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Projects / Programmes source: ARIS

Microspectroscopy-based optimization of the effects of laser pulses on the retina

Research activity

Code Science Field Subfield
7.00.00  Interdisciplinary research     

Code Science Field
B120  Biomedical sciences  Molecular biophysics 

Code Science Field
1.03  Natural Sciences  Physical sciences 
Keywords
multimodal molecular imaging, fluorescence, two-photon absorption, laser technologies, photocoagulation, age-related macular degeneration
Evaluation (rules)
source: COBISS
Researchers (13)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  20208  PhD Zoran Arsov  Biotechnology  Researcher  2016 - 2019  135 
2.  18473  PhD Vladimir Debelič  Neurobiology  Researcher  2016 - 2019  46 
3.  13674  PhD Brigita Drnovšek Olup  Neurobiology  Researcher  2016 - 2019  344 
4.  21546  PhD Tilen Koklič  Physics  Researcher  2016 - 2019  139 
5.  39926  Marko Kozinc  Technology driven physics  Researcher  2018 - 2019 
6.  36989  Uroš Orthaber  Technology driven physics  Beginner researcher  2016 - 2017  12 
7.  30967  Ana Pajtler  Medical sciences  Researcher  2016 - 2019  42 
8.  34747  PhD Rok Podlipec  Physics  Researcher  2016 - 2019  85 
9.  18273  PhD Janez Štrancar  Physics  Head  2016 - 2019  374 
10.  32057  PhD Iztok Urbančič  Physics  Researcher  2016 - 2019  133 
11.  25125  PhD Mojca Urbančič  Neurobiology  Researcher  2016 - 2019  222 
12.  24276  PhD Andrej Vrečko  Physics  Researcher  2016 - 2019  30 
13.  30871  PhD Maja Zorc  Physics  Technical associate  2016 - 2019  57 
Organisations (3)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  91,002 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,761 
3.  1617  OPTOTEK razvoj in proizvodnja optične in laserske opreme d.o.o. (Slovene)  Ljubljana  5326389  32 
Abstract
BACKGROUND Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. It mainly affects older adults and is still considered as un-preventable. It is therefore projected that AMD might affect 200 million people in 2020 worldwide, which will pose a significant socio-economic burden especially on the aging population of the industrialized countries. PROBLEM The most severe of the AMD forms is caused by an abnormal growth of blood vessels behind the retina. The current treatment of choice consists of regular intraocular injections of anti-vascular endothelial growth factors that need to be applied every few weeks for lifetime. Though such treatment is likely to prevent blindness and can sometimes improve the patient’s vision, it is extremely unpleasant, costly, and accompanied by several vision-threatening complications. The current therapeutic alternative relies on thermal degradation of the abnormal tissue by visible laser light, e.g. by photocoagulation. Its main drawback is the poor localization of the photo-induced effect and consecutive damage of the neighboring healthy tissue. AIM The uttermost goal of the proposed project is to improve the photocoagulation therapy by precisely targeted illumination with specific focusing of laser pulses and concomitant monitoring of the induced photocoagulation, limiting the intolerable damage of the healthy retinal tissue. SOLUTION The improved spatial precision of photocoagulation will be achieved by exploiting the two-photon absorption of the high-power near infrared (NIR) laser pulses in hemoglobin. This non-linear process occurs only in the limited focus volume, allowing the NIR light to pass not only through the optically transparent ocular tissue, but also through otherwise absorbing layers of healthy retinal blood vessels and melanin pigment layer that lie in front of the abnormal blood vessels of AMD. The same localization principle will be used for pre-treatment diagnostics and real-time evaluation of the therapy. Following the most recent trends in medical diagnostics, multimodal molecular imaging with microspectroscopic and lifetime analysis of retinal autofluorescence will be applied to identify local molecular properties of the tissue. The abnormal presence of hemoglobin and the degree of its photocoagulation will be deduced from the measured fluorescence spectral shape and lifetime. IMPACT (Scientific, social, economic) The proposed project is expected to introduce a novel theranostic approach based on two-photon absorption processes and molecular imaging by an innovative laser source. Integrating all the acquired knowledge, the technology for a new generation of microspectroscopically guided ophthalmic photocoagulators will be developed by Optotek, an internationally renowned Slovenian company for laser medical devices. Extremely broad further benefits can be foreseen, ranging from less invasive and cheaper methods for AMD treatment, improved public health and increased productivity of the aging population, to new jobs in a highly prospective environment.   TEAM STRENGTHS The partners involved combine a multitude of knowledge, skills, and equipment, necessary for the success of the project. The main expertise of the Laboratory of biophysics (LBF) from “Jožef Stefan” Institute is the development of fluorescence-based microspectroscopy techniques. Optotek has recently invented a new compact and price-competitive high-power pulsed laser, which will serve as the starting point for the further development of the demonstrator. The latter will be coupled to other technological solutions of OD-OS, a German company specialized in laser retinal treatment. Eye clinic at University medical center Ljubljana (UKC), Schepens Eye Research Institute at Harvard Medical School (USA) and Vienna Institute for Research in Ocular Surgery (VIROS; Austria) will serve as regular medical consultants, guiding and evaluating the progress of the research from
Significance for science
