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Topical dexamethasone decelerates epithelial migration on the canine tympanic membrane.

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Název: Topical dexamethasone decelerates epithelial migration on the canine tympanic membrane.
Autoři: Kim, Jihyun1 (AUTHOR), Oh, Taeho1 (AUTHOR), Bae, Seulgi1 (AUTHOR) sgbae@knu.ac.kr
Zdroj: Veterinary Dermatology. Apr2025, Vol. 36 Issue 2, p159-164. 6p.
Druh dokumentu: Article
Author Affiliations: 1Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
Full Text Word Count: 3847
ISSN: 0959-4493
DOI: 10.1111/vde.13314
Přístupové číslo: 183821327
Databáze: Veterinary Source
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  Value: <anid>AN0183821327;f1001apr.25;2025Mar20.07:25;v2.2.500</anid> <title id="AN0183821327-1">Topical dexamethasone decelerates epithelial migration on the canine tympanic membrane </title> <p>Background: Epithelial migration (EM) is integral to normal ear structure and function. Glucocorticoids are considered the first‐line therapy for various external ear disorders; however, their effects on EM on the tympanic membrane (TM) and the external auditory canal (EAC) are understudied. Hypothesis/Objectives: To test the hypothesis that topical dexamethasone decelerates EM on the TM, this study aimed to evaluate the effects of topical dexamethasone on EM on the TMs of dogs. Animals: Seven ears of four healthy dogs. Materials and Methods: The migration distance of an ink drop deposited on the posterior quadrant of the pars tensa (TM EM rate) of dogs was calculated over 3 weeks from images captured with a video‐otoscope. The results were compared by paired Student's t‐test to those obtained from a subsequent experiment in which the same dogs were administered a fresh ink drop at the same position as previously (control group), yet additionally administered 0.1% dexamethasone (0.2 mL/ear) daily for the first 14 days (treatment group). Results: One of eight ears was excluded because of an anatomical problem. The TM EM rate of the remaining seven ears decreased by 46.74% in the treatment group compared with the control group (p < 0.05). Conclusions and Clinical Relevance: Topical dexamethasone decelerates EM on the TM of normal dogs' ears. In turn, it is extrapolated that debris removal from the EAC may be slowed, negatively impacting the EAC environment. Consequently, when dogs with otitis receive topical dexamethasone treatment, additional treatment, such as ear canal cleaning, may be required to minimise the effects of impaired TM EM.</p> <p>Zusammenfassung: Die epitheliale Migration (EM) ist ein integraler Bestandteil der normalen Ohrstruktur und ‐funktion. Glucocorticoide werden als Erstlinientherapie für verschiedene Erkrankungen des externen Ohres betrachtet; nichtsdestotrotz sind ihre Auswirkungen auf die EM des Trommelfells (TM) und auf den äußeren Gehörkanal (EAC) nicht ausreichend untersucht. Hypothese/Ziele: Um die Hypothese, dass topisch angewandtes Dexamethason die EM des TM verlangsamt, auszutesten, war das Ziel dieser Studie, die Evaluierung der Auswirkungen des topisch angewandten Dexamethasons auf die EM des TMs von Hunden. Tiere: Sieben Ohren von vier gesunden Hunden. Materialien und Methoden: Die Migration eines Tropfens Tinte, der im hinteren Quadranten der Pars tensa (TM EM Quote) der Hunde abgesetzt wurde, wurde drei Wochen lang aus Bildern, die mit einem Videootoskop gemacht wurden, kalkuliert. Die Ergebnisse wurden mit einem gepaarten Stichproben‐t‐Test mit jenen verglichen, die in einem nachfolgenden Experiment, wo bei denselben Hunden ein frischer Tropfen Tinte an derselben Position wie zuvor (Kontrollgruppe) verabreicht wurde, wobei allerdings für die ersten 14 Tage (Behandlungsgruppe) täglich 0.1% Dexamethason (0.2 mL/Ohr) verabreicht wurde. Ergebnisse: Eines von acht Ohren wurde aufgrund