04.01.2023

Retina and choroid without secrets. STOC tomography enables unprecedented views of eye structure – new paper in iScience by prof. M. Wojtkowski et al.

Another milestone in eye imaging has been achieved. Polish scientists have developed a technique that enables visualization of the retina and choroid at discrete depths.

Modern imaging of eye tissues would not be possible without the use of Optical Coherence Tomography (OCT) scans. This method, one of the world’s most popular and accurate diagnostic techniques, has enabled us to understand more fully the mechanisms of many diseases and to select therapies more effectively. However, OCT is not a perfect technique. Coherent noise and/or limited axial range have prevented high-resolution imaging, as well as precluding full penetration of all layers of the retina and choroid.

Researchers at the International Centre for Translational Eye Research (ICTER) found a way around these limitations and developed Spatio-Temporal Optical Coherence Tomography (STOC-T). The latest research by the team led by Prof. Maciej Wojtkowski confirms that this method makes it possible now to view the retina and choroid with high resolution at distinct depths in the frontal section. No one in the world had succeeded previously.

The eye only sometimes reveals everything.

Imaging technologies such as scanning laser ophthalmoscopy and angiography with fluorescein (AF) or indocyanine green (ICG) dyes have translated to more accurate treatment of many eye diseases, but OCT has remained as the gold standard of clinical care. It is painless and non-invasive, but its limitations (noted above) make it challenging to distinguish essential morphological elements of the eye. OCT angiography (angio-OCT) makes it possible to visualize the microcirculation of the retina and choroid without injecting dyes, but the image quality still leaves much to be desired, and in many cases is not better than classic OCT. The imaging difficulty is exacerbated by the structural complexity of the choroid, as well as its functional diversity, including nourishing the outer layers of the retina.

The structure of the choroid is described as four layers: the Haller layer (the outermost layer, consisting of blood vessels of larger diameter); the Sattler layer (a layer of blood vessels of medium diameter); the choriocapillaris (a layer of capillaries); and Bruch’s membrane (the deepest layer of the choroid). The choriocapillaris (CC), retinal pigment epithelium (RPE), and photoreceptor cells constitute a unified metabolic complex whose structural and functional integrity is crucial for visual function.  Monitoring disruption of this tripart complex is essential for documenting retinal dysfunction, including age-related macular degeneration (AMD), diabetic retinopathy, uveitis, or other degenerative diseases of the retina.

The best currently available (though imperfect) method for visualizing choroidal vessels is ICG angiography, which is time-restrictive, allowing vessel observation only for a short time after dye injection. ICG angiography, however, cannot distinguish the different layers of the choroid nor reveal the complexity of the CC, which can only be seen to a limited extent with angio-OCT; but angio-OCT also falls short. Thus, angio-OCT images obtained at different depths of the choroid have been shown to have a similar appearance, suggesting that they may contain other layers, including the Sattler layer. Overall, the inability to distinguish among the layers makes any quantitative analysis of vessel density pointless.

From left to right: Prof. Maciej Wojtkowski, Piotr Węgrzyn, MSc and Mounika Rapolu, PhD.

Look deeper

In a previous paper titled “Light-adapted flicker optoretinograms captured with a Spatio-Temporal Optical Coherence-Tomography (STOC-T) system,” ICTER researchers described the Spatio-Temporal Optical Coherence Tomography (STOC-T) time-frequency OCT system they invented for capturing retinal optoretinograms.

Now, Prof. Maciej Wojtkowski’s team at ICTER, in a paper titled “Spatio-Temporal Optical Coherence Tomography Provides Full Thickness Imaging of the Chorioretinal Complex“, has shown that retinal images obtained using STOC-T maintain a uniform resolution of ~ 5 μm in all three dimensions, across a thickness of about 800 μm. This, in turn, allows them to obtain high-contrast, volumetric images of the choriocapillaris with reduced scattering effects.

“We applied known data processing algorithms and developed new ones to handle and process the acquired data sets to obtain high-contrast 3D data (volumes) for the retina in large fields of view. The technology and algorithms made it possible to image the retina and choroid at high transverse resolution at different depths, making the differentiation of morphology visible for the first time within the Sattler, Haller, and choriocapillaris layers,” says Prof. Maciej Wojtkowski of ICTER.

Image of a selected layer in the human choroid obtained by the new STOC-T method.

The main limitation for clinical application of this breakthrough technique is the current camera price, around 100,000 euros. The ICTER scientists expect that as the volume of camera production increases, the cost would gradually drop, although it is difficult to predict to what level. Indeed, many research facilities need help to afford such an expensive tool.

STOC tomography enables distinct imaging of all primary layers of the choroid while making difficult-to-image layers visible over a large transverse and axial range. The data can only be analyzed offline due to the low transmission speed between the camera and the computer. Considerable computer processing power is required to process all the vast amounts of data generated, but this can be reduced somewhat by using machine learning algorithms such as deep learning.

