How Much Does Filler Apparatus Influence Ease of Injection (and Hence, Potential Safety)?

PURPOSE: To document the relative contributions of intrinsic filler fluid dynamics versus delivery systems for ease of injection-specifically, to measure extrusion force variability across different syringes and needles (with the characterization of intrinsic rheological fluid properties vs. delivery apparatus contributions to ease of injection). METHODS: Six different fillers were tested: Belotero balance (Bel), Juvederm Voluma XC (Vol), Revanesse Versa (Rev), Restylane Lyft (Res), Radiesse (Rad), and Teosyal RHA3 (RHA). Extrusion force was measured in Newtons (N) for each by testing using the provided injection apparatus (needle + syringe), and also by standardizing all fillers to the same syringe and then varying needle sizes (30-ga, 27-ga, 25-ga/1.5-inch, 25-ga/2-inch, and 22-ga). Five trials were conducted for each scenario, with comparison via t -test (2-tailed, unpaired, assuming unequal variance). RESULTS: The following results were noted: (1) in order of least to highest extrusion force in box-provided syringe + needle at 0.2 ml volume, the following were noted: Vol < RHA = Bel (27-ga) < Bel (30-ga) < Rev < Res = Rad; (2) for each filler (except for Vol which was similar), the box-provided syringe involved greater extrusion force than the standardized syringe used in this study (each 1-cc, p < 0.05); (3) for 27-ga and 30-ga needles, after standardization of delivery syringe at 0.2 ml volume, a significant difference was noted (proportional to increasing resistance): Bel = Vol = RHA3 < Res < Rev < Rad (for needles of 30-ga [ p < 0.05] and 27-ga [ p < 0.01]); (4) for testing cannulas after standardization of syringes no reproducible order was noted with increasing resistance when using 25-ga/1.5-inch long, 25-ga/2-inch, and 22g/2-inch cannulae; and (5) confirming expectation (validating study technique), the extrusion force was significantly higher for smaller needles and longer needles. CONCLUSIONS: The delivery apparatus appeared to be the most influential contributor to filler injection extrusion force, with significant changes in ease of injection correlated to the filler's intrinsic rheological properties, such as viscosity (when standardized to the same syringe for needles tested). Knowledge of such data could influence the injector's ability to maximize patients' safety and clinical results.

Patient Satisfaction and Management of Postoperative Complications Following Ablative Carbon Dioxide Laser Resurfacing of the Lower Eyelids.

PURPOSE: To describe postoperative management following ablative carbon dioxide laser resurfacing of the lower eyelids. METHODS: A retrospective review of patients who consecutively underwent bilateral lower eyelid ablative carbon dioxide laser resurfacing by a single experienced oculoplastic surgeon over a 6-year period was conducted. Patient satisfaction, aesthetic outcomes, and postoperative complications were evaluated as adjunctive or monotherapy. RESULTS: Among 424 patients included in the study, most were female (n = 356, 84.0%) and Caucasian (n = 404, 95.3%), with Fitzpatrick skin types II-III (n = 381, 89.9%). Mean age was 62.8 years (standard deviation: 9.7 years). Most (n = 324, 76.4%) underwent fractional ablative carbon dioxide laser resurfacing of the lower eyelids, whereas 91 (21.5%) received traditional laser resurfacing and 9 (2.1%) had both fractional and traditional laser resurfacing during the same session. At the time of lower eyelid laser resurfacing, most patients also underwent concurrent procedures, including upper (n = 321, 75.7%) and lower blepharoplasty (n = 348, 82.1%); a small proportion of patients (n = 39, 9.2%) did not undergo any concurrent surgical procedure. In addition to ablative laser resurfacing of the lower eyelids, 25 (5.9%) had upper eyelid laser resurfacing, 60 (14.2%) had full-face laser resurfacing, 55 (13.0%) had neck laser resurfacing, and 42 (9.9%) had additional treatment of solar lentigines or dyschromias on the face. Median follow-up duration was 3.9 months (interquartile range: 2.0-11.0 months). In the immediate postoperative period, 22 patients (5.2%) developed contact dermatitis from topical antibiotic eye drops and/or ointment prescribed postblepharoplasty. Postinflammatory hyperpigmentation was observed in 40 patients (9.4%) despite topical prophylaxis; all were eventually successfully treated with a combination of topical nonprescription and prescription creams and/or oral tranexamic acid. A localized herpetic outbreak occurred in 3 (0.7%) who underwent full-face laser resurfacing and 1 (0.2%) who underwent periocular laser resurfacing only; all were successfully treated with oral antiviral therapy. Two (0.5%) developed culture-proven atypical mycobacterial infection of the resurfaced lower eyelid skin and were treated with combination antibiotic therapy for several months until resolution. A small scar was noted in 4 patients (0.9%), which resolved after local corticosteroid injections. No patient developed persistent scarring or ectropion. Patient satisfaction was overall high, with 363 (85.6%) very satisfied and 48 (11.3%) satisfied with the aesthetic outcome of lower eyelid laser resurfacing. CONCLUSIONS: Ablative carbon dioxide laser resurfacing of the lower eyelids can be a useful tool in the armamentarium of the experienced oculoplastic surgeon, with excellent aesthetic results, high patient satisfaction, and low complication rates as adjunctive or monotherapy. Proper and timely management of postoperative complications is essential to maximizing successful cosmetic outcomes.

