Top

Graefe's Archive for Clinical and Experimental Ophthalmology

Published in:

01-01-2012 | Cornea

UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study

Authors: Karim Makdoumi, Jes Mortensen, Omid Sorkhabi, Bo-Eric Malmvall, Sven Crafoord

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 1/2012

Abstract

Background

The aim of this work as to investigate the photochemical interaction used in corneal crosslinking (CXL) as the primary therapy for bacterial keratitis.

Methods

A prospective non-randomized study was conducted including 16 patients with a clinical diagnosis of bacterial keratitis. No patient had any prior antibiotic treatment for the current infection. Photography and microbial culturing of the infected cornea were performed. Riboflavin was topically administered for 20 min and ultraviolet light (UVA) exposure settings for treatment of keratoconus were used. After the procedure, clinical examinations were done at least once daily until signs of improvement had been established. The frequency of examinations was thereafter reduced. Antibiotic therapy was initiated if infectious progression was suspected. The trial was registered at ISCRTN.org (no: 21432643).

Results

All eyes responded to the photochemical treatment with improvement in symptoms and signs of reduced inflammation. Epithelial healing was achieved in all cases. Antibiotic administration was necessary in two cases. One patient required a human amniotic membrane transplant.

Conclusions

This trial illustrates that photosensitization of riboflavin using UVA at 365 nm has the potential to induce healing in patients with microbial keratitis. The results from the treatment of these 16 patients with corneal ulcers indicate that UVA-riboflavin photochemical therapy merits a controlled study in order to assess its efficacy and safety compared to antibiotics.

Keay L, Edwards K, Naduvilath T, Taylor HR, Snibson GR, Forde K, Stapleton F (2006) Microbial keratitis predisposing factors and morbidity. Ophthalmology 113:109–116PubMedCrossRef

Bourcier T, Thomas F, Borderie V, Chaumeil C, Laroche L (2003) Bacterial keratitis: predisposing factors, clinical and microbiological review of 300 cases. Br J Ophthalmol 87:834–838PubMedCrossRef

Wong T, Ormonde S, Gamble G, McGhee CN (2003) Severe infective keratitis leading to hospital admission in New Zealand. Br J Ophthalmol 87:1103–1108PubMedCrossRef

McLeod SD, LaBree LD, Tayyanipour R, Flowers CW, Lee PP, McDonnell PJ (1995) The importance of initial management in the treatment of severe infectious corneal ulcers. Ophthalmology 102:1943–1948PubMed

Ibrahim YW, Boase DL, Cree IA (2009) Epidemiological characteristics, predisposing factors and microbiological profiles of infectious corneal ulcers: the Portsmouth corneal ulcer study. Br J Ophthalmol 93:1319–1324PubMedCrossRef

Green M, Apel A, Stapleton F (2008) Risk factors and causative organisms in microbial keratitis. Cornea 27:22–27PubMedCrossRef

Saeed A, D'Arcy F, Stack J, Collum LM, Power W, Beatty S (2009) Risk factors, microbiological findings, and clinical outcomes in cases of microbial keratitis admitted to a tertiary referral center in Ireland. Cornea 28:285–292PubMedCrossRef

Jeng BH, Gritz DC, Kumar AB, Holsclaw DS, Porco TC, Smith SD, Whitcher JP, Margolis TP, Wong IG (2010) Epidemiology of ulcerative keratitis in Northern California. Arch Ophthalmol 128:1022–1028PubMedCrossRef

McGowan JE Jr (2006) Resistance in nonfermenting Gram-negative bacteria: multidrug resistance to the maximum. Am J Med 119:S29–S36, discussion S62-70PubMedCrossRef

10.

Harris AD, McGregor JC, Furuno JP (2006) What infection control interventions should be undertaken to control multidrug-resistant Gram-negative bacteria? Clin Infect Dis 43(Suppl 2):S57–S61PubMedCrossRef

11.

Rice LB (2007) Emerging issues in the management of infections caused by multidrug-resistant Gram-negative bacteria. Cleve Clin J Med 74(Suppl 4):S12–S20PubMedCrossRef

12.

Falagas ME, Bliziotis IA (2007) Pandrug-resistant Gram-negative bacteria: the dawn of the post-antibiotic era? Int J Antimicrob Agents 29:630–636PubMedCrossRef

13.

Souli M, Galani I, Giamarellou H (2008) Emergence of extensively drug-resistant and pandrug-resistant Gram-negative bacilli in Europe. Euro Surveill 13(47). pii:19045

14.

Bertino JS (2009) Impact of antibiotic resistance in the management of ocular infections: the role of current and future antibiotics. Clin Ophthalmol 3:507–521PubMedCrossRef

15.

Betanzos-Cabrera G, Juarez-Verdayes MA, Gonzalez-Gonzalez G, Cancino-Diaz ME, Cancino-Diaz JC (2009) Gatifloxacin, moxifloxacin, and balofloxacin resistance due to mutations in the gyrA and parC genes of Staphylococcus epidermidis strains isolated from patients with endophthalmitis, corneal ulcers and conjunctivitis. Ophthalmic Res 42:43–48PubMedCrossRef

16.

Ramos-Esteban JC, Bamba S, Jeng BH (2008) Treatment of multidrug-resistant Flavobacterium indologenes keratitis with trimethoprim-sulfamethoxazole. Cornea 27:1074–1076PubMedCrossRef

17.

Moshirfar M, Meyer JJ, Espandar L (2007) Fourth-generation fluoroquinolone-resistant mycobacterial keratitis after laser in situ keratomileusis. J Cataract Refract Surg 33:1978–1981PubMedCrossRef

18.

de la Cruz J, Behlau I, Pineda R (2007) Atypical mycobacteria keratitis after laser in situ keratomileusis unresponsive to fourth-generation fluoroquinolone therapy. J Cataract Refract Surg 33:1318–1321PubMedCrossRef

19.

Wollensak G (2006) Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol 17:356–360PubMedCrossRef

20.

Caporossi A, Mazzotta C, Baiocchi S, Caporossi T (2010) Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. Am J Ophthalmol 149:585–593PubMedCrossRef

21.

Wollensak G, Spoerl E, Seiler T (2003) Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 135:620–627PubMedCrossRef

22.

Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE (2008) Collagen crosslinking with riboflavin and ultraviolet—a light in keratoconus: long-term results. J Cataract Refract Surg 34:796–801PubMedCrossRef

23.

Wittig-Silva C, Whiting M, Lamoureux E, Lindsay RG, Sullivan LJ, Snibson GR (2008) A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results. J Refract Surg 24:S720–S725PubMed

24.

Vinciguerra P, Camesasca FI, Albe E, Trazza S (2009) Corneal collagen cross-linking for ectasia after excimer laser refractive surgery: 1-year results. J Refract Surg: 1–12

25.

Mazzotta C, Traversi C, Baiocchi S, Sergio P, Caporossi T, Caporossi A (2006) Conservative treatment of keratoconus by riboflavin-uva-induced cross-linking of corneal collagen: qualitative investigation. Eur J Ophthalmol 16:530–535PubMed

26.

Ashwin PT, McDonnell PJ (2010) Collagen cross-linkage: a comprehensive review and directions for future research. Br J Ophthalmol 94:965–970PubMedCrossRef

27.

Schnitzler E, Sporl E, Seiler T (2000) Irradiation of cornea with ultraviolet light and riboflavin administration as a new treatment for erosive corneal processes, preliminary results in four patients. Klin Monbl Augenheilkd 217:190–193PubMedCrossRef

28.

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

29.

Micelli Ferrari T, Leozappa M, Lorusso M, Epifani E, Micelli Ferrari L (2009) Escherichia coli keratitis treated with ultraviolet A/riboflavin corneal cross-linking: a case report. Eur J Ophthalmol 19:295–297PubMed

30.

Moren H, Malmsjo M, Mortensen J, Ohrstrom A (2010) Riboflavin and ultraviolet a collagen crosslinking of the cornea for the treatment of keratitis. Cornea 29:102–104PubMedCrossRef

31.

Khan YA, Kashiwabuchi RT, Martins SA, Castro-Combs JM, Kalyani S, Stanley P, Flikier D, Behrens A (2011) Riboflavin and ultraviolet light A therapy as an adjuvant treatment for medically refractive Acanthamoeba keratitis: report of 3 cases. Ophthalmology 118:324–331

32.

Makdoumi K, Mortensen J, Crafoord S (2010) Infectious keratitis treated with corneal crosslinking. Cornea 29:1353–1358PubMedCrossRef

33.

