Systemic Review and Meta Analysis on Topical Pain Control in Corneal Abrasions

 Background Information:

Corneal abrasions are responsible for the largest proportion of eye-related chief complaints in patients presenting to emergency departments in the United States. There is substantial variability in physician practice when it comes to pain control. Ophthalmology literature has shown that amore recent studies have favored topical NSAIDs and anesthetics as beneficial without increased complications.^3-5 Interestingly, the lack of clinical evidence for topical anesthetic complications, such as corneal melting, has resulted in controversy regarding its non-dilutional use. The authors of this systematic review and meta-analysis sought to compare healing rates, pain control and complications between all topical pain therapies and their control for patients presenting with corneal abrasions.

Paper: Yu CW, et al. Topical Pain Control for Corneal Abrasions: A Systematic Review and Meta-Analysis. Acad Emerg Med. 2021 Jan 28. PMID: 33508879

Clinical Question:

• What are the healing rates, pain control and complications between all topical pain management and control for patients presenting with traumatic corneal abrasions?

What They Did:

• Systematic review and meta-analysis using the following four databases: CENTRAL, MEDLINE, EMBASE and Web of Science.
• Authors searched these databases manually and contacted the authors of relevant studies to gather unpublished data
• All published randomized control trials or observational studies comparing intervention to a control group for any of the following pain control interventions were included:
  • Topical anesthetics
  • Topical NSAIDs
  • Topical steroids
  • Topical cycloplegics
  • Eye patching
  • Bandage contact lens (BCL)
• The authors defined traumatic corneal abrasions as any corneal epithelial deficit from trauma, including those from corneal FB removal.
• The data extracted from the trials included the following:
  • Study characteristics (author, year, single/multi-center, design, country and funding)
  • Corneal abrasion details (ie. mechanism of injury, method of diagnosis, type of assessor)
  • Outcomes (number of patients healed at each time point, size of epithelial defect, pain scores, use of oral analgesia, complications)
• Corneal abrasions were classified as being either:
  • Simple
  • Complicated (ie. at high risk for infection, contact lens wearers or with previous penetrating eye trauma/corneal pathology)
  • Both simple and complicated
  • Foreign bodies only
  • Rust rings only

Inclusion Criteria:

• Only studies that included a non-intervention control were included
• Of note, cycloplegics were not considered a control group and only an intervention group

Exclusion Criteria:

• Studies that had corneal abrasions caused by surgeries or spontaneously in the setting of other corneal pathologies were excluded

Outcomes:

Primary

• Percentage of corneal abrasions healed at 24, 48 and 72 hours
• Pain control at 24 and 48 hours

Secondary

• Use of oral analgesia
• Incidence of complications (ie. ulcers, keratitis, recurrent corneal erosion, corneal melt or perforation)

Results:

• 78 Full text papers, including supplementary materials, were reviewed
• 33 of these papers met inclusion criteria (31 RCTs and 2 retrospective cohorts)
• There were 4,167 patients in total with corneal abrasions included
• Mechanism of Injury was reported in 21 of the 33 studies
• No studies investigated topical steroids

Critical Results:

Topical NSAIDs

• Five studies compared epithelial healing in patients receiving placebo and topical NSAIDs such as indomethacin, ketorolac and oxyphenbutazone
• At 24 hours there was no difference in healing between the NSAID and control group in 4 of the studies
• At 48 hours, a meta-analysis of 3 studies (n = 132) showed no significant difference between the NSAID and control group (RR 1.07, 95% CI [0.95 – 1.19])
• Healing at 72 hours was only reported in one study (n=32) and found all patients had healed in both groups
• At 24 hours, there were lower pain scores in the NSAID group reported in 8 out of 9 studies
• A meta analysis found significantly lower pain scores in the NSAID group at 24 hours (SMD -0.69, 95% CI [-0.98, -0.41]) and 48 hours (SMD -0.56, 95% CI [-1.02, -0.10])
• Similarly a significantly lower proportion of patients used oral analgesia in the NSAID group compared to the control (RR 0.47, 95% CI [0.33 – 0.66]
• No significant difference in rate of complications between the NSAID and control groups were noted in the 9 studies included in the meta-analysis (RR 0.67, 95% CI [0.13 – 3.41])

Topical Anesthetics

• One study (n = 33) looked at 24-hour healing using diluted proparacaine and found no significant difference in healing compared to control (although % of healed abrasions was not reported)
• At 48 hours, three studies found 78.9% of patients receiving topical anesthetics had complete healing with no statistically significant difference compared to control group (RR 0.94, 95% CI [0.83 – 1.06])
• No studies reported healing at 72 hours
• Two studies found a significant difference in pain scores between tetracaine 0.5% and control and between amethocaine 0.4% and control.
• Four complications were reported across five studies (n = 738) in patients receiving topical anesthetics compared to five complications in control groups.
  • 2 corneal infiltrates
  • 1 acute iritis
  • 1 allergic conjunctivitis
• No significant difference was seen between two groups in 4 RCTs addressing complications of topical anesthetics (RR 0.72, 95% CI [0.20 – 2.54])

Patching

• There was no significant difference in healing at 24 hours (RR 0.94, 95% CI [0.86 – 1.02]), 48 hours (RR 0.98, 95% CI [0.93 – 1.02]) or 72 hours (RR 1.01, 95% CI [0.98 – 1.05])
• There was no significant difference in patient-reported pain between patching and control at 24 hours in 9 studies or in the 4 studies of the meta-analysis (SMD -0.77, 95% CI [-0.53 – 0.39])
• Among 7 RCTs there was a non-statistically significant trend towards a higher rate of complications in the patching compared to the control group

Bandage Contact Lenses (BCL)

