Evaluation of demographic feature and Consequences and Complications of Abuse of Topical Anesthetic Drops and Response to Treatment in Patients with Ocular disorders referred to the ophthalmology

doi:10.21203/rs.3.rs-4965800/v1

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Evaluation of demographic feature and Consequences and Complications of Abuse of Topical Anesthetic Drops and Response to Treatment in Patients with Ocular disorders referred to the ophthalmology

https://doi.org/10.21203/rs.3.rs-4965800/v1

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Objective: Topical anesthetic drops are extensively employed in ophthalmology, commonly utilized during foreign object removal and eye surgeries. The improper application of these local anesthetics can lead to severe complications, including blindness.

Material and Methods: This cross-sectional study included all patients with complaints of foreign body sensation, exposure to ultraviolet rays, or misuse of local anesthetic eye drops referred to the ophthalmology emergency department at Sina Hospital in Hamadan from March to September 2020. After obtaining consent, each participant completed a questionnaire, providing information aligned with the research objectives, overseen by an ophthalmologist. Patients experiencing complications from the misuse of anesthesia drops received appropriate treatment and underwent a 1-month follow-up. The collected data were subsequently analyzed using SPSS 21 software.

Results: In this study, 192 patients (185 men and 7 women) were enrolled, with an average age of 42.69 ± 12.45 years. Among them, 76.56% presented with foreign body complaints in the eye. The most prevalent symptoms were lacrimation (84.37%) and photophobia (73.95%). Before seeking medical attention, a majority of patients had employed non-medical methods, notably eye closure (63.15%) and tea application (45.31%). Recommendations from pharmacy staff (38.27%) and colleagues (33.33%) were most frequently cited as sources of familiarity. Gender (P = 0.37) and education (P = 0.21) showed no correlation with the frequency of tetracaine abuse. Tetracaine abuse was more frequent among those with a history of previous use (P < 0.001). Patients who abused tetracaine exhibited a higher rate of ocular complications, including keratopathy and vision loss (P = 0.011).

Conclusion: A significant number of patients resort to local anesthetic drops based on non-specialist recommendations. The prevalence of local anesthetic use is consistent across genders and education levels, with awareness of side effects not acting as a deterrent. The arbitrary use of local anesthetics elevates the risk of ocular complications, including keratopathy and vision loss.

Tetracaine

Complications

Demographics

Local Anesthesia Drops

Pain resulting from corneal scratches due to foreign bodies or trauma is a common complaint in the Emergency Department (ED). Common therapeutic interventions for these patients include the use of local anesthetic drops such as tetracaine and the removal of foreign bodies if present. Subsequently, patients can be sent home with oral pain relievers, topical non-steroidal anti-inflammatory drops, and topical antibiotics (1–2).

Carl Koller, an Austrian ophthalmologist, used topical cocaine for glaucoma surgery in 1884, introducing local anesthesia to modern medicine. This advancement revolutionized medical and surgical practices, but the widespread use of these substances quickly revealed their potential for serious toxicity, misuse, and addiction. These side effects prompted efforts to search for safer and more effective drugs. Many local anesthetics have since been developed and are still widely used for topical prescription (3).

Topical anesthetics have been used in ophthalmology for over a century and are increasingly employed in eye examinations and surgeries. The most common drugs in this category include Benoxinate, Tetracaine, Cocaine (Proparacaine), Proxymetacaine (Oxybuprocaine), and Lidocaine (4). Tetracaine is more commonly used in Iran and North America, while Proparacaine is more prevalent in Europe. Tetracaine has been reported to have up to five times the corneal effect of Proparacaine. These two topical anesthetics have a rapid onset (10–20 seconds) and a short duration of action (10–15 minutes), working by disrupting sodium transfer across neuronal membranes, stabilizing the membrane potential, and preventing action potential generation and pain blockade (5).

