March 17, 2021
New publication from the MACUSTAR consortium in BMC Medical Research Methodology: Challenges, facilitators and barriers to screening study participants in early disease stages-experience from the MACUSTAR study
Recruiting asymptomatic participants with early disease stages into studies is challenging and only little is known about facilitators and barriers to screening and recruitment of study participants. Thus we assessed factors associated with screening rates in the MACUSTAR study, a multi-centre, low-interventional cohort study of early stages of age-related macular degeneration (AMD). Screening rates per clinical site and per week were compiled and applicable recruitment factors were assigned to respective time periods. A generalized linear mixed-effects model including the most relevant recruitment factors identified via in-depth interviews with study personnel was fitted to the screening data.
Publication: Jan H. Terheyden, Charlotte Behning, Anna Lüning, Ludmila Wintergerst, Pier G. Basile, Diana Tavares, Beatriz A. Melício, Sergio Leal, George Weissgerber, Ulrich F. O. Luhmann, David P. Crabb, Adnan Tufail, Carel Hoyng, Moritz Berger, Matthias Schmid, Rufino Silva, Cecília V. Martinho, José Cunha-Vaz, Frank G. Holz and Robert P. Finger, on behalf of the MACUSTAR consortium, Challenges, facilitators and barriers to screening study participants in early disease stages-experience from the MACUSTAR study, BMC Medical Research Methodology, https://doi.org/10.1186/s12874-021-01243-8
December 07, 2020
New review article from the MACUSTAR consortium in Ophthalmologica: Use of composite endpoints in early and intermediate age-related macular degeneration clinical trials – state-of-the-art and future directions
The slow progression of early AMD stages to advanced AMD requires the use of surrogate endpoints in clinical trials. The use of combined endpoints may allow for shorter and smaller trials due to increased precision. The review article gives an overview of the use of composite endpoints as primary outcome measures in clinical studies of early AMD stages. After reviewing a total of 673 abstracts and applicable full-text articles, 33 articles were eligible and thus were included in the qualitative synthesis. The main composite endpoint categories were: Combined structural and functional endpoints, combined structural endpoints, combined functional endpoints and combined multi-categorical endpoints. The majority of the studies included binary composite endpoints. There was a lack of sensitivity analyses of different endpoints against accepted outcomes (i.e. progression) in the literature. Various composite outcome measures have been used but there is a lack of standardization. To date no agreement on the optimal approach to implement combined endpoints in clinical studies of early stages of AMD exists and no surrogate endpoints have been accepted for AMD progression.
Publication: Jan H. Terheyden, Steffen Schmitz-Valckenberg, David P. Crabb, Hannah Dunbar, Ulrich F. O. Luhmann, Charlotte Behning, Matthias Schmid, Rufino Silva, José Cunha-Vaz, Adnan Tufail, George Weissgerber, Sergio Leal, Frank G. Holz, Robert P. Finger, Use of composite endpoints in early and intermediate age-related macular degeneration clinical trials – state-of-the-art and future directions, Ophthalmologica, https://doi.org/10.1159/000513591
November 27, 2020
The annual meeting of the MACUSTAR Management Board took place as a virtual meeting. Members from all over Europe attended the discussion on the current progress of the Clinical Study as well as current topics. 40 members of the consortium and the IMI were present at the three-hour meeting.
July 18, 2020
New publication from the MACUSTAR consortium in Trials: Clinical study protocol for a low-interventional study in intermediate age-related macular degeneration developing novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention—MACUSTAR
The protocol published in the peer-reviewed journal Trials describes the low-interventional clinical multicenter study MACUSTAR employing a novel two-part design. The cross-sectional part (total duration, 1 month) and the longitudinal part (total duration, 36 months) include participants with iAMD and control groups with early/late/no AMD. The cross-sectional part’s primary objective is a technical evaluation of functional, structural, and patient-reported outcomes. The longitudinal part’s primary objective is to assess the prognostic significance in functional, structural, and patient-reported outcomes for the progression from iAMD to late AMD. All data will be used to support a biomarker qualification procedure by regulatory authorities.
