Patellar tendinopathy is an overuse condition that affects up to 14% of elite athletes who practice jumping sports (high and long jump, basketball, and volleyball).1,2 Characterized by neovascularization and innervation in and around the tendon, the first-line approach is conservative. A twice-daily eccentric loading regime for 12 weeks may improve the state of intratendinous neovascularization and the symptoms of tendinopathy,3 but the rationale of this is still uncertain. It is possible that eccentric loading induces vessel disruption and collapse, relying on the evidence that symptoms are relieved when sclerosing agents are injected into the site of neovascularization, under ultrasound (US) guidance.4
These vessels may also be disrupted when applying mechanical stresses, as observed when injecting large volumes of fluid between the posterior aspect of the paratenon of the patellar tendon and Hoffa body (ie, the area from where the neovessels penetrate the tendinopathic lesion).5 In preliminary studies in patients with recalcitrant tendinopathy with evidence at color or power Doppler of neovascularity of the main body of the patellar5 and Achilles tendon,6,7 a high-volume image-guided injection (HVIGI) decreased the amount of pain perceived by patients and improved functional activities in the short term and long term. This is a 15-month follow-up study that assesses the short-term effect of HVIGI of normal saline solution in 32 patients with recalcitrant tendinopathy of the patellar tendon at the attachment of the lower pole of the patella.
MATERIALS AND METHODS
All patients were managed after they had signed a written consent and after approval by the local ethics committee. Patients were informed about the finalities of the study and were asked to be available to be contacted and attend the clinic to undergo imaging, clinical, and functional assessment. Patients were given information regarding possible hypersensitivity reactions to aprotinin8 and risk of infection. In the event of adverse events and serious adverse events, it was planned that the investigators would have assessed whether they were related to procedure. Investigators would have informed the local ethical committees of any serious adverse events or serious adverse effects.
Patients were included if they had clinical and imaging (gray scale and neovascularization at power Doppler) diagnosis of patellar tendinopathy, unresponsive after at least 3 months of eccentric exercises, and other measures such as modification of activities, extracorporeal shockwave therapy, massage, ultrasonotherapy, hyperthermia, or low-level laser therapy. Patients with concurrent musculoskeletal disorders or degenerative joint disease changes to the knee, complete or partial patellar tendon tears, or prior surgery on the affected patellar tendon were excluded from the study. Forty-four patients (41 men, 3 women) who underwent HVIGI treatment between 2004 and 2007 for the management of recalcitrant patellar tendinopathy respected the criteria to be included and gave their consent to be enrolled in the study. We succeeded in contacting all the patients. We proposed to perform an US scan with gray scale and color Doppler evaluation on all 37 patients who were reviewed in person. Of these, 32 agreed, and the other 5 patients stated that they could see no point in receiving the scan as they had achieved acceptable control of symptoms. We succeeded in obtaining US scans with gray scale and color Doppler evaluation in 32 patients (Figure 1).
Clinical and Imaging Assessment
The first author (N.M.) made the clinical diagnosis in all patients, by history, clinical examination, and US findings. Pain during isometric contraction of the quadriceps muscle was assessed against resistance and passive maximum stretching. The alignment of the extensor mechanism was assessed clinically and on radiographs (plain and skyline views). Ultrasonography was performed in all instances by a certified musculoskeletal radiologist, and the presence of an area of hypoechogenicity or of intratendinous calcification in both longitudinal and transverse scans was considered as diagnostic for tendinopathy. Maximal anteroposterior thickness of the patellar tendon was measured in millimeters using the scanner's (Logiq 9; GE Healthcare, Bucks, United Kingdom) digital measuring device. Gray-scale US was performed using a dedicated high-resolution 8 to 12 MHz probe (GE Healthcare). Neovascularization was evaluated with a modified Ohberg semiquantitative grading system using the same machine, by the same experienced musculoskeletal radiologist who used a standardized protocol for both baseline and follow-up measurements.9
Before undertaking HVIGI treatment, all patients were assessed for pain and function; visual analog scales10 and the Victorian Institute of Sport Assessment—patellar tendon (VISA-P) questionnaire11 were administered to each patient. The latter is a specifically designed questionnaire ranging from 0 to 100 to evaluate severity of symptoms, function, and ability to participate in sport of patients with patellar tendinopathy. A perfect score of 100 points represents a fully functional knee. All patients were also assessed clinically. The Royal London Hospital test was performed: the clinician elicits local tenderness by palpating the tendon with the knee extended and the quadriceps relaxed (Figure 2A). The tenderness significantly decreases or becomes totally painless when the knee is flexed, the quadriceps is contracted, and the ankle dorsiflexed (Figure 2B).
