Background and Objective Due to the significant risk profile associated with traditional ablative resurfacing, a safer and less invasive treatment approach known as fractional deep dermal ablation (FDDA™) was recently developed. We report the results of the first clinical investigation of this modality for treatment of photodamaged skin. Study Design/Materials and Methods Twenty‐four subjects received treatments on the inner forearm with a prototype fractional CO2 laser device (Reliant Technologies Inc., Mountain View, CA) at settings of 5–40 mJ/MTZ and 400 MTZ/cm2. Clinical and histological effects were assessed by study investigators 1 week, 1 month, and 3 months following treatment. Thirty subjects were then enrolled in a multi‐center study for treatment of photodamage using the same device. Subjects received 1–2 treatments on the face and neck, with energies ranging from 10 to 40 mJ/MTZ and densities ranging from 400 to 1,200 MTZ/cm2. Study investigators assessed severity of post‐treatment responses during follow‐up visits 48 hours, 1 week, 1 month, and 3 months following treatment. Using a standard quartile improvement scale (0–4), subjects and investigators assessed improvement in rhytides, pigmentation, texture, laxity and overall appearance 1 and 3 months post‐treatment. Results Clinical and histologic results demonstrated that fractional delivery of a 10,600 nm CO2 laser source offers an improved safety profile with respect to traditional ablative resurfacing, while still effectively resurfacing epidermal and dermal tissue. Forearm and facial treatments were well‐tolerated with no serious adverse events observed. Eighty‐three percent of subjects exhibited moderate or better overall improvement (50–100%), according to study investigator quartile scoring. Conclusions FDDA™ treatment is a safe and promising new approach for resurfacing of epidermal and deep dermal tissue targets. Lasers Surg. Med. 41:78–86, 2009. © 2009 Wiley‐Liss, Inc.

Previous studies identified various mechanisms of light scattering reduction in tissue induced by chemical agents. Our results suggest that dehydration is an important mechanism of optical clearing in collagenous and cellular tissue. Photographic and optical coherence tomography images indicate that air-immersed skin and tendon specimens become similarly transparent to glycerol-immersed specimens. Transmission electron microscopy images reveal that dehydration causes individual scattering particles such as collagen fibrils and organelles to become more densely packed, but does not significantly alter size. A heuristic particle-interaction model predicts that the scattering particle volume fraction increase can contribute substantially to optical clearing in collagenous and cellular tissue.

We present a gentle mechanical method for the noninvasive transepidermal delivery of topically applied optical skin clearing agents. Optical skin clearing reduces light scattering in highly turbid skin with the aid of hyperosmotic chemicals such as glycerol, polyethylene glycol, and solutions of dextrose. Transepidermal delivery of such agents is believed to be most patient compliant and most likely to be used in a clinical environment. Optical skin clearing has the potential to expand the current limited use of laser light in medicine for diagnostic and therapeutic applications. Light scattering limits the penetration depth of collimated light into skin. In order to increase the diffusion of topically applied optical skin clearing agents into skin, we present a gentle mechanical delivery method involving glycerol and dextrose as optical skin clearing agents and fine 220-grit sandpaper to rub the clearing agent into the tissue. Gentle rubbing causes abrasion of the superficial skin layer including the stratum corneum, which otherwise prevents these optical skin clearing agents from freely diffusing into skin. Results indicate very fast optical skin clearing rates. In vivo hamster skin turned transparent within 2 min. The 1e light penetration depth increased by 36+/-3.75% for dextrose and 43+/-8.24% for glycerol. Optical skin clearing was reversed using phosphate buffered saline solution. Skin viability was observed 70 h post-treatment and showed scabbing and erythema on a few percent of the total optically cleared skin surface.

The use of an inexpensive diode laser can significantly enhance the delivery of topically applied glycerol for optical skin clearing. The laser use involves application of an absorption substrate onto the skin surface. Using carbon paper left no unwanted residue behind and is considered optimal for this purpose.

IntroductionWe incorporated patient feedback from human factors studies (HFS) in the patient-centric design and validation of ava®, an electromechanical device (e-Device) for self-injecting the anti-tumor necrosis factor certolizumab pegol (CZP).MethodsHealthcare professionals, caregivers, healthy volunteers, and patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease participated in 11 formative HFS to optimize the e-Device design through intended user feedback; nine studies involved simulated injections. Formative participant questionnaire feedback was collected following e-Device prototype handling. Validation HFS (one EU study and one US study) assessed the safe and effective setup and use of the e-Device using 22 predefined critical tasks. Task outcomes were categorized as “failures” if participants did not succeed within three attempts.ResultsTwo hundred eighty-three participants entered formative (163) and validation (120) HFS; 260 participants performed one or more simulated e-Device self-injections. Design changes following formative HFS included alterations to buttons and the graphical user interface screen. All validation HFS participants completed critical tasks necessary for CZP dose delivery, with minimal critical task failures (12 of 572 critical tasks, 2.1%, in the EU study, and 2 of 5310 critical tasks, less than 0.1%, in the US study).ConclusionCZP e-Device development was guided by intended user feedback through HFS, ensuring the final design addressed patients’ needs. In both validation studies, participants successfully performed all critical tasks, demonstrating safe and effective e-Device self-injections.FundingUCB Pharma.Plain Language SummaryPlain language summary available on the journal website.Electronic supplementary materialThe online version of this article (10.1007/s12325-017-0645-1) contains supplementary material, which is available to authorized users.