In reference to two recent articles published in the February and March issues of Optician, entitled, Osmolarity: an overview by Dr. Marian Elder & Professor Sruthi Srinivasan and Effective new slitlamp techniques for tear hyperosmolarity in dry eye by Steve Meynell & Clare Privato, I-MED Pharma would like to correct some erroneous and misleading information.
The articles specifically state, ‘The I-Pen is a newer point-of-care tear osmometer that uses electrical impedance technology, but studies have shown it not to be as accurate in separating normal eyes from dry eyes as the TearLab.’
This statement is erroneous and has no basis for substantiation. This information was derived from two studies questioning the reliability of the I-Pen, namely the Rocha/Chan study and the Nolfi study. In the Rocha/Chan study the I-Pen was tested in an incorrect manner, resulting in inaccurate findings. I-MED’s contention that the study protocol did not use the I-Pen device appropriately and that the I-Pen data is inaccurate and unusable is supported by the following facts:
1 The article states, ‘After opening the microcentrifuge tube, the tip of each device was placed gently atop the fluid residing in the cap.’ The I-Pen user manual clearly states, ‘attach a new Single Use Sensor onto the System Reader and touch the tip of the Single Use Sensor to the inner tissue of the lower eyelid.’
Unlike the other osmolarity devices in the study, the I-Pen was designed and programmed to work only when in contact with tissue. The algorithm that converts the electrical impedance readings into osmolarity only works in this fashion. Using the I-Pen on ‘fluid residing in the cap’ of the standard solution is not a valid testing method and understandably resulted in incorrect osmolarity measurements.
2 The study protocol for the article was prepared by Michael Berg, vice-president of regulatory at TearLab Corporation. Before the article was published, both TearLab and Mr Berg were provided with documents from I-Med confirming point 1 above. They were also provided with an I-Med internal report and internal data that showed that when modified for use in standard solutions, the I-Pen accurately measures impedance.
The I-Med report concluded the following: ‘A series of saline solutions ranging from 100 to 500 mOsmol/L were prepared for testing with a modified I-Pen device. The device had to be modified because the commercial model does not have the ability to perform direct measurements of solutions. The modified I-Pen was able to measure impedance of the saline solutions. The results of these tests demonstrate that the device is capable of providing a nearly linear result for the reading with a coefficient of variance (R2) of 0.97.’
3 The I-Pen is sold as a diagnostic tool for use in humans and animals, not for measuring the osmolarity of contrived solutions. When Mr Berg was cross-examined by I-Med’s Canadian lawyers about the study, he made the following admission:
Q And based on what you just told me, sitting here today, you are not able to say whether the I-Pen is more or less reliable and accurate in human subjects than the TearLab device would be; is that correct?
A That’s correct.
This study has since been re-done, with the original authors using the correct techniques, and in turn, producing reliable results for the I-Pen. This new study has now been submitted for review and is awaiting publication.
In addition to the fact that the re-done study provides very favourable results, I-Med Pharma can also confirm that several of the authors use the I-Pen device exclusively in their clinics.
TearLab released a second study comparing TearLab to I-Pen. The lead on this study, Dr Jerry Nolfi, OD, MBA previously served as a Member of the Clinical Advisory Board at TearLab Corporation and was TearLab’s distributor in Canada. Furthermore, I-Med has no records of anyone being trained in the use of the I-Pen in the clinic where the experiment took place. This second study also paints a poor picture of the efficacy of the I-Pen. I-Med Pharma has no idea how the results were obtained and/or whether the tests using the I-Pen were performed correctly.
This study also incorrectly references two other studies (Duench et al & Sniegowski et al) suggesting a wide variance in temperature readings, which has an impact on impedance measurements. However, Duench looks at bulbar, not palpebral conjunctival temperature and Sniegowski studies temperature variations in the exposed ocular surface and not the unexposed palpebral conjunctiva at all.
A study by Holden et al looking at temperatures of the palpebral conjunctiva, showed they found a mean temperature of 36.2°C ± 0.6°C which is very steady and has very low (± 1.4%) variability on which I-Med Pharma has based its assumption of the palpebral conjunctival having a stable temperature. Finally, this study also references the Rocha/Chan study, which TearLab has already admitted in court was done incorrectly.
In summary, I-Med Pharma felt that it was necessary to rebut the statements written about the I-Pen in the aforementioned articles and clearly outline the fact that the proper study protocol was not followed and the method in which the I-Pen was tested was inaccurate. Given these facts, the results of these two studies must be deemed erroneous and unreliable.
