text:
Q: Parameter username of loadUserByUsername in custom UserDetailsService is always empty I am working on a form based login using spring-security with a customized UserDetailsService. The login form seems to be submitted correctly. While debugging the application I found out that the submitted request arrived at the attemptAuthentication method of the UsernamePasswordAuthenticationFilter. But it looks like the the request parameter cannot be mapped to the username and password field because they remain empty. Therefore also the parameter username of the loadByUsername method of my custom UserDetailsService remains empty and I am not able to successfully login.
I have tried a lot, but for now I have no clue what the problem could be. I am also quite new to spring-security, but I suppose I am not too far away.
I summarized the code as much as possible. If you need more information please let me now.
First I set up the springSecurityFilterChain in web.xml:
<welcome-file-list>
    <welcome-file>index.xhtml</welcome-file>
</welcome-file-list>

<context-param>
    <param-name>contextConfigLocation</param-name>
    <param-value>
        classpath:WEB-INF/applicationContext.xml,
        classpath:WEB-INF/applicationContext-security.xml
    </param-value>
</context-param>

<context-param>
    <param-name>log4jConfigLocation</param-name>
    <param-value>classpath:log4j.properties</param-value>
</context-param>

<!-- Filter Config -->
<filter>
    <filter-name>springSecurityFilterChain</filter-name>
    <filter-class>org.springframework.web.filter.DelegatingFilterProxy</filter-class>
</filter>

<!-- Filter Mappings -->
<filter-mapping>
    <filter-name>springSecurityFilterChain</filter-name>
    <url-pattern>/*</url-pattern>
    <dispatcher>FORWARD</dispatcher>
    <dispatcher>REQUEST</dispatcher>
</filter-mapping>

<!-- Spring Configuration -->
<listener>
    <listener-class>
        org.springframework.web.context.ContextLoaderListener
    </listener-class>
</listener>
<listener>
    <listener-class>
        org.springframework.web.context.request.RequestContextListener
    </listener-class>
</listener>

That is my applicationContext.xml with the reference to customUserDetailsService:
<bean id="propertyConfigurer"
      class="org.springframework.beans.factory.config.PropertyPlaceholderConfigurer">
    ...
</bean>

<bean id="dataSource"
      class="org.springframework.jdbc.datasource.DriverManagerDataSource">
    ...
</bean>

<bean id="entityManagerFactory"
      class="org.springframework.orm.jpa.LocalContainerEntityManagerFactoryBean">
    ...
</bean>

<!-- Authentification -->
<bean id="customUserDetailsService" class="com.seraphim.security.auth.CustomUserDetailsService"/>

<!-- Transaction -->
<bean id="transactionManager" class="org.springframework.orm.jpa.JpaTransactionManager"/>

<context:component-scan base-package="com.seraphim"/>

<context:annotation-config/>

<tx:annotation-driven transaction-manager="transactionManager"/>

The applicationContext-security.xml with the appropriate authentication-provider:
<http
    auto-config="true"
    access-denied-page="/accessDenied.jsp">

    <intercept-url
            pattern="/pages/**"
            access="ROLE_ADMIN,ROLE_USER"/>
    <intercept-url
            pattern="/**"
            access="IS_AUTHENTICATED_ANONYMOUSLY"/>

    <form-login
            login-processing-url="/j_spring_security_check"
            login-page="/index.xhtml"
            default-target-url="/pages/main.xhtml"
            authentication-failure-url="/index.xhtml"/>

    <logout
            logout-url="/logout*"
            logout-success-url="/"/>

</http>

<authentication-manager>
    <authentication-provider user-service-ref="customUserDetailsService">
        <password-encoder hash="md5"/>
    </authentication-provider>
</authentication-manager>

In faces-config.xml I have added a LoginErrorPhaseListener to detect BadCredentialsException and added the LoginBean:
<lifecycle>
    <phase-listener>com.seraphim.security.auth.LoginErrorPhaseListener</phase-listener>
</lifecycle>

<managed-bean>
    <managed-bean-name>loginBean</managed-bean-name>
    <managed-bean-class>
        com.seraphim.bean.LoginBean
    </managed-bean-class>
    <managed-bean-scope>
        request
    </managed-bean-scope>
</managed-bean>

index.xhtml is has username an password field an is submitted to the loginBean:
<h:form id="loginForm">

    <h:outputLabel for="j_username" value="User:"/>
    <p:inputText id='j_username' label="user" required="true"/>

    <h:outputLabel for="j_password" value="Password:"/>

    <h:inputSecret id='j_password' label="pass2" required="true"/>

    <h:outputLabel for="_spring_security_remember_me" value="Remember "/>
    <p:selectBooleanCheckbox id='_spring_security_remember_me'/>

    <h:outputLabel/>
    <h:commandButton type="submit" id="login" action="#{loginBean.doLogin}" value="Login"/>

</h:form>

LoginBean.java
@Component
@Scope("request")
public class LoginBean {

  public String doLogin() throws IOException, ServletException {

    ExternalContext context = FacesContext.getCurrentInstance().getExternalContext();

    RequestDispatcher dispatcher = ((ServletRequest) context.getRequest())
            .getRequestDispatcher("/j_spring_security_check");

    dispatcher.forward((ServletRequest) context.getRequest(), (ServletResponse) context.getResponse());

    FacesContext.getCurrentInstance().responseComplete();

    // It's OK to return null here because Faces is just going to exit.
    return null;

  }
}

Now in CustomUserDetailsService.java the correct user should be loaded, but here the method parameter username is always empty (not null). And therefore of course no valid user is found:
public class CustomUserDetailsService implements UserDetailsService {

@Resource
IUserDao userDao;

@Override
public UserDetails loadUserByUsername(String username) throws UsernameNotFoundException {

    User user = userDao.findByUsername(username);

    if (user == null) {
        throw new UsernameNotFoundException("user not found");
    }

    // build roles for user
    Collection<GrantedAuthority> authorities = new ArrayList<GrantedAuthority>();
    authorities.add(new GrantedAuthorityImpl("ROLE_USER"));
    if(user.isAdmin()) {
        authorities.add(new GrantedAuthorityImpl("ROLE_ADMIN"));
    }

    return new org.springframework.security.core.userdetails.User(
            user.getUsername(),
            user.getPassword(),
            user.isEnabled(),
            user.isAccountNonExpired(),
            user.isCredentialsNonExpired(),
            user.isAccountNonLocked(),
            authorities);
}

}

Hope you can help me on this one.

A: If you integrate Spring Security with JSF this way you need to set prependId = "false" in your form, otherwise field names required by Spring Security will be prepended with form id:
<h:form id="loginForm" prependId = "false">...</h:form>


