Evisceration with implantation of an intrascleral silicone prosthesis in dogs: A retrospective study of 107 cases (2010-2019).

OBJECTIVE: To retrospectively analyze the preoperative clinical characteristics and surgical outcomes of evisceration with implantation of an intrascleral silicone prosthesis (EIISP) procedures in dogs and evaluate whether brachycephalic dogs are more prone than non-brachycephalic dogs to develop postoperative complications after EIISP. ANIMAL STUDIED: Ninety-One dogs (19 of which were brachycephalic) were included. PROCEDURES: Medical records from 2010 to 2019 were reviewed. Signalment, reason for EIISP, postoperative complications, follow-up time, and postoperative eye appearance were analyzed. RESULTS: The most frequently represented breeds were French Bulldog [11/91 (12%) dogs], Jack Russell Terrier [6/91 (7%)], and Shih Tzu [6/91 (7%)]. Brachycephalic dogs were statistically younger than non-brachycephalic dogs at the time of EIISP (p = 1.61 × 10-5 ). Uncontrolled glaucoma was the most common reason for EIISP in both groups. Short-term complications (from D0 to D15) seen in 7/91 (8%) dogs included epithelial corneal ulcers (n = 3), keratoconjunctivitis sicca (KCS) (n = 2), and prosthesis extrusion (n = 2). Long-term complications seen in 26/91 (29%) dogs included KCS (n = 11), epithelial corneal ulcers (n = 7), stromal ulcers (n = 3), entropion (n = 4), and prosthesis extrusion (n = 1). Extrusion of the prosthesis occurred twice in eyes that had undergone diode laser transscleral cyclophotocoagulation. The risk of postoperative complications was not significantly different between brachycephalic and non-brachycephalic dogs (p = .3). CONCLUSIONS: Brachycephalic status in dogs does not appear to influence the risk of complications from EIISP. Nevertheless, the present study is a reminder that EIISP focuses on esthetics, and considering the possible complications associated with it, it does not provide a benefit to the patient compared to enucleation.

Canine keratoconjunctivitis sicca therapeutics: literature review / Terapêutica da ceratoconjuntivite seca canina: revisão bibliográfica

Keratoconjunctivitis sicca (KCS) is a disease commonly seen in dogs that is characterized by the reduction or absence of lacrimal secretions. It can be classified as qualitative or quantitative, and both categories are able to elicit conjunctival and corneal inflammation, ocular pain, progressive corneal disease, and vision impairment. This disease's treatment is based on reestablishing and maintaining ocular surface homeostasis. Patients may benefit from different therapeutic protocols, such as the use of lacrimomimetics, that increase lacrimal stability, helping to retain ocular humidity; lacrimostimulants, that promote lacrimal secretion; fatty acids, which play a role on meibum synthesis and block pro-inflammatory cytokine genic expression; blood products, based on promotion of epithelial growth factors; and stem cells, due to their self-renewing capabilities. Stable cases may benefit from the use of steroidal or non-steroidal anti-inflammatory agents on the control of clinical signs. Refractory cases may eventually benefit from surgical therapies, which include techniques for parotid duct transposition, gland transplants, and lacrimal puncta occlusion.

A ceratoconjuntivite seca (CCS) é uma doença comumente observada em cães caracterizada pela ausência ou redução das secreções lacrimais. Pode ser classificada como qualitativa ou quantitativa, sendo que ambas as categorias são capazes de desencadear inflamação da conjuntiva e da córnea, dor ocular, doença corneana progressiva e redução da visão. O tratamento desta doença é contínuo e se baseia no restabelecimento e manutenção da homeostase do sistema da superfície ocular. Os pacientes podem se beneficiar de diferentes protocolos terapêuticos, tais como o uso de lacrimomiméticos, que aumentam a estabilidade lacrimal ajudando na retenção da umidade ocular; lacrimoestimulantes para a promoção de secreção de lágrimas; ácidos graxos, que desempenham papel na síntese de meibum e bloqueiam a expressão gênica de citocinas pró-inflamatórias; produtos derivados do sangue, baseando-se nos fatores de crescimento de promoção epitelial; e células tronco, devido à sua capacidade de auto renovação. Em casos estáveis, o uso de anti-inflamatórios esteroidais ou não esteroidais pode ser benéfico no controle de sinais clínicos. Casos refratários ao tratamento podem eventualmente se beneficiar de terapias cirúrgicas, que incluem as técnicas de transposição de ducto parotídeo, transplantes glandulares e oclusão da puncta lacrimal.

Changes in tear production in a dog with keratoconjunctivitis sicca for a year after inevitable nictitating membrane gland resection due to suspicion of a malignant tumour.

Since the removal of the NM causes KCS in dogs, it was contraindicated to remove the NM unless unavoidable such as in a malignant tumour. However, to the best of author's knowledge, there are no reports of conjunctivitis and keratitis owing to decreased tear production following removal of the NM gland. This case study demonstrates the tear production changes in a dog for a year after removal of the nictitating membrane (NM) due to suspicion of a malignant tumour. A 13-year-old spayed female English Cocker Spaniel who had suffered from severe ocular discharge, discomfort, keratoconjunctivitis sicca (KCS), and NM enlargement in the right eye was brought to our hospital. The dog could not tolerate treatment with topical 0.2% cyclosporine or corticosteroids. The dog's right eye had NM gland prolapse, severe follicular conjunctivitis and a very low Schirmer tear test-1 (STT-1) value of 3 mm/min. Furthermore, the result of fine needle aspiration of the enlarged NM gland suggested a risk of malignancy. Despite the risk of KCS, complete NM resection was performed to diagnose the tumour. Fortunately, the final histopathological evaluation revealed chronic inflammation without any evidence of malignancy. Contrary to concerns that the STT-1 value would further decrease after the removal of the NM gland, the STT-1 value remained elevated compared to that before surgery, and the clinical symptoms improved for a year. It is generally known that NM gland resection is not recommended due to the risk of developing iatrogenic KCS unless a malignant tumour is suspected. In this case, surgical removal of the inflammatory NM gland that was not responsive to medications had a positive effect on KCS. Since the inflammatory and structural disease of the NM was strengthening KCS, the outcome was thought to be different from that when the normal third eyelid was removed.

