We are about to begin the process of editorial planning for our 2016 editorial calendar. As always, we reach out to you—our readership and constituency—for your thoughts and comments about ideas and themes you would like for us to consider. If you have thoughts on topics we should cover more, please email us at cltoday@pentavisionmedia.com.

CooperVision, Inc. has named Jerry Warner as President, North America. Warner is responsible for determining the strategic direction of the company’s largest region, driving sustainable business growth and deeper customer relationships in the United States and Canada.

Warner previously served as CooperVision’s Senior Vice President of Global Marketing. He joined the company in 2012 as Vice President, Life Cycle Management.

Prior to joining CooperVision, Warner was with Bausch + Lomb for 17 years. During that time, he held numerous leadership positions, including Vice President of Marketing / General Manager of Global Contact Lens; Vice President of Global Strategy for Contact Lens; and Director of Marketing for Lens Care – North America. Earlier in his career, he served in a variety of sales, marketing and trade marketing roles with Bristol Myers Squibb at the territory and management levels.

Eleven Biotherapeutics, Inc. announced top-line results from the OASIS study, the company’s first pivotal Phase 3 study of its lead drug candidate, EBI-005, in moderate to severe dry eye disease (DED). The co-primary endpoints of the Phase 3 study were the total corneal fluorescein staining score and the patient-reported measurement related to ocular pain and discomfort based on the ocular surface disease index (OSDI), comparing the mean change from baseline at week 12 for treatment with EBI-005 to treatment with vehicle control. In this study, EBI-005 did not meet either of these two co-primary endpoints.

There was no statistically significant difference between the EBI-005 treated group and the vehicle control group on the co-primary endpoints or any secondary endpoints. Patients with dry eye disease in both the EBI-005 and vehicle treatment groups showed statistically significant improvement from baseline on the co-primary endpoints. While the change from baseline on the co-primary endpoints was greater in the vehicle group than the EBI-005 group, the differences between the two groups were not statistically significant and the company believes the differences were not clinically meaningful. EBI-005 was generally well tolerated in the Phase 3 study with fewer than 5% of patients reporting eye irritation and no treatment related serious adverse events. Approximately 13% of patients in the study reported some use of artificial tears, with no difference in artificial tear use between the EBI-005 treated and vehicle control groups. Overall, 92% of patients completed the study, with 33 patients having dropped out of the EBI-005 group and 20 patients having dropped out of the vehicle control group.

According to the company announcement, based on these top-line results, the company will not be initiating the second Phase 3 study of EBI-005 in DED. The company plans to further assess the results from the OASIS study to fully inform their evaluation of future plans in DED, including the ongoing Phase 3 safety study.

Eleven continues to prepare to advance EBI-005 into late-stage clinical development for allergic conjunctivitis, with plans to initiate a pivotal Phase 3 study in patients with moderate to severe allergic conjunctivitis in the second half of 2015.

Have you seen an interesting case lately? Would you like to share it with your colleagues? An image from that case could appear in this column in the coming weeks!

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What are integrins and why are they important in ocular surface disease

Integrins are transmembrane cell-surface protein receptors that are the bridges for cell-cell and cell-extracellular matrix interactions: these proteins are designed to transfer information from the outside of the cell to the inside.¹ Integrins are the main way by which cells both bind to and respond to their environment.² When triggered, integrins activate chemical pathways that result in a response such as regulation of the cell cycle, cell shape, and/or motility or new receptors being added to the cell membrane. Integrins allow for rapid and flexible responses to events at the cell surface and are “integral” to many biological systems. Integrins are important in a variety of cellular functions such as growth, development, immune response, and wound repair. For example, integrins signal platelets to initiate an interaction with coagulation factors in wound healing. Integrins are also considered major players in the inflammatory cascade of dry eye: the chronic inflammatory process in dry eye disease is mediated by integrin-modulated CD4+ lymphocytes activation (T-cells) in response to desiccating stress of any nature.³

Currently modulation of integrin function is a target of therapeutics indicated for the treatment of dry eye. I am excited about the prospects of novel integrin-antagonistic molecules in development and look forward to their commercial availability.

1. Secko DM. Surface Receptors: A Biological Conduit for Information Transfer. The Science Creative Quarterly. 2006 July. Accessed online 5/25/15. http://www.scq.ubc.ca/cell-surface-receptors-a-biological-conduit-for-information-transfer/
2. Aplin AE, Howe A, Alahari SK, Juliano RL. Signal transduction and signal modulation by cell adhesion receptors: the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharmacol Rev. 1998 50: 197-263.
3. Sheppard J, Semba C. A novel topical integrin antagonist (lifitegrast) for the treatment of dry eye: results of a multicenter, randomized, prospective, double-masked, placebo-controlled study. Paper presented at: XXXI Congress of the European Society of Cataract and Refractive Surgeons; 2013 Oct 5-9; Amsterdam, The Netherlands.

