SGEM#315: Comfortably Numb with Topical Tetracaine for Corneal Abrasions

Date: January 5th, 2021 Reference: Shipman et al. Short-Term Topical Tetracaine Is Highly Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial. Annals of EM 2020 Dr. Glaucomflecken Guest Skeptic: Dr. Will Flanary is an ophthalmologist, writer, and comedian who moonlights in his free time as “Dr. Glaucomflecken” on Twitter and TikTok. Effortlessly blending humor with education, Dr. Glaucomflecken has spent the last five years informing audiences on a wide range of topics, like navigating the confusing world of over-the-counter eyedrops, the horrifying consequences of sleeping in contact lenses, and his recent experiences as a patient in the medical system. Case: A 32-year-old healthy man presents with left eye pain. He was giving his 9-month-old a hug and got poked in the eye with a sharp little fingernail.  His visual acuity is 20/20 bilaterally and he doesn’t wear corrective lenses or contact lenses. He tried some over-the-counter red eye drops that did not seem to work. In the emergency department (ED), tetracaine drops are applied prior to slit lamp examination and the pain is completely resolved. On examination, you see a vertical corneal abrasion with no evidence of ulceration and no foreign body. You prescribe antibiotic drop and prepare to discharge him home when he asks, “can I get some of those numbing drops to use at home”? Background: Even small corneal abrasions can cause significant pain because the cornea is highly innervated. The first documented use of topical ophthalmologic anesthetics was in 1818. A cocaine derivative was employed to effectively block nerve conduction in the superficial cornea and conjunctiva (Rosenwasser). A number of proposed dangers have limited the use of topical anesthetic agents for the treatment of corneal abrasion associated pain. These dangers include delayed healing secondary to mitosis inhibition and decreased corneal sensation. The latter issue is of concern because of the potential for the abrasion to progress to an ulcer without the patient noticing. Additionally, these agents may have direct toxicity to corneal epithelium with prolonged use, leading to increased corneal thickness, opacification, stromal infiltration, and epithelial defects. The fear of these complications has led to the pervasive teaching that topical anesthetics should never be used for outpatient management of corneal abrasions. This is reflected in the condemnation of their use in major Emergency Medicine textbooks, including Rosen’s and Tintinalli’s. Some of the evidence used to support the claim of local anesthetics causing corneal harm comes from case reports, animal models or local anesthetic injected directly into the anterior chamber of the eye for cataract surgery. More information on the where the no topical anesthetic use on corneal abrasions come from can be found on a REBEL EM blog post. We covered and randomized control trial by Waldman et al on topical tetracaine for simple corneal abrasions on SGEM#83. The bottom line from that episode was that tetracaine appears safe for uncomplicated corneal abrasions and provides more effective pain relief than saline eye drops. We also did a critical appraisal of a systematic review by Swaminathan et al looking at topical anesthetics for these types eye injuries on SGEM#145. The SGEM bottom line from that review was that the best evidence we currently have demonstrates that dilute topical anesthetic drops of either proparacaine or tetracaine are safe for use in ED patients with simple corneal abrasions to provide analgesia. The studies are small, but the data contained in them is far superior to the case series published 50 years ago which led to the dogma that using them is dangerous. Clinical Question: What is the efficacy of topical tetracaine in the treatment of simple corneal abrasions? Reference: Shipman et al. Short-Term Topical Tetracaine Is Highly Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial. Annals of EM 2020 Population: Adults 18 years to 80 years of age with suspected acute cornea abrasion Exclusions: Contact lens wearer, previous corneal surgery or transplant in the affected eye, injury greater than 36 hours old, had a grossly contaminated foreign body, or had coexisting ocular infection. Intervention: Tetracaine 0.5% one drop every 30 minutes as needed for pain for a maximum of 24 hours plus topical antibiotics (polymyxin B sulfate/ trimethoprim sulfate, two drops every four hours into the affected eye) and oral analgesic (hydrocodone/acetaminophen 