DOI: 10.1111/aos.16609 ISSN: 1755-375X

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

Nika Medic, Ingrid Boldin, Bujar Berisha, Bernadette Matijak‐Kronschachner, Haleh Aminfar, Gerold Schwantzer, Wolfgang G. K. Müller‐Lierheim, Gysbert‐Botho van Setten, Jutta Horwath‐Winter
  • Ophthalmology
  • General Medicine



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).


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.


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.


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.

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