Using STOC-T for retinal imaging makes it possible to reconstruct the morphology of the cones of the human eye in a non-invasive manner. Thanks to the camera above, the STOC-T method makes it possible to capture the retina in a fraction of a second and record its entire depth in extremely high, unprecedented resolution. In clinical practice, even before the patient has time to blink, his or her eye will already be fully imaged, with an accuracy that allows single cells to be viewed. STOC tomography has the potential to usher in a new era in the diagnosis of eye diseases, although much more practical refinement needs to be done before it can be routinely disseminated in the clinic.

Author of the press release: Marcin Powęska

Cited paper:

Journal: iScience VOLUME 25, ISSUE 12, title: “Spatio-temporal optical coherence tomography provides full thickness imaging of the chorioretinal complex”, authors: Egidijus Auksorius, Dawid Borycki, Piotr Wegrzyn, Bartosz L. Sikorski, Kamil Lizewski, Ieva Zickiene, Mounika Rapolu, Karolis Adomavicius, Slawomir Tomczewski, Maciej Wojtkowski. DOI: https://doi.org/10.1016/j.isci.2022.105513.

03.01.2023

A new way to monitor blood flow in the brain. The πNIRS technique could revolutionize medical diagnostics – paper in Biomed by Dawid Borycki, PhD et al.

Monitoring the proper blood supply to the brain is crucial, not only to prevent neurological diseases but also to treat them. The parallel near-infrared interferometric spectroscopy technique, or simply πNIRS, could make life easier for doctors and patients worldwide.

Blood drives our entire body and is especially important for brain function. On average, about 50 ml/min/100 g flows through brain tissue – about 80-90 ml/min/100 g through the gray matter and 20-30 ml/min/100 g through the white matter. When there is a lack of oxygen and, therefore, a lack of proper blood supply, the death of nerve cells occurs – then we speak of a stroke. It affects about 70,000 people every year in Poland.

This is why it is essential to monitor cerebral blood flow in disease prevention and treatment. Neurology knows many effective methods for doing so, but many of them have their weaknesses. Now a team of neuroscientists led by ICTER researchers has developed a technique that can significantly improve the monitoring of cerebral blood flow in vivo. It is described in a paper titled. “Continuous-wave parallel interferometric near-infrared spectroscopy (CW πNIRS) with a fast two-dimensional camera,” by Saeed Samaei; Klaudia Nowacka; Anna Gerega; Zanna Pastuszak; Dawid Borycki, which appeared in the journal Biomedical Optics Express.

How to monitor cerebral blood flow?

Cerebral blood flow (CBF) uses about 15% of cardiac output to deliver the essential substances (oxygen and glucose) to the brain and take away the unnecessary ones (products of metabolism). Any deviation from the norm can cause temporary brain dysfunction and irreversible trigger diseases, with Alzheimer’s disease at the forefront. That’s why non-invasive monitoring of CBF is so important – we have several practical tools for doing so.

The first that comes to mind is functional magnetic resonance imaging (fMRI), probably the most widely used diagnostic test in the world, which also works well here. It allows monitoring local changes in brain blood supply and associated fluctuations in neuronal activity in vivo. The technique offers high-resolution images but is quite expensive and difficult to use in young children, for example. This is where optical methods come to the rescue.

Brain oxygenation can be assessed using functional near-infrared spectroscopy (fNIRS). This technique allows non-invasive measurement of regional cerebral oxygenation by using selective absorption of radiation of electromagnetic waves in the range of 660-940 nm by chromophores in the human body. It is often used as a tool to help monitor a patient’s condition, including during neurosurgery.

On the other hand, blood flow can be continuously monitored by diffuse correlation spectroscopy (DCS). Their most advanced modifications are based on continuous-wave (CW) lasers, which prevent absolute measurements. Interferometric near-infrared spectroscopy (iNIRS) can help here. Still, previous studies have shown that this method is too slow to detect immediate changes in blood flow that translate into neuronal activity. This is because it is a single-channel system, which measures the intensity of only the single-mode of the light collected from the sample.

Dawid Borycki, PhD (left) and Saeed Samaei (right). Photo: Karol Karnowski, PhD.

Innovative πNIRS

A team of researchers at ICTER decided to modify iNIRS, relying on parallel near-infrared interferometric spectroscopy (πNIRS) for multi-channel detection of cerebral blood flow. To achieve this, it was necessary to alter the iNIRS detection system. In πNIRS, the collected optical signals are recorded with a two-dimensional CMOS camera operating at an ultrafast frame rate (~1 MHz). Each pixel in the recorded image sequence effectively becomes an individual detection channel. With this approach, it is possible to obtain similar data as with iNIRS, but much faster – even by orders of magnitude!

Such an improvement, in turn, translates into greater sensitivity of the system and accuracy of detection itself. It is possible to detect rapid changes in blood flow related to the activation of neurons, for example, in response to an external stimulus or administered drug. The solution could be helpful for diagnosing CBF-related neuronal disorders and evaluating the effectiveness of therapeutic approaches, e.g., for neurodegenerative diseases.

  • This project will improve rapid, non-invasive systems for human cerebral blood monitoring in vivo. Continuous and non-invasive monitoring of blood flow could help treat significant brain diseases. In addition, quick detection of cerebral blood flow will bring us closer to developing a non-invasive brain-computer interface (BCI) that could help people with disabilities. Finally, our project will strengthen the tradition of Polish development in diffusion optics – says Dawid Borycki of ICTER.
Dawid Borycki, PhD. Photo: Karol Karnowski, PhD.

Tests have confirmed that the technique used effectively monitors prefrontal cortex activity in vivo. Moreover, it can be further improved thanks to the development of LiDAR technology and ultrafast volumetric imaging of the eye, reducing the cost of CMOS cameras. Thus, the πNIRS technique can monitor cerebral blood flow and absorption changes from more than one spatial location.

The data obtained by the πNIRS technique can be applied to the diagnosis of cerebral circulatory disorders, which will facilitate the evaluation of the patient’s condition and allow the prediction of early and long-term treatment results.

Author of the press release: Marcin Powęska

Photos by: Karol Karnowski, PhD

Commentary on photos:

In experiments conducted at ICTER, a team of researchers (Saeed Samaei, Klaudia Nowacka) led by Dawid Borycki used laser light along with an ultrafast camera to measure blood flow in the brain. The measurements showed that this novel technique, called parallel interferometric (π) NIRS, is sensitive enough to non-invasively analyze prefrontal cortex activation while reading unfamiliar text. which contributes to the development of a non-invasive brain-computer interface. Which contributes to the development of a non-invasive brain-computer interface.

Cited paper:

Saeed Samaei, Klaudia Nowacka, Anna Gerega, Żanna Pastuszak, and Dawid Borycki, “Continuous-wave parallel interferometric near-infrared spectroscopy (CW πNIRS) with a fast two-dimensional camera,” in Biomedical Optics Express, Vol. 13, Issue 11, pp. 5753-5774 (2022) https://doi.org/10.1364/BOE.472643

02.01.2023

Interview on how Data science is helping the search for more effective anti-cancer therapies by Marcin Tabaka, PhD

The scientist talks about ongoing research at ICTER in single-cell genomics, machine-learning algorithms, and single-cell sequencing technology.

The interview with the leader of the Computational Genomics Group Marcin Tabaka, PhD was produced by the Pro Science agency for SAS blog Data Science robię.

Link to the interview: Data science pomaga szukać skuteczniejszych terapii antynowotworowych (datasciencerobie.pl).

23.11.2022

Eyes well – dressed. We talk about the latest fashion trends in eyewear optics with the owner of the Studio Optyk optical store, Jarosław Bugaj

Nowadays, eyewear is a product that combines such diverse fields of knowledge and human activity as materials engineering, advanced digital technologies, ophthalmology and optical knowledge, precision craftsmanship, industrial design and art, and even luxury brand marketing. And in this view, they fit perfectly into the translational nature of an eye research centre like ICTER. Therefore, today we would like to introduce you to the topic of eyeglasses and eyewear fashion from the perspective of a person for whom their production, individual selection and repair are a personal passion and professional challenge.

Is it true that each of us will need at least a pair of eyeglasses during our lifetime? 

– Yes, it is true. It is inevitable. Sooner or later, even if we have not had to deal with glasses, at some point in our lives we might develop a young presbyopia, which is the loss of elasticity of the intraocular lens. Suddenly, we find that our hand needs to be longer to provide the proper distance to read the fine print. Then it is time to visit the ophthalmologist, measure the refraction, and check how much the natural lens is no longer efficient.

– So this means that we improve our correction by fitting lenses. But after all, we want to look well and fashionable, regardless of gender and age. 

– Yes, and then, in addition to the choice of lenses, we are faced with the choice of frames, which is not as easy as we thought. There are a lot of factors to consider and, above all, at the end of the day you have to like yourself and feel good in that eyewear. Often, we also want it to be in line with current trends. It used to be that glasses did not mean that much as today; they were rather considered a necessary evil. One had to wear them because he or she could not see properly without them. Nowadays, we also care about looking good in glasses and having something remarkable on our face; comfort and quality of craftmanship are also important. You could say that there are waves in eyewear optics; for example, there was a fashion for wire frames, then came the style for frames made of mass (plastic), and more recently transparent. Now it is all a bit mixed up. On top of that, each of us has individual preferences. Some people prefer strong frames that are clearly noticeable on the face and will mark their character, and others prefer softer, more subtle frames. It is essential that it is stylish and comfortable and that the patient feels good in the eyeglasses because it is a prosthesis of our sight, after all.

– Who sets the fashion trends in eyewear? 

– These days, major fashion houses mainly create fashion trends for ladies and gentlemen through their biggest, often exclusive, and most recognizable brands. In almost every seasonal collection, eyewear – mainly sunglasses but also corrective frames – is an integral part of the designs presented on the catwalk. Trends are also currently set by celebrities and influencers. Famous people, artists, and so-called stars often appear in eyeglasses, wearing increasingly exciting models, especially sunglasses, including those from the catwalks. Thus, they are arousing the interest of at least part of the public. We often have patients who ask for frames that a particular celebrity wears. This is interesting insofar as each face needs a slightly different frame. The one in which Christopher looks elegant and chic will not necessarily satisfy Charles, who also may feel uncomfortable wearing such frames. You also need to pay particular attention to individual preferences when choosing glasses.

 – Eyewear fashion is mainly shaped by the dictates of fashion houses. But other trends may impact on what we wear every day, too. A strong trend at the moment is ecology and sustainability. What does this trend look like in eyewear fashion? 

 – More and more manufacturers use recycled materials to make frames for sun and eyeglasses. We collaborate with a company that produces frames from raw materials from recycled ocean rubbish. More and more admixtures of wood and other natural materials appear in frames, which were initially poorly used due to their fragility and breakability. Nowadays, they are enriched with special accelerated plates, which make the luminaire more flexible and usable for longer. 

– Speaking of materials, what other materials besides those mentioned are used to create the frames?

Obviously, plastic. Today it is characterized by its enormous strength and lightness. These are usually thick frames, although lightweight, and also quite soft and therefore recommended especially for children. For this purpose, zylonite, or cellulose acetate – a hypoallergenic plastic – is used, and epoxy resin, which, when heated, is very malleable and easily adapts to the shape of the face. Metals such as surgical steel, aluminum, titanium, or beryllium are also used to manufacture frames. It all depends on the customer’s preference and wallet, as some frames, such as titanium, can be pretty expensive.

– Can you give a second life to your old eyeglasses? 

– Yes, some companies and foundations, also in Poland, collect used or unused frames and eyeglasses from opticians. In fact, I always have frames in my salon that I will not use, also for spare parts when repairing my customers’ glasses. From time to time, we pack them up and send them to the place where the frames are refurbished. Then a group of ophthalmologists and/or optometrists go to third countries and make glasses for people locally from these collected frames, so that they can be reused so that someone enjoys it. We walk around in a frame for a few years and it doesn’t wear out completely; after a few treatments, it can be refreshed. These are also helpful training materials for schools that train personnel of optical stores and optometrists, and this field of education has been growing rapidly in Poland for at least 10 years.

– Can you tell us about your adventure in optics?  

– My company is a family business. The business was developed by my father and he taught me the craft from childhood. I cannot imagine doing anything else. I am fascinated by glasses, optical technology, the selection of frames, how the eyeball is constructed, how the image forms on the retina. My dream is to go into optometry in the future. The current direction of optometry in Poland helps doctors to focus on the treatment of eye diseases, not only on the selection of vision correction. This is all the more so because technologies are becoming more and more advanced, the designs of the spectacle lenses themselves are basically changing from year to year, and the ophthalmologist is not necessarily aware of these design changes. The doctor focuses on the diseases, the final correction of the vision defect remains at the level of the personnel of optical store. When selecting glasses and frames, I prefer to check the prescription I get from the client, especially if it is for progressive or relaxed lenses, where there are progression channels or aberration zones. These are not big differences between the main prescription and my correction, often 0.5 dioptres or a slightly altered cylinder axis, but we are able to fine-tune this initial examination so as to squeeze the most out of the lens. Today’s lenses are more precise and require opticians to be more precise in their measurements as well. They are made using digital technology, where every 0.1 mm in fitting height or pupil distance or progression channel fit makes a huge difference to the patient. This significantly impacts patient’s comfort and adaptation to the new eyeglasses.


– Talking about technology, can you please tell us whether augmented reality is being used in the selection of frames, for example. Is this happening? 

– Yes, there are optical companies that are experimenting with it. The patient then stands in front of a device, a computer takes a scan of his or her face, then, based on an algorithm, calculates what frame would be optimal for that face and prints it in 3D. How this works in practice, I haven’t seen yet, but I’m curious to see if this selection – which is basically pure mathematics – will work in practice. After all, every face is different, and of course the computer can make very accurate scans, but whether this exact calculation will be good for a particular patient may always be a matter of dispute, as subjective issues come into play here, of one’s own judgement, which the machine is unable to assess. Of course, it is possible to write a program in which the patient can enter his or her preferences for such a setting, but there is no certainty that the final result will satisfy the patient. This already works in some places, but it is still not commercially applicable on a large scale. 

– Now, we often have several eyeglasses with different frames, especially when we have a visual impairment and do not want or cannot use contact lenses. We treat them a bit like a perfume or a watch. I am wearing this outfit today and I would like to wear matching eyeglasses.  

– Exactly, for me this is about sunglasses. I have a whole lot of them and I cannot get rid of any of them because I like them all. Today, glasses are an integral part of our image, whether we have a visual impairment or not. 

– While we are on the subject of functional glasses, what other types of glasses are still used in different areas of life? 

– There are, for example, sports glasses whose lenses are dedicated to golfers, pool players, runners, etc., who for various reasons cannot use contact lenses. Often these are special lenses, especially progressive lenses, designed to provide optimum functional comfort when playing specific sports. For example, for colliers who need to have full-spectrum vision. There are also safety glasses for people who work in difficult conditions – welders, turners – in which there is also the possibility of correction. An interesting example is ballistic goggles, designed mainly for advanced shooters over the age of 40, who encounter the problem inherent in all presbyopes, wanting to see the bow and target like in the good old days, but whose visual defect no longer allows them to do so. And this is also where dedicated glasses have their uses. 