eines anatomischen Problems ausgeschlossen. Die TM EM Quote der verbleibenden sieben Ohren nahm in der Behandlungsgruppe um 46.74% im Vergleich zur Kontrollgruppe ab (p < 0.05). Schlussfolgerungen und klinische Bedeutung: Topisch angewandtes Dexamethason verlangsamt die EM des TM in normalen Hundeohren. In der Folge kann extrapoliert werden, dass der Abtransport des Debris aus dem EAC verlangsamt sein könnte, was das Umfeld des EAC negativ beeinflusst. Folglich könnte es nötig sein, dass Hunde mit einer Otitis, die topisch Dexamethason verabreicht bekommen, eine zusätzliche Behandlung wie eine Ohrreinigung erhalten, um den Einfluss des beeinträchtigten TM EM zu minimieren.</p> <p>摘要: 背景: 上皮迁移(EM)是正常耳朵结构和功能不可或缺的一部分。糖皮质激素被认为是治疗各种外耳疾病的一线疗法；然而，它们对鼓膜(TM)和外耳道(EAC)EM的影响研究不足。 假设/目的: 为了验证局部地塞米松减缓EM对TM的作用的假设，本研究旨在评估局部地塞米松对EM对犬TM的影响。 动物: 四只健康犬的七只耳朵。 材料和方法: 根据视频耳镜拍摄的图像，在三周内计算沉积在犬颞部后象限的墨滴的迁移距离(TM EM率)。通过配对学生t检验将结果与后续实验中获得的结果进行比较，在后续实验中，相同的犬在与之前相同的位置给予新鲜墨滴(对照组)，但在前14天每天额外给予0.1%地塞米松(0.2 mL/耳)(治疗组)。 结果: 由于解剖问题，八只耳朵中有一只被排除在外。与对照组相比，治疗组其余7只耳朵的TM EM率降低了46.74% (p < 0.05)。 结论和临床意义: 局部应用地塞米松可减缓正常犬耳TM上的EM。反之，可以推断EAC的碎片清除速度可能会减慢，对EAC的环境产生负面影响。因此，当患有中耳炎的犬接受局部地塞米松治疗时，可能需要额外的治疗，如耳道清洁，以尽量减少TM EM受损的影响。</p> <p>Résumé: Contexte: La migration épithéliale (ME) fait partie intégrante de la structure et de la fonction normales de l'oreille. Les glucocorticoïdes sont considérés comme le traitement de première intention pour divers troubles de l'oreille externe; cependant, leurs effets sur la migration épithéliale dans la membrane tympanique (MT) et le conduit auditif externe (CAE) sont peu étudiés. Hypothèse/objectifs: Pour vérifier l'hypothèse selon laquelle la dexaméthasone topique ralentit la ME sur la MT, cette étude vise à évaluer les effets de la dexaméthasone topique sur l'EM sur les MT des chiens. Animaux: Sept oreilles de quatre chiens en bonne santé. Matériels et méthodes: La distance de migration d'une goutte d'encre déposée sur le quadrant postérieur de la pars tensa (taux d'EM de la MT) des chiens a été calculée sur trois semaines à partir d'images capturées à l'aide d'un vidéo‐otoscope. Les résultats ont été comparés par un test t de Student apparié à ceux obtenus lors d'une expérience ultérieure au cours de laquelle les mêmes chiens ont reçu une goutte d'encre fraîche au même endroit que précédemment (groupe témoin), mais ont reçu en plus 0.1% de dexaméthasone (0.2 mL/oreille) par jour pendant les 14 premiers jours (groupe de traitement). Résultats: Une oreille sur huit a été exclue en raison d'un problème anatomique. Le taux de ME de la MT des sept oreilles restantes a diminué de 46.74% dans le groupe traité par rapport au groupe témoin (p < 0.05). Conclusions et pertinence clinique: La dexaméthasone topique ralentit la ME sur la MT des oreilles de chiens normaux. En retour, on peut extrapoler que l'élimination des débris du CAE peut être ralentie, ce qui a un impact négatif sur l'environnement du CAE. Par conséquent, lorsque les chiens atteints d'otite reçoivent un traitement topique à la dexaméthasone, un traitement supplémentaire, tel que le nettoyage du conduit auditif, peut être nécessaire pour minimiser les effets de l'altération de la ME de la MT.</p> <p>要約: 背景: 上皮移行(EM)は正常な耳の構造と機能に不可欠である。グルココルチコイドは様々な外耳障害に対する第一選択薬と考えられているが、鼓膜(TM)および外耳道(EAC)のEMに対する作用については十分な研究がなされていない。 仮説/目的: デキサメタゾン外用薬が鼓膜のEMを減速させるという仮説を検証するため、本研究ではイヌの鼓膜のEMに対するデキサメタゾン外用薬の効果を評価することを目的とした。 対象動物: 4頭の健常犬の7つの耳。 材料と方法: ビデオオトスコープで撮影した画像から、犬の鼓膜緊張部下部後方に付着したインク滴の移動距離(耳介EM率)を3週間にわたって算出した。同じイヌに前回と同じ位置に新鮮なインク滴を投与し(対照群)、さらに最初の14日間、0.1%デキサメタゾン(0.2 mL/耳)を毎日投与した実験(治療群)で得られた結果と、一対のスチューデントのt検定で比較した。 結果: 8耳のうち1耳は解剖学的問題のため除外された。残りの7耳のTM EM率は、対照群と比較して治療群で46.74%減少した(p < 0.05)。 結論と臨床的意義: デキサメタゾン局所投与は、正常犬の耳のTM上のEMを減速させる。その結果、EACからのゴミの除去が遅くなり、EAC環境に悪影響を及ぼすことが推定される。その結果、外耳炎を起こした犬がデキサメタゾン外用療法を受ける場合、外耳道EMの障害による影響を最小限に抑えるために、外耳道洗浄などの追加治療が必要になる可能性があった。