The Role of Biological Agents and Immunomodulators in Treatment Strategies for Thyroid Eye Disease: An Evidence-based Review.

Graves' Disease is an autoimmune disease where circulating antibodies bind to the thyrotropin receptors on the thyroid gland. These bound antibodies mimic thyroid stimulating hormone without the normal feedback from the anterior pituitary, causing hyperthyroidism and thyrotoxicosis. These antibodies also interact with orbital tissues and cause the characteristic orbital findings of thyroid eye disease (TED). It is not clearly understood why anatomically and physiologically distinct tissues like the thyroid gland and orbit are affected selectively, or why the orbital disease tends to be self-limited. Identifying and understanding these processes is critical to targeting therapy. In the active phase of the disease patients may experience orbital inflammation, eyelid and conjunctiva edema (chemosis), eyelid retraction, proptosis, ocular motility restriction, and optic nerve compression. Current treatment strategies for the ocular symptoms have been predominantly directed at symptomatic relief. More recently, investigators have concentrated their efforts to better understanding the underlying pathophysiologic processes to direct therapy at these processes. This review examines the current literature exploring a variety of newer therapeutic alternatives, including immunomodulative and suppressive agents, targeted at strategic points of the active-phase TED pathophysiological pathways. Specifically, biological agents including rituximab, adalimumab, intravenous immunoglobulin and others are reviewed with considerations for pathophysiology, extent of literature support, and adverse effects. [Full article available at http://rimed.org/rimedicaljournal-2016-06.asp, free with no login].

Increased CD40+ Fibrocytes in Patients With Idiopathic Orbital Inflammation.

OBJECTIVE: To investigate the phenotypic and functional characteristics of peripheral and tissue-infiltrating stem cells called fibrocytes in patients with idiopathic orbital inflammation (IOI). METHODS: Seven patients with IOI were studied. In the 3 patients requiring orbital biopsy, fibrocytes were identified in orbital tissue from patients with IOI compared with healthy controls using immunohistochemistry. Fibrocytes from the peripheral blood of all 7 patients and controls were quantified and phenotyped by flow cytometry and immunofluorescence for expression of CD34, alpha smooth muscle actin, CD40, and collagen 1. Quantitation of CD40-mediated interleukin-6 (IL-6) production was measured using enzyme-linked immunosorbent assay. RESULTS: Orbital biopsy specimens from patients with IOI demonstrate tissue infiltration by fibrocytes (n = 3). Fibrocytes are present in the peripheral blood of IOI patients (n = 7) but are scarce in healthy donors (n = 19). Fibrocytes from IOI patients express substantial levels of CD40, and ligation of CD40 increases IL-6 expression. CONCLUSIONS: Fibrocytes are present in the peripheral blood and orbital tissues of patients with IOI and constitutively express CD40 and express IL-6 in response to ligation. This site-specific predilection of CD34(+) fibrocytes to sites of orbital inflammation and fibrosis may suggest a role in IOI. Moreover, CD40-mediated activation cytokine production may contribute to the proinflammatory and profibrotic features of IOI and may provide a mechanism for future targeted therapy.

