Application of OSA-VET® and qualiquantitative tear tests in brachycephalic dogs with and without keratoconjunctivitis sicca | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Application of OSA-VET® and qualiquantitative tear tests in brachycephalic dogs with and without keratoconjunctivitis sicca Jéssica N. Voitena, Tatiane O. C. Marinho, Fabiano Montiani-Ferreira, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4427211/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Nov, 2024 Read the published version in Veterinary Research Communications → Version 1 posted 11 You are reading this latest preprint version Abstract The aim was to compare the outcomes acquired from the OSA-Vet® device with conventional quantitative and qualitative tear tests and between groups within each test, in brachycephalic dogs both healthy and those diagnosed with keratoconjunctivitis sicca. The dogs were divided into four groups: healthy dogs (HD), with mild KCS (MIKCS); moderate KCS (MOKCS); severe KCS (SKCS). All patients underwent ocular surface diagnostic examination in the following order, with a 10-minute interval between tests: non-invasive tear film breakup time (TBUTNI - OSA-Vet®), tear meniscus height (TMH-OSA-Vet®), meniscometry (I-Tear® test), Schirmer Tear Test-1 (STT-1), and tear film breakup time (TBUT). Kruskal-Wallis H tests were performed to establish the difference between the groups and Spearman´s correlation coefficient test to assess the correlation between tests. And an analysis of variance (ANOVA) followed by Tukey-Kramer post-hoc test was performed for TMH. Results with (p<0.05) were considered statistically significant. The correlation of conventional tests in relation to those obtained by OSA-Vet® proved to be low, except between TBUTNI (OSA-Vet®) and TBUT in MOKCS, with a strong correlation (r=0.925). In the comparison between TBUTNI (OSA-Vet®) and TBUT in MIKCS the correlation was moderate (r=0.547) as well as STT-1 and I-Tear® test in MOKCS (r=0.416). In the comparison between groups, the main result observed was a significant difference between all the KCS groups and HD, in the TBUT and TBUTNI (OSA-Vet®) test. The OSA-Vet® and conventional tests are useful for evaluating the ocular surface of brachycephalic dogs. However, the OSA-Vet® does not correlate well with conventional standardized tests. Tear film tear film breakup time Schirmer’s Tear Test meniscometry dry eye I-Tear Figures Figure 1 1 INTRODUCTION Dry eye disease (DED) is a complex ophthalmic disorder with multiple underlying causes that result in the loss of the tear film stability, leading to ocular surface irritation and inflammation (de Oliveira et al. 2019). DED can be categorized into two types: one characterized by inadequate production of the aqueous layer of the tear film, termed quantitative deficiency, and another marked by excessive tear evaporation, known as qualitative deficiency, resulting from insufficient production of lipids or mucin (Berdoulay et al. 2005; Nascimento et al. 2022). In addition to the ophthalmic assessment, a variety of diagnostic tests are available for the diagnosis of DED. These tests are typically categorized into quantitative tests, such as the Schirmer Tear Test (STT-1), lacrimal meniscometry test, phenol red thread tear test, and endodontic absorbent paper point test; and qualitative tests including tear film breakup time (TBUT), tear osmolarity measurement, ferning test, and assessment with dyes such as rose bengal and lissamine green (Miyasaka et al. 2019). The Ocular Surface Analyser – Vet (OSA-Vet®, SBM Sistemi) has been developed to non-invasively evaluate the meibomian glands and the tear film, aiding in the diagnosis of DED. The OSA-Vet® performs several tests, such as interferometry (measurement of the thickness of the lipid layer), tear meniscus height (TMH), meibography, non-invasive tear film breakup time (TBUTNI) and ocular surface topography (George and Mohan 2019; Totuk et al. 2021; Kim et al. 2022). There are relatively few articles comparing the use of OSA-Vet® with conventional tests and documenting data from dolichocephalic or mesocephalic dogs (Viñas et al. 2019; Iwashita et al. 2022; Jeong et al. 2022; Kim et al. 2022; Hisey et al. 2023). Due to the limited availability of data in the literature concerning brachycephalic dogs (Faghihi and Rajaei 2023), the purpose of this study was to evaluate and compare the parameters of conventional strip tests (STT-1 and I-Tear® test) and TBUT with the images obtained by OSA-Vet® (TMH and TBUTNI) in healthy and DED-affected brachycephalic dogs and to determine if these measurements correlate with one another. 2 MATERIALS AND METHODS 2.1 Ethics committee The study was submitted and approved by the Animal Ethics Committee of the Federal University of Paraná - Sector Palotina (protocol n° 06/2021), according to the ethical principles of the Guidelines for Ethical Research in Veterinary Ophthalmology (GERVO). In addition, informed consent was obtained from all owners. 2.2 Animals Forty-five brachycephalic dogs, 30 females (66.66%) and 15 males (33.33%), aged between eight months and 13 years (mean 6.58±3.75 years; median 5,5 years) were included in the study. Inclusion criteria for this study involved brachycephalic dogs that showed absence of major palpebral disorders (entropion, distichiasis, ectopic lash, trichiasis), in absence of other ocular and/or systemic diseases, and not receiving any topical medications. Patients with corneal ulcers, poor diagnostic compliance, and with STT-1 higher than 25 mm/min were excluded from the study. According to these criteria, 83 eyes were included in the study. 2.3 Experimental Design Dogs were divided into four groups: healthy dogs (HD): STT-1 15 to 25 mm/min; and dogs with different degrees of KCS; mild KCS (MIKCS): STT-1 11 - 14 mm/min; moderate KCS (MOKCS): STT-1 6 - 10 mm/min; severe KCS (SKCS): STT-1 0-5 mm/min. All patients underwent complete ophthalmological evaluation in this order: evaluation with OSA-Vet® (TBUTNI and TMH), meniscometry (I-Tear® test), STT-1-1, ophthalmic evaluation with slit lamp and TBUT. The interval between tests was 10 minutes, to allow for tear turnover. All ophthalmic examinations were performed by the same examiner (JNV) on awake animals and with minimal physical restraint. The examination room was under the same conditions of temperature 18.5°C - 25.5°C and average humidity 65%. 2.4 Statistical analysis D'Agostino-Pearson test for normal distribution was applied to each variable. All variables, except TMH, did not follow a normal distribution. Analysis of variance (ANOVA) followed by Tukey-Kramer test (for TMH) or Kruskal-Wallis H test (for all other tests) were performed to evaluate for differences between the groups within each test. Spearman’s correlation coefficient between the same test results in the same groups were analyzed. MedCalc® Statistical Software version 20.027 (MedCalc Software Ltd, Ostend, Belgium) was used to analyze the data. The data analysis showed a normal distribution only for TMH; therefore, the results of TMH were presented as mean ± standard deviation. The other tests were not normally distributed and were described as median (interquartile range). 