± 7.14 years (range: 32–56 years). All patients reported that they had obtained topical anesthetics directly from local pharmacies without a prescription. The affected eye was the right eye in 6 (46.15%) patients, the left eye in another 6 (46.15%) patients, and bilateral involvement was reported in 1 (7.7%) patient. All patients showed stromal ring infiltrations on slit lamp examination (Fig. 1).

Fig. 1.

Slit-lamp images of two patients (A: a 48-year-old man, B: a 47-year-old man) with topical anesthetic abuse keratopathy showing stromal ring infiltrations

In all cases, the abused anesthetic was tetracaine 0.5% eye drops. The most common risk factors reported were occupational exposures, including welding (5 cases, 38.5%), metal grinding (3 cases, 23.1%), construction work (2 cases, 15.4%), and plumbing (2 cases, 15.4%). Additionally, one case (7.7%) had a history of intravenous drug abuse.

Positive microbiology results included Staphylococcus epidermidis (3 cases, 23.1%), Staphylococcus aureus (3 cases, 23.1%), and Streptococcus pneumoniae (1 case, 7.7%), while the remaining 7 cases (53.8%) showed negative culture findings.

The patients were treated with broad-spectrum topical antibiotic regimens, including levofloxacin (5 cases, 35.7%), ceftazidime/vancomycin (5 cases, 35.7%), and ofloxacin (4 cases, 28.6%). The median duration of topical anesthetic abuse was 8.5 (IQR: 2) days. Four patients (30.8%) required hospitalization, while the remaining nine patients (69.2%) were treated on an outpatient basis.

Based on Snellen visual acuity, the proportion of eyes achieving ≥ 5/10 or better increased from 2/14 at baseline to 12/14 at follow-up. The median initial visual acuity (logMAR) was 0.61 (IQR: 0.50), which significantly improved to 0.154 (IQR: 0.125) at the 3 months follow-up visit (Wilcoxon signed-rank test, p = 0.000). Notably, only one patient with the history of drug abuse developed corneal perforation due to the poor treatment compliance as a significant complication after 3 months.

Discussion

In this study, we presented a case series of 14 eyes with corneal toxic keratopathy following topical anesthetic abuse.

It has been spoused that topical anesthetic induces toxic keratopathy results from the interplay of direct epithelial and stromal toxicity, disruption of the cytoskeleton, impairment of tear and blink reflexes [14–20].

Repeated anesthetic exposure may destabilize the plasma membranes of corneal epithelial cells, impair endothelial metabolism, and induce corneal epithelial cells degeneration [15, 21, 22]. It has shown that topical anesthetics may disrupt the actin cytoskeleton and dissociate vinculin–actin adhesion complexes, leading to impaired epithelial migration and adhesion [15, 23].

Additionally, topical anesthetics may exert direct toxic effects on keratocytes, resulting in stromal infiltration, edema, and melting, and endothelial toxicity that may manifest as pleomorphism, focal necrosis, and loss of endothelial cells with abnormal intercellular junctions [6, 14]. It has reported that dissociation of vinculin-based complexes may release antigens that trigger immune recognition and the characteristic ring stromal infiltrations in patients with topical anesthetics abuse [14, 15].

Meanwhile, topical anesthetic abuse also may decrease tear secretion by inhibiting the impulses of corneal nerve and corneal sensation, that result in reduced blink reflex, and impairment of tear film stability as well as neurotrophic ulcers and penetration of toxins into the anterior chamber [3, 21]. This impairment of the trophic function of the corneal nerves may result in intolerable pain of the insensitive cornea, that force the affected person to more frequently administration of the anesthetic and lead to a vicious cycle [24].

Patients with anesthetic toxic keratopathy may present with increasing ocular pain, tearing, photophobia, central or paracentral epithelial defects, ring infiltrations, and/or hypopyon [7]. These nonspecific clinical features may overlap with a wide spectrum of corneal conditions such as herpes simplex keratitis, fungal keratitis, bacterial keratitis, Acanthamoeba keratitis, and even atypical mycobacterial keratitis, that can make timely diagnosis challenging [3, 10, 24].

