Our institutional ethics committee approved this study prior to enrollment of the first patient (R074h/62). All patients provided written informed consent before participation in this trial. This study was designed as a cohort study.
Patients who visited the orthopedic out-patient clinic at Phramongkutklao Hospital from October 2019 to November 2019 with a chief complaint of knee pain were evaluated. The inclusion criteria were unilateral or bilateral knee OA according to 2016 American College of Rheumatology (ACR) clinical classification criteria for early diagnosis of knee OA15 and dissatisfaction with conservative treatment or an inability to take analgesic medication with the following condition; knee OA with Kellgren-Lawrence (KL) II-III, KL IV with refusal for surgery, contraindication for nonsteroidal anti-inflammatory drugs (NSAIDs) or contraindication for surgery.13 The exclusion criteria comprised patients who had a history that contributed to secondary knee OA, such as post-infection or inflammatory joint disease, viscosupplement treatment within the previous 6 months, intra-articular corticosteroid injection within the previous 3 months or hypersensitivity to hyaluronic acid.
All of the patients underwent US measurement for synovial thickness before intra-articular injection of cross-linked HA, at 4 weeks, and 3 months after injection. Standing knee radiographs (anteroposterior and lateral views) were applied to classify disease severity with KL classification.16
An ultrasonogram machine (GE Healthcare model LOGIQ® e); preset: musculoskeletal – knee in B mode, 12L-RS wideband linear probe (12-MHz) was used. The patients were set in a supine position on an examination table with knees maintained in a flexed but relaxed position at 30 degrees. (Fig. 1) A midline scanning technique was used by vertically applying a linear probe at just proximal to the superior pole of the patella.17− 19 The quadriceps were identified as parallel lines of muscle fibers originating from the superior pole of the patella. Suprapatellar pre-femoral fat pad, which would be identified as a heterogenous fatty streak, was located just proximally to the anterior region of the femoral condyles. The homogenous echoic layer of tissue overlying the fat pad was the synovium.20,21 The thickest part of the synovium was measured in millimeters to one decimal. (Fig. 2)
All patients received a single intra-articular injection of cross-linked hyaluronic acid; Hyruan ONE (LG Chem, Ltd. Jeollabuk-Do, Republic of Korea). Injection was performed in a supine position. The knee was flexed approximately 90 degrees and prepared in a sterile fashion, after which 2 mL of 2% lidocaine hydrochloride with 1:80,000 epinephrine was infiltrated into the skin and subcutaneous tissue at the lateral soft spot of the knee joint just inferior to the lower pole of the patella with a 21-gauge needle. The accuracy of the injection was assessed by an unobstructed injection of lidocaine into the knee joint. In cases of joint effusion, the fluid would be aspirated into a separate syringe. The same needle was left in place and then a syringe prefilled with 60 mg/3 mL of cross-linked HA was injected.22 All patients were under the same post-injection pain control protocol with a prescription of tramadol and acetaminophen. The patients were advised not to take any other medications relevant to the treatment of the knee or arthritis.
Synovial thickness, detected by US measurement of the knee OA patients in each KL classification, was recorded as the baseline characteristic before IAHA. At 4 weeks and 3 months after injection, the US measurements were repeated to observe changes in the synovial thickness. Knee pain was also evaluated at every visit by recording the visual analog scale for pain (pain VAS).
All data were given as means ± standard deviation (SD). Statistical comparisons were performed using paired Student’s t-test for comparison of synovial thickness before and after IAHA. The synovial thickness changes in different groups of knee OA patients, according to KL classification, were assessed by unpaired t-test. A significant level was p-value < 0.05. Statistical analysis was performed with STATA/MP12.