Topical applications of allogeneic adipose-derived mesenchymal stem cells ameliorate the canine keratoconjunctivitis sicca.

BACKGROUND: Canine keratoconjunctivitis sicca (KCS) is predominantly an immune-mediated disease. Current therapy of canine KCS is mainly by immunosuppressant, but the effectiveness was limited in some patients. In the past few years, some studies showed the results of the use of mesenchymal stem cells in treating canine KCS via periocular injections. However, the periocular injection procedure requires sedation or general anesthesia, and may lead to iatrogenic or incidental injury during the injection process. The aim of this study was to investigate the efficacy of topical allogenic canine adipose-derived mesenchymal stem cells (cAD-MSCs) in clinical patients of canine KCS. RESULTS: The cAD-MSCs used in this study were characterized for their capability of tri-lineage differentiation and immunomodulatory properties. In addition, preparation methods for eye drops of cAD-MSCs was developed and its optimal preservation was tested. The canine KCS patients were recruited for clinical trial and divided into two groups based on their history of previous treatment. All patients received topical cAD-MSCs treatment once per week for 6 consecutive weeks and complete ophthalmic examinations were performed 1 week before treatment (week 0) and at 3rd, 6th, 9th weeks, respectively. The results showed that the quantity and quality of tears have improved significantly following topical cAD-MSCs treatment based on Schirmers tear test-1 and tear break-up time. More than half of all patients were found improved in the tear quantity. In particular, 56.5% of the patients that were unresponsive to prior immunosuppressant therapy had an effective increase in tear volume. The severity of clinical signs was also ameliorated according to the numeric rating scale score from both patient owners and the clinician. CONCLUSION: To sum up, topical cAD-MSCs may be beneficial especially in KCS patients with poor owner compliance for frequent daily use of eye drops or those who are unresponsive to immunosuppressant therapy.

Oral mucosa transplantation may improve tear film osmolarity in dogs with keratoconjunctivitis sicca - a preliminary study / [Transplante da mucosa oral na melhoria da osmolaridade do filme lacrimal em cães com ceratoconjuntivite seca - estudo preliminar]

The objective of this study was to evaluate the use of cyclosporine 1% alone or associated with oral mucosa transplantation (OMT) in dogs with dry keratoconjunctivitis (KCS). Schirmer Tear Test (STT-1) and Tear Film Osmolarity (TFO) were measured in both eyes of 30 adult dogs (before and 45 days after treatment. The animals were divided into three groups (10 dogs for group): control (normal dogs), group I (GI, treated with 1% cyclosporine alone), and group II (GII, treated with 1% cyclosporine and OMT). All STT-1 and TFO values were subjected to the Shapiro-Wilk normality test, and all were normally distributed. STT-1 and TFO values before and after treatment were subjected to the T-Student Test. The STT­1 and TFO values of the right eye were subjected to Repeated Measures ANOVA followed by a Tukey Test for comparison between groups I and II. Means with a value of p≤0.05 were considered significant. There was a decreased osmolarity in both groups after treatment. Mean osmolarity in GII (322.60±16.56 mOsm/L) was significantly lower than GI (336.40±5.66 mOsm/L). The OMT associated with cyclosporine 1% improved the osmolarity of the tear film in dogs with KCS with a seeming synergism between the clinical and surgical treatments.(AU)

Avaliou-se o uso de ciclosporina 1% isolada ou associada ao transplante de mucosa oral (TMO) em cães com ceratoconjuntivite seca (CCS). O teste lacrimal de Schirmer (TLS-1) e a osmolaridade do filme lacrimal (OFL) foram medidos em ambos os olhos, em 30 cães adultos, antes e 45 dias após o tratamento. Os animais foram divididos em três grupos (10 cães por grupo): controle (cães saudáveis), grupo I (GI, tratados apenas com ciclosporina 1%) e grupo II (GII, tratados com 1% de ciclosporina associada ao TMO). Todos os valores do TLS-1 e da OFL foram submetidos ao teste de normalidade Shapiro-Wilk, e todos foram distribuídos normalmente. Os valores de TLS-1 e OFT antes e depois do tratamento foram submetidos ao teste T-Student. Os valores TLS-1 e OFT do olho direito foram submetidos à ANOVA de medidas repetidas, seguida por um teste de Tukey para comparação entre os grupos I e II. Valor de P≤0,05 foi considerado significativo. Houve uma diminuição da osmolaridade em ambos os grupos após o tratamento. A osmolaridade média no GII (322,60±16,56 mOsm/L) foi significativamente inferior à no GI (336,40±5,66 mOsm/L). O TMO associado à ciclosporina 1% melhorou a osmolaridade do filme lacrimal em cães com CCS, com uma sinergia aparente entre os tratamentos clínicos e cirúrgicos.(AU)

Interferon therapies in small animals.