On the other hand, affected corneas are at the risk of superimposed infectious keratitis [5], perhaps due to the impairment of epithelial barrier function and promoting bacterial colonization [6]. In this regard, in our study 46.2% of cases showed positive culture results, and most common pathogens included Gram-positive cocci such as, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae. Also, fungal superinfections caused by Candida and Aspergillus species have also been reported in cases of topical anesthetic abuse keratopathy [5, 6].

However, in our series, 53.8% of the culture results were negative, this finding should be interpreted with caution. Badenoch et al. showed that topical anesthetics possessed antimicrobial activity, inhibiting microbial growth in vitro and also in vivo in an animal model [25], which may increase the possibility of false-negative results. Subsequently, patients obtaining topical antibiotics directly from pharmacies without prescription prior to presentation may have increased the rate of false-negative culture results in this study. Hence, repeat interval microbiological culture testing as well as empiric broad-spectrum antimicrobial therapy is recommended in all cases with a presumed diagnosis of topical anesthetic abuse keratopathy, in order to minimize the risk of potential superinfection [26].

The median duration of topical anesthetic abuse to presentation in this case series was 8.5 days (range 6 days to 12 days), which is slightly reduced from that reported in previous studies ranging from 9 to 18 days [6, 8, 27]. It has been observed that patients with continued and longer duration of topical anesthetic abuse often experience delayed re-epithelialization [7], which may explain the lower number of severe complications reported in our study compared to previous studies [6, 8].

It is reported that risk factors related to the development of topical anesthetic toxic keratopathy include occupational exposures, self-treatment for suppressing the postoperative pain after refractive surgeries, contact lens administration, psychiatric disorders, and substance abuse [6, 8, 13, 24, 28].

Regarding the occupational exposures, welding and construction-related activities have been described in the literature [8], may be due to the frequent occurrence of ultraviolet keratitis or foreign body related ocular injuries. Consistent with these findings, this study also showed that most affected individuals were engaged in metal and construction related occupations, with welding being the most common, followed by masonry, machining, plumbing, and carpentry, all of which involve a substantial risk of exposure to metallic or wooden fragments and dust particles. Also consistent with previous studies [7, 8], almost all of cases in our study were male, and this is likely explained by the predominance of men in occupations associated with metal and construction-related activities [29]. It is proposed that due to repeated occupational exposures to corneal foreign body injuries, these individuals may use self-treatment with topical anesthetics obtained directly from pharmacies without prescription, rather than seeking prompt ophthalmic consultation, thereby significantly increase their risk of developing topical anesthetic toxic keratopathy.

These findings underscore the importance of occupational eye safety and the routine use of protective eyewear, as well as stricter regulation of non-prescription access to topical anesthetics, as preventive interventions.

It has reported psychiatric disorders such as depression, bipolar disorder, suicidal tendency, substance abuse and Munchausen syndrome are related to the increase risk of topical anesthetic abuse [13, 26]. Poor compliance with medical advice is a further risk factor. For example, despite medical advice for cessation of topical anesthetic after diagnosis, some patients may continue to self-adminster topical anesthetics during admission [30], possibly due to poorly tolerated ocular pain or coexistent psychiatric disorders. This delays epithelial healing with poorer prognosis [30]. Comprehensive psychiatric assessment and support as well as adequate pain management should is a crucial component of the management strategy for all patients presenting with anesthetic toxic keratopathy [7, 26].

The recommended treatment strategy for anesthetic toxic keratopathy includes firstly, the immediate and early discontinuation of topical anesthetic use, adequate pain management via systemic pathways. This can substantially affect compliance and adherence to therapy, affecting the prognosis and final clinical outcomes [6, 24]. Secondly, corneal scrape to identify infective pathogens, conservative therapy with broad-spectrum topical antibiotics, and ocular lubrication [24]. Yugci et al. reported that the epithelialization period was significantly shorter in patients managed with mono-antibiotic therapy compared to those treated with combination antibiotic therapy [7]. Nevertheless, broad-spectrum coverage and repeated microbiological cultures should be considered to ensure adequate management minimize the risk of infectious complications.