IMPACT ON THE DEVELOPMENT OF THE SCIENTIFIC DISCIPLINES The proposed project will implement the state-of-the-art nonlinear optical phenomena to improve the localization of the laser light absorption, thus reducing damage to the healthy tissue, as well as to diagnose the very local condition of the retina prior to and during treatment. By application and development of two state-of-the-art microspectroscopy techniques (FMS and FLIM), the project will contribute to the capabilities of fluorescence-based molecular imaging in the eye, merging the expertise of LBF and UKC. The introduction of diode-pumped solid state laser technology by Optotek brings new opportunities for the development of therapeutic laser sources. An important contribution is expected from development of novel image analysis and laser-tissue interaction modeling software tools, which will significantly improve the control of the laser light and of its effect on the tissue. An immediate effect of project activities is expected within the international ophthalmology community due to the strong involvement of the R&D and clinical personnel of UKC, OD-OS, Harvard and VIROS. Through international expert connections, further applications of the technology to other neovascular complications will be sought. Due to its outstandingly interdisciplinary character the proposed project will boost the complementary knowledge transfer between different scientific disciplines. Hence, this project will undoubtedly impact the fields of biophysics, ophthalmology and the technology of the medical devices.   CONSISTENCY WITH THE RESEARCH POLICY OF THE REPUBLIC OF SLOVENIA (RS) AND EU The proposed project clearly follows the directives and priorities of the two main strategic documents: the Research and innovation Strategy of RS 2011-2020 (RISS) and the Strategy of development of RS 2014-2020 (SDS). By connecting a very relevant age-related degeneration to the novel biophysical research concepts, high scientific excellence is anticipated. The interdisciplinary character is expected to boost the publication IF, aiming at the letter format journal with IF above 10. We expect increasing the intellectual property (IP)-related income of the public research organization, becoming less dependent on the public financing. The proposal encourages the team to protect the generated IP and to finalize developments into the product as soon as possible. The most appropriate means of legal protection (patent, trade secret, copyright) or public presentation of project results (conference contribution, scientific articles, public announcement) will be identified. The consortium is actively developing international integration and studies the possibilities of the H2020 proposal within ICT-KET or even FTI calls. The project will provide students the access to the state-of-the-art research and development in the fields of biophysics and biophysical methods, ophthalmology, optics and photonics technologies, laser technologies, etc.
Significance for the country
IMPACT ON THE SOCIETY AND THE HEALTH OF THE CITIZENS The proposed theranostic approach aims at a less invasive AMD treatment (no recurring injections) at a reduced cost (6 MEUR/year spent in Slovenia).   IMPACT ON THE COMPANY AND THE PHOTONICS INDUSTRY SECTOR Introduction of the world’s first ns-pulsed diode-pumped solid state laser can boost Optotek’s global market share within their existing ophthalmic applications from 15% in 2014 to 20% in 2020. At the therapeutic market for standard photocoagulation, which is 3 times bigger (300 MEUR), Optotek will target 5% share in 2023 (currently 0%). Together this will increase the added value from 48 kEUR per employee in 2014 to 70 kEUR in 2020. Most importantly, the proposed AMD-theranostic system opens a completely new market: currently only 10% of AMD cases are treatable (drug sales 2.4 billion EUR in 2012 and growing), whereas no method exists for 112 million patients with early stage AMD. This application thus represents by far the highest potential for Optotek (estimated market )400 MEUR), which could increase the added value to 100 kEUR per employee by 2022. The novel AMD-theranostic system is also expected to define a new segment of smart diagnostic/therapeutic systems for ophthalmology and other medical fields, strengthening R&D activities and investments in Optotek, bringing new employments and attracting the best students. Thus, a 100-fold return of investment of Optotek (25%) and ARRS (75%) is anticipated in the next 10 years. CONSISTENCY WITH THE POLICIES OF THE REPUBLIC OF SLOVENIA (RS) AND EU The novel theranostic approach targets the 1st priority axis (PA) of the Strategy of the development of RS 2014-2020 (SDS) (”Competitive economy”) and the 1st PA of the Operational program of RS 2014-2020 (OP) (“International competitiveness of research, innovation & technological development”). Career building opportunities due to increased R&D investment and knowledge flow between public research institutions and companies target the 2nd PA of SDS (”Knowledge & employment”) and PA 10 of OP (“Knowledge, skills & lifelong learning to enhance employability”). The proposal is consistent with the concept of value chains (Strategy of Smart Specialization of RS 2014-2020, priority area “S-Industry 4.0”, domains “Medicine” & “Smart factories”).   THE ADEQUACY OF THE PLANNED DISSEMINATION ACTIVITIES AND IP PROTECTION Steering committee will judge the commercialization potential of the results for their legal protection or public presentation. Two international patent applications are anticipated, which will be managed by Optotek and technology transfer service at IJS. For profitable results, Optotek and OD-OS will identify the market size and estimate the costs of commercialization, including clinical trials. Optotek and UKC will investigate the possibilities to validate the technology in a real environment and identify other applications of the technology. Demonstrators will be presented at ophthalmic trade fairs.
Most important scientific results Interim report, final report
Most important socioeconomically and culturally relevant results Interim report, final report
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