Periodic Reporting for period 3 - MOON (Multi-modal Optical Diagnostics for Ocular and Neurodegenerative Disease)
Reporting period: 2019-11-01 to 2022-02-28
According to the Photonics21 strategic roadmap1 for 2014-2018 demographic changes in Europe will have drastic consequences for European citizens and their healthcare system as increased life expectancy will lead to a dramatic increase of age-related diseases.
Reviewing the prevalence of major retinal diseases as well as major neurodegenerative diseases we observe both Age-related Macula Degeneration (AMD) and Alzheimer’s Disease (AD) as those with highest number of people being affected in Europe.
MOON will focus on the development of two step-changing diagnostic imaging systems: the first (MOON 1) combines Optical Coherence tomography (OCT) and non-invasive OCT Angiography (OCTA) with an unprecedented large field of view, and diagnostic imaging quality, targeting early retinal disease diagnostics. The second system (MOON 2) is a multi-band and multimodal functional imaging platform for in-depth diagnostics of ocular and neurodegenerative diseases on a molecular level combining the chemical specificity of Raman spectroscopy with the structural and functional sensitivity of OCT. For this task novel light source technology, advanced Raman spectrometers, and multimodal test eyes will be developed. The diagnosis with the MOON technology will be fully non-invasive and non-contact through a simple scan of the retina. An important step will be the validation of the system in vivo in a clinical setting by closely involving clinical collaborators.
Reviewing the prevalence of major retinal diseases as well as major neurodegenerative diseases we observe both Age-related Macula Degeneration (AMD) and Alzheimer’s Disease (AD) as those with highest number of people being affected in Europe.
MOON will focus on the development of two step-changing diagnostic imaging systems: the first (MOON 1) combines Optical Coherence tomography (OCT) and non-invasive OCT Angiography (OCTA) with an unprecedented large field of view, and diagnostic imaging quality, targeting early retinal disease diagnostics. The second system (MOON 2) is a multi-band and multimodal functional imaging platform for in-depth diagnostics of ocular and neurodegenerative diseases on a molecular level combining the chemical specificity of Raman spectroscopy with the structural and functional sensitivity of OCT. For this task novel light source technology, advanced Raman spectrometers, and multimodal test eyes will be developed. The diagnosis with the MOON technology will be fully non-invasive and non-contact through a simple scan of the retina. An important step will be the validation of the system in vivo in a clinical setting by closely involving clinical collaborators.
The highlights of the first reporting period were
- the testing of the MOON akinetic laser technology in OCT systems on healthy retinas,
- the finalizing of the MOON 1 demonstrator by CZ and shipment to MUW
- the setup of the Raman reference database of biomarkers by IPHT
- and the implementation of the fluorescence channel of the multimodal imaging platform MOON2 by TNO.
The MOON1 demonstrator exhibits unravelled performance features when compared to both commercially available as well as research OCT platforms. It covers large field of view of up to 90deg, supports greater than 1MHz laser sweep rates, operates at 1060nm center wavelength, has an active tracking system, allows for dual transverse resolution settings, and features OCT angiography over a field of view similar to fluorescence angiography.
Model eyes have been built to be particularly used for multimodal platforms and the coregistration of the various channels. It contains features visible in Raman spectroscopy, fluorescence imaging, and OCT.
Highlights of the second reporting period were
- the demonstration, that Raman spectroscopy can be applied to the human eye, given the constraints on laser power as applied to the eye, as well as the measurement duration;This paved the way for preparing the in-vivo human study with the multimodal MOON2 system.
-finalization of the MOON 2 platform, incorporating now fluorescence, OCT, a specifically designed Raman channel, as well as retinal tracking capability.
-ethics clearance as well as clearance by the national authorities for the MOON1 system for human in-vivo studies that started in the same period;
- first clinical cases materializing impressively the clinical potential of the MOON 1 technology.
In the third and final project period the following results have been achieved:
- the multimodal MOON2 system including the akinetic laser chip technology by INNOLUME received clearance by the national authorities for in-vivo human studies. Both the study on patients with age-related macula degeneration as well as with patients of Alzheimer disease have been initiated.
- worldwide first clinical results produce key know-how of how to obtain clinically relevant spontaneous Raman spectra from the human retina in-vivo; this IP is in evaluation for a patent submission by MUW including partners that contributed to the MOON2 system; in addition a publication targeting a high impact journal is in preparation;
- clinical results on age-related macula degeneration patients indicate the possibility to tell healthy from diseased retinas apart. This is in preparation for a publication after the patent and first publication has been finalized.
-clinical results on Alzheimer disease need further processing using advanced machine learning algorithms; first results are encouraging and will be disseminated through high impact journals;
-a route to market report has been prepared for the MOON1 and MOON2 technology as well as the exploitation strategy;
- the testing of the MOON akinetic laser technology in OCT systems on healthy retinas,
- the finalizing of the MOON 1 demonstrator by CZ and shipment to MUW
- the setup of the Raman reference database of biomarkers by IPHT
- and the implementation of the fluorescence channel of the multimodal imaging platform MOON2 by TNO.
The MOON1 demonstrator exhibits unravelled performance features when compared to both commercially available as well as research OCT platforms. It covers large field of view of up to 90deg, supports greater than 1MHz laser sweep rates, operates at 1060nm center wavelength, has an active tracking system, allows for dual transverse resolution settings, and features OCT angiography over a field of view similar to fluorescence angiography.
