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SGEM#83: In Your Eyes (Topical Tetracaine for Corneal Abrasions)

SGEM#83: In Your Eyes (Topical Tetracaine for Corneal Abrasions)

Podcast Link: SGEM83
Date:  July 12th, 2014 

Rebel Skeptics: Dr. Salim Rezaie is an Assistant Professor in the Department of Emergency Medicine and Internal Medicine at the University of Texas at San Antonio. You may better know him from his website REBEL EM or twitter handle @srrezaie.

Case Scenario: 47 year old man is playing Marco Polo in the pool with his daughters. He is accidentally hit in the eye and sustains a uncomplicated corneal abrasion

Question: Is the use of topical 1.0% tetracaine for 24 hours safe and effective for the treatment of uncomplicated corneal abrasions?

Background: Corneal abrasions are very common presentations to the emergency department and very painful. We have all been warned that topical anesthetics to take home should not be given to patients with corneal injuries. The fear is that these drops could delay/decrease healing, prevent recognition of eye foreign bodies, cause keratitis or worsen corneal symptoms.

fact-or-fictionSome of this information comes from animal models or local anesthetic injected directly into the anterior chamber of the eye for cataract surgery:

  • Duffin RM, Olson RJ. Tetracaine toxicity. Ann Ophthalmol. 1984;16(9)836,838. 
  • Judge AJ, et al. Corneal endothelial toxicity of topical anesthesia. Ophthalmology. 1997;104(9):1373–1379.
  • Guzey M, et al. The effects of bupivacaine and lidocaine on the corneal endothelium when applied into the anterior chamber at the concentrations supplied commercially. Ophthalmologica. 2002;216(2):113–117.

Are the dangers of topical anesthetics for simple corneal abrasions fact or fiction?

Article: Waldman N et al.  Topical Tetracaine used for 24 Hours is Safe and Rated Highly Effective by Patients for the Treatment of apain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial. Acad Emerg Med 2014; 21: 374 – 382.

  • Population: Patients presenting to the ED of Southland Hospital in New Zealand with Corneal Abrasions (N = 116)
  • Intervention: Acetaminophen 500mg plus 1% tetracaine hydrochloride topical eye drops
  • Comparison: Acetaminophen 500mg plus placebo (saline eye drops)
  • Outcome:
    • Primary Outcome Safety: Repeat fluorescein/slit lamp ED examinations at 48 hours, 1-week, and 1-month telephone interviews for corneal complications
    • Secondary Outcomes Pain: 100-mm VAS pain scores recorded every 2 hours while awake for 48 hours and patient perceived overall effectiveness with a numeric rating scale (NRS) of 0 – 10.
  • Exclusions: Injury > 36hrs before presentation, < 18 years of age, previous eye surgery or cataracts, wear contact lenses, injury to both eyes, suffering from infectious or chemical conjunctivitis, grossly contaminated foreign bodies, suffering from an ocular infection, current herpes keratitis, allergy to tetracaine, injury requiring urgent ophthalmologic evaluation (i.e. penetrating eye injuries, large corneal abrasions, or injuries causing a disruption of vision), and unable to attend follow up at 48 hours

Authors Conclusions: “Topical Tetracaine used for 24 hours is safe, and while there was no significant difference in patient VAS pain ratings over time, patient surveys on overall effectiveness showed that patients perceived tetracaine to be significantly more effective than saline.”

checklist-cartoonQuality Check List for Random Control Trials:

  1. The study population included or focused on those in the ED? Yes
    • Comment: These were all patients presenting to a regional ED in New Zealand
  2. The patients were adequately randomized? Yes 
    • They used numbered sealed envelopes to randomize patients
  3. The randomization process was concealed? Yes

    • Both the authors and the patients were blinded
  4. The patients were analyzed in the groups to which they were randomized? Yes 
    • Two arms 1% tetracaine vs. saline eye drops
  5. The study patients were recruited consecutively (i.e. no selection bias)? Yes 
    • Patient enrollment into the study could occur at any time during the day or night, 7 days a week and was dictated in part by staffing levels and demands on the department
  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? 
    • Some patients commented on the fact that the drops they were using burned like the tetracaine used in the ED at their initial evaluation. This may have unblinded some physicians and some patients
  8. All groups were treated equally except for the intervention. Yes 
  9. Follow-up was complete (i.e. at least 80% for both groups). No 
    • Only 70% of patients had 48 hour follow-up
  10. All patient-important outcomes were considered. Yes
    • specifically pain relief and corneal complications
  11. The treatment effect was large enough and precise enough to be clinically significant. No
    • Twenty-three patients were removed from data analysis after 48 hour check up. This was due to retained rust rings, making the study underpowered to detect differences in corneal complications and pain scale evaluation.

