Article

PDF
Access to the PDF text
Service d'aide à la décision clinique
Advertising


Free Article !

Journal Français d'Ophtalmologie
Volume 35, n° 6
pages 412-419 (juin 2012)
Doi : 10.1016/j.jfo.2011.07.017
Received : 1 July 2011 ;  accepted : 19 July 2011
Efficacy of 0.18% hypotonic sodium hyaluronate ophthalmic solution in the treatment of signs and symptoms of dry eye disease
Efficacité d’une solution ophtalmique hypotonique de 0,18 % de hyaluronate de sodium pour le traitement des signes et des symptômes du syndrome de l’œil sec
 

V. Baeyens a, A. Bron b, C. Baudouin c, , d

the Vismed/Hylovis Study Group1

  Vismed/Hylovis Study Group: Dr. Jérôme Allali, Dr. Yvon Arnoux, Dr. Marc Arrata, Pr. Christophe Baudouin, Dr. Mustapha Benchaboune, Dr. Nina Besnainou, Pr. Tristan Bourcier, Pr. Anthony Bron, Pr. Frédéric Chiambaretta, Pr. Béatrice Cochener, Pr. Joseph Colin, Dr. Jean-Philippe Colliot, Pr. Catherine Creuzot-Garcher, Pr. Bernard Delbosc, Dr. Marie Delfour-Malecaze, Dr. Olivier Dussueil, Dr. Jean-Luc Febbraro, Dr. Eric Galtier, Dr. Alain-Nicolas Gilg, Dr. Brigitte Girard, Pr. A. Jonathan Jackson, Dr. Vinod Kumar, Pr. Marc Labetoulle, Pr. Laurent Laroche, Pr. Christopher Liu, Pr. François Malecaze, Dr. Evelyne Mathiot-Michel, Pr. Jonathan Moore, Pr. Paul Murphy, Dr. Philippe Partouche, Dr. Joëlle Partouche –Ferber, Pr. Pierre-Jean Pisella, Dr. Sylvia Platkiewicz, Dr. Philippe Protat, Dr. Jean-Yves Redor, Pr. Pierre-Yves Robert, Dr. Stéphane Roncin, Dr. Anne Sabadel, Dr. Florence de Saint-Etienne, Pr. Sunil Shah, Dr. Gilles Sultan, Dr. Bertrand Vabres, Dr. Marie-Claude Veschambre, Dr. Patrice Vigot, Pr. James Wollfhson.

a TRB Chemedica International SA, 12, rue Michel-Servet, P.O. Box 352 1211, Geneva 12, Switzerland 
b Oxford Eye Hospital, Headley Way, Headington, Oxford OX3 9DU, UK 
c Service d’ophtalmologie, hôpital des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France 
d Institut de la Vision, university Paris 6, 28, rue de Charenton, 75012 Paris, France 

Corresponding author.
Summary
Background/aims

To compare the safety and efficacy of hypotonic 0.18% sodium hyaluronate solution (0.18% SH) versus saline and versus 0.3% carbomer for the treatment of signs and symptoms of moderate dry eye syndrome.

Methods

A total of 304patients were randomized (1:1:1) in this parallel-group, multi-center, phase III trial. They were instructed to instill one drop of the allocated product in each eye two to four times per day over 84 days. The primary efficacy criterion was the change from baseline at Day 28 in symptom frequency score. The superiority of 0.18% SH (Vismed®) over saline and its non-inferiority versus carbomer were statistically tested.

Results

At Day 28, there was a statistically significant superiority of 0.18% SH over saline in change from baseline for subjective symptom frequency score (P =0.0376, primary endpoint) and objective fluorescein staining score (P =0.0074, secondary endpoint). 0.18% SH had an excellent safety profile over 84days. A strong trend was observed in favour of 0.18% SH to cause less blurred vision than carbomer throughout the trial (P =0.0798 at Day 28).

Conclusion

0.18% SH caused a statistically significant improvement in both a subjective endpoint (symptom frequency score) and an objective endpoint (fluorescein staining score). 0.18% SH was well tolerated and resulted in low incidence of adverse events.