Martins SA, Combs JC, Noguera G, Camacho W, Wittmann P, Walther R, Cano M, Dick J, Behrens A (2008) Antimicrobial efficacy of riboflavin/UVA combination (365 nm) in vitro for bacterial and fungal isolates: a potential new treatment for infectious keratitis. Invest Ophthalmol Vis Sci 49:3402–3408PubMedCrossRef

34.

Schrier A, Greebel G, Attia H, Trokel S, Smith EF (2009) In vitro antimicrobial efficacy of riboflavin and ultraviolet light on Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa. J Refract Surg 25:S799–S802PubMedCrossRef

35.

Makdoumi K, Backman A, Mortensen J, Crafoord S (2010) Evaluation of antibacterial efficacy of photo-activated riboflavin using ultraviolet light (UVA). Graefes Arch Clin Exp Ophthalmol 248:207–212PubMedCrossRef

36.

Goodrich RP, Edrich RA, Li J, Seghatchian J (2006) The Mirasol PRT system for pathogen reduction of platelets and plasma: an overview of current status and future trends. Transfus Apher Sci 35:5–17PubMedCrossRef

37.

Ruane PH, Edrich R, Gampp D, Keil SD, Leonard RL, Goodrich RP (2004) Photochemical inactivation of selected viruses and bacteria in platelet concentrates using riboflavin and light. Transfusion (Paris) 44:877–885CrossRef

38.

Cardo LJ, Rentas FJ, Ketchum L, Salata J, Harman R, Melvin W, Weina PJ, Mendez J, Reddy H, Goodrich R (2006) Pathogen inactivation of Leishmania donovani infantum in plasma and platelet concentrates using riboflavin and ultraviolet light. Vox Sang 90:85–91PubMedCrossRef

39.

Cardo LJ, Salata J, Mendez J, Reddy H, Goodrich R (2007) Pathogen inactivation of Trypanosoma cruzi in plasma and platelet concentrates using riboflavin and ultraviolet light. Transfus Apher Sci 37:131–137PubMedCrossRef

40.

Tonnetti L, Proctor MC, Reddy HL, Goodrich RP, Leiby DA (2010) Evaluation of the Mirasol pathogen [corrected] reduction technology system against Babesia microti in apheresis platelets and plasma. Transfusion (Paris) 50:1019–1027CrossRef

41.

Wollensak G, Spoerl E, Wilsch M, Seiler T (2004) Keratocyte apoptosis after corneal collagen cross-linking using riboflavin/UVA treatment. Cornea 23:43–49PubMedCrossRef

42.

Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE (2006) Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg 32:279–283PubMedCrossRef

43.

Dhaliwal JS, Kaufman SC (2009) Corneal collagen cross-linking: a confocal, electron, and light microscopy study of eye bank corneas. Cornea 28:62–67PubMedCrossRef

44.

Spoerl E, Wollensak G, Dittert DD, Seiler T (2004) Thermomechanical behavior of collagen-cross-linked porcine cornea. Ophthalmologica 218:136–140PubMedCrossRef

45.

Wollensak G, Spoerl E, Seiler T (2003) Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking. J Cataract Refract Surg 29:1780–1785PubMedCrossRef

46.

Spoerl E, Wollensak G, Seiler T (2004) Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res 29:35–40PubMedCrossRef

47.

Wang F (2008) UVA/riboflavin-induced apoptosis in mouse cornea. Ophthalmologica 222:369–372PubMedCrossRef

Title: UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study
Authors: Karim Makdoumi
Jes Mortensen
Omid Sorkhabi
Bo-Eric Malmvall
Sven Crafoord
Publication date: 01-01-2012
Publisher: Springer-Verlag
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 1/2012
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-011-1754-1

At a glance: The STEP trials

Springer Medicine

UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2012

Nicotine reduces VEGF-secretion and phagocytotic activity in porcine RPE

Optical low-coherence reflectometry enables preoperative detection of zonular weakness in pseudoexfoliation syndrome

Ab externo laser photocoagulation for the treatment of spontaneous iris stromal cyst

RGMA and neogenin protein expression are influenced by lens injury following optic nerve crush in the rat retina

Randomized crossover study of latanoprost and travoprost in eyes with open-angle glaucoma

The PI3K/Akt pathway mediates the expression of type I collagen induced by TGF-β2 in human retinal pigment epithelial cells