</p> <p>Resumo: Contexto: A migração epitelial (ME) é essencial para a estrutura e função normais das orelhas. Os glicocorticoides são considerados a terapia de primeira linha para vários distúrbios da orelha externa; no entanto, seus efeitos na ME na membrana timpânica (MT) e no canal auditivo externo (CAE) são pouco estudados. Hipótese/Objetivos: Testar a hipótese de que a dexametasona tópica desacelera a ME na MT. Este estudo teve como objetivo avaliar os efeitos da dexametasona tópica na ME nas MTs de cães. Animais: Sete orelhas de quatro cães saudáveis. Materiais e métodos: A distância de migração de uma gota de tinta depositada no quadrante posterior da pars tensa (taxa de ME da MT) de cães foi calculada ao longo de três semanas a partir de imagens capturadas com um videootoscópio. Os resultados foram comparados pelo teste t de Student pareado com aqueles obtidos de um experimento subsequente no qual os mesmos cães receberam uma gota de tinta fresca na mesma posição anterior (grupo controle), mas adicionalmente receberam 0.1% de dexametasona (0.2 mL/orelha) diariamente durante os primeiros 14 dias (grupo de tratamento). Resultados: Uma das oito orelhas foi excluída devido a um problema anatômico. A taxa de ME da MT das sete orelhas restantes diminuiu em 46.74% no grupo de tratamento em comparação com o grupo controle (p < 0.05). Conclusões e relevância clínica: A dexametasona tópica desacelera a ME na MT das orelhas de cães normais. Por sua vez, é extrapolado que a remoção de detritos do CAE pode ser retardada, impactando negativamente o ambiente do CAE. Consequentemente, quando cães com otite recebem tratamento com dexametasona tópica, tratamentos adjuvantes, como limpeza do canal auditivo, podem ser necessários para minimizar os efeitos da ME e da TM prejudicada.</p> <p>RESUMEN: Introducción: La migración epitelial (EM) es fundamental para la estructura y el funcionamiento normales del oído. Los glucocorticoides se consideran la terapia de primera línea para diversos trastornos del oído externo; sin embargo, sus efectos sobre la EM en la membrana timpánica (MT) y el conducto auditivo externo (EAC) no se han estudiado lo suficiente. Hipótesis/Objetivos: Para probar la hipótesis de que la dexametasona tópica desacelera la EM en la MT, este estudio tuvo como objetivo evaluar los efectos de la dexametasona tópica sobre la EM en las MT de perros. Animales: Siete orejas de cuatro perros sanos. Materiales y métodos: La distancia de migración de una gota de tinta depositada en el cuadrante posterior de la pars tensa (tasa de EM de la MT) de perros se calculó durante tres semanas a partir de imágenes capturadas con un videootoscopio. Los resultados se compararon mediante la prueba t de Student pareada con los obtenidos en un experimento posterior en el que se administró a los mismos perros una gota de tinta fresca en la misma posición que antes (grupo de control), pero se les administró además dexametasona al 0.1% (0.2 mL/oreja) diariamente durante los primeros 14 días (grupo de tratamiento). Resultados: Se excluyó una de las ocho orejas debido a un problema anatómico. La tasa de EM de la MT de las siete orejas restantes disminuyó un 46.74% en el grupo de tratamiento en comparación con el grupo de control (p < 0.05). Conclusiones y relevancia clínica: La dexametasona tópica desacelera la EM en la MT de las orejas de los perros normales. A su vez, se extrapola que la eliminación de residuos del CAE puede ralentizarse, lo que afecta negativamente al entorno del CAE. En consecuencia, cuando los perros con otitis reciben tratamiento tópico con dexametasona, puede ser necesario un tratamiento adicional, como la limpieza del conducto auditivo, para minimizar los efectos del deterioro de la EM en la MT.