Effects of prostaglandin analog therapy on the ocular surface of glaucoma patients

Michael B Horsley, Malik Y KahookRocky Mountain Lions Eye Institute, Department of Ophthalmology, University of Colorado Denver, Aurora, CO, USAPurpose: To quantify changes in tear break-up time (TBUT), corneal staining and ocular surface disease index (OSDI) in glaucoma patients after switching therapy from latanoprost with 0.02% benzalkonium chloride (BAK) to travoprost with sofZia™.Methods: Prospective consecutive case series evaluating patients before and 8 weeks after switching from latanoprost with BAK to travoprost with sofZia™ in patients with baseline TBUT less than 6 seconds.Results: Forty eyes of 20 consecutive patients using latanoprost with BAK were switched to travoprost with sofZia™. Mean TBUT prior to starting travoprost was 2.02 ± 0.71 seconds and increased to 6.34 ± 1.31 seconds 8 weeks after the switch (p < 0.001). Mean inferior corneal staining scores decreased from 2.40 ± 0.87 to 1.38 ± 0.59 (p < 0.001). Mean OSDI scores decreased from 26.31 ± 8.25 to 16.56 ± 6.19 (p < 0.001).Discussion: This report focuses on the status of the ocular surface, as documented by TBUT, corneal staining and OSDI, in patients switched from latanoprost with BAK to travoprost without BAK. The switch resulted in a statistically significant increase in TBUT and decreases in corneal staining and OSDI in patients with low baseline TBUT values.Conclusion: BAK, a common preservative for glaucoma drops, may increase OSD by disrupting the tear film and increasing conjunctival inflammation. In this study, a change from a BAK-preserved prostaglandin analog (PGA) to a non-BAK-preserved PGA resulted in a measurable improvement of TBUT, corneal staining and OSDI. Further studies are needed to better understand the impact of BAK-preserved medications on the ocular surface.Keywords: ocular surface, glaucoma, benzalkonium chloride, prostaglandin analo

Trabeculectomy with intraoperative retrobulbar triamcinolone acetonide

Use of topical steroids is an important component of postoperative care after filtration surgery. Efficacy of postoperative medications is affected by patient adherence and physical limitations in the elderly population often prohibit proper dosing of ophthalmic drops. We describe a technique for the use of intraoperative retrobulbar triamcinolone acetonide in trabeculectomy surgery and report on postoperative outcomes. This technique appears safe and may be an attractive method of delivering a steroid depot at the time of trabeculectomy

Sustained Intraocular Pressure Elevation After Intravitreal Injection of Bevacizumab and Ranibizumab Associated with Trabeculitis

Anti-vascular endothelial growth factor agents are frequently used to treat a variety of ocular neovascular diseases. While agents like bevacizumab and ranibizumab appear to be safe and effective, there have been reports of severe intraocular inflammation as well as sustained elevation of intraocular pressure (IOP) after single or multiple intravitreal injections of these protein-based therapeutics. The true mechanism leading to inflammation and/or sustained spikes in IOP remains unknown. We report a patient with sustained IOP elevation and kerato-precipitates on the trabecular meshwork after multiple injections of both bevacizumab and ranibizumab. We propose that monomer antibodies, aggregated proteins, or other high molecular weight molecules might lead to inflammation in the trabecular meshwork and subsequent elevation in IOP

Effect of audible and visual reminders on adherence in glaucoma patients using a commercially available dosing aid

We studied the effects of audible and visual alarms on adherence with a recommended dosing regimen in the management of glaucoma. Forty-two patients were begun on therapy with the Travatan® Dosing Aid (TDA) and randomly divided into two observation groups – one with visual and audible alarm functions turned on and the other with alarms off. Dosing information was analyzed for mean rates of adherence, missed days, and dosing at the wrong time. Twenty patients were randomized to the TDA alarm on group and 22 to the alarm off group. The rates of adherence were 87.9% and 79.7% (p = 0.02), rates of missed dosing were 7.6% and 14.4% (p = 0.03), and rates of dosing at the incorrect times were 7.1% and 9.8% (p = 0.19), respectively for alarm on versus alarm off groups. In the alarm on group, the adherence rate was significantly higher and proportion of missed dosing was significantly lower. It is still yet to be determined whether there is a relationship between adherence and progression of glaucoma

Contamination of anti-vegf drugs for intravitreal injection. How Do Repackaging and Newly Developed Syringes Affect the Amount of Silicone Oil Droplets and Protein Aggregates?

