Metavee Boonsiri, MD; Katherine C. Marks, MD; Chérie M. Ditre, MD Cosmetic Enhancement Center, Penn Medicine in Radnor, University of Pennsylvania, Radnor, Pennsylvania
Disclosure: The authors report no relevant conflicts of interest.
Abstract
Practitioners are increasingly using topical anesthetics in the field of dermatology. Application of topical anesthetics prior to performing dermatologic procedures has proven to decrease pain and discomfort associated with these procedures. Despite the prevalent use of topical anesthetics, there are few standard guidelines for about which products provide optimal and safest use. Adverse events are often correlated with improper application of topical anesthetics. A few case reports have cited adverse events related to the use of compounded products that the United States Food and Drug Administration has not approved, such as benzocaine, lidocaine, tetracaine. In this article, the authors report the possible ocular side effects due to the use of benzocaine, lidocaine, tetracaine. Careful attention must be paid to this compounded product, and better formulations are needed in order to prevent adverse events. (J Clin Aesthet Dermatol. 2016;9(3):48–50.)
Topical anesthetics are now widely used in dermatologic procedures. Application of topical anesthetics has proven to decrease pain and discomfort associated with these procedures, including cosmetic procedures, such as filler injectables, laser hair removal, and skin resurfacing with laser and light-based devices.[1],[2] To date, there are several compounded topical anesthetics available for physicians for in-office use on their patients. One of the most commonly used is benzocaine, lidocaine, tetracaine, which can vary in percent as well as rheology, namely yielding a gritty or smooth texture.[1]
However, no standard guidelines exist for optimal use, dosage, formulation, and safety of all topical anesthetics. Improper use of topical anesthetics can lead to severe consequences, including death.[1],[3],[4]
In this article, the authors report the case of corneal abrasions due to a compounded topical anesthetic: benzocaine 20%, lidocaine 8%, tetracaine 4% (BLT). The bilateral corneal abrasions occurred after skin resurfacing treatment despite the use of corneal shields throughout the procedure. The authors present this case to alert physicians to be aware of the potential for such complications and suggest the need for better formulation of these topical anesthetic creams.
Case report
A 64-year-old Caucasian woman presented for treatment of fine lines and wrinkles, seborrheic keratoses, and lower and upper eyelid dermatochalasis with marked hyperpigmentation. Full-face laser resurfacing with the Active FX™ application of the Lumenis UltraPulse® Encore™ was selected. Tetracaine 0.5% ophthalmic solution was applied to both eyes, and bacitracin ophthalmic ointment was applied to the inner surface of the Stefanovsky metallic eye shield prior to intraocular insertion. One hour prior to the procedure, a topical anesthetic compound of benzocaine, lidocaine, and tetracaine (BLT, CAP Pharmacy) 20:8:4% cream was applied to the patient’s entire face, including the upper and lower eyelids. When the BLT cream was removed, the patient noted a stinging sensation at the corner of her right eye; however, she felt that her face was sufficiently anesthetized. The laser settings used during treatment of the periorbital region were 125mJ. The shape, size, and density setting were three. The entire procedure was performed with a single pass technique. Following removal of the eye shields, the patient complained of stinging, burning, and difficulty opening her eyes. After flushing both eyes with ophthalmic normal saline continuously for 15 minutes, the patient complained of blurry vision. She was then taken to the ophthalmology department for emergency examination. Slit lamp evaluation of the eye shields found no irregularities or defects. Ophthalmologic evaluation of the patient revealed a large corneal abrasion of the right eye and severe punctate keratopathy of the left eye. Vision was 20/200 OD and 20/400 OS. Treatment consisted of tobramycin ophthalmic ointment and a headband patch to the right eye since marked skin inflammation after laser therapy made occlusion with tape difficult. Homatropine ophthalmic drops and Tylenol with codeine were given for pain. The patient had a total of three ophthalmology appointments for evaluation and treatment in the five days following injury. On her final visit, the right cornea was completely healed, while the left cornea showed persistent punctate changes. However, her final vision was back to normal with measurements of 20/40 OD and 20/80 OS. These lens changes were consistent with the patient’s past medical history of a cataract of the left eye.
