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, Oliver; Koschmieder, Anita; Mueller-Lierheim, Wolfgang G.K.; Peschel, Sabine; Setten, Gysbert‐Botho van

doi:10.1159/000501712

Cited by 15 publications

(13 citation statements)

References 39 publications

(52 reference statements)

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“…37,41 Hyperosmolarity values not only of >380 mOsm/L (and up to 441 mOsm/L) but also of normal to hypoosmolarity can be found in patients with severe DE. 43,44 A temporary decrease in hyperosmolarity (as a transient ''osmocorrection'') can be achieved through the use of hypo-osmolar to iso-osmolar eye drops. 11,45 In that case, the instillation of eye drops results, by a simple dilution of the hyperosmolar tear, in a decrease in tear hyperosmolarity (toward its normalization) that lasts for a couple of minutes and is related to the (short) turnover of the aqueous phase of the tears.…”

Section: Reduced Hyperosmolarity and Its Associated Cellular Stress Wmentioning

confidence: 99%

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Cationic Emulsion-Based Artificial Tears as a Mimic of Functional Healthy Tear Film for Restoration of Ocular Surface Homeostasis in Dry Eye Disease

Daull

Amrane

Ismail

et al. 2020

Journal of Ocular Pharmacology and Therapeutics

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Dry eye disease (DED) is a complex multifactorial disease that affects an increasing number of patients worldwide. Close to 30% of the population has experienced dry eye (DE) symptoms and presented with some signs of the disease during their lifetime. The significant heterogeneity in the medical background of patients with DEs and in their sensitivity to symptoms renders a clear understanding of DED complicated. It has become evident over the past few years that DED results from an impairment of the ocular surface homeostasis. Hence, a holistic treatment approach that concomitantly addresses the different mechanisms that result in the destabilization of the tear film (TF) and the ocular surface would be appropriate. The goal of the present review is to compile the different types of scientific evidence (from in silico modeling to clinical trials) that help explain the mechanism of action of cationic emulsion (CE)-based eye drop technology for the treatment of both the signs and the symptoms of DED. These CEbased artificial tear (AT) eye drops designed to mimic, from a functional point of view, a healthy TF contribute to the restoration of a healthy ocular surface environment and TF that leads to a better management of DE patients. The CE-based AT eye drops help restore the ocular surface homeostasis in patients who have unstable TF or no tears.

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Section: Reduced Hyperosmolarity and Its Associated Cellular Stress Wmentioning

confidence: 99%

“… 37 , 41 Hyperosmolarity values not only of >380 mOsm/L (and up to 441 mOsm/L) but also of normal to hypo-osmolarity can be found in patients with severe DE. 43 , 44 …”

Section: The Cationic Emulsions For Dry Eye Managementmentioning

confidence: 99%

Cationic Emulsion-Based Artificial Tears as a Mimic of Functional Healthy Tear Film for Restoration of Ocular Surface Homeostasis in Dry Eye Disease

Daull

Amrane

Ismail

et al. 2020

Journal of Ocular Pharmacology and Therapeutics

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“…However, the preparation, storage and transport of autologous serum has its logistic, ethical and legal, as well as regulative, challenges. Therefore is the observation that autologous serum eye drops can, at least temporarily, successfully be replaced by HMW HA eye drops [126] clinically important and very promising. Serum, on the other hand, is used as a diagnostic medium as it may reflect general disease [127].…”

Section: Epithelial Lesions-the Effect Of Attritionmentioning

confidence: 99%

Impact of Attrition, Intercellular Shear in Dry Eye Disease: When Cells are Challenged and Neurons are Triggered

Setten

2020

IJMS

Self Cite

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The mechanical component in the pathophysiology of dry eye disease (DED) deserves attention as an important factor. The lubrication deficit induced impaired mechano-transduction of lid pressure to the ocular surfaces may lead to the dysregulation of homeostasis in the epithelium, with sensations of pain and secondary inflammation. Ocular pain is possibly the first sign of attrition and may occur in the absence of visible epithelial damage. Attrition is a process which involves the constant or repeated challenge of ocular surface tissues by mechanical shear forces; it is enhanced by the thinning of corneal epithelium in severe DED. As a highly dynamic process leading to pain and neurogenic inflammation, the identification of the impact of attrition and its potential pathogenic role could add a new perspective to the current more tear film-oriented models of ocular surface disease. Treatment of DED addressing lubrication deficiencies and inflammation should also consider the decrease of attrition in order to stimulate epithelial recovery and neural regeneration. The importance of hyaluronic acid, its molecular characteristics, the extracellular matrix and autoregulative mechanisms in this process is outlined. The identification of the attrition and recognition of its impact in dry eye pathophysiology could contribute to a better understanding of the disease and optimized treatment regimens.

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“…Recent clinical data on humans suggest that due to the molecular weight dependent physiological functions of hyaluronan the use of eye drops containing 0.15% hylan A is favorable in the therapy of severe OSD and in some cases may even be a substitute for autologous serum eye drops [19]. The results of a comprehensive multi-center study on the potential improvement of signs and symptoms of patients suffering from severe dry eyes by the use of 0.15% hylan A eye drops (HYLAN M study) will be published soon.…”

Section: Clinical Performance Of Hylan a Containing Eye Drops In The mentioning

confidence: 99%

“…Recently published clinical results seem to indicate that very high molecular weight hyaluronan eye drops do not only act as water binding lubricants, but may actively target the underlying pathophysiological mechanisms of ocular surface disease [19,20]. In the following the current understanding of ocular surface homeostasis will, therefore, be summarized, and the molecular weight dependent physical properties of hyaluronan eye drops be discussed, proposals for terminology of molecular weight and classification of hyaluronan eye drops will be provided, and the concept of mucoadhesion based on entanglement between hyaluronan and mucus molecules will be illuminated.…”

Section: Introductionmentioning

confidence: 99%

Why Chain Length of Hyaluronan in Eye Drops Matters

Müller-Lierheim¹

2020

Diagnostics

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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.

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Hyaluronic Acid as an Alternative to Autologous Human Serum Eye Drops: Initial Clinical Results with High-Molecular-Weight Hyaluronic Acid Eye Drops

Cited by 15 publications

References 39 publications

Cationic Emulsion-Based Artificial Tears as a Mimic of Functional Healthy Tear Film for Restoration of Ocular Surface Homeostasis in Dry Eye Disease

Cationic Emulsion-Based Artificial Tears as a Mimic of Functional Healthy Tear Film for Restoration of Ocular Surface Homeostasis in Dry Eye Disease

Impact of Attrition, Intercellular Shear in Dry Eye Disease: When Cells are Challenged and Neurons are Triggered

Why Chain Length of Hyaluronan in Eye Drops Matters

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