scholarly journals High Molecular Weight Hyaluronan Promotes Corneal Nerve Growth in Severe Dry Eyes

2020 ◽  
Vol 9 (12) ◽  
pp. 3799
Author(s):  
Gysbert-Botho van Setten ◽  
Oliver Stachs ◽  
Bénédicte Dupas ◽  
Semra Akkaya Turhan ◽  
Berthold Seitz ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Laser Scanning Microscopy ◽  
Nerve Plexus ◽  
Control Group ◽  
Eye Drops ◽  
Artificial Tears ◽  
Trophic Effect ◽  
Corneal Nerves ◽  
Subbasal Nerve Plexus

The purpose of this study was to investigate the effect of high molecular weight hyaluronan (HMWHA) eye drops on subbasal corneal nerves in patients suffering from severe dry eye disease (DED) and to evaluate the damage of subbasal corneal nerves associated with severe DED. Designed as an international, multicenter study, 16 patients with symptoms of at least an Ocular Surface Disease Index (OSDI) score of 33, and corneal fluorescein staining (CFS) of at least Oxford grade 3, were included and randomized into 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 baseline visit, and after eight weeks, the subbasal nerve plexus of 16 patients were assessed by confocal laser scanning microscopy (CSLM). The images were submitted to a masked reading center for evaluation. Results showed a significant increase of total nerve fiber lengths (CNFL) in the HMWHA group (p = 0.030) when compared to the control group, where the total subbasal CNFL did not significantly change from baseline to week 8. We concluded that in severe DED patients, HMWHA from topically applied eye drops could cross the epithelial barrier and reach the subbasal nerve plexus, where it exercised a trophic effect.

scholarly journals 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

2020 ◽  
Vol 9 (11) ◽  
pp. 3536 ◽  
Author(s):  
Gysbert-Botho van Setten ◽  
Christophe Baudouin ◽  
Jutta Horwath-Winter ◽  
Daniel Böhringer ◽  
Oliver Stachs ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Dry Eye ◽  
Tear Film ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Control Group ◽  
Eye Drops ◽  
Artificial Tears ◽  
Ocular Surface Disease Index

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.

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

2019 ◽  
Vol 10 (2) ◽  
pp. 244-255 ◽  
Author(s):  
Ria Beck ◽  
Oliver Stachs ◽  
Anita Koschmieder ◽  
Wolfgang G.K. Mueller-Lierheim ◽  
Sabine Peschel ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
High Molecular Weight ◽  
Dry Eye ◽  
Autologous Serum ◽  
Control Group ◽  
Eye Drops ◽  
Very High ◽  
Serum Eye Drops ◽  
Better Than

Introduction: Autologous serum eye drops (ASED) are used in the treatment of most severe stages of dry eye. Once introduced, it is currently considered impossible to return to other lubricating eye drops or other commercially available therapeutic regimen. Materials and Methods: In a randomized study, non-preserved high-molecular-weight hyaluronic acid eye drops were offered as an alternative to 11 patients using autologous serum treatment for at least 3 months. The control group (n = 5) continued their treatment with ASED. The verum group (n = 6) used very-high-molecular-weight hyaluronic eye drops (Comfort Shield®) instead of the ASED. Results: From four of initially six patients in the verum group that finished the study, 2 (50%) preferred to stay with the very-high-molecular-weight hyaluronic acid eye drops beyond the trial period, the other two returned to the earlier therapy with ASED. The control group continued their treatment as before and finished the study after 8 weeks. Conclusion: For the first time, artificial eye drops, i.e., high-molecular-weight hyaluronic acid eye drops, offered an acceptable alternative to ASED. Some patients perceived these drops as even better than the patient’s own serum. This is the first evidence that optimization of the molecular structure of hyaluronic acid can be used to create eye drops that are perceived to be better than other tested tear substitutes and even patients’ own serum. This offers a new treatment perspective for patients with very severe dry eye disease.

scholarly journals The Effects of High Molecular Weight Hyaluronic Acid Eye Drop Application in Environmental Dry Eye Stress Model Mice

2020 ◽  
Vol 21 (10) ◽  
pp. 3516 ◽  
Author(s):  
Takashi Kojima ◽  
Taeko Nagata ◽  
Haruka Kudo ◽  
Wolfgang G. K. Müller-Lierheim ◽  
Gysbert-Botho van Setten ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
High Molecular Weight ◽  
Dry Eye ◽  
Ophthalmic Solution ◽  
Low Molecular Weight ◽  
Eye Drops ◽  
Office Work ◽  
Lissamine Green ◽  
Inflammatory Effect

Hyaluronic acid (HA) ophthalmic solution is widely used in dry eye treatment worldwide. However, there are no reports comparing the dry eye treatment effects of high molecular weight HA with low molecular weight HA. Sixty eight-week-old C57BL/6 mice were assigned to the following 6 groups and exposed to environmental dry eye stress (EDES) that mimics office work environment: (1) 0.1% low molecular weight HA (LMWHA) eye drops, (2) 0.3% LMWHA eye drops, (3) 3% diquafosol sodium (DQ) eye drops, (4) 0.15% high molecular weight HA (HMWHA) eye drops, (5) no treatment with exposure to EDES (EDES+/Treatment−), and (6) no treatment without exposure to EDES (EDES−/Treatment−). After EDES, the HMWHA group had significantly longer break-up time (BUT) than the 0.1%, 0.3% LMWHA groups and the DQ group. After EDES, the HMWHA group had significantly lower lissamine green staining scores than the LMWHA and DQ groups. Subepithelial presumed dendritic cell density in the HMWHA group was significantly lower than the EDES+/Treatment− group. After EDES exposure, Conjunctival Muc5AC mRNA expression in the HMWHA group was significantly higher than the 0.1 and 0.3% LMWHA groups. Ophthalmic HMWHA solution may have a better dry eye treatment effect than LMWHA or DQ solution, owing to its anti-inflammatory effect.

scholarly journals Assessment of Corneal subbasal nerve plexus using confocal in vivo microscopy in patients with pseudoexfoliation syndrome after phacoemulsification

2018 ◽  
Vol 11 (2) ◽  
pp. 13-18 ◽  
Author(s):  
Vitaly V. Potyomkin ◽  
Tatyana S. Varganova ◽  
Irina V. Terehova ◽  
Elena V. Ageeva
Keyword(s):  
Cataract Surgery ◽  
Main Group ◽  
Nerve Plexus ◽  
Pseudoexfoliation Syndrome ◽  
Control Group ◽  
In Vivo Microscopy ◽  
Before And After ◽  
The Impact ◽  
Subbasal Nerve Plexus

Phacoemulsification (PE) is the leading method of cataract surgery. Purpose. To assess the impact of PE on corneal subbasal nerve plexus in patients with pseudoexfoliation syndrome (PEX) using confocal in vivo microscopy. Methods. 42 patients (42 eyes) were enrolled in the study. The main group consisted of 24 patients (24 eyes) with PEX syndrome, and 18 patients (18 eyes) without it composed the control group. Confocal in vivo microscopy was performed before and after PHACO. Results. In patients with PEX after PE, an increase in number of nerve branches and pellet-like structures in them were noticed (p < 0,05).

Efficacy of Single-dose Intra-articular Injection of High-molecular-weight Hyaluronic Acid in Patients suffering from Primary Osteoarthritis of Knee

2017 ◽  
Vol 28 (3) ◽  
pp. 89-94 ◽  
Author(s):  
N Romi Singh ◽  
Jotin S Yengkhom ◽  
MS Chongreilen Chiru ◽  
Kaustav B Thakur ◽  
Utpalendu Debnath
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
Single Dose ◽  
High Molecular Weight ◽  
Control Group ◽  
Study Group ◽  
Osteoarthritis Of Knee ◽  
American College Of Rheumatology ◽  
Primary Osteoarthritis ◽  
Study Population

ABSTRACT Aim To find the effectiveness of single-dose intra-articular (IA) injection of high-molecular-weight hyaluronic acid (HMWHA) in patients suffering from primary osteoarthritis (OA) of knee. Study design A randomized control trial. Duration of the study One-and-a-half years, commencing from October 2014. Settings Physical Medicine and Rehabilitation (PMR) Department, Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, India. Study population All patients suffering from OA knee, who fulfilled the American College of Rheumatology (ACR) criteria for classification of idiopathic OA knee and attending the department during the study period. Materials and methods Sixty-five patients were randomized to receive either visco-supplementation with single-dose IA injection of HMWHA (study group) or methylprednisolone (control group) and follow-up was done at 1, 3, and 6 months. Outcome measures were done with Western Ontario and McMaster University (WOMAC) and visual analog scale (VAS) for pain. Results Both the groups showed significant improvement in both WOMAC and VAS pain score at the end of 3 months. But at the end of 6 months, improvement in terms of WOMAC (p = 0.09) and VAS pain (p = 0.07) scores in control group was not significant, whereas the study group maintained statistically significant improvement. Conclusion A single dose of IA HMWHA is effective in reducing pain and disability in patients with primary OA of knee. How to cite this article Yengkhom JS, Nongmaithem RS, Chiru MSC, Thakur KB, Debnath U. Efficacy of Single-dose Intra-articular Injection of High-molecular-weight Hyaluronic Acid in Patients suffering from Primary Osteoarthritis of Knee. Indian J Phy Med Rehab 2017;28(3):89-94.

Inhibition of tumor angiogenesis in vivo by a monoclonal antibody targeted to domain 5 of high molecular weight kininogen

Blood ◽  
2004 ◽  
Vol 104 (7) ◽  
pp. 2065-2072 ◽  
Author(s):  
James S. Song ◽  
Irma M. Sainz ◽  
Stephen C. Cosenza ◽  
Irma Isordia-Salas ◽  
Abdel Bior ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Monoclonal Antibody ◽  
Cell Growth ◽  
Tumor Cell ◽  
High Molecular Weight ◽  
Control Group ◽  
Dependent Manner ◽  
Tumor Cell Growth ◽  
High Molecular Weight Kininogen

Abstract We have shown that human high molecular weight kininogen is proangiogenic due to release of bradykinin. We now determined the ability of a murine monoclonal antibody to the light chain of high molecular weight kininogen, C11C1, to inhibit tumor growth compared to isotype-matched murine IgG. Monoclonal antibody C11C1 efficiently blocks binding of high molecular weight kininogen to endothelial cells in a concentration-dependent manner. The antibody significantly inhibited growth of human colon carcinoma cells in a nude mouse xenograft assay and was accompanied by a significant reduction in the mean microvascular density compared to the IgG control group. We also showed that a hybridoma producing monoclonal antibody C11C1 injected intramuscularly exhibited markedly smaller tumor mass in a syngeneic host compared to a hybridoma producing a monoclonal antibody to the high molecular weight kininogen heavy chain or to an unrelated plasma protein. In addition, tumor inhibition by purified monoclonal antibody C11C1 was not due to direct antitumor effect because there was no decrease of tumor cell growth in vitro in contrast to the in vivo inhibition. Our results indicate that monoclonal antibody C11C1 inhibits angiogenesis and human tumor cell growth in vivo and has therapeutic potential for treatment of human cancer. (Blood. 2004;104:2065-2072)

scholarly journals Chitosan-based biomaterials used in critical-size bone defects: radiographic study in rat's calvaria

2012 ◽  
Vol 41 (5) ◽  
pp. 312-317 ◽  
Author(s):  
Rubens Spin-Neto ◽  
Felipe Leite Coletti ◽  
Rubens Moreno de Freitas ◽  
Chaíne Pavone ◽  
Sérgio Paulo Campana-Filho ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Bone Density ◽  
High Molecular Weight ◽  
Critical Size ◽  
Bone Defects ◽  
Control Group ◽  
Low Molecular Weight ◽  
Chitosan Hydrochloride ◽  
Low Molecular Weight Chitosan ◽  
High Molecular Weight Chitosan

OBJECTIVE: This study evaluated, using digital radiographic images, the action of chitosan and chitosan hydrochloride biomaterials, with both low and high molecular weight, used in the correction of critical-size bone defects (CSBD's) in rat's calvaria. MATERIAL AND METHOD: CSBD's with 8 mm in diameter were surgically created in the calvaria of 50 Holtzman rats and these were filled with a blood clot (Control), low molecular weight chitosan, high molecular weight chitosan, low molecular weight chitosan hydrochloride and high molecular weight chitosan hydrochloride, for a total of 10 animals, which were divided into two experimental periods (15 and 60 days), for each biomaterial. The radiographic evaluation was made using two digital radiographs of the animal's skull: one taken right after the bone defect was created and the other at the moment of the sacrifice, providing the initial and the final radiographic bone density in the area of the defect, which were compared. RESULT: Analysis of radiographic bone density indicated that the increase in the radiographic bone density of the CSBD's treated with the proposed biomaterials, in either molecular weight, in both observed periods, where similar to those found in control group. CONCLUSION: Tested chitosan-based biomaterials were not able to enhance the radiographic density in the CSBD's made in rat's calvaria.

scholarly journals Effects of cross-linked high-molecular-weight hyaluronic acid on epidural fibrosis: experimental study

2015 ◽  
Vol 22 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Semra Isık ◽  
M. Özgür Taşkapılıoğlu ◽  
Fatma Oz Atalay ◽  
Seref Dogan
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
High Molecular Weight ◽  
Sham Group ◽  
Fibrous Tissue ◽  
Fibroblast Cell ◽  
Control Group ◽  
Epidural Fibrosis ◽  
Sprague Dawley ◽  
Positive Effects

OBJECT Epidural fibrosis is nonphysiological scar formation, usually at the site of neurosurgical access into the spinal canal, in the intimate vicinity of and around the origin of the radicular sheath. The formation of dense fibrous tissue causes lumbar and radicular pain. In addition to radicular symptoms, the formation of scar tissue may cause problems during reoperation. The authors aimed to investigate the effects of cross-linked high-molecular-weight hyaluronic acid (HA), an HA derivative known as HA gel, on the prevention of epidural fibrosis by using histopathological and biochemical parameters. METHODS Fifty-six adult female Sprague-Dawley rats were evaluated. The rats were divided into 4 groups. Rats in the sham group (n = 14) underwent laminectomy and discectomy and received no treatment; rats in the control group (n = 14) underwent laminectomy and discectomy and received 0.9% NaCl treatment in the surgical area; rats in the HA group (n = 14) received HA treatment at the surgical area after laminectomy and discectomy; and rats in the HA gel group (n = 14) underwent laminectomy and discectomy in addition to receiving treatment with cross-linked high-molecular-weight HA in the surgical area. All rats were decapitated after 4 weeks, and the specimens were evaluated histopathologically and biochemically. The results were statistically compared using the Mann-Whitney U-test. RESULTS Compared with the sham and control groups, the HA and HA gel groups showed significantly lower fibroblast cell density and tissue hydroxyproline concentrations (p < 0.05). There was statistically significant lower dural adhesion and foreign-body reaction between the control and HA gel groups (p < 0.05). Granulation tissue and epidural fibrosis were significantly lower in the HA and HA gel groups compared with the sham group (p < 0.05). There were no significant differences in any histopathological parameters or biochemical values between Groups 3 and 4 (p > 0.05). CONCLUSIONS Cross-linked high-molecular-weight HA had positive effects on the prevention of epidural fibrosis and the reduction of fibrotic tissue density. The efficacy of this agent should also be verified in further experimental and clinical studies.

scholarly journals “Keratrop” eye drops efficacy in dry eye syndrome treatment in diabetic patients

The Eye ◽  
2020 ◽  
Vol 22 (4(132)) ◽  
pp. 36-41
Author(s):  
F. A. Bakhritdinova ◽  
F. A. Haydarova ◽  
K. I. Narzikulova ◽  
I. F. Nabieva
Keyword(s):  
Diabetes Mellitus ◽  
Dry Eye ◽  
Tear Film ◽  
Dry Eye Syndrome ◽  
Control Group ◽  
Diabetic Patients ◽  
Eye Drops ◽  
Artificial Tears ◽  
Antidiabetic Treatment ◽  
Patients With Diabetes

Significance. Prevalence of diabetes mellitus (DM) is increasing worldwide. People with diabetes are at higher risk to dry eye syndrome (DES). The increasing dependence of society on computers, air conditioning, and visual workload, etc. results in an increase in the manifestations of DES in diabetic patients. A significant part of the socially active population with diabetes requires prescription of drugs aimed at correcting disorders associated with both hyperglycemia and dry eyes. Conservative treatment of DES in case of diabetes includes prescription of artificial tears, metabolic, immunocorrecting, hormonal, antiallergic therapies as well as treatment of meibomian gland dysfunction (MGD). The tear substitutes, however, cannot always satisfy the needs of doctors and patients due to the imperfections of their formulas. Therefore, more and more new drugs are introduced to the market that require a comprehensive assessment.Purpose. To evaluate the clinical efficacy of Keratrop eye drops – a new artificial tear formulation – in dry eye syndrome treatment in patients with diabetes mellitus (DM).Methods. The study included 65 patients (130 eyes) with dry eye syndrome stages I and II associated with mild and moderate diabetes. These were adult patients of both sexes who had not previously received artificial tears as treatment and were undergoing either inpatient or domiciliary care. All studied patients provided a written informed consent and were divided into 2 groups by random sampling. The main group (35 patients) was receiving Keratrop instillations 2 times a day during 14 days, in the course of antidiabetic treatment. Instillations of “artificial tear” were not prescribed to patients of the control group (30 patients), and they only received antidiabetic treatment prescribed by the endocrinologist. Before and after treatment, all patients underwent standard ophthalmic examinations, meibography imaging, tear film assessment and filled in OSDI questionnaires.Results. The study showed that during treatment, in patients of the experimental group – with both I and II dry eye syndrome stages – a significant decrease in subjective and objective manifestations was observed, along with an improvement in the tear film stability. In the control group, positive dynamics was observed only in patients with the first stage of dry eye syndrome.Conclusion. Dry eye syndrome treatment in patients with diabetes should be comprehensive and must include both basic antidiabetic therapy and instillation of tear substitutes.

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