Letter to the Editor: The New Face of Fillers: Integrating Evidence, Experience and a Little Imagination at the Next Frontier

Recently in an article titled, "Inflammation in Rosacea and Acne: Implications for Patient Care," J Drugs Dermatol. 2011;10(6):614-620, Dr. Fleischer states that the safety of doxycycline 40 mg has only been studied for nine months, and these data have not yet been published. We would like to draw to his attention that these data have indeed been published by Preshaw PM, Novak MJ, et al. "Modified-Release Subantimicrobial Dose Doxycycline Enhances Scaling with Root Planing in Subjects with Periodontal Disease" in J Periodontol. 2008;79:440-452. In this article, nine months of doxycycline 40 mg versus placebo use was studied in a cohort of periodontal patients coming in for regular evaluations and root planing. There was no increase of adverse events, nor was there any increase in bacterial resistance in the oral flora demonstrated over the normal spontaneous level of mutation which occurs in bacteria over the nine-month duration of the study. We believe it is very important to include this publication to complete the review that Dr. Fleischer has written.

Best regards,

Ronald W. Gottschalk MD

Medical Director
Galderma Laboratories, L.P.

It's been a busy year for fillers-on both sides of the Atlantic. In the US, 2011 was notable for a first-time FDA expansion in the usage of an already-approved product (Restylane, Medicis) to encompass lip augmentation, and for the new approval of another (Belotero Balance, Merz) that has previously been available in Europe and elsewhere. A third product (Juvéderm Voluma, Allergan) is currently in clinical trials but also already in use outside the US. In Europe, the year was marked by the emergence of a new, multi-product family of HA fillers (Emervel, Galderma).

It is interesting, but, upon reflection, perhaps not surprising that all these developments involve hyaluronic acid (HA) products. HAs were our first fillers after collagen, and, as such, our experience with them is more extensive than with fillers that have followed. However, experience has only deepened the mystery in some respects. A decade and a half after HAs were initially approved in Europe and almost a decade after approval in the US, we still grapple to understand fundamental aspects of their behavior, such as the determinants of longevity. These knowledge gaps have driven research that has led to the formulation of new HA products and refinement in our injection strategies for existing ones. Our use of different fillers to achieve specific aesthetic objectives has been likened to an artist's use of a palette of paints to create a complete picture. Metaphorically speaking, the recent approvals of new HA products and clinical indications represent both a quantitative and a qualitative expansion in the fillers palette.

Advances in scientific understanding have enabled a revisiting of previously accepted dogma. Longevity, once solely related to insoluble (crosslinked) HA concentration, may now be considered also to depend on water binding capacity and neocollagenesis, with the role of soluble (uncrosslinked) HA of various molecular weights still to be determined. There has also been a bridging of the gap between scientific theory and clinical reality. The clinical relevance of filler rheology-measurement of the flow-related properties of elastic modulus (G prime) and viscosity-is demonstrated by evidence level II split-face comparator studies showing that higher G prime fillers are more volume-efficient for filling the nasolabial folds.^1-3 The study of tissue integration patterns has allowed a satisfying connection of the dots between filler rheology and clinical behavior: histopathologic examination of skin after intradermal implantation of various HA products reveals that their pattern of tissue integration is a direct reflection of viscosity, with higher viscosity products remaining as a bolus while products of lower viscosity spread within the tissue.⁴