Discussion
The potential mechanisms of injury responsible for the ocular changes observed in the authors’ patient could be thermal, chemical, or mechanical damage to the cornea. Although patients usually find great benefit from laser correction of photodamage, acne scars, and wrinkles, the potential for laser-induced ocular injury is a persistent concern.[5] Moreover, the water-abundant cornea is susceptible to injury with the far-infrared wavelength emitted by the CO2 laser, as both superficial corneal epithelium and deeper corneal scarring can occur with unintended laser exposure. Protection of the patient’s eyes is therefore a crucial component of any laser resurfacing procedure.[5] Figure 1 shows characteristic corneal abrasion consistent with thermal, chemical, or mechanical damage to cornea.
When laser treatment takes place on the eyelids or near the periorbital region, corneal shields, in this case metal, are typically used. Although these devices are meant to protect the patient’s eyes from injury, improper placement or preparation of the shields may result in corneal abrasion. Dislocation of the shields during treatment or transfer of thermal laser energy to the eye may also lead to corneal damage. Injury due to the retention of thermal energy within eye shields during laser skin resurfacing has been proposed.[5] Several studies have evaluated unintentional CO2 laser contact to the eye throughout such procedures, which can heat a corneal shield adequately enough to result in ocular injury.[6],[7] Plastic corneal shields showed significant thermal damage with the lasers tested in several studies. However, it was found that the metallic corneal shields did not produce enough heat transfer to cause damage to the eye.[5] Ries et al[7] found that the temperature elevation in the Stefanovsky metallic eye shield at three intensity settings (5, 10, and 20 watts of continuous energy for 10 seconds) of the CO2 laser was quite small (? T 0–5°C) due to the highly reflective surface of the shield itself.[7] Therefore, it is felt that thermal injury was not the cause of ocular injury in the authors’ patient.
There are many reports of chemical injury to the eyes leading to the development of corneal abrasions during laser resurfacing procedures.[6],[8],[9] Christian et al6 report the case of a 54-year-old woman who developed bilateral corneal ulcerations after CO2 laser resurfacing of the entire face, including the periocular region. Although metallic eye shields were in place throughout the procedure, the injury was thought to be either thermal or chemical in nature. Nevertheless, they concluded that EMLA cream (Eutectic Mixture of Local Anesthetics; lidocaine 2.5% and prilocaine 2.5%; AstraZeneca, Wilmington, Delaware) was a possible cause of corneal abrasions in their patient.[6] McKinlay et al[8] report the case of a 20-year-old woman who presented with severe conjunctival injection and extensive corneal de-epithelialization following treatment of facial scars with a flash-pump dye laser due to extravasation of EMLA cream accidentally into the eye during treatment.[8] While she felt immediate discomfort after it had entered her eye, this feeling subsided until several hours post-treatment. Since EMLA cream is a topical anesthetic, it can mask other chemical ocular injuries. Additionally, as the procedure continued under occlusion of a corneal protector, the ocular damage was likely intensified. Eaglstein also reports two patients who developed corneal abrasions from inadvertent exposure of the eye to EMLA cream prior to erbium laser resurfacing. Seepage of EMLA cream into the eyes of the patients took place either during the anesthetizing period two hours prior to the procedure or when the EMLA cream was wiped away immediately before insertion of the corneal shields. A small amount of EMLA cream may have actually gotten onto the eye during the insertion of the shields as well. Both patients complained of eye pain and burning after removal of the shields, and they eventually developed corneal abrasions consistent with chemical burns.[9]
It is most likely that the corneal damage sustained by the authors’ patient was due to seepage of topical BLT cream, which was gritty in formulation, into the eyes that was applied after the corneal shields were placed. The patient reported that she touched the corner of her eye and this in turn may be the reason it got under the shields. She could not feel the trapped gritty BLT due to her corneas being anesthetized by the tetracaine used prior to the shield placement. It was not until the shields were removed that she then felt the discomfort. The authors were able to conclude that her corneal abrasions were from the grit of the BLT and not thermal damage or chemical damage.
The authors review here how the BLT compound is formulated and the reason for the variability in the texture of the compound. In order to create the BLT compound, powdered forms of the anesthetic components are added together in an oil base. Since these powdered components have variable consistencies, the mixture is run through an ointment mill prior to distribution in an attempt to decrease the individual particle sizes. However, if the BLT components do not dissolve completely in the compound, then some of the small particles, or grit, could remain. This would leave the compound with a coarse texture, which was the case with the BLT cream used in the authors’ procedures. This coarse texture made it easy for the material to cause the corneal abrasions. Since the patient’s eyes were already anesthetized due to tetracaine ophthalmic solution use before insertion of the lens, she could not sense whether or not any of the particulate matter entered the eye. The authors speculate that a small piece of grit introduced from the BLT cream into her eyes was then occluded under the corneal protectors during the length of the procedure, which then caused a mechanical injury, resulting in further irritation to the cornea.
The authors do not believe that the pH of the BLT cream alone caused the corneal abrasion. The BLT compound had a pH of 7.6, which would indicate a slightly basic environment, but not significant enough to compare with EMLA cream, which is highly alkaline (pH 9.0) and can therefore cause severe eye injuries by saponification.[3]
It is also possible that the very high concentrations of active anesthetics in the BLT compound were responsible for the corneal injury sustained by the author’s patient. Moreover, several studies have shown that even a single application of topical anesthetic can cause harmful changes in the corneal epithelium.[3] In December 2006, the United States Food and Drug Administration (FDA) issued a press release indicating that compounded topical anesthetic creams contain high doses of local anesthetics and when these different anesthetics are combined into one product, the potential for harm from each individual anesthetic increases. Care must be used with these topical anesthetics.[4]
Local anesthetic concentrations of 0.5 to 2% are typically used in ocular formulations. For the skin, the 20:8:4% concentrations of the anesthetic comprising BLT cream are substantially higher than those used in intraocular formulations. Topical anesthetics used clinically in ophthalmologic procedures include cocaine, proparacaine, tetracaine, and lidocaine. Proparacaine and tetracaine are used to perform tonometry, to remove foreign bodies on the conjunctiva and cornea, and for superficial corneal surgery. Lidocaine is used for infiltration and retrobulbar block anesthesia. Generally, 0.5% proparacaine hydrochloride ophthalmic solution is favored over tetracaine for use as an anesthetic during ophthalmology procedures since tetracaine is known to disrupt epithelium at 0.5% concentrations.[10]
The authors hope that this article will enlighten other physicians about the care that is needed to protect the eye during such procedures, especially given the potential ocular dangers that exist. It is their recommendation that all topical anesthetics be removed carefully prior to the insertion of intraocular shields to prevent potential introduction of these agents. Further investigation and formula standardization should be considered for these compounded anesthetics since the formulations are not regulated by the FDA and may be inconsistent.
References
1. Sobanko J, Miller C, Alster T. Topical anesthetics for dermatologic procedures: a review. Dermatol Surg. 2012;38(5):709–721.
2. Alster T, Lupton J. Evaluation of a novel topical anesthetic agent for cutaneous laser resurfacing. Dermatol Surg. 2002;28(11):1004–1006.
3. Berkman S, MacGregor J, Alster T. Adverse effects of topical anesthetics for dermatologic procedures. Expert Opin Drug Saf. 2012;11(3):415–423.
4. The US FDA is warning five pharmacies to cease compounding and distributing standardized versions of topical anaesthetic creams. Reactions Weekly. 2006;NA;(1132):3.
5. Russell S, Dinehart S, Davis I, Flock S. Efficacy of corneal eye shields in protecting patients’ eyes from laser irradiation. Dermatol Surg. 1996;22(7):613–616.
6. Christian M, Cox D, Smith C, et al. Ocular damage due to chlorhexidine versus eyeshield thermal injury. Dermatol Surg. 2001;27(2):153–157.
7. Ries W, Clymer M, Reinisch L. Laser safety features of eye shields. Lasers Surg Med. 1996;18(3):309–315.
8. McKinlay J. EMLA cream-induced eye injury. Arch Dermatol. 1999;135(7):855–856.
9. Eaglstein F. Chemical injury to the eye from EMLA cream during erbium laser resurfacing. Dermatol Surg. 1999;25(7):590–591.
