Treatment for Infectious Keratitis

Since corneal cross-linking (CXL) as a treatment for infectious keratitis (IK) was first reported in the literature 15 years ago, it has been the subject of more than 250 published articles and applied with different strategies across many clinical situations.¹ Overall, evidence on the efficacy of this procedure known as Photoactivated Chromophore for Infectious Keratitis (PACK)-CXL is favourable.

Still, it is an area of ongoing evolution—the procedure is not without potential complications, and there remains a need for randomised controlled clinical trials using standardised outcome measures to determine the place of PACK-CXL in clinical practice, according to Rohit Shetty MD, PhD.

What is clear, however, is safe and effective PACK-CXL can address an unmet need, considering the prevalence and cost burdens of IK and the potential for blindness with failed antimicrobial therapy, he said.

Highlighting some selected literature on PACK-CXL, Dr Shetty noted the published papers appear in both peer-reviewed and non-peer-reviewed journals, include a large number of retrospective case series and case reports, and discuss treatment for different pathogenic causes of IK at every stage using several treatment protocols. Initial investigations focused on PACK-CXL combined with antimicrobial treatment for infections that failed to respond to conventional maximal topical and systemic antimicrobial therapy. Additional research placed the technique as monotherapy for both primary treatment and rescue cases.

A systematic review and meta-analysis published in 2019 found PACK-CXL and antimicrobial therapy accelerated corneal healing compared to antimicrobial therapy alone.² Results of a randomised, controlled trial—which Dr Shetty co-authored—found the treatment success rate was about 90% in groups treated with either antimicrobial therapy or PACKCXL with no difference in the mean time to corneal healing.³

“Even if the infection is eradicated, the cornea may be left with a scar,” Dr Shetty said. “If PACK-CXL shortens the time to healing, it could theoretically reduce scarring by minimising exposure to microbial-produced factors that promote fibrosis.”

As with any new therapy, the benefits must be weighed against the risks. Aside from lack of efficacy, reported PACKCXL complications include conjunctival injection, increased uveitis and hypopyon, corneal endothelial cell loss, and herpes simplex keratitis exacerbation.

“It is important to understand the cause of the keratitis before using PACK-CXL for treatment,” said Dr Shetty, adding the technique appears to have better efficacy for treating bacterial infections compared to fungal and Acanthamoeba keratitis.

PACK-CXL for IK has been performed using different protocols that vary in terms of UV fluence and duration of irradiation. In addition, rose bengal-aided photodynamic therapy using a 532 nm light source has been explored.

Looking ahead, Dr Shetty expects to hear more about a new approach to CXL developed by Dr Farhad Hafezi in which patients are treated with a transepithelial procedure at the slit-lamp with the aid of a second-generation corneal penetration enhancer.

“This is a very exciting advance that I believe will shape the future,” Dr Shetty said.

Dr Shetty spoke during Cornea Day of the 2023 ESCRS Congress in Vienna.

Rohit Shetty MD, PhD is Vice Chairman of Narayana Nethralaya Eye Institute, Bangalore, India. drrohitshetty@yahoo.com

1. Iseli HP, Thiel MA, Hafezi F, Kampmeier J, Seiler T. “Ultraviolet A/riboflavin corneal cross-linking for infectious keratitis associated with corneal melts,” Cornea. 2008; 27(5): 590–594.

2. Ting DSJ, Henein C, Said DG, Dua HS. “Photoactivated chromophore for infectious keratitis—Corneal cross-linking (PACK-CXL): A systematic review and meta-analysis,” Ocul Surf. 2019; 17(4): 624–634. 

3. Hafezi F, Hosny M, Shetty R, et al. PACK-CXL Working Group. “PACK-CXL vs. antimicrobial therapy for bacterial, fungal, and mixed infectious keratitis: a prospective randomized phase 3 trial,” Eye Vis (Lond). 2022; 9(1): 2.