To what extent are citizens of Israel currently afraid of being hurt in street violence? A clear majority—60% of the Jewish respondents and 62% of the Arab respondents—are currently afraid of being harmed by street violence.
And how well are the police coping with the street violence? A large majority rate the performance of the police as "inadequate" or "barely adequate" in this area: 61% of the Jews and 58% of the Arabs.
Should an open-door policy be adopted toward refugees who were persecuted in their countries of origin? Eighty percent of the Jews and 70% of the Arabs oppose adopting such a policy toward refugees.
And what about an "open door" for job seekers who are not refugees? Here too the opponents have a majority, though smaller: 71% of the Jews and 61% of the Arabs.
Are there refugees and migrant workers where you live? In light of the troubling findings above, we checked whether the respondents are experiencing a high level of daily friction with foreigners. The findings are surprising: 79.5% of the Jewish respondents, and about the same rate of Arab respondents, said that where they live there are only a few, very few, or no refugees/ migrant workers at all!
To what extent is the government to blame? Among the Jews, 59% think the government is fully to blame and another 34.5% think that it is partially to blame. Among the Arabs, only 27% assign full blame to the government and 43% lay partial blame on it.
Are all the foreign workers undesirable? Here we found huge gaps in the positions of the Jewish respondents: there is a majority that is moderately not disturbed or not disturbed at all, by the presence of workers from South America (51%), Eastern Europe (59%), Thailand (53%), and the Philippines (61%). However, a majority is disturbed by the presence of foreigners from African countries such as Ghana or Nigeria (62%), Sudan or Eritrea (73%), and by Palestinian workers (73%). No gaps turned up among the Arab respondents: regarding each of the aforementioned groups, there was a majority of 70%–90% who were moderately not disturbed or not disturbed at all, by the presence of the workers.
What is the support level for the demonstrations by south Tel Aviv residents against the presence of the Africans? An overwhelming majority of the Jews— 83%—expressed support for the demonstrations. Among the Arabs, the support stood at only 25%.
And what about identification with the violence that south Tel Aviv residents perpetrated against the Africans? Some 33.5% of Jewish respondents said they could identify with the use of violence (62% could not). As for the Arabs, 23% could identify with it (65.5% could not).
How justified is Police Chief Danino's proposal to give the Africans work permits? Fifty-five percent of the Jewish respondents think his proposal is not justified; 70% of the Arabs think the same.
Are Unauthorized Africans a "Cancer" in the State of Israel?
This month's survey focused on two issues: the public's attitude toward the foreigners now living in Israel, in the wake of the recent demonstrations and other dramatic events surrounding their presence in the country, and the presidential elections in Egypt.
First, the foreigners in Israel: Whether because of the recent events or the public's sense of a general increase of violence in the streets, the Israeli public reports a very low feeling of personal security. A clear majority—60% of the Jewish respondents and 62% of the Arab respondents—currently fear being harmed by street violence. We segmented the Jewish sample according to several categories and found that, not surprisingly, the fear of being hurt by violence is stronger among women than men (69% vs. 50%) and among older people than younger people (73% of those 55 and older vs. 60% of those aged 18–30).
We gauged the extent to which the fear of violence is linked to living near foreigners. Here the first finding is that a majority of the respondents do not live in an environment where there are significant numbers of foreigners at all. We asked: "Are there refugees and migrant workers where you live?" Some 79.5% of the Jewish respondents, and about the same rate of Arab respondents, said that where they live there are only a few, very few, or no refugees/ migrant workers at all! Therefore, for the Jewish sample, we carried out a cross-section between those living or not living near foreigners, on the one hand, and the fear of street violence, on the other. The findings reveal a connection, albeit not a strong one: among respondents living in areas with many foreigners, 64% reported a high fear of violence, but so did 60% of those living in areas without foreigners nearby. This raises doubt about the often-heard claim that it is direct exposure or vulnerability that accounts for negative positions and feelings toward the presence of foreigners, with all the implications of such positions and feelings.
The high fear of street violence is accompanied by a low evaluation of the police's effectiveness in preventing it. A clear-cut majority rates the performance of the police in this area as "inadequate" or "barely adequate": 61% of the Jews and 58% of the Arabs. In the Jewish sample we found no significant difference between men and women in this context. Some difference was found based on age, with younger people seeing the effectiveness of the police in dealing with street violence as worse than it is seen by older people. A segmentation by self-definition of degree of religiosity reveals that more Haredim and religious respondents assess the work of the police negatively (62% and 59% respectively) than do traditional and secular people (44% and 53% respectively).
Along with the widespread low rating of the ability of the police to prevent crime, the public perceives the government as culpable for creating the problem of foreigners. Fifty-nine percent of the Jews say the government is fully to blame and another 34.5% say that it is partially to blame (a total of 93.5%). As for the Arabs, only 27% assign full blame to the government, while 43% lay partial blame on it (a total of 70%). A segmentation of the responses of the Jewish sample regarding the extent of the government's responsibility by the respondent's voting in the Knesset elections shows that, anomalously, voters for Meretz and Shas are close to each other in the high level of blame they attribute to the government compared to voters for the rest of the parties.
What policy does the public want to see on the issue of the foreigners? Eighty percent of the Jews and 70% of the Arabs oppose adopting an open-door policy toward refugees. And what about an open-door policy for job seekers who are not refugees? Here too the opponents have a majority, though smaller: 71% of the Jews and 61% of the Arabs. According to the data we have, it is hard to determine clearly why the opposition to opening the door to refugees is higher than for opening it to job seekers. Possibly the latter are perceived as people who at some point will return to their countries, or are seen as a smaller threat because they are looking for work, and perhaps they are regarded by the Israeli public as more "decent" people. But, as stated above, our data do not enable us to assign cause and effect.
A segmentation of the Jewish sample by Knesset voting shows that only among Meretz voters does a majority (70%) favor an open-door policy for refugees. A segmentation by the respondents' self-definition of degree of religiosity reveals an overwhelming majority in all the groups that opposes an open door for refugees. There is, though, a significant disparity between groups: whereas only 2% of Haredim favor an open door policy, about one-fourth of the secular do. The religious and the traditional are located in the middle on this issue. As for job seekers, even among Meretz voters, a majority opposes an open door. The pattern of disparities by religiosity is similar to that found for refugees. A segmentation of the attitudes toward an open-door policy for refugees and for job seekers by degree of personal fear of street violence turned up no significant difference between those who are afraid and those who are not. Not surprisingly, though, we found certain gaps regarding this question between respondents living in areas where there are numerous foreigners, and respondents living where there are almost no foreigners or none at all. Although in both groups the opponents of an open door clearly exceed those favoring such a policy, those living in areas of the first kind are more dead-set against an open policy than those living in areas where few foreigners or none at all reside.
We looked into how much the public identifies or does not identify with the statement by Member of Knesset Miri Regev that the Africans living illegally in Israel are a cancer in the body of the country. It turned out that more than half (52%) of the Jews endorse this statement, while only 19% of the Arab respondents agreed with it. A segmentation of the responses of the Jewish respondents by Knesset voting reveals huge disparities: 86% of Shas voters agreed with the characterization of the unauthorized Africans in the country as a cancer, as did 73% of Yisrael Beiteinu and 71% of National Union voters. Just behind these were 69% of Jewish Home voters and 66% of Likud voters. Only 35% of Labor, 32% of Kadima, and 4% of Meretz voters, however, identified with the statement. Self-definition of level of religiosity also yields huge disparities: 81.5% of the Haredim, 66% of the religious, 58% of the traditional, and 38% of the secular agreed with the assertion.
How much support is there for the demonstrations against the presence of Africans by residents of south Tel Aviv? Here we practically found a "national consensus": an overwhelming majority of 83% of the Jews expressed support for the demonstrations; among the Arabs, the number came to only 25%. A segmentation of the Jewish sample by Knesset voting shows that at the two extremes are Shas voters on the one side (100% support) and, on the other side, Meretz voters, a majority of whom (54%) also support the demonstrations. Older people are clearly more supportive than younger ones. Gender and religiosity did not play a clear and significant role here.
We then moved on to a much more sensitive question: What about identification with the violence that south Tel Aviv residents have perpetrated against the Africans? Very surprisingly, considering that most people do not tend to openly report sympathy for acts that are broadly condemned by society, 33.5% of the Jews said they could identify with the use of violence (62% could not). Among the Arabs, 23% could identify with the use of violence (65.5% could not). A segmentation by Knesset voting for the Jewish sample indicated that the only party for which a majority of voters identified with the violent acts was Shas. A segmentation by religiosity revealed that only a minority in all groups identified with the violence. But while this minority was 26% among secular voters, it was 38% among traditional respondents, 41.5% among religious respondents, and 43% among Haredim.
Finally on this issue, we looked into reactions to Police Chief Danino's proposal to grant work permits to the Africans. It turns out that 55% of the Jews do not see this proposal as justified, nor do 70% of the Arabs interviewed. A segmentation of the Jewish sample by Knesset voting reveals a majority who justify Danino's position among Meretz (87.5%), Kadima (64%), and Labor (55%) voters. For all the rest of the parties, the majority of voters do not justify it. A segmentation by level of religiosity revealed that only among the secular does a majority concur with the idea of enabling unauthorized Africans in the country to work (55%). Among the other groups, about one-third or fewer go along with it.
Negotiation Index is comprised of two questions, one focusing on public support for peace negotiations and the other on the degree to which the public believes that such talks will actually lead to peace. The aggregated replies to these two questions are calculated, combined, and standardized on a scale of 0–100, in which 0 represents total lack of support for negotiations and lack of belief in their potential to bear fruit, and 100 represents total support for the process and belief in its potential. Each month, the Negotiations Index presents two distinct findings, one for the general Israeli population and the other for Jewish Israelis.
The Peace Index is a project of the Evens Program in Mediation and Conflict Resolution at Tel Aviv University and the Israel Democracy Institute. This month's survey was conducted by telephone on 30-31 May by the Dahaf Institute. The survey included 600 respondents, who constitute a representative sample of the adult Jewish population of Israel. The measurement error for a sample of this size is 4.5%; statistical processing was done by Ms. Yasmin Alkalay.