– Where do you get from the eyewear that you offer? What are the leading countries in the production of frames and how does Poland rank against this?
 

– Poland ranks quite well, we have more and more domestic manufacturers of frames and the quality of these frames does not differ from their foreign competitors. The frames are really well made, high-quality materials are used in their production, and in terms of price they are definitely more friendly than foreign ones. I also have a wide range of frames from Italy and France in my showroom, as I love them for their design and often handmade, they are perfectly shaped and provide a high wearing quality. I also appreciate frames from Spain, which explode with colour and bold, modern styling, and are very lightweight and fun to wear. Polish frames are brilliantly made, but the design itself still needs work, and in this respect, we often take inspiration from foreign manufacturers. 

– How do you see the future of the eyewear industry?
 

– Since I have been in eyewear optics for more than 20 years, the industry has undergone a real revolution. Changes are happening right before our eyes, and they are being set by lifestyle, as customers’ needs are changing along with lifestyle changes. Hence the incredible popularity of sunglasses, which, in addition to their protective function, are actually a fashion accessory, new ideas from frame manufacturers for shapes, overlays, striking temples – everything that allows you to stand out from the crowd, emphasize your individuality and often also your material status. When it comes to design, many frame models are making a comeback. It could be said that every type of frame will have its time, albeit in a new guise. Also, material technology allows for incomparably more in design than before. 

Modern software on the ground of optical services is also entering the salons, including biometrics and VR technologies, which make it possible to acquire the extensive amount of data necessary to make individualized lenses optimally tailored to the needs of the individual patient. Such software is also being developed in Poland. In this respect, we are collaborating with Szajna in Gdynia, which is a manufacturer of progressive lenses and offers a VR diagnostic device to track the behaviour of the eye in real time with different accommodation and vision conditions. The data thus acquired provides additional information about the patient’s eye behaviour under different conditions and enables the optimal selection of progressive lenses. 

The future is happening today, and the optical industry itself has great potential for growth, not least because of the ever-increasing number of people requiring vision correction at different stages of life. I follow the latest eyewear trends with curiosity and attention in order to be able to provide my customers with a high-quality product that fully satisfies them medically, functionally and aesthetically.  

– Thank you very much for meeting me and I wish you the best of luck in the further development of your business!
 

The interview was written by Joanna Kartasiewicz, Research Funding Manager
, in collaboration with Jarosław Bugaj, owner of Studio Optyk Optical Store in Wolomin, near Warsaw. https://www.facebook.com/studiooptykwolomin/ 

Special thanks to Szajna company for the opportunity of testing their VR solution.

13.10.2022

Fascinated with the eye: Prof. Marco Ruggeri translates clinical needs into research, new ophthalmic technologies, and patents

On September 23, 2022, Prof. Marco Ruggeri of the Bascom Palmer Eye Institute visited our centre. His area of expertise includes instrumentation and quantitative imaging technologies for diagnostic and surgical applications in ophthalmology. Having a signed letter of intent with the Bascom Palmer Eye Institute, we discussed potential cooperation looking for joint projects to pursue, especially in the field of ophthalmic procedures. Our scientists Dr. Andrea Curatolo, Dr. Karol Karnowski, Dr. Slawomir Tomczewski, and Marcin Marzejon, M.D., gave Prof. Ruggeri a tour of the laboratories and discussed current research. Prof. Wojtkowski also met with the guest to talk about future projects. During the visit, Prof. Ruggeri gave an interview to our Communications and PR department about the popularization and dissemination of science in the United States and his approaches to promoting research and reaching the widest public with expert knowledge in the field of eye health and new ophthalmic technologies.

Interview with prof. Marco Ruggeri

Please tell us how your specialization translates into improvements in the state of expertise and excellence in vision research.

I work within several niches. First, we want to improve vision in old age so that people can preserve their vision quality later in their life. We first seek to understand why we lose our ability to focus on things up close with age by a condition known as presbyopia. To do so, we are studying the mechanics of accommodation, which is the autofocusing system of the human eye. This is the key part of the process as if we do not know how it works, we will not be able to fix it. We need to find out why we lose this ability as we age so we can counteract it. Since my specialty is optics and imaging, the way I do this is by visualizing and analyzing with our imaging technology what happens inside the eye in real life when we look at near objects and how that changes as we age. We also use this technology to assess the efficacy of the existing procedure to correct this condition, which is important as it provides feedback to manufacturers so that they can improve their products.

I also work on imaging technology for the early detection of eye diseases such as for example, keratoconus. This is important because, with our technology, clinicians will be able to act early and manage the condition in time to maximally preserve vision in patients. But there is more to it because these tools that we develop also provide clinicians with a way to understand whether the current therapies that they are using are effective or not, therefore improving the management of the disease.

As investigators working in translational research, our goal is to move basic science discoveries and technologies more quickly and efficiently into practice. Our vision research center is the ideal place to do so because we are literally located across the street from the hospital of Bascom Palmer Eye Institute, which is one of the largest in the nation. Our approach is to talk to clinicians and identify what the real clinical needs are, and then find a solution. We ask them what scientific discoveries would be game-changers in the field of ophthalmology and would make their life easier, and their feedback is worth focusing on. For example, our institute holds clinical grand rounds every Thursday morning where ophthalmologists confer on complex clinical cases that they discuss by listing different approaches to a given disease or injury. This is one of the best ways to understand what the clinical needs are. You just go there, listen, look at what they are doing, keep quiet, take notes, get ideas and talk to them. I have been doing this for years, and by now, I know most of the ophthalmologists at my hospital quite well. Some of these clinicians eventually became friends. I text them when I need their feedback on a research project, and they text me when they have a new clinical need. I realize this may not be a conventional way of setting scientific priorities, but for me, it proved to be extremely effective. And it has an additional benefit as it is an excellent way to disseminate my scientific work. I also send ophthalmologists my publications, presentations of my scientific work, and share with them the knowledge I explore, primarily driven by a grassroots clinical need.

To recap the life cycle of my work, I first look at a clinical need, and when I identify a meaningful project, I apply for funding to implement it. This is done by preparing a grant application together with a clinician. From the application submission to the funding of large multimillion-dollar from federal entities such as the National Institute of Health takes years, so it is important to be disciplined and act early. Once we receive the funding, I conduct joint research with the ophthalmologists, and the pathway is usually the same; we develop instrumentation and methods, we go into clinical studies on patients and see how it can affect clinical practice. The ultimate goal is to benefit the eye care of patients, so when we reach the end of a research project, and the technology is developed, we start approaching companies to see if they are willing to commercialize our technology bringing it to fruition for patients.

How did your adventure with optical imaging begin, and why did you choose this particular field?

It first started with the eye, even before optical imaging. The eye is a very fascinating part of the body from many points of view. It encompasses mechanical and optical functions, it converts light into electrical signals that travel to the brain and can be used as a window to the rest of the body. I got involved in eye research in Italy during my master’s degree thesis project in electrical engineering – an optical sensor to monitor the glucose concentration in the eye as a potential means of assessing blood glucose. Instead of detecting glucose concentration in the blood, the goal was to measure it non-invasively through the anterior chamber of the eye using an optical technique named polarimetry. That is how I got interested in eye research, but at that time, it was not imaging yet. After graduating, I looked for opportunities to work abroad in the field of measurement technologies applied to eye research. I then found a position as a research associate in the team at Bascom Palmer Eye Institute, developing one of the first implementations of high-resolution OCT retinal imaging for studying the human retina and the retina of small animal models of retinal diseases. It was during that time that I became familiar with the pioneering work of Prof. Wojtkowski on spectral domain OCT imaging. This year marks my seventeenth year at Bascom Palmer Eye Institute.

Are patients in the US aware that more accurate eye imaging methods lead to more effective therapies for eye diseases?

In my experience, not enough.

How do you disseminate your research results and publications?

I participated in the National Alliance for Eye and Vision Research, an organization that promotes advocacy and public education for the eye and vision research sponsored by the National Institute of Health and other federal agencies in the US. Every year they select a few researchers in the field of vision and train them to educate Congressional legislators, the media, and consumers about the value of eye and vision research. For example, we met with government policymakers and explained the importance of allocating taxpayers’ money to eye research and persuading them to promote more research funding for eyesight in the next bill. In the long run, this will save taxpayers money because the funded research will be spent to improve health care.

OCT imaging is a prime example of how technology can lead to significant savings of public funds, with an estimated of more than $10 billion in spending reductions over the last 15 years. The cost saving are the results of clinicians being able to provide more personalized eye care by using OCT to decide when prescription injection are needed to treat some forms of macular degeneration. Thanks to OCT, this process has been optimized by reducing the number of injections needed as well as complication and discomfort to patients.

As for the general population, there are not many channels to disseminate our research and stress its importance, but when it comes to popularizing science, I try to use the same simple language and message as for policy makers, showing the benefits of research applied in ophthalmology. Working in a hospital, I have the great opportunity to explain this directly to patients when they take part to our clinical studies. Other channels to reach the wider public are social media, such as Instagram, LinkedIn, Facebook.

What are the activities of the Bascom Palmer Eye Institute towards the promotion and PR of eye research and science?

Our communications and marketing department regularly publishes a magazine named “Images“ which focuses on the medical and scientific advances at our institution. For example, you can read how our doctors and scientists lead the fight against macular degeneration and how we help babies to see. We have also established a program with the local museum of science in Miami where scientists and clinicians from our institution organize evening seminars to educate the public to our research. Besides that, Bascom Palmer has official channels on social media too, and we are encouraged to work with them to promote our work directly on our institution profiles.

In your opinion, what is the best formula for bringing the nature, importance, and essence of the work of a scientist engaged in eye research to a wider public?

In general, scientists are more comfortable with the conventional and formal ways to disseminate research, such as publications in scientific journals, seminars, and presentations at conferences.  While this is important to passing on the benefits of our research to other researchers and professional practitioners, it has a limited outreach for the wider community. The newer generation of scientists is generally doing a better job at promoting the importance of their research on informal channels like social media platforms. Having a marketing department is a great tool for informing the public about research findings. As I explained before, direct contact with patients is helpful. Visits to schools are also a good way to introduce young people to science and get them used to the importance of scientific research. Popular science articles can also be published in the mainstream press, or events can be organized with the local museums for this purpose.

Do you notice any differences in the American and European approaches to science PR, and if so, what are they?

Europeans have made a great effort to promote their research; for example, we observe that scientists are encouraged to have their own laboratory websites or social media accounts. In the US, the promotion of scientists’ work is usually handled by the university’s communications departments. Europe also has great promotional mechanisms in place; for example, when receiving a grant, you are encouraged to advertise your research on a Twitter account. In the US, a special marketing department works for you; they are always looking for news, but we are not pressured, and it is only up to us how much we use their resources to make ourselves known to a wider audience.

What is your greatest professional goal in serving the public?

Generating solutions to improve eye care. The overriding sense of my work is to bring improvements to patients’ vision, ideally moving from research to commercial technology. My dream is that one day people in need can benefit from the technology I have developed.

What are your impressions of Poland and cooperation with Polish scientists so far?

I visited Poland in September of this year for the first time. My impression is that the Polish government is greatly investing significant amounts of resources and money in research. I see that scientific units have access to many grants and other sources of research funding. The cutting-edge technology developed by your centre and other institutions suggests that the level of education is very advanced in your country. Taking part in various conferences where I met Polish scientists, I can confirm that they never failed to present top-notch research. In addition, you are very open and value cooperation. I strongly believe in collaboration among scientists, and I consider that global research should evolve in the direction of international and interdisciplinary cooperation to unite forces and become complementary in what we do. This is the power of today’s science, enabled by modern technology and communication tools.

Thank you very much for the interview and for your visit to ICTER, Professor Marco Ruggeri. We look forward to working with you and can’t wait to start joint scientific projects.

From the left to the right: Dr. Andrea Curatolo, Prof. Marco Ruggeri, and Prof. Maciej Wojtkowski.

Photo: Dr. Karol Karnowski.

The interview was conducted by the Communication and PR Manager, Dr. Anna Przybyło-Józefowicz.

13.10.2022

World Sight Day 2022

World Sight Day celebrated annually on the second Thursday of October, is a global event meant to draw attention to blindness and vision impairments. It was originally initiated by the Sight First Campaign of Lions Club International Foundation in 2000. It has since been integrated into VISION 2020 and is coordinated by IAPB in cooperation with the World Health Organization. Every year they have different themes to celebrate World Sight Day. In 2021, The ‘Love Your Eyes’ campaign encourages individuals to take care of their own eye health and draws attention to over a billion people worldwide who have vision loss and do not have access to eye care services. 

Vision plays the most important role in seeing this beautiful world. The eye and the brain work together to help in proper vision mechanisms. These include cornea, lens, retina and optic nerves. Cornea is the front layer of the eye and it works by bending the light that enters into the eye. Lens is behind the iris and the pupil and it works with your cornea to focus the light that enters into the eye, much like a camera. The lens brings the image in front of you into a sharp focus, which allows you to see clearly. Retina is located at the back of the eye, which transforms the light into electrical signals. These signals are sent to the brain where they are recognized as images and the optic nerve transmits the electrical signals formed in the retina to the brain. Finally, the brain creates the images with the received electrical signal or stimulus. The photoreceptor cells involved in the visual cycle are the rods, cons the photosensitive ganglion cells. The rods mainly deal with low light level and do not mediate colour vision. On the other hand, the cones can code the colour of an image and contains three different types of cones. Each cone has different opsin so they will respond to a certain wavelength, or colour and light. The classical visual cycle is initiated by the conversion of a single photon of light energy into an electrical signal in the retina. The signal transduction occurs because of opsin which is a G protein-coupled receptor and it contains 11-cis-retinal chromophore. When a photon strikes, the phototransduction mechanism begins along with several cascade mechanisms. 11-cis-retinal undergoes photoisomerization to all-trans-retinal leading to a change in the conformation of opsin GPCR. The collective changes in the receptor potential of rods and cone cells due to phototransduction triggers nerve impulses that our brain interprets as a vision. After the isomerization procedure, and release from opsin, all-trans-retinal is reduced to all-trans-retinol and then transferred to the retinal pigment epithelium. In retinal pigment epithelium cells, several steps take place like esterification and many other that lead to the generation of 11-cis-retinol which is further oxidized to 11-cis-retinal before returning to the photoreceptors to combine with opsin to form rhodopsin.  

The vision in vertebrates is completely dependent on the continuous supply of 11-cis-retinal chromophore. There are several enzymes involved in the visual cycle and mutation in the genes of retinoid cycle proteins frequently causes impaired vision. Mutation in retinol dehydrogenase enzyme 5 causes only a mild clinical phenotype defect in the eye but mutation in RPE65 causes the severe blinding disease called Leber congenital amaurosis (LCA). Mutations in the gene rhodopsin are the major cause of Retinal Pigmentosa, in the form of autosomal dominant and recessive retinal pigmentosa. Knockout mice with a mutation in the rod opsin gene stop to form rod outer segment and have no rod electroretinographic (ERG) response but shows a cone response early in life and eventually disappear at three months of age.  