The full text of this article is available in PDF format.
Résumé
Contexte/objectifs

Comparer l’efficacité et la sécurité d’une solution hypotonique de hyaluronate de sodium à 0,18 % (HS 0,18 %) par rapport à une solution saline et une solution de carbomère à 0,3 % pour le traitement des signes et des symptômes d’un syndrome d’œil sec modérément sévère.

Méthodes

Au total, 304patients ont été randomisés (1:1:1) dans cet essai en groupes parallèles, multicentrique, de phase III. Ils ont reçu l’instruction d’instiller dans chaque œil une goutte du produit attribué deux à quatre fois par jour durant 84jours. Le critère principal était le changement par rapport à la valeur basale du score de la fréquence des symptômes à j28. La supériorité du HS 0,18 % (Vismed®) sur la solution saline et sa non-infériorité par rapport au carbomère ont été testées statistiquement.

Résultats

À j28, une supériorité statistiquement significative du HS 0,18 % sur la solution saline pour le critère principal (p =0,0376) et pour le score objectif de la coloration à la fluorescéine (p =0,0074, critère secondaire) a été démontrée. Le HS 0,18 % a révélé un excellent profil de sécurité tout au long des 84jours de l’étude. Une tendance marquée en faveur du HS 0.18% qui a causé moins de vision trouble que le carbomère, s’est dessinée durant l’essai (p =0,0798 à j28).

Conclusion

Le HS 0,18 % a entraîné une amélioration statistiquement significative sur deux critères, un subjectif (score de la fréquence des symptômes) et un objectif (score de coloration à la fluorescéine). Le HS 0,18 % a été très bien toléré tout en induisant une faible incidence d’effets indésirables.

The full text of this article is available in PDF format.

Keywords : Dry eye, Artificial tears, Sodium hyaluronate, Ocular lubricants

Mots clés : Œil sec, Larmes artificielles, Hyaluronate de sodium, Lubrifiants oculaires


Introduction

According to the recent definition of the dry eye workshop (DEWS) [1], dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort [2] visual disturbance and tear film instability [3] with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film [4] and inflammation of the ocular surface [5].

The recent exploitation of polymers with novel rheological properties, such as hyaluronic acid, led to the formulation of artificial tears with beneficial effects on the relief of dry eye [6, 7, 8, 9, 10]. The most important property of SH solutions is their viscoelasticity [11]. This property allows such solutions, when instilled into the eye, to behave differently during and between blinks [12]. During blinks, shear stress causes the molecules of SH in a solution to align with one another. As a result, the solution becomes elastic and relatively non-viscous, and spreads easily over the surface of the cornea. Between blinks, the molecules of SH form a tangled meshwork, and the solution becomes less elastic and more viscous. Consequently, the precorneal tear film is stabilised and the residence time of the solution on the surface is maximised. SH is also highly effective in entrapping water. Therefore, evaporation of water from SH solutions is slow and the beneficial effects of such solutions are prolonged [13]. Finally, SH solutions adhere well to the mucins of the ocular surface, forming long-lasting coatings [14].

The patented formulation of Vismed® contains a specific fraction of SH with a high degree of purity and present at a concentration of 0.18% together with essential physiological ions. This eyedrop is free from preservative and has been formulated to be hypotonic, in order to compensate the hypertonicity of tears in patients experiencing ocular dryness [15].

The objective of the present study was to assess the efficacy and safety of 0.18% SH (Vismed®) versus saline (as a basic standard reference product) and carbomer (as a standard treatment with a marketing authorisation in most European Economic Area countries) in patients with bilateral moderate dry eye syndrome. Vismed® is also currently marketed under the brand name Hylovis® in France and is under development for the treatment of dry eye disease in the United States under the trade name Rejena®.

