A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis.

Gene therapy approaches using adeno-associated viral vectors have been successfully tested in the equine post-traumatic osteoarthritis (PTOA) model. Owing to differences in the levels of transgene expression and adverse tissue reactions observed in published studies, we sought to identify a safe therapeutic dose of scAAVIL-1ra in an inflamed and injured joint that would result in improved functional outcomes without any adverse events. scAAVIL-1ra was delivered intra-articularly over a 100-fold range, and horses were evaluated throughout and at the end of the 10-week study. A dose-related increase in IL-1ra levels with a decrease in PGE2 levels was observed, with the peak IL-1ra concentration being observed 7 days post-treatment in all groups. Perivascular infiltration with mononuclear cells was observed within the synovial membrane of the joint treated with the highest viral dose of 5 × 1012 vg, but this was absent in the lower-dosed joints. The second-highest dose of scAAVeqIL-1ra 5 × 1011 vg demonstrated elevated IL-1ra levels without any cellular response in the synovium. Taken together, the data suggest that the 10-fold lower dose of 5 × 1011vg scAAVIL-1ra would be a safe therapeutic dose in an equine model of PTOA.

Comparing the clinical success rate of the dorsolateral approach to the medial approach for injection of the centrodistal joint in the horse.

BACKGROUND: Centrodistal joint injection is an important component of lameness evaluation and treatment. Successful injection is poor for the medial approach. The dorsolateral approach is an alternative but has not been validated with contrast medium. Radiograph-guidance has not been studied to determine its necessity or benefit for either approach. OBJECTIVES: To determine if the dorsolateral approach to the centrodistal joint is more successful than the medial approach. To determine if radiograph-guidance is beneficial. STUDY DESIGN: Prospective, randomised study. METHODS: Three operators injected 98 centrodistal joints in total, each horse served as its own control. In Phase 1, injections were performed by standard technique. In the Phase 2, operators were allowed to use radiography to assist needle placement. Contrast deposition was evaluated by a single radiologist. RESULTS: Without radiographic assistance, 10/25 (40%) joints were successfully injected using either the medial or dorsolateral approach. With radiographic assistance, 19/24 (79%) joints were successfully injected using the medial approach, 11/24 (46%) joints were successfully injected using the dorsolateral approach. MAIN LIMITATIONS: The population consisted of aged horses representing a variety of breeds with existing osteoarthritis, and multiple operators were recruited. CONCLUSIONS: The dorsolateral approach was equivalent to the medial approach when traditional injection techniques were used. Radiograph-guidance improved success of the medial approach, but not the dorsolateral approach. Many injections performed from the dorsolateral approach (32/49; 65%) resulted in extensive perivascular subcutaneous contrast deposition after infiltration into the tarsal canal. Further research is needed to improve injection success of the centrodistal joint when using the dorsolateral approach.

Clinical study evaluating the accuracy of injecting the distal tarsal joints in the horse.

BACKGROUND: Osteoarthritis (OA) of the centrodistal (CD) and tarsometatarsal (TMT) joints is a common cause of lameness in horses. Intra-articular diagnostic anaesthesia and/or therapeutic injection are relied upon to help diagnose and treat many horses with OA of these joints. OBJECTIVES: The objective of this study was to determine the accuracy of arthrocentesis of the CD and TMT joints using a sample population of equine surgeons and surgery residents. STUDY DESIGN: Randomised experimental study. METHODS: Six operators each injected four CD and four TMT joints in 12 sedated horses. The operators were randomly assigned to inject either the left CD and right TMT or the right CD and left TMT on four randomly assigned horses. The joints were injected with a 4 ml solution of contrast medium (2 ml), sterile saline (1.5 ml) and amikacin (0.5 ml). A minimum of two radiographs of each joint was obtained to evaluate the presence of contrast medium within the target joint. RESULTS: The TMT joint was successfully injected in 23/24 joints (96% accuracy). The CD joint was successfully injected in 10/24 joints (42% accuracy). Communication between the TMT and CD joints was visible in 26% of successful TMT injections. Communication between the CD and TMT joints was visible in 20% of successful CD injections. MAIN LIMITATIONS: Despite specific requests to do so, we were unable to standardise the injection technique across all operators. CONCLUSIONS: The accuracy of injecting the TMT and CD joints of sedated horses was 96 and 42%, respectively. The CD joint was frequently missed with contrast medium being placed in the periarticular tissues. These data support the clinical impression of the difficulty of injecting the CD joint and suggests that practitioners should utilise ancillary methods, such as radiographs, to ensure proper needle placement.