Corneal collagen cross-linking for infectious keratitis

What is the aim of this review?
The aim of this Cochrane Review was to find out the effect of photoactivated chromophore for collagen cross-linking (PACK-CXL), a potential treatment for people with bacterial infectious keratitis. Infectious keratitis is an infection of the cornea, which is the clear, dome-shaped tissue on the front of the eye. We collected and analyzed all relevant studies to answer this question and found three relevant studies.

Key messages
There is no evidence that PACK-CXL combined with standard antibiotics (medications that treat bacterial infection) is more or less effective than standard antibiotics alone in regard to complete healing and treatment failure. Five ongoing trials (1136 participants) may provide better answers in the next update of this review.

What was studied in this review?
PACK-CXL uses ultraviolet light from a special machine to strengthen the cornea. This treatment is called 'cross-linking' because it promotes the binding of collagen fibers in the eye. The collagen fibers work like support beams to keep the cornea stable.

What are the main results of this review?
We included three studies in this review that compared PACK-CXL combined with standard antibiotics versus standard antibiotics alone. The studies had a total of 59 participants with bacterial keratitis (59 eyes). Follow-up was conducted between 14 to 120 days after treatment. The studies were conducted in Egypt, Iran, and Thailand between 2010 and 2014.

There is no evidence that PACK-CXL with standard antibiotics is more effective than standard antibiotics alone for complete healing. We have very low confidence in this finding because of the low number of participants and high risk of bias. There is also no evidence of a different treatment failure rate between PACK-CXL with standard antibiotics versus standard antibiotics alone. We have low confidence in this finding because of the low number of participants and high risk of bias. One trial involving 32 participants reported no adverse events from PACK-CXL at 14 days.

How up-to-date is this review?
The review authors searched for studies that had been published up to 8 July 2019.

Authors' conclusions: 

The current evidence on the effectiveness of PACK-CXL for bacterial keratitis is of low certainty and clinically heterogenous in regard to outcomes. There are five ongoing RCTs enrolling 1136 participants that may provide better answers in the next update of this review. Any future research should include subgroup analyses based on etiology. A core outcomes set would benefit healthcare decision-makers in comparing and understanding study data.

Read the full abstract...
Background: 

Infectious keratitis is an infection of the cornea that can be caused by bacteria, viruses, fungi, protozoa, or parasites. It may be associated with ocular surgery, trauma, contact lens wear, or conditions that cause deficiency or loss of corneal sensation, or suppression of the immune system, such as diabetes, chronic use of topical steroids, or immunomodulatory therapies. Photoactivated chromophore for collagen cross-linking (PACK-CXL) of the cornea is a therapy that has been successful in treating eye conditions such as keratoconus and corneal ectasia. More recently, PACK-CXL has been explored as a treatment option for infectious keratitis.

Objectives: 

To determine the comparative effectiveness and safety of PACK-CXL with standard therapy versus standard therapy alone for the treatment of bacterial keratitis.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 7); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Science Information database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 8 July 2019.

Selection criteria: 

We included randomized controlled trials (RCTs), quasi-RCTs, and controlled clinical trials (CCTs) of PACK-CXL for bacterial keratitis. We included quasi-RCTs and CCTs as we anticipated that there would not be many RCTs eligible for inclusion.

Data collection and analysis: 

Two review authors working independently selected studies for inclusion in the review, assessed trials for risk of bias, and extracted data. The primary outcome was proportion of participants with complete healing at four to eight weeks. Secondary outcomes included visual acuity, morphology, adverse events, and treatment failure at four to eight weeks.

Main results: 

We included three trials (two RCTs and one quasi-RCT) in this review for a total of 59 participants (59 eyes) with bacterial keratitis. Trials were all single-center and were conducted in Egypt, Iran, and Thailand between 2010 and 2014. 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 (risk ratio (RR) 1.53, 95% confidence interval (CI) 0.88 to 2.66; participants = 15). We judged the certainty of the evidence to be very low due to the small sample size and high risk of selection and performance bias. The high risk of selection bias reflects the overall review. Masking of participants was not possible for the surgical arm. No participant had a best-corrected visual acuity of 20/100 or better at eight weeks (very low certainty evidence). There is also no evidence that use of PACK-CXL with standard therapy results in fewer instances of treatment failure than standard therapy alone (RR 0.50, 95% CI 0.05 to 4.98; participants = 32). We judged the certainty of evidence to be low due to the small sample size and high risk of selection bias. There were no adverse events reported at 14 days (low certainty evidence). Data on other outcomes, such as visual acuity and morphological characteristics, could not be compared because of variable time points and specific metrics.

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