Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 
  • Users Online: 775
  • Home
  • Print this page
  • Email this page

   Table of Contents      
Year : 2019  |  Volume : 67  |  Issue : 10  |  Page : 1701-1702

Commentary: PACK-CXL in fungal keratitis

Division of Ophthalmology and Visual Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK

Date of Web Publication23-Sep-2019

Correspondence Address:
Dr. Rashmi Deshmukh
Division of Ophthalmology and Visual Sciences, Eye ENT Centre, Queens Medical Centre, University of Nottingham, Derby Road Nottingham, NG7 2UH
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_993_19

Rights and Permissions

How to cite this article:
Deshmukh R. Commentary: PACK-CXL in fungal keratitis. Indian J Ophthalmol 2019;67:1701-2

How to cite this URL:
Deshmukh R. Commentary: PACK-CXL in fungal keratitis. Indian J Ophthalmol [serial online] 2019 [cited 2020 Sep 28];67:1701-2. Available from: http://www.ijo.in/text.asp?2019/67/10/1701/267474

Corneal collagen crosslinking (CXL) was initially described as a treatment to stabilize progressive keratoconus.[1] It halts the progression of ectasia by inducing formation of covalent bonds among collagen fibers to prevent stromal weakening. This was the rationale behind studying the effects of CXL on corneal melts of noninfectious origin in 2000.[2] Iseli et al. then proceeded to evaluate the results of CXL in advanced infectious keratitis refractory to therapy and found that CXL was effective in these cases as well.[3] Furthermore, Makdoumi et al. conducted a study that demonstrated CXL to be effective in early microbial keratitis.[4] Since then, there have been multiple studies on the use of CXL in management of infective keratitis, and it has come to be known as photo-activated chromophore for infectious keratitis (PACK)-CXL.

The antimicrobial effect of CXL is due to the interaction between the ultraviolet-A (UV-A) radiation with the riboflavin acting as a chromophore. UV-A radiation itself is known to have antimicrobial properties and damages both RNA and DNA. This property is made use of when UV-A is used for disinfecting water and air. In addition, the reactive oxygen species generated during the photochemical reaction result in new covalent bonds and improve the resistance of corneal stroma against enzymatic degradation.[5] Most of the studies till date have used the standard Dresden protocol with UV-A radiation exposure of 3 mW/cm 2 for 30 min.[6] However, reports exist about the successful use of accelerated protocol using 9 mW/cm 2 for 10 min.[7]

The effects of PACK-CXL have been studied on various etiologies of infective keratitis. In 2013, a meta-analysis by Alio et al. reported that the effectiveness of CXL to reduce the corneal melt was in the following order from most to least: Gram-negative bacteria, Gram-positive bacteria, Acanthamoeba, and fungus.[6] The poor response in fungal infections may be explained by the fact that fungal infections penetrate deeper and CXL is known to have effect in the anterior two-third of the corneal stroma. Tabibian et al. used PACK-CXL as a first line of treatment and found that early fungal keratitis being superficial responded well to CXL alone. The fungus isolated was Aureobasidium pullulans.[7] Vajpayee et al. conducted a retrospective study on moderate grade mycotic keratitis and found that in these cases, addition of CXL to medical treatment did not affect the final outcome. Aspergillus was the most common fungus to be isolated in their study.[8] In advanced and deep stromal fungal ulcers, CXL has been shown to be ineffective.[9] It has been reported that use of 0.25% riboflavin has a higher fungicidal effect than 0.1% riboflavin.[10] Özdemir et al. used 0.25% riboflavin and accelerated CXL protocol and showed that CXL was effective in Fusarium and Candida keratitis as well. The effect was better when PACK-CXL was combined with medical treatment.[11]

