Limited Efficacy of Autologous Mesenchymal Stromal Cell Injections in Immunomodulatory‐Dependent Dogs With Aqueous Deficient Dry Eye Disease

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OBJECTIVE: Aqueous deficient dry eye disease (ADDE) results from a quantitative reduction in aqueous tears. We sought to determine the clinical effect of autologous mesenchymal stromal cell (MSC) injections into the region of the lacrimal gland and the gland of the third eyelid in immunomodulatory-dependent ADDE-affected dogs. METHODS: Dogs (n = 4) were enrolled that met the inclusion criteria for ADDE (consistent clinical signs combined with Schirmer tear test I [STT-I] value < 15 mm/min, responsive to topical immunomodulatory therapy, and documented drop in STT-I after cessation of therapy). By applying these stringent criteria, there was a high failure rate for inclusion. Autologous MSCs were harvested, expanded, and unilaterally injected after cessation of immunomodulatory therapy. Examinations, ophthalmic diagnostics, clinical scoring, and owner surveys were performed at regular intervals post-injection. RESULTS: No adverse ocular events were associated with the MSC injections. There were variable responses between dogs, with one dog exhibiting an immediate increase in STT-I that remained elevated (5.5-fold increase); two dogs had a smaller and temporary increase in STT-I over baseline (0.6-0.7-fold increases), and one dog had no increases detected over the initial 6 months. Repeated injections did not improve clinical or diagnostic values. CONCLUSIONS: Autologous MSC injections were well-tolerated in dogs with ADDE. Results were variable in this small sample size. Despite initial improvement in 3 of 4 dogs, the positive response was variable in magnitude of response and duration of effect. Repeated injections did not sustain this response. Future studies using conditioned MSCs and/or exosomal therapy are warranted.