text:
The relative clinical...
The relative clinical effectiveness of ranibizumab and bevacizumab in diabetic macular oedema: an indirect comparison in a systematic review
CCBYNC Open access
BMJ 2012; 345 doi: https://doi.org/10.1136/bmj.e5182 (Published 13 August 2012) Cite this as: BMJ 2012;345:e5182
John A Ford, research assistant1,
Andrew Elders, statistician1,
Deepson Shyangdan, research fellow2,
Pamela Royle, senior research fellow2,
Norman Waugh, professor of public health medicine and health technology assessment2
1Health Services Research Unit, University of Aberdeen, Health Services Building, Aberdeen AB25 2ZD, UK
2Warwick Evidence, Division of Health Sciences, Warwick Medical School, Coventry, UK
Correspondence to: J A Ford john.ford{at}uea.ac.uk
Accepted 16 July 2012
Objective To indirectly compare the effectiveness of ranibizumab and bevacizumab in the treatment of diabetic macular oedema.
Design Systematic review and indirect comparison.
Data sources Medline (1996–September 2011), Embase (1996–September 2011), and the Cochrane Central Register of Controlled Trials (Issue 4, 2011).
Selection criteria for studies Randomised trials evaluating ranibizumab or bevacizumab in diabetic macular oedema with a common comparator and sufficient methodological similarity to be included within an indirect comparison were eligible for inclusion.
Main outcome measures The primary outcome was the proportion of patients with an improvement in best corrected visual acuity of more than two lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Secondary outcomes included mean changes in best corrected visual acuity and in central macular thickness, and adverse events. Best corrected visual acuity was converted to logMAR units, a linear scale of visual acuity with positive values representing increasing visual loss. Indirect comparisons were done using Bayesian methods to estimate relative treatment effects of bevacizumab and ranibizumab.
Results Five randomised controlled trials with follow-up of 6–12 months and a common comparator (multiple laser treatment) were sufficiently similar to be included in the indirect comparison. Generally studies were small, resulting in wide credible intervals. The proportions of patients with an improvement in best corrected visual acuity of >2 lines were 21/77 participants (27%) for bevacizumab and 60/152 participants (39%) for ranibizumab (odds ratio 0.95 (95% credible interval 0.23 to 4.32)). The wide credible intervals cannot exclude a greater improvement, or worse outcome, for either drug. The mean change in best corrected visual acuity non-significantly favoured bevacizumab (treatment effect −0.08 logMAR units (−0.19 to 0.04)). The difference in mean change in central macular thickness was not statistically significant between ranibizumab and bevacizumab (treatment effect −6.9 μm (−88.5 to 65.4)).
Conclusions Results suggest no difference in effectiveness between bevacizumab and ranibizumab, but the wide credible intervals cannot exclude the possibility that either drug might be superior. Sufficiently powered, direct head to head trials are needed.
Diabetic retinopathy is a major cause of visual loss and a leading cause of blindness.1 Diabetic macular oedema, a common complication of diabetic retinopathy, is caused by accumulation of excess extracellular fluid in the macula, disruption of the blood-retina barrier, and abnormal permeability, associated with increased levels of vascular endothelial growth factor.2 Visual impairment caused by macular oedema may be reversible in the early stages, but prolonged oedema causes irreversible damage.
Laser photocoagulation has been the mainstay of treatment for diabetic macular oedema and is soundly evidence based.3 However, laser treatment mainly preserves vision rather than restoring it, and some patients do not respond.4 New treatments targeting vascular endothelial growth factor, such as ranibizumab, bevacizumab, and pegaptanib, have shown promise not only in preserving vision but also in improving it.5 6 7 8 These treatments have been widely used in age related macular degeneration, and their use in diabetic macular oedema is growing.
Bevacizumab (Avastin, Genentech/Roche) targets all isoforms of vascular endothelial growth factor and was developed to restrict vascular growth in the treatment of colorectal and other cancers. It has been widely used outside its licensed indication9 as an intravitreal treatment for macular oedema. Ranibizumab (Lucentis, Genentech/Roche) is a fragment of the same parent molecule as bevacizumab. It is considerably more expensive than bevacizumab (costs of £50–£105 for bevacizumab v £742 for ranibizumab). The cost of ranibizumab to the UK National Health Service is lower because of a patient access scheme that is currently confidential. In a previous study of classic age related macular degeneration, it was estimated that ranibizumab would have to be 40% more effective at preventing visual loss than bevacizumab to justify the marginal costs and achieve no more than £30 000 per quality adjusted life year.10 Pegaptanib (Macugen, Eyetech Pharmaceuticals/Pfizer) is a PEGylated aptamer, with a high affinity to vascular endothelial growth factor 165 and was licensed for the treatment of exudative age related macular degeneration in 2004 but was not approved by the National Institute of Health and Clinical Excellence (NICE).11
There have been no trials directly comparing ranibizumab and bevacizumab for treatment of diabetic macular oedema, although one is under way in Austria.12 NICE has recently carried out a technology appraisal of ranibizumab for diabetic macular oedema. Ranibizumab, even with the patient access scheme, was not found to be cost effective compared with laser photocoagulation.13 The decision was appealed by Novartis, Royal College of Nursing, Royal College of Ophthalmologists, and jointly from four patient groups. NICE rejected these appeals in November 2011.14
Our aim was to compare the clinical effectiveness of ranibizumab and bevacizumab as measured by best corrected visual acuity and central macular thickness in diabetic macular oedema.
A literature search was performed to identify randomised controlled trials evaluating bevacizumab or ranibizumab in treating diabetic macular oedema. We searched Medline (1996–September 2011), Embase (1996–September 2011), and the Cochrane Central Register of Controlled Trials (issue 4, 2011). There were no language restrictions. The flow of studies is shown in fig 1⇓.
Fig 1 Selection of studies for systematic review and meta-analysis
The search terms for Medline were:
1. (ranibizumab or lucentis or bevacizumab or avastin).tw.
2. randomized controlled trial.pt.
3. controlled clinical trial.pt.
4. (randomly or randomised or randomized).tw.
5. 2 or 3 or 4
6. 1 and 5
7. (diabet* adj2 macular adj2 (edema or oedema)).tw.
8. diabetic maculopathy.tw.
9. 7 or 8
10. 6 and 9
These terms were adapted as appropriate for the other databases (for full details of the literature searches, see appendix 1 in the linked data supplement on bmj.com).
In addition, searches of clinicaltrials.gov and the European Union Clinical Trials Register were done for unpublished studies. One trial comparing ranibizumab and bevacizumab for diabetic macular oedema was identified.12 The authors were contacted, and we were informed that the study was currently recruiting participants. We also searched meeting abstracts—including those of the Association for Research in Vision and Ophthalmology, American Diabetes Association, and European Association for the Study of Diabetes—from 2002 to November 2011. No new studies were found.
To meet the inclusion criteria, studies were required to be randomised, include patients with diabetic macular oedema, evaluate ranibizumab or bevacizumab in one intervention arm, and measure best corrected visual acuity. We excluded trials in which one or more arms was undergoing surgical procedures such as cataract removal. Article titles were screened for eligibility by two reviewers, and abstracts or full texts were reviewed as necessary.
Studies were assessed for common comparators. A common comparator is a study arm that is similar in more than one trial and can therefore be used to connect trials. Using common comparators, we created several networks. Studies selected for potential inclusion in the network were assessed for similarity in four criteria: baseline patient population, administration and frequency of common comparator, outcomes assessment, and length of follow-up. Only one network was found to be methodologically suitable after assessing for similarity. The common comparator linking intervention arms was multiple laser photocoagulation. Bevacizumab 1.25 mg and ranibizumab 0.5 mg were included in the network, along with laser therapy. Other doses of bevacizumab and ranibizumab were considered, but the aforementioned doses were chosen as they are used in clinical practice.
Data from suitable trials were extracted by one author and checked by a second (JAF and DS). The two authors agreed, so it was not necessary to involve a third adjudicating author. Data extracted included study details, inclusion and exclusion criteria, baseline patient characteristics, dose, follow-up, change in best corrected visual acuity, and change in central macular thickness. In the event that salient data (such as standard deviations) were missing, study authors were contacted. Potential for bias was assessed using the Cochrane risk of bias tool.
The primary outcome measure was the proportion of patients with an improvement in best corrected visual acuity of more than two lines (or 10 letters) on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Secondary outcomes were mean change from baseline in best corrected visual acuity (logarithm of the minimum angle of resolution (logMAR)), mean change from baseline in central macular thickness and adverse events. Best corrected visual acuity data was converted to logMAR units, a linear scale of visual acuity with positive values representing increasing visual loss. Reporting of results follows preferred reporting items for systematic reviews and meta-analyses guidelines.15
After data extraction and assessment of risk of bias, we carried out meta-analyses of the available direct evidence for each outcome, pooling pairwise comparisons between laser and either bevacizumab or ranibizumab using Review Manager software. The results were used for descriptive purposes and also for assessing heterogeneity and potential inconsistency with the indirect evidence.
An indirect comparison of bevacizumab 1.25 mg alone versus ranibizumab 0.5 mg alone was then performed for each outcome using WinBUGS Bayesian Markov chain Monte Carlo software.16 This involved taking direct evidence from published reports of trials that had compared either bevacizumab or ranibizumab with laser therapy (the common comparator) and entering the data into a simulation model to estimate the distribution of treatment effects that would be expected if a large number of head to head trials were to be conducted. Applying methods described by Lu and Ades17 and Dias,18 we estimated a treatment effect to be the median value from the posterior distribution of odds ratios generated from a random effects simulation model, assuming a level of between-study heterogeneity observable in the available data. In each analysis, two Markov chains were used with 20 000 iterations (following a "burn-in" of 10 000 iterations). We derived 95% credible intervals from the 2.5 and 97.5 centiles of the posterior distributions. If a 95% credible interval crossed the line of no effect (that is, it included a value of 1 for odds ratios or 0 for differences in means), then the result was interpreted as being non- significant.
Assumptions relating to heterogeneity and consistency were assessed using methods described by Song et al.19 Differences in follow-up periods between studies were addressed in the analysis of the proportion of patients with improved vision, by fitting a binomial likelihood model with a complementary log-log link function which treated study length as an additional rate parameter.18 Normal likelihood models with identity link functions were used in the comparisons of best corrected visual acuity and central macular thickness to calculate mean differences between interventions.
Secondary analyses compared bevacizumab alone with ranibizumab plus prompt laser or ranibizumab plus deferred laser. These analyses were conducted using the same methods as the primary analyses, with the exception that a logit link function was used in the proportion models because follow-up was similar.
Our initial aim was to include a comparison of each anti-vascular endothelial growth factor drug alone and in combination with laser. However, the included studies allowed comparison of only bevacizumab alone, ranibizumab alone, and ranibizumab plus laser. There was no direct evidence that compared bevacizumab plus laser with any comparator, so it could not be included in the analysis.
The results of the literature search are shown in fig 1⇑. Details of the included studies20 21 22 23 24 25 26 27 28 29 are shown in table 1⇓, and details of the excluded studies30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 are given in appendix 2 of the data supplement. Only five trials (reported in 10 published articles) were sufficiently homogenous with a common comparator to be included in the indirect comparison. Methodological heterogeneity was caused by either different sample populations (such as patients with previous failed laser therapy37) or different treatments (such as post-cataract surgery42 45 or quantity of laser treatments39 40). Nine studies could not be fitted into the network diagram because of a lack of common comparator.37 38 39 40 41 42 43 44 45
Characteristics of studies included in review of ranibizumab and bevacizumab for treatment of diabetic macular oedema
The final network diagram is shown in fig 2⇓. Two studies compared bevacizumab with laser therapy,20 23 two studies compared ranibizumab with laser therapy,25 26 and one study compared ranibizumab plus prompt or deferred laser therapy with laser therapy.29 Follow-up in three studies was 12 months, and in two studies was six months. Best corrected visual acuity was the primary outcome in all five studies. Tables 2⇓ and 3⇓ show the results from each included study for our primary and secondary outcomes. Table 4⇓ shows the results of separate meta-analyses before indirect comparison. The assumption of heterogeneity was shown to be appropriate in the posterior distribution, and no inconsistency was observed with the methods described by Song et al.47
