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This multi-assay test shows high sensitivity and predictive value, which can help distinguish inflammatory dry eye from other types of the condition.
Take-home message: This multi-assay test shows high sensitivity and predictive value, which can help distinguish inflammatory dry eye from other types of the condition.
Reviewed by George Ousler, MD
Clinicians trying to better diagnose dry eye could get help from a new diagnostic system. BioLight Life Sciences recently reported positive results for TeaRx, a multi-assay test intended to evaluate multiple components of the tear film. The company said its novel diagnostic shows high sensitivity, high specificity, and high positive predictive value, which are at the higher claimed range of existing dry eye tests.
“We are developing a point-of-care diagnostic test that can identify one or more of the underlying causes of dry eye syndrome in a particular patient,” said BioLight CEO Suzana Nahum Zilberberg. “As well as being very useful to clinicians in diagnosing the causes of dry eye and monitoring treatment, this tool could be useful for pharmaceutical companies that need a companion diagnostic to accompany novel products and for clinical research efforts seeking to develop new drug candidates.”
Existing dry eye tests can identify a single factor related to dry eye such as hyper osmolarity (TearLab) or elevated MMP9 levels (RPS InflammaDry), noted George Ousler, MD, Director of Dry Eye Research for Ora.
“Dry eye syndrome is multifactorial,” he said. “There are a number of underlying etiologies. We know, for example, that the tear film has three major components, the lipid, aqueous, and mucin layers. You can have deficiencies in any one layer or in multiple layers. There can be corneal sensitivity issues as well as influential factors such as adverse, environmental conditions, visual tasking, systemic medications that are known to cause drying and more. It is relatively straightforward to conclude that the patient has a dry eye problem, but often quite difficult to clarify the particular factors at play in any individual patient. Having a diagnostic tool that could provide that clarification could be quite helpful.”
Using multiple assays
Nimrod Bin-Nun, CEO of BioLight’s portfolio company, DiagnosTear, was more direct in his assessment of current generation dry eye diagnostics.
“It is naïve to think that one test can diagnose or that one drug can treat the multiple factors that lie behind dry eye syndrome,” he said. “The only way to diagnose a multi-factorial syndrome like dry eye is by using multiple assays. We have developed several assays that measure concentrations of different proteins, different inflammatory factors and other substances in the tear film taken from different locations in the eye. Measuring a combination of components relating to different physiological pathways can contribute significantly to both diagnosing these patients and personalizing their treatment.”
The company has not disclosed which substances or parameters it is measuring in tear film. What researchers are willing to say is that a model combing multiple tear film components and demographics produced a sensitivity of 86% and a positive predictive value of 87% for dry eye.
These results are better than those typically seen in existing office-based testing systems, including Schirmer’s Test, tear film break-up time, corneal staining, symptomatic questionnaires and are well positioned versus other commercialized diagnostic tests such as RPS InflammaDry and TearLab.
Timing of the trial could be helpful, Dr. Ousler said. There is currently only one drug indicated for the treatment of dry eye in the United States-cyclosporine, an anti-inflammatory-but there are multiple agents in development, including other anti-inflammatories, secretagogues, hormonal therapies, and more. Appropriate patient selection for each of these drug candidates is a potential barrier for both successful clinical trials and effective treatment.
“Because there are so many treatment modalities that will be coming to the market relatively soon, we are going to have to have some clarity as to which drug is most appropriate for each dry eye subtype,” he said. “We are going to want to be able to match the patient to the medication that is most appropriate based on the underlying mechanism of action for that specific drug. If I have a novel mucin secretagogue, I am going to want to have a test to say ‘Yes, this patient has a mucin-deficient dry eye’ rather than an inflammatory dry eye. Having a test like this to use as a differential diagnosis to select your treatment modality of choice would be a benefit.”
BioLight is looking at TeaRx as more than a quick and easy point-of-care diagnostic. It would also like to see the test, or a later version, designated as a companion diagnostic for novel therapeutic agents. The diagnostic first needs marketing approval in the United States and other jurisdictions.
BioLight has conducted all of its early U.S. clinical trials to support its path with the FDA which, based on previous approvals, is anticipated to be under the 510(k) pathway. Mr. Bin-Nun noted that the TeaRx trial used the same standardized grading scale for dry eye severity that was used for the approval of the InflammaDry.
Diagnostic test trials can be relatively quick to design and execute; the first TeaRx trial with about 200 patients was completed in less than two months.
“We are planning a pre-submission to the FDA in the near future, aiming to establish the regulatory pathway,” said Ms. Zilberberg. “Once we understand the pathway we need to follow, we will initiate the appropriate clinical trials. Based on the trials we have conducted in the United States so far, we don’t think it will be a long process, which would be a great benefit for early approval and early clinical use.”
George Ousler, MD, Director of dry eye research for Ora
Suazana Nahum Zilbergerg, CEO of BioLight
Nimrod Bin-Nun, CEO of DiagnosTear