Publication: Jan H. Terheyden, Frank G. Holz, Steffen Schmitz-Valckenberg, Anna Lüning, Matthias Schmid, Gary S. Rubin, Hannah Dunbar, Adnan Tufail, David P. Crabb, Alison Binns, Clara I. Sánchez, Carel Hoyng, Philippe Margaron, Nadia Zakaria, Mary Durbin, Ulrich Luhmann, Parisa Zamiri, José Cunha-Vaz, Cecília Martinho, Sergio Leal, Robert P. Finger: Clinical study protocol for a low-interventional study in intermediate age-related macular degeneration developing novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention—MACUSTAR, Trials, https://doi.org/10.1186/s13063-020-04595-6
March 23, 2020
The MACUSTAR project has completed recruitment of over 700 individuals with age-related macular degeneration for the clinical study on the development of novel endpoints for intermediate age-related macular degeneration (iAMD). A total of 20 designated clinical sites in Europe participated and enrolled 585 iAMD patients and over 130 age-matched control subjects without AMD, with early and late AMD. A review period of up to three years will assess disease progression and risk factors with a series of functional tests, imaging modalities and patient-reported outcomes. Novel functional tests for the specific visual deficit in iAMD include dark-adapted microperimetry and standardized dark adaptation, as well as, state-of-the-art high-resolution retinal imaging including optical coherence tomography (OCT) and OCT angiography.
November 15-16, 2019
The annual meeting of the MACUSTAR Management Board took place in Berlin, Germany. Members from all over Europe discussed topics around the Clinical Study as well as recent advances of the work packages. In addition, the recruitment period was adjusted following a review of the recruitment status. A representative of the IMI participated in the event.
September 6, 2019
The lecture “MACUSTAR – An IMI2 study on AMD outcomes” held by Prof. Frank Holz at the annual meeting of the European society of retina specialists (EURETINA) in Paris, France was met with great interest. The symposium of the European Vision Clinical Research network (EVICR.net) allowed discussions on several innovative studies in the field.
April 29, 2019
This year’s meeting of the MACUSTAR Scientific Advisory Board (SAB) took place at ARVO 2019 in Vancouver, British Columbia. More than 30 participants from the SAB and the MACUSTAR consortium attended the meeting. Topics around the Clinical Study as well as structural, functional and patient-reported endpoints addressed in the MACUSTAR were discussed intensively.
April 28, 2019
From the ARVO annual meeting, 2019:
- Illumination affects mobility performance in patients with age-related macular degeneration
by Hannah Dunbar, Hannah1,2 ; Ariel Zenouda4 ; Saddek Mohand-Saïd3 ; Adnan Tufail 1,2 ; Jose A. Sahel3,4 ; Gary S. Rubin1,2 on behalf of the MACUSTAR Consortium
(1. Visual Neuroscience, UCL Institute of Ophthalmology, London, United Kingdom; 2.Moorfields Eye Hospital NHS Foundation Trust, United Kingdom; 3. INSERM-DHOS CIC 1423, CHNO des Quinze-Vingts, Paris, France; 4. Streetlab SAS, Institut de la Vision, France)
Data from ongoing MACUSTAR navigation performance assessments were reported at ARVO 2019. Researchers at University College London (UCL) and Institut de la Vision, Paris invited subjects recruited at Moorfields Eye Hospital and Centre National d’Ophtalmologie des Quinze-Vingts respectively, to take part in a navigation performance test. Subjects were asked to navigate 4 obstacle seeded mazes under 4 different light conditions: 3 static conditions (256, 4, 1 lux) and 1 transition condition (256 reducing to 1 lux) at their fastest comfortable pace whilst avoiding obstacles: 3 normal controls and 28 subjects with age-related macular degeneration took part. Light level had a significant impact on walking speed and number of navigation errors (collisions or disorientation), with significantly slower walking speeds in the transition condition as compared to the brightest condition (256 lux) and significantly more errors in the transition condition compared to all other light conditions. These results suggest subjects with AMD experience increased difficulty with navigation under a transient reducing light condition (i.e. walking from a brightly lit area to a dimly lit area), as compared to static low light conditions to which they have been adapted. This work is ongoing.
December 12, 2018
The MACUSTAR clinical study now recruits at all 20 sites.
November 9-10, 2018
The MACUSTAR Management Board met in Basel, Switzerland to discuss the current progress of the study. In a round table discussion as well as in smaller working groups, current topics were discussed and the recent advances of the work packages were presented. More than 40 members of the consortium and the IMI from all over Europe were present at our meeting.