Fig 2 Network diagram showing the different treatments with ranibizumab or bevacizumab for diabetic macular oedema compared with multiple laser therapy
Primary results from studies included in review of ranibizumab and bevacizumab for treatment of diabetic macular oedema: improvement in best corrected visual acuity of >2 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale
Secondary results from studies included in review of ranibizumab and bevacizumab for treatment of diabetic macular oedema: mean changes in best corrected visual acuity and in central macular thickness
Summary of pooled estimates of treatment effect of ranibizumab and bevacizumab compared with laser therapy from studies included in review for treatment of diabetic macular oedema
Quality of studies
All studies included were of good quality (table 5⇓). Sequence generation was appropriate in all studies except in the READ-2 study,26 where the method was unclear. Allocation concealment was described in only one study,23 In the other four studies it was unclear. Three studies were appropriately masked,23 25 26 the remaining two20 28 were not because of the impracticality of masking patients to laser photocoagulation. Only one study failed to address incomplete data outcomes.25 Four studies used an intention to treat method. In one study a per protocol method was used.23 All studies were judged to be of low risk of bias from selective reporting because it was clear from the published articles that all main pre-specified outcomes were reported.
Risk of bias in the studies included in review of ranibizumab and bevacizumab for treatment of diabetic macular oedema
Best corrected visual acuity
As shown in table 6⇓, the proportion of patients with an improvement of more than two lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale seemed comparable in both the bevacizumab and ranibizumab groups (odds ratio 0.95 (95% credible interval 0.23 to 4.32)). The differences between bevacizumab and ranibizumab with prompt or deferred laser seemed to favour the bevacizumab group but were also statistically non-significant (prompt laser addition odds ratio 0.80 (0.19 to 3.11), deferred laser addition odds ratio 0.61 (0.12 to 2.84)). However, wide credible intervals cannot exclude the possibility that one drug is superior.
Indirect comparisons of ranibizumab and bevacizumab for treatment of diabetic macular oedema: proportion with improvement of >2 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale
As shown in table 7⇓, the mean change in best corrected visual acuity seemed to favour bevacizumab, but again this was not statistically significant (treatment effect −0.08 logMAR units (−0.19 to 0.04)), so superiority for either drug cannot be excluded. The addition of laser did not provide additional benefit to the ranibizumab group (prompt laser addition −0.10 units (−0.22 to 0.00), deferred laser addition treatment effect −0.10 (−0.23 to 0.03)).
Indirect comparisons of ranibizumab and bevacizumab for treatment of diabetic macular oedema: mean changes in best corrected visual acuity (logMAR)
Central macular thickness
Similarly, table 8⇓ shows that there was no statistically significant difference between ranibizumab and bevacizumab for mean change in central macular thickness. The difference in central macular thickness seemed greater in the bevacizumab group compared with ranibizumab alone (treatment effect −6.9 μm (−88.5 to 65.4)), but not with the addition of laser. However, none of these results was statistically significant, and the wide credible intervals cannot exclude a greater improvement, or worse outcome, for either drug.
Indirect comparisons of ranibizumab and bevacizumab for treatment of diabetic macular oedema: mean changes central macular thickness (μm)
Assessment of adverse events shows no consistent increase in adverse events in either group (table 9⇓). The DRCRN 2010 trial,28 the trial with the longest follow-up, reported more cardiovascular events in the sham injection plus laser therapy group than in the ranibizumab group (11.5% v 5.1%). In a two year retrospective study of bevacizumab, hypertension was slightly more prevalent in the ranibizumab and bevacizumab arms in the DRCRN 201028 and BOLT studies.21 However, hypertension was more common in the control arm in the DRCRN 2007 study.39 Endophthalmitis was a rare adverse event but was slightly more common in the intervention arms, apart from in the DRCRN 2010 trial,28 where endophthalmitis was more common in the control arm.
Adverse events in randomised controlled trials and large observational studies of ranibizumab and bevacizumab for treatment of diabetic macular oedema
Principal findings
This is the first study to compare bevacizumab and ranibizumab for treatment of diabetic macular oedema in an indirect comparison. Indirect comparisons are subject to potential biases and should be interpreted with caution. There was no evidence of a difference in effectiveness between bevacizumab and ranibizumab when measured by proportion of patients who improved by more than two lines on the ETDRS scale, mean change in best corrected visual acuity measured in logMAR units, or mean change in central macular thickness. Included studies were of low statistical power because of small numbers of participants. This coupled with moderate heterogeneity between studies resulted in wide credible intervals around estimates of treatment effects.
Strength and limitations of study
There are strengths and weaknesses of indirect comparisons.63 In the absence of head to head trials, an indirect comparison is the best we can do to estimate the treatment effect between two interventions, albeit with greater uncertainty than in direct head to head randomised controlled trials.63
The need for a common comparator and similarity in design resulted in 12 trials being excluded from the indirect comparison. In any meta-analysis there is a trade-off between reducing heterogeneity between studies and including enough studies to be able to draw meaningful conclusions. We excluded all studies that were not similar. This resulted in a more robust network but fewer trials. This can result in reduced precision in indirect comparisons. Additional studies could have been added, but this would have increased heterogeneity, and we felt this would have compromised the validity of our results.
There were differences between study populations. Three ranibizumab trials included patients who had either been treated or not treated previously with laser therapy.25 26 28 One bevacizumab trial21 included patients who had been treated previously with laser therapy, and the other bevacizumab trial23 included patients who were laser naïve. By pooling the last two trials, a group of laser experienced and laser naïve patients was created. In addition, studies differed in the management of patients with two eligible eyes. The Soheilian study21 included both eyes: BOLT,20 RESTORE,25 and READ-226 studies included the worse eye; and DRCRN28 randomised both eyes, ensuring one eye was assigned to the control group. Further minor differences were the size of population, the length of follow-up in each trial, and the use of sham injections. Follow-up varied between six and 12 months. Three studies used sham injections alongside laser, whereas two studies used laser alone (see table 1⇑).
Assessment of the indirect comparison models showed that they were all suitable. Diagnostics, including inspection of Brooks-Gelman plots, indicated appropriate convergence and low levels of autocorrelation. Residual deviance statistics indicated that the models fitted well. Heterogeneity was observed in some of the pairwise meta-analyses, and so moderate heterogeneity was assumed in the indirect comparisons. The posterior distributions for between study variance indicated that this heterogeneity assumption was reasonable. The importance of checking for consistency between direct and indirect evidence in indirect comparisons has also been highlighted by a recent review, which indicated that inconsistency may be more common than previously observed.64 However, for all outcomes in the study, there was no statistically significant inconsistency between the indirect estimates and the available direct evidence.
It could be argued that the number of patients treated with bevacizumab was insufficient to provide safety data. However, a survey reported by Fung et al65 presented data on 7113 injections in 5228 patients from 70 centres in 12 different countries. The commonest adverse events were rare and included corneal abrasion (0.15%), mild ocular discomfort (0.14%), inflammation or uveitis (0.14%), and blood pressure increase (0.21%). The authors concluded that bevacizumab was not associated with an increase in adverse events.
Comparison with other studies
There are currently no randomised studies comparing bevacizumab and ranibizumab for the treatment of diabetic macular oedema. However, three randomised controlled trials comparing ranibizumab and bevacizumab in age related macular degeneration have recently been published.66 67 68 These found similar efficacy with ranibizumab and bevacizumab. The CATT trial67 reported more systemic adverse events in the bevacizumab group (risk ratio 1.29 (95% confidence interval 1.01 to 1.66)). The IVAN trial (n=610) found a lower incidence of heart failure or arteriothrombolic events in the bevacizumab group (odds ratio 0.23 (0.05 to 1.07), P=0.03) and no difference in serious adverse events (odd ratio 1.35 (0.80 to 2.27), P=0.25).68
Campbell et al conducted a population based nested case-control study of 91 378 older adults with a history of physician diagnosed retinal disease.69 The authors found that neither ranibizumab nor bevacizumab was associated with significant risks of ischaemic stroke, acute myocardial infarction, congestive heart failure, or venous thromboembolism. In an observational study, Ladas et al70 retrospectively compared 450 patients with diabetic macular oedema who received either bevacizumab or ranibizumab (1275 injections and 725 injections respectively) and found no difference in ocular or non-ocular events.
Meaning of the results
Caution is needed when interpreting the results since the small number of studies resulted in wide credible intervals and reduced precision. Our results indicate no difference in effectiveness between ranibizumab and bevacizumab. The number of patients found to have a gain of two or more lines on the ETDRS scale was similar with bevacizumab and with ranibizumab. Mean change in best corrected visual acuity non-significantly favoured bevacizumab.
Assessment of adverse events shows similar incidences between drugs. Bevacizumab has been shown to increase the risk of cardiovascular events when used systemically in colorectal cancer.71 72 However, far smaller doses are used intraocularly, and little reaches the systemic circulation. Cardiovascular disease is of particular importance in diabetes. However, it has been suggested that among patients treated with ranibizumab for age related macular degeneration, those with diabetes are at no higher risk than others.73 In a two year retrospective study of bevacizumab treatment for diabetic macular oedema, Arevalo et al30 found the rate of cardiovascular events to be only 1.7%. Although cardiovascular events do not appear to be increased with intravitreal anti-vascular endothelial growth factor drugs, large scale safety studies are still needed. It should also be noted that most trials exclude patients with recent cardiovascular events. Endophthalmitis secondary to anti- vascular endothelial growth factor treatment is a rare event, as shown in table 9⇑.
The anti-vascular endothelial growth factor drugs represent a significant advance in the treatment of diabetic macular oedema. The implication of this comparison for policy makers and clinicians is that there is no evidence from which to infer superiority of ranibizumab over bevacizumab in diabetic macular oedema, and therefore it is unlikely that ranibizumab would be cost effective compared with bevacizumab. The National Institute of Health and Clinical Excellence (NICE) concluded that ranibizumab was not cost effective compared with laser therapy.74 It is likely that bevacizumab would be cost effective compared with laser. However, since bevacizumab is not licensed for the treatment of diabetic macular oedema and there is a licensed alternative (ranibizumab), General Medical Council guidance would not recommend the use of bevacizumab.75 Clinicians and policy makers face a dilemma of using an unlicensed but clinically effective and probably cost effective treatment compared with an expensive alternative with similar outcomes. If the second option is chosen, the extra cost to the National Health Service in England alone may be in the order of £400m ($630m, €510m), which would be taken away from other groups of patients.76
We recommend that there should be an independent, head to head trial of ranibizumab and bevacizumab for treating diabetic macular oedema. This should be long enough to answer questions about the duration of treatment and should examine the place of laser therapy in the treatment pathway.
What is already known on this topic
The anti-vascular endothelial growth factor drugs ranibizumab and bevacizumab have been shown to be effective in the treatment of diabetic macular oedema
No head to head trial has been done, so their relative effectiveness is not known
This indirect comparison has found no evidence to suggest a difference in effectiveness between bevacizumab and ranibizumab
However, wide credible intervals cannot exclude a greater improvement, or worse outcome, for either drug
Cite this as: BMJ 2012;345:e5182
We thank the study authors who provided additional information: Wen Xing, Catey Bunce, and Michel Michaelides for the BOLT study; Peter Campochiaro and Afsheen Khwaja for READ-2; Mehdi Yaseri and Masoud Soheilian for Soheilian et al. We also thank Graeme MacLennan, Health Services Research Unit, University of Aberdeen, for his statistical advice.
Contributors: All authors contributed to the design, interpretation, and writing of the manuscript and approved the final manuscript. PR carried out the searches. JAF, DS, and PR screened titles and extracted data. AE carried out the indirect comparison. JAF is the guarantor. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.