Materials and methods
Study design

This was a double-blind, randomized, controlled, parallel-group, 3-arms, phase III trial carried out in 45 centres in France and the UK. A total of 304 patients were randomized to receive one drop of 0.18% SH (n =106) or saline (n =101) or carbomer (n =97) in each eye two to four times per day during 84 days. The study involved five visits, namely D-16 to D-7 (recruitment, run-in medication with a saline solution), D0 (inclusion, baseline), and D28, D56 and D84 as follow-up visits (Table 1). The primary efficacy criterion was the change from baseline at D28 in symptom frequency (global score for both eyes, sum of frequency scores (0=none; 1= sometimes; 2= often; 3=constantly) of soreness, scratchiness, dryness, grittiness and burning: maximum score=15). Secondary efficacy criteria were: symptom frequency at D56 and D84, symptom intensity on a 0-100mm visual analogue scale (VAS), impact of symptoms on daily life activities, staining with lissamine green and fluorescein, Schirmer I, tear film break-up time (BUT), number of instillations and global efficacy evaluation. Comfort of the eye drops, best-corrected visual acuity (BCVA), slit lamp examination and adverse events reporting were used for safety evaluation. The final protocol was approved by the following independent ethics committees: the Comités de Protection des Personnes in France and by the South East Research Ethics Committee in UK. The present clinical trial was registered in the EudraCT database (European Union Drug Regulating Authorities Clinical Trials) under the number 2007-001708-19. The study was consistent with international conference on harmonization of technical requirements for registration of pharmaceuticals for human use (ICH), good clinical practice (GCP) and the applicable regulatory requirements including the Declaration of Helsinki.

Study materials

Solutions of 0.18% SH and saline were supplied in heat-sealed monodoses containing 0.3mL of sterile, clear and colourless solution (150 mOsm/L). A commercially carbomer product (Lacryvisc®, Laboratoires Alcon, France) was used in its original monodoses, corresponding to 0.5g of sterile, clear and colourless solution. Lacryvisc® contains 0.3% (3mg/g) carbomer.

In this study, given that a commercially available presentation of carbomer with different shape of ampoule compared to 0.18% SH and saline was used as a comparator, carbomer was repackaged under the cGMP requirements. Each monodose was relabelled in order to keep the patient blinded to the treatment received. Four strips of five monodoses were packed in a sealed laminated aluminum foil sachet similar to 0.18% SH and saline.

Study population

Male and female patients aged between 18 and 80 years, with at least a 3-month history of dry eye and two symptoms among soreness, scratchiness, dryness, grittiness and burning occurring at least often, were enrolled in the study. Furthermore, three of the four following objective criteria were to be fulfilled at inclusion: Schirmer test of less than 10mm wetting/5min, BUT of less than 10seconds, total scores of corneal staining with fluorescein of at least 3/7 and lissamine of at least 3/12 [16].

Main exclusion criteria were severe dry eye, refractive surgery within the last 12 months or any other ocular surgery or trauma within the last 6 months prior to study inclusion.

Statistics

Statistical analysis was performed on both eyes for symptom intensity (0-100mm VAS) and frequency, impact of symptoms on daily life activities and on the target eye for the other objective parameters. The target eye was defined as the most severely affected eye as assessed by Schirmer I test at baseline. In case there was no difference in the two eyes for that parameter, the right eye was chosen, by default, as the target eye. Clinical objectives were to test the superiority of 0.18% SH over saline and, when superiority was demonstrated, to test the non-inferiority of 0.18% SH relatively to carbomer.

The determination of the sample size was based on two previous studies comparing saline and 0.18% SH (unpublished study ) and carbomer [17]. The following hypotheses were made: decreases in symptom frequency equal to 2.9, 1.8 and 2.7 in the 0.18% SH, saline and carbomer group, respectively, and equal standard deviations in all groups, i.e. 2.2. Since the testing procedure is a two-step one, the level for significance was equal to 0.05 for each of the step. For the superiority test, a one-sided (0.18% SH versus saline) alpha level equal to 0.05 and a power equal to 90% were set, leading to 70 patients per group. For the non-inferiority test (0.18% SH versus carbomer) a one-sided alpha level equal to 0.05, a power of 90%, a non-inferiority level equal to 0.8, and a decrease 0.2 higher in the 0.18% SH group than in the carbomer one were set, leading to 84 patients per group. The size of each group was therefore set to 100 patients, in order to take into account patients with no efficacy data after inclusion and to have enough patients for a per protocol analysis. The analysis was performed using SAS statistical software.

