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Exploração dos Fatores de Risco e das Estratégias de Gestão Avançada das Úlceras Refratárias da Córnea no Cão e no Gato: Desafios Clínicos e Inovações Terapêuticas
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Advisor(s)
Abstract(s)
As úlceras refratárias da córnea em cães e gatos representam um desafio terapêutico de grande
relevância em oftalmologia veterinária, devido à sua etiopatogenia complexa e ao elevado risco de
complicações graves. A sua abordagem exige uma estratégia multimodal que integre tratamento
antimicrobiano, anti-inflamatório, medicina regenerativa, identificação e terapêutica de causas
primárias. Antibioterapia tópica convencional revelaa-se frequentemente insuficiente perante o
surgimento de estirpes bacterianas multirresistentes, nomeadamente Pseudomonas
aeruginosa e Staphylococcus pseudointermedius resistentes à meticilina. A associação de doxiciclina
oral com agentes anticolagenases, como o soro autólogo ou o EDTA tetracíclico, é essencial para limitar
a degradação do estroma corneano.
O tratamento cirúrgico e as abordagens inovadoras como os hidrogéis termossensíveis, as
nanopartículas de sílica mesoporosa ou os colírios enriquecidos com PRP permitem melhorar a
administração localizada de princípios ativos e estimular a cicatrização estromal. Paralelamente, as
terapias genéticas (CRISPR-Cas9, ARNi) e a fagoterapia abrem novas perspetivas face à crescente
resistência aos antibióticos. O controlo da fibrose corneana assenta na utilização de inibidores do
fatore de crescimento TGF-β ou em técnicas como a terapia fotodinâmica.
O desenvolvimento de biomarcadores lacrimais preditivos, como a N-acetilglucosamina, permite um
acompanhamento personalizado da cicatrização. Por fim, o avanço dos modelos 3D e dos ensaios
clínicos integrados na abordagem One Health abre caminho à melhor transposição das inovações
terapêuticas entre a medicina veterinária e humana. Esta tese sublinha a importância de uma
abordagem integrativa e personalizada para otimizar o prognóstico visual e limitar as sequelas
cicatriciais nas formas refratárias.
Refractory corneal ulcers in dogs and cats represent a major therapeutic challenge in veterinary ophthalmology due to their complex etiopathogenesis and high potential for severe complications. Their management requires a multimodal approach that integrates antimicrobial, anti-inflammatory, regenerative strategies, identification and primary causes therapy. Conventional topical antibiotic therapies are often insufficient in the face of emerging multidrug-resistant bacterial strains, particularly Pseudomonas aeruginosa and methicillin-resistant Staphylococcus pseudointermedius. The combination of oral doxycycline with anticollagenases such as autologous serum or tetracycline EDTA has proven essential in limiting corneal melting. Surgical treatment and innovative approaches such as thermosensitive hydrogels, mesoporous silica nanoparticles, or PRP-enriched eye drops, improve targeted drug delivery and stimulates stromal healing. In parallel, gene therapies (CRISPR-Cas9, RNAi) and phage therapy offer new perspectives in addressing antibiotic resistance. The control of corneal fibrosis relies on the use of TGF-β inhibitors or techniques such as photodynamic therapy. The development of predictive tear film biomarkers, such as N-acetylglucosamine, enables personalized monitoring of the healing process. Finally, the rise of 3D models and One Health clinical trials paves the way for better translation of therapeutic innovations between veterinary and human medicine. This thesis highlights the importance of an integrative and personalized approach to optimize visual prognosis and minimize scarring in refractory cases.
Refractory corneal ulcers in dogs and cats represent a major therapeutic challenge in veterinary ophthalmology due to their complex etiopathogenesis and high potential for severe complications. Their management requires a multimodal approach that integrates antimicrobial, anti-inflammatory, regenerative strategies, identification and primary causes therapy. Conventional topical antibiotic therapies are often insufficient in the face of emerging multidrug-resistant bacterial strains, particularly Pseudomonas aeruginosa and methicillin-resistant Staphylococcus pseudointermedius. The combination of oral doxycycline with anticollagenases such as autologous serum or tetracycline EDTA has proven essential in limiting corneal melting. Surgical treatment and innovative approaches such as thermosensitive hydrogels, mesoporous silica nanoparticles, or PRP-enriched eye drops, improve targeted drug delivery and stimulates stromal healing. In parallel, gene therapies (CRISPR-Cas9, RNAi) and phage therapy offer new perspectives in addressing antibiotic resistance. The control of corneal fibrosis relies on the use of TGF-β inhibitors or techniques such as photodynamic therapy. The development of predictive tear film biomarkers, such as N-acetylglucosamine, enables personalized monitoring of the healing process. Finally, the rise of 3D models and One Health clinical trials paves the way for better translation of therapeutic innovations between veterinary and human medicine. This thesis highlights the importance of an integrative and personalized approach to optimize visual prognosis and minimize scarring in refractory cases.
Description
Keywords
Animais de companhia Antibioterapia Oftalmologia Úlceras da córnea Antibiotic therapy Corneal ulcers Ophthalmology Pets