Antiproteolytic Agents (Enzyme Inhibitors) and Chelating Agents in Animals

Deep and melting ulcers are usually associated with Pseudomonas spp or beta-hemolytic streptococci. Proteases, hydrolases, and collagenases produced by bacteria, neutrophils, epithelial cells, dying keratocytes, and macrophages cause rapid collagenolysis and melting of stroma that can rapidly progress to a descemetocoele and possible corneal perforation within 24 hours. Topical 1%–2% disodium ethylenediaminetetraacetic acid (EDTA) (drops and ointment), 5%–10% N-acetylcysteine, and 0.1% tetracyclines (oxytetracycline and doxycycline) inhibit matrix metalloproteinases (MMP) by binding calcium and zinc. Undiluted topical autologous and homogenous serum or plasma has alpha 2-macroglobulin and alpha-1 proteinase inhibitor that act to inhibit MMP and serine protease. Frozen serum or plasma retain anti-protease efficacy for up to 180 days. Antiprotease drops should be applied 2–4 hours initially to inhibit melting and then can be decreased to every 4–6 hours. Oral doxycycline (10 mg/kg every 24 hours) is also effective as an antiproteolytic agent and can be combined with topical antiprotease drops.

Corneal calcium deposits can occur in age-related corneal degenerations, often in older animals. These can present as innocuous lines of calcium which can coalesce into a more crystalline form. If these small deposits slough from the epithelial surface they can cause painful micro-ulcers. Sloughing of larger deposits can leave deep stromal defects, and sometimes a descemetocoele. These can be difficult to surgically correct. Treatment involves trying to stop progression by administering a topical chelating agent (1% EDTA drops or 2% ointment), topical antimicrobials, and lubricating gel.