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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:

  1. The study population included or focused on those in the emergency department. Yes
  2. The patients were adequately randomized. Yes
  3. The randomization process was concealed. Yes
  4. The patients were analyzed in the groups to which they were randomized. Yes
  5. The study patients were recruited consecutively (i.e. no selection bias). Yes
  6. The patients in both groups were similar with respect to prognostic factors. Yes
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Unsure
  8. All groups were treated equally except for the intervention. Yes
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes
  10. All patient-important outcomes were considered. Unsure
  11. 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, while the placebo effect could represent part of the effect size it is unlikely to be responsible for the entire difference observed.

4) Safety: Clearly the biggest issue regarding the acceptance of tetracaine as an appropriate treatment for abrasion pain isn’t efficacy, but safety. We all know it’s efficacious. I guess it would have been interesting to see if it worked better in men than women because, in my experience, men have a lower pain tolerance. However, safety studies are hard to do and often require a lot of subjects. I get the sense that this study, with a primary outcome of “tetracaine works,” was really done to provide another glancing blow to the “tetracaine prescribing is dangerous” crowd by mentioning the lack of adverse effects as a secondary outcome. Maybe with enough glancing blows, standard of care will change, and maybe it should.

We know that adverse events are systematically under-reported in RCTs (Hodkinson et al. BMJ Open 2013). Trials are usually powered for efficacy not safety. I liked that they did not claim safety in their conclusion from the abstract. However, at the end of the discussion they claim: “short-term topical tetracaine is a safe and efficacious analgesic for acute, uncomplicated corneal abrasions”.  This is an over-interpretation of the data and they said in their limitation section that their study was not powered for safety. It would have been more accurate to say we did not observe and increase in harm. Claiming safety shifts the burden of proof. It is on those claiming harm that need to conduct a trial demonstrating a net increase in adverse events with short-term topical anesthetics for simple corneal abrasions.

5) Outcomes: I think the decrease in opioid consumption is a very interesting and compelling outcome in this study. It is well recognized that we have an opioid crisis in the US. This could be another strategy to minimize the harm from these drugs.

I cannot remember ever prescribing an opioid for a patient with a simple corneal abrasion. We need to change the goal from achieving 0/10 pain and focus on addressing suffering. We have an evolved nervous system to sense pain and it can provide us with important information. What we don’t want is patients suffering. Re-framing expectations is an important part of emergency medicine whether it is corneal abrasions, acute back pain, migraine headaches or other painful conditions.

It would also have also been interesting to ask about return to work as a patient-oriented outcome (POO). Many of the corneal abrasions I see are work related (grinding injury with metallic FB). Would the use of topical tetracaine allow them to continue working rather than missing a couple days of work due to pain?

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusions.

SGEM Bottom Line: Topical tetracaine use for 24-48 hours provides effective pain control and seems to be safe when prescribed early after corneal abrasions and you are confident it is only a simple corneal abrasion.

Case Resolution: 

  • Will: I would apply a bandage contact lens, start ofloxacin four times a day and see him back in 3-5 days for contact lens removal. For larger abrasions, I may extend follow up to five days or maybe a week to allow plenty of time for the abrasion to heal before I remove the lens. Regarding NSAIDS, don’t do it. Too expensive and not much better for pain control than opioids, which are not that helpful anyway.
  • Ken: I would give him prescription for topical antibiotics and the 0.5% tetracaine left over from the small ampules we have in the ED. With good instructions on when to return to the ED.

Dr. Will Flanary

Clinical Application:

  • Will: This will not change my clinical practice.
  • Ken: This changes my routine clinical practice. I was hesitant before to provide the small amount of tetracaine to those with foreign bodies.

What Do I Tell My Patient? 

  • Will: I tell them it will hurt like hell but be dramatically better after 24 hours. If I place a contact lens, I’ll tell them it will feel scratchy, but they will still be able to function ok
  • Ken: A corneal abrasion will hurt like heck for 24 hours but will dramatically improve after a day or two. If you have a decrease in your vision, an increase in your pain or are worried please come back to the ED for re-assessment.

Keener Kontest: Last weeks’ winner was Katrine Finsnes . She knew the it was in 2019 when the National Institute of Health began allowing the adoption of retired lab animals as opposed to euthanization.

Listen to the SGEM podcast to hear this weeks’ question. Send your answer to [email protected] with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

 Other FOAMed: REBEL EM

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.