Topical anesthetic eye drops are primarily used in emergency departments, providing exceptional pain relief for painful eyes. Additionally, these drugs are used without prescriptions for immediate ocular relief (6, 7). In cases of foreign body eye injuries, affected patients may resort to obtaining drugs illegally, where these eye drops are readily available for relieving eye pain, sensation of a foreign body, and alleviating eye discomfort (6, 7). Most patients misuse these drugs following keratitis due to ultraviolet keratopathy (UVK) or removal of corneal foreign bodies (8).

While topical anesthetics are generally considered safe, rare side effects may occur. Balanced prescription for specific diagnoses, along with careful clinical monitoring of treatment effects, can minimize risks. Nevertheless, self-administration of these drugs may lead to more harm than benefit (9). The systemic and non-systemic effects of topical anesthetics can directly and indirectly impact epithelial cells, desmosomes, cellular structures, and keratocytes (11–12). Non-systemic effects may include the loss of microvilli, leading to instability of the tear film, resulting in corneal dryness, prevention of epithelial regeneration, and subsequent creation of a stable, resistant epithelium, followed by secondary neurotrophic changes (11–12). Ring infiltration has also been observed in users of topical anesthetics, and these toxic effects improve upon discontinuation of drug use (13).

Inappropriate use of topical anesthetics can lead to serious consequences, such as epithelial defects, stromal edema, Descemet's membrane folding, stromal infiltration, corneal thinning, development of desmatocele, corneal perforation, and corneal scarring (14–15). Depending on the duration and quantity of use (number of drug applications) and individual response, ulcers may form (14). In various cases, the use of topical anesthetics has led to scarring and vascularization of the cornea, corneal opacification, and corneal perforation, resulting in corneal transplantation (15, 16, 17). In some instances, severe and progressive corneal damage has led to eye enucleation (5).

Ensuring minimal pain and discomfort in patients with eye injuries has always been one of the primary concerns of physicians. They have prescribed some drugs, such as topical anti-inflammatory, antiallergic, and artificial tear medications, to address these complaints. However, some patients who do not sufficiently improve with prescribed medications seek new alternatives (18, 19).

Self-treatment and non-specialized removal of foreign bodies from the eye using local anesthetic eye drops like tetracaine can be a dangerous method, especially when used by non-experts. Clinical evidence indicates that unauthorized use of these drops has commonly resulted in decreased vision in individuals such as welders, grinders, blacksmiths, aluminum workers, and similar professions (7, 15).

Long-term use of topical anesthetics can lead to mitotic inhibition and cellular migration, causing severe toxic keratopathy with epithelial defects, sterile focal infiltration, and stromal infiltration (15, 20). Ultimately, advanced cases may result in corneal destruction or peripheral neovascularization (21).

the clinical presentation of toxic anterior segment syndrome (TASS) from pinpoint epitheliopathy to corneal lysis and perforation is variable. Focal ring infiltrates may be mistakenly diagnosed as infectious keratitis, as they share a similar clinical image (22). After establishing the diagnosis, a negative microbial infection history is usually obtained, making the most critical therapeutic issue the improvement of epithelial defects, convincing the patient to discontinue the use of anesthetic drops, and treating concurrent inflammation. Psychiatric consultation, hospital admission, and close monitoring are usually necessary, as low pain tolerance with or without psychiatric disorders may lead these patients toward suicidal tendencies (23).

The use of these topical anesthetics can lead to uncommon side effects. Addressing these unusual side effects may involve hospitalization, oral corticosteroids, contact lens bandaging, and surgical interventions such as conjunctival flap, corneal transplantation, and keratoplasty (24–25).