A board-certified musculoskeletal radiologist assessed any abnormality and any evidence of neovascularization using a power Doppler with a high-resolution US and a 13 MHz probe (Sonoline Elegra; Siemens, Erlangen, Germany). The contralateral nonpainful tendon was also examined. Once the diagnosis of patellar tendinopathy was confirmed, the procedure was undertaken. After appropriate cleansing of the skin over the anterior aspect of the knee, using an aseptic technique and assisted by a nurse, a 21-gauge needle attached to a 30-cm connecting tube was inserted under US guidance immediately posterior to the patellar tendon, at the interface between the tendon and the Hoffa body, immediately adjacent to the area of neovascularization. Ten mL of bupivacaine 0.5% (Marcaine; AstraZeneca, Luton, United Kingdom), 62 500 international units of aprotinin (Trasylol; Bayer, Pittsburgh, PA) (Kir, Lepetit, Italy), and a 40 mL bolus of normal saline were injected together under pressure by syringe.12 If symptoms were still present 2 weeks after the initial injection and neovascularity was evident at US color Doppler, a further HVIGI was proposed to the patient. In this instance, however, instead of aprotinin, 25 mg of hydrocortisone acetate were added to the injection solution. Power Doppler US was used to assess whether any neovascularization was still present after the injection.
Patients were allowed to walk on the injected leg immediately but advised to rest from strenuous activity for 3 to 4 days. Patients returned to their referring clinicians 2 weeks after the injection for advice about further physiotherapy and return to sport. They were then instructed to begin an eccentric loading program under the guidance of a chartered physiotherapist.
The primary end point was the difference in the VISA-P score from baseline to 15 months after management. For clinical purposes, patients were examined, and the VISA-P score was collected at baseline and at 15-month follow-up.
At the last appointment, at an average of 15 ± 2.5 months after HVIGI management, patients were clinically assessed by an independent investigator not involved in the preoperative assessment and injection. The VAS scale and the VISA-P questionnaire were administered to all patients. At the final follow-up, outcomes were classified as excellent, good, fair, or poor based on objective and subjective assessments.13 Subjectively, patients were asked to rate the results of the procedure according to the presence of pain and return to sporting activities. Subjective outcome was considered excellent when pain had been completely relieved and patients had returned to the preinjury sporting level without any significant symptoms. A good result was a full return to sport with only intermittent or mild discomfort; a fair result was defined as a discomfort that does not allow return to preinjury level, and patients abandon any competitive sport activity, being able to train at a reduced intensity. A poor result was considered when patients had to give up practice sport or complained of discomfort and disability in daily activities or they were able to train up to a maximum of twice per week for a maximum of 10 minutes.
Descriptive statistics was calculated. Kolmogorov–Smirnov tests determined that the interval data from the VISA-P questionnaires and visual analogue scale (VAS) values were normally distributed. For the purposes of this study, only the initial and 15-month follow-up recordings were analyzed. Student t tests were used to compare the values before and 1 year after injection. The association between tendon dimensions and neovascularity and VISA-P results was analyzed using analysis of variance. In this instance, an F test was used to determine statistical significance. A P value of <0.05 was considered statistically significant. All data were analyzed with SPSS (Statistical Package for Social Scientists 1, version 12.0.1; SPSS1 Inc, Chicago, Illinois).