Purpose: The particle counts and the nature of particles of three different antivascular endothelial growth factor agents (VEGF) in different containers in a laboratory setting were compared. Methods: Original prefilled ranibizumab glass syringes, original vials with aflibercept, and repacked ready-to-use plastic syringes with bevacizumab from a compounding pharmacy and a compounding company (CC) were analyzed. Particle counts and size distributions were quantified by different particle characterization methods (nephelometry, light obscuration, Micro-Flow Imaging, nanotracking analysis, resonant mass measurement). Using high-performance size-exclusion chromatography (HP-SEC), levels of protein drug monomer and soluble aggregates were determined. Results: Nearly all samples showed similar product quality. Light obscuration and Micro-Flow Imaging showed a 4-fold to 9-fold higher total particle count in compounding company bevacizumab (other samples up to 42,000 particles/mL). Nanotracking analysis revealed highest values for compounding company bevacizumab (6,375 million particles/mL). All containers showed similar amounts of silicone oil microdroplets. Ranibizumab showed lowest particle count of all tested agents with only one monomer peak in HP-SEC. Repackaged bevacizumab from different suppliers showed varying product quality. Conclusion: All three tested agents are available in similar quality regarding particulate purity and silicone oil microdroplet count. Repackaging can have a major impact on the quality

A Burst Mode, Ultrahigh Temperature UF4 Vapor Core Reactor Rankine Cycle Space Power System Concept

Static and dynamic neutronic analyses have been performed on an innovative burst mode (100's of MW output for a few thousand seconds) Ulvahigh Temperature Vapor Core Reactor (UTVR) space nuclear power system. The NVTR employs multiple, neutronically-coupled fissioning cores and operates on a direct, closed Rankine cycle using a disk Magnetohydrodynamic (MHD) generater for energy conversion. The UTVR includes two types of fissioning core regions: (1) the central Ultrahigh Temperature Vapor Core (UTVC) which contains a vapor mixture of highly enriched UF4 fuel and a metal fluoride working fluid and (2) the UF4 boiler column cores located in the BeO moderator/reflector region. The gaseous nature of the fuel the fact that the fuel is circulating, the multiple coupled fissioning cores, and the use of a two phase fissioning fuel lead to unique static and dynamic neutronic characteristics. Static neutronic analysis was conducted using two-dimensional S sub n, transport theory calculations and three-dimensional Monte Carlo transport theory calculations. Circulating-fuel, coupled-core point reactor kinetics equations were used for analyzing the dynamic behavior of the UTVR. In addition to including reactivity feedback phenomena associated with the individual fissioning cores, the effects of core-to-core neutronic and mass flow coupling between the UTVC and the surrounding boiler cores were also included in the dynamic model The dynamic analysis of the UTVR reveals the existence of some very effectlve inherent reactivity feedback effects that are capable of quickly stabilizing this system, within a few seconds, even when large positive reactivity insertions are imposed. If the UTVC vapor fuel density feedback is suppressed, the UTVR is still inherently stable because of the boiler core liquid-fuel volume feedback; in contrast, suppression of the vapor fuel density feedback in 'conventional" gas core cavity reactors causes them to become inherently unstable. Due to the strength of the negative reactivity feedback in the UTVR, it is found that external reactivity insertions alone are inadequate for bringing about significant power level changes during normal reactor operations. Additional methods of reactivity control such as variations in the gaseous fuel mass flow rate, are needed to achieve the desired power level oontrol