Imaging of the Angiofibrotic Switch in Neovascular AMD
Multimodal Imaging of Subretinal Fibrosis in Neovascular AMD
1 other identifier
observational
120
1 country
1
Brief Summary
The content of this research project is to identify the angiofibrotic switch, the transition from angiogenesis to fibrosis, in neovascular age-related macular degeneration (nAMD) longitudinally. Despite optimal treatment about 50% of eyes with nAMD develop fibrosis within 2 years, causing irreversible damage to the retina and functional loss. Objective measurement of fibrosis, however, is challenging, since clinical staging is subjective and current imaging modalities such as color fundus photography (CFP), fluorescein angiography (FA) and optical coherence tomography (OCT) often do not allow clear delineation. Novel imaging modalities such as polarization-sensitive OCT (PS-OCT), OCT angiography (OCTA) and adaptive-optics OCT (AO-OCT) offer identification of fibrous components and microvasculature of fibrotic lesions non-invasively with highest precision and shall thus be used in this study. Hypotheses: The investigators hypothesize to detect and quantify subclinical (i.e. not detectable on dilated fundus examination) areas of fibrosis using PS-OCT and determine the rate and exact location within the neovascular lesion. Furthermore, the investigators expect neuroretinal and microvascular changes, which will be assessed by AO-OCT and OCTA. Methods: Eighty eyes of 80 patients with chronic nAMD will be included and examined cross- sectionally to evaluate the accuracy of PS-OCT to detect and quantify fibrosis in comparison to gold standard imaging modalities. In addition, OCTA and AO-OCT will be performed to analyze the relationship between fibrous, neovascular and neuroretinal structures. Furthermore, forty eyes of 40 participants with treatment-naïve nAMD will be included and followed over 12 months with predefined follow-up intervals. Novel non-invasive imaging will be applied to objectively determine the exact time and extent of the angiofibrotic switch in nAMD during state-of-the- art therapy. This approach has not been done before and is clinically relevant for multiple reasons: Firstly, only little is known about the development of fibrosis in AMD during therapy. Secondly, the clinical diagnosis of subretinal fibrosis is subjective and does not allow reliable quantification. Thirdly, current gold standard imaging modalities (i.e. CFP and FA) for detection of fibrosis involve invasive and time-consuming procedures and do not allow three-dimensional analysis. Finally, our study may identify objective endpoints for future interventional trials.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started May 2019
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 10, 2019
CompletedFirst Posted
Study publicly available on registry
February 12, 2019
CompletedStudy Start
First participant enrolled
May 1, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 28, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
April 28, 2022
CompletedFebruary 20, 2020
February 1, 2020
3 years
February 10, 2019
February 19, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Detection of subretinal fibrosis by PS-OCT
The primary objective is to determine how well the fibrosis present/not present classification of the novel PS-OCT imaging works compared to gold standard imaging techniques. To assess the primary objective, a 95% confidence interval for the proportion of correct fibrosis yes/no classifications by the novel PS-OCT imaging compared to the gold standard will be computed. To assess this objective, data from cohort 1 will be used.
15 months
Secondary Outcomes (1)
Extension of fibrosis area quantified on PS-OCT and correlated to standard imaging modalities
33 months
Other Outcomes (5)
Correlation of fibrosis and co-localized vascular changes (comparison between OCTA and PS-OCT)
36 months
Correlation of fibrosis localization and co-localized retinal function (comparison between MP, PS-OCT, OCTA, OCT and AO-OCT)
36 months
Correlation of morphology (fibrosis) and visual outcome (comparison between BCVA and PS-OCT, OCTA, AO-OCT, OCT)
36 months
- +2 more other outcomes
Study Arms (2)
Cohort 1
80 participants with neovascular AMD and a minimum history of 12 months of anti- VEGF therapy will be included in cohort 1 and examined only once (1 study visit).
Cohort 2
40 participants with treatment-naive neovascular AMD receiving standardized anti- VEGF therapy will be included in cohort 2 and followed for 12 months (6 study visits).
Interventions
Best-corrected visual acuity (BCVA) will be measured using Early Treatment of Diabetic Retinopathy Study (ETDRS) charts at 4 meters and 1 meter, respectively.
Optical Coherence Tomography (OCT) is a non-invasive diagnostic technique that renders an in vivo cross sectional view of the retina.
Color fundus photography is a non-invasive, fast and reliable imaging method providing a true-to-life depiction of the ocular fundus.
OCTA, an extension of conventional OCT, offers noninvasive imaging of the retinal and choroidal vasculature.
PS-OCT, a functional exten- sion of conventional OCT technology, enables differentiation of retinal layers based on their distinct interference with the polarization state of the probing light beam, as opposed to mere light intensity.
Microperimetry allows testing of retinal sensitivity at specific locations in the area of the fovea, parafovea or even more peipheral areas of the macula.
AO-OCT, an extension of conventional OCT, offers non-invasive imaging of the retina with improved lateral resolution of up to 2-3 μm.
FA imaging is a standard imaging technique used for the diagnosis of vascular pathologies of the retina such as choroidal neovascularization.
Eligibility Criteria
There will be two study cohorts in this trial: 1. 80 participants with neovascular AMD and a minimum history of 12 months of anti- VEGF therapy will be included in cohort 1 and examined only once (1 study visit). 2. 40 participants with treatment-naive neovascular AMD receiving standardized anti- VEGF therapy will be included in cohort 2 and followed for 12 months (6 study visits).
You may qualify if:
- Chronic neovascular AMD with anti-VEGF treatment of a minimum duration of 12 months (cohort 1)
- Treatment-naïve active neovascular AMD (cohort 2)
- years of age or older
- Visual acuity 20/25-20/320
- At least one druse (\>63μm) in either eye or late AMD in the fellow eye
- Fibrosis \<50% of total lesion area at baseline (cohort 2)
You may not qualify if:
- Previous treatment for CNV in the study eye (cohort 2)
- Presence of other progressive retinal disease likely to affect visual acuity
- Contraindications for treatment with anti-VEGF
- Pregnancy
- Dyslexia
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Medical University of Vienna
Vienna, 1090, Austria
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Philipp Roberts, MD PhD
Medical University of Vienna
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal investigator
Study Record Dates
First Submitted
February 10, 2019
First Posted
February 12, 2019
Study Start
May 1, 2019
Primary Completion
April 28, 2022
Study Completion
April 28, 2022
Last Updated
February 20, 2020
Record last verified: 2020-02