</p> <p>Keywords: dexamethasone; dog; epithelial migration; glucocorticoid; tympanic membrane</p> <p> <bold>Background</bold> – Epithelial migration (EM) is integral to normal ear structure and function. Glucocorticoids are considered the first‐line therapy for various external ear disorders; however, their effects on EM on the tympanic membrane (TM) and the external auditory canal (EAC) are understudied. <bold>Hypothesis/Objectives</bold> – To test the hypothesis that topical dexamethasone decelerates EM on the TM, this study aimed to evaluate the effects of topical dexamethasone on EM on the TMs of canines. <bold>Conclusions and Clinical Relevance</bold> – Topical dexamethasone decelerates EM on the TM of normal dogs' ears. In turn, it is extrapolated that debris removal from the EAC may be slowed, negatively impacting the EAC environment. Consequently, when dogs with otitis receive topical dexamethasone treatment, additional treatment, such as ear canal cleaning, may be required to minimise the effects of impaired TM EM.</p> <p> <img src="https://imageserver.ebscohost.com/img/embimages/rdk/F10/01apr25/vde13314-toc-0001.jpg?ephost1=dGJyMMvl7ESepq84wtvhOLCmsE2epq5Srqa4SK6WxWXS" alt="vde13314-toc-0001.jpg" title="." /> </p> <p></p> <hd id="AN0183821327-3">INTRODUCTION</hd> <p>The tympanic membrane (TM) is a thin, concave septum that separates the external auditory canal (EAC) and the tympanic cavity.[[<reflink idref="bib1" id="ref1">1</reflink>]] The TM is composed of three layers: an outer epithelial layer that is continuous with the skin of the EAC; a middle, fibrous connective tissue layer; and an inner mucosal layer that is continuous with the tympanic cavity.[[<reflink idref="bib2" id="ref2">2</reflink>]]</p> <p>The epithelial cells of the TM and ear canal desquamate throughout the external ear canal and migrate to the distal end of the ear canal, contributing to debris removal and repair of TM damage.[[<reflink idref="bib4" id="ref3">4</reflink>], [<reflink idref="bib6" id="ref4">6</reflink>]] As epithelial cells migrate, they desquamate and mix with ceruminous and sebaceous gland secretions and other debris to form cerumen within the ear canal,[<reflink idref="bib5" id="ref5">5</reflink>] which is cleared as it moves from the TM to the opening at the distal end of the ear canal through epithelial migration (EM).[<reflink idref="bib4" id="ref6">4</reflink>] Therefore, the migration of epithelial cells on the TM and ear canal is integral for healthy ear maintenance and function. EM also contributes to the recovery of TM damage,[[<reflink idref="bib5" id="ref7">5</reflink>]] as during TM perforation, the edges of the perforation site are first closed by a layer of epithelial cells and then by a layer of intermediate fibres.[<reflink idref="bib6" id="ref8">6</reflink>]</p> <p>Glucocorticoid drugs are useful in most animals with otitis, regardless of the underlying cause.[<reflink idref="bib7" id="ref9">7</reflink>] Both topical and systemic applications are possible, yet topical glucocorticoids are preferred in most cases of otitis. Glucocorticoids help relieve pain and itching, and reduce exudate production and glandular secretion. Owing to these effects, glucocorticoids are considered useful agents.[[<reflink idref="bib7" id="ref10">7</reflink>], [<reflink idref="bib9" id="ref11">9</reflink>]]</p> <p>However, although the effects of glucocorticoids on inflammation have been well‐studied, minimal research has investigated the effects of glucocorticoids on epithelial cells of the TM and ear canal.[[<reflink idref="bib10" id="ref12">10</reflink>], [<reflink idref="bib12" id="ref13">12</reflink>], [<reflink idref="bib14" id="ref14">14</reflink>]] We hypothesise that topical dexamethasone will decelerate the EM rate on healthy canine TMs.</p> <hd id="AN0183821327-4">MATERIALS AND METHODS</hd> <p></p> <hd id="AN0183821327-5">Ethics</hd> <p>All aspects of this study were approved and conducted in compliance with the relevant Institutional Animal Care and Use Committee (2023–0284).