Interferons (IFNs) are cytokines that play an important role in the immune response of animals and humans. A number of studies reviewed here have evaluated the use of human, canine and feline IFNs as treatments for infectious, inflammatory and neoplastic disease in dogs and cats. Recombinant canine IFN-γ is deemed an efficacious therapy for canine atopic dermatitis. Recombinant feline IFN-ω is effective against canine parvoviral enteritis and has also been recommended for canine atopic dermatitis. Based on limited evidence, recombinant canine IFN-α could be a topical treatment option for dogs with gingivitis and keratoconjunctivitis sicca. Conclusive evidence is lacking for other diseases and large randomised controlled trials are needed before IFNs can be recommended for other indications.

Clinical-dosimetric relationship between lacrimal gland dose and keratoconjunctivitis sicca in dogs with sinonasal tumors treated with radiation therapy.

BACKGROUND: Dogs with sinonasal tumor can develop keratoconjunctivitis sicca (KCS) after radiation therapy (RT). In humans, the incidence of xerophtalmia is associated with the mean radiation dose received by the ipsilateral lacrimal gland (LG). HYPOTHESIS/OBJECTIVES: The eyes receiving a higher mean LG dose are more likely to develop KCS. The aim of the study was to determine a starting threshold dose to use as dose constraint for intensity-modulated radiation therapy (IMRT). ANIMALS: Dogs with nasal tumors treated with RT between August 2013 and December 2016. METHODS: Case control retrospective study of dogs with sinonasal tumor treated with 42 Gray (Gy) in 10 fractions using IMRT. Dogs were included if development of KCS after RT was documented (cases) or adequate follow-up information with Schirmer tear test (STT) result for ≥6 months after RT was available (controls). Lacrimal glands were contoured and dose distribution was calculated using the original treatment plan to determine prescribed doses to LGs. RESULTS: Twenty-five dogs were treated with RT and 5 dogs (20%) developed KCS. Fifteen dogs met the inclusion criteria including 5 unilateral KCS and 10 control dogs, resulting in 5 KCS eyes and 25 control eyes. KCS developed at a median of 111 days (84-122) after 1st RT. The mean LG dose reached using a 4.2 Gy per fraction was 33.08 Gy (range: 23.75-42.33) for KCS eyes and 10.33 Gy (1.8-24.77) for control eyes (P < .001). The minimum LG mean dose for developing KCS was 23.75 Gy. No eyes that received a mean LG dose <20 Gy developed KCS versus 5/7 (71%) developed with >20 Gy. CONCLUSION AND CLINICAL IMPORTANCE: Contouring and applying a dose constraint on LGs should be performed when using IMRT in dogs with sinonasal tumors to reduce the risk of KCS.

Antimicrobial susceptibility and minimal inhibitory concentration of bacteria isolated from the eyes of dogs with keratoconjunctivitis sicca / Susceptibilidade antimicrobiana e concentração inibitória mínima de bactérias isoladas dos olhos de cães com ceratoconjuntivite seca

The objective of this study was to evaluate the antimicrobial susceptibility profile of bacteria isolated from the eyes of dogs with keratoconjunctivitis sicca (KCS). We evaluated 65 dogs diagnosed with KCS and 30 healthy dogs (Control Group). Conjunctival swab samples were collected after KCS was diagnosed. Microbiological examinations were performed, including aerobic culture, antimicrobial susceptibility testing and minimum inhibitory concentration (MIC) determination for chloramphenicol, tobramycin, ofloxacin and moxifloxacin. MICs of the fifteen most resistant strains of Staphylococcus pseudintermedius (Staphylococcus intermedius Group, SIG) and the fifteen most resistant strains of gram-negative bacteria were determined. By percentage, the microorganisms exhibited the highest susceptibility to polymyxin B, tobramycin and chloramphenicol and the lowest to tetracycline. Three multi-drug-resistant strains of SIG were detected: one displayed isolated susceptibility to cefazolin, another to vancomycin, and another to polymyxin B and amikacin. The species of bacteria isolated from the eyes of dogs with KCS presented variable susceptibility to the antibiotics tested. We found evidence of the emergence of quinolone-resistant strains of SIG and further evidence of increased ocular prevalence. These findings reinforce the need to identify the bacteria involved and their antimicrobial susceptibility profile, as secondary infections can serve as exacerbating and perpetuating factors in KCS.(AU)

O objetivo deste estudo foi avaliar o perfil de susceptibilidade antimicrobiana de bactérias isoladas de olhos de cães com ceratoconjuntivite seca (CCS). Foram avaliados 65 cães com diagnóstico de CCS e 30 cães saudáveis ​​(Grupo Controle). Depois do diagnosticado de CCS, suabes conjuntivais foram coletados. Exames microbiológicos foram realizados, incluindo cultura aeróbia, teste de susceptibilidade antimicrobiana e determinação da concentração inibitória mínima (CIM) para cloranfenicol, tobramicina, ofloxacina e moxifloxacina. Para determinar a CIM, foram selecionadas as quinze cepas mais resistentes de Staphylococcus pseudintermedius (Staphylococcus intermedius Group-SIG) e as quinze cepas mais resistentes de bactérias gram-negativas. Os microrganismos apresentaram maior suscetibilidade percentual à polimixina B, tobramicina e cloranfenicol e menor suscetibilidade à tetraciclina. Três cepas de SIG resistentes a múltiplos medicamentos foram detectadas, do quais um demonstrou suscetibilidade isolada à cefazolina, outro à vancomicina e outro à polimixina B e à amicacina. As espécies de bactérias isoladas dos olhos de cães com CCS apresentaram suscetibilidade variável aos antibióticos testados. Encontramos evidências do surgimento de cepas resistentes à quinolona de S. pseudintermedius e outras evidências de aumento da prevalência ocular. Esses achados reforçam a necessidade de identificar as bactérias envolvidas e seu perfil de susceptibilidade aos antimicrobianos, pois as infecções secundárias podem servir como fatores exacerbantes e perpetuantes na CCS.(AU)

Comprehensive Clinical, Diagnostic, and Advanced Imaging Characterization of the Ocular Surface in Spontaneous Aqueous Deficient Dry Eye Disease in Dogs.

PURPOSE: To perform a comprehensive clinical, diagnostic, and imaging characterization of the ocular surface in West Highland White Terriers (WHWTs) diagnosed with aqueous deficient dry eye (ADDE) disease. METHODS: Six ADDE-affected and 13 ADDE-unaffected WHWT dogs were enrolled and underwent clinical assessment and disease scoring, tear osmolarity, phenol red thread test, Schirmer tear test, tear film breakup time, fluorescein staining, Rose bengal and lissamine green vital dye staining, meibometry, corneal esthesiometry, ultrasound pachymetry, optical coherence tomography, in vivo confocal microscopy, and conjunctival biopsy. Subjective assessment of their condition was provided by owner-reported surveys. RESULTS: ADDE-affected WHWT dogs had higher median clinical disease (conjunctiva: 5.75 vs. 0.00; cornea: 14.00 vs. 5.00; total: 17.50 vs. 5.00), vital staining (Rose bengal: 2.25 vs. 1.50; lissamine green: 2.00 vs. 1.00), and histologic disease (conjunctiva: 2 vs. 0) scores when compared with the controls. In addition, ADDE-affected WHWTs had significantly lower phenol red thread test (5.0 vs. 17.5, mm/15 s), Schirmer tear test (3 vs. 20, mm/min), tear film breakup time (3.6 vs. 13.9, s) values and higher area under the curve values for meibometry (394 vs. 245, meibometry units [MU]). There were no significant differences in other tear film tests performed. Advanced imaging revealed decreased tear meniscus height (optical coherence tomography) and variable pigment deposition within corneal epithelial cells (in vivo confocal microscopy). CONCLUSIONS: This comprehensive assessment of ADDE-affected WHWTs depicts the ocular surface changes associated with quantitative lacrimal gland dysfunction. Importantly, ADDE-affected WHWTs may prove a valuable naturally occurring ADDE model for investigating underlying pathophysiological mechanisms and the development of novel therapeutics.

Nuclear parameters and chromatin remodeling in epithelial cells and lymphocytes from the palpebral conjunctiva of dogs with keratoconjunctivitis sicca.

OBJECTIVE: To study parameters related to nuclear morphology and chromatin remodeling in epithelial cells and lymphocytes from the inferior palpebral conjunctiva of dogs with and without keratoconjunctivitis sicca (KCS). ANIMALS STUDIED: Thirty-two dogs (64 eyes) were included in the study. Based on the tear production measured by Schirmer tear test 1, the dogs were distributed into control and KCS groups. PROCEDURES: Epithelial cells and lymphocytes were collected by conjunctival brush cytology, fixed on glass slides, and subjected to the Feulgen reaction, a topochemical method specific for DNA/chromatin. Feulgen-stained cells were studied by microscopy and video image analysis to establish nuclear size (area and perimeter) and shape (relative nuclear roundness factor = RNRF), DNA content (ploidy), and compaction and texture of chromatin. RESULTS: Conjunctival samples in the KCS group showed infiltration of inflammatory and immune cells. Micronuclei, snake-like chromatin, aberrant chromosomes, and goblet cells were not detected. Compared with the controls, cells on the conjunctival surface of dogs with KCS showed altered nuclei. Conjunctival epithelial cells were more affected by KCS (changes in nuclear size, shape, DNA content, and chromatin compaction) than lymphocytes (changes in chromatin compaction, only). Significant chromatin decompaction was observed in both conjunctival epithelial cells and lymphocytes. CONCLUSIONS: Our results show that KCS promotes chromatin remodeling in epithelial cells and lymphocytes on the conjunctival surface of dogs. The changes described in this study are different from those reported for conjunctival cell nuclei of human KCS patients.

Oral omega 3 in different proportions of EPA, DHA, and antioxidants as adjuvant in treatment of keratoconjunctivitis sicca in dogs / Ômega 3 oral em diferentes proporções de EPA, DHA e antioxidantes como adjuvante no tratamento de ceratoconjuntivite seca em cães

ABSTRACT Purpose: To compare the efficacy of 0.03% to­pical tacrolimus in combination with oral omega (ω) 3 with different ratios of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and antioxidants as adjuvant in the treatment of keratoconjunctivitis sicca (KCS) in dogs. Methods: Forty-five dogs with KCS were evaluated monthly for 6 months. Evaluations included performance of the Schirmer tear, fluorescein, and lissamine green tests. Tear film break-up time (TBUT) was assessed. Conjunctival cytology was evaluated at the beginning, middle, and end of the study. Conjunctiva was biopsied at the beginning and end of the study. Dogs were randomly assigned to one of the three groups (n=15): Group T (topical tacrolimus 0.03%), Group TO (topical tacrolimus + ω-1.5 EPA: 1 DHA), or Group TOA (topical tacrolimus + ω-1 EPA:4.5 DHA + antioxidants). Results: There was a significant improvement in clinical signs in all groups. TBUT increased throughout treatment in all groups; this effect was most pronounced in Group TO. Cytological analysis performed at the end of the study period, showed decreased levels of lymphocytes, neutrophils, and metaplastic and squamous cells in Groups T, TO, and TOA. Histological analysis performed at the end of the study period showed decreased levels of lymphocytes and neutrophils and increased levels of goblet cells. These effects were most pronounced in Group TO. Conclusion: Oral treatment with ω-3 containing a higher proportion of EPA than DHA increased the effectiveness of topical tacrolimus 0.03% in the treatment of keratoconjunctivitis sicca in dogs.