3 RESULTS The dog breeds included in the study were: Shih-Tzu (n =18/45, 40%), Pug (n:10/45, 22.2%), Lhasa Apso (n:6/45, 13.3%), French Bulldog (n:6/45, 13.3%), English Bulldog (n:1/45, 2.22%), English Toy Spaniel (n:1/45, 2.22%), Chihuahua (n:1/45, 2.22%), Maltese (n:1/45, 2.22%), and Pekingese (n:1/45, 2.22%), totaling 83 eyes. The results obtained by conventional tests as well as by OSA-Vet® in dogs with and without keratoconjunctivitis sicca are listed in Table 1. For dogs without KCS, the median STT-1 was 20(3.5) mm/min, similar to the mean values described as normal in the literature (18.89 ± 2.62 to 21.7 ± 4.9 mm/min) (Iwashita et al. 2022; Faghihi and Rajaei 2023), while the median I-Tear® test was 8(4) mm/5s, also similar to the values that reported in the literature (mean 7.4 ± 2.0 mm/5s) (Bolzanni et al. 2020). In relation to the groups with various degrees of KCS, the mean values of the TMH (OSA-Vet®) test were 0.39±0.18mm in MIKCS, 0.33±0.17mm in MOKCS and 0.24±0.13mm in SKCS. Regarding the I-Tear® test the median (interquartile range) were 7(5.5) mm/5s in MIKCS, 4(6) mm/5s in MOKCS and 1(2.25) mm/5s in SKCS. For dogs in the HD group, results were 0.51 ± 0.17mm for TMH and 8(4) mm/5s for I-Tear® test (Table 1 and Figure 1). The median (interquartile range) TBUT was 1 (1.75) s in MIKCS, 0 (1.75) s in MOKCS and 3 (6)s in HD group. The median (interquartile range) TBUTNI was 1 (2.75) s in MIKCS, 0 (0)s in MOKCS, 0 (0)s in SKCS and 3 (6.25) s in HD group (Table 1 and Figure 1). In I-Tear® test there was significant difference between groups MIKCS vs SKCS, HD vs SKCS and HD vs MOKCS. In the TMH (OSA-Vet®) there was a significant difference between groups MIKCS vs SKCS, HD vs SKCS, HD vs MOKCS and HD vs MIKCS. Regarding TBUT and TBUTNI (OSA-Vet®) both tests showed a significant difference between groups for dogs with and without KCS. (Table 2). According to Spearman´s Correlation Coefficient (r s ), between TBUT-NI (OSA-Vet®) and TBUT, there was moderate, positive and significant correlation within the group HD (0.547) and very strong, positive and significant in MOKCS (0.925). The other correlations were either weak or not significant. 4 DISCUSSION The clinical management of DED in dogs can be challenging due to the multiple underlying disease processes that alter tear film quantity and quality, as well as the advanced stage of the disease when dogs are evaluated. Therefore, the use of newer imaging and diagnostic testing may help to establish the diagnosis of DED at an earlier stage, allowing prompt and necessary treatment. Prior to widespread utilization, correlations between more traditional diagnostics tests with newer diagnostic modalities, particularly in healthy and DED-affected brachycephalic dogs, is necessary. When correlated, STT-1 and I-Tear test showed a moderate and not significant correlation only for dogs with severe dry eye, while the correlation was weak in the other groups. Previous studies have shown a strong correlation between STT-1 and I-Tear test in dogs with KCS (Miyasaka et al. 2019; Nascimento et al. 2022). This correlation is stronger with increasing severity of tear deficiency. Another study reports a weak positive correlation between these tests (Rajaei et al. 2014). However, these previous studies were performed also on dolichocephalic and mesocephalic breeds, not just brachycephalic as in our study. In our study, the results of the TBUT and TBUTNI (OSA-Vet®) tests, with median values of 3(6)s and 3(6.25)s for TBUT and TBUTNI respectively, were below the reported reference values for dogs with normal STT-I (Featherstone and Heinrich 2021). Other studies have reported a mean TBUT of 5.3±2.4s in the ShihTzu (Sebbag et al. 2022) breed, and 6±2s and 5.4±1.9s for the right eye and left eye, respectively, in brachycephalic breeds (Jeong et al. 2022). A study performed exclusively in healthy Pug dogs had TBUT values that were consistently higher than those found in our study (Labelle et al. 2013). Therefore, our study reveals that brachycephalic dogs in the HD group exhibited reduced TBUT values compared to the literature's reported average TBUT time for dogs in general, which typically falls between 19.7±5s and 21.53±7.42s (Featherstone and Heinrich 2021; Faghihi and Rajaei 2023). This difference could stem from various factors including examiner subjectivity, environmental conditions (such as temperature and humidity), and the quantity of fluorescein applied during the TBUT assessment (Seyer et al. 2021). Dogs with MOKCS demonstrated a strong correlation between TBUT and TBUTNI (OSA-Vet®) tests, furthering the utility of the TBUTNI to identify patients with moderate KCS when compared with the traditional TBUT test. However, in other groups the data did not show the same behavior, making it difficult to infer replacement in all situations. Some factors may be related to this correlation divergence, such as the patient’s cooperation when performing the test and the operator’s interpretation. There is a paucity of studies that focus on validating the TBUTNI (OSA-Vet®) with the traditional TBUT, highlighting the need for further studies to explore the utility of the TBUTNI test to evaluate patients with qualitative tear evaluation. With the exception of TBUTNI (OSA-Vet®), which showed a strong correlation with TBUT in the MOKCS group, the correlation between the results of the other diagnostic tests used and the OSA-Vet® device was low to moderate in all groups. There was a significant difference between TBUT and TBUTNI (OSA-Vet®) tests among all groups with KCS compared to HD, the ability of these non-traditional diagnostic testing to discriminate between healthy, mild, moderate and severe cases was not clear enough to be considered as accurate. Nevertheless, even with this difference, the values obtained in our study were below what the literature considers normal TBUT in dogs. The results found in our study were similar to those found in other studies in which brachycephalic dogs were evaluated, reaffirming that this conformational group has decreased TBUT even without quantitative KCS (Moore et al. 2001; Sebbag et al. 2022; Sebbag and Sanchez 2022). The results found in our study for TBUT or TBUTNI (OSA-Vet®) tests demonstrated their ability in diagnosing qualitative tear film disorder in brachycephalic dogs. Importantly, the use of either the TFBUT or TBUTNI to evaluate the tear film can facilitate an earlier diagnosis of DED and initiation of treatment at a less advanced stage of disease (Moore et al. 2001; Hisey et al. 2023). An advantage of the TBUTNI (OSA-Vet®) is that there is no interference from factors that may cause an erroneous result at the time of the exam, such as the volume and/or concentration of fluorescein, which may differ, making the TBUT less reliable (Moore et al. 2001; Iwashita et al. 2022; Faghihi and Rajaei 2023). However, the TBUTNI (OSA-Vet) has some subjectivity associated with the measurement as it requires the examiner to manually open the lids and determine the point at which the projected interference patterns demonstrate a disturbance, consistent with the breakup of the tear film. In conclusion, the results of this study demonstrated that it is not yet possible to replace conventional tests by the OSA-Vet® equipment, however it may be useful as an adjunctive diagnostic test for assessing tear film disorders. Brachycephalic dogs with KCS had comparable results between the TBUT and TBUTNI (OSA-Vet®) tests, demonstrating the potential utility of the TBUTNI (OSA-Vet) to assess tear film quality. Finally, more studies are needed to further validate the OSA-Vet and establishing reference values for different breeds. Declarations Conflict of interest The authors state that there is no conflict of interest. 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/. Authors’ contributions: J.N.V collected the data and wrote the manuscript T.O.C.M. collected the data F.M.F. conceptualized the idea and the statistical analysis D.N.C. conceptualized the idea and collected the data J.L.V.C. collected the data N.S.J. collected the data B.C.L. reviewed the manuscript O.C. reviewed the manuscript F.L.C.B. conceptualized the idea and reviewed the manuscript. References Berdoulay A, English RV, Nadelstein B (2005) Effect of topical 0.02% tacrolimus aqueous suspension on tear production in dogs with keratoconjunctivitis sicca. Vet Ophthalmol 8(4):225-232. Bolzanni H, Oriá AP, Raposo ACS, & Sebbag L (2020) Aqueous tear assessment in dogs: Impact of cephalic conformation, inter‐test correlations, and test‐retest repeatability. Vet Ophthalmol 23(3):534-543. de Oliveira JK, Williams DL, Bollmann C, de Seabra NM, Bortolini M, Montiani‐Ferreira F (2019) Comparative efficacy of topical oclacitinib 0.1% and tacrolimus 0.01% in canine keratoconjunctivitis sicca. Vet Ophthalmol 22(5):633-643. Faghihi H, Rajaei SM (2023) Tear film breakup time and Schirmer tear test in normal dogs: effects of age, sex, reproductive status, skull type, and nasolacrimal duct patency. Vet Ophthalmol v. 26, p. 72-80. Featherstone HJ, Heinrich CL (2023) Ophthalmic examination and diagnostics. In: Gelatt KA, ed. Veterinary Ophthalmology. 6th ed. John Wiley & Sons, Inc; 564-777, c.10. George R, Mohan P. Ocular surface analyzer. Kerala J. Ophthalmol.2019;31:72-74. Hisey EA, Galor A, Leonard BC (2023) A comparative review of evaporative dry eye disease and meibomian gland dysfunction in dogs and humans. Vet Ophthalmol 00:1-15. Iwashita H, Sebbag L, Leonard BC, & Saito A (2022) A review of diagnostic tests for qualitative and quantitative tear film deficiency in dogs. Vet Ophthalmol. Jeong D, Kang S, Shim J, Lee E, Jeong Y, Seo K (2022) Evaluation of ocular surface parameters in dogs with and without meibomian gland dysfunction. Vet Rec 121(2):e1682. Kim Y, Kang S, Kim S, Shim J, Go S, Seo K (2022) Reference values for selected dry eye tests in normal Beagle dogs: a pilot study. J. Vet. Sci 23(1). Labelle AL, Dresser CB, Hamor RE, Allender MC, & Disney JL (2013) Characteristics of, prevalence of, and risk factors for corneal pigmentation (pigmentary keratopathy) in Pugs. J. Am. Vet. Med. Assoc 243(5):667-674. Miyasaka K, Kazama Y, Iwashita H, Wakaiki S, Saito A (2019) A novel strip meniscometry method for measuring aqueous tear volume in dogs: Clinical correlations with the Schirmer tear and phenol red thread tests. Vet Ophthalmol 22(6): 864-871. Moore CP, McHugh JB, Thorne JG, Phillips TE (2001) Effect of cyclosporine on conjunctival mucin in a canine keratoconjunctivitis sicca model. Investig. Ophthalmol. Vis. Sci 42: 653–659. Nascimento FF, Passareli JVGC, Zulim LFDC, Silva DA, Giuffrida R, Estanho GJG, Andrade SF (2022) Comparison of strip meniscometry and Schirmer tear test results and tear film breakup time between healthy dogs and dogs with dry eye disease. Arq. Bras. Oftalmol. Rajaei SM, Ansari Mood M, Asadi F, Rajabian MR, Aghajanpour L (2018) Strip meniscometry in dogs, cats, and rabbits. Vet Ophthalmol 21(2):210-213. Sebbag, L, Sanchez, RF (2022) The pandemic of ocular surface disease in brachycephalic dogs: The brachycephalic ocular syndrome. Vet Ophthalmol 26, 31-46. Sebbag L, Silva APS, Santos ÁP, Raposo ACS, Oriá AP (2022) An eye on the Shih Tzu dog: Ophthalmic examination findings and ocular surface diagnostics. Vet Ophthalmol 26, 59-71. Seyer LD, Wills RW, & Betbeze CM (2021) Investigation of fluorescein stain–based tear film breakup time test reliability in dogs in a clinical setting. Am. J. Vet. Res 82(12):1019-1025. Totuk ÖMG, Kabadayı K, Özkapı C,Aykan Ü (2021) Efficacy of Intense Pulsed Light Treatment for Moderate to Severe Acute Blepharitis or Blepharoconjunctivitis: A Retrospective Case Series. Turk J Ophthalmol 51(2):89. Viñas M, Maggio F, D'Anna N, Rabozzi R, Peruccio C (2019) Meibomian gland dysfunction (MGD), as diagnosed by non-contact infrared Meibography, in dogs with ocular surface disorders (OSD): a retrospective study. BMC Vet Res 15(1):443. Tables Table 1 . Number of eyes in each group (n), median (interquartile range) and mean ± standard deviation of the test results obtained by conventional eye tests and by the OSA-Vet® device in brachycephalic dogs healthy (HD) and with keratoconjunctivitis sicca (MIKCS, MOKCS and SKCS) distributed in four groups. Variables HD MIKCS MOKCS SKCS n 44/83 11/83 11/83 17/83 STT-1 (mm/min) 20(3.5) 14(2) 10(2) 0(3) I-Tear ® test (mm/5s) 8(4) 7(5.5) 4(6) 1(2.25) TMH (OSA-Vet®) (mm) 0.51 ± 0.17 0.39 ± 0.18 0.33 ± 0.17 0.24 ± 0.13 TBUT(s) 3(6) 1(1.75) 0(1.75) 0(0.25) TBUTNI (OSA-Vet®) (s) 3(6.25) 1(2.75) 0(0) 0(0) Abbreviations: STT-1, Schirmer Tear Test-1; TMH, Tear meniscus height; TBUT, Tear film breakup time; TBUTNI, Non-invasive tear film breakup time; OSA-Vet® Ocular Surface Analyser – Vet. Table 2. P-value in the comparison between groups within each test. Groups I-Tear® test TMH (OSA-Vet®) TBUTNI (OSA-Vet®) TBUT MOKCS-SKCS 0,074 0,1852 0,6223 0,6846 MIKCS-SKCS 0,0017 a 0,0318 b 0,3611 0,4458 HD-SKCS <,0001 a <,0001 b <,0001 a 0,0006 a MIKCS-MOKCS 0,1962 0,4433 0,7015 0,7458 HD-MOKCS 0,0166 a 0,0026 b 0,0047 a 0,0132 a HD-MIKCS 0,4297 0,0364 b 0,0178 a 0,0368 a Abbreviations: TMH, Tear meniscus height; TBUT, Tear film breakup time; TBUTNI, Non-invasive tear film breakup time; OSA-Vet® Ocular Surface Analyser – Vet. a Significant difference between the two groups according to Kruskal-Wallis H test b Significant difference between the two groups according to Tukey-Kramer test. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 26 Nov, 2024 Read the published version in Veterinary Research Communications → Version 1 posted Editorial decision: Revision requested 12 Oct, 2024 Reviews received at journal 10 Oct, 2024 Reviewers agreed at journal 09 Oct, 2024 Reviews received at journal 21 Jun, 2024 Reviews received at journal 10 Jun, 2024 Reviewers agreed at journal 31 May, 2024 Reviewers agreed at journal 31 May, 2024 Reviewers invited by journal 31 May, 2024 Submission checks completed at journal 29 May, 2024 Editor assigned by journal 29 May, 2024 First submitted to journal 15 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4427211","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":312812941,"identity":"c3130c8e-467a-42ba-b517-f91b14cc812a","order_by":0,"name":"Jéssica N. 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Jesus","email":"","orcid":"","institution":"University São Judas Tadeu","correspondingAuthor":false,"prefix":"","firstName":"Nadja","middleName":"S.","lastName":"Jesus","suffix":""},{"id":312812950,"identity":"c75e4ad3-57d0-403f-8427-761960a59329","order_by":6,"name":"Brian C Leonard","email":"","orcid":"","institution":"University of California, Davis, University of California, Davis","correspondingAuthor":false,"prefix":"","firstName":"Brian","middleName":"C","lastName":"Leonard","suffix":""},{"id":312812952,"identity":"c6b9d67f-600a-4f5c-9fe9-560240b101b9","order_by":7,"name":"Olicies da Cunha","email":"","orcid":"","institution":"Federal University of Paraná (UFPR)","correspondingAuthor":false,"prefix":"","firstName":"Olicies","middleName":"da","lastName":"Cunha","suffix":""},{"id":312812955,"identity":"542fd476-a5f5-45b2-a695-4e7669d11f6e","order_by":8,"name":"Fábio L.C. Brito","email":"","orcid":"","institution":"Faculdade Qualittas","correspondingAuthor":false,"prefix":"","firstName":"Fábio","middleName":"L.C.","lastName":"Brito","suffix":""}],"badges":[],"createdAt":"2024-05-15 20:38:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4427211/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4427211/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11259-024-10610-x","type":"published","date":"2024-11-26T15:56:54+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":58248047,"identity":"75c72a50-822b-4957-8e7d-e49ed769bc97","added_by":"auto","created_at":"2024-06-13 02:44:43","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":165522,"visible":true,"origin":"","legend":"\u003cp\u003eImage representing the eyes and their respective tests with the OSA-Vet® device in groups HD (A, B and C), MIKCS (D, E and F), MOKCS (G, H and I) and SKCS (J, K, L). Photo of brachycephalic eyes for each study group (A, D, G, J), demonstration of meniscometry measurement with OSA-Vet® (B, E, H, K), image of the TBUTNI examination with the OSA-Vet® (C, F, I, L).\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4427211/v1/ed9bed7fe78cdb45b338a868.jpg"},{"id":70381565,"identity":"06dbb7c6-a710-468b-8e7a-ddd8dacc5dd7","added_by":"auto","created_at":"2024-12-02 16:12:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":554002,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4427211/v1/304e1240-f9da-42fd-a88c-35bb8026ca45.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Application of OSA-VET® and qualiquantitative tear tests in brachycephalic dogs with and without keratoconjunctivitis sicca","fulltext":[{"header":"1 INTRODUCTION ","content":"\u003cp\u003eDry eye disease (DED) is a complex ophthalmic disorder with multiple underlying causes that result in the loss of the tear film stability, leading to ocular surface irritation and inflammation (de Oliveira et al. 2019). DED can be categorized into two types: one characterized by inadequate production of the aqueous layer of the tear film, termed quantitative deficiency, and another marked by excessive tear evaporation, known as qualitative deficiency, resulting from insufficient production of lipids or mucin (Berdoulay et al. 2005; Nascimento et al. 2022).\u003c/p\u003e\n\u003cp\u003eIn addition to the ophthalmic assessment, a variety of diagnostic tests are available for the diagnosis of DED. These tests are typically categorized into quantitative tests, such as the Schirmer Tear Test (STT-1), lacrimal meniscometry test, phenol red thread tear test, and endodontic absorbent paper point test; and qualitative tests including tear film breakup time (TBUT), tear osmolarity measurement, ferning test, and assessment with dyes such as rose bengal and lissamine green (Miyasaka et al. 2019).\u003c/p\u003e\n\u003cp\u003eThe Ocular Surface Analyser \u0026ndash; Vet (OSA-Vet\u0026reg;, SBM Sistemi) has been developed to non-invasively evaluate the meibomian glands and the tear film, aiding in the diagnosis of DED. The OSA-Vet\u0026reg; performs several tests, such as interferometry (measurement of the thickness of the lipid layer), tear meniscus height (TMH), meibography, non-invasive tear film breakup time (TBUTNI) and ocular surface topography (George and Mohan 2019; Totuk et al. 2021; Kim et al. 2022).\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eThere are relatively few articles comparing the use of OSA-Vet\u0026reg; with conventional tests and documenting data from dolichocephalic or mesocephalic dogs (Vi\u0026ntilde;as et al. 2019; Iwashita et al. 2022; Jeong et al. 2022; Kim et al. 2022; Hisey et al. 2023).\u003csup\u003e\u0026nbsp;\u003c/sup\u003eDue to the limited availability of data in the literature concerning brachycephalic dogs (Faghihi and Rajaei 2023), the purpose of this study was to evaluate and compare the parameters of conventional strip tests (STT-1 and I-Tear\u0026reg; test) and TBUT with the images obtained by OSA-Vet\u0026reg; (TMH and TBUTNI) in healthy and DED-affected brachycephalic dogs and to determine if these measurements correlate with one another.\u003c/p\u003e"},{"header":"2 MATERIALS AND METHODS","content":"\u003cp\u003e\u003cstrong\u003e2.1 Ethics committee\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was submitted and approved by the Animal Ethics Committee of the Federal University of Paran\u0026aacute; - Sector Palotina (protocol n\u0026deg; 06/2021), according to the ethical principles of the Guidelines for Ethical Research in Veterinary Ophthalmology (GERVO). In addition, informed consent was obtained from all owners.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Animals\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eForty-five brachycephalic dogs, 30 females (66.66%) and 15 males (33.33%), aged between eight months and 13 years (mean 6.58\u0026plusmn;3.75 years; median 5,5 years) were included in the study. Inclusion criteria for this study involved brachycephalic dogs that showed absence of major palpebral disorders (entropion, distichiasis, ectopic lash, trichiasis), in absence of other ocular and/or systemic diseases, and not receiving any topical medications. Patients with corneal ulcers, poor diagnostic compliance, and with STT-1 higher than 25 mm/min were excluded from the study. According to these criteria, 83 eyes were included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Experimental Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDogs were divided into four groups: healthy dogs (HD): STT-1 15 to 25 mm/min; and dogs with different degrees of KCS; mild KCS (MIKCS): STT-1 11 - 14 mm/min; moderate KCS (MOKCS): STT-1 6 - 10 mm/min; severe KCS (SKCS): STT-1 0-5 mm/min. All patients underwent complete ophthalmological evaluation in this order: evaluation with OSA-Vet\u0026reg; (TBUTNI and TMH), meniscometry (I-Tear\u0026reg; test), STT-1-1, ophthalmic evaluation with slit lamp and TBUT. The interval between tests was 10 minutes, to allow for tear turnover.