Adjunctive CXL with Antibiotics Can Be Better in Certain Infectious Keratitis Cases

PACK-CXL may exhibit efficacy when the keratitis is localized to the anterior–middle stroma; however, it becomes ineffective and poses safety concerns in instances of deep infiltrations. These images (from a different study) show the results of the procedure in three different patients. Photo: Olshaker H, et al. Front Pharmacol. Sept 06, 2023. Click image to enlarge. The current management protocol for infectious keratitis involves antimicrobial treatment and, when necessary, surgical interventions. However, treatment resistance due to undiagnosed or misdiagnosed predisposing factors, as well as high antimicrobial resistance in bacteria like Staphylococcus aureus and multidrug-resistant strains like Pseudomonas aeruginosa species, can be a potential challenge. Also, excessive use of broad-spectrum antibiotics or a mixture of topical antibacterial, antiviral and antifungal drugs may enhance drug toxicity and accelerate the development of resistance patterns. Topical antimicrobials have limited penetration and can lead to complications such as corneal perforation, melting and scarring. Ineffective treatment of IK may delay corneal epithelization and result in non-healing corneal ulcers. Corneal crosslinking (CXL) demonstrates potential in the treatment of infectious keratitis, particularly bacterial variants, but questions remain about its safety and effectiveness. Studies have shown that adjuvant PACK-CXL can accelerate corneal healing and infiltrate resolution, but prolonged impacts of CXL in corneal infections have not been extensively investigated.Researchers in Iran assessed the effectiveness and safety of CXL in treating infectious keratitis. By combining the findings from systematic reviews and meta-analyses, their study indicated that the duration of re-epithelialization, the rate of keratitis healing and the necessity for ultimate penetrating keratoplasty (PK) were the primary outcomes extensively examined concerning CXL for infectious keratitis.Five systematic reviews out of 53 identified records were included in the umbrella review. Due to the structure of the included studies, the researchers were unable to conduct statistical analysis. Four studies were included that mainly evaluated the role of adjuvant corneal CXL in bacterial keratitis, and the other study focused mainly on fungal keratitis. The studies reported heterogeneous results.Two systematic reviews reported a shorter period for corneal epithelium healing in the adjuvant CXL group compared to the standard antibiotic therapy, especially in fungal keratitis. However, two studies showed no significant change in re-epithelization duration. One meta-analysis reported a reduction in corneal infiltrate size seven days after adjuvant corneal CXL compared to the standard antibiotic therapy. None of the included studies reported a difference in corneal complications, such as perforation and the need for PK, in the CXL group compared to standard antibiotic therapy.“Based on the included studies, adjuvant corneal crosslinking might be safe in bacterial or fungal keratitis treatments,” the researchers wrote in their paper, which was published in BMC Ophthalmology. “It should be noted that, currently, the PACK-CXL has not been approved as a first-line treatment for infectious keratitis, but it is an adjunctive therapeutic intervention besides the standard antimicrobial therapy.”The team also noted that the unification of the CXL protocol for infectious keratitis, especially regarding the de-epithelization procedure before CXL, should be addressed. Also, the evidence regarding the therapeutic role of CXL in keratitis due to Acanthamoeba was too limited, and recommendations could not be given in this regard. Click here for the journal source.  Farhadi F, Salehi-Pourmehr H, Arasteh A, et al. Corneal crosslinking for infectious keratitis of various causes: an umbrella review. BMC Ophthalmol. 2025;25(1):238.