Mechanistic domains in canine corneal ulcer progression: a conceptual framework for adjunctive management

Canine corneal ulcers are commonly encountered in clinical practice and may progress to stromal melting and perforation if not appropriately managed. Adjunctive therapy has traditionally focused on collagenolysis inhibition and is often guided by morphological severity rather than dominant biological drivers. While anticollagenase strategies remain essential, ulcer progression involves interconnected processes, including inflammatory amplification, impaired epithelial repair, and ocular surface instability. This conceptual analysis therefore seeks to develop a mechanism-based conceptual framework that prioritizes these biological processes and guides adjunctive therapeutic decision-making.

A targeted literature search was conducted using PubMed and Scopus for studies published between January 2000 and February 28, 2026. Relevant canine, animal model, and human studies were narratively synthesized to identify key pathophysiologic drivers and construct a mechanism-based hierarchical framework for adjunctive therapy. Interventions were categorized according to primary mechanistic targets and levels of supporting canine evidence.

The proposed framework delineates four therapeutic domains (Structural Preservation, Inflammatory Modulation, Regenerative Augmentation, and Functional Optimization) together with a meta-level component termed Precision Stratification. Structural Preservation, centered on protease inhibition, represents the highest biological priority in cases of active stromal melting. Inflammatory Modulation targets upstream amplification processes, whereas Regenerative Augmentation and Functional Optimization address epithelial repair and ocular surface stability, respectively. Precision Stratification is conceptualized as a meta-level decision-support component that aligns domain prioritization with dominant biological drivers. Evidence strength varies across domains; structural preservation strategies are supported by the broadest canine clinical evidence, whereas inflammatory modulation, regenerative, and precision-oriented strategies rely predominantly on translational or investigational data.

The principal contribution of this work is the development of a mechanism-based hierarchical framework for adjunctive management of canine corneal ulcers. The framework preserves the central role of protease inhibition while situating it within a broader biologically structured model of corneal ulcer progression. Canine-specific validation of domain-targeted interventions and development of objective stratification tools represent important priorities for future investigation.