his cross-sectional study was conducted on patients presenting with complaints of foreign body sensation, exposure to ultraviolet radiation, and misuse of topical anesthetic eye drops who visited the ophthalmic emergency department of Sina Hospital in Hamadan from September 2019 to September 2020. A consent form was prepared for the patients, and upon their agreement and signing of the consent form, they were enrolled in the study. Patients were questioned about their self-administered use of topical anesthetic eye drops. For each individual, a questionnaire containing information relevant to the research objectives was completed by an ophthalmologist. Demographic characteristics and background information regarding the misuse of topical anesthetic eye drops were collected. Visual acuity was determined using the Snellen chart, and examinations were performed with a slit lamp. Patients were questioned about the duration of misuse of the eye drops. All patients with complications resulting from the misuse of topical anesthetic drops were appropriately treated. To assess treatment outcomes, a follow-up examination was conducted one month later using the slit lamp and Snellen chart. The induced complications included corneal ulcer, corneal abrasion, blurred vision, conjunctival redness, tear reduction, and photophobia. For the treatment of induced complications, based on the ophthalmologist's recommendation, if symptoms were mild, treatment with appropriate antibiotics and artificial tear drops was administered for one month. In cases of severe symptoms, hospitalization in the ophthalmology ward and surgical intervention were considered if necessary. The choice of antibiotic was based on the antibiogram. Until the antibiogram results were determined, damaged eyes were treated with a drop of fluoroquinolone group eye drops (such as 0.3% ciprofloxacin) every 6 hours.

2 − 1. Data Analysis:

Data were analyzed using SPSS software version 21. A significance level of 5% was considered statistically significant. Descriptive statistics, including mean and standard deviation, were used to describe and report quantitative variables based on the normal distribution of data. For qualitative variables, ratios and percentages were provided. Independent t-test and ANOVA test were used for comparing quantitative variables between two groups and more than two groups, respectively. Additionally, the chi-square test and Fisher's exact test were employed to investigate the relationship between qualitative variables.

2–2. Research Limitations:

Lack of re-attendance of patients for follow-up and continuation of the study.

Patient dissatisfaction with discontinuation of the use of topical anesthetic eye drops.

2–3. Ethical Considerations:

Participation in the study was voluntary, and individuals entered the study if they were willing. The names and personal information of individuals were not disclosed individually and remained confidential. This study has been approved by the Research Ethics Committee of Hamadan University of Medical Sciences with the code IR.UMSHA.REC.1399.135.

This study, conducted with the aim of "determining the demographic characteristics, consequences, and side effects of the misuse of local anesthetic eye drops, and the treatment response in patients experiencing eye complications, referred to the ophthalmology clinic of Sina Hospital in Hamadan from September 98 to September 99," involved the examination of 192 patients. The average age of the patients was 12.45 ± 42.69 years, with a minimum of 18 and a maximum of 76 years. The highest frequency was observed in the age group of 30 to 39 years (36.45%), followed by 40 to 49 years (24.47%).

The most common reason for patient referral, as depicted in the following chart, was a foreign body in the eye (76.56%). Excessive tearing was the most common symptom (84.37%), followed by photophobia (73.95%) in the second position. The frequency of clinical symptoms in these patients is outlined in the following table.

Only 55 individuals (28.65%) used protective equipment during work. Of the patients, 190 (98.95%) had used one or more non-medical treatments to alleviate their problems, as detailed in the table.

Among the patients, 81 individuals (42.18%) had used tetracaine drops before seeking medical attention. Of these, 2 were female and 79 were male, and there was no statistically significant difference between genders (p = 0.37). Regarding education, 40 individuals had education below diploma, 28 had a diploma, and 13 had a bachelor's degree, with no significant difference in prevalence observed among these groups (p = 0.21).

The frequency of familiarity with tetracaine among users is presented in the table, with pharmacy recommendations (38.27%) and colleagues (33.33%) being the most common sources. The frequency of awareness of tetracaine side effects in the entire patient population was 19.27%. Among those aware of the side effects, 32.43% used tetracaine, while this figure was 44.51% among those unaware, with no significant difference (p = 0.12).

Seventy-eight individuals with a history of tetracaine use were identified, and among them, 70 individuals (89.74%) had reused tetracaine, which was statistically significant (p < 0.001). The average duration of tetracaine use was 0.90 ± 2.31 days, with the highest usage occurring 4 days before the medical visit. The frequency of use based on the duration is illustrated in the chart, with the highest frequency observed for usage over 3 days.