</p> <hd id="AN0183821327-6">Animals</hd> <p>Four 4‐year‐old male beagles (<emph>n</emph> = 8 ears) without any history of otitis were included in the experiment, and physical examinations were conducted to evaluate the general health of the dogs.</p> <p>Before the study, the ear canals were evaluated using a video‐otoscope (WelchAllyn); only dogs with no damage to the TM and no evidence of infection or inflammation on ear swab samples were included in the study. No oral medications other than heartworm prophylaxis were administered during the study period, and no topical preparations other than our therapeutic otic solution were applied.</p> <hd id="AN0183821327-7">Study design</hd> <p>Eight different TMs (from four left ears and four right ears) were evaluated twice, once as the control group and again as the treatment group. No otic treatment was applied to the control group, while the treatment group received 0.1% dexamethasone (dexamethasone injection; Jeil Pharmaceutical) at a dose of 0.2 mL/ear, applied into the external ear canal opening daily for 14 days. To evaluate the TM EM rate, waterproof ink (Tana Lee Temporary Coloring Tattoo Ink; Oyecoskorea) was placed on the TM (Day [D]0). In the treatment group, ink was placed on the TM immediately before dexamethasone was applied. For sedation before ink spotting, 0.01 mg/kg of medetomidine hydrochloride (Domitor; Zoetis) and 2 mg/kg of alfaxalone (Alfaxan; Jurox) were administered intravenously. Customised equipment was developed using a 1 mL syringe and a polytetrafluoroethylene (PTFE) Teflon tube (0.5 mm inner and 0.9 mm outer diameter; Uxcell) (Figure 1). Guided by a video‐otoscope, the customised instrument inserted through a port in the video‐otoscope and an ink drop was placed on the posterior quadrant of the pars tensa. Ink drops were evaluated on D0, D7 ± 1 and D14 ± 1, until either D21 ± 1 or until the ink was released from the pars tensa.</p> <p> <img src="https://imageserver.ebscohost.com/img/embimages/rdk/F10/01apr25/vde13314-fig-0001.jpg?ephost1=dGJyMMvl7ESepq84wtvhOLCmsE2epq5Srqa4SK6WxWXS" alt="vde13314-fig-0001.jpg" title="1 Customised instrument to apply ink to the pars tensa." /> </p> <p></p> <hd id="AN0183821327-9">Malleus width measurement for calibration</hd> <p>One week after the migration evaluation of the ink, the malleus width was measured to calibrate all the TM EM rates. Index tape was cut into 2.0 × 2.0 mm squares to use as a reference scale and then applied to the short process of the malleus under the same sedation as the ink application method (Figure 2). Then, the width of the scale and the short process of the malleus were measured in pixels using Photoshop (v24.7.1, 2023; Adobe Systems). Based on the assumption that both malleus widths were the same, the tape was applied to only one ear. Then, using the ratio, the actual size was measured indirectly.</p> <p> <img src="https://imageserver.ebscohost.com/img/embimages/rdk/F10/01apr25/vde13314-fig-0002.jpg?ephost1=dGJyMMvl7ESepq84wtvhOLCmsE2epq5Srqa4SK6WxWXS" alt="vde13314-fig-0002.jpg" title="2 Malleus width measurement with 2.0 × 2.0 mm tailored tape as a referential scale. Yellow star, referential scale; blue line, width of referential scale; red line, width of malleus; D, dorsal; V, ventral; C, caudal; and R, rostral." /> </p> <p></p> <hd id="AN0183821327-11">Evaluation of the TM EM rate</hd> <p>The captured TM images were aligned over time using Photoshop. The centre points of two ink dots at consecutive time intervals were connected by a line. All of the distances were summed and divided by the number of days assessed to obtain the TM EM rate per day (Figure 3).