10. Rosenwasser G. Complications of topical ocular anesthetics. Int Ophthalmol Clin. 1989;29(3):153–158.
Metavee Boonsiri, MD; Katherine C. Marks, MD; Chérie M. Ditre, MD Cosmetic Enhancement Center, Penn Medicine in Radnor, University of Pennsylvania, Radnor, Pennsylvania
Disclosure: The authors report no relevant conflicts of interest.
Abstract
Practitioners are increasingly using topical anesthetics in the field of dermatology. Application of topical anesthetics prior to performing dermatologic procedures has proven to decrease pain and discomfort associated with these procedures. Despite the prevalent use of topical anesthetics, there are few standard guidelines for about which products provide optimal and safest use. Adverse events are often correlated with improper application of topical anesthetics. A few case reports have cited adverse events related to the use of compounded products that the United States Food and Drug Administration has not approved, such as benzocaine, lidocaine, tetracaine. In this article, the authors report the possible ocular side effects due to the use of benzocaine, lidocaine, tetracaine. Careful attention must be paid to this compounded product, and better formulations are needed in order to prevent adverse events. (J Clin Aesthet Dermatol. 2016;9(3):48–50.)
Topical anesthetics are now widely used in dermatologic procedures. Application of topical anesthetics has proven to decrease pain and discomfort associated with these procedures, including cosmetic procedures, such as filler injectables, laser hair removal, and skin resurfacing with laser and light-based devices.[1],[2] To date, there are several compounded topical anesthetics available for physicians for in-office use on their patients. One of the most commonly used is benzocaine, lidocaine, tetracaine, which can vary in percent as well as rheology, namely yielding a gritty or smooth texture.[1]
However, no standard guidelines exist for optimal use, dosage, formulation, and safety of all topical anesthetics. Improper use of topical anesthetics can lead to severe consequences, including death.[1],[3],[4]
In this article, the authors report the case of corneal abrasions due to a compounded topical anesthetic: benzocaine 20%, lidocaine 8%, tetracaine 4% (BLT). The bilateral corneal abrasions occurred after skin resurfacing treatment despite the use of corneal shields throughout the procedure. The authors present this case to alert physicians to be aware of the potential for such complications and suggest the need for better formulation of these topical anesthetic creams.
Case report
A 64-year-old Caucasian woman presented for treatment of fine lines and wrinkles, seborrheic keratoses, and lower and upper eyelid dermatochalasis with marked hyperpigmentation. Full-face laser resurfacing with the Active FX™ application of the Lumenis UltraPulse® Encore™ was selected. Tetracaine 0.5% ophthalmic solution was applied to both eyes, and bacitracin ophthalmic ointment was applied to the inner surface of the Stefanovsky metallic eye shield prior to intraocular insertion. One hour prior to the procedure, a topical anesthetic compound of benzocaine, lidocaine, and tetracaine (BLT, CAP Pharmacy) 20:8:4% cream was applied to the patient’s entire face, including the upper and lower eyelids. When the BLT cream was removed, the patient noted a stinging sensation at the corner of her right eye; however, she felt that her face was sufficiently anesthetized. The laser settings used during treatment of the periorbital region were 125mJ. The shape, size, and density setting were three. The entire procedure was performed with a single pass technique. Following removal of the eye shields, the patient complained of stinging, burning, and difficulty opening her eyes. After flushing both eyes with ophthalmic normal saline continuously for 15 minutes, the patient complained of blurry vision. She was then taken to the ophthalmology department for emergency examination. Slit lamp evaluation of the eye shields found no irregularities or defects. Ophthalmologic evaluation of the patient revealed a large corneal abrasion of the right eye and severe punctate keratopathy of the left eye. Vision was 20/200 OD and 20/400 OS. Treatment consisted of tobramycin ophthalmic ointment and a headband patch to the right eye since marked skin inflammation after laser therapy made occlusion with tape difficult. Homatropine ophthalmic drops and Tylenol with codeine were given for pain. The patient had a total of three ophthalmology appointments for evaluation and treatment in the five days following injury. On her final visit, the right cornea was completely healed, while the left cornea showed persistent punctate changes. However, her final vision was back to normal with measurements of 20/40 OD and 20/80 OS. These lens changes were consistent with the patient’s past medical history of a cataract of the left eye.
Discussion
The potential mechanisms of injury responsible for the ocular changes observed in the authors’ patient could be thermal, chemical, or mechanical damage to the cornea. Although patients usually find great benefit from laser correction of photodamage, acne scars, and wrinkles, the potential for laser-induced ocular injury is a persistent concern.[5] Moreover, the water-abundant cornea is susceptible to injury with the far-infrared wavelength emitted by the CO2 laser, as both superficial corneal epithelium and deeper corneal scarring can occur with unintended laser exposure. Protection of the patient’s eyes is therefore a crucial component of any laser resurfacing procedure.[5] Figure 1 shows characteristic corneal abrasion consistent with thermal, chemical, or mechanical damage to cornea.
When laser treatment takes place on the eyelids or near the periorbital region, corneal shields, in this case metal, are typically used. Although these devices are meant to protect the patient’s eyes from injury, improper placement or preparation of the shields may result in corneal abrasion. Dislocation of the shields during treatment or transfer of thermal laser energy to the eye may also lead to corneal damage. Injury due to the retention of thermal energy within eye shields during laser skin resurfacing has been proposed.[5] Several studies have evaluated unintentional CO2 laser contact to the eye throughout such procedures, which can heat a corneal shield adequately enough to result in ocular injury.[6],[7] Plastic corneal shields showed significant thermal damage with the lasers tested in several studies. However, it was found that the metallic corneal shields did not produce enough heat transfer to cause damage to the eye.[5] Ries et al[7] found that the temperature elevation in the Stefanovsky metallic eye shield at three intensity settings (5, 10, and 20 watts of continuous energy for 10 seconds) of the CO2 laser was quite small (? T 0–5°C) due to the highly reflective surface of the shield itself.[7] Therefore, it is felt that thermal injury was not the cause of ocular injury in the authors’ patient.
There are many reports of chemical injury to the eyes leading to the development of corneal abrasions during laser resurfacing procedures.[6],[8],[9] Christian et al6 report the case of a 54-year-old woman who developed bilateral corneal ulcerations after CO2 laser resurfacing of the entire face, including the periocular region. Although metallic eye shields were in place throughout the procedure, the injury was thought to be either thermal or chemical in nature. Nevertheless, they concluded that EMLA cream (Eutectic Mixture of Local Anesthetics; lidocaine 2.5% and prilocaine 2.5%; AstraZeneca, Wilmington, Delaware) was a possible cause of corneal abrasions in their patient.[6] McKinlay et al[8] report the case of a 20-year-old woman who presented with severe conjunctival injection and extensive corneal de-epithelialization following treatment of facial scars with a flash-pump dye laser due to extravasation of EMLA cream accidentally into the eye during treatment.[8] While she felt immediate discomfort after it had entered her eye, this feeling subsided until several hours post-treatment. Since EMLA cream is a topical anesthetic, it can mask other chemical ocular injuries. Additionally, as the procedure continued under occlusion of a corneal protector, the ocular damage was likely intensified. Eaglstein also reports two patients who developed corneal abrasions from inadvertent exposure of the eye to EMLA cream prior to erbium laser resurfacing. Seepage of EMLA cream into the eyes of the patients took place either during the anesthetizing period two hours prior to the procedure or when the EMLA cream was wiped away immediately before insertion of the corneal shields. A small amount of EMLA cream may have actually gotten onto the eye during the insertion of the shields as well. Both patients complained of eye pain and burning after removal of the shields, and they eventually developed corneal abrasions consistent with chemical burns.[9]
It is most likely that the corneal damage sustained by the authors’ patient was due to seepage of topical BLT cream, which was gritty in formulation, into the eyes that was applied after the corneal shields were placed. The patient reported that she touched the corner of her eye and this in turn may be the reason it got under the shields. She could not feel the trapped gritty BLT due to her corneas being anesthetized by the tetracaine used prior to the shield placement. It was not until the shields were removed that she then felt the discomfort. The authors were able to conclude that her corneal abrasions were from the grit of the BLT and not thermal damage or chemical damage.