The average age of patients at treatment was 35 years (range, 24-69 years). All subjects were secondary and tertiary referrals from other healthcare professionals after an average period of 18.4 ± 18 months (range, 5-84 months) from the onset of symptoms. All patients complained at clinical examination of anterior knee pain over the area between the lower pole of the patella and the patellar tendon. All patients showed US changes of patellar tendinopathy before the HVIGI treatment, with evidence of tendon thickening at the attachment to the lower pole of the patellar tendon, and hypoechogenic changes (Figure 3). The maximal tendon thickness and power Doppler findings at baseline and at the last follow-up are reported in Table 1. The neovascularization disappeared in all patients immediately after the injection (Figure 4). The average number of injections was 1.8 (1-3). The maximum tendon thickness (P = 0.07) and neovascularization grading (P = 0.07) were not found to be associated with the VISA-P score and number of injections administered (P = 0.07).
At the last follow-up, the mean VISA-P score, pain VAS, and function VAS were all significantly improved compared with baseline. Of 32 physically active patients, 23 (72%) had returned to sport at the same level they practiced before the onset of symptoms, 8 (25%) practiced at a lower level, and 1 had abandoned sport. After failure of all conservative management (all after a further HVIGI), 3 patients underwent surgical exploration of the affected tendon by an average time of 4 months after the last injection. The 3 patients who had undergone surgical exploration reported to have fully recovered at the last follow-up, although their mean VISA-P score averaged 72. In the 25 athletes who had received a further injection, this took place at an average of 2.7 ± 1.8 weeks (range, 2-6 from the first injection). At the final follow-up, 23 of the 32 athletes (72%) were classified as good to excellent and 9 as poor.
The main finding of this study is that HVIGI treatment reduces pain and improves function of patients with recalcitrant patellar tendinopathy. At 15-month follow-up, VAS and VISA-P scores were significantly improved compared with baseline, most of athletes (72%) had returned to sport at the same level they practiced before the onset of symptoms, and 79.5% of patients rated their condition as good or excellent. Neovascularization accompanies the ingrowth of the neonerves, which are supposed to be responsible for the symptoms of patellar tendinopathy. HVIGI may mechanically stress the neovessels and the neonerves around the symptomatic patellar tendon, producing their disruption and possibly collapse.3,14 We used a mixture of ingredients. Aprotinin is a broad-spectrum serine protease inhibitor that inhibits plasmin, trypsin, and kallikrein and inhibits their proteolytic action and their vasoactive effect in the first stages of inflammation. It may block matrix metalloproteinases (MMPs): MMP-1, MMP-8, MMP-13 (collagenases); MMP-2 and MMP-9 (gelatinases) are inhibited either directly or by inhibition of plasminogen and plasmin.15,16 Aprotinin has been used for the management of tendinopathy,17,18 but it has been recently withdrawn worldwide because postoperative thrombosis, organ dysfunctions, and allergic effects were reported after its injection.19 In our setting, we now use only hydrocortisone acetate.5 Corticosteroid injections reduce pain and swelling and improve the US appearance of the tendon, probably in relationship to their vasoconstrictive action mediated by prostacyclin, adrenoceptors, and inhibition of nitric oxide synthetase.20 In other investigations, hydrocortisone acetate has been used in the mixture of high-volume injections primarily to prevent an inevitable acute mechanical inflammatory reaction produced by the large amount of fluid injected in the proximity the tendon.5
The injection was placed immediately posterior to the patellar tendon, at the interface between the tendon and the Hoffa body. Given the rich innervation of the Hoffa body, it is possible that the local anesthetic provided a decrease in symptoms, so patients experienced less pain when undertaking their rehabilitation, and this contributed to their recovery.