7.5/325 mg, one or two tablets as needed every six hours) Comparison: Placebo (balanced artificial tear solution) one drop every 30 minutes as needed for pain for a maximum of 24 hours plus topical antibiotics (polymyxin B sulfate/ trimethoprim sulfate, two drops every four hours into the affected eye) and oral analgesic (hydrocodone/acetaminophen 7.5/325 mg, one or two tablets as needed every six hours) Outcome: Primary Outcome: Pain score using a numeric rating scale (NRS from 0-10) measured at the follow-up ED visit in 24-48 hours. Secondary Outcomes: Use of hydrocodone for breakthrough pain, and any adverse events. Authors’ Conclusions: “Short term tetracaine is effective for corneal abrasions.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). Yes The patients in both groups were similar with respect to prognostic factors. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Unsure All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Unsure The treatment effect was large enough and precise enough to be clinically significant. Yes Key Results: They enrolled 118 patients into the trial. The median age was in the mid 30’s and 60% were male. Baseline NRS for pain was 7 out of 10. Just over 10% had a metallic foreign body and more than ¼ had another foreign body. Topical tetracaine was highly effective in reducing pain from simple corneal abrasions. Primary Outcome: Pain on NRS (0-10) at 24 to 48 hour follow-up Tetracaine 1 vs. placebo 8, difference 7 (95% CI 6 to 8) Secondary Outcomes:  Amount of hydrocodone tablets ingested (1 vs. 7) Adverse events (4% vs 11%) 1) Ophthalmologists vs. EM Physicians: There has been a divide between these two specialties. Ophthalmologists probably have some selection bias because you see the worst cases or those that have had complications. This bias can be quantified in this trial. Only about 1 in 5 patients referred to ophthalmology actually attended the consultation one week after injury. Ophthalmologists have a potential selection bias (only referred patients) and treat abrasions differently than EM doctors. We use bandage contact lenses and virtually never prescribe opioids. This will be helpful in framing the discussion of this paper and discussing the motivation for EM physicians to find alternative ways of treating abrasions (ie. tetracaine over opioids) 2) Simple Corneal Abrasions: This is very important. They had a good list of exclusion criteria in the manuscript such as length of time until evaluation in the ED, other ocular infection, grossly contaminated foreign bodies, or other injuries. There were even more listed in exclusion criteria listed in ClinicalTrials.gov that included: “pregnancy, retained foreign body, penetrating eye injury, immunosuppression, allergy to study medication, inability to attend follow up, inability to fluently read and speak English or Spanish, or any injury requiring urgent ophthalmologic evaluation (large or complicated abrasions with significant vision loss, corneal ulcers, corneal lacerations).” Previous studies have excluded corneal injuries with foreign bodies. I liked that they only excluded ones that were “grossly contaminated”. More than 1/3 of the cohort did have either a metallic or some other foreign body. This expands the external validity of the study. Establishing the diagnosis of “simple abrasion” is critical when considering prescribing tetracaine, but unfortunately, the diagnosis is not always straight forward. Severe dry eye and exposure keratopathy is another thing that is often misdiagnosed as an abrasion in the ED. 3) Blinding: The authors correctly acknowledge that the study could have been unblinded for a couple of reasons. Anyone who has used tetracaine knows it comes with a very strong burning sensation. The packaging of the tetracaine (bottle) and placebo (four ampules) were different. They never did confirm with the patients that blinding was maintained by asking which group they thought they had been allocated to. It’s hilarious to think you can adequately mask a study like this because 20 minutes out the door, and the patient will absolutely know if they have saline or tetracaine. I’m more interested in the people who received saline but kept using it. Wishful thinking, I guess. Should we be even using the term “blinding” in a trial involving eye injuries? The lack of blinding could certainly have introduced a placebo effect, but this is usually about 2-3 points on the NRS. The decrease in pain in this trial was 6 points in the treatment group and a 7-point difference compared to the placebo group. So,