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 does not see an immediate path forward for EBI-005 in dry eye disease, and the company will not be initiating the second Phase 3 study of EBI-005 in dry eye disease which was planned to start in the second half of this year. The company plans to further assess the results from the OASIS study to fully inform their evaluation of future plans in dry eye disease, 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.

Iwicki has 25 years of experience as a pharmaceutical industry leader across multiple therapeutic areas. He has extensive experience building brands and has been instrumental in the success of a number of drugs, including Prilosec, Diovan, Zelnorm, Lunesta, and Latuda. Prior to joining Kala, Iwicki served as President and Chief Executive Officer of Civitas Therapeutics, Inc. which was acquired by Acorda Therapeutics, Inc. Prior to joining Civitas, Iwicki served as Chief Executive Officer of Blend Therapeutics and as Chief Executive Officer of Sunovion Pharmaceuticals, Inc. He also served as senior vice president and head of the cardiovascular business unit at Novartis AG. He began his career with sales and management positions at Merck & Co., Inc. and Astra/Merck.

For more information on Kala, please visit the company’s new website at www.kalarx.com.

While There’s No “I” in Team – Teamwork is Essential to Successfully Treat Dry Eye

Building a successful dry eye practice starts with a team approach. A team comprised of doctors, front desk personnel, technicians and even a dry eye coordinator when possible. Once the team is assembled, it needs constant coaching and attention to keep everyone working together towards a common goal.

Education
Start with a solid foundation. Create a mission statement for your dry eye center and develop a protocol for diagnosing and treating patients. This protocol should be agreed upon by all doctors within the practice and modified over time as technology and research develops. Educate your staff. Set aside time for staff training and education on a monthly or quarterly basis. Open and frequent communication sparks positivity and this will make it easier to introduce new diagnostics and treatments in the future.

Empower
Make sure all team members are committed and realize how important their role is to the big picture of a successful dry eye practice. This will foster trust and with that trust you can build your brand. Your staff is the embodiment of this brand. They are the first and last point-of-contact with patients. Within the team, choose a dry eye champion, one person that is quick to learn and has a passion for helping patients. This staff member can be trained to be your dry eye coordinator. After the doctor makes the diagnosis and develops a treatment plan, the coordinator can step in to continue the patient education and help discuss pricing for any fee-for-service procedures you offer.

Commitment
Share your passion to treat the ocular surface with your staff. Share your commitment to put the patient first. Set monthly or quarterly goals and celebrate the successes as a team. A team that cares about the patient and the mission of the practice will be motivated to strive for excellence. Ongoing positive feedback on a job well done goes a long way.

This week’s abstract focuses on a study conducted by Schargus and co-workers¹ that evaluated the MMP-9 in tears and tear film osmolarity in a group of elderly patients (n=20; age = 72.0±6.1yrs) with previously undiagnosed dry eye. The authors also examined the correlation between clinical dry eye tests and MMP-9 in this group of patients. Dry eye symptoms (Ocular Surface Disease Index questionnaire) and signs (tear break-up time, Schirmer test, ocular surface staining) were evaluated in these patients. Enzyme-linked immunosorbent assay [ELISA] test was also used to determine and confirm the concentrations of MMP-9 in tears collected via Schirmer strips.

Patients were classified into four groups: symptoms (classification A: OSDI ≥10), suspected mild dry eye (classification B), osmolarity difference > 8 mOsm/L between both eyes (classification C), and osmolarity cutoff at 308 mOsm/L (classification D: >308 mOsm/L). Eleven percent of the symptomatic group and 14% of the suspected mild dry eye were positive for MMP-9. ELISA tests confirmed that the InflammaDry MMP-9 tests were accurate. Sixty-seven percent of the symptomatic and 64% of the suspected mild dry eye were positive for tear osmolarity. Tear film osmolarity showed a trend toward correlation with symptoms, whereas the quantitative MMP-9 values showed a trend toward correlation with corneal staining. The authors conclude that MMP-9 is possibly a late-stage sign that is hardly overexpressed in mild dry eye, whereas tear osmolarity tends to be a more frequent early indicator of ocular surface instability within mild dry eye patients. A limitation of this study is the small sample size. Further studies with a higher number of patients are needed to understand correlations between elevated tear osmolarity and MMP-9.

