Effects of topically applied heterologous serum on reepithelialization rate of superficial chronic corneal epithelial defects in dogs

• Autores: J. Seth Eaton, Steven R. Hollingsworth, Bradford J. Holmberg, Michael H. Brown, Patricia J. Smith, David J. Maggs
• Localización: JAVMA: Journal of the American Veterinary Medical Association, ISSN-e 0003-1488, Vol. 250, Nº. 9, 2017, págs. 1014-1022
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • JECTIVE To assess the effects of topical application of undiluted heterologous serum on time to corneal reepithelialization in dogs with superficial chronic corneal epithelial defects (SCCEDs).

    DESIGN Multicenter, randomized, double-masked, controlled clinical trial.

    ANIMALS 41 client-owned dogs.

    PROCEDURES After collection of baseline clinical and historical data, dogs were randomly assigned to receive topically applied undiluted heterologous serum (n = 22) or isotonic saline (0.9% NaCl) solution (19) along with tobramycin and atropine. Epithelial debridement (at all visits) and grid keratotomy (at visits 2, 3, and 4) of SCCEDs were performed. Ophthalmic examination including fluorescein application was performed once weekly for 4 weeks or until corneal reepithelialization. Clinicians and owners were masked to treatment group.

    RESULTS No differences in baseline data were detected between treatment groups. No difficulties with medication administration, noncompliance, or adverse reactions were noted. All SCCEDs in both groups healed by 4 weeks after treatment began. Median time to reepithelialization (2 weeks) was not significantly different between serum-treated and placebo-treated eyes. Irrespective of treatment group, median time to reepithelialization was not significantly different for Boxers versus non-Boxer breeds. Direct correlations were detected between time to reepithelialization and vascularization score at study entry, vascularization score at time of reepithelialization, and ulcer area at study entry in both groups. Time to reepithelialization was not correlated with age, sex, or duration of signs in either group.

    CONCLUSIONS AND CLINICAL RELEVANCE Topical application of undiluted heterologous serum was well tolerated by dogs with SCCEDs but, as an adjunct to standard treatment, did not reduce time to corneal reepithelialization.

    Superficial corneal ulcers are encountered in veterinary and human patients and are characterized by loss of corneal epithelium, exposure of corneal stroma without stromal loss, and, often, marked discomfort. They are readily diagnosed by slit-lamp biomicroscopy and fluorescein retention by the exposed corneal stroma.1 Factors such as conformation-related exposure, adnexal disease, or tear deficiency can reduce protection of the corneal surface and contribute to epithelial cell damage or loss, but are not always evident on examination.1 In dogs, a form of chronic superficial corneal ulceration with no identifiable cause or complicating factor is common. Such ulceration is often referred to as indolent ulcer or SCCED. This disorder is most commonly diagnosed in middle-aged to older dogs, and the Boxer breed is overrepresented.1,2 The cardinal clinical feature unique to SCCEDs is a lip of nonadherent epithelium surrounding the epithelial defect.1,2 Debridement of this loose tissue is diagnostic and a common component of therapeutic approaches used for this condition.2–4 The pathogenesis of SCCED remains poorly understood, with some proposing that it represents a primary epithelial abnormality,5 while others claim that stromal dysfunction or anatomic derangement is causative or contributory.6 It is possible that both contribute to the pathogenesis of this disease, maybe in different degrees, depending on chronicity.

    Because of the ill-defined pathogenesis, definitive treatment of SCCED remains controversial. However, in combination with standard topical antimicrobial treatment and corneal epithelial debridement, anterior stromal puncture techniques such as punctate or grid keratotomy or diamond-burr debridement are widely used, with or without bandage contact lenses, and are associated with variable clinical success rates.1–4,7–11 Adjunctive use of topical treatments is associated with favorable effects on healing rates of SCCEDs.3,12–18 In humans, serum has been used as an adjunctive topical treatment for many ocular surface diseases, especially ulcerative corneal disease. In particular, topical application of serum has been associated with improvements in corneal healing rates and comfort in patients with persistent corneal epithelial defect, which is a disease with a similar clinical appearance to SCCED.19–29 The clinical benefits of topical treatment with serum are believed to be at least partially due to high concentrations of numerous growth factors, particularly epidermal growth factor, as well as vitamin A, fibronectin, and others.30 Collectively, the abundance of such components in serum is believed to promote epithelial health and wound healing capacity.25,31 Serum has also been used as a therapeutic agent in veterinary patients, particularly those with corneal malacia, wherein the antiproteinase activity of serum reduces enzymatic corneal stromal degradation.32,33 To the authors’ knowledge, however, no published reports exist of studies evaluating the effect of topically applied serum in dogs with SCCED. Therefore, the purpose of the multicenter, randomized, double-masked clinical trial reported here was to assess the effects on corneal wound healing of topical application of undiluted serum as an adjunct to standard treatment in dogs with SCCED. We hypothesized that, relative to placebo, adjunctive treatment with topically applied, undiluted serum would promote wound healing and shorten time to reepithelialization of spontaneously arising SCCED in client-owned dogs.