</p> <p> <img src="https://imageserver.ebscohost.com/img/embimages/rdk/F10/01apr25/vde13314-fig-0003.jpg?ephost1=dGJyMMvl7ESepq84wtvhOLCmsE2epq5Srqa4SK6WxWXS" alt="vde13314-fig-0003.jpg" title="3 Tympanic membrane (TM) photographs captured at Day (D)0, D7, D14 and D21 overlapped using Photoshop and displayed as one image of ink migrating on TM. Gross comparison of tympanic membrane (TM) epithelial migration (EM) rate in the control (a) and treatment (b) groups. The ink drop path over time is visualised with outlines of progressively darker colours. The ink drop deviation in the treatment group was slower than that in the control group. Short green bar, midpoint of the ink drops; green line, migrated distance between the two chronological time intervals; D, dorsal; V, ventral; C, caudal; and R, rostral." /> </p> <p></p> <hd id="AN0183821327-13">Statistical methods</hd> <p>Prism (v10.0.2; GraphPad Software, Inc.) was used for statistical analysis. The paired Student's <emph>t</emph>‐test was used to compare the difference in TM EM rates between the control and treatment groups. A <emph>p</emph>‐value <0.05 was considered statistically significant.</p> <hd id="AN0183821327-14">RESULTS</hd> <p>Of the eight ears on both sides of four beagles, one right ear was excluded owing to difficulty with ink spotting because of an anatomical problem. Therefore, the TM EM rates were obtained from the remaining seven ears.</p> <p>A comparison of the ink movement between the two groups is shown in Figure 3. The TM EM rate for each group is shown in Table 1. The mean TM EM rates for the treatment and control groups were 51.9 ± 27.3 and 111.0 ± 43.3 μm/day (95% confidence interval), respectively (Figure 4). Compared with the control group, the TM EM rate in the treatment group decreased by 46.74% (<emph>p</emph> < 0.01).</p> <p>1 TABLE Mean tympanic membrane (TM) epithelial migration (EM) rate per day for the left and right ears of dogs.</p> <p> <ephtml> <table><thead valign="bottom"><tr><th align="left">Ear laterality</th><th align="left">TM EM rate (μm/day)</th></tr><tr><th align="left">Treatment group</th><th align="left">Control group</th></tr></thead><tbody valign="top"><tr><td align="left">Left</td><td align="char" char="±">54.4 ± 33.9</td><td align="char" char="±">124.1 ± 48.3</td></tr><tr><td align="left">Right</td><td align="char" char="±">48.5 ± 13.3</td><td align="char" char="±">93.7 ± 27.2</td></tr><tr><td align="left">Total</td><td align="char" char="±">51.9 ± 27.3</td><td align="char" char="±">111 ± 43.3</td></tr></tbody></table> </ephtml> </p> <p> <img src="https://imageserver.ebscohost.com/img/embimages/rdk/F10/01apr25/vde13314-fig-0004.jpg?ephost1=dGJyMMvl7ESepq84wtvhOLCmsE2epq5Srqa4SK6WxWXS" alt="vde13314-fig-0004.jpg" title="4 Comparison of the tympanic membrane (TM) epithelial migration (EM) rate in the treatment and the control groups. The TM EM rate was significantly lower in the treatment group than in the control group (*p < 0.05)." /> </p> <p></p> <hd id="AN0183821327-16">DISCUSSION</hd> <p>This study demonstrated that the application of a topical glucocorticoid to the TMs of healthy dogs decreased the EM rate. Dexamethasone 0.1% was selected among various glucocorticoids because it has high potency and is commonly used as a topical agent for canine otitis externa (OE).[<reflink idref="bib10" id="ref15">10</reflink>] Additionally, a previous study has confirmed that the application of dexamethasone to the TM in chinchilla hinders TM healing in acute otitis media related TM perforations.[<reflink idref="bib12" id="ref16">12</reflink>]</p> <p>Several animal studies have shown that topical dexamethasone application delays tissue recovery from TM perforation.[[<reflink idref="bib11" id="ref17">11</reflink>], [<reflink idref="bib15" id="ref18">15</reflink>]] Glucocorticoid treatment also has been demonstrated to arrest EM in rats.[[<reflink idref="bib12" id="ref19">12</reflink>]] Healing of a TM perforation includes epithelial proliferation, EM, fibroblast proliferation, angiogenesis, activation of various growth factors and cytokines, and tissue remodelling.