Imaging of the Angiofibrotic Switch in Neovascular AMD

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.

Conditions

• Age-related Macular Degeneration
• Choroidal Neovascularization

Interventions

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Best-corrected Visual acuity testing (BCVA)

Best-corrected visual acuity (BCVA) will be measured using Early Treatment of Diabetic Retinopathy Study (ETDRS) charts at 4 meters and 1 meter, respectively.

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Optical coherence tomography (OCT)

Optical Coherence Tomography (OCT) is a non-invasive diagnostic technique that renders an in vivo cross sectional view of the retina.

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Color fundus photography (CFP)

Color fundus photography is a non-invasive, fast and reliable imaging method providing a true-to-life depiction of the ocular fundus.

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Optical coherence tomography angiography (OCTA)

OCTA, an extension of conventional OCT, offers noninvasive imaging of the retinal and choroidal vasculature.

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Polarization-sensitive optical coherence tomography (PS-OCT)

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.

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Microperimetry (MP)

Microperimetry allows testing of retinal sensitivity at specific locations in the area of the fovea, parafovea or even more peipheral areas of the macula.

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Adaptive-optics optical coherence tomography (AO-OCT)

AO-OCT, an extension of conventional OCT, offers non-invasive imaging of the retina with improved lateral resolution of up to 2-3 μm.

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Fluorescein angiography (FA)

FA imaging is a standard imaging technique used for the diagnosis of vascular pathologies of the retina such as choroidal neovascularization.

Sponsors & Collaborators

• Medical University of Vienna

  lead OTHER

Principal Investigators

• Philipp Roberts, MD PhD · Medical University of Vienna

Eligibility

Min Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-05-01

Primary Completion

2022-04-28

Completion

2022-04-28

Countries

• Austria

Study Locations