• No studies evaluated epithelial healing in patients receiving BCL compared to control
• One study found no difference in pain control at 24 hours between the BCL and control groups. This same study found that BCL did not change the use oral analgesia

Cycloplegics

• No studies evaluated epithelial healing or pain scores in patients receiving cycloplegic drops

Strengths:

• Study was conducted following the guidance of both the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines
• The primary outcome of corneal abrasions healed at a specific time and pain control are clinically relevant patient oriented outcomes
• Each study was reviewed by two reviewers independently by title and abstract, and then later by full text. Discrepancies were resolved by a third reviewer
• The authors obtained accurate translations for articles not published in English
• Explicitly defined corneal abrasion
• Had finite timelines for healing and pain control
• Assessed for Risk of Bias on the overall Meta-analysis level and the individual study level

Limitations:

• Included studies have overall high risk of bias and imprecision
• Only a small number of properly conducted RCTs exist on this topic which limits ability to make substantial conclusion from a meta-analysis
• Many studies included had high drop-out rates, with 3 studies not even reporting the rate
• Pain intensity was measured using subjective pain scores which have high individual variability and may not capture the overall effectiveness of the intervention
• Complications were mostly self-reported and likely under-reported
• There was significant heterogeneity in the cause of abrasions, size of abrasions and use of adjunct medications

Discussion: 

• The studies in this review rarely evaluated the primary endpoints set by the authors. For instance no studies evaluating topical anesthetics reported healing at 72 hours. This was no fault of the individual studies but rather the outcome set by the authors of this review
• The authors suggest that the lack of an increase in complication rates with topical NSAIDs supports their use as a short-term treatment for uncomplicated corneal abrasions
• An important point to highlight is that looking to improve pain at 48 hours (and the failure of topicals to do so) is less clinically relevant since most corneal abrasions either heal at 24 hours or are pain free. Additionally, all the studies used in this review were flawed with respect to this due to their follow-up issues
• Included in the complications were ophthalmologic diagnoses (ie. infectious keratitis) or evidence of persistent symptoms at follow-up greater than one week where diagnoses were not reported
• Although less commonly used due to inability to notice changes and administer drops, the results of this meta-analysis showed an increase in complication rates with pressure patching without a meaningful reduction in patient discomfort.
• This meta-analysis found limited studies evaluating BCL and topical cycloplegics as treatment options in traumatic corneal abrasions. Therefore there is insufficient evidence to support or refute their use in healing or pain control.
• Topical anesthetics provide excellent short-term relief of ocular pain. A while back, we discussed the procedure of diluting proparacaine and giving it to the patient here on REBEL EM with explicit written out directions on its use.⁶ Following the results of their meta-analysis the authors also advocate for dilutional proparacaine formulation.
• The authors are applauded for having a structured means and system for assessing Risk of Bias.  For the entire Meta-Analysis they used the Cochrane Risk of Bias Tool and the MINORS Criteria and on the individual study level they used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool.
• The results of this review need to be cautiously interpreted as a large majority of the studies in this review were limited by small sample sizes, follow-up issues and high risks of bias

Author’s Conclusions:

• There was strong evidence to support that topical NSAIDs reduce pain associated with corneal abrasions in the first 48 hours and the need for oral analgesia. The existing evidence was insufficient to support or refute the use of topical anesthetics, cycloplegics, steroids, or BCL for pain control in corneal abrasions. Pressure patching was ineffective at pain reduction and may increase the risk of complications. Delays in healing or other complications were not significantly different between any intervention or control for simple, uncomplicated corneal abrasions; however, larger RCTs are required to identify any differences in rare complications.

Our Conclusion:

• While this review provides some valuable data on some of the analgesic options to treat corneal abrasions, the small sample sizes of the studies and bias preclude any drastic practice changes.
• The evidence in this meta-analysis shows lower pain scores and no significant complications with the use of topical NSAIDs.
• A more important take-away from this was the minimal rate of complications associated with topical anesthetics and the lack of significant difference between their use and the control groups in 4 randomized control trials.
• Although additional studies are needed to ascertain the true risk of “corneal melting” and other complications with topical anesthetics, emergency physicians should continue to use diluted proparacaine when treating patients with corneal abrasions in the emergency department.

Clinical Bottom Line:

• Topical NSAIDs when used in the first 48 hours may help reduce pain with no significant complications and, alongside with diluted proparacaine, may be considered an alternative therapeutic option in patients presenting to the emergency department with corneal abrasions

REFERENCES:

1. Yu CW, et al. Topical Pain Control for Corneal Abrasions: A Systematic Review and Meta-Analysis. Acad Emerg Med. 2021 Jan 28. PMID: 33508879
2. Menghini M, et al. Treatment of traumatic corneal abrasions: a three-arm, prospective, randomized study. Ophthalmic Res. 2013; May 3. PMID: 23652196
3. Ball IM, et al. Dilute proparacaine for the management of acute corneal injuries in the emergency department. CJEM. 2010 Sep; PMID: 20880433
4. Alberti MM, et al. Combined indomethacin/gentamicin eyedrops to reduce pain after traumatic corneal abrasion. Eur J Ophthalmol. 2001 Jul-Sep. PMID: 11681501
5. Donnenfeld ED, et al. Controlled evaluation of a bandage contact lens and a topical nonsteroidal anti-inflammatory drug in treating traumatic corneal abrasions. Ophthalmology. 1995 Jun; PMID: 7777307
6. Rezaie S, “Topical Anesthetic Use on Corneal Abrasions”, REBEL EM blog, April 21, 2014. Available here

   Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srreziae) and Anand Swaminathan, MD (Twitter: @EMSwami)

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