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Critical Role of Post-Contact Lens Tear Exchange and the Risk of Microbial Keratitis

Microbial keratitis (MK) is likely the most serious potential complication of contact lens wear based on its potential to result in sight threatening outcomes. Although the associations of contact lens wear and more specifically continuous wear contact lens use with MK is well known, the specific mechanism(s) that are involved are still yet to be established.

Researchers recently tested the hypothesis that tear fluid at the posterior contact lens surface can lose antimicrobial activity over time during lens wear. Daily disposable lenses were worn for 1, 2, 4, 6, or 8 hours immediately after removal from their packaging or after presoaking in sterile saline for 2 days to remove packaging solution. Unworn lenses were also tested, some coated in tears “aged” in vitro for 1 or 8 hours. Results found that the posterior surfaces of lenses worn by patients for 8 hours supported more P. aeruginosa growth than lenses worn for only 1 hour, if lenses were presoaked before wear (∼2.4-fold, p = 0.01). This increase was offset if lenses were not presoaked to remove packaging solution (p = 0.04 at 2 and 4 hours). Irrespective of presoaking, lenses worn for 8 hours showed more growth on their posterior surface than unworn lenses coated with tear fluid that was aged for 8 hours in vitro (∼8.6-fold, presoaked, p = 0.003; ∼5.4-fold from packaging solution, p = 0.004). The authors stated that in vitro incubation did not impact tear antimicrobial activity. They concluded that post-lens tear fluid can lose antimicrobial activity over time during contact lens wear, supporting the idea that efficient tear exchange under a lens is critical for homeostasis. The researchers further stated that additional studies are needed to determine applicability to other lens types, wearing modalities, and relevance to contact lens-related infections.

In the 1990’s SiHy lenses were developed with dramatic increases in oxygen transmission which we hoped would be the key to reducing the risk of MK in CL wear. However, to our great disappointment this did not come to fruition. Today we continue to explore those mechanisms that might provide the answer to this very serious problem. Post-lens tear exchange appears to be one of those important mechanisms. It therefore seems intuitive that fitting characteristics, lens design characteristics and lens wearing modalities that would promote better post-lens tear exchange may reduce the risk of MK in contact lens wear.

Wu YT1, Zhu LS, Tam KP, Evans DJ, Fleiszig SM. Pseudomonas aeruginosa Survival at Posterior Contact Lens Surfaces after Daily Wear. Optom Vis Sci. 2015 May 7. [Epub ahead of print]

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Tear fluid contains antioxidative compounds, vitamin C, glutathione, superoxide dismutase, and lactoferrin (LF), which protect the corneal epithelium from the effects of ultraviolet irradiation, direct airflow, and chemical agents. However, these natural defenses against oxidative stress can decrease, favoring the development of anterior eye disorders, such as keratoconus, dry eye, and Sjögren syndrome. LF is an iron-binding glycoprotein, present in mammalian secretions such as tears and milk, endowed with different physiological functions such as antimicrobial, antiviral, and antioxidant activities. In this work, the researchers studied the capability of different soft contact lenses to adsorb and release LF to restore cellular viability in oxidative stress conditions.

Three types of contact lenses (filcon V, galyfilcon A, and filcon IB) were loaded with LF and then incubated with TsA or human corneal epithelial primary cells. After oxidative stress induction with 250 μm or 125 μm H2O2, cell viability was evaluated.

Data showed that the highest quantity of LF loaded in contact lenses was between 61 μg (for filcon V) and 39 μg (for filcon IB); the release was between 49% and 100% of protein adsorbed. LF released from contact lenses maintained its antioxidant activity at least for 24 hours and was able to protect human epithelial cells from the detrimental effects of oxidative stress.

The researchers concluded that these results demonstrate that LF-loaded contact lenses could represent a new therapeutic approach to treat ocular surface pathologies characterized by high levels of oxidative stress.

Pastori V, Tavazzi S, Lecchi M. Lactoferrin-Loaded Contact Lenses: Eye Protection Against Oxidative Stress. Cornea. 2015 Jun;34(6):693-7. Doi: 10.1097/Ico.0000000000000435.

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