Model eyes have been built to be particularly used for multimodal platforms and the coregistration of the various channels. It contains features visible in Raman spectroscopy, fluorescence imaging, and OCT.
Highlights of the second reporting period were
- the demonstration, that Raman spectroscopy can be applied to the human eye, given the constraints on laser power as applied to the eye, as well as the measurement duration;This paved the way for preparing the in-vivo human study with the multimodal MOON2 system.
-finalization of the MOON 2 platform, incorporating now fluorescence, OCT, a specifically designed Raman channel, as well as retinal tracking capability.
-ethics clearance as well as clearance by the national authorities for the MOON1 system for human in-vivo studies that started in the same period;
- first clinical cases materializing impressively the clinical potential of the MOON 1 technology.
In the third and final project period the following results have been achieved:
- the multimodal MOON2 system including the akinetic laser chip technology by INNOLUME received clearance by the national authorities for in-vivo human studies. Both the study on patients with age-related macula degeneration as well as with patients of Alzheimer disease have been initiated.
- worldwide first clinical results produce key know-how of how to obtain clinically relevant spontaneous Raman spectra from the human retina in-vivo; this IP is in evaluation for a patent submission by MUW including partners that contributed to the MOON2 system; in addition a publication targeting a high impact journal is in preparation;
- clinical results on age-related macula degeneration patients indicate the possibility to tell healthy from diseased retinas apart. This is in preparation for a publication after the patent and first publication has been finalized.
-clinical results on Alzheimer disease need further processing using advanced machine learning algorithms; first results are encouraging and will be disseminated through high impact journals;
-a route to market report has been prepared for the MOON1 and MOON2 technology as well as the exploitation strategy;
The development of compact akinetic high-speed swept source technology in MOON already represents a significant step beyond state of the art. Fast and phase stable light sources especially at the longer wavelength of 1060nm with the potential to become cheaper at large numbers are the key elements for the next generation optical coherence tomography (OCT) platforms. Wide field OCT angiography over a large field of view, that was up to recent only possible with planar fundus imaging techniques, is now recorded in a few seconds in 3D, with diagnostic image quality. This can further minimize the need for invasive, laborious, and risky fluorescein angiography. The retinal periphery has gained large clinical interest today, as early onset of diseases such as diabetic retinopathy but also signs of age related macula degeneration may be seen only in such enlarged field of view settings. This has immediate implications on the socio-economic system, as pathologic changes can be treated early on.
The most intriguing advancement through MOON is to pave the way for obtaining molecular fingerprinting in the living human retina by using Raman spectroscopy. Combining Raman spectroscopy with OCT will on the one hand provide highly sensitive morphological features with OCT, on the other hand it is possible to target specific disease biomarkers by Raman spectroscopy. So far, standard Raman spectroscopy has not been shown in the human eye. Identifying molecular biomarkers of the selected diseases and setting up the protocol for establishing a reference data base sets a standard operation procedure for clinical Raman spectroscopy, that can be followed by addressing other major diseases after MOON.
The multimodal MOON 2 platform is supported by a multimodal eye phantom, that has been developed within the MOON project. This eye phantom is not only a key asset for the MOON project, but might be of value for various other ophthalmic imaging platforms on the market. Especially also in view of the strict medical device regulations, having a phantom mimicking the optical properties of the human eye, simulating as well ametropic eye conditions, allows for validation but also as reference of commercial imaging platforms.
If successfully translated, MOON provides diagnostic tools to the clinician that are easy to operate, easy to access, cost-effective, and allow for early diagnosis of disease onset, before the quality of life has been already reduced, irreversible damages are done, and treatment becomes ineffective. Already by delaying the onset of wet AMD or hospitalization for dementia patients by early diagnosis based on MOON there is an enormous cost saving potential for the European economy.
The most intriguing advancement through MOON is to pave the way for obtaining molecular fingerprinting in the living human retina by using Raman spectroscopy. Combining Raman spectroscopy with OCT will on the one hand provide highly sensitive morphological features with OCT, on the other hand it is possible to target specific disease biomarkers by Raman spectroscopy. So far, standard Raman spectroscopy has not been shown in the human eye. Identifying molecular biomarkers of the selected diseases and setting up the protocol for establishing a reference data base sets a standard operation procedure for clinical Raman spectroscopy, that can be followed by addressing other major diseases after MOON.
The multimodal MOON 2 platform is supported by a multimodal eye phantom, that has been developed within the MOON project. This eye phantom is not only a key asset for the MOON project, but might be of value for various other ophthalmic imaging platforms on the market. Especially also in view of the strict medical device regulations, having a phantom mimicking the optical properties of the human eye, simulating as well ametropic eye conditions, allows for validation but also as reference of commercial imaging platforms.
If successfully translated, MOON provides diagnostic tools to the clinician that are easy to operate, easy to access, cost-effective, and allow for early diagnosis of disease onset, before the quality of life has been already reduced, irreversible damages are done, and treatment becomes ineffective. Already by delaying the onset of wet AMD or hospitalization for dementia patients by early diagnosis based on MOON there is an enormous cost saving potential for the European economy.