Key Results:  

  • Primary:
    • 48 hours: No statistical difference in healing identified by fluorescein uptake between the two groups
      • 20 patients had persistent symptoms (10/46 tetracaine vs. 10/47 placebo)
    • 1 Week: Persistent symptoms in five patients (1 tetracaine and 4 placebo)
    • 1 Month: No complications reported by either group
  • Secondary:
    • No difference in 100mm VAS pain scores at an given time between the two groups
    • Patient perceived effectiveness at 1 week (0- not effective and 10- completely effective)
      • Statistically difference (7.7 for tetracaine vs. 3.8 for saline group)
Dr. Salim Rezaie

Dr. Salim Rezaie

Comments:  This was the largest randomized clinical trial to date (n=116) to evaluate the use of topical anesthetics for corneal abrasions. There was no significant difference in healing between the two groups. However, only 93 patients returned for the primary outcome of follow-up at 48 hours.

Another problem was the large number of patients with retained rust rings (13-tetracaine and 10-placebo). This was unanticipated and made it challenging to analyze the data.

The study was underpowered to detect a difference in efficacy between the two groups both in 100mm-VAS pain scale. This represents a common limitations to randomized control trials. They are powered for the primary outcome not for the secondary outcome. However, their goal was to look at safety and that did not show a difference at 48hrs, 1-week or 1-month.

Patients self rated their pain about 50/100 on the VAS. Within 12 hours both groups had dropped to below 10 and at 24 hours approached zero. This speaks to the amazing healing properties of the cornea and made it nearly impossible to show a clinically significant difference between the two groups at 48 hours.

In addition, the study may have been unblinded. Tetracaine causes some local irritation and patients commented on the drops burning like the tetracaine drops used in the initial ED evaluation. A placebo drop which caused mild local irritation could have been used rather than saline. This potential unblinding may have caused the secondary outcome of patient-perceived overall effectiveness to be inflated. Researchers could have simply asked participants which group they thought they were assigned.

Finally, patient compliance with drops was not recorded. This makes it unclear whether drops were used as instructed.

This data agrees with a couple other smaller studies looking at acute corneal injuries:

  • Ting et al. Management of Ocular Trauma in Emergency (MOTE) Trial: A pilot randomized double-blinded trial comparing topical amethocaine with saline in the outpatient management of corneal trauma. J Emerg Trauma Shock, 2(1):10-14, Jan-April, 2009
  • Ball et al. Dilute proparacaine for the management of acute corneal injuries in the emergency department. CJEM 12(5):389, September 2010

Author’s conclusion compared to our conclusion: One small randomized control trial does not prove safety but it does help chip away at the myth that these drugs are toxic when used correctly.

The Bottom Line: Tetracaine appears safe for uncomplicated corneal abrasions and provides more effective pain relief than saline eye drops.

Dr. Louis Probst

Dr. Louis Probst

Consult Ophthalmology: Dr. Louis Probst from Michigan. He would evaluate the injury and be most concerned about infection. The next step would be to treat the patient symptomatically. This includes:

  • Antibiotic eye drops (4th generation fluroquinolone plus polytrim for gram positive coverage)
  • Bandage contact lens
  • Non-steroidal anti-inflammatory drugs (NSAID) eye drops

These patients would then traditionally be follow-up every 24 hours by ophthalmology until the corneal defect had healed.

Screen Shot 2014-07-11 at 11.26.10 PMCase Resolution: You offer the Marco Polo playing dad some 1% tetracaine drips to use as needed every two hours for the next 24 hours. The drops sting and burn when used but make it much easier to get to sleep that night. He is seen in the emergency department for follow-up in 48 hours. The pain is gone and the abrasion has completely healed.

Clinical Application: Topical anesthetics are better at patient perceived pain relief compared to oral pain medications and saline eye drops. Evidence is not robust, but indicates when topical anesthetics are used appropriately, and for a short duration of time (24 hours) there are no corneal complications.

What do I tell my patients? You have scratched your cornea. Here are some eye drops to help treat the pain. It is safe to use for 24 hours. Your vision is important so we have arranged to see you back in the emergency department in two days. Please come back earlier if you have increased pain, decreased vision or otherwise concerned.

