What are the benefits of adjunctive collagen cross-linking (PACK-CXL) in infectious keratitis outcomes compared to antimicrobial therapy alone?

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Last updated: April 11, 2025View editorial policy

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From the Guidelines

Adjunctive collagen cross-linking (PACK-CXL) is beneficial in the treatment of infectious keratitis, particularly bacterial keratitis, as it can accelerate healing and reduce treatment duration when used in conjunction with standard antimicrobial therapy. The use of PACK-CXL in the treatment of infectious keratitis has been supported by recent studies, including a randomized controlled study published in 2024 1, which found that patients who received a single cross-linking treatment in addition to standard medical therapy had faster re-epithelialization and shorter treatment duration than the control group receiving standard medical therapy alone.

Key Benefits of PACK-CXL

  • Faster re-epithelialization
  • Shorter treatment duration
  • Potential to inhibit corneal melting, especially in bacterial keratitis
  • Effective as an adjunctive therapy, particularly in cases refractory to medical therapy

The procedure involves the application of riboflavin drops to the cornea followed by controlled UV-A light exposure, which creates reactive oxygen species that strengthen corneal collagen fibers and kill pathogens. It is essential to note that PACK-CXL works best when performed early in the disease course and is particularly valuable for treatment-resistant infections or when antimicrobial susceptibility is unknown. However, it should be used cautiously in deep infections (>300 microns) and is contraindicated in herpetic keratitis, as it can worsen outcomes 1.

Considerations for PACK-CXL Use

  • Should be used in conjunction with standard antimicrobial therapy
  • Requires specialized equipment and training
  • Can be performed as an outpatient procedure under topical anesthesia
  • Patients should continue their prescribed antimicrobial medications after the procedure
  • Cautious use in deep infections and contraindicated in herpetic keratitis

From the Research

Benefits of Adjunctive Collagen Cross-Linking (PACK-CXL) in Infectious Keratitis Outcomes

  • The use of collagen cross-linking in the management of corneal infections, including infectious keratitis, has been explored as a potential treatment option 2.
  • Photoactivated chromophore for collagen cross-linking (PACK-CXL) has been investigated as a treatment for infectious keratitis, with some studies suggesting its effectiveness in treating bacterial keratitis 3.
  • The current evidence on the effectiveness of PACK-CXL for bacterial keratitis is of low certainty and clinically heterogenous in regard to outcomes 3.

Comparison to Antimicrobial Therapy Alone

  • A review of three trials (two RCTs and one quasi-RCT) found that it is very uncertain whether PACK-CXL with standard antibiotic therapy is more effective than standard antibiotic therapy alone for re-epithelialization and complete healing 3.
  • Another study found that riboflavin/ultraviolet-A (UVA) as an adjunct treatment for infectious keratitis appeared to be most effective when the infection depth was limited, and the success rate was higher for bacterial infections than fungal infections 4.
  • Published data show that CXL is effective and safe as an adjunct to antibiotic treatment in selected cases of bacterial keratitis, but the benefit of CXL probably varies according to the etiology of the infection 5.

Safety and Efficacy

  • The safety and efficacy of CXL in infectious keratitis have been discussed in several reviews, with some studies suggesting its potential as an adjunctive treatment option 2, 5, 6.
  • However, the role of CXL in infectious keratitis remains unclear despite the reported success in some clinical cases, and further investigations are warranted concerning the efficacy and safety of treating infectious keratitis with CXL 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Collagen cross-linking and corneal infections.

Current opinion in ophthalmology, 2013

Research

Corneal collagen cross-linking for bacterial infectious keratitis.

The Cochrane database of systematic reviews, 2020

Research

Photoactivated riboflavin treatment of infectious keratitis using collagen cross-linking technology.

Journal of refractive surgery (Thorofare, N.J. : 1995), 2012

Research

Collagen Cross-Linking in the Management of Microbial Keratitis.

Ocular immunology and inflammation, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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