The Stargardt Macular Degeneration is the most commonly inherited maculopathy occurs in the young age. The symptoms of this disease start with blurred vision with progressive loss of central vision, central blind spots and a diminished ability to perceive colours. It is characterized by the accumulation of lipofuscin pigment in the RPE cells, which leads to the degeneration and death of the photoreceptor cells. This disease is mainly caused by the mutation in ABCR4 gene.

In the visual cycle, all-trans-retinal is reduced to a less toxic form all-trans-retinol by several alcohol dehydrogenases like RDH8 and RDH12. No mutation in RDH8 has been associated with a retinal dystrophy in humans. Mice with a knockout mutation in the RDH8 gene show normal kinetics of rhodopsin regeneration and delayed recovery of sensitivity following exposure to bright light.

There are three ways to treat the disease caused by mutations in retinoid cycle genes that have been investigated yet. The first is the replacement of defective genes by viral gene therapy. Replacement of the gene has been successful in models organism mice and dogs for LCA caused by a mutation in the RPE65 gene.  Clinical trials in humans with RPE65mediated LCA are set to begin soon.The second strategy involves the pharmacologic replacement of missing chromophore. It is suitable for diseases caused by impaired chromophore biogenesis, such as RPE65-mediated LCA.

As we are already discussed every enzyme/protein has its own significance in the visual cycle, the third strategy for the remedy of visual impairment is to slow down the synthesis of chromophore by inhibiting some steps in the visual cycle or limiting the availability of all-trans-retinol precursors. This approach is applicable to diseases associated with the accumulation of toxic lipofuscin fluorophores such as A2E. By partially depleting rhodopsin, the amount of all-trans-retinal released by light exposure is reduced.

Apart from them, there are so many common diseases associated with vision which are also the leading cause of blindness and low vision at an early stage of life. Some of the prominent diseases are age-related macular degeneration, cataract, diabetic retinopathy and glaucoma. Refractive errors are the most common eye disease reported in a majority of the population. These include myopia (near-sightedness), hyperopia (farsightedness), astigmatism (distorted vision at all distances). These can be rectified/corrected by eyeglasses, contact lenses and laser therapy, which is nowadays also a common approach. Cataract is another disease which is a leading cause of blindness across worldwide. In the cataract, patient observed clouding of the eye’s lens which leads to blurring of the vision. It can be cured with the help of laser therapy but access barriers, treatment costs and lack of awareness in developing and poor countries makes it one of the serious cause of vision loss. Diabetic retinopathy is a common complication generated due to diabetes. In this disease, new fragile blood vessels get generated and they are quite leaky in nature. Diabetic retinopathy usually affects both eyes.

In the current era, few routes of drug delivery are possible to rectify visual impairment or ocular diseases with retinoid analogues. These potentially available retinoid drugs could be delivered by eye drops, intraocular injection into different compartments of the eye, or periorbital injections into the fat surrounding the eye. The major drawback in the field of ophthalmology is not having high-resolution images of retina. But Nowadays the ray of hope is emerging with a new application of two-photon microscopy that exploits the intrinsic fluorescence of retinoids, permits visualization of RPE-cell structures in live animals. With further development, this technique may provide new information about retinoid metabolism and the response to treat the eye disease in humans.

Authorship: Integrated Structural Biology Group

22.09.2022

“Two photon vision and two photon eye imaging (2×2-PhotonVis)” project 

The “Two photon vision and two photon eye imaging (2×2-PhotonVis)” project was carried out within IChF PAN (Instytut Chemii Fizycznej PAN) and later ICTER from December 2017 to September 2022. The main goal of this project was to develop novel and original optical methods and instrumentation for functional testing of human and animal vision, using two-photon absorption and two-photon excited fluorescence processes.

The project broadened our knowledge about the optical properties of human and rodent retina and its susceptibility to non-linear optical processes of two-photon isomerization of rhodopsin chromophores and two-photon excitation fluorescence in RPE cells. The project resulted in nine papers published in JCR-indexed journals.

The POIR.04.04.00-00-3D47/16 project is carried out within the TEAM TECH programme of the FNP Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund.

Author: Slawomir Tomczewski, PhD
Grant awardee and project leader: Prof. Maciej Wojtkowski
Website of the #TeamTech project: https://2photon.icter.pl/
Image source: figure 8 – https://doi.org/10.1172/jci.insight.121555

30.08.2022

“The face of a modern Renaissance man” – an interview with Dr. Jakub Bogusławski, engineer of useful lasers

Jakub Boguslawski, Ph.D., is a scientist and engineer working on a new generation of compact, femtosecond fiber lasers for biomedical applications. He is currently a postdoctoral researcher in the Physical Optics and Biophotonics group at the International Centre for Translational Eye Research (ICTER), and an assistant professor at the Faculty of Electronics, Photonics, and Microsystems at Wrocław University of Science and