RESUMO Objetivo: Comparar a eficácia do tacrolimus 0,03% tópico associado ao ômega 3 oral, com diferentes proporções de ácido eicosapentaenoico (EPA), ácidos docosa-hexaenoicos (DHA) e antioxidantes, como adjuvante no tratamento de cães acometidos por ceratoconjuntivite seca. Métodos: Quarenta e cinco cães atendidos no Hospital Veterinário da UNOESTE portadores de ceratoconjuntivite seca foram avaliados mensalmente por 6 meses pelo Teste Lacrimal de Schirmer, Teste de Fluoresceína, Tempo de Ruptura do Filme Lacrimal, Teste de Rosa Bengala, citologia da conjuntiva no início, meio e fim do projeto e biopsia da conjuntiva no início e final do projeto. Os cães foram distribuídos aleatoriamente em 3 grupos (n=15): grupo T (tacrolimus 0,03% tópico), grupo TO (tacrolimus + ômegas 1.5 EPA/1 DHA oral) e grupo TOA (tacrolimus + ômegas 1 EPA/4,5 DHA + antioxidantes oral). Resultados: Houve uma melhora significativa nos sinais clínicos em ambos os grupos. No tempo de ruptura do filme lacrimal todos os grupos apresentaram aumento no decorrer do tratamento, sendo que o grupo TO foi o que apresentou melhor resultado em todos momentos quando comparado aos demais grupos. Ao final do experimento, os grupos T, TO e TOA apresentaram na análise citológica, diminuição de linfócitos, neutrófilos, células metaplásicas e escamosas, e na análise histopatológica, diminuição de linfócitos e neutrófilos e aumento das células caliciformes, com o grupo TO com melhor desempenho. Conclusão: O tratamento oral com ω-3 contendo uma maior proporção de EPA do que o DHA aumentou a eficácia do tacrolimus tópico 0,03% no tratamento de ceratoconjuntivite sicca em cães.

Comparison of the efficacy of 0. 03% tacrolimus eye drops diluted in olive oil and linseed oil for the treatment of keratoconjunctivitis sicca in dogs / Comparação do colírio tacrolimus 0, 03% em óleo de oliva e linhaça no tratamento da ceratoconjuntivite seca em cães

ABSTRACT Objective: To compare the efficacy of 0.03% tacrolimus eye drops diluted in two different vehicles (linseed oil and olive oil) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. Methods: This study included 60 dogs. Of this group, 20 were healthy and allocated to the control group, and 40 were diagnosed with bilateral KCS and randomly allocated to either the TO (tacrolimus in olive oil) or the TL (tacrolimus in linseed oil) groups. Ophthalmic examinations, Schirmer Tear Test-1 (STT-1), Tear Film Break-up Time (TBUT) and Fluorescein Test (FT) were carried out monthly, along with cytological and histopathological examinations at the beginning and end of the study. Results: The clinical signs, corneal ulcers, Schirmer Tear Test-1 values, and Tear Film Break-up Time values improved in both groups after one month of treatment. Cytological examination at the end of the study showed decreased lymphocytes, neutrophil, metaplastic, and squamous cell counts in both groups, while the histopathological analysis showed decreases in lymphocytes and neutrophils and an increase in goblet cell density (cells/mm2). The decreases in neutrophil count were more significant (p<0.05) in the TL group for both types of examination. Conclusion: In sum, 0.03% tacrolimus eye drops diluted in olive oil and linseed oil were effective in the treatment of keratoconjunctivitis sicca. None of the evaluated parameters differed significantly between the two groups, except for neutrophil count which was significantly lower in the TL group. Thus, linseed oil may be considered as an alternative diluent for tacrolimus eye drops.

RESUMO Objetivo: Comparar a eficácia do tacrolimus 0,03% colírio, diluído em óleo de linhaça e óleo de oliva, no tratamento de ceratoconjuntivite seca em cães. Métodos: Foram utilizados 60 cães; 20 cães saudáveis como grupo controle, e 40 cães com diagnóstico de ceratoconjuntivite seca bilateral, distribuídos aleatoriamente em dois grupos: Tacrolimus em óleo de oliva (TO) e Tacrolimus em óleo de semente de linhaça (TL). Os animais foram avaliados mensalmente com exames oftálmicos, Teste lacrimal de Schirmer-1 (TLS-1), Tempo de ruptura do filme lacrimal (TRFL) e Teste de Fluoresceína (TF), e mensalmente com citologia conjuntival e com exame histopatológico no início e final do estudo. Resultados: Nos dois grupos de tratamento os sinais clínicos, Teste lacrimal de Schirmer-1, óleo de semente de linhaça e Tempo de ruptura do filme lacrimal apresentaram melhora após um mês de tratamento. E no final do estudo, na análise citológica, ambos apresentaram diminuição de linfócitos, neutrófilos, células metaplásicas e células escamosas, e na análise histopatológica houve diminuição de linfócitos, neutrófilos e o aumento de células caliciformes. No grupo óleo de semente de linhaça, a diminuição de neutrófilos foi mais significativa (p<0,05) em ambas análises. Conclusão: Em suma, tacrolimus 0,03% colírio diluído em óleo de oliva e óleo de linhaça foram eficientes no tratamento de ceratoconjuntivite seca. Nenhum dos parâmetros avaliados diferiu significativamente entre os dois grupos, exceto a contagem de neutrófilos, que foi significativamente menor no grupo TL. Assim, o óleo de linhaça pode ser considerado como um diluente alternativo para o colírio tacrolimus.

