Efficacy and Safety of Teprotumumab in Patients With Thyroid Eye Disease of Long Duration and Low Disease Activity.

CONTEXT: Early inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease, including disabling proptosis. Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, previously demonstrated efficacy in acute, high-inflammation TED trials. OBJECTIVE: We present data from the first placebo-controlled trial with teprotumumab in chronic/low disease activity TED. METHODS: This randomized double-masked, placebo-controlled trial, conducted at 11 US centers, enrolled adult participants with TED duration of 2 to 10 years, Clinical Activity Score (CAS) ≤ 1 or no additional inflammation or progression in proptosis/diplopia for ≥1 year, proptosis ≥3 mm from before TED and/or from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab, and no steroids within 3 weeks of baseline. Patients received (2:1) intravenous teprotumumab or placebo once every 3 weeks (total 8 infusions). The primary endpoint was proptosis (mm) improvement at Week 24. Adverse events (AEs) were assessed. RESULTS: A total of 62 (42 teprotumumab and 20 placebo) patients were randomized. At Week 24, least squares mean (SE) proptosis improvement was greater with teprotumumab (-2.41 [0.228]) than with placebo (-0.92 [0.323]), difference -1.48 (95% CI -2.28, -0.69; P = .0004). Proportions of patients with AEs were similar between groups. Hyperglycemia was reported in 6 (15%) vs 2 (10%) and hearing impairment in 9 (22%) vs 2 (10%) with teprotumumab and placebo, respectively. AEs led to discontinuation in 1 teprotumumab (left ear conductive hearing loss with congenital anomaly) and 1 placebo patient (infusion-related). There were no deaths. CONCLUSION: Teprotumumab significantly improved proptosis vs placebo in longstanding/low inflammation TED, demonstrating efficacy regardless of disease duration/activity. The safety profile was comparable to that previously reported.

Tweeting for Success: The Role of Twitter in Enhancing SCImago Journal Rank for Specialty Surgical Journals.

Background The cornerstone of surgical education and practice is the surgical journal, but the ability to disperse the vital information within their pages had previously been limited. The use of Twitter by surgical journals has increased in recent years and has allowed these journals to reach a wider audience than they previously could. In this article, we discuss the role Twitter engagement has on a journal's impact factor, visibility, and prestige. Methods The authors compiled a list of journals using the SciMago Journal and Country rank platform. Included journals' Twitter profiles were then assessed using Twitonomy, an online platform that collects and processes data regarding individual Twitter profiles. Statistical analysis was conducted to determine the relationship between Twitter use and SCImago Journal Rank (SJR). Results Simple linear regression and multiple linear regression models determined that the only variables that had a statistically significant impact on all journals were the age of the Twitter account (p=0.003) and the percentage of retweets (p=0.001). When it comes to specialty-specific journals, further analysis showed that the only significant factor regarding its impact on SJR was the percentage of retweets (p=0.007). Conclusions Surgical journals' regular use of Twitter is important in the dissemination of important information to a wide audience. This article shows that the most important variable to determine the impact and visibility of a surgical journal is the percentage of retweets. Further research should be performed to better understand how to use Twitter and other social media platforms to reach a larger audience.

Screening patients with the corneal navigator.

PURPOSE: To present a corneal topography screening device for the detection of corneal ectasias and various refractive procedures based on corneal topography patterns. METHODS: A database of corneal topography patterns were analyzed and used to "train" a neural network on nine different corneal topography patterns using nineteen corneal topography indices of corneal shape and power. RESULTS: Sample normal and corneal topographies were recognized correctly. CONCLUSIONS: The use of the corneal navigator to screen various corneal topographies aids clinical diagnosis.

Advantages and disadvantages of the Zernike expansion for representing wave aberration of the normal and aberrated eye.

PURPOSE: Zernike expansion has been selected for use in describing wavefront aberrations in the human eye. The advantages and limitations of this approach are assessed for eyes with varying degrees of aberration. METHODS: Corneal topography examinations were taken with the Nidek OPD-Scan topographer/aberrometer. These higher data density corneal topography examinations were converted to height data and subsequently to wavefront representations. System noise was evaluated with a 2D frequency analysis of 43-D test balls. Both Zernike polynomials and 2D Fourier transforms were used to evaluate fidelity in the presentation of the point spread function. A display format for potential clinical use was developed based upon Zernike decomposition. RESULTS: Systematic noise from the corneal topographer was found to be minimal and, when eliminated, produced small changes in the point spread function. Using Zernike decomposition up to the 30th order failed to preserve the higher frequency aberrations present in aberrated eyes. Use of a Zernike decomposition display with a fixed micron scale presented only clinically significant details of spherical aberration, coma, trefoil, irregular components above third order and total higher-order aberrations (above second order). CONCLUSIONS: Zernike polynomials excel in extracting the low-order optical characteristics of visual optics. Zernikes accurately represent both low- and high-order aberrations in normal eyes where high-order aberrations are clinically insignificant. For eyes after corneal surgery or eyes with corneal pathology such as keratoconus that have significant higher-order aberrations, the Zernike method fails to capture all clinically significant higher-order aberrations.

Effect of inhibition of inflammatory mediators on trauma-induced stromal edema.

PURPOSE: To determine the specific biochemical pathways involved in the initial-phase inflammatory response that causes stromal edema after epithelial debridement of the rabbit cornea. METHODS: Adult New Zealand White rabbit corneas were treated with 2 mM synthetic inhibitor of metalloproteinase (SIMP)-1, 1 mM DFU (a specific cyclooxygenase [COX]-2 inhibitor) in 50/50 dimethyl sulfoxide (DMSO)/Ringer's solution, 300 KIU aprotinin (a serine protease inhibitor), 0.05% or 0.10% IL-1 receptor type II solution, 1 mM gliotoxin (a Ras farnesyltransferase inhibitor), or vehicle alone (the control). These were applied topically in vivo in five doses over a 3-hour period except IL-1 receptor type II, which was applied in vitro. After rabbits were killed, the corneas were mounted in perfusion chambers with the endothelium bathed in a modified Ringer's solution and the epithelium bathed with silicone oil. Corneal thickness was measured with an automatic specular microscope. The corneal thickness typically stabilized 1 hour after mounting. After stabilization, the corneal epithelium was removed with a rotating bristle brush and stromal thickness monitored for 1 hour. Paired control corneas were treated similarly. RESULTS. Stromal swelling after epithelial debridement was significantly less in most treated corneas, compared with untreated controls: 18.4 +/- 5.3 microm vs. 28.6 +/- 7.7 microm (n = 6, P = 0.004); SIMP-1, 18.7 +/- 10.2 microm vs. 34.3 +/- 10.2 microm (n = 7, P = 0.02); DFU, 19.3 +/- 10.2 microm vs. 23.5 +/- 8.4 microm (n = 6, P = 0.01); and IL-1 receptor type II (0.05%), 26.2 +/- 5.6 microm vs. 30.4 +/- 5.6 microm (n = 5, P = 0.03) and (0.10%), 26.6 +/- 5.6 microm vs. 32.1 +/- 7.4 microm (n = 8, P = 0.03). Gliotoxin was not effective (21.5 +/- 8.0 microm vs. 21.9 +/- 6.2 microm; n = 5, P = 0.94). CONCLUSIONS: The reduction of stromal edema after topical administration of the inhibitors demonstrates the involvement of the COX-2 enzyme, the matrix metalloproteinase family, plasminogens, and the IL-1 system in the trauma-induced inflammatory response of the rabbit cornea. The inflammatory process in the cornea associated with trauma can proceed along multiple redundant parallel pathways.