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New knowledge about hyaluronic acid may help patients with severe dry eye disease

26 April 2021

High molecular weight hyaluronic eye drops 0.15 per cent, provided superior improvement of symptoms in patients with severe dry eye disease, when compared to other lubricant eye drops. This is the result of a clinical study from 2016–2020 published in the Journal of Clinical Medicine, coordinated by Ophthalmologist and Docent Gysbert van Setten at St. Erik Eye Hospital and Karolinska Institutet.

Opthalmologist Gysbert van Setten has been studying DED for 30 years.

The tear film is a thin fluid layer of water and various fats, which covers the entire surface of the eye. Dry eye disease is an increasingly common disease engaging between five to eight per cent of the population in developed countries. The basic pathology behind DED is mainly a decrease of tear film volume and/or quality, possibly even a combination of both. It can be caused by many different internal and external factors and increases with age.

Usually the early symptoms are mild, with some itching and irritation.. In cases of severe DED, patients experience symptoms of ocular burning or stinging, ocular discomfort, ocular pain, and visual instability, resulting in a considerable loss of quality of life. In severe DED, patients become totally dependent on tear film substitutes and, not seldom, have to use anti-inflammatory components.

Severe DED has a significant socio-economic effect due to considerable direct treatment costs as well as indirect costs due to a loss of work productivity.

Gysbert van Setten, Opthalmologist at St. Erik Eye Hospital and Docent at the Department of Clinical Neuroscience, Karolinska Institutet, has been studying DED for more than 30 years at different universities in the world.

"To decrease subjective discomfort, lubrication is the common treatment in all stages of the disease. But according to our most recent studies, the key target of therapy is not only to provide moisture but to reduce friction and its effect on a cellular level. Improving the ocular surface condition is a much more difficult task,” he  says.

Hyaluronic acid most efficient treatment

Amongst the agents used for medical therapy, hyaluronic acid (HA) has been shown most efficient in DED treatment. However, therapeutic efficiency varies according to concentration and molecular weight of HA used. 

"In this aspect our most recent experimental study on high molecular weight HA is of major importance as it clearly shows that the molecular weight does have a decisive role for the effects achieved, favoring the use of 0.15 per cent high molecular weight HA. These results were supported by clinical data based on a five year multinational study. Additionally we could show, for the first time, the enhancement of nerve regeneration in severe DED due to treatment with high molecular weight HA," says Gysbert van Setten.

The five year clinical study, which was both prospective, double blind and randomised, included 84 patients. Half of the patients received HA 0.15 per cent and the other half, in the control group, received their usual eye drops for eight weeks. The results showed a significant improvement in symptoms in those who received HA 0.15 per cent.

When the ocular surface dryness worsens, the external application frequency of tear film substitutes increases. This increased exposure of the surface to treatment also enhances the need for optimised treatment agents. 

"This is where available severe DED treatments clearly reach their limitations. As the last resort even the patient’s own serum, which is extracted from the patient's own blood, can be used as tear film substitute. However, even here we have shown in a case report that high molecular weight HA, for some patients, may serve as an alternative to the patient’s own serum," Gysbert van Setten says.

How to get help with dry eye disease

  • As a patient the level of your dry eye complaints is decisive. Often initial advice by pharmacists or ophthalmic care providers (opticians/general practitioners) can give you essential care guidance. 
  • If you experience more severe or accentuated complaints you should consult an ophthalmologist (eye doctor) early on. Opthalmologists are available in multiple eye clinics of your choice.
  • Whatever inital care you might have received, you should record every used treatment in order to identify suitable or non-suitable treatment lines. This therapy record will significantly facilitate the eye doctor’s choice and composition of any further treatment.

Read more about the research results

The HYLAN M Study: Efficacy of 0.15% High MolecularWeight Hyaluronan Fluid in the Treatment of Severe Dry Eye Disease in a Multicenter Randomized Trial, Gysbert-Botho van Setten, Christophe Baudouin, Jutta Horwath-Winter, Daniel Böhringer, Oliver Stachs, Ebru Toker, Sultan Al-Zaaidi, Jose M. Benitez-del-Castillo, Ria Beck, Osama Al-Sheikh, Berthold Seitz, Stefano Barabino, Herbert A. Reitsamer and Wolfgang G.K. Müller-Lierheim, Journal of Clinical Medicine, online 2 november 2020, doi: 10.3390/jcm9113536.

High Molecular Weight Hyaluronan Promotes Corneal Nerve Growth in Severe Dry Eyes, Gysbert-Botho van Setten, Oliver Stachs, Bénédicte Dupas, Semra Akkaya Turhan, Berthold Seitz, Herbert Reitsamer, KarstenWinter, Jutta Horwath-Winter, Rudolf F. Gutho and Wolfgang G.K. Müller-Lierheim, Journal of Clinical Medicine, online 5 oktober 2020, doi: 10.3390/jcm9123799. 

Hyaluronic Acid as an Alternative to Autologous Human Serum Eye Drops: Initial Clinical Results with High-Molecular-Weight Hyaluronic Acid Eye Drops, Beck R, Stachs O, Koschmieder A, Mueller-Lierheim W.G.K., Peschel S and van Setten G-B, Case Rep Ophthalmol, online 30 September 2019, doi: 10.1159/000501712.

The Effects of High Molecular Weight Hyaluronic Acid Eye Drop Application in Environmental Dry Eye Stress Model Mice, Takashi Kojima,Taeko Nagata,Haruka Kudo,Wolfgang G. K. Müller-Lierheim, Gysbert-Botho van Setten, Murat Dogru and Kazuo Tsubota, International Journal of Molecular Sciences, online 15 May 2020, doi: 10.3390/ijms21103516.