Optical coherence tomography, clinical photography, thermal imaging, and laser speckle contrast imaging
Three-dimensional photography was used to quantify the bleb size after i.d. injection. No bleb formation was observed after s.c. injection. After i.d. injection bleb formation was observed after both adalimumab and saline injections, which resolved in less than a day (Figure 5A-B ). i.d. adalimumab administration but not s.c. adalimumab administration or injection of placebo caused local redness after injection (Figure 5C ). Optical coherence tomography was used to examine breach of epidermis and fluid disposition. Penetration of the epidermis was visible for 92% of cases 10 minutes after administration of both placebo injections and s.c. adalimumab injection. All i.d. adalimumab injections showed epidermal penetration 10 minutes post dose (Figure 5D-F ). Fluid disposition and vasodilatation in the dermis were visible more clearly for i.d. injections than s.c. injections.
Cutaneous microcirculation of the upper legs following injections was quantified using LSCI. A significant increase in blood flow for i.d. adalimumab injections compared to i.d. placebo, s.c. adalimumab, and s.c. placebo injections was shown 10 minutes post-dose (p< 0.0001, (Figure 5G )), followed by a decrease, reaching baseline on day 3 (data not shown). The bleb surface area was quantified using LSCI’s perfused area measurements. The perfused areas were significant larger after i.d. adalimumab injections compared to i.d. placebo (p< 0.0001), and also compared to s.c. adalimumab (p=0.0012) and placebo injections (p< 0.0001) (Figure 5H-I ).
Injection site temperature was measured in a temperature-controlled room using infrared thermography and corrected using standardized control areas (Supplementary figure 1 ).