The CooperVision FORCE Student Awards acknowledges student projects from the universities of the UK and Ireland and offers the students shortlisted a chance to present their findings to panels of experts at a UK and international level. There were two projects shortlisted from the UK and Ireland this year. This article will outline the runner-up.
Runner-up: Rebecca English
Title: The i-Pen. Comparison with conventional tear film assessments and normative data for clinicians
Supervisor: Dr Julie McClelland
As pointed out in the introduction to this presentation, interest in the measurement of the osmolarity of the tear film has increased greatly since the publication of the latest definition of dry eye disease from the TFOS DEWSII report as follows: ‘Dry eye is a multifactorial disease of the ocular surface characterised by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.’ Indeed, both aqueous deficient and evaporative dry eye are known to promote hyperosmolarity, so accurate measurement of this is an important part of the accurate diagnosis of dry eye disease.
Osmolarity
Rebecca English then went on to offer an excellent summary of tear osmolarity. ‘Osmolarity is the osmotic concentration of a solution expressed as osmoles of solute per litre of solution. Tear osmolality represents the salt concentration of tears. Reduced tear osmolarity triggers an inflammatory response by releasing mediators and proteases. These mediators along with tear hyperosmolarity can damage epithelial and goblet cells leading to a loss of the epithelial glycocalyx. The T-cells activate these inflammatory mediators which act on the ocular surface, thus causing damage. This damage is evident from characteristic punctate epitheliopathy and tear film instability which can then progress to quicker, shorter tear break-up times. Early tear break-up increases the levels of tear hyperosmolarity and the cycle of ocular damage continues.’
She continued: ‘Osmolarity testing is considered the best method of detecting dry eye at the earliest stages which leads to a quicker diagnosis. High tear osmolarity readings are associated with ocular surface damage and therefore early detection is vital.’
Figure 2 i-Pen use in clinic
The i-Pen
The aim of English’s project was to compare the osmolarity results gained from a recently introduced hand-held osmolarity measuring device, the i-Pen (figure 1), with a range of conventional measurements used to assess tear status.
As the instrument might not have been familiar to all, she then gave a useful introduction to the device. ‘The i-Pen was developed by Imed Pharma to measure tear osmolarity in vivo. It is classified as a Class 1 medical device with measuring ability and is quick, easy to use and transportable.’
‘The i-Pen auto-calibrates and doesn’t require a sample of tear fluid, meaning less risk of tear evaporation. Separate single use sensors are inserted into the device and then placed on the conjunctiva of the lower lid medially for a few seconds (figures 2 and 3). This technique is minimally invasive and no anaesthetic eye drops are required.
‘Two hundred and fifty measures are taken in four seconds with a final value displayed in units of mOsmol/L. The tear osmolarity is determined by measuring the electrical impedance level of the saline concentration of extracellular fluid within conjunctival tissue instead of that within the tears.
Figure 3 The i-Pen is placed on the conjunctiva of the lower lid medially for a few seconds
‘Limited data exist comparing the i-Pen to conventional standard measure of tear assessment. Therefore, my project aimed to:• Compare measures obtained from the i-Pen to conventional subjective and objective measures of tear film assessment
• Provide clinicians with normative data for use in everyday practice.’
Method
English recruited 60 healthy adult subjects, aged between 18 and 60 years. Participants with known ocular pathologies (such as cataracts, glaucoma, strabismus or amblyopia) were excluded. All procedures were performed under standard illumination conditions and the appropriate ethical approval was obtained and written informed consent was obtained from all participants.
Participants then each completed three well established and validated dry eye questionnaires:
• The Speed questionnaire
• The Ocular Surface Disease Index
• McMonnies Questionnaire
Next, the following clinical measurements were taken:
• Best corrected visual acuity
• Non-invasive tear break-up time (using a keratometer)
• i-Pen osmolarity
• Fluorescein tear break-up time
Interestingly, participants were also asked about their recent intake of coffee. As English explained, ‘Many people suggest that coffee dehydrates the tear film hence leading to symptoms of DED. Yet a recent Japanese study has found that caffeine can stimulate tear production.’
Results
These were summarised as follows:
• Twenty-eight males and 32 females participated. Using ANOVA, there was no significance found between tear osmolarity readings and gender (P=0.550). However, the mean osmolarity readings were higher in females (308.81 mOsmol/L) as opposed to males (305.82 mOsmol/L)
• i-Pen results averaged 307.41 mOsmol/L
• A weak correlation between age and osmolarity was observed perhaps due to the similar age of most of the participants with at least 42 subjects aged between 18 to 25
• Regression analysis demonstrated a significant correlation between tear osmolarity readings and tear break-up time measured using the Bausch and Lomb keratometer mires
(P = 0.00)
• i-Pen tear osmolarity readings and TBUT invasive with fluorescein was found to have a strong association. (Regression analysis p=0.00)
Noting that ‘novel normative data will provide useful for clinicians and will allow optometrists to monitor treatment in practice,’ English then presented the mean osmolarity values for the i-Pen for each age group (table 1).
Table 1 Normative data for clinicians. Mean i-Pen tear osmolarity measures and 95% confidence limits (mean ± 1.96 x SD) of tear osmolarities for each age category
ConclusionEnglish offered the following points in conclusion:
• The strongest correlation found was between tear osmolarity and tear break-up time both invasive and non-invasive tests. This suggests that tear osmolarity measures obtained with the i-Pen do correlate with tests used every day in practice to assess dry eye. This strong correlation is suggestive that tear osmolarity testing could be incorporated into practice as a means of dry eye screening and assessment. In general, higher osmolarity measures meant lower TBUT times both invasively and non-invasively.
• The age range in this study was set at 18 to 60 years. However, the spread of participants was very much limited to a younger cohort due to the results being collected from a university population. Over 42 of the subjects were below the age of 25 (70%) hence this will have affected the results regarding tear osmolarity measures and age and repeating the study with a wider age range would be beneficial.
• Contact lens wear is thought to be a causative factor in DED. This was not shown in the above study, as no significant correlation was found between contact lens wearers and higher tear osmolarity measures. Again, population factors may have affected the results.
• Sixty participants were included in this study which is a relatively small sample size. Had this study been conducted with a larger set of subjects a more accurate and balanced display of results may have been found.
• No significance was found between gender and tear osmolarity measures, yet a higher tear osmolarity mean was found for females (308.82mOsmol/L) in comparison to males (305.81mOsmol/L).
• This cohort included a relatively healthy population. Inclusion of participants with dry eye disease would provide useful comparative data for clinicians.
Good design, good analysis, excellent interpretation. A study that bodes well for future research.