The case reported by Thakur et al.[12] shows successful resolution of a corneal fungal infiltrate at the site of phaco-tunnel. They used 0.1% riboflavin with Dresden protocol. Although the organism was not isolated, the aqueous tap was positive for fungal genome. It is possible that PACK-CXL had a synergistic effect with the already administered antifungal medical treatment. The case highlights that CXL was effective in deep fungal infiltrate when used as an adjuvant treatment. Since there are prior studies to show that deep fungal infiltrates have a poor response to CXL, it is difficult to comment whether this infection would have responded to PACK-CXL alone [Table 1]. Nevertheless, further studies on the effects of CXL on fungal keratitis are needed to understand whether deep stromal infiltrates are likely to respond well.
Table 1: Studies on PACK-CXL in fungal keratitis

Click here to view

  References Top

Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003;135:620-7.  Back to cited text no. 1
Schnitzler E, Sp Sp E, Seiler T. Irradiation of cornea with ultraviolet light and riboflavin administration as a new treatment for erosive corneal processes, preliminary results in four patients. Klin Monatsbl Augenheilkd 2000;217:190-3.  Back to cited text no. 2
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;27:590-4.  Back to cited text no. 3
Makdoumi K, Mortensen J, Sorkhabi O, Malmvall BE, Crafoord S. UVA-riboflavin photochemical therapy of bacterial keratitis: A pilot study. Graefes Arch Clin Exp Ophthalmol 2012;250:95-102.  Back to cited text no. 4
Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res 2004;29:35-40.  Back to cited text no. 5
Alio JL, Abbouda A, Valle DD, Del Castillo JMB, Fernandez JAG. Corneal cross linking and infectious keratitis: A systematic review with a meta-analysis of reported cases. J Ophthalmic Inflamm Infect 2013;3:47.  Back to cited text no. 6
Tabibian D, Richoz O, Riat A, Schrenzel J, Hafezi F. Accelerated photoactivated chromophore for keratitis-corneal collagen cross-linking as a first-line and sole treatment in early fungal keratitis. J Refract Surg Thorofare NJ 1995. 2014;30:855-7.  Back to cited text no. 7
Vajpayee RB, Shafi SN, Maharana PK, Sharma N, Jhanji V. Evaluation of corneal collagen cross-linking as an additional therapy in mycotic keratitis. Clin Experiment Ophthalmol 2015;43:103-7.  Back to cited text no. 8
Uddaraju M, Mascarenhas J, Das MR, Radhakrishnan N, Keenan JD, Prajna L, et al. Corneal cross-linking as an adjuvant therapy in the management of recalcitrant deep stromal fungal keratitis: A randomized trial. Am J Ophthalmol 2015;160:131-4.e5.  Back to cited text no. 9
Bilgihan K, Kalkanci A, Ozdemir HB, Yazar R, Karakurt F, Yuksel E, et al. Evaluation of antifungal efficacy of 0.1% and 0.25% riboflavin with UVA: A comparative in vitro study. Curr Eye Res 2016;41:1050-6.  Back to cited text no. 10
Özdemir HB, Kalkancı A, Bilgihan K, Göçün PU, Öǧüt B, Karakurt F, et al. Comparison of corneal collagen cross-linking [PACK-CXL] and voriconazole treatments in experimental fungal keratitis. Acta Ophthalmol 2019;97:e91-6.  Back to cited text no. 11
Thakur A, Gupta A, Handa S. Application of photoactivated chromophore for infectious keratitis-corneal collagen crosslinking for fungal phaco-tunnel infection. Indian J Ophthalmol 2019;67:1700.  Back to cited text no. 12
  [Full text]  
Erdem E, Harbiyeli II, Boral H, Ilkit M, Yagmur M, Ersoz R. Corneal collagen cross-linking for the management of mycotic keratitis. Mycopathologia 2018;183:521-7.  Back to cited text no. 13
Basaiawmoit P, Selvin SST, Korah S. PACK-CXL in reducing the time to heal in suppurative corneal ulcers: Observations of a pilot study from South India. Cornea 2018;37:1376-80.  Back to cited text no. 14


  [Table 1]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
Article Tables

 Article Access Statistics
    PDF Downloaded95    
    Comments [Add]    

Recommend this journal