Thyrotropin receptor and CD40 mediate interleukin-8 expression in fibrocytes: implications for thyroid-associated ophthalmopathy (an American Ophthalmological Society thesis).

PURPOSE: To better understand the pathogenesis of thyroid-associated orbitopathy (TAO) through elucidating the role of thyrotropin receptor (TSHR) and CD40 in the expression of interleukin-8 (IL-8) in peripheral blood fibrocytes. Fibrocytes infiltrate the orbit of patients with TAO, where they differentiate into fibroblasts. Fibrocyte precursors occur with increased frequency in the peripheral blood expressing TSHR and CD40 in TAO patients. We hypothesize that in vitro derived fibrocytes and peripheral blood fibrocyte precursors express proinflammatory chemoattractant molecules including IL-8 initiated by TSHR and CD40 signaling. Since nearly all TAO patients express activating antibodies to TSHR, this is particularly relevant for activation of peripheral blood fibrocytes. METHODS: TSHR and CD40 expression on peripheral blood fibrocytes was determined by flow cytometry. IL-8 RNA was quantitated by real-time polymerase chain reaction. IL-8 protein production was measured by Luminex and flow cytometry. Thyroid-stimulating hormone and CD40 ligand-stimulated phosphorylation of Akt in peripheral blood fibrocytes was studied by flow cytometry. RESULTS: Both TSHR- and CD40-mediated signaling lead to IL-8 expression in mature fibrocytes. Fibrocyte precursors assayed directly from circulating peripheral blood demonstrate intracellular IL-8 expression with addition of thyroid-stimulating hormone or CD40 ligand. TSHR- and CD40-induced IL-8 production is mediated by Akt phosphorylation. CONCLUSIONS: Peripheral blood TSHR(+) and CD40(+) fibrocytes express IL-8 and may promote the recruitment of inflammatory cells, mitogenesis, and tissue remodeling in TAO. TSHR- and CD40-mediated IL-8 signaling is mediated by Akt. Delineating the molecular mechanisms of fibrocyte immune function may provide potential therapeutic targets for TAO.

Increased expression of TSH receptor by fibrocytes in thyroid-associated ophthalmopathy leads to chemokine production.

CONTEXT: The molecular basis for anatomically dispersed clinical manifestations in Graves' disease (GD) eludes our understanding. Bone marrow-derived, pluripotent fibrocytes represent a subset of peripheral blood mononuclear cells and infiltrate the orbital and thyroid tissues in GD. These cells may be involved in the pathogenesis of thyroid-associated ophthalmopathy (TAO). OBJECTIVE: The objective of the study was to quantify fibrocyte display of functional cell surface TSH receptor (TSHR), identify the profile of chemokines they express after TSHR activation, and determine whether circulating TSHR(+) peripheral blood fibrocytes are more frequent in situ in patients with TAO. DESIGN/SETTING/PARTICIPANTS: Using a newly developed technique, fibrocytes were directly identified in peripheral blood from 31 patients with TAO and 19 healthy subjects receiving care at a multidisciplinary academic center. MAIN OUTCOME MEASURES: The frequency in situ of fibrocytes (collagen 1(+), CD45(+), CD34(+), CD14(+), CD86(+) peripheral blood mononuclear cells) was assessed by multiparameter flow cytometry and correlated to clinical disease activity and smoking status. Levels of TSHR-displaying fibrocytes and their response to TSH and TSHR-activating antibody, M22, were measured by flow cytometry, Luminex, and real-time PCR. RESULTS: The levels of TSHR expression by fibrocytes are substantially higher than those found in orbital fibroblasts. Moreover, the frequency of TSHR(+) fibrocytes in patients with TAO was greater than that in healthy subjects in situ. Their abundance is not influenced by disease activity or smoking history. These cells produce high levels of several cytokines and chemokines including IL-8, regulated upon activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 when treated with TSH or M22. TSH induces IL-8 production at the pretranslational level. This induced cytokine can be detected in intact fibrocytes ex vivo. CONCLUSIONS: Frequency of circulating TSHR(+) fibrocytes is markedly increased in patients with TAO, and they express proinflammatory chemokines in response to TSH. Because they infiltrate both orbit and thyroid in GD, they may represent the link between systemic immunoreactivity and organ-specific autoimmunity.