Application frequency - key indicator for the efficiency of severe dry eye disease treatment - evidence for the importance of molecular weight of hyaluronan in lubricating agents.

PURPOSE: Lubricant eye drops are the main therapeutic resource for dry eye disease (DED), with each drop representing the equivalent of ocular surface disease treatment. Thus, any reduction in the frequency of eye drop application reflects a degree of therapeutic success. Considering also the socioeconomic burden of DED, we investigated eye drop application frequency (DF) as a parameter to potentially track the success of therapy in severe DED. Hyaluronan (HA)-containing eye drops have become the first choice for tear substitution in many countries, and recent data indicate that the average molecular weight (Mw) of HA determines the therapeutic efficacy of such eye drops. This post-hoc subgroup analysis of a previously published multicentre prospective randomized open-label study, HYLAN M, is set out to compare the effects of very high Mw HA (hylan A) eye drops to comparator eye drops, containing lower Mw HA (control). METHODS: Patients with severe DED (n = 47), recruited as part of the larger HYLAN M prospective, multicentre, open-label study, were randomized into two groups: hylan A and control group. In the hylan A group, 24 patients replaced their HA-containing eye drops with eye drops containing 0.15% hylan A, whereas the 23 control patients continued to use comparator HA eye drops. The DF was recorded daily by all participants over 8 weeks, and other subjective and objective parameters of DED were assessed at the time of inclusion (baseline), as well as at week 4 and 8. RESULTS: There was a significant decrease in DF in the hylan A users between the baseline and week 4 (p = 0.004), remaining stable until week 8. Indeed, in contrast to the baseline, the hylan A group had a significantly lower DF than the control group at weeks 4 (p = 0.018) and 8 (p = 0.008). Likewise, the ocular surface disease index (OSDI) improved significantly between the time of inclusion and week 4 (p < 0.001) in hylan A users, remaining stable until week 8. The OSDI was similar in both groups at the baseline but it was significantly lower in the hylan A group than in the control group at week 4 (p = 0.002), remaining lower at week 8. Such a decrease in the DF and OSDI was not witnessed in the control group at any time point. The objective parameters assessed did not differ significantly within or between the two groups. CONCLUSION: When treating severe DED, the DF can be significantly reduced by using very high Mw HA (3 MDa) lubricant eye drops, which better alleviate DED symptoms and decrease the OSDI scores. These drops not only provide an attractive and comfortable alternative for patients with severe DED but also offer the possibility of reducing the disease's socioeconomic burden, both for affected individuals and society as a whole.

Effectiveness of 0.15% hylan A eye drops in ameliorating symptoms of severe dry eye patients in Saudi Arabia.

PURPOSE: The aim of the HYLAN A study was to investigate if symptoms and/or signs of patients suffering from severe dry eye disease (DED) in Saudi Arabia can be improved by substituting individually optimized artificial tear therapy by high molecular weight hyaluronan (HMWHA) eye drops. METHODS: The HYLAN M study, a multicenter prospective randomized open-label study, was performed in 11 centers in eight countries. Patients suffering from severe DED were electronically randomized in two parallel arms. patients with symptoms of at least ocular surface disease index (OSDI) 33 and corneal fluorescein staining (CFS) of at least Oxford grade 3 were included . The patients in the control group continued with their individual optimized therapy as by the time of inclusion. The patients in the hylan A group replaced their individual lubricant eye drops by preservative-free eye drops containing 0.15% hylan A. The total OSDI scores as well as the OSDI subscores for pain and for visual disturbances of each patient at baseline, at 4 weeks, and at 8 weeks of treatment was used to analyse the improvement of symptoms. We focus and report the results obtained at the two study centers in Riyadh ,Saudi Arabia (King Khaled Eye Specialist Hospital and Riyadh Military Hospital). RESULTS: A total of 13 patients were included in the study. The majority of the study participants were middle aged (40-65 years). Overall, female patients accounted for 76.9% of all study participants. At the initiation of the study, both hylan A and control groups had relatively similar total OSDI scores together with pain and vision subscores. At 4-week follow-up, both groups demonstrated a noticeable decrease in all study variables. Nevertheless, the OSDI scores improved significantly in the group of patients treated with hylan A eye drops at 8 weeks, whereas the scores increased in the control group. CONCLUSION: Saudi Arabia has a very high prevalence of patients with severe dry eye disease. Ethnicity, climate, and a high incidence of diabetes mellitus may contribute to this situation. Lubricant eye drops frequently do not provide adequate relief from ocular pain and instable vision in severe chronic ocular surface disease. High molecular weight hyaluronan (HMWHA) eye drops provide superior relief of symptoms of patients suffering from severe DED. This includes ocular pain as well as unstable vision.

The HYLAN M Study: Efficacy of 0.15% High Molecular Weight Hyaluronan Fluid in the Treatment of Severe Dry Eye Disease in a Multicenter Randomized Trial.

The aim of the HYLAN M study was to investigate if symptoms and/or signs of patients suffering from severe dry eye disease (DED) can be improved by substituting individually optimized artificial tear therapy by high molecular weight hyaluronan (HMWHA) eye drops. In this international, multicenter study, patients with symptoms of at least ocular surface disease index (OSDI) 33 and corneal fluorescein staining (CFS) of at least Oxford grade 3 were included. A total of 84 per-protocol patients were randomized in two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the week 8 visit, the average OSDI of the verum group had improved by 13.5 as compared to the control group (p = 0.001). The best corrected visual acuity (BCVA) had improved by 0.04 logMAR (p = 0.033). CFS, tear film break-up time (TBUT), Schirmer I, lid wiper epitheliopathy (LWE), mucocutaneous junction (Yamaguchi score), and tear osmolarity were not significantly different between the verum and control groups (p > 0.050). We conclude that for most patients with severe DED, 0.15% HMWHA eye drops provide excellent improvement of symptoms without impairment of dry eye signs.

Why Chain Length of Hyaluronan in Eye Drops Matters.

The chain length of hyaluronan (HA) determines its physical as well as its physiological properties. Results of clinical research on HA eye drops are not comparable without this parameter. In this article methods for the assessment of the average molecular weight of HA in eye drops and a terminology for molecular weight ranges are proposed. The classification of HA eye drops according to their zero shear viscosity and viscosity at 1000 s-1 shear rate is presented. Based on the gradient of mucin MUC5AC concentration within the mucoaqueous layer of the tear film a hypothesis on the consequences of this gradient on the rheological properties of the tear film is provided. The mucoadhesive properties of HA and their dependence on chain length are explained. The ability of HA to bind to receptors on the ocular epithelial cells, and in particular the potential consequences of the interaction between HA and the receptor HARE, responsible for HA endocytosis by corneal epithelial cells is discussed. The physiological function of HA in the framework of ocular surface homeostasis and wound healing are outlined, and the influence of the chain length of HA on the clinical performance of HA eye drops is illustrated. The use of very high molecular weight HA (hylan A) eye drops as drug vehicle for the next generation of ophthalmic drugs with minimized side effects is proposed and its advantages elucidated. Consequences of the diagnosis and treatment of ocular surface disease are discussed.