1. Schargus M, Ivanova S, Kakkassery V, Dick HB, Joachim S. Correlation of Tear Film Osmolarity and 2 Different MMP-9 Tests with Common Dry Eye Tests in a Cohort of Non-Dry Eye Patients. Cornea. Apr 23 2015.

Correlation of Tear Film Osmolarity and 2 Different MMP-9 Tests with Common Dry Eye Tests in a Cohort of Non–Dry Eye Patients

Marc Schargus, Svetlana Ivanova, Vinodh Kakkassery, H. Burkhard Dick and Stephanie Joachim. Cornea. Apr 23 2015.

PURPOSE: Given that early-stage dry eye is difficult to diagnose, the purpose of this study was to evaluate the performance of matrix metalloproteinase 9 (MMP-9) and tear film osmolarity (TFO) in a cohort of elderly patients with potential dry eye disease (DED).

METHODS: A group of 20 patients, aged 60 years and above, previously undiagnosed with DED were selected. The following DED tests were performed: tear osmolarity, MMP-9 (InflammaDry), Schirmer test, tear film break-up time, Ocular Surface Disease Index (OSDI) questionnaire, corneal fluorescein staining, and conjunctival lissamine green staining. MMP-9 concentrations in tears collected through Schirmer strips were analyzed by an MMP-9 enzyme-linked immunosorbent assay [ELISA]. Subjects were classified by symptoms (classification A: OSDI ≥10, n = 9), based on suspected mild dry eye (classification B: n = 14), TFO difference .8 mOsm/L between both eyes (classification C: n = 13), and TFO cut-off at 308 mOsm/L (classification D: .308 mOsm/L, n = 11).

RESULTS: Eleven percent (1/9) of the symptomatic and 14% (2/14) of the suspected mild dry eye were positive for MMP-9. InflammaDry MMP-9 tests were confirmed to be accurate through an ELISA.

Sixty-seven percent (6/9) of the symptomatic and 64% (9/14) of the suspected mild dry eye were positive for tear osmolarity. None of the evaluated tear film parameters showed a significant correlation, although tear osmolarity and symptoms trended toward significance (r2 = 0.433, P = 0.06), whereas MMP-9 and corneal staining showed a positive association (r2 = 0.376, P = 0.10).

CONCLUSIONS: Similar to corneal staining, the MMP-9 is likely a late-stage sign that is rarely overexpressed in mild subjects, whereas tear osmolarity tends to be a more frequent early indicator of ocular surface disequilibrium within mild subjects.

Answer: Think about the components of your dry eye examination. I am sure that you thoroughly evaluate the lids, meibomian glands, cornea, and conjunctiva with and without your favorite dyes. You likely (hopefully) express the meibomian glands to evaluate the meibum and observe several habitual blink cycles. If your office is so equipped, you may perform osmometry with the TearLab Osmolarity System, meibography with the Oculus Keratograph 5M, and an MMP-9 assessment with the RPS InflammaDry point-of-care assay. I would guess, however, that the minority of clinicians actually look at the physiologic behavior of the tears themselves.

Prior to instilling fluorescein or any other dye, observe the tear fluid dynamics across the ocular surface. Take note of particulate matter floating within the tear meniscus and precorneal tear film. Watch the extent and rate of downward movement of the tears with the downstroke of the lid, as well as the extent and rate of upward movement as the eyelid recoils to its fully opened position. Healthy tear films display somewhat rapid movement in response to the shearing force of the eyelids across the ocular surface. Insufficient or dysfunctional tear films, however, tend to distribute poorly and sluggishly, often appearing to be more stagnant during and immediately following the blink. This near-stagnant tear movement in dry eye patients could be related to poor lid apposition (and thus a decreased applied shearing force) or to an increased viscosity of the tears.

The source of this increased viscosity is multifactorial and somewhat theoretical. Increased ionic concentration (hyperosmolarity) can increase intermolecular interactions, thereby disrupting fluid flow across the surface. Tear film viscosity is also likely negatively correlated with the tear fluid’s volume, lubricity, and surfactant concentration. While it is well accepted in fluid dynamics that viscosity increases with even minor decreases in temperature, it remains to be known whether the differences in corneal temperature in dry eye and normal patients can actually disrupt tear spread across the surface.

Clinically, much can be learned about a patient’s tear film by just observing it with the slit lamp. For improved documentation and analysis, the Dry Eye Suite on the Keratograph 5M includes a video option for evaluating and video-documenting tear fluid dynamics across the cornea.