For more on this topic, checkout REBEL EM, where Salim discusses:

  1. Historical case reports, case series, and animal studies (The dogma of topical anesthetics being unsafe for corneal abrasions)
  2. Other trials evaluating the safety and effectiveness of topical anesthetics
  3. My review of the current paper we discussed plus commentary article that was released shortly after this publication
  4. How your pharmacist can make a 1:10 dilution of topical anesthetics
  5. Take home message for safety of topical anesthetics

Additional FOAMed Resource:

Keener Kontest: There was no winner from last week. I guess the Swedish Skeptic, Katrin Hruska, came up with a question that was just too hard.

If you want to play the Keener Kontest this week then listen to the podcast for the question. Email me your answer at with “keener” in the subject line. The first person to correctly answer the question will receive a cool skeptical prize.


Upcoming conferences:

  • QueBEEM Quebec City September 29th and 30th
  • EuroBEEM Prague  December 5th and 6th

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


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  • Meghan Groth

    Hey guys, thanks for posting on this! I just had a quick question regarding your conclusions compared to the authors conclusions. Technically, the study investigators did not enroll enough patients to meet their original power calculation, so while highly unlikely…there may have been a difference in their primary outcome if they had a (slightly) larger sample size, but they weren’t able to detect it. What’s more, an even smaller population was available at 48 hours for evaluation of the primary outcome. This seems to me like an example of type II error. It’s a bit misleading what the authors do in the “Follow-up” section of Figure 1, they actually say zero patients in each group were lost to follow up.
    So, in your post/podcast you acknowledge that the study was underpowered to detect a difference in the secondary outcome of efficacy so we can’t take away that tetracaine is more efficacious. However you then go on to say that tetracaine is probably safe (and the authors are even so bold as to state this in the title of the article), but I’m not sure this is supported given that they were also underpowered for the primary outcome. Thoughts?

    • TheSGem

      Thanks Meghan for listening and reading so carefully.

      Our conclusion compared to the author’s conclusion could have said one “underpowered” RCT to be more accurate. Even if it was adequately powered one RCT does not “prove” conclusion. Given the results in context with the rest of the literature it should provide some reassurance about using these drops.

      With regards to efficacy, it was the self reported patient perceived effectiveness. Our comments pointed out the limitations of the study. While not being as bold as the authors saying “highly effective” we simply said provides more effective pain relief than saline eye drops. The “more” was used instead of something like “significant” because of the power issue. We could have added “may” provide more effective pain relief…

      So I agree the authors seemed more enthusiastic in their title and conclusions than their study would support. We tried to point out the strengths and weaknesses while watering down the enthusiasm a bit.

      While the evidence from this one study is not robust enough to prove efficacy and safety it is the “best” evidence we have to date. Often the best evidence is flawed evidence.

      Thanks again for listening and being so skeptical.

    • Salim R. Rezaie

      Hello Meghan,

      TY for listening and reading. I echo what Ken has said. One underpowered RCT does not prove anything. But I have a couple of thoughts:

      1. The evidence against topical anesthetics comes from animal studies, case reports, and case studies. These are a weaker level of evidence than RCTs (Yes even underpowered ones)

      2. There have been 4 Optho studies evaluating this with photorefractive keratectomy (PRK), which is essentially a corneal laceration:

      Verma et al 1995 — 44 patients
      Verma et al 1997 — 38 patients
      Shahinian et al 1997 — 10 patients
      Brilakis et al 2000 — 49 patients

      And 3 ED studies evaluating this:

      Bartfield et al 1994 — 23 patients
      Ball et al 2009 — 33 patients
      Waldman et al 2014 — 116 patients

      Even if you put all these studies together, which is not really feasible because each of them was looking for something else, but the one unifying theme….complete corneal healing at 72 hours.

      That being said…I 100% agree with your statement, but there has not been a stronger level of evidence to say that topical anesthetics are not safe or efficacious.

      So how do I make sense of all of the above:

      1. Bad Case Reports, Case Series, and Animal Studies looking at toxicities of topical anesthetics and a handful of patients abusing topical anesthetics for weeks to months = BAD EVIDENCE!!!

      2. 7 RCTs that are underpowered = BETTER EVIDENCE, but not the end all!!!

      3. Take Home Message: Patient satisfaction is better with topical anesthetics, no bad outcomes at 72 hours….would like to see a well powered study, but until that time, this is most likely a safe practice in the correct patient population for 24 hours.


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  • TheSGem

    We just got a systematic review on this topic published with some #FOAMed friends.