The majority of patients improve with only medical therapy, and in more severe cases such as patients with persistent epithelial defects, corneal melting, corneal perforation, and persistent ocular pain, additional surgical interventions such as amniotic membrane transplantation (AMT), and keratoplasty may be required [6, 10, 30, 31]. Early AMT and autologous serum may contribute accelerate reepithelization, regenerate neurotrophy, prevent corneal scarring and improve the prognosis [10, 24].

In our study, the CDVA improved significantly at the 3-month follow-up compared to the presentation and all patients experienced visual acuity improvement. This finding is in agreement with previous studies reporting overall favorable prognosis and visual outcomes following appropriate management of topical anesthetic abuse keratopathy [6]. However, severe complications such as superinfection, corneal perforation, evisceration, and endophthalmitis may occur in cases with poor compliance, emphasizing the necessity of regular follow-up and close monitoring [6].

Nevertheless, preventive interventions play a key role for minimizing the burden of anesthetic toxic keratopathy [13]. The ease of accessibility of over-the-counter (OTC) availability of topical anesthetics in some regions of the world, with a lack of strict regulations, and insufficient public and healthcare provider awareness all increase the risk of this condition in developing countries [13]. Ideally healthcare systems should apply strict prohibition of non-prescription sales of topical anesthetics, educational campaigns aimed at both the general population and healthcare providers, and occupational safety measures such as mandatory protective eyewear for workers in high-risk occupations to address these issues [7, 13, 27].

This study has some limitations. Firstly, no psychiatric evaluation was performed in initial examinations. Secondly, advanced corneal imaging methods such as in vivo confocal microscopy or anterior segment OCT were not performed, that could have provided more detailed structural information. Thirdly, endothelial cell counts were not assessed with specular microscopy, limiting our ability to quantify potential endothelial damage. Fourth, negative culture findings should be interpreted cautiously, as these results may be affected by prior antibiotic exposure and the potential antimicrobial effects of topical anesthetics. Fifth, because patients often use topical anesthetics repeatedly in response to pain and were unable to recall the exact number of daily applications, reliable frequency data could not be obtained, limiting our ability to analyze dose-related effects of topical anesthetics. In addition, the relatively small sample size further reduces the strength of the conclusions. Finally, the relatively short follow-up period and the possibility of underreporting further limit the generalizability of our findings.

Hence, larger studies that contribute to the body of knowledge will aid in adding to the evidence of outcome measures in this serious and potentially catastrophic ocular condition.

Conclusion

Topical anesthetic abuse keratopathy is an overlooked but serious and preventable public health problem, particularly among high-risk occupational groups and individuals with psychiatric disorders. Favorable outcomes depend on the early discontinuation of the anesthetic agent and initiation of appropriate therapy, including broad-spectrum antibiotics, ocular lubrication, pain management, and psychiatric support for all patients, as well as surgical interventions in severe cases. Autologous serum and AMT may accelerate epithelial healing, provide rapid pain relief, and improve prognosis. Raising public awareness, enforcing protective strategies in the workplace, and implementing legislation to restrict over-the-counter access to topical anesthetics are critical to preventing this vision-threatening condition.

Abbreviations

CDVA

Corrected distance visual acuity

CF

Count fingers

HM

Hand motion

LP

Light perception

NLP

No light perception

AMT

Amniotic membrane transplantation

OTC

Over-the-counter

Author contributions

AA and MM conceptualized the study. MM performed the statistical analyses. The manuscript was drafted by MM, with AA, MM, AC, FR, ZK, and MR contributing to editing and revisions. All authors reviewed and approved the final manuscript.

Funding

The authors did not receive any funding for this study.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This study conducted in compliance with the ethical standards of the Human Ethics Committee of Shiraz University of Medical Sciences and in accordance with the principles of the Helsinki Declaration. Prior to participation, all individuals were thoroughly informed about the study objectives, and provided written informed consent.

Consent for publication

The participants in the study were fully informed about the goals of the study and completed the ethical consent forms.

Competing interests

The authors declare no competing interests.