The frequency of eye complications in the studied population is presented in the table, indicating that 48 individuals (25%) experienced eye complications. Of the 81 individuals using tetracaine, 28 (34.56%) developed eye complications, while among the 111 non-users, 20 individuals (18.01%) suffered from complications, showing a significant difference (p = 0.007).

All patients with corneal infiltration were successfully treated with medical treatment, including topical antibiotic drops, artificial tears, oral analgesics, and cycloplegic eye drops. No patient required hospitalization or surgical treatment, including amniotic membrane use or corneal transplantation. For 4 patients, in addition to medical treatment, contact lenses were used for corneal bandaging. All 4 of these patients had a history of tetracaine use.

Corneal ulcer was the most common complication, occurring in 45 individuals (23.43%). Of the 111 individuals not using tetracaine, 20 (18.01%) developed corneal ulcers, while among the 81 tetracaine users, 25 (30.86%) were affected, with a significant difference (p = 0.029).

Ten individuals (5.2%) complained of visual impairment, with 9 of them using tetracaine. This finding was statistically significant (p = 0.002).

Out of 45 patients with corneal ulcer, 10 patients required cornea transplant and other patients recovered with medical treatment.

Table 1

Exploring the Frequency and Side Effects of Tetracaine Drops: Unveiling Patterns in Usage History, Incidence of Side Effects, Corneal Ulcers, and Complaints of Vision Loss
Using Tetracaine	Using Tetracain			Number	Complication frequency (%)	p-value
	yes		no
yes	103		11	114	9.64	0.001 >
no	8		70	78	98.74
total	111		81	42.18
	complication
	yes		no
yes	20		91	111	18.01	0.007
no	28		53	81	34.52
total	48		144	192	25
	Complaint of loss of vision
	yes	no
no	1	110		111	0.90	0.002
yes	9	72		81	11.11
total	10	182		192	5.20
	corneal ulcer
	yes	no
No	20	91		111	18.01	0.029
yes	25	56		81	30.86
total	45	147		192	23.43

In the present study, most patients were male, and the majority were in the age range of 30 to 39 years. This is consistent with the findings of Shirzadeh et al. (26), where 86.4% of patients seeking medical attention were male. Considering the serious side effects of local anesthetic eye drops, such as keratitis, corneal thinning, desmetocel, corneal opacity, corneal perforation, and even blindness, along with the young average age of these individuals and the serious economic damage caused by the impairment of this workforce, educational and corrective measures are essential to protect these patients.

According to our findings, the most common clinical symptoms in these patients were tear shedding, photophobia, congestion, and a foreign body sensation. In Shirzadeh et al.'s study (26), 55.6% of patients complained of tear shedding, which was the most common symptom. In our study, the most common reason for patients' visits and the most common reason for using tetracaine eye drops was the presence of a foreign body. Similar to Erdem et al.'s study (22) and Yeniad et al.'s study (24), the most common complaint of patients misusing these drops was a foreign body sensation. Additionally, based on our findings, a small percentage of patients use protective equipment during work, highlighting the importance of further education and recommending the use of protective measures to reduce injuries in these patients.

Most of the patients in our study had used non-medical methods before seeking medical attention, with the most common being closing their eyes and rinsing with strong tea. In Aslan et al.'s study (21), the most common non-medical treatment was the use of potatoes (22%), followed by rin sing with strong tea (17%), and the least common was closing the eyes (2%). This discrepancy between our findings and theirs emphasizes the importance of increased education and discouragement of the use of such unscientific methods in these patients.

Regarding the relationship between patients' gender and their education level with the consumption of tetracaine, no significant result was found in our study. In contrast, Sharifi et al. (8) and Aslan et al. (21) stated in their studies that the higher the level of education, the higher the use of local anesthetics, which contradicts our current findings.

