Efficacy of Injected Liquid Silicone is Related to Peak Plantar Foot Pressures in the Neuropathic Diabetic Foot

Introduction It is well established that increased plantar foot pressure is an important predictive risk factor for the development of diabetic foot ulceration.1,2 High foot pressures usually occur at sites with bony prominence and have been strongly associated with reduced plantar tissue thickness.3 However, it is important to consider that increased plantar pressure and/or thinner padding under the forefoot will only lead to foot ulceration in association with a loss of protective sensation.4 Normal preventative care of diabetic neuropathic patients at risk of foot ulceration includes prescription of special socks, insoles, footwear, and regular podiatry treatments. However, compliance with prescribed footwear is not always adequate. In the treatment of the neuropathic diabetic foot at risk of foot ulceration or ulcer recurrence, the injection of liquid silicone in the foot has been used for more than thirty years at one center with a high level of reported success and minimal side effects.5,6 In addition, in the same center, the injection of liquid silicone has also been used successfully in the treatment of callus, corns, and localized painful areas in nondiabetic persons.5,6 Recently, we reported the results of a randomized, double-blind, clinical trial in diabetic neuropathic patients, which confirmed past anecdotal reports.7 It was shown that peak plantar pressures could be reduced and plantar tissue thickness increased through injection of liquid silicone at areas of high plantar pressure and callus.7 Although this technique has been used for many years in one center, there is still little objective data available on the effect of liquid silicone on the foot. Therefore, data from the aforementioned study were further analyzed in order to gain more insight into the effectiveness of treatment of injection with liquid silicone. Specifically, the aim of this analysis was to investigate in more detail the relationship between pretreatment values of plantar pressure and tissue thickness and the degree of change after treatment with liquid silicone. Patients and Methods Patients. The original study was approved by the local ethics committee, and all subjects received full information about the study before giving signed consent. The methodology was as previously published.7 Briefly, twenty-eight patients with diabetes attending the Manchester Diabetes Centre were enrolled for the study. Inclusion criteria were the following: established neuropathy, vibration perception threshold (VPT) greater than 25 Volts or a neuropathy disability score (NDS) greater than six,8,9 and the presence of callus under at least one metatarsal head. Patients with peripheral vascular disease (absence of more than one foot pulse in both feet or ankle brachial pressure index less than 0.9) and with an active or previous ulcer in the past six months were not selected for the study. The patients were randomized to active treatment (n = 14) or to equal amounts of placebo (saline) treatment (n = 14). Areas of injection were chosen under metatarsal head sites with callus or widened skin striae or at sites with high plantar pressure. Study design. All subjects underwent a neuropathic and vascular baseline investigation using the aforementioned criteria. Plantar pressure was assessed at chosen injection sites after callus was debrided. Patients received six injections at two weekly intervals and were seen for follow-up assessments at three, six, and twelve months after first injection. Throughout the first year of the study, the patients were treated by the same study podiatrist, after which they went back to their local foot care clinic. All patients in the study continued to receive the same treatment as is offered to all patients at high risk of foot ulceration, including receiving specialist footwear and regular podiatry treatment. Patients were dispensed different footwear as per individual consultation. Outcome measures. Dynamic plantar pressures were measured during barefoot walking using the optical pedobarograph (Department of Medical Physics and Clinical Engineering, Royal Hallamshire Hospital, Sheffield, United Kingdom).10,11 A minimum of five steps was measured for each foot, depending on the patients’ balance. Any steps regarded as atypical or out of balance during data collection, as judged by the investigator, were not saved and thus not used for analysis. Peak pressures were analyzed for each area of injection and were averaged over the number of steps measured. The measurement was standardized for each patient in such a way that at each follow-up visit the pressure was measured during the same step after initiation of gait (second or third step for all subjects). Method of injection. Patients were randomized according to a random number sequence. All investigators and patients were blinded to the treatment regime throughout the study, with the exception of the podiatrist administering the injections, who did not participate in any of the assessments or analyses. A total of six injections were given per site at two weekly intervals. Between one and five sites were selected for injection, depending on the number of callus sites. Thus, each patient received a total of between six and thirty injections. The volume of silicone or saline per injection was 0.2mL for each site; the total maximum volume injected was 1.2mL per injection site. The total volume injected was spread out over six injections in order to increase the cushioning effect of silicone and to decrease the possibility of fluid migration by allowing the tissue to respond to the injection by imbedding the silicone in a web of collagen fibers.5 An area with previous ulceration was only chosen for injection when healed for a minimum of six months. Before injection, all areas to be injected were debrided of callus and were cleaned using a 70-percent isopropyl alcohol wipe. A skin refrigerant (fluro-ethyl) was sprayed over the site of injection for two to three seconds prior to injection. Local anesthesia (mepivacaine 3%) was used if needed. A disposable luer-lock syringe and a 25-gauge, 1- or 1.5-inch needle were used for injection. A needle guide was attached to the syringe to assist in a more precise injection. The liquid silicone or saline was implanted subcutaneously in equal amounts beneath and within 1 to 2mm of the central point of callus. After injections, the sites were covered with a sterile adhesive bandage strip and the patient was advised to keep the area dry for 24 hours and to check the site for any signs of inflammation or infection. Patients were allowed to resume regular activities immediately following injection. Calculations and statistical analysis. Data are presented as mean ± standard deviation or median (inter-quartile range). Data from the individual injection sites was used for analysis. The number of injection sites depended on the number of callus sites and ranged between one and five per patient. In view of the fact that post-treatment values of the outcome measures are not independent of the baseline values, it was not possible to use correlation analysis to test for relationships. Linear regression analysis was therefore used to study relationships between outcome measurements and baseline values. For all calculations an alpha of 0.05 was used. Results Descriptive characteristics of the study population are detailed in Table 1. There was no significant difference in age, duration of diabetes, severity of neuropathy, and mean peak baseline plantar forefoot pressure between the two groups. Significant regression equations were derived for the silicone-treated group for both the change in plantar tissue thickness and peak plantar pressure with their respective baseline values (Tables 2 and 3). Between 10 and 23 percent of the variation of the change in plantar tissue thickness after treatment with liquid silicone was explained by baseline tissue thickness; however, there was no relationship between the percentage change and baseline thickness (Table 2, Figure 1). Between a third and a half of the variation of the decrease in peak plantar pressure after treatment with liquid silicone was explained by baseline pressure (Table 3, Figures 2 and 3). There was no relationship seen between baseline and follow-up measurements for the placebo-treated group. Discussion The results of this study suggest that patients presenting with reduced levels of plantar tissue thickness and elevated peak plantar pressures may benefit most from injections of liquid silicone in the foot. Equally, subjects with lower plantar pressure before treatment did not seem to obtain as much of a benefit from this treatment. The observation that the magnitude of change after silicone injection was greater with a lower baseline tissue thickness and a higher baseline peak pressure agrees with results from Perry and colleagues,12 who reported the greatest reduction of pressure by running shoes at sites with the highest initial pressure. The fact that no relationship was observed between baseline thickness and absolute change in plantar tissue thickness could possibly be explained by the natural differences in subcutaneous thickness at different metatarsal heads. Weight-bearing plantar tissue thickness is naturally much thinner under the fifth metatarsal head than compared to more medial sites.3,13 A similar magnitude of increase in tissue thickness after silicone treatment is expected for all metatarsal heads; therefore, the greatest percentage improvement will be observed at sites with the lowest baseline thickness (i.e., towards the lateral metatarsal heads, which are naturally thinner than the medial side). It is also important to note that tissue thickness at the first ray was measured from the metatarsal head, and not from the sesamoid bones, which are positioned underneath the head. It is possible that the tissue thickness of clinical significance is from the sesamoid bones and not the metatarsal head; however, this is currently not known. These are probably the reasons why no relation between absolute change and baseline thickness was observed. Conclusion In conclusion, injection of liquid silicone in the foot appears to be a beneficial and effective method of increasing plantar tissue thickness and reducing plantar pressure in the high-risk diabetic foot. The largest improvement is seen in patients with lower tissue thickness and higher peak pressure pretreatment. The use of this form of treatment for augmentation of the plantar fat pad may also be seen as the provision of an internal orthosis. The advantage of using an internal orthosis is that it may eliminate some of the issues related to compliance and efficacy as observed in treatment of the foot by external orthoses, which are easy to remove. Further work is required in this area in order to confirm or challenge the findings reported up to today in this promising area of preventative care in the diabetic foot.