\u003c/p\u003e\n\u003cp\u003eAll ophthalmic examinations were performed by the same examiner (JNV) on awake animals and with minimal physical restraint. The examination room was under the same conditions of temperature 18.5\u0026deg;C - 25.5\u0026deg;C and average humidity 65%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4 Statistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eD\u0026apos;Agostino-Pearson test for normal distribution was applied to each variable. All variables, except TMH, did not follow a normal distribution. Analysis of variance (ANOVA) followed by Tukey-Kramer test (for TMH) or Kruskal-Wallis H test (for all other tests) were performed to evaluate for differences between the groups within each test. Spearman\u0026rsquo;s correlation coefficient between the same test results in the same groups were analyzed. MedCalc\u0026reg; Statistical Software version 20.027 (MedCalc Software Ltd, Ostend, Belgium) was used to analyze the data. The data analysis showed a normal distribution only for TMH; therefore, the results of TMH were presented as mean \u0026plusmn; standard deviation. The other tests were not normally distributed and were described as median (interquartile range).\u0026nbsp;\u003c/p\u003e"},{"header":"3 RESULTS","content":"\u003cp\u003eThe dog breeds included in the study were: Shih-Tzu (n =18/45, 40%), Pug (n:10/45, 22.2%), Lhasa Apso (n:6/45, 13.3%), French Bulldog (n:6/45, 13.3%), English Bulldog (n:1/45, 2.22%), English Toy Spaniel (n:1/45, 2.22%), Chihuahua (n:1/45, 2.22%), Maltese (n:1/45, 2.22%), and Pekingese (n:1/45, 2.22%), totaling 83 eyes.\u003c/p\u003e\n\u003cp\u003eThe results obtained by conventional tests as well as by OSA-Vet\u0026reg; in dogs with and without keratoconjunctivitis sicca are listed in Table 1.\u003c/p\u003e\n\u003cp\u003eFor dogs without KCS, the median STT-1 was 20(3.5) mm/min, similar to the mean values described as normal in the literature (18.89 \u0026plusmn; 2.62 to 21.7 \u0026plusmn; 4.9 mm/min) (Iwashita et al. 2022; Faghihi and Rajaei 2023), while the median I-Tear\u0026reg; test was 8(4) mm/5s, also similar to the values that reported in the literature (mean 7.4 \u0026plusmn; 2.0 mm/5s) (Bolzanni et al. 2020).\u003c/p\u003e\n\u003cp\u003eIn relation to the groups with various degrees of KCS, the mean values of the TMH (OSA-Vet\u0026reg;) test were 0.39\u0026plusmn;0.18mm in MIKCS, 0.33\u0026plusmn;0.17mm in MOKCS and 0.24\u0026plusmn;0.13mm in SKCS. Regarding the I-Tear\u0026reg; test the median (interquartile range) were 7(5.5) mm/5s in MIKCS, 4(6) mm/5s in MOKCS and 1(2.25) mm/5s in SKCS. For dogs in the HD group, results were 0.51 \u0026plusmn; 0.17mm for TMH and 8(4) mm/5s for I-Tear\u0026reg; test (Table 1 and Figure 1).\u003c/p\u003e\n\u003cp\u003eThe median (interquartile range) TBUT was 1 (1.75) s in MIKCS, 0 (1.75) s in MOKCS and\u0026nbsp;3 (6)s in HD group. The\u0026nbsp;median (interquartile range) TBUTNI was 1 (2.75) s in MIKCS, 0 (0)s in MOKCS, 0 (0)s in SKCS and\u0026nbsp;3 (6.25) s in HD group\u0026nbsp;(Table 1 and Figure 1).\u003c/p\u003e\n\u003cp\u003eIn I-Tear\u0026reg; test there was significant difference between groups MIKCS vs SKCS, HD vs SKCS and HD vs MOKCS. In the TMH (OSA-Vet\u0026reg;) there was a significant difference between groups MIKCS vs SKCS, HD vs SKCS, HD vs MOKCS and HD vs MIKCS. Regarding TBUT and TBUTNI (OSA-Vet\u0026reg;) both tests showed a significant difference between groups for dogs with and without KCS. (Table 2).\u003c/p\u003e\n\u003cp\u003eAccording to Spearman\u0026acute;s Correlation Coefficient (r\u003csub\u003es\u003c/sub\u003e), between TBUT-NI (OSA-Vet\u0026reg;) and TBUT, there was moderate, positive and significant correlation within the group HD (0.547) and very strong, positive and significant in MOKCS (0.925). The other correlations were either weak or not significant.\u003c/p\u003e"},{"header":"4 DISCUSSION","content":"\u003cp\u003eThe clinical management of DED in dogs can be challenging due to the multiple underlying disease processes that alter tear film quantity and quality, as well as the advanced stage of the disease when dogs are evaluated. Therefore, the use of newer imaging and diagnostic testing may help to establish the diagnosis of DED at an earlier stage, allowing prompt and necessary treatment. Prior to widespread utilization, correlations between more traditional diagnostics tests with newer diagnostic modalities, particularly in healthy and DED-affected brachycephalic dogs, is necessary. When correlated, STT-1 and I-Tear test showed a moderate and not significant correlation only for dogs with severe dry eye, while the correlation was weak in the other groups. Previous studies have shown a strong correlation between STT-1 and I-Tear test in dogs with KCS (Miyasaka et al. 2019; Nascimento et al. 2022). This correlation is stronger with increasing severity of tear deficiency. Another study reports a weak positive correlation between these tests (Rajaei et al. 2014). \u0026nbsp;However, these previous studies were performed also on dolichocephalic and mesocephalic breeds, not just brachycephalic as in our study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our study, the results of the TBUT and TBUTNI (OSA-Vet\u0026reg;) tests, with median values of 3(6)s and 3(6.25)s for TBUT and TBUTNI respectively, were below the reported reference values for dogs with normal STT-I (Featherstone and Heinrich 2021). Other studies have reported a mean TBUT of 5.3\u0026plusmn;2.4s in the ShihTzu\u003csup\u003e\u0026nbsp;\u003c/sup\u003e(Sebbag et al. 2022) breed, and 6\u0026plusmn;2s and 5.4\u0026plusmn;1.9s for the right eye and left eye, respectively, in brachycephalic breeds (Jeong et al. 2022). A study performed exclusively in healthy Pug dogs had TBUT values that were consistently higher than those found in our study (Labelle et al. 2013).\u003csup\u003e\u0026nbsp;\u003c/sup\u003e Therefore, our study reveals that brachycephalic dogs in the HD group exhibited reduced TBUT values compared to the literature\u0026apos;s reported average TBUT time for dogs in general, which typically falls between 19.7\u0026plusmn;5s and 21.53\u0026plusmn;7.42s (Featherstone and Heinrich 2021; Faghihi and Rajaei 2023).\u003csup\u003e\u0026nbsp;\u003c/sup\u003eThis difference could stem from various factors including examiner subjectivity, environmental conditions (such as temperature and humidity), and the quantity of fluorescein applied during the TBUT assessment (Seyer et al. 2021).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDogs with MOKCS demonstrated a strong correlation between TBUT and TBUTNI (OSA-Vet\u0026reg;) tests, furthering the utility of the TBUTNI to identify patients with moderate KCS when compared with the traditional TBUT test. However, in other groups the data did not show the same behavior, making it difficult to infer replacement in all situations. Some factors may be related to this correlation divergence, such as the patient\u0026rsquo;s cooperation when performing the test and the operator\u0026rsquo;s interpretation. There is a paucity of studies that focus on validating the TBUTNI (OSA-Vet\u0026reg;) with the traditional TBUT, highlighting the need for further studies to explore the utility of the TBUTNI test to evaluate patients with qualitative tear evaluation.\u003c/p\u003e\n\u003cp\u003eWith the exception of TBUTNI (OSA-Vet\u0026reg;), which showed a strong correlation with TBUT in the MOKCS group, the correlation between the results of the other diagnostic tests used and the OSA-Vet\u0026reg; device was low to moderate in all groups.\u0026nbsp;There was a significant difference between TBUT and TBUTNI (OSA-Vet\u0026reg;) tests among all groups with KCS compared to HD, the ability of these non-traditional diagnostic testing to discriminate between healthy, mild, moderate and severe cases was not clear enough to be considered as accurate. Nevertheless, even with this difference, the values obtained in our study were below what the literature considers normal TBUT in dogs. The results found in our study were similar to those found in other studies in which brachycephalic dogs were evaluated, reaffirming that this conformational group has decreased TBUT even without quantitative KCS (Moore et al. 2001; Sebbag et al. 2022; Sebbag and Sanchez 2022).\u003c/p\u003e\n\u003cp\u003eThe results found in our study for TBUT or TBUTNI (OSA-Vet\u0026reg;) tests demonstrated their ability in diagnosing qualitative tear film disorder in brachycephalic dogs. Importantly, the use of either the TFBUT or TBUTNI to evaluate the tear film can facilitate an earlier diagnosis of DED and initiation of treatment at a less advanced stage of disease (Moore et al. 2001; Hisey et al. 2023). An advantage of the TBUTNI (OSA-Vet\u0026reg;) is that there is no interference from factors that may cause an erroneous result at the time of the exam, such as the volume and/or concentration of fluorescein, which may differ, making the TBUT less reliable (Moore et al. 2001; Iwashita et al. 2022; Faghihi and Rajaei 2023). However, the TBUTNI (OSA-Vet) has some subjectivity associated with the measurement as it requires the examiner to manually open the lids and determine the point at which the projected interference patterns demonstrate a disturbance, consistent with the breakup of the tear film.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, the results of this study demonstrated that it is not yet possible to replace conventional tests by the OSA-Vet\u0026reg; equipment, however it may be useful as an adjunctive diagnostic test for assessing tear film disorders. \u0026nbsp; Brachycephalic dogs with KCS had comparable results between the TBUT and TBUTNI (OSA-Vet\u0026reg;) tests, demonstrating the potential utility of the TBUTNI (OSA-Vet) to assess tear film quality. Finally, more studies are needed to further validate the OSA-Vet and establishing reference values for different breeds.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003eThe authors state that there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOpen Access\u0026nbsp;\u003c/strong\u003eThis 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\u0026rsquo;s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article\u0026rsquo;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/.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u0026nbsp;\u003c/strong\u003eJ.N.V collected the data and wrote the manuscript T.O.C.M. collected the data \u0026nbsp;F.M.F. conceptualized the idea and the statistical analysis \u0026nbsp;D.N.C. conceptualized the idea and collected the data J.L.V.C. collected the data N.S.J. collected the data B.C.L. reviewed the manuscript O.C. reviewed the manuscript F.L.C.B. conceptualized the idea and reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBerdoulay A, English RV, Nadelstein B (2005) Effect of topical 0.02% tacrolimus aqueous suspension on tear production in dogs with keratoconjunctivitis sicca. Vet Ophthalmol 8(4):225-232.\u003c/li\u003e\n\u003cli\u003eBolzanni H, Ori\u0026aacute; AP, Raposo ACS, \u0026amp; Sebbag L (2020) Aqueous tear assessment in dogs: Impact of cephalic conformation, inter‐test correlations, and test‐retest repeatability. Vet Ophthalmol 23(3):534-543.\u003c/li\u003e\n\u003cli\u003ede Oliveira JK, Williams DL, Bollmann C, de Seabra NM, Bortolini M, Montiani‐Ferreira F (2019) Comparative efficacy of topical oclacitinib 0.1% and tacrolimus 0.01% in canine keratoconjunctivitis sicca. Vet Ophthalmol 22(5):633-643.\u003c/li\u003e\n\u003cli\u003eFaghihi H, Rajaei SM (2023) Tear film breakup time and Schirmer tear test in normal dogs: effects of age, sex, reproductive status, skull type, and nasolacrimal duct patency. Vet Ophthalmol v. 26, p. 72-80.\u003c/li\u003e\n\u003cli\u003eFeatherstone HJ, Heinrich CL (2023) Ophthalmic examination and diagnostics. In: Gelatt KA, ed. Veterinary Ophthalmology. 6th ed. John Wiley \u0026amp; Sons, Inc; 564-777, c.10.\u003c/li\u003e\n\u003cli\u003eGeorge R, Mohan P. Ocular surface analyzer. Kerala J. Ophthalmol.2019;31:72-74.\u003c/li\u003e\n\u003cli\u003eHisey EA, Galor A, Leonard BC (2023) A comparative review of evaporative dry eye disease and meibomian gland dysfunction in dogs and humans. Vet Ophthalmol 00:1-15.\u003c/li\u003e\n\u003cli\u003eIwashita H, Sebbag L, Leonard BC, \u0026amp; Saito A (2022) A review of diagnostic tests for qualitative and quantitative tear film deficiency in dogs. Vet Ophthalmol. \u003c/li\u003e\n\u003cli\u003eJeong D, Kang S, Shim J, Lee E, Jeong Y, Seo K (2022) Evaluation of ocular surface parameters in dogs with and without meibomian gland dysfunction. Vet Rec 121(2):e1682.\u003c/li\u003e\n\u003cli\u003eKim Y, Kang S, Kim S, Shim J, Go S, Seo K (2022) Reference values for selected dry eye tests in normal Beagle dogs: a pilot study. J. Vet. Sci 23(1).\u003c/li\u003e\n\u003cli\u003eLabelle AL, Dresser CB, Hamor RE, Allender MC, \u0026amp; Disney JL (2013) Characteristics of, prevalence of, and risk factors for corneal pigmentation (pigmentary keratopathy) in Pugs. J. Am. Vet. Med. Assoc 243(5):667-674.\u003c/li\u003e\n\u003cli\u003eMiyasaka K, Kazama Y, Iwashita H, Wakaiki S, Saito A (2019) A novel strip meniscometry method for measuring aqueous tear volume in dogs: Clinical correlations with the Schirmer tear and phenol red thread tests. Vet Ophthalmol 22(6): 864-871.\u003c/li\u003e\n\u003cli\u003eMoore CP, McHugh JB, Thorne JG, Phillips TE (2001) Effect of cyclosporine on conjunctival mucin in a canine keratoconjunctivitis sicca model. Investig. Ophthalmol. Vis. Sci 42: 653\u0026ndash;659.\u003c/li\u003e\n\u003cli\u003eNascimento FF, Passareli JVGC, Zulim LFDC, Silva DA, Giuffrida R, Estanho GJG, Andrade SF (2022) Comparison of strip meniscometry and Schirmer tear test results and tear film breakup time between healthy dogs and dogs with dry eye disease. Arq. Bras. Oftalmol. \u003c/li\u003e\n\u003cli\u003eRajaei SM, Ansari Mood M, Asadi F, Rajabian MR, Aghajanpour L (2018) Strip meniscometry in dogs, cats, and rabbits. Vet Ophthalmol 21(2):210-213.\u003c/li\u003e\n\u003cli\u003eSebbag, L, Sanchez, RF (2022) The pandemic of ocular surface disease in brachycephalic dogs: The brachycephalic ocular syndrome. Vet Ophthalmol 26, 31-46.\u003c/li\u003e\n\u003cli\u003eSebbag L, Silva APS, Santos \u0026Aacute;P, Raposo ACS, Ori\u0026aacute; AP (2022) An eye on the Shih Tzu dog: Ophthalmic examination findings and ocular surface diagnostics. Vet Ophthalmol 26, 59-71.\u003c/li\u003e\n\u003cli\u003eSeyer LD, Wills RW, \u0026amp; Betbeze CM (2021) Investigation of fluorescein stain\u0026ndash;based tear film breakup time test reliability in dogs in a clinical setting. Am. J. Vet. Res 82(12):1019-1025.\u003c/li\u003e\n\u003cli\u003eTotuk \u0026Ouml;MG, Kabadayı K, \u0026Ouml;zkapı C,Aykan \u0026Uuml; (2021) Efficacy of Intense Pulsed Light Treatment for Moderate to Severe Acute Blepharitis or Blepharoconjunctivitis: A Retrospective Case Series. Turk J Ophthalmol 51(2):89.\u003c/li\u003e\n\u003cli\u003eVi\u0026ntilde;as M, Maggio F, D\u0026apos;Anna N, Rabozzi R, Peruccio C (2019) Meibomian gland dysfunction (MGD), as diagnosed by non-contact infrared Meibography, in dogs with ocular surface disorders (OSD): a retrospective study. BMC Vet Res 15(1):443.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Number of eyes in each group (n), median (interquartile range) and mean \u0026plusmn; standard deviation of the test results obtained by conventional eye tests and by the OSA-Vet\u0026reg; device in brachycephalic dogs healthy (HD) and with keratoconjunctivitis sicca (MIKCS, MOKCS and SKCS) distributed in four groups.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.21554770318021%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.901060070671377%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHD\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.021201413427562%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIKCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMOKCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSKCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.21554770318021%\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.901060070671377%\" valign=\"top\"\u003e\n \u003cp\u003e44/83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.021201413427562%\" valign=\"top\"\u003e\n \u003cp\u003e11/83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e11/83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e17/83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.21554770318021%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSTT-1 (mm/min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.901060070671377%\" valign=\"top\"\u003e\n \u003cp\u003e20(3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.021201413427562%\" valign=\"top\"\u003e\n \u003cp\u003e14(2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e10(2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e0(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.21554770318021%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eI-Tear\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026reg;\u0026nbsp;test (mm/5s)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.901060070671377%\" valign=\"top\"\u003e\n \u003cp\u003e8(4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.021201413427562%\" valign=\"top\"\u003e\n \u003cp\u003e7(5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e4(6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e1(2.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.21554770318021%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTMH\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(OSA-Vet\u0026reg;) (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.901060070671377%\"\u003e\n \u003cp\u003e0.51 \u0026plusmn; 0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.021201413427562%\"\u003e\n \u003cp\u003e0.39 \u0026plusmn; 0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\"\u003e\n \u003cp\u003e0.33 \u0026plusmn; 0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\"\u003e\n \u003cp\u003e0.24 \u0026plusmn; 0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.21554770318021%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTBUT(s)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.901060070671377%\" valign=\"top\"\u003e\n \u003cp\u003e3(6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.021201413427562%\" valign=\"top\"\u003e\n \u003cp\u003e1(1.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e0(1.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e0(0.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.21554770318021%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTBUTNI (OSA-Vet\u0026reg;) (s)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.901060070671377%\" valign=\"top\"\u003e\n \u003cp\u003e3(6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.021201413427562%\" valign=\"top\"\u003e\n \u003cp\u003e1(2.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.431095406360424%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: STT-1, Schirmer Tear Test-1; TMH, Tear meniscus height; TBUT, Tear film breakup time; TBUTNI, Non-invasive tear film breakup time; OSA-Vet\u0026reg; Ocular Surface Analyser \u0026ndash; Vet.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e P-value in the comparison between groups within each test.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"102%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.259896729776248%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eI-Tear\u0026reg; test\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTMH (OSA-Vet\u0026reg;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.555938037865747%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTBUTNI (OSA-Vet\u0026reg;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.006884681583475%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTBUT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.259896729776248%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eMOKCS-SKCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e0,074\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e0,1852\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.555938037865747%\" valign=\"top\"\u003e\n \u003cp\u003e0,6223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.006884681583475%\" valign=\"top\"\u003e\n \u003cp\u003e0,6846\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.259896729776248%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIKCS-SKCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e0,0017\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e0,0318\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.555938037865747%\" valign=\"top\"\u003e\n \u003cp\u003e0,3611\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.006884681583475%\" valign=\"top\"\u003e\n \u003cp\u003e0,4458\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.259896729776248%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eHD-SKCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;,0001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;,0001\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.555938037865747%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;,0001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.006884681583475%\" valign=\"top\"\u003e\n \u003cp\u003e0,0006\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.259896729776248%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIKCS-MOKCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e0,1962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e0,4433\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.555938037865747%\" valign=\"top\"\u003e\n \u003cp\u003e0,7015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.006884681583475%\" valign=\"top\"\u003e\n \u003cp\u003e0,7458\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.259896729776248%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eHD-MOKCS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e0,0166\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e0,0026\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.555938037865747%\" valign=\"top\"\u003e\n \u003cp\u003e0,0047\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.006884681583475%\" valign=\"top\"\u003e\n \u003cp\u003e0,0132\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.259896729776248%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eHD-MIKCS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e0,4297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.588640275387263%\" valign=\"top\"\u003e\n \u003cp\u003e0,0364\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.555938037865747%\" valign=\"top\"\u003e\n \u003cp\u003e0,0178\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.006884681583475%\" valign=\"top\"\u003e\n \u003cp\u003e0,0368\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: TMH, Tear meniscus height; TBUT, Tear film breakup time; TBUTNI, Non-invasive tear film breakup time; OSA-Vet\u0026reg; Ocular Surface Analyser \u0026ndash; Vet.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eSignificant difference between the two groups according to Kruskal-Wallis H test\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u0026nbsp;\u003c/sup\u003eSignificant difference between the two groups according to Tukey-Kramer test.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"veterinary-research-communications","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"verc","sideBox":"Learn more about [Veterinary Research Communications](https://www.springer.com/journal/11259)","snPcode":"11259","submissionUrl":"https://submission.nature.com/new-submission/11259/3","title":"Veterinary Research Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Tear film, tear film breakup time, Schirmer’s Tear Test, meniscometry, dry eye, I-Tear","lastPublishedDoi":"10.21203/rs.3.rs-4427211/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4427211/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"The aim was to compare the outcomes acquired from the OSA-Vet® device with conventional quantitative and qualitative tear tests and between groups within each test, in brachycephalic dogs both healthy and those diagnosed with keratoconjunctivitis sicca. The dogs were divided into four groups: healthy dogs (HD), with mild KCS (MIKCS); moderate KCS (MOKCS); severe KCS (SKCS). All patients underwent ocular surface diagnostic examination in the following order, with a 10-minute interval between tests: non-invasive tear film breakup time (TBUTNI - OSA-Vet®), tear meniscus height (TMH-OSA-Vet®), meniscometry (I-Tear® test), Schirmer Tear Test-1 (STT-1), and tear film breakup time (TBUT). Kruskal-Wallis H tests were performed to establish the difference between the groups and Spearman´s correlation coefficient test to assess the correlation between tests. And an analysis of variance (ANOVA) followed by Tukey-Kramer post-hoc test was performed for TMH. Results with (p\u003c0.05) were considered statistically significant. The correlation of conventional tests in relation to those obtained by OSA-Vet® proved to be low, except between TBUTNI (OSA-Vet®) and TBUT in MOKCS, with a strong correlation (r=0.925). In the comparison between TBUTNI (OSA-Vet®) and TBUT in MIKCS the correlation was moderate (r=0.547) as well as STT-1 and I-Tear® test in MOKCS (r=0.416). In the comparison between groups, the main result observed was a significant difference between all the KCS groups and HD, in the TBUT and TBUTNI (OSA-Vet®) test. The OSA-Vet® and conventional tests are useful for evaluating the ocular surface of brachycephalic dogs. However, the OSA-Vet® does not correlate well with conventional standardized tests.","manuscriptTitle":"Application of OSA-VET® and qualiquantitative tear tests in brachycephalic dogs with and without keratoconjunctivitis sicca","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-13 02:44:38","doi":"10.21203/rs.3.rs-4427211/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-12T08:56:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-10T14:06:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"274801401862337792120016817058483830967","date":"2024-10-09T15:00:17+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-21T08:04:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-10T19:10:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"283173174723579993173845015152121451954","date":"2024-05-31T18:21:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"121146312654499001570019836712977168951","date":"2024-05-31T17:19:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-31T17:05:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-29T04:51:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-29T04:51:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Veterinary Research Communications","date":"2024-05-15T20:32:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
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