New dry eye disease study compares two preservative-free artificial tear drops

During this year’s European Society of Ophthalmology (SOE) meeting in Lisbon, Portugal, Marc Labetoulle, MD, PhD, shared research findings in a poster session. Prof Labetoulle is chair and professor of ophthalmology at Paris-Saclay University and professor at Quinze-Vingts National Vision Hospital, both in Paris, and head of the ophthalmology department at Bicêtre Hospital, Le Kremlin-Bicêtre, France.

His presentation, featured in the ocular surface segment of the programme, was titled “A multicentre clinical study of two preservative-free artificial tears with sodium hyaluronate for the treatment of dry eye.” In an interview with Ophthalmology Times Europe, Prof Labetoulle provided more context for the research, discussed key clinical outcomes and illuminated the often-challenging nature of restoring ocular surface comfort.

See the full Q&A below.

Hattie Hayes, editor: Please give a brief overview of this multicentre study.

Marc Labetoulle, MD, PhD

Marc Labetoulle, MD, PhD: The aim of the study was to compare the performance and safety in patients with moderate to severe dry eye disease (DED) of a novel preservative-free tear substitute with another (already on the market and well-known) preservative-free 0.18% sodium hyaluronate (SH) tear substitute.

It was a multicentre and investigator-masked study, with ocular staining at 28 days of treatment as the non-inferiority primary endpoint, and symptoms of DED as the secondary endpoint (among others).The study product was a solution of 0.24% SH, carbomers, medium chain triglycerides, glycerol and sodium hydroxide, thus expected to provide both mucomimetic properties (high concentration of SH and presence of carbomers) and enhanced stability of the tear film (thanks to the presence of triglycerides). The comparator product was a usual tear substitute containing the most frequent concentration (0.18%) of SH. Both were non-preserved products.

HH: What were the quality-of-life measures assessed in this study?

ML: The quality of life was assessed with the Ocular Surface Disease-Quality of Life (OSD-QoL^®) validated questionnaire.¹ This is a robust questionnaire that has been demonstrated as able to cover most of the aspects of life bothersome of ocular surface diseases, and more particularly DED.

HH: Were there any differences in performance between the multicomponent drop and the aqueous-based comparator which surprised you?

ML: The primary endpoint was from a change in baseline in the ocular surface fluorescein staining (OSFS) score (0–15 per the extended Oxford scheme) on day 28. According to the non-inferiority nature of the study, the analysis was made using the per-protocol population. The primary endpoint was met with groups within the non-inferiority margin of 2 grades (after 28 days, the OSFS score decreased by a mean (±SD) of 2.1 (± 1.7) from a baseline of 5.7 (± 1.2) in the SH-CB-TG group and by 1.5 (± 1.6) from a baseline of 5.8 (± 1.3) in the control group.

One noteworthy finding is that a significant difference was observed between the two groups using the OSD-QoL questionnaire that had been previously validated in several studies to explore the burden of ocular surface diseases.

HH: Restoring a functional tear film can be incredibly complex. What are the key first steps to assessing a patient’s dry eye pathology and symptoms?

ML: For the patient’s perspective, symptoms (stinging, burning, etc; ranging from discomfort to actual pain) are with no doubt the most important consequence of DED. It is thus crucial to let them describe their feelings, including how much they impact the quality of life. This not only permits to set the first step the “therapeutic alliance” between the patient and the doctor but also allows the health care professional (HCP) to evaluate the severity of the disease. Moreover, this also could uncover differential / associated diagnosis, e.g. allergies.

The second step is a precise, yet not too much-time consuming, analysis of the ocular surface which enables to estimate if there is a huge discrepancy between subjective symptoms and objective signs. Albeit considered as a very common hallmark of DED, any important discrepancy between signs and symptoms must be considered as a warning by the HCP, prompting them to search for some underlying level of neurotrophic keratopathy (much more signs than symptoms) or some participation of neuropathic pain (much more symptoms than signs), two frequent complications (or associated conditions) of severe DED.

HH: Continuing that line of thought, in a clinical setting, how should you counsel a HCP whose patient who is frustrated with dry eye treatments?

ML: This is unfortunately not a rare situation. However most of the time, there are eventually solutions for this patient. Compliance to previous prescription is important to check—some patients may be less compliant with the medications proposed by HCPs, regarding either the dosage and/or the frequency of intakes, which can impact efficacy.

Re-assessment of the medical history (including DED, but not only) may provide information that had been missed first, especially on associated conditions (e.g. allergy, previous surgery, concomitant treatment or systemic diseases). Together with underlying neurotrophic keratopathy or neuropathic pain, the level of inflammation of the ocular surface may be an explanation for a poor response to conventional tear substitutes. According to the level of inflammation and its cause (e.g. blepharitis, Sjogren disease), the anti-inflammatory treatment may be introduced and adapted.

HH: How did you approach patient selection for this study? Were there any exclusion criteria to keep in mind when assessing the outcomes?

ML: Beside very classical exclusion criteria (very low vision in at least one eye, absence of contraception in women with of childbearing potential), potential participants could not be included in case of severe blepharitis (or other eye disease), use of contact lenses or history of eye surgery or trauma in the previous 90 days, or ocular allergic disease in the past year. Patients using ocular medications or therapies other than tear substitutes could not be included as well. These exclusion criteria are inherent to most of trials on DED, since they allow to avoid confounding factors at time of efficacy and tolerance results analysis.

HH: What are the key clinical takeaways from the outcomes of this study?

ML: In terms of improvement of ocular staining, the study product is non-inferior to the control product, a well-known tear substitute already on the market. And, in terms of symptoms and quality of life, there is an advantage for this novel tear substitute that combines SH, carbomers and triglyceride in in patients with moderate to severe dry eye disease.

Reference

1. Baudouin C, Creuzot-Garcher C, Hoang-Xuan T, et al. Severe impairment of health-related quality of life in patients suffering from ocular surface diseases. J Fr Ophtalmol 2008;31(4):369-378; doi: 10.1016/s0181-1