[[<reflink idref="bib10" id="ref20">10</reflink>], [<reflink idref="bib13" id="ref21">13</reflink>]] The expression of growth factors, including epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and transforming growth factor‐alpha (TGF‐α), is increased,[<reflink idref="bib13" id="ref22">13</reflink>] and all three layers of the TM are thickened.[<reflink idref="bib10" id="ref23">10</reflink>] When subcutaneously administered, dexamethasone suppresses the expression of these growth factors,[<reflink idref="bib14" id="ref24">14</reflink>] and it may disrupt healing of the perforation edge of the TM by halting macrophage chemotaxis, immunosuppression and cellular proliferation.[<reflink idref="bib10" id="ref25">10</reflink>]</p> <p>This study used a software program to accurately measure the movement distance of ink placed on the TM. This approach allowed the display of all ink movement that occurred over several days on one screen, enabling the measurement of the distance between ink markings. In a previous study,[<reflink idref="bib4" id="ref26">4</reflink>] the distance between ink markings was expressed in pixels through a program similar to that used in this experiment. However, the width of the malleus was measured directly with a calliper after the dog was euthanised to express the distance between ink markings in micrometres. In contrast to that study, the actual width of the malleus was obtained indirectly by attaching a reference index near the malleus and using a proportional equation, allowing completion of the experiment without sacrificing animals.</p> <p>There are some limitations to this study. First, no agent was applied to the control group. As such, it was not possible to evaluate whether administering a liquid agent into the ear canal may have contributed to the decreased TM EM rate. However, a previous study[<reflink idref="bib14" id="ref27">14</reflink>] showed that after applying stem cell‐conditioned media to the TM, the TM EM rate increased significantly compared with that of a control group. This suggests that the composition of the topical agent is a more critical factor in changing the TM EM rate than the stimulation effect of the topical agent itself. Second, given that this study included only four dogs, a larger sample size is needed to obtain more statistically significant results. Third, as all of the subjects were healthy dogs, the results may differ in dogs with otitis.</p> <p>EM is among the most vital physiological function of the TM. It is essential for removing dead skin cells and foreign substances from the TM and EAC.[<reflink idref="bib4" id="ref28">4</reflink>] A decreased TM EM rate can negatively impact the removal rate of dead skin cells and foreign substances from the EAC, which, in turn, can adversely affect the EAC environment. This effect is particularly significant for dogs with OE, which requires efficient debris drainage from the ear canal. Therefore, in cases where topical dexamethasone application is essential, additional measures, such as EAC irrigation, may be necessary to minimise the effects of decelerated EM.</p> <hd id="AN0183821327-17">CONCLUSIONS</hd> <p>Topical dexamethasone decelerates TM EM in normal dog ears. In turn, debris removal from the EAC may be slowed, negatively impacting the EAC environment.</p> <hd id="AN0183821327-18">AUTHOR CONTRIBUTIONS</hd> <p> <bold>Jihyun Kim:</bold> Methodology; software; data curation; investigation; validation; formal analysis; visualization; writing – original draft. <bold>Taeho Oh:</bold> Writing – review and editing; project administration. <bold>Seulgi Bae:</bold> Conceptualization; methodology; project administration; resources; writing – review and editing; visualization; formal analysis; supervision; funding acquisition; writing – original draft.</p> <hd id="AN0183821327-19">FUNDING INFORMATION</hd> <p>Self‐funded.