Of the patients who used tetracaine in this study, 38.27% obtained it from pharmacies, and 33.33% were familiar with this drug through their colleagues. In Sharifi et al.'s study (8), most patients gained knowledge of the effectiveness of the drug from their colleagues, indicating the influence of non-specialist recommendations on drug use.

Based on our findings, the awareness of individuals about the side effects of local anesthetic drugs has no correlation with their use of these drugs. Furthermore, individuals with a history of using such drugs were more susceptible to reusing them. Therefore, there is a need to emphasize increasing awareness in these patients about the side effects of drugs and discourage self-medication.

With medical treatment, including topical antibiotic drops, artificial tears, oral analgesics, and cycloplegic drops, all patients with corneal infiltration were successfully treated. No patient required hospitalization or surgical treatment, such as amniotic membrane use or corneal transplantation. For four patients, in addition to medical treatment, contact lenses were used for corneal dressing. All four of these patients had a history of tetracaine use.

Our findings indicate that the use of tetracaine in these patients increases the risk of eye complications such as corneal ulcers and visual impairment. Similar to our study, Waldman et al. (27) and Pharmakakis et al. (15) demonstrated that misuse of local anesthetic drugs leads to an increase in complications in these patients. Therefore, measures should be taken to reduce self-medication in this regard.

Based on our findings, the most common reason for these patients to seek medical attention is complaints of a foreign body sensation, with the most prevalent clinical finding being tear shedding and photophobia. The majority of these individuals resort to self-administering non-medical methods for treatment. A significant number of these patients, influenced by non-specialist recommendations, use local anesthetic eye drops on their own. The prevalence of self-administration of local anesthetics is similar across genders and different educational levels, and awareness of the side effects of these drugs does not deter their usage in these individuals. Self-administration of local anesthetic drugs leads to an increase in ocular complications, including keratopathy and visual impairment.

Ethics approval and consent to participate:

Consent for publication

Not applicable.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Competing interests:

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding:

This study was supported by internal funding. All authors read and approved the final manuscript.

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We thank all the people who have helped us in this way