The authors review here how the BLT compound is formulated and the reason for the variability in the texture of the compound. In order to create the BLT compound, powdered forms of the anesthetic components are added together in an oil base. Since these powdered components have variable consistencies, the mixture is run through an ointment mill prior to distribution in an attempt to decrease the individual particle sizes. However, if the BLT components do not dissolve completely in the compound, then some of the small particles, or grit, could remain. This would leave the compound with a coarse texture, which was the case with the BLT cream used in the authors’ procedures. This coarse texture made it easy for the material to cause the corneal abrasions. Since the patient’s eyes were already anesthetized due to tetracaine ophthalmic solution use before insertion of the lens, she could not sense whether or not any of the particulate matter entered the eye. The authors speculate that a small piece of grit introduced from the BLT cream into her eyes was then occluded under the corneal protectors during the length of the procedure, which then caused a mechanical injury, resulting in further irritation to the cornea.
The authors do not believe that the pH of the BLT cream alone caused the corneal abrasion. The BLT compound had a pH of 7.6, which would indicate a slightly basic environment, but not significant enough to compare with EMLA cream, which is highly alkaline (pH 9.0) and can therefore cause severe eye injuries by saponification.[3]
It is also possible that the very high concentrations of active anesthetics in the BLT compound were responsible for the corneal injury sustained by the author’s patient. Moreover, several studies have shown that even a single application of topical anesthetic can cause harmful changes in the corneal epithelium.[3] In December 2006, the United States Food and Drug Administration (FDA) issued a press release indicating that compounded topical anesthetic creams contain high doses of local anesthetics and when these different anesthetics are combined into one product, the potential for harm from each individual anesthetic increases. Care must be used with these topical anesthetics.[4]
Local anesthetic concentrations of 0.5 to 2% are typically used in ocular formulations. For the skin, the 20:8:4% concentrations of the anesthetic comprising BLT cream are substantially higher than those used in intraocular formulations. Topical anesthetics used clinically in ophthalmologic procedures include cocaine, proparacaine, tetracaine, and lidocaine. Proparacaine and tetracaine are used to perform tonometry, to remove foreign bodies on the conjunctiva and cornea, and for superficial corneal surgery. Lidocaine is used for infiltration and retrobulbar block anesthesia. Generally, 0.5% proparacaine hydrochloride ophthalmic solution is favored over tetracaine for use as an anesthetic during ophthalmology procedures since tetracaine is known to disrupt epithelium at 0.5% concentrations.[10]
The authors hope that this article will enlighten other physicians about the care that is needed to protect the eye during such procedures, especially given the potential ocular dangers that exist. It is their recommendation that all topical anesthetics be removed carefully prior to the insertion of intraocular shields to prevent potential introduction of these agents. Further investigation and formula standardization should be considered for these compounded anesthetics since the formulations are not regulated by the FDA and may be inconsistent.
References
1. Sobanko J, Miller C, Alster T. Topical anesthetics for dermatologic procedures: a review. Dermatol Surg. 2012;38(5):709–721.
2. Alster T, Lupton J. Evaluation of a novel topical anesthetic agent for cutaneous laser resurfacing. Dermatol Surg. 2002;28(11):1004–1006.
3. Berkman S, MacGregor J, Alster T. Adverse effects of topical anesthetics for dermatologic procedures. Expert Opin Drug Saf. 2012;11(3):415–423.
4. The US FDA is warning five pharmacies to cease compounding and distributing standardized versions of topical anaesthetic creams. Reactions Weekly. 2006;NA;(1132):3.
5. Russell S, Dinehart S, Davis I, Flock S. Efficacy of corneal eye shields in protecting patients’ eyes from laser irradiation. Dermatol Surg. 1996;22(7):613–616.
6. Christian M, Cox D, Smith C, et al. Ocular damage due to chlorhexidine versus eyeshield thermal injury. Dermatol Surg. 2001;27(2):153–157.
7. Ries W, Clymer M, Reinisch L. Laser safety features of eye shields. Lasers Surg Med. 1996;18(3):309–315.
8. McKinlay J. EMLA cream-induced eye injury. Arch Dermatol. 1999;135(7):855–856.
9. Eaglstein F. Chemical injury to the eye from EMLA cream during erbium laser resurfacing. Dermatol Surg. 1999;25(7):590–591.
10. Rosenwasser G. Complications of topical ocular anesthetics. Int Ophthalmol Clin. 1989;29(3):153–158.
