Evaluation of risk factors for treatment failure in canine patients undergoing photoactivated chromophore for keratitis – corneal cross-linking (PACK-CXL): a retrospective study using additive bayesian network analysis

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Abstract

Background

Infectious keratitis is a common ophthalmic condition in canine patients. Sequelae can include keratomalacia and corneal perforation, a vision threatening outcome. Photoactivated chromophore for keratitis – corneal cross-linking (PACK-CXL) is a non-surgical, adjunctive treatment method for infectious keratitis. The goal of this retrospective, multicenter study was to determine risk factors for treatment failure following PACK-CXL in canine patients suffering from suspected infectious keratitis. Medical records from four veterinary ophthalmology services were reviewed, and information related to patient demographics, ophthalmic findings, the PACK-CXL protocol used, and epithelialization time was collected and analyzed. Due to the potential for intervariable relationships, an additive Bayesian network (ABN) analysis was performed to evaluate these complex relationships.

Results

Records for 671 eyes (668 dogs) were included in the analysis. Based on the ABN, in the population included here, patients who underwent an accelerated PACK-CXL protocol were less likely to experience treatment failure versus patients treated with a slow protocol. Mutual dependencies between exposure variables were identified by ABN, which would have been overlooked using classical regression. Corneal re-epithelialization time was shortened following PACK-CXL combined with topical medical therapy compared to PACK-CXL alone.

Conclusions

No risk factors associated with treatment failure were identified in the population included in the present study. Canine patients may benefit from the use of accelerated PACK-CXL protocols, especially when combined with topical antibiotics and anti-collagenolytic therapy. The reasons for this apparent positive impact on treatment outcome remain unclear.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12917-023-03779-x.

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Most cited references 43

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Steve Walker, Martin Mächler, Ben Bolker … (2022)

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Induction of cross-links in corneal tissue.

E Spoerl, M Huhle, T Seiler (1998)

The aim of this study was to investigate the possibility of induction of cross-links in corneal tissue in order to increase the stiffness as a basis for a future conservative treatment of keratectasia. Collagenous biomaterials can be stabilized by chemical and physical agents. The epithelium of enucleated porcine eyes was removed. Eight test groups, 10 eyes each, were treated with UV-light (lambda=254 nm), 0.5% riboflavin, 0.5% riboflavin and UV-light (365 nm) blue light (436 nm) and sunlight, and the chemical agents-glutaraldehyde (1% and 0.1%, 10 min) and Karnovsky's solution (0.1%, 10 min). Strips of 5 mm in width and 9 mm in length were cut from each cornea and the stress-strain behaviour of the strips was measured to assess the cross-linking process. For comparison, ten untreated corneas were measured by the same method. Compared to untreated corneas treatment with riboflavin and UV-irradiation as well as weak glutaraldehyde or Karnovsky's solutions resulted in an increased stiffness of the cornea. The biomechanical behaviour of the cornea can be altered by glutaraldehyde, Karnovsky's solution, and with riboflavin and UV-irradiation which offers the potential of a conservative treatment of keratoconus. To optimize this effect further investigation is necessary regarding the dose-response and in-vivo application. Copyright 1998 Academic Press Limited.

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Increased resistance of crosslinked cornea against enzymatic digestion.

Eberhard Spoerl, Gregor Wollensak, Theo Seiler (2004)

Collagen-crosslinking using combined riboflavin/ UVA treatment has been developed by us as a new treatment for keratoconus by stiffening the collagenous matrix. Recently, we have started to use the same method for the treatment of corneal ulcers. The aim of the present study was to evaluate the influence of the crosslinking treatment on the resistance of the cornea against enzymatic degradation. 60 enucleated porcine eyes were treated with the photosensitizer riboflavin and UVA-irradiation (370 nm; irradiance of 1, 2 or 3 mW/cm2) for 30 minutes and compared with 20 untreated control eyes. After crosslinking treatment, the corneal buttons were trephined and exposed to pepsin, trypsin and collagenase solutions. The extent of the corneal digestion was monitored daily. Selected cases were examined by light microscopy. The corneal buttons crosslinked with riboflavin/ UVA at 3 mW/cm2 were dissolved only by day 13 following pepsin digestion and by day 14 following collagenase treatment versus 6 days in the untreated control corneas. Digestion by trypsin was observed on day 5 in buttons crosslinked at 3 mW/cm2 compared to day 2 in the control corneas. Microscopically, a prolonged preservation especially of the anterior portion of the crosslinked corneas could be demonstrated. Photochemical crosslinking of the cornea using riboflavin and UVA results in a markedly increased resistance versus collagen digesting enzymes. The findings support the use of the new method in the treatment of corneal ulcers.

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Author and article information

Contributors

M. E. Kowalska: malwina.kowalska@uzh.ch

Journal

Journal ID (nlm-ta): BMC Vet Res

Journal ID (iso-abbrev): BMC Vet Res

Title: BMC Veterinary Research

Publisher: BioMed Central (London )

ISSN (Electronic): 1746-6148

Publication date (Electronic): 2 November 2023

Publication date PMC-release: 2 November 2023

Publication date Collection: 2023

Volume: 19

Electronic Location Identifier: 227

Affiliations

[1 ]Ophthalmology Section, Equine Department, Vetsuisse Faculty, University of Zurich, ( https://ror.org/02crff812) Zurich, Switzerland

[2 ]Epidemiology Section, Vetsuisse Faculty, University of Zurich, ( https://ror.org/02crff812) Zurich, Switzerland

[3 ]AniCura Vision Vet Veterinary Eye Clinic, Bologna, Italy

[4 ]Veterinary Vision, Penrith, UK

[5 ]Clinique Vétérinaire d’Ophtalmologie Spécialisée, Blagnac, France

Article

Publisher ID: 3779

DOI: 10.1186/s12917-023-03779-x

PMC ID: 10621152

SO-VID: 164d835e-5113-49a7-9852-23c22714b180

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 4 October 2022

Date accepted : 7 October 2023

Custom metadata

ScienceOpen disciplines: Veterinary medicine

Keywords: photoactivated chromophore for keratitis – corneal cross-linking,pack-cxl,canine,corneal ulcer,infectious keratitis,additive bayesian network,directed acyclic graph

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ScienceOpen disciplines: Veterinary medicine

Keywords: photoactivated chromophore for keratitis – corneal cross-linking, pack-cxl, canine, corneal ulcer, infectious keratitis, additive bayesian network, directed acyclic graph

Evaluation of risk factors for treatment failure in canine patients undergoing photoactivated chromophore for keratitis – corneal cross-linking (PACK-CXL): a retrospective study using additive bayesian network analysis

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Abstract

Background

Results

Conclusions

Supplementary Information

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Horses and Humans Research Foundation

Most cited references 43

Fitting Linear Mixed-Effects Models Usinglme4

Induction of cross-links in corneal tissue.

Increased resistance of crosslinked cornea against enzymatic digestion.

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