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A Collaborative Resource of Heidelberg Multimodal Imaging of Intermediate and Early Atrophic AMD Cases to Study Prediction of Disease Progression

Active, not recruiting
Conditions
Prediction
Age Related Macular Degeneration
Intermediate AMD
Atrophy
Interventions
Diagnostic Test: Collection of both retrospective and prospective data collection in 3 visits.
Registration Number
NCT05698316
Lead Sponsor
Association for Innovation and Biomedical Research on Light and Image
Brief Summary

This is a multicentre retrospective and prospective cohort study with the goal to develop a well-characterised multimodal image database of eyes with intermediate AMD with and without early atrophy. The main objectives are:

1. Develop a collaborative well-characterised database on intermediate AMD with or without early atrophy.

2. Grading of these images to explore imaging markers of progression.

3. Develop predictive models as a secondary analysis of our dataset.

This study will recruit around 1.000 eyes in 6 months. All consenting patients who have had at least 3 clinic visits with multimodal imaging done at least at 6 months interval between 2 visits and meet the inclusion and exclusion criteria will be included in the study for retrospective data collection. Those with one visit remaining to complete 2 years, images will be acquired prospectively. In addition to the images, routine demographic data (age and sex) and available visual acuity (VA) (BCVA if possible, VA with Pinhole or VA with patient's glasses) will be collected. Multimodal imaging includes mandated macular OCT with or without enhanced depth imaging and infrared imaging. Fundus autofluorescence (AF) and multicolor imaging are optional. All imaging must be done on Heidelberg Spectralis system.

Detailed Description

Age-related macular degeneration (AMD) is the commonest cause of visual impairment in older people in Europe. It is a slowly progressing complex disorder. The clinical progression is best described as early, intermediate, and advanced based on the latest classification system on colour fundus photographs. However, multimodal imaging has enabled visualisation of further changes in the retina on optical coherence tomography (OCT), infrared imaging, and autofluorescence. So, a large database of imaging data of intermediate AMD will facilitate researchers to study the disease progression in detail. This study is a collaborative effort by investigators across many Member Sites in Europe that are members of EVICR.net to pool datasets for secondary analysis.

EVICR.net is a network of Ophthalmological Clinical Research Sites, dedicated to performing multinational clinical research in ophthalmology with the highest standards of quality, following the European and International Directives for Clinical Research in order to strengthen the capacity of the European Union to study the determinants of ophthalmic diseases and to develop and optimise the use of diagnostic, prevention and treatment strategies in ophthalmology.

EVICR.net Eye Platform is a long-term initiative to establish a platform to gather high quality ophthalmology data generated in Europe and allow the secondary use of data in performing large data analysis and foster clinical research.

With this Eye Platform EVICR.net aims to provide technological solutions that allow overcoming privacy and regulation issues associated with the sharing of data from different institutions/countries, in a secure, easy to use manner.

With EVICR.net Eye Platform, the Members Sites will have the opportunity to participate in clinical research with secondary use data analysis; Authorship of publications and presentations of Results; the opportunity to propose new analysis to answer key research questions; and increase overall visibility and stature as researchers

Background:

On colour fundus photographs, drusen size and changes in retinal pigment epithelium are used to classify the severity of AMD into early, intermediate and advanced stages.Early AMD is characterised by medium sized drusen of 63 µm to 124 µm with no RPE changes. Intermediate AMD include large drusen (≥125 µm) or medium-sized drusen with pigmentary changes. These eyes with intermediate AMD have a high risk of progression to advanced AMD, including either geographic atrophy or exudative AMD due to macular neovascularisation (MNV). Visual deterioration is seen in these two advanced stages. Therefore, there is an unmet need to identify those at risk of disease progression to advanced AMD so that preventive options can be evaluated and implemented. However, a significant amount of research is required to better understand the risk of disease progression.

With the advent of multimodal imaging, there is growing evidence of new imaging markers of disease progression in eyes with intermediate AMD. For example, on infrared reflectance (IR), optical coherence tomography (OCT) and autofluorescence (AF), subretinal drusenoid deposits (SDD) are seen in some eyes with intermediate AMD and these have been identified as a predictor of fast progression to advanced AMD. Multimodal images have also shown that early atrophic changes may occur in intermediate AMD before the classical diagnosis of atrophy seen as hypoautofluorescence on AF. The Classification of Atrophy Meetings (CAM) group defined a few imaging characteristics as precursors of geographic atrophy and designated them together as incomplete retinal pigment epithelium and outer retinal atrophy (iRORA). A region of signal hypertransmission into the choroid of \<250um, a corresponding zone of attenuation or disruption of the RPE, with or without the persistence of basal laminar deposits (BLamD) and evidence of overlying photoreceptor degeneration, i.e., subsidence of the inner nuclear layer (INL) and outer plexiform (OPL), presence of a hyporeflective wedge in the Henle fiber layer (HFL), thinning of the outer nuclear layer (ONL), disruption of the external limiting membrane (ELM), or disintegrity of the ellipsoid zone (EZ), and when these criteria do not meet the definition of complete retinal pigment epithelium and outer retinal atrophy (cRORA) that defines geographic atrophy on colour photographs. cRORA is defined as zone of hyper transmission of ≥250 µm, zone of attenuation or disruption of RPE band of ≥250 µm with evidence of overlying photoreceptor degeneration characterised by features that include outer nuclear layer (ONL) thinning, external limiting membrane (ELM) loss, and ellipsoid zone (EZ) or interdigitating zone (IZ) loss. Multimodal imaging also showed that drusen sizes on OCT are indeed larger than visualised on colour photographs. On en-face OCT, large drusen is defined as drusen diameter ≥145 µm, medium drusen diameters 100 µm to 144 µm, and small drusen diameters \<100 µm. So, these markers and other novel imaging characteristics may better predict disease progression from intermediate AMD.However, a large multimodal image resource is required to develop such prediction models.