The following datasets were defined: The intent-to-treat (ITT) data set was defined as patients who had at least one administration of the allocated product and a value at baseline for the parameter of the primary endpoint. The full analysis set (FAS) was defined as patients who had at least one administration of the allocated product and a non-missing value for the primary criterion at baseline and at least one time after instillation. The per-protocol (PP) dataset included all patients of the FAS data set without major deviation of the protocol.

After acquisition of baseline data, in the case of missing values, the last observation carried forward (LOCF) method was applied using at each visit the last observation available for analysis on FAS and with LOCF baseline value included for analysis on ITT population.

Results
Patient disposition

Among the 304 patients included and randomized, 303 received at least one administration of any product (safety population) and 30 were prematurely discontinued mainly for “lack of efficacy”. Reasons for premature discontinuation were evenly distributed between the treatment groups (data not shown). The ITT, FAS, and PP data sets consisted of 303, 287 and 280 patients, respectively.

Demographic data

There were no statistically significant differences between the three groups for demographic and baseline characteristics (data not shown). Patients were predominantly female (85.4%) and had a mean (±SD) age of 59.3 (15.0) years (min: 20; max: 90; median: 61 years). The two forms of dry eye reported in this study, Sjögren’s syndrome or age-related dry eye, were evenly distributed across the three treatment groups. 65.5% of the patients reported non-ophthalmic histories, mainly vascular and connective tissue disorders.

Primary efficacy endpoint

At D28, there was a statistically significant superiority of 0.18% SH over saline, for change from baseline for the symptom frequency score in the FAS population (p =0.0376) (Figure 1), the ITT population (p =0.0361) and the PP population (p =0.0462) (Table 2). Non inferiority of 0.18% SH versus carbomer was demonstrated in the FAS population at 0.8 points, the non-inferiority level (–0.8) being outside the 95% confidence interval [0.00, ∞[at D28. This non-inferiority was also demonstrated for the ITT and the PP populations at D28.



Figure 1


Figure 1. 

Difference from baseline at D28 in symptom frequency summed scores, for soreness, dryness, scratchiness, itchiness and burning (each rated on a 0 to 3 scale, maximum total score 15).

Zoom

Secondary efficacy endpoints

Results for the secondary efficacy endpoints are summarized in Table 3 and Figure 2. For symptom frequency, a statistically significant superiority of 0.18% SH over saline was shown at D56 (P =0.0499). Since –0.8 points was outside the 95% confidence interval [0.00, ∞[, the non-inferiority of 0.18% SH relatively to carbomer could be demonstrated. In addition, results for objective corneal staining with fluorescein showed a statistically significant superiority of 0.18% SH versus saline at D28 (P =0.0074) and D56 (P =0.0360). The study product 0.18% SH caused a greater increase in mean values of tear film BUT compared with both saline and carbomer, at all the visits, which was statistically significant (0.18% SH versus saline, p =0.039) at D56. Interestingly, the average number of instillations throughout the study was lower in the 0.18% SH group and the difference compared with saline was statistically significant at D84 (P =0.0355). A strong trend in favour of 0.18% SH to cause a larger decrease in values of lissamine green staining (compared to saline) and Schirmer I test (compared to saline and to carbomer) was also shown. There was a decrease of symptom intensity and their impact on daily life activities in the three groups at each time point, but no statistical superiority of 0.18% SH over saline was observed.



Figure 2


Figure 2. 

Efficacy evaluation by the patient and the investigator, reported at the end of each follow-up visit (D28, D56 and D84).

Zoom

The ratio of patients judging their assigned product as “very effective” was higher in the 0.18% SH group (23.2%, 31.0% and 34.0% at D28, D56 and D84, respectively) compared with the saline (16.7%, 15.6% and 27.1% at D28, D56 and D84, respectively) and carbomer groups (16.5%, 28.6% and 27.5% at D28, D56 and D84, respectively) for the FAS population (Figure 2): there was a statistically significant difference favouring 0.18% SH vs. saline at D28 (P [Mantel-Haenszel]=0.0376) and D56 (P [Mantel-Haenszel]=0.0260. Results for the investigator’s evaluation were in concordance with patient’s evaluation, with a statistically significant difference (P [Mantel-Haenszel]=0.0164) in favour of 0.18% SH vs. saline at D56 in the FAS population.

Safety criteria

Among the 12 AEs reported, five were related to eye disorders and seven to general disorders and administration site conditions and four of them were reported as serious. All SAEs were considered unexpected and unrelated to the study product. The analysis of adverse events did not show a difference between the three groups.

Slit lamp examination and BCVA did not show any statistically significant differences in change from baseline, between the three groups, for the safety population. Regarding the comfort of eye drops, saline appeared to caused less blurred vision at D28, D56 and D84 (17.5%, 18.3 and 15.4%, respectively) than 0.18% SH (48.0%, 46.9% and 50.0%, respectively) and carbomer groups (59.1%, 48.6% and 55.2%, respectively). A strong trend was drawn in favour of 0.18% SH to cause less blurred vision than carbomer at D28 (P [Fisher]=0.0798), D56 (P [Fisher]=0.0747) and D84 (P [Fisher]=0.2922).

Discussion

The present study showed that 0.18% SH alleviated both objective signs and subjective symptoms of dry eye. The superiority of 0.18% SH over saline and its non-inferiority compared to carbomer was statistically significant for the primary efficacy endpoint (symptom frequency at D28) and for the following secondary efficacy criteria: symptom frequency at D56, fluorescein staining and Schirmer I.

The satisfactory results obtained for the objective efficacy criteria are the expression of a non-negligible impact of 0.18% SH on dry eye physiopathology. More particularly, fluorescein staining data, significantly in favour of 0.18% SH, indicated its beneficial effect on the integrity of the ocular surface. The average number of instillations per day was significantly lower with 0.18% SH compared with carbomer and saline over the 3-month treatment period. This difference, close to 10% between 0.18% SH and saline, represents an improvement in comfort and compliance for the patient.

Since no standard placebo has been established for use in clinical trials of dry eye [18], we chose to use 0.9% sodium chloride solution (saline) as the basic reference product. Comparison with saline has proven to be a significant challenge for many candidates for the treatment of both signs and symptoms of dry eye disease [10]. In this trial, even though a strong apparent response to treatment with saline was observed, probably reflecting in part, a placebo effect, a statistically significant superiority of 0.18% SH over saline in both signs and symptoms of dry eye was established.

Each of the products tested caused the relief of ocular dryness. The product comparison showed more discrepancies at short term (D28, P [Wilcoxon rank sum test]=0.0376) than at long term where the difference was less significant (D84, P [Wilcoxon rank sum test]=0.4587). One should hypothesize that more serious is the dry eye, the more field of action each product will have. This could explain why the product efficacy comparison appeared more relevant at D28 than at D84. In that light, treatment with 0.18% SH appeared as the most efficient in terms of rapidity of onset. Another explanation would be that saline response may be due to improved compliance in patients using a prescribed product in a clinical trial [18].

Several prospective, randomized, controlled clinical studies compared 0.18% SH with other ocular products [17, 19, 20, 21]. In these studies, 0.18% SH was well tolerated and caused an improvement in objective signs and/or subjective symptoms of dry eye.

Results from a single-drop, pharmacodynamic study showed that SH solutions increased tear film stability and uniformity and decreased tear film osmolarity [20]. A study published by Vogel [21], in 444 patients also reported a statistically significant decrease in both subjective frequency of symptoms and objective sign of lissamine green staining with 0.18% SH compared to its vehicle, which supports our findings [10, 16]. Results for the comparison of 0.18% SH and carbomer are in concordance with the study of Johnson et al. [22], where 0.18% SH was slightly superior to carbomer in acheiving an improvement in the integrity of corneal and conjunctival epithelium. The authors also found that 0.18% SH had less propensity to cause visual disturbance upon instillation.

Conclusion

In conclusion, 0.18% SH (Vismed®) was significantly more efficient than saline in reducing symptom frequency as well as objective signs of dry eye. In addition, the present study highlighted the better comfort of 0.18% SH relative to carbomer, as well as a lower number of instillations required. In many clinical trials of dry eye, the responses of subjective symptoms and objective signs to therapy do not always correlate. In the present trial, however, success was achieved in both the subjective frequency of symptoms and the objective sign of staining with fluorescein, which appears to offer a clinical advantage for the drop. The overall results for each of the measures used to assess safety indicate that 0.18% SH had an excellent safety profile over 84 days, with a good tolerance, resulting in low incidence of adverse events.

Disclosure of interests

Pr. Christophe Baudouin and Pr Anthony Bron declare that they have no conflict of interest concerning this article.

Dr. Vincent Baeyens: My current employer as of 1 March 2012 is: Santen GmbH, Industriestrasse 1, D-82110 Germering. My current title is: Director and Head of Clinical Operations, Europe, GCD&MA.


Acknowledgements

The authors thank Jean-Claude Peyrieux for statistical advice and Dr. Marie Gaumet, PhD for medical writing.

References

The Definition and Classification of Dry Eye Disease. Report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (DEWS). The ocular surface 2007;5:75–92.
Begley C.G., Chalmers R.L., Abetz L., Venkataraman K., Mertzanis P., Caffery B., and al. The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity Invest Ophthalmol Vis Sci 2003 ;  44 : 4753-4761 [cross-ref]
Goto E., Yagi Y., Matsumoto Y., Tsubota K. Impaired functional visual acuity of dry eye patients Am J Ophthalmol 2002 ;  133 : 181-186 [inter-ref]
Tomlinson A., Khanal S., Ramaesh K., Diaper C., McFadyen A. Tear film osmolarity: determination of a referent for dry eye diagnosis Invest Ophthalmol Vis Sci 2006 ;  47 : 4309-4315 [cross-ref]
Pflugfelder S.C., Jones D., Ji Z., Afonso A., Monroy D. Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjogren’s syndrome keratoconjunctivitis sicca Curr Eye Res 1999 ;  19 : 201-211 [cross-ref]
Mazzacane D., Braggio F. Randomized controlled trial of high-molecular-weight hyaluronic acid in dry eye syndromes Ann Ottalmol Clin Ocul 1993 ;  119 : 1-15
Taiti L., Scrivanti M., Mencucci R., Bardi L., Salvi G. A double-masked crossover comparison of a new artificial tear preparation containing hyaluronic acid (L02A) and a reference artificial tear preparation containing hydroxypropyl-methylcellulose in dry-eye syndrome treatment Ann Ottalmol Clin Ocul 1996 ;  119 : 33-46
Milazzo G., Papa V., Pasquale A., Russo S., Di Bella A. Efficacy of sodium hyaluronate eye drops of different osmolarities in the symptomatic treatment of dry eye patients Adv Exp Med Biol 2002 ;  506 : 1233-1235 [cross-ref]
Aragona P., Papa V., Micali A., Santocono M., Milazzo G. Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye Br J Ophthalmol 2002 ;  86 : 181-184 [cross-ref]
Baeyens V, Baudouin C, Dorsey F, the French Vismed Study Group. Efficacy and safety of sodium hyaluronate 0.18% vs. sodium chloride 0.9% in patients with bilateral moderate dry eye. Poster presented at the Association for Research in Vision and Ophthalmology (ARVO) meeting, Fort Lauderdale, FL, USA, April 25–29, 2004.
Abelson M.B., Nally L., Ousler G.W. Dry eye, today and tomorrow Rev Ophthalmol 2000 ;  VII : 132-134
Tiffany J.M. Viscoelastic properties of human tears and polymer solutions Adv Exp Med Biol 1994 ;  350 : 267-270 [cross-ref]
Nakamura M., Hikida M., Nakano T., Hamano T., Kinoshita S. Characterization of water retentive properties of hyaluronan Cornea 1993 ;  12 : 433-436 [cross-ref]
Saettone M.F., Chetoni P., Torracca M.T., Burgalassi S., Giannacini B. Evaluation of mucoadhesive properties and in vivo activity of ophthalmic vehicles based on hyaluronic acid Int J Pharm 1989 ;  51 : 203-212 [cross-ref]
Gilbard J.P., Carter J.B., Sang D.N., Refojo M.F., Hanninen L.A., Kenyon K.R., and al. Morphologic effect of hyperosmolarity on rabbit corneal epithelium Ophthalmology 1984 ;  91 : 1205-1212
Bron A.J., Evans V.E., Smith J.A. Granding of corneal and conjunctival staining in the context of other dry eye tests Cornea 2003 ;  22 : 640-650 [cross-ref]
Zeher M, Bereczki A, Sohajda Z, et al. A 1-month study of efficacy and safety of 0.18 per cent sodium hyaluronate (Vismed) vs. 0.3 per cent carbomer and 0.9 per cent saline in patients with bilateral moderate dry eye syndrome. Poster presented at the 7th International Symposium on Ocular Pharmacology and Therapeutics (ISOPT), Budapest, Hungary, February 28–March 2, 2008.
Foulks G.N. Challenges and pitfalls in clinical trials of treatments for dry eye Ocul Surf 2003 ;  1 : 20-30 [cross-ref]
Brignole F., Pisella P.J., Dupas B., Baeyens V., Baudouin C. Efficacy and safety of 0.18% sodium hyaluronate in patients with moderate dry eye syndrome and superficial keratitis Graefes Arch Clin Exp Ophthalmol 2005 ;  243 : 531-538 [cross-ref]
Montes-Mico R., Caliz A., Alio J.L. Changes in ocular aberrations after instillation of artificial tears in dry-eye patients J Cataract Refract Surg 2004 ;  30 : 1649-1652 [cross-ref]
Vogel R., Crockett R.S., Oden N., Laliberte T.W., Molina L. Demonstration of efficacy in the treatment of dry eye disease with 0.18% sodium hyaluronate ophthalmic solution (Vismed, Rejena) Am J Ophthalmol 2010 ;  149 : 594-601 [cross-ref]
Johnson M.E., Murphy P.J., Boulton M. Carbomer and sodium hyaluronate eyedrops for moderate dry eye treatment Optom Vis Sci 2008 ;  85 : 750-757 [cross-ref]

1  Vismed/Hylovis Study Group: Dr. Jérôme Allali, Dr. Yvon Arnoux, Dr. Marc Arrata, Pr. Christophe Baudouin, Dr. Mustapha Benchaboune, Dr. Nina Besnainou, Pr. Tristan Bourcier, Pr. Anthony Bron, Pr. Frédéric Chiambaretta, Pr. Béatrice Cochener, Pr. Joseph Colin, Dr. Jean-Philippe Colliot, Pr. Catherine Creuzot-Garcher, Pr. Bernard Delbosc, Dr. Marie Delfour-Malecaze, Dr. Olivier Dussueil, Dr. Jean-Luc Febbraro, Dr. Eric Galtier, Dr. Alain-Nicolas Gilg, Dr. Brigitte Girard, Pr. A. Jonathan Jackson, Dr. Vinod Kumar, Pr. Marc Labetoulle, Pr. Laurent Laroche, Pr. Christopher Liu, Pr. François Malecaze, Dr. Evelyne Mathiot-Michel, Pr. Jonathan Moore, Pr. Paul Murphy, Dr. Philippe Partouche, Dr. Joëlle Partouche –Ferber, Pr. Pierre-Jean Pisella, Dr. Sylvia Platkiewicz, Dr. Philippe Protat, Dr. Jean-Yves Redor, Pr. Pierre-Yves Robert, Dr. Stéphane Roncin, Dr. Anne Sabadel, Dr. Florence de Saint-Etienne, Pr. Sunil Shah, Dr. Gilles Sultan, Dr. Bertrand Vabres, Dr. Marie-Claude Veschambre, Dr. Patrice Vigot, Pr. James Wollfhson.


© 2012  Elsevier Masson SAS. All Rights Reserved.
EM-CONSULTE.COM is registrered at the CNIL, déclaration n° 1286925.
As per the Law relating to information storage and personal integrity, you have the right to oppose (art 26 of that law), access (art 34 of that law) and rectify (art 36 of that law) your personal data. You may thus request that your data, should it be inaccurate, incomplete, unclear, outdated, not be used or stored, be corrected, clarified, updated or deleted.
Personal information regarding our website's visitors, including their identity, is confidential.
The owners of this website hereby guarantee to respect the legal confidentiality conditions, applicable in France, and not to disclose this data to third parties.
Close
Article Outline