September 23, 2018
The team of the MACUSTAR project was present at EURETINA 2018 Congress from September 20 to September 23 in Vienna, Austria. We had good and intensive discussions at the Investigator Meeting on Thursday. Later that day, Frank Holz and Robert Finger also presented the MACUSTAR study in the symposium of the European Vision Clinical Research Network (EVICR.NET), “Focus on Multinational Clinical Research”.
August 28, 2018
New publication from the macustar consortium in Ophthalmologica: Development and clinical validation of functional, structural and patientreported endpoints in intermediate age-related macular degeneration
The article published in the peer-reviewed journal Ophthalmologica summarizes the methods used in the macustar clinical study to assess AMD and its impact on function and quality of life. For example, high-resolution imaging techniques will provide information on anatomical changes in the retina. Besides conventional visual function tests, vision under low-light conditions and contrast vision will be determined. Researchers will also capture the light sensitivity of the macula, the duration of dark adaptation, and reading speed and visual path navigation under low-light conditions. In addition, questionnaires will provide information on how visual impairment is perceived by the study participants. The macustar consortium aims to identify the best method or combination of methods that indicate if a novel therapeutic approach can stop AMD progression in the future.
Publication: Robert P. Finger, Steffen Schmitz-Valckenberg, Matthias Schmid, Gary S. Rubin, Hannah Dunbar, Adnan Tufail, David P. Crabb, Alison Binns, Clara I. Sánchez, Philippe Margaron, Guillaume Normand, Mary Durbin, Ulrich F. O. Luhmann, Parisa Zamiri, José Cunha-Vaz, Friedrich Asmus, Frank G. Holz: Development and clinical validation of functional, structural and patientreported endpoints in intermediate age-related macular degeneration, Ophthalmologica, DOI: 10.1159/000491402.
May 23, 2018
From the ARVO Annual Meeting, 2018:
- Patients with AMD report difficulty with vision-related activities and functioning under visually challenging conditions at all stages of the disease in individual interviews and focus group discussions. The difficulties include reading, social interaction/recognizing people, mobility/safety and the socio-emotional impact of these difficulties.
by Robert P. Finger (University of Bonn, Bonn, Germany)
Age-relate macular degeneration (AMD) leads to vision problems in low contrast or low luminance situations. To date, it is difficult to capture these problems in a standardized way using patient-report. Thus, we interviewed patients and collected aspects of these problems important to them which broadly fall into the categories of reading, social interaction/recognizing people, mobility/safety and the socio-emotional impact of these difficulties. These aspects should be considered when developing an instrument to capture patient-reported difficulty with vision-related activities and functioning under visually challenging conditions for AMD.
May 17, 2018
From the ARVO Annual Meeting, 2018:
- Pilot study determines that a dark adaptation test location at the edge of the macular region provides good discrimination between healthy and intermediate AMD states within a clinically viable testing timeframe
by Alison M. Binns, Laura Edwards, Deanna Taylor, David Crabb (Optometry and Visual Science, City, University of London, London, United Kingdom)
A pilot study was conducted at City, University of London to determine the optimal test conditions for the longitudinal evaluation of dark adaptation in people with intermediate age-related macular degeneration (iAMD) for the MACUSTAR study. The rod intercept time was assessed using the AdaptDX device under 5 test conditions over 2 visits: 76%, 70% and 65% rhodopsin bleach at 5 degrees eccentricity and 76% and 70% bleach at 12 degrees. Fourteen people with iAMD and 10 controls attended for 2 visits. Nearly half of the participants with iAMD produced an unacceptably long recovery time (>20mins) using a 76% bleach at 5 degrees eccentricity. The 76% bleach at 12 degrees provided almost equivalent separation between iAMD and controls but recovery was achieved within 20 minutes for almost all participants. The latter condition was therefore deemed to be most suitable for this clinical application.
The work has also been published in the journal Investigative Ophthalmology and Visual Science under the DOI: 10.1167/iovs.18-24211
Mar 26, 2018
The first patient was screened for the macustar clinical study today in Coimbra, Portugal.
The macustar clinical study can be found on ClinicalTrials.gov also. Patients will be recruited until February 2019.
Feb 15, 2018
European medicines agency (EMA) supports the approach of the MACUSTAR clinical study to develop functional and/or structural biomarkers as possible future primary endpoints for clinical trials
Oct 20, 2017
macustar kick-off meeting
Sept 8, 2017
macustar Investigators’ Meeting at EURETINA congress
Robert Finger, EURETINA 2017 (David Crabb, twitter, @crabb-lab)
Sept 1, 2017
Official start of the macustar project