Funding: No external funding required.
All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: the authors had support from University of Aberdeen and Warwick University for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; JAF, DS, PR and NW have undertaken an Evidence Review Group report for NICE on ranibizumab for diabetic macular oedema, which may be relevant to the submitted work.
Ethical approval: Not required
Protocol: No protocol exists for this study. The study arose out of a single technology appraisal for NICE.
Data sharing: Further details available in the ERG report on the NICE website (www.nice.org.uk/nicemedia/live/13125/53408/53408.pdf).
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.
Williams R, Airey M, Baxter H, Forrester J, Kennedy-Martin T, Girach A. Epidemiology of diabetic retinopathy and macular oedema: a systematic review. Eye (Lond)2004;18:963-83.
Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH, et al. Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev2003;19:442-55.
Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol1985;103:1796-806.
Lee CM, Olk RJ. Modified grid laser photocoagulation for diffuse diabetic macular edema. Long term visual results. Ophthalmology1991;98:1594-604
Simo R, Hernandez C. Intravitreous anti-VEGF for diabetic retinopathy: hopes and fears for a new therapeutic strategy. Diabetologia2008;51:1574-80.
Parravano M, Oddone F, Tedeschi M, Schiano LD, Chiaravalloti A, Ripandelli G, et al. Retinal functional changes measured by microperimetry in neovascular age-related macular degeneration patients treated with ranibizumab. Retina2009;29:329-34.
Goyal S, Lavalley M, Subramanian ML. Meta-analysis and review on the effect of bevacizumab in diabetic macular edema. Graefes Arch Clin Exp Ophthalmol2010;249:15-27.
Yilmaz T, Cordero-Coma M, Gallagher MJ, Teasley LA. Systematic review of intravitreal bevacizumab injection for treatment of primary diabetic macular oedema. Acta Ophthalmol2011;89:709-17.
McCartney M. Off-label prescribing in macular degeneration. BMJ 201:343:d6778.
Raftery J, Clegg A, Jones J, Tan SC, Lotery A. Ranibizumab (Lucentis) versus bevacizumab (Avastin): modelling cost effectiveness. Br J Ophthalmol2007;91:1244-6.
National Institute for Health and Clinical Excellence. Ranibizumab and pegaptanib for the treatment of age-related macular degeneration: NICE technology appraisal guidance 155. 2008. http://guidance.nice.org.uk/TA155.
Medical University of Vienna. Bevacizumab versus ranibizumab for diabetic retinopathy. 2007. http://clinicaltrials.gov/ct2/show/NCT00545870?term=NCT00545870&rank=1.
National Institute for Health and Clinical Excellence. Ranibizumab for the treatment of diabetic macular oedema. NICE technology appraisal guidance TA237. 2011. http://guidance.nice.org.uk/TA237.
National Institute for Health and Clinical Excellence. Ranibizumab for the treatment of diabetic macular oedema; appeal decision. NICE technology appraisal guidance TZ237. 2011. www.nice.org.uk/nicemedia/live/13125/57323/57323.pdf.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Goetzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med2009;6:e1000100.
Lunn DJ, Thomas A, Best N, Spiegelhalter D. WinBUGS—a Bayesian modelling framework: concepts, structure, and extensibility. Stat Computing2000;10:325-37.
Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med2004;23:3105-24.
Dias S, Welton NJ, Sutton AJ. Ades AE. NICE DSU technical support document 2: a generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. 2011. www.nicedsu.org.uk.
Song F, Loke Y, Walsh T, Glenny AM, Eastwood AJ, Altman DG. Methodological problems in the use of indirect comparisons for evaluating healthcare interventions: survey of published systematic reviews. BMJ2009;338:b1147.
Michaelides M, Fraser-Bell S, Hamilton R, Kaines A, Egan C, Bunce C, et al. Macular perfusion determined by fundus fluorescein angiography at the 4-month time point in a prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (Bolt study): report 1. Retina2010;30:781-6.
Michaelides M, Kaines A, Hamilton RD, Fraser-Bell S, Rajendram R, Quhill F, et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology2010;117:1078-86.
Soheilian M, Ramezani A, Bijanzadeh B, Yaseri M, Ahmadieh H, Dehghan MH, et al. Intravitreal bevacizumab (avastin) injection alone or combined with triamcinolone versus macular photocoagulation as primary treatment of diabetic macular edema. Retina2007;27:1187-95.
Soheilian M, Ramezani A, Obudi A, Bijanzadeh B, Salehipour M, Yaseri M, et al. Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema. Ophthalmology2009;116:1142-50.
Soheilian M, Ramezani A, Yaseri M, Mirdehghan SA, Obudi A, Bijanzadeh B. Initial macular thickness and response to treatment in diabetic macular edema. Retina2011;31:1564-73.
Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, et al. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology2011;118:615-25.
Nguyen QD, Shah SM, Heier JS, Do DV, Lim J, Boyer D, et al. Primary end point (six months) results of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) study. Ophthalmology2009;116:2175-81.
Nguyen QD, Shah SM, Khwaja AA, Channa R, Hatef E, Do DV, et al. Two-year outcomes of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) study. Ophthalmology2010;117:2146-51.
Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology2010;117:1064-77.
Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL III, Friedman SM, et al. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology2011;118:609-14.
Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H, Sanchez JG, Wu L, Maia M, et al. Primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results from the Pan-American Collaborative Retina Study Group at 6-month follow-up. Ophthalmology2007;114:743-50.
Googe J, Brucker AJ, Bressler NM, Qin H, Aiello LP, Antoszyk A, et al. Randomized trial evaluating short-term effects of intravitreal ranibizumab or triamcinolone acetonide on macular edema after focal/grid laser for diabetic macular edema in eyes also receiving panretinal photocoagulation. Retina2011;31:1009-27.
Kohly RP, Muni RH, Kertes PJ. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular EDEMA. Evidence-Based Ophthalmology2010;11:199-201.
Seo JW, Park IW. Intravitreal bevacizumab for treatment of diabetic macular edema. Korean J Ophthalmol2009;23:17-22.
Sheth S, Rush R, Natarajan S, Gillies M. Intravitreal triamcinolone acetonide versus combined intravitreal bevacizumab and dexamethasone in diffuse diabetic macular oedema. Clin Experimental Ophthalmol2011;39:673-81.
Solaiman KA, Diab MM, Abo-Elenin M. Intravitreal bevacizumab and/or macular photocoagulation as a primary treatment for diffuse diabetic macular edema. Retina2010;30:1638-45.
Wang Y-S, Li X, Wang H-Y, Zhang Z-F, Li M-H, Su X-N. Intravitreal bevacizumab combined with/without triamcinolone acetonide in single injection for treatment of diabetic macular edema. Chin Med J2011;124:352-8.
Ahmadieh H, Ramezani A, Shoeibi N, Bijanzadeh B, Tabatabaei A, Azarmina M,et al. Intravitreal bevacizumab with or without triamcinolone for refractory diabetic macular edema; a placebo-controlled, randomized clinical trial. Graefes Arch Clin Experimental Ophthalmol2008;246:483-9.
Cheema RA, Al-Mubarak MM, Amin YM, Cheema MA. Role of combined cataract surgery and intravitreal bevacizumab injection in preventing progression of diabetic retinopathy: prospective randomized study. J Cataract Refractive Surg2009;35:18-25.
Diabetic Retinopathy Clinical Research Network, Scott IU, Edwards AR, Beck RW, Bressler NM, Chan CK,et al. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology2007;114:1860-7.
Faghihi H, Roohipoor R, Mohammadi SF, Hojat-Jalali K, Mirshahi A, Lashay A,et al. Intravitreal bevacizumab versus combined bevacizumab-triamcinolone versus macular laser photocoagulation in diabetic macular edema. Eur J Ophthalmol2008;18:941-8.
Lam DS, Lai TY, Lee VY, Chan CK, Liu DT, Mohamed S,et al. Efficacy of 1.25 mg versus 2.5 mg intravitreal bevacizumab for diabetic macular edema: six-month results of a randomized controlled trial. Retina2009;29:292-9.
Lanzagorta-Aresti A, Palacios-Pozo E, Menezo Rozalen JL, Navea-Tejerina A. Prevention of vision loss after cataract surgery in diabetic macular edema with intravitreal bevacizumab: a pilot study. Retina2009;29:530-5.
Paccola L, Costa RA, Folgosa MS, Barbosa JC, Scott IU, Jorge R. Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study). Br J Ophthalmol2008;92:76-80.
Massin P, Bandello F, Garweg JG, Hansen LL, Harding SP, Larsen M,et al. Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care2010;33:2399-405.
Takamura Y, Kubo E, Akagi Y. Analysis of the effect of intravitreal bevacizumab injection on diabetic macular edema after cataract surgery. Ophthalmology2009;116:1151-7.
Abu El-Asrar AM, Al-Mezaine HS, Ola MS. Changing paradigms in the treatment of diabetic retinopathy. Curr Opin Ophthalmol2009;20:532-8.
Boscia F. Current approaches to the management of diabetic retinopathy and diabetic macular oedema. Drugs2010;70:2171-200.
Ciulla TA, Rosenfeld PJ. Anti-vascular endothelial growth factor therapy for neovascular ocular diseases other than age-related macular degeneration. Curr Opin Ophthalmol2009;20:166-74.
Fard MA, Yazdanei AA, Malihi M. Prophylactic intravitreal bevacizumab for diabetic macular edema (thickening) after cataract surgery: prospective randomized study. Eur J Ophthalmol2011;21:276-81.
Guthoff R, Schrader W, Hennemann K, Meigen T, Gobel W. Prognostic factors for visual outcome after intravitreal drug therapy for chronic diabetic macular oedema. Klinische Monatsblatter fur Augenheilkunde2011;228:468-72.
Hernandez-Da Mota SE, Chacon-Lara A, Hernandez-Vazquez E. Use of triamcinolone and bevacizumab in 25G phaco-vitrectomy surgery for the treatment of cataract and diabetic macular edema. Archivos de la Sociedad Espanola de Oftalmologia2008;83:293-300.
Karim R, Tang B. Use of antivascular endothelial growth factor for diabetic macular edema. Clin Ophthalmol2010;4:493-517.
Kubicka-Trzaska A. Intravitreal ranibizumab in diabetic macular edema. Klinika Oczna2010;112:333-6.
Meyer CH. Current treatment approaches in diabetic macular edema. Ophthalmologica2007;221:118-31.
Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. J Am Med Assoc2007;298:902-16.
Nguyen QD, Tatlipinar S, Shah SM, Haller JA, Quinlan E, Sung J,et al. Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. Am J Ophthalmol2006;142:961-9.
Ozkiris A. Pattern electroretinogram changes after intravitreal bevacizumab injection for diabetic macular edema. Documenta Ophthalmologica2010;120:243-50.
Parravano M, Menchini F, Virgili G. Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for diabetic macular oedema. Cochrane Database Syst Rev 2009;4:CD007419.
Schwartz SG, Flynn J, Scott IU. Emerging therapies for diabetic macular edema. Expert Rev Ophthalmol2009;4:163-71.
Schwartz SG, Flynn J, Scott IU. Pharmacotherapy for diabetic retinopathy. Expert Opin Pharmacother2009;10:1123-31.
Scott IU, Bressler NM, Bressler SB, Browning DJ, Chan CK, Danis RP,et al. Agreement between clinician and reading center gradings of diabetic retinopathy severity level at baseline in a phase 2 study of intravitreal bevacizumab for diabetic macular edema. Retina2008;28:36-40.
Waisbourd M, Goldstein M, Loewenstein A. Treatment of diabetic retinopathy with anti-VEGF drugs. Acta Opthalmologica2011;89:203-7.
Glenny AM, Altman DG, Song F, Sakarovitch C, Deeks JJ, D'Amico R, et al. Indirect comparisons of competing interventions. Health Technol Assess2005;9:1-134.
Song F, Xiong T, Parekh-Bhurke S, Loke YK, Sutton AJ, Eastwood AJ, et al. Inconsistency between direct and indirect comparisons of competing interventions: meta-epidemiological study. BMJ 2011;343:d4909.
Fung AE, Rosenfeld PJ, Reichel E. The International Intravitreal Bevacizumab Safety Survey: using the internet to assess drug safety worldwide. Br J Ophthalmol2006;90:1344-9.
Biswas P, Sengupta S, Choudhary R, Home S, Paul A, Sinha S. Comparative role of intravitreal ranibizumab versus bevacizumab in choroidal neovascular membrane in age-related macular degeneration. Indian J Ophthalmol2011;59:191-6.
The CATT Research Group. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med2011;364:1897-908.
Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Wordsworth S, et al. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN Randomized Trial. Ophthalmology2012;119:1399-411.
Campbell RJ, Gill SS, Bronskill SE, Paterson JM, Whitehead M, Bell CM. Adverse events with intravitreal injection of vascular endothelial growth factor inhibitors: nested case-control study. BMJ2012;345:e4203.
Ladas ID, Karagiannis DA, Rouvas AA, Kotsolis AI, Liotsou A, Vergados I. Safety of repeat intravitreal injections of bevacizumab versus ranibizumab: our experience after 2,000 injections. Retina2009;29:313-8.
Kamba T, McDonald DM. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer2007;96:1788-95.
Hurwitz H, Saini S. Bevacizumab in the treatment of metastatic colorectal cancer: safety profile and management of adverse events. Semin Oncol2006;33:S26-34.
Lanzetta P, Burian G, Weichselberger A, Hashad Y. Safety profiles of diabetic versus non-diabetic AMD patients in randomized controlled clinical studies with ranibizumab. Invest Ophthalmol Vis Sci2010;51:91.
National Institute for Health and Clinical Excellence. Macular oedema (diabetic)—ranibizumab: appraisal consultation document. 2011. http://guidance.nice.org.uk/TA/Wave23/30/Consultation/DraftGuidance.
General Medical Council. Good medical practice. 2006. www.gmc-uk.org/guidance/good_medical_practice.asp.
Cummins E, Lois N, Waugh N. ERG comments on the Novartis responses to the ACD on ranibizumab for diabetic macular oedema. 2011. www.nice.org.uk/nicemedia/live/13125/55338/55338.pdf.
See other articles in issue 7875
PDF1 response
Data supplement
John A Ford, Andrew Elders, Deepson Shyangdan, Pamela Royle, Norman Waugh
Ford John A, Elders Andrew, Shyangdan Deepson, Royle Pamela, Waugh Norman. The relative clinical effectiveness of ranibizumab and bevacizumab in diabetic macular oedema: an indirect comparison in a systematic review BMJ 2012; 345 :e5182
Articles by John A Ford
Articles by Andrew Elders
Articles by Deepson Shyangdan
Articles by Pamela Royle
Articles by Norman Waugh
You are going to email the following The relative clinical effectiveness of ranibizumab and bevacizumab in diabetic macular oedema: an indirect comparison in a systematic review