Assessment of corneal and conjunctival metaplasia by impression cytology during the treatment of canine keratoconjunctivitis sicca.

The purpose of this study was to assess the condition of cells in the conjunctiva and corneal epithelium prior to and during cyclosporine- or tacrolimusbased treatment of keratoconjunctivitis sicca (KCS). The study was performed on 40 dogs with KCS. The dogs were divided into two groups of 20 animals each. In Group I, 0.75% cyclosporine eye drops were administered three times a day, while in Group II 0.02% tacrolimus eye drops were administered twice daily. Additionally, each group was subdivided into three subgroups based on the results of the Schirmer I tear test (STT I). Evaluation of cellular metaplasia in the cornea and the palpebral and bulbar conjunctiva based on the Nelson-Adams scale was performed by impression cytology using Millipore round filters (Millipore VSWP 01300 DA) of 25 µm pore diameter applied to the studied area. Ophthalmological and cytological examinations were performed prior to the treatment as well as after one and two months of therapy. In both groups, a decrease in Nelson-Adams values was observed, corresponding to the increasing STT values [Rxy Spearman statistically significant correlation coefficient values between -0.75 (P < 0.001) and -0.45 (P < 0.01)]. The absence of goblet cells was observed in all dogs, regardless of the KCS stage. Goblet cells reappeared following both tacrolimus- and cyclosporine-based treatment in impression cytology specimens classified as 0 in the Nelson-Adams scale. The extent of corneal and conjunctival metaplasia in the course of tacrolimus- and cyclosporine-based treatment of KCS decreases with increasing STT values.

Comparison of the efficacy of 0.03% tacrolimus eye drops diluted in olive oil and linseed oil for the treatment of keratoconjunctivitis sicca in dogs.

OBJECTIVE: To compare the efficacy of 0.03% tacrolimus eye drops diluted in two different vehicles (linseed oil and olive oil) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. METHODS: This study included 60 dogs. Of this group, 20 were healthy and allocated to the control group, and 40 were diagnosed with bilateral KCS and randomly allocated to either the TO (tacrolimus in olive oil) or the TL (tacrolimus in linseed oil) groups. Ophthalmic examinations, Schirmer Tear Test-1 (STT-1), Tear Film Break-up Time (TBUT) and Fluorescein Test (FT) were carried out monthly, along with cytological and histopathological examinations at the beginning and end of the study. RESULTS: The clinical signs, corneal ulcers, Schirmer Tear Test-1 values, and Tear Film Break-up Time values improved in both groups after one month of treatment. Cytological examination at the end of the study showed decreased lymphocytes, neutrophil, metaplastic, and squamous cell counts in both groups, while the histopathological analysis showed decreases in lymphocytes and neutrophils and an increase in goblet cell density (cells/mm2). The decreases in neutrophil count were more significant (p<0.05) in the TL group for both types of examination. CONCLUSION: In sum, 0.03% tacrolimus eye drops diluted in olive oil and linseed oil were effective in the treatment of keratoconjunctivitis sicca. None of the evaluated parameters differed significantly between the two groups, except for neutrophil count which was significantly lower in the TL group. Thus, linseed oil may be considered as an alternative diluent for tacrolimus eye drops.

Canine oral mucosa evaluation as a potential autograft tissue for the treatment of unresponsive keratoconjunctivitis sicca.

PURPOSE: Labial mucosa transplantation for the treatment of canine keratoconjunctivitis sicca (KCS) has been reported recently. Postoperative alleviation of clinical signs was noted and assumed to be the result of labial salivary glands providing lubrication to the ocular tissue. The aim of this study was to evaluate the presence of minor salivary glands (MSG) in the canine oral mucosa. METHODS: Oral mucosal biopsies were collected from six dogs that died (n = 1) or were euthanized (n = 5) for reasons unrelated to this study. The breeds included were two Doberman Pinschers, one Labrador Retriever, one Portuguese Water Dog, one German Shepherd Dog, and one mixed canine. Three were spayed females, and three were castrated males with the median age of 9 years (range, 6-13 years). Samples were obtained by an 8-mm punch biopsy at the following locations of the canine oral cavity: upper rostral labial mucosa at midline, lower rostral labial mucosa at midline, upper labial mucosa near the commissure, lower labial mucosa near the commissure, and buccal mucosa approximately 1 cm caudal to the commissure. Samples were routinely processed with hematoxylin and eosin, and periodic acid-Schiff stains. Samples were evaluated by light microscopy. RESULTS: At the selected locations, no MSG or other secreting cells were detected. CONCLUSIONS: Minor salivary glands are not associated with alleviation of canine KCS symptoms following labial mucosa transplantation. Further studies are needed to determine the mechanism leading to the transient improvement of KCS symptoms in canine patients following labial mucosa transplantation.

Use of clinical vignette questionnaires to investigate the variation in management of keratoconjunctivitis sicca and acute glaucoma in dogs.