Babineau MR, Sanchez LD. Ophthalmologic Procedures in the Emergency Department. Emergency Medicine Clinics of North America. 2008;26(1):17-34.
Thyagarajan SK, Sharma V, Austin S, Lasoye T, Hunter P. An audit of corneal abrasion management following the introduction of local guidelines in an accident and emergency department. Emergency Medicine Journal. 2006;23(7):526-9.
Calatayud J, González Á. History of the development and evolution of local anesthesia since the coca leaf. Anesthesiology: The Journal of the American Society of Anesthesiologists. 2003;98(6):1503-8.
McGee HT, Fraunfelder F. Toxicities of topical ophthalmic anesthetics. Expert Opinion on Drug Safety. 2007;6(6):637-40.
Rosenwasser GO, Holland S, Pflugfelder SC, Lugo M, Heidemann DG, Culbertson WW, et al. Topical anesthetic abuse. Ophthalmology. 1990;97(8):967-72.
Swaminathan A, Otterness K, Milne K, Rezaie S. The Safety of Topical Anesthetics in the Treatment of Corneal Abrasions: A Review. Journal of Emergency Medicine. 2015;49(5):810-5.
Puls HA, Cabrera D, Murad MH, Erwin PJ, Bellolio MF. Safety and Effectiveness of Topical Anesthetics in Corneal Abrasions: Systematic Review and Meta-Analysis. Journal of Emergency Medicine. 2015;49(5):816-24.
Sharifi A, Mokhtari M, Hosein Esmaeili H, Sarafi Nejad A. Prevalence of Abuse of Ophtalmic Anesthetic Drops among Welders in Kerman City (2007). 2015.
Sharifi A, Sharifi H, Karamouzian M, Mokhtari M, Esmaeili HH, Nejad AS, et al. Topical ocular anesthetic abuse among Iranian welders: time for action. Middle East African journal of ophthalmology. 2013;20(4):336.
Varga JH, Rubinfeld RS, Wolf TC, Stutzman RD, Peele KA, Clifford WS, et al. Topical anesthetic abuse ring keratitis: report of four cases. Cornea. 1997;16(4):424-9.
Peyman G, Rahimy M, Fernandes M. Effects of morphine on corneal sensitivity and epithelial wound healing: implications for topical ophthalmic analgesia. British journal of ophthalmology. 1994;78(2):138-41.
Catterall WA, Mackie K. Local anesthetics. Goodman & Gilman's the pharmacological basis of therapeutics: McGraw-Hill, New York (NY); 2011. p. 565-82.
Sutphin J, Dana R, Florakis G. Section 8: External disease and cornea. San Francisco, CA: American Academy of Ophthalmology. 2009;2010:240-1.
Pharmakakis N, Katsimpris J, Melachrinou M, Koliopoulos J. Corneal complications following abuse of topical anesthetics. European journal of ophthalmology. 2002;12(5):373-8.
Ardjomand N, Faschinger C, Haller-Schober E-M, Scarpatetti M, Faulborn J. A clinico-pathological case report of necrotizing ulcerating keratopathy due to topical anaesthetic abuse. Der Ophthalmologe. 2002;99(11):872-5.
Sugar A. Topical anesthetic abuse after radial keratotomy. Journal of Cataract & Refractive Surgery. 1998;24(11):1535-7.
Verma S, Marshall J. Control of pain after photorefractive keratectomy. Journal of Refractive Surgery. 1996;12(3):358-431.
Ball IM, Seabrook J, Desai N, Allen L, Anderson S. Dilute proparacaine for the management of acute corneal injuries in the emergency department. Canadian Journal of Emergency Medicine. 2010;12(5):389-94.
Chen H-T, Chen K-H, Hsu W-M. Toxic keratopathy associated with abuse of low-dose anesthetic: a case report. Cornea. 2004;23(5):527-9.
Aslan L, Sucakli MH, Bozkurt S, Aslankurt M, Aksoy A, Celik M. Use of topical anesthetic and non-medical alternatives in welding workers regarding ophthalmic problems. Cutaneous and ocular toxicology. 2014;33(2):150-3.
Erdem E, Undar IH, Esen E, Yar K, Yagmur M, Ersoz R. Topical anesthetic eye drops abuse: are we aware of the danger? Cutaneous and ocular toxicology. 2013;32(3):189-93.
Epstein DL, Paton D. Keratitis from misuse of corneal anesthetics. New England Journal of Medicine. 1968;279(8):396-9.
Yeniad B, Canturk S, Esin Ozdemir F, Alparslan N, Akarcay K. Toxic keratopathy due to abuse of topical anesthetic drugs. Cutaneous and Ocular Toxicology. 2010;29(2):105-9.
tetracaine abuse: Management guidelines. Iranian Red Crescent Medical Journal. 2011;13(1):55.
Goldich Y, Zadok D, Avni I, Hartstein M. Topical anesthetic abuse keratitis secondary to floppy eyelid syndrome. Cornea. 2011;30(1):105-6.
Shirzadeh E, Shomoossi N, Abdolahzadeh H. Topical anesthetic misuse in patients admitted to Sabzevar Eye Clinic in Iran. Acta facultatis medicae Naissensis. 2016;33(4):287-94.
Waldman N, Winrow B, Densie I, Gray A, McMaster S, Giddings G, et al. An observational study to determine whether routinely sending patients home with a 24-hour supply of topical tetracaine from the emergency department for simple corneal abrasion pain is potentially safe. Annals of emergency medicine. 2018;71(6):767-78.

No competing interests reported.

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Evaluation of demographic feature and Consequences and Complications of Abuse of Topical Anesthetic Drops and Response to Treatment in Patients with Ocular disorders referred to the ophthalmology

Status:

Version 1

Abstract

Introduction

Methods

2 − 1. Data Analysis:

2–2. Research Limitations:

2–3. Ethical Considerations:

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1