Intralesional interferon alpha-2b as a novel treatment for periocular squamous cell carcinoma in horses.

OBJECTIVE: To determine the safety and efficacy of perilesional human recombinant interferon alpha-2b (IFNα2b) for treatment of periocular squamous cell carcinoma (PSCC) in horses. ANIMALS STUDIED: Eleven horses (12 eyes) with PSCC were enrolled in this prospective clinical study with owner consent. PROCEDURES: Systemically healthy horses were included in the study following confirmation of PSCC via biopsy. Every two weeks for a maximum of six treatments, horses were sedated and perilesional injection of IFNα2b (10 million IU) was performed. Tumors were measured prior to each injection and at one, three, and 12 months after treatment completion. A greater than 50% reduction in tumor size was considered positive response to treatment (i.e., partial or complete response). Development of anti-IFNα2b antibodies was assessed using serum samples obtained after treatment initiation and compared with treatment responses. Antibody concentrations were analyzed using a mixed model. Statistical significance was considered p < 0.05. RESULTS: Each horse received four to six perilesional injections of IFNα2b. Five of 12 eyes (4/11 horses) responded to treatment. Two of five eyes showed complete resolution of gross PSCC. No systemic adverse effects were seen. Local swelling occurred during treatment protocol in 6/11 horses but resolved without intervention. All horses developed serum anti-IFNα2b antibodies. There was no evidence of statistical difference in antibody concentration between responders and non-responders. CONCLUSIONS: Perilesional administration of IFNα2b was found to be well-tolerated in horses with PSCC, and induced tumor regression in 42% of treated eyes. Treatment failure appears unrelated to the development of IFNα2b antibodies.

Novel ocular immunotherapy induces tumor regression in an equine model of ocular surface squamous neoplasia.

Ocular surface squamous neoplasia (OSSN) is the major cause of corneal cancer in man and horses worldwide, and the prevalence of OSSN is increasing due to greater UVB exposure globally. Currently, there are no approved treatments for OSSN in either species, and most patients are managed with surgical excision or off-label treatment with locally injected interferon alpha, or topically applied cytotoxic drugs such as mitomycin C. A more broadly effective and readily applied immunotherapy could exert a significant impact on management of OSSN worldwide. We therefore evaluated the effectiveness of a liposomal TLR complex (LTC) immunotherapy, which previously demonstrated strong antiviral activity in multiple animal models following mucosal application, for ocular antitumor activity in a horse spontaneous OSSN model. In vitro studies demonstrated strong activation of interferon responses in horse leukocytes by LTC and suppression of OSSN cell growth and migration. In a trial of 8 horses (9 eyes), treatment with topical or perilesional LTC resulted in an overall tumor response rate of 67%, including durable regression of large OSSN tumors. Repeated treatment with LTC ocular immunotherapy was also very well tolerated clinically. We conclude therefore that ocular immunotherapy with LTC warrants further investigation as a novel approach to management of OSSN in humans.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Effect of topical administration of 0.1% diclofenac sodium ophthalmic solution at four frequencies on intraocular pressure in healthy Beagles.

OBJECTIVE: To evaluate effects of topical ophthalmic administration of diclofenac on intraocular pressure (IOP) when applied at 4 frequencies to eyes of Beagles. ANIMALS: 8 ophthalmologically normal Beagles. PROCEDURES: The study involved four 5-day experimental periods each separated by a 16-day washout period. During each period, 1 drop of 0.1% diclofenac sodium ophthalmic solution was administered to the right eye at 4 treatment frequencies (1, 2, 3, or 4 times/d); 1 drop of eyewash was administered to the left eye as a control treatment. A complete ophthalmic examination was performed on days 0 (day before first treatment) and 5 of each experimental period. Gonioscopy was performed on day 0 of the first period. The IOPs were measured at 7 am and 7 pm on days 1 through 5. RESULTS: No abnormalities were detected during neuro-ophthalmic and ophthalmic examinations on day 0 of each experimental period. No adverse reactions to administration of diclofenac or eyewash were observed at any time point. No abnormalities were detected during ophthalmic examinations performed on day 5, and IOPs remained < 25 mm Hg in all 4 periods. No significant differences were identified between the treated and control eyes or among the 4 treatment frequencies. CONCLUSIONS AND CLINICAL RELEVANCE: Topical ophthalmic administration of diclofenac up to 4 times/d in dogs with no ophthalmic abnormalities did not significantly increase the IOP. Additional research is needed to evaluate the effect of topical ophthalmic administration of diclofenac on IOP in dogs with anterior uveitis.