Ultrasonography is a reliable tool to confirm the clinical diagnosis of patellar tendinopathy and precisely perform the injections within the extratendinous space,21 allowing to visualize in real time the distribution of the fluid at the interface between the tendon and the Hoffa body. Color Doppler allows to assess the state of tendon and paratendon neovascularization.22
These results confirm that HVIGI is effective and compares well with findings already reported in previous studies.5–7 The success rate in terms of return to the desired level of sport was 77%. Seven athletes had not been able to return to the same level of sport, despite a further HVIGI. This approach respects the anatomy and physiology of this condition and, in the short term, provides results encouraging in terms of function and symptoms.23 We also recommend eccentric loading as it enables patients to exercise the tendon in a physiological fashion, with the aims to modify the internal structure of the tendon by improving collagen arrangement, and prevent recurrences.24,25
Imaging findings were improved compared with what observed at baseline. At 15 months from the index injection, the anteroposterior diameter of the patellar tendon was significantly lower. This probably depends on the fact that vessels are disrupted. In addition, we could expect that the relief of symptoms would allow patients to train properly, without any biomechanical adaptation of the patellar tendon in terms of lengthening, stretching, and thickening. There is evidence that intratendinous changes at US are not associated with outcome of conservative management and that these changes may be self-resolving over time, particularly if patients modify the intensity and type of sport activity. However, it may be important to disrupt neovessels and neonerves.
Although we did not report complications or side effects, HVIGI was ineffective in 3 patients; these 3 patients underwent surgical exploration. The reasons for failure may be related to an incomplete disruption of the vessels and neonerves or to the impossibility to prevent the recurrence of both tendon vascularization and nerve ingrowth in the short term. These findings likely reflect the intrinsic bias in the type of patients referred to us, as they were tertiary referrals to the senior author. Therefore, a variety of management modalities had already been implemented and failed, and the athletes would all have otherwise been candidates for surgery.26 It is remarkable that, after HVIGI, the neovessels were no longer visible, but they became visible later. This confirms that the presence of neovascularity is not in itself pathological and may be the result of tendon remodeling or of tendon response to a stimulus, including physical training. However, neonerves accompany neovessels and are an indication that neurogenic inflammation can be at the basis of the perpetuation of the failed healing response, which is the essential lesion of overuse tendinopathies. In this respect, therefore, the presence of neovascularity is not necessarily a sign of pathology but only an indication of the metabolic activity that the tendon is experiencing.27
Patients were followed up for an average of 15 months. By that time, should the intervention not have worked, our patients would have been likely to have undergone surgery. Also, this length of follow-up was chosen because we wished to minimize the number of patients defaulting from the study; we felt that it would have been difficult to ask patients to return for assessment several years later.
Inevitable criticisms are the retrospective nature of the study, the relatively small number of patients, and the absence of a control group of individuals who did not receive an injection. However, our patients had been referred to us after having already failed several other modalities of conservative management in the form of physiotherapy, eccentric exercises, and other modalities, including extracorporeal shock therapy and “classical” corticosteroid injections.
Also, it is unclear what component of the HVIGI produces its therapeutic effect: the high volume of fluid used or the drugs used in the injection. Appropriate studies should be performed to clarify this point.
A strength of this study is that one experienced musculoskeletal radiologist performed all injections, and an independent investigator examined the patients at follow-up.
The effects of HVIGI, although apparently only partially successful, should be considered encouraging.
Aprotinin is no longer available. Therefore, we continue to use HVIGI in the management of patients with recalcitrant patellar according to the protocol described in our previous work,5 using hydrocortisone instead of aprotinin. Given the morbidity and long-term effect of patellar tendinopathy in athletes, it might be desirable to undertake HVIGI at an earlier stage of the condition, hopefully providing a better prognosis.
High-volume injection at the interface between the deep surface of the patellar tendon and Hoffa body markedly improves symptoms and function of the knee in the short term, aiding a quicker return to sport.6,28 In experts hands, this method is easy to perform in a clinical setting and relatively inexpensive.
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Keywords:Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
patellar tendinopathy; ultrasound-guided injections; clinical outcomes; return to sport