The Heidelberg Spectralis device enables multimodal imaging, and the OCT scans can be segmented by in-built automated Heidelberg software and manually corrected where necessary. So, a large database of Heidelberg imaging data of intermediate AMD will facilitate researchers to study the disease progression in detail.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
1000
Inclusion Criteria

Each dataset per patient should have one eye as the study eye with:

  • Intermediate AMD with no atrophy and no subretinal drusenoid deposits
  • Intermediate AMD with no atrophy with subretinal drusenoid deposits
  • Intermediate AMD with early atrophy (iRORA) with no Subretinal drusenoid deposits
  • Intermediate AMD with early atrophy (iRORA) with Subretinal drusenoid deposits
  • Intermediate AMD with evidence of cRORA

Non-study eye images will not be exported but information about the status of the macula should be added using the following options:

  • Established Geographic Atrophy (cRORA)
  • Exudative AMD (presence of MNV)
  • Early AMD
  • Healthy macula
Exclusion Criteria
  • Both eyes have exudative AMD or geographic atrophy at baseline.
  • Co-existent ocular disease: Any other ocular condition that, in the investigator's opinion, might affect or alter visual acuity during the study.
  • Any patient who has opted out of their information being used for research nationally or locally at any Member Site.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Age related macular degenerationCollection of both retrospective and prospective data collection in 3 visits.Collection of both retrospective and prospective data collection in 3 visits.
Primary Outcome Measures
NameTimeMethod
Incidence of conversion to atrophy at two years24 months

Number of patients who developed new or increasing atrophy

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (25)

Department of Ophthalmology University of Freiburg

🇩🇪

Freiburg, Germany

Department of Ophthalmology St. Franziskus/Hospital Münster

🇩🇪

Münster, Germany

Espaço Médico de Coimbra

🇵🇹

Coimbra, Portugal

Department of Ophthalmology, University Hospital, Nantes

🇫🇷

Nantes, France

Department of Ophthalmology University of Bonn

🇩🇪

Bonn, Germany

Department of Ophthalmology Justus/Liebig/University/Giessen

🇩🇪

Giesen, Germany

Department of Ophthalmology University of Muenster Medical Center

🇩🇪

Münster, Germany

Eye Clinic Sulzbach, Knappschaft Hospital Saar

🇩🇪

Sulzbach, Germany

Royal Victoria Eye and Ear Research Foundation

🇮🇪

Dublin, Ireland

Eye Unit, University Hospital Maggiore della Carità

🇮🇹

Novara, Italy

Medical Retina Service, Operative Unit Ophthalmology / MultiMedica Spa (IRCCSMM)

🇮🇹

Milan, Italy

Department of Ophthalmology University of Udine

🇮🇹

Udine, Italy

Department of Ophthalmology Radboud University Medical Centre Nijmegen

🇳🇱

Nijmegen, Netherlands

AIBILI-CEC (AIBILI- Clinical Trials Centre)

🇵🇹

Coimbra, Portugal

Instituto de Oftalmologia Dr. Gama Pinto

🇵🇹

Lisboa, Portugal

Department of Ophthalmology Porto Medical School / Hospital S. João

🇵🇹

Porto, Portugal

Institut Català de Retina (ICR), Clinical Trial Unit

🇪🇸

Barcelona, Spain

Institut de la Màcula Centro Médico Teknon

🇪🇸

Barcelona, Spain

Valles Ophthalmology Research, S.L.

🇪🇸

Barcelona, Spain

University Hospital Basel, University Eye Clinic, Basel

🇨🇭

Basel, Switzerland

Swiss Visio Retina Research Center, Swiss Visio Montchoisi

🇨🇭

Lausanne, Switzerland

Clinical Eye Research Centre - St. Paul's Eye Unit, Royal Liverpool University Hospital

🇬🇧

Liverpool, United Kingdom

Clinical Trial Unit, Dep. Ophth., Gloucestershire Hospitals NHS Foundation Trust

🇬🇧

Cheltenham, United Kingdom

NIHR Moorfields Clinical Research Facility, Moorfields Eye Hospital, NHS Foundation Trust

🇬🇧

London, United Kingdom

Clínica Oftalmológica AIKEN / Fundación Aiken de la Comunitat Valenciana

🇪🇸

Valencia, Spain

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