There is little peer-reviewed research assessing therapeutic effectiveness in canine eye disease. Current treatments used in first opinion and ophthalmology referral practices are also somewhat poorly documented. The aim of this study was to investigate the current management of canine keratoconjunctivitis sicca (KCS) and acute primary angle-closure glaucoma (PACG) by veterinary surgeons. Questionnaires using clinical vignettes were administered to a cross section of general practitioners ('GPs') and veterinarians engaged in or training for postgraduate ophthalmology practice ('PGs'). Similar treatment recommendations for KCS (topical cyclosporine, lubricant, antibiotic) were given by both groups of veterinarians with the single exception of increased topical antibiotic use by GPs. Treatment of acute glaucoma diverged between groups: PGs were much more likely to recommend topical prostaglandin analogues and a wider array of both topical and systemic treatments were recommended by both groups. Systemic ocular hypotensive agents were suggested infrequently. Our results suggest that treatments may vary substantially in ocular conditions, particularly in conditions for which neither guidelines nor high-quality evidence exists. This study highlights the need for novel strategies to address evidence gaps in veterinary medicine, as well as for better evaluation and dissemination of current treatment experience.

Effect of 0, 15% sodium hialuronate and 0, 5% carboxymethylcellulose on tear film breakup time in healthy dogs and in dogs with keratoconjunctivitis sicca / Efeito do hialuronato de sódio a 0, 15% e da carboximetilcelulose sódica a 0, 5% no tempo de ruptura do filme lacrimal de cães saudáveis e com ceratoconjuntivite seca

This study aimed to evaluate the effect of the 0.15% sodium hyaluronate (SH) and of 0.5% carboxymethylcellulose (CMC) on tear film breakup time (TFBUT) in 10 healthy dogs and in 32 eyes of dogs with keratoconjunctivis sicca (KCS). In addition, the goblet cell density (GCD) of this population was quantified. TFBUT was assessed at baseline and at different time points following the instillation of SH and CMC. KCS was graded as mild, moderate, and severe. GCD were quantified from conjunctival biopsies. The number of GCD differed significantly between patients with mild and moderate KCS (P<0.01). TFBUT of healthy dogs increased only for 1 minute after treatment with SH (P<0.01). Regarding baseline and treatments, SH significantly increased TFBUT for up to 30 minutes on the ocular surface, in comparison to CMC, in all categories of KCS (P<0.01). TFBUT and GCD correlated positively when the healthy and diseased eyes were grouped (r=0.41, P=0.006). It can be concluded that in dogs with KCS, SH lasts longer periods on the ocular surface than CMC, but such agents does not increase TFBUT in healthy dogs. Additionally, tear film stability tends to reduce in a linear fashion from the mild to severe form of KCS.(AU)

Objetivou-se avaliar os efeitos do hialuronato de sódio a 0,15% (HS) e da carboximetilcelulose a 0,5% (CMC) no teste de ruptura do filme lacrimal (TRFL) em 10 cães saudáveis e em 32 olhos de cães com ceratoconjuntivite seca (CCS). Ademais, quantificou-se a densidade de células caliciformes (DCC) deles. Mensurou-se o TRFL em momentos distintos antes e após a instilação do HS e da CMC. Graduou-se a CCS em leve, moderada e severa. Quantificou-se a DCC a partir de biópsias conjuntivais. A DCC diferiu apenas entre pacientes com CCS leve e severa (P<0,01). Em cães saudáveis, o TRFL se elevou apenas após um minuto do tratamento com HS (P<0,01). Relativamente ao período basal e entre os tratamentos, o HS elevou o TRFL de forma mais eficaz e permaneceu por até 30 minutos na superfície ocular, comparativamente à CMC, em todas as categorias de CCS (P<0,01). Ao se agruparem os olhos saudáveis e os com CCS, o TRFL se correlacionou com a DCC (r=0.41, P=0.006). Conclui-se que o HS permanece por maior tempo na superfície ocular que a CMC em cães com CCS, mas que tais substâncias não elevam o TRFL em cães saudáveis. Ademais, a estabilidade do filme lacrimal tende a se reduzir de modo linear da forma leve até à severa da CCS.(AU)

Eficácia dos colírios ciclosporina e tacrolimo no tratamento de ceratoconjuntivite seca em cães / Efficacy of cyclosporine and tacrolimus drops in the treatment of keratoconjunctivitis sicca in dogs

O objetivo deste estudo foi avaliar os efeitos do tacrolimo e da ciclosporina na produção lacrimal de cães com ceratoconjuntivite seca (CCS) durante 90 dias. Para tanto, foram utilizados colírios de tacrolimo 0,02% (TcL) e ciclosporina 0,1% (CsA) em 14 cães com CCS. Os animais foram distribuídos em dois grupos e avaliados antes do início do tratamento (T0) e aos 15 (T1), 30 (T2), 45 (T3), 60 (T4), 75 (T5) e 90 (T6) dias após o início do tratamento. Na avaliação clínica, observou-se maior redução da secreção ocular, da opacidade e do edema corneano e da vascularização conjuntival. no grupo tacrolimo. No teste de Schirmer, verificou-se produção basal de 6(4,07 e 5,86(2,85mm/min no TcL e CsA, respectivamente, com aumento significativo da produção lacrimal em ambos os grupos, contudo houve aumento significativo da produção lacrimal a partir dos 15 dias de tratamento no grupo TcL (17,88(5,51mm/min), mas apenas a partir dos 45 dias no grupo CsA (11,86(4,74mm/min). Conclui-se que o uso do colírio tacrolimo aumentou em 68,83% a produção lacrimal em 90 dias de tratamento, comparado com a ciclosporina (56,82%), além de diminuir as manifestações clínicas inerentes à CCS, quando comparado à terapia com ciclosporina.(AU)

The objective of this study was to evaluate the effects of tacrolimus and cyclosporine on the lacrimal production of dogs with ketaroconjunctivitis sicca (KCS) for 90 days. Tacrolimus 0.02% (TcL) and 0.1% cyclosporine (CsA) eye drops were used in 14 dogs with KCS. The animals were randomly assigned to two groups and evaluated before treatment (T0) and at 15 (T1), 30 (T2), 45 (T3), 60 (T4), 75 (T5) and 90 (T6) days after initiation of treatment. Clinical evaluation showed significant reduction of ocular secretion, corneal opacity and edema and conjunctival vascularization in the tacrolimus group. Schirmer test showed basal lacrimal production of 6(4.07 and 5.86(2.85mm/min for TcL and CsA, respectively, with significant increase in lacrimal production in both groups. There was a significant increase in lacrimal production after 15 days of treatment in the TcL group (17.88(5.51mm/min), but only after 45 days in the CsA group (11.86(4.74mm/min). Tacrolimus drops increased lacrimal production in 68.83% after 90 days of treatment, compared to cyclosporine (56.82%), and also reduced clinical manifestations related to KCS when compared to cyclosporine.(AU)

Caracterização clínica e histopatológica de bulbos oculares de cães e gatos (2005-2015) / Clinical and histopathologic characterization of ocular bulbs in dogs and cats (2005-2015)

Objetivou-se realizar a caracterização clínica e histopatológica de bulbos oculares de cães e gatos, removidos cirurgicamente por indicação clínica, no período entre 2005-2015. Foram realizados 101 procedimentos de remoção do bulbo ocular, 93 enucleações (92%) e 8 exenterações (8%). Os procedimentos foram realizados em 80 cães, (79% dos casos) e em 21 gatos (21% dos casos). Os cães submetidos à intervenção cirúrgica apresentavam perfurações oculares (n=31, 39%), glaucoma (n=19, 24%), protrusão ocular (n=13, 16%), diagnósticos sugestivos de neoplasia (n=10, 12,5%) e outros (n=3, 2,97%). Dentre os gatos os diagnósticos clínicos compreenderam perfuração ocular (n=9, 49%), glaucoma (n=3, 14,2%), microftalmia (n=3, 14,2%), sugestivo de neoplasia (n=2, 9,5%), protrusão ocular (n=2, 9,5%) e outros (n=2, 9,5%). Vinte e sete amostras de bulbos oculares foram submetidas para avaliação histopatológica, sendo 23 provenientes de cães e quatro de gatos. Dentre as amostras de origem canina, sete exibiram achados histopatológicos compatíveis com glaucoma, sete perfurações oculares, seis neoplasias intraoculares, duas panoftalmites e um quadro de Phthisis bulbi. Nos bulbos oculares de gatos foram diagnosticadas duas neoplasias intraoculares, uma microftalmia e uma perfuração ocular. Constatou-se que o glaucoma secundário, as neoplasias e as perfurações oculares estão entre as principais causas de enucleação em cães, e associadas a alterações primárias como a ceratoconjuntivite seca e as uveítes. Estas afecções, diferentemente das neoplasias, podem ter êxito terapêutico mediante diagnóstico e tratamento precoces, prevenindo a cegueira e a remoção do bulbo ocular.(AU)

This study aimed to carry out the clinical and histopathologic characterization of ocular bulbs from dogs and cats, surgical removed as clinical indication between 2005-2015. Hundred-one procedures were performed, 93 enucleations (92%) and 8 exenterantions (8%). The procedures were performed on 80 dogs (79% of cases) and 21 cats (21% of cases). The dogs underwent to surgery had ocular perfuration (n=31, 39%), glaucoma (n=19, 24%), ocular protrusion (n=13, 16%), diagnosis suggestive of neoplasia (n=10, 12, 5%) and other (n=3, 2.97%). Among the clinical diagnosis cats comprise ocular perforation (n=9, 49%), glaucoma (n=3, 14.2%), microphthalmia (n=3, 14.2%), suggestive of neoplasia (n=2, 9.5%), ocular protrusion (n=2, 9.5%) and other (n=2, 9.5%). Twenty-seven samples of ocular bulbs were sent for histopathologic evaluation in Veterinary Pathology Laboratory, being 23 from dogs and four cats. Among the samples of dogs, seven exhibited histopathologic findings compatible with glaucoma, seven ocular perforations, six had intraocular neoplasias, two panoftalmites and condition of Phthisis bulbi. The ocular bulbs of cats received the diagnosis of two intraocular neoplasias, one microphthalmia and ocular perforation. It was found that the secondary glaucoma and ocular perforations are among the leading causes of enucleation in dogs, and associated with primary disorders such as keratoconjunctivitis sicca and uveitis. These disorders, unlike neoplasia, may have therapeutic success through early diagnosis and treatment, preventing blindness and removal of the eyeball.(AU)

Clinical and light microscopic studies of the conjunctival tissues of dogs with bilateral keratoconjunctivitis sicca before and after treatment with topical 2% cyclosporine.

We determined the concentrations of goblet and immune cells in conjunctival imprints and tissues of canines with keratoconjunctivitis sicca (KCS) before and after cyclosporine A (CsA) treatment. Twelve dogs with bilateral KCS were assigned to three groups: untreated, treatment group 1, and treatment group 2. The treatment groups were treated topically with 2% ophthalmic CsA solution for 45 days; CsA treatment group 2 was followed for an additional 30 days after discontinuation of the drug. Schirmer tear test (STT) scores were recorded prior to CsA treatment and on alternate days throughout the experiment. CsA treatment improved the STT scores, restored conjunctival histology, increased goblet and epithelial cell numbers, and decreased numbers of inflammatory cells. Although the STT scores regressed slightly at day 30 after discontinuing the treatment, the scores were higher than the baseline values. Topical CsA treatment resolved clinical signs of KCS, improved STT scores and restored normal conjunctival histology.