redpajama_set_name: RedPajamaCommonCrawl


text:
Things to do in Montreux, Switzerland
August 26, 2019 (Last Updated: May 29, 2020)
Situated on the eastern shore of Lake Geneva and backed by a staggering panorama of Alpine peaks, French-speaking Montreux is one of the finest resort towns in the area known as the Swiss Riviera.
Easily reached by road, rail, and air, the mild Montreux weather and welcoming ambience has attracted everyone from Tchaikovsky to Freddie Mercury.
In many ways a quintessential Swiss town of well-to-do residents and endless magical views, Montreux is a place to wind your way from the hilltop Old Town to the lakeshore, by way of its thriving market stalls, before heading further afield to check out all the region has to offer.
Although it may not be as famous as some of the other cities in Switzerland, Montreux is definitely worthy of a visit.
If you plan to visit Montreux as part of your Switzerland travels, this article will give you the lowdown on what to do in Montreux.
What's in this Article
Montreux's Lakeside promenade
Chillon Castle
Statue of Freddie Mercury
Chaplin's World
Cruises on Lake Geneva
Montreux Casino and Queen: The Studio Experience
Things to do near Montreux
Vevey Old Town
Läderach ChocoAtelier Vevey
Alimentarium Food Museum
Excursions from Montreux, Switzerland
Lavaux Vineyards
Aigle Castle
Rochers-de-Naye
The Olympic Museum, Lausanne
Major festivals in Montreux, Switzerland
Montreux Noël
Where is Montreux?
How to get to Montreux, Switzerland
Geneva to Montreux by train
Lucerne or Interlaken to Montreux on the GoldenPass Line
Geneva Airport to Montreux by private transfer
Where to stay in Montreux
5-star hotels in Montreux
Montreux Riviera Card
Flowers are a feature of the lakeside promenade at Montreux.
Montreux's lakeside promenade is a special place for a stroll at any time of day, with a popular path that runs for thirteen kilometres right through Montreux. Starting in the neighbouring lakeside town of Vevey, the footpath stretches to the Château de Chillon (Chillon Castle) and small town of Villeneuve.
Sometimes called the Chemin Fleuri (Flower Path), the Montreux promenade is awash with bright blooms, intriguing public artworks, and spiky palms (yes, palms!), which together with the sparkling waters of the lake, and surrounding snow-capped mountains, create a real spectacle.
I just loved strolling along the promenade, admiring the flowers and interesting sculptures. It's a great spot for people-watching, too!
The lakeside promenade is a great way to get from Montreux to Chillon Castle.
Switzerland's most visited historical monument, the fairy-tale edifice of Chillon Castle (Château de Chillon Montreux) is a must-see when in Montreux. A picturesque way to reach the fortified castle, complete with turreted towers, is via the Chemi Fleuri (mentioned above).
Should the four kilometre walk be a little too much, you can reach take the #201 bus from the centre of Montreux to Chillon Castle, too.
The castle's maze of medieval halls, towers, prison cells, and connecting courtyards originally date from the 12th century.
Its ancient stone walls seem to rise right out of the lake itself, and offer completely uninterrupted views of the lake, across to France; views that have been captured in oils by Turner and in the written word by Lord Byron, who also etched his name into the walls of the dungeon.
GET EUROPEAN TRAVEL TIPS, NEWS, SPECIAL OFFERS AND INSPIRATION DELIVERED TO YOUR INBOX EVERY MONTH. CLICK HERE TO SIGN UP!
It's worth taking the time to explore the interior of the castle which was once home to the Dukes of Savoy and was later used as a prison. Many of the castle's rooms can be visited and there are informative audiovisual display boards and temporary exhibitions to help visitors learn more about the castle's history.
April to September – 9am to 6pm
October and March – 9.30am to 5pm
November to February – 10am to 4pm
Closed 1 January and 25 December
Adults CHF 12.50 / Children (6 to 15 years) CHF 6 / Families CHF 29
Free entry for holders of the Swiss Travel Pass
Click here to pre-purchase your admission tickets to Chillon Castle.
TIP: Allow around 45 minutes to walk from the Tourist Office in Montreux to Chillon Castle and at least one hour to visit the Castle.
Freddie Mercury fell in love with Montreux and made the city his home. Fans pay homage to him at this statue on the lakeside promenade.
Honouring the life of a modern-day icon, the lakefront at the Place de Marche hosts a statue of Freddie Mercury, lead singer of the legendary rock group Queen. Located in front of the old covered market, where you'll still find market stalls each Friday, it has become a place of pilgrimage and homage to fans.
The statue itself became famous the world over after it featured on the cover art of the group's last studio album, 1995's Made in Heaven, with vocals recorded in the band's Mountain Studios in the town before Mercury's death from AIDS at the age of 45.
Be patient if you want to take a photo of the statue without people in it. It can be difficult!
A tribute to the on and off-screen antics of silent movie star Charlie Chaplin, Chaplin's World is a museum situated on the 14-hectare estate, Manoir de Ban, in Corsier-sur-Vevey, just a short journey away from central Montreux.
It's where the short-statured mime spent 25 years of his life, and has almost 2,000 square metres of exhibition space dedicated to the star of The Tramp and The Great Dictator.
Daily except 1 January and 25 December.
Adults CHF 27 / Children (6 – 15 years) CHF 20 / Families CHF 80
Click here to pre-purchase your admission tickets to Chaplin's World.
Cruises aboard Lake Geneva's paddle steamers are a popular activity for those visiting Montreux.
Connecting 40 ports on both the Swiss and French stretches of Lake Geneva, stepping aboard one of the historic paddle steamers – including the Simplon and La Suisse – that glide across the lake's surface is an unforgettable and unmissable experience.
With the Alps as your almost constant backdrop, a lake cruise is lovely, even if you don't have a specific destination in mind.
As well as ferrying passengers around the lake, these beautiful vessels from the Belle Époque era of the 19th century also offer gourmet cruises that are the perfect accompaniment to a few days in Montreux.
You can't miss the sound of a paddle steamer sounding its horn as you wander along the lakeside promenade.
Cruises are available all year (Sundays only in winter).
Fares:
Fares vary depending on the distance travelled and Montreux Riviera Card holders (see details below) receive a 50% discount.
Seven of Queen's 15 albums were recorded at Mountain Studios in Montreux, part of Casino Barrière de Montreux. At Queen: The Studio Experience, the studios have been left pretty much as they were in the mid-1990s and are a real shrine to all things Queen in Montreux.
Fans of the group will love the memorabilia, including hand-written song lyrics, as well as the chance to get hands-on at the mixing desks and stand on the exact spot where Freddie Mercury made his last recordings.
Of course, the Casino Montreux also provides a sophisticated space, whether you prefer the poker tables or the one-armed bandits.
Queen: The Studio Experience opening hours:
Daily from 10.30am to 10pm.
Entry is free.
The pretty town Vevey is just a few kilometres from Montreux and can be reached via the lakeside promenade.
Whether by strolling along the Chemin Fleuri or setting sail on the lake, you're sure to reach nearby Vevey at some point during your stay in Montreux, Switzerland. Here's what you can find in this charming town.
Just a few kilometres west along the lake, at the end of the Chemin Fleuri, is Vevey's alluring Old Town.
Its lakeside central square, the Grande Place, just demands a stop for a cup of coffee and a pastry, while its narrow, pedestrianised, stone-clad streets are dotted with the workshops of artists and craftsmen, independent boutiques, and tiny bistros just waiting to be explored.
Why not enjoy a self-guided food tour around Vevey? Click here for details and prices.
Läderach has been creating fine artisan Swiss chocolate since the family-firm was launched in the early 1960s.
Step across the threshold of their store in Vevey, and you can not only indulge in the huge range of chocolates for sale, but also trial the 'Chocolate gourmet' course – your chance to sample a variety of the chocolates on offer – or a themed workshop, where you can produce your very own creations.
Monday to Friday from 9am to 6.30pm
Saturday from 8am to 5pm
TIP: Chocolate gourmet courses and workshops are by reservation only.
Tracing the history of food, the Alimentarium in Vevey can be located by the giant fork which emerges from the lake.
With a lakeside location marked out by a giant fork stuck into the lake, the Alimentarium Food Museum is an initiative of the locally-based company, Nestle. The first museum in the world entirely dedicated to food, it uncovers the eating habits of the past, present, and future when it comes to both culture and nutrition.
Being a food museum, you won't be surprised to learn that it also hosts daily cookery workshops, where you can make and taste Swiss and international favourites.
October to March – 10am to 5pm
April to September – 10am to 6pm
Closed on Mondays (except public holidays)
Adults CHF 13 / Children (6 – 16 years) CHF 4
Once you've admired all Montreux and Vevey have to offer, why not consider some of these excursions, easily achieved as a day trip from Montreux.
The sunny terraces of the Lavaux Vineyards produce some of Switzerland's finest wines.
A UNESCO World Heritage Site since 2007, the Lavaux Vineyards comprise almost 850 hectares of terraced vines, stretching for 30 kilometres along Lake Geneva west of Vevey. The largest contiguous vineyard in the country, the vines here trace their history back almost a thousand years.
Keen walkers can download a smartphone app to follow a 10.4 kilometre trail through the vineyards of Lavaux. Hiking trails wind up and down the neat rows, but for those who prefer to enjoy the panoramic views without the effort, trolley tours are the perfect solution – click here for prices.
If you'd like to try the local drop (and why not?!), the stylish Vinorama Wine Centre is the place to head to learn more about what makes excellent wine, as well as sampling some of the 300 vintages in its cellar.
You can also partake in a cellar door visit by luxury panoramic coach. There's a 1.5 hour visit, with wine tasting, to Domaine du Daley – click here for further details and prices or why not enjoy a 3.5 hour panoramic dinner tour to Auberge du vigneron? Click here for further details.
Surrounded by vineyards, the beguiling medieval structure of Château d'Aigle was once home to various Knights and nobles and was then used as a prison until 1976, when it was converted into the Vine and Wine Museum you'll find today.
