Studying intermediate-stage AMD

Development of clinical endpoints for clinical trials in intermediate AMD

Roibeard O’hEineachain

Posted: Saturday, September 1, 2018

A new European-wide research project now under way, called MACUSTAR, is aiming to investigate a set of tests to analyse functional and structural changes in eyes with intermediate age-related macular degeneration (iAMD).

“The aim of the MACUSTAR project is to develop clinical endpoints and prognostic indicators for use in interventional studies investigating the prevention or delay of progression of iAMD to late-stage AMD, or to improve the functional deficit characteristic to iAMD. At the moment, there is an unmet need to prevent progression of intermediate but there are no FDA- or EMA-approved clinical endpoints to test new therapies,” project co-ordinator Prof Frank G. Holz MD, Department of Ophthalmology, University of Bonn, Germany, told EuroTimes in an interview.

To define the new clinical endpoints, a multi-centre study will carry out a state-of-the art structural assessment of the retina, and a toolbox of functional testing and patient-reported outcomes instruments. The five-year project will recruit 750 patients from 20 clinical centres in seven countries across Europe. The recruitment is ongoing and will continue until March 2019 and the last patient examination will be completed in 2022, Dr Holz explained.

The study will examine the morphological and functional characteristics of the different stages of AMD as well as the functional, morphological and patient-reported changes that occur during iAMD progression. Another aspect of the study is to determine structure-function correlations, he said.

“The vast proportion of patients in the study are those with iAMD. But iAMD is associated with quite heterogeneous manifestations and functional deficits. iAMD always progresses. So, we will look at progression over the course of three years in each patient examined. We also have subgroups of 50 patients with early AMD and late AMD, and also 50 normal patients, so that we can contrast what we find in intermediate AMD patients to those other groups’ disease states,” Dr Holz added.

Colour fundus photograph showing intermediate AMD

Structural assessments of the retina will include high-resolution optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy including fundus autofluorescence and OCT angiography.

A subset of patients will be examined using quantitative autofluorescence and swept-source OCT and also adaptive optics. Functional tests include visual acuity, mesopic and scotopic microperimetry, reading speed, Moorfields Acuity Test (vanishing optotypes) and also navigation performance.

Traditionally, AMD is diagnosed based on structural analysis of the retina via clinical exam along with OCT or fundus photography. Stages of the disease are typically categorised by drusen characteristics and the presence of pigmentary changes. Over the past decades, research has shown that before the development of late-stage AMD rod function or dark adaptation may be impaired. Such functional impairments will be assessed in depth in the context of the study.

The MACUSTAR is being funded with €16 million by the European Innovative Medicines Initiative (IMI), which is the biggest public-private partnership in life science. Within the European Framework Research Programme Horizon 2020, IMI is funded jointly by the European Commission and EFPIA (European Federation of Pharmaceutical Industries and Associations). The MACUSTAR consortium includes researchers from academic institutions in the Netherlands, France, Portugal and the United Kingdom. It also includes four industrial companies: Bayer, Zeiss, Novartis and Roche.

Frank G. Holz: