PetSavers – Corneal cytology and canine ulcerative keratitis

2 July 2021

Corneal ulceration is one of the most common ocular conditions seen in dogs. Uncomplicated superficial ulcers usually heal within 5-7 days by epithelial sliding with minimal scarring. However, bacterial invasion of such ulcers can lead to rapid disease progression and stromal involvement. This is in part due to the ability of bacteria to release toxins and proteinases, which further destroy the corneal stroma. Ultimately, the most concerning sequelae are corneal perforations or severe scarring and resultant vision impairment, blindness or loss of the eye. Corneal ulceration is also extremely painful, and urgent treatment is always required not only to salvage vision but also for analgesia and the welfare of the dog.

One of the objectives in the successful treatment of bacterial infection is the correct targeting of anti-microbial therapy which relies on bacterial identification. In clinical practice, this can be achieved by cytology and/or culture. Results of cytology are more instant, especially if performed in-house, compared to culture which can take a few days. It is usually recommended to perform both to maximise the identification of potential pathogens involved in canine ulcerative keratitis and to allow targeted antibiotic therapy. However, this approach is costly to the client. Therefore, the use of diagnostic testing in cases of ulcerative keratitis can be a clinical dilemma for some veterinary surgeons, especially when client finances are limited. In addition, due to the lag time (~3 days) between sampling and availability of culture results, by which time the ulcer may deteriorate, many veterinary surgeons adopt a ‘polypharmacy’ approach. This means that they use a combination of topical antibiotics with a spectrum wide enough to cover the most common bacteria causing progressive ulcerative keratitis in dogs in the UK.

A ‘polypharmacy’ approach is of course not desirable, given that correct antimicrobial targeting is not only important for resolution of the disease process, but on a wider global scale it is important in the prevention of antimicrobial resistance. Antimicrobial use in animals can contribute to the emergence of resistant bacteria that can be transferred to humans. This can then reduce the effectiveness of antimicrobials in treating human disease, thus putting human life at risk. Responsible use of antimicrobials is part of the Royal College of Veterinary Surgeons Code of Professional Conduct (section 4.22).  For these reasons, use of diagnostic testing is indicated to correctly target therapies and therefore avoid antimicrobial resistance.

Unlike culture, the results of in-house cytology are inexpensive and instantly available. Bearing in mind that infectious keratitis requires immediate therapy to prevent the painful and sight-threatening sequelae of the disease, in-house cytology would be the most appropriate test to guide a clinician’s initial anti-microbial choice. However, correct interpretation of cytological samples is likely to depend on the experience of the person assessing the slides, and there are conflicting reports in the literature on the diagnostic value of these tests. Thus there is a clinical need for further investigation into the diagnostic value of cytology compared to culture, and an understanding of whether veterinary surgeons without advanced training in laboratory medicine can successfully perform in-house cytology.

What are the aims of this research?

To assess the accuracy of corneal cytology performed by veterinary surgeons with varying experience in the management of ocular diseases as a tool to improve the choice of adequate antibiotic treatment in canine infectious ulcerative keratitis:

1. Assess the agreement of cytological findings with culture findings in cases of canine ulcerative keratitis
2. Assess the inter-observer agreement of cytological findings between veterinary surgeons of different training levels: ophthalmologists, pathologists and general practitioners

What have we learned so far?

Data collection for this study is now complete with the collection of corneal cytology and cultures from 150 canine ulcerative keratitis cases. Statistical analysis is still in progress and so it is too early to report on our findings; however, we hypothesise the following:

1. Cytology and culture findings will not show perfect agreement
2. There will be a variation in the cytological findings in canine ulcerative keratitis between veterinary surgeons of different training levels, with surgeons having specific training in corneal cytology (i.e. pathologists) showing better agreement with culture.

What will be the benefits of this research?

This study aims to provide further evidence on the usefulness and need for corneal cytology, culture, or both, to improve the effectiveness of canine ulcerative keratitis treatments, and to avoid possible sight-threatening consequences. In addition, this study should highlight the need for appropriate training in the evaluation of corneal cytology to prevent misdiagnosis. The results of this study will hopefully provide guidance on a sampling and assessment strategy for the use of cytology in the diagnosis and treatment of canine ulcerative keratitis.

Thinking about applying for PetSavers’ funding?

Without PetSavers’ funding this study would not have been possible. It has allowed for the costs of cytology and culture to be subsidised for client-owned dogs to have complete culture and sensitivity testing in-house, and external cytological analysis of their corneal ulcers.

Most research in the veterinary world comes from referral practice and so there is a natural case selection bias. There is a lack of published research from general practitioners and so I would urge any practitioners to consider carrying out research in practice. PetSavers is an excellent source of funding for such projects. I recommend contacting specialists about your ideas for research, many of whom would be very excited to be involved. Personally, this research has formed the foundation research project for my residency giving me the opportunity to carry out a prospective study and be successful in a grant application.

Work on the project has been carried out with collaborators at Cytopath Ltd., Ledbury, Herefordshire (E. Scurrell, M. Rozmanec, A. Civello) and several general practitioners in the UK (R. Goss, Maes Glas Veterinary Group, Bridgend, Wales; C. Watkins and H. Kearns, Belmont Vets, Hereford). Vicki Adams, Veterinary Epidemiology Consultant at Animal Cancer Trust is also acknowledged for her assistance with the study design and statistical analysis. We are very grateful to PetSavers for their generous funding of this study.