However, even if you're not a wine aficionado, the castle is well worth a visit, if only to take in its high walls, round corner towers, and shapely red-tiled roofs.
Trains depart Montreux for Aigle at least twice per hour. Journey time is 10 minutes. The Castle is a 15 minute walk from the train station.
1 April to 31 October – 10am to 6pm (closed Mondays in April, May, June, September and October)
1 November to 31 March – 10am to 5pm (daily except Mondays)
Closed 1 January and 25 December.
Admission fees (includes Castle and Museum tour):
Adults CHF 11 / Child (6 – 16 years) CHF 5 / Family discounts available
An excursion to Rochers de Naye by cogwheel train makes a great day out.
A natural platform 2,000 metres above Montreux, in the mountains of Parc Naturel regional Gruyere Pays-Enhaut, Rochers-de-Naye not only offers great views of Lake Geneva and surroundings vistas, but also the chance to meet the beaver-like marmots that inhabit the mountains (and Santa Claus at Christmas, too).
While here, make sure you check out La Rambertia gardens, home to around 1,000 species of native plants.
The best way to get to Rochers-de-Naye is undoubtedly the cogwheel train that runs from Montreux Gare station, which takes about an hour.
The Peak Walk is just one of the reasons to visit Glacier 3000.
Just 50 minutes from Montreux you'll find the spectacular Glacier 3000, a hub for mountain enthusiasts whatever the time of year. A cable car operates from Col du Pillon, whisking visitors to the mountain peak in just 15 minutes.
Glacier 3000 boasts the first suspension bridge between two mountains, known as Peak Walk, the world's highest bobsleigh track, the Alpine Coaster, as well as the chance to hike across the glacier plateau, experience dog sledding, tobogganing, and cross-country skiing.
But it's the natural sights that are the real draw. The views take in no less than twenty-four 4,000-metre peaks, including icons like the Eiger, Jungfrau, Matterhorn, and Mont Blanc.
Summer season – 6 May to 20 October 2019/8 May to 18 October 2020 from 9am to 4.50pm (cableway operates every 20 minutes)
Winter season – 9 November 2019 to 3 May 2020 from 9am to 4.30pm (cableway operates every 20 minutes)
Closed for maintenance – 21 Oct to 8 November 2019/19 October to 6 November 2020
Cable car fares:
Entry to Glacier 3000, including return cable car fare costs – Adults CHF 80 / Child (6 – 15 years) CHF 40.
Skip the line and buy your Glacier 3000 tickets in advance – click here for details
TIP: Swiss Pass, Swiss Half Fare Card and Regional Pass Berner Oberland holders receive a 50% discount when purchasing tickets from the Glacier 3000 ticket desk.
Additional charges apply for the Alpine Coaster, dog sledding, tobogganing, etc.
Getting to Glacier 3000 from Montreux:
If you don't have your own vehicle, you can reach the Glacier 3000 cableway station at Col du Pillon aboard the GoldenPass train to Gstaad station and then taking a connecting bus to Col du Pillon Glacier 3000 stop.
You can also take a bus directly from Montreux to the Glacier 3000 cableway station at Col du Pillon. Click here for ticket prices.
Castles, chocolate and cheese are the theme of a visit to Gruyeres.
Known for its cheese, Gruyères is a fantastic example of a medieval town, complete with cobbled streets and a 13th Century château nestled at the summit of a hill on the edge of town.
Le Moléson mountain is another excellent regional destination for hiking and sledding, among other activities, while the Maison Cailler Chocolate Factory is a hit with young and old alike.
A novel way to travel from Montreux to Gruyeres is by the Cheese Train (which operates from January to April), with passengers served regional cheese and wine en route, or by the Chocolate Train from May to October.
You can also take an organised day trip from Montreux to Gruyeres. One of the most popular tours includes a visit to both the chocolate and cheese factories with tastings, a visit to the Castle and free time to explore the town. Click here for further details and prices.
Further reading: Things to do in Gruyeres
Geneva is a cosmopolitan city on the shores of the beautiful lake of the same name.
At the opposite end of Lake Geneva to Montreux, you'll find the city after which the body of water is named. Arrive by boat, and you won't fail to see its magnificent 140-metre high Jet d'Eau fountain.
Step ashore into a vibrant city that offers everything from further spectacular views – including of Mont Blanc – unrivalled shopping opportunities, and plenty of historical places of interest. Be sure to visit the Reformation Wall.
Trains from Montreux to Geneva departure regularly – journey time is just over an hour.
Further reading: Geneva, the heart of Europe
The cobbled streets of Yvoire are awash with flowers during the warmer months.
Across the lake (and the border) in France, the beautiful village of Yvoire has a history that stretches back 700 years yet is still evident today, with ramparts, fortified gateways, and a 14th Century castle all in evidence.
Besides these, you'll find an attractive yacht marina, the galleries of local artists, and, if you're visiting during the summer, an abundance of colourful blooms spilling out of flower boxes.
Yvoire is nicknamed the 'French Flower of Village' and is an esteemed member of the Most Beautiful Villages of France organisation – and is absolutely gorgeous, especially in the summer.
The fastest way to reach Yvoire from Montreux is by car but for a more relaxing journey, why not catch the train to Geneva and join a self-guided tour to Yvoire including a lake cruise? Click here for details and prices.
Further reading: Why you should visit Yvoire, the French Flower Village
Ever wondered how the Olympic Games came to be? Look no further than The Olympic Museum in Lausanne, just 30 kilometres from Montreux.
With 1,500 objects occupying 3,000 square metres of exhibition space across three levels, visitors can discover the development of the games from their ancient Greek counterpart, and learn about some of the most important Olympians in the organisation's 120-year modern history.
Lausanne is just a 30 minute train ride from Montreux.
1 May to October 15 – daily from 9am to 6pm
16 October to 30 April – Tuesday to Sunday from 10am to 6pm
Closed on 1 January and 25 December.
Admission fees:
Adults CHF 18 / Child (6 – 16 years) CHF 10 / Family discounts available
Tickets for the Olympic Museum Lausanne can be purchased in advance – click here for details.
Find more Montreux attractions and excursions on this link
The famous Montreux Jazz Festival takes place in June and July each year. One of the largest festivals of its kind anywhere in the world, it has been an annual occurrence for more than 50 years and attracts in excess of 250,000 visitors.
Taking place in the Montreux Convention Centre, it has previously welcomed such esteemed artists as Ella Fitzgerald and Deep Purple (who wrote Smoke on the Water after witnessing a fire at the Casino).
Visit the official website for details on the next Montreux Jazz Festival
Come November each year, Montreux turns from jazz to thoughts of the festive season. The town's Montreux Noël (also known as Marche Noel Montreux or Festival Montreux) celebrations create a whole new reason to visit Montreux.
In addition to the traditional Montreux Christmas market of wooden huts, twinkling lights, and people in costume on the lake, there's another in Chillon Castle, a Christmas village in Caux, and the chance to visit the home of Santa Claus on Rochers-de-Naye.
The Christmas Market in Montreux runs from around 21 November to 24 December each year.
Montreux is situated on the shores of Lake Geneva in the Canton of Vaud in the south east of Switzerland. It is 94 kilometres from Geneva, 89 kilometres from Bern, 148 kilometres from Interlaken and 219 kilometres from Zurich.
The nearest international airport to Montreux is at Geneva.
If you don't have your own vehicle, the best way to reach Montreux is by train.
The main SBB (Swiss National Railways) train station is Montreux Gare. It has regular services to towns and cities across Switzerland with connections to all major destinations in Europe. Click here to check timetables and prices.
There are several trains an hour in either direction on this route with some services running directly to and from Geneva Airport. Trains from Geneva to Montreux and vice versa take about one hour.
The views as you approach Montreux on the GoldenPass Line train are stunning.
One of the most popular – and scenic – ways to arrive in Montreux is onboard the GoldenPass Line train. The entire journey is made up of three sections on three different trains – Lucerne to Interlaken, Interlaken to Zweisimmen and Zweisimmen to Montreux – but travellers can choose to travel as much or as little of the route as they prefer.
The GoldenPass Line train is the preferred way for many travellers to get from Interlaken to Montreux.
Whichever part of the journey you experience, the panoramic windows onboard the train will provide you with stunning views of the Swiss countryside. The section from Gstaad to Montreux is regarded as the most picturesque, especially the descent through the Lavaux vineyards to Lake Geneva.
Individual tickets can be purchased for the GoldenPass Line, whilst Swiss Travel Pass holders can travel for free (more details here) and Regional Pass Berner Oberland pass holders travel free between Lucerne and Saanen and receive a 50% discount on the Saanen to Montreux leg (click here for further details).
If you are flying into Geneva, you can arrange a private transfer to take you to Montreux. Private transfers are very convenient as not only will the driver be waiting for you on arrival but your group will be transferred directly to your accommodation. Click here to check prices.
Regardless of your preferred style of accommodation in Montreux, hotel, apartment, B&B or hostel, you'll have plenty to choose from.
Below are some of the top-rated hotels on the Montreux Riviera.
Hotel Fairmont – click here to check prices
Royal Plaza Hotel Montreux – click here to check prices
Grand Hotel Suisse – click here to check prices
Hotel Eden Palace Au Lac – click here to check prices
Hotel Eurotel – click here to check prices
Hotel Splendid – click here to check prices
La Rouvenaz – click here to check prices
Guests staying at hotels and holiday apartments in Montreux will be provided with a free Montreux Riviera Card for the duration of their stay. The Card entitles the holder to travel for free on public transport (trains and buses) in the Montreux Riviera area and also provides discounts on admission to numerous museums and attractions including cruises on Lake Geneva.
Be sure to ask your accommodation provider for the Montreux Riviera Card when you check in.
Switzerland: The perfect destination for hiking and cycling holidays
Things to do in Lauterbrunnen
The Grand Tour of Switzerland by car | 14 day itinerary
Switzerland Newsletter confirmation
Love where you're going, guaranteed with GetYourGuide Originals