</p> <hd id="AN0183821327-20">CONFLICT OF INTEREST STATEMENT</hd> <p>The authors have <emph>no conflicts of interest</emph> to declare.</p> <ref id="AN0183821327-21"> <title> REFERENCES </title> <blist> <bibl id="bib1" idref="ref1" type="bt">1</bibl> <bibtext> Cole LK. Anatomy and physiology of the canine ear. Vet Dermatol. 2009 ; 20 : 412 – 421.</bibtext> </blist> <blist> <bibl id="bib2" idref="ref2" type="bt">2</bibl> <bibtext> Dyce KM, Sack WO, Wensing CJG. Textbook of veterinary anatomy‐E‐book. Amsterdam : Elsevier Health Sciences ; 2009. p. 346 – 351.</bibtext> </blist> <blist> <bibl id="bib3" type="bt">3</bibl> <bibtext> Bacha WJ Jr, Bacha LM. Color atlas of veterinary histology. Chichester : John Wiley & Sons ; 2012. p. 282 – 290.</bibtext> </blist> <blist> <bibl id="bib4" idref="ref3" type="bt">4</bibl> <bibtext> Tabacca NE, Cole LK, Hillier A, Rajala‐Schultz PJ. Epithelial migration on the canine tympanic membrane. Vet Dermatol. 2011 ; 22 : 502 – 510.</bibtext> </blist> <blist> <bibl id="bib5" idref="ref5" type="bt">5</bibl> <bibtext> Njaa BL, Cole LK, Tabacca N. Practical otic anatomy and physiology of the dog and cat. Vet Clin North Am Small Anim Pract. 2012 ; 42 : 1109 – 1126.</bibtext> </blist> <blist> <bibl id="bib6" idref="ref4" type="bt">6</bibl> <bibtext> Wang W‐Q, Wang Z‐M, Chi F‐L. Spontaneous healing of various tympanic membrane perforations in the rat. Acta Otolaryngol. 2004 ; 124 : 1141 – 1144.</bibtext> </blist> <blist> <bibl id="bib7" idref="ref9" type="bt">7</bibl> <bibtext> Bonagura JD, Twedt DC. Kirk's current veterinary therapy XV. Amsterdam : Elsevier Health Sciences ; 2013. p. 459 – 462.</bibtext> </blist> <blist> <bibl id="bib8" type="bt">8</bibl> <bibtext> Gortel K. Otic flushing. Vet Clin North Am Small Anim Pract. 2004 ; 34 : 557 – 565.</bibtext> </blist> <blist> <bibl id="bib9" idref="ref11" type="bt">9</bibl> <bibtext> Jackson HA, Marsella R. BSAVA manual of canine and feline dermatology. Quedgley : British Small Animal Veterinary Association ; 2012.</bibtext> </blist> <blist> <bibtext> Ishimoto S‐I, Ishibashi T, Bottaro DP, Kaga K. Direct application of keratinocyte growth factor, basic fibroblast growth factor and transforming growth factor‐α du1ring healing of tympanic membrane perforation in glucocorticoid‐treated rats. Acta Otolaryngol. 2002 ; 122 : 468 – 473.</bibtext> </blist> <blist> <bibtext> Hebda PA, Yuksel S, Dohar JE. Effects of ciprofloxacin‐dexamethasone on myringotomy wound healing. Laryngoscope. 2007 ; 117 : 522 – 528.</bibtext> </blist> <blist> <bibtext> Antonelli PJ, Winterstein AG, Schultz GS. Topical dexamethasone and tympanic membrane perforation healing in otitis media: a short‐term study. Otol Neurotol. 2010 ; 31 : 519 – 523.</bibtext> </blist> <blist> <bibtext> Ishimoto S‐i, Ishibashi T. Induction of growth factor expression is reduced during healing of tympanic membrane perforations in glucocorticoid‐treated rats. Ann Otol Rhinol Laryngol. 2002 ; 111 : 947 – 953.</bibtext> </blist> <blist> <bibtext> Suh H, Kim S, Oh T, Bae S. Canine stem cell conditioned media accelerates epithelial migration in the canine tympanic membrane. Vet Sci. 2022 ; 9 : 69.</bibtext> </blist> <blist> <bibtext> Dirain CO, Kosko B, Antonelli PJ. Effects of common ear drops on tympanic membrane healing in rats. Otolaryngol Head Neck Surg. 2018 ; 158 : 917 – 922.</bibtext> </blist> </ref> <aug> <p>By Jihyun Kim; Taeho Oh and Seulgi Bae</p> <p>Reported by Author; Author; Author</p> </aug> <nolink nlid="nl1" bibid="bib10" firstref="ref12"></nolink> <nolink nlid="nl2" bibid="bib12" firstref="ref13"></nolink> <nolink nlid="nl3" bibid="bib14" firstref="ref14"></nolink> <nolink nlid="nl4" bibid="bib11" firstref="ref17"></nolink> <nolink nlid="nl5" bibid="bib15" firstref="ref18"></nolink> <nolink nlid="nl6" bibid="bib13" firstref="ref21"></nolink>
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