Where my book lovers at?! I'm all about a good coffee table book and would be even more about it if I had a coffee table. Buttt a girl can dream, right? At least I have the chance to decorate with some fun bookends. These are the coolest ways to decorate a boring bookshelf and I think I found some pretty cute ones! Not a big book lover? How about a clutch that looks like a book? Yep, it's as amazing at it seems.
Omg I love those cat bookends!


More and more people may well style and design a house nonetheless some individuals who is going to model a very good property even as will see inside Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... pic. As soon as you must transform your household, then Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... photograph will be probably your sources. Getting options is the first step you must acquire, together with Home Furniture Modesto Ca image stock will furnish you a lot of dazzling creative ideas. This particular Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... pic is very advisable for your needs because it displays a stunning style and design that one could content. You can actually know Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... image and to pick the points that you may employ in your house. You can actually content this type of Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... photograph absolutely, or you can also combine that with your own individual suggestions. The following Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... pic is really Hi Definition photograph who has submitted through the admin actually on October 6, 2017 at 4:50 pm as you move the final amount associated with guests is exactly 1.
Like the additional pictures around Home Furniture Modesto Ca pic collection, Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... graphic is High-Defiintion picture. We can determine that will Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... photo will be an HIGH-DEFINITION pic as a result of experiencing that dimension within the which is 980 x 400 while the size exactly is 56 KB. Possibly in case you discover the following truth, you will be motivated so that you can download this particular Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... snapshot. If you would like obtain Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... snapshot, you will be able to click here. And additionally for those who are who wish to article the following Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... photo to the web log, anyone far better add original source link. With any luck, Home Furniture Modesto Ca Welcome To Modestou0027s Favorite Furniture Store Where You Can Find Inspiration In Our Beautiful Showroom. Our Staff Is Here To Help You Create Your Dream Home ... photo will allow you to, thank you so much.


Everyone's Talking about "False Flags … Isn't that Another Bogus Historical Conspiracy Theory?
Forget Boston, 9/11 and Oklahoma City … Is False Flag Terror Even a REAL Historical Concept?
Forget Boston, 9/11 and Oklahoma City … Is False Flag Terrorism Even a REAL Concept?
More people are using the term "false flag" than ever before.
Some claim that the Boston marathon bombing, 9/11 and the Oklahoma City bombing were false flag attacks.
Others claim that anyone who uses the phrase "false flag" is a nut conspiracy theorist.
This post does not discuss Boston, 9/11 or Oklahoma City. It simply looks at whether there is any real historical concept regarding false flags.
2 years before, American Senator George Smathers had suggested that the U.S. make "a false attack made on Guantanamo Bay which would give us the excuse of actually fomenting a fight which would then give us the excuse to go in and [overthrow Castro]".
As reported by BBC, the New York Times, and Associated Press, Macedonian officials admit that the government murdered 7 innocent immigrants in cold blood and pretended that they were Al Qaeda soldiers attempting to assassinate Macedonian police, in order to join the "war on terror".
The bottom line is that governments from around the world have – according to their own admissions – carried out false flags.
Any discussion about a specific terrorist attack cannot start with the assumption that it couldn't be a false flag attack, or that it must be a false flag attack.


text:
PlayStation 3PlayStation Vita
The Legend of Heroes: Trails of Cold Steel I & II Coming West
By Ishaan Sahdev June 5, 2015
The Legend of Heroes: Trails of Cold Steel is coming to North America and Europe this Fall. Xseed will release the game on both PS3 and PS Vita. Here's how they describe the game:
Taking place on the same continent as fan-favorite Trails in the Sky, Trails of Cold Steel is the first game in the series to tread Erebonian soil and explore the inner political conflicts of this oft-mentioned powerhouse in detail. With a standalone story that also delves into the expansive lore that has become synonymous with the series, players take on the role of military students at a time of great turmoil, enjoying school life and bonding with fellow students to earn new abilities in battle, then utilizing those abilities via speedy, tactical turn-based combat with the newly-developed "ARCUS" system.
Xseed will publish Trails of Cold Steel in North America, while NIS America will handle European publishing duties. Xseed have said they are also publishing Trails of Cold Steel II.
Trails of Cold Steel
Ishaan Sahdev
Ishaan specializes in game design/sales analysis. He's the former managing editor of Siliconera and wrote the book "The Legend of Zelda - A Complete Development History". He also used to moonlight as a professional manga editor. These days, his day job has nothing to do with games, but the two inform each other nonetheless.


Whether you shoot Canon or Nikon, there can be a vicious learning cycle. You need a technical edge in the fast-paced, ever changing digital world.
For example, Nikon's just released the D700 - an FX prosumer DSLR with full sensor. Your new D700 just arrived by FedEx, with a paper manual (my D300 had 421 pages). Along with a new set of functions, it's time to wade into a new, complex manual, hoping there are not obfuscations.
Because your freezing fingertips don't need to think when you're in one of those fast-changing perfect lighting situations where you're about to capture a National Geographic quality snow image.
Yes, there are actually several of them.
1. Download that camera manual as a PDF from your camera maker and do a word search. It's way faster than reading the paper version.
2. Buy Thom Hogan's Nikon D300 guide. At 769 pages in PDF format, it's much bigger than Nikon's manual, and much more clearly presented. Besides that, Thom's experience as a Nikon shooter adds a lot of value to observations in his thoughtful guide.
3. Get on the net and look at videos provided by Nikon and other Nikon shooters; a bunch of them are eager to be first to discuss a gearhead's delight. I have found some of those videos mislead me; try the tip. If you don't like it, or if it conflicts with another special setting, chunk it.
4. See if there is a description of new functions on Nikonians forum.
I've got some buddies who shoot Canon 40 D's. I imagine they'd like to know about Thom Hogan's tip for why and when you shoot 14 bit on the D300/D700. In a Texas nutshell, "At Magic Hour, whether shooting regular or HDR, set your camera to 14 bit. You get four times the data in shadows and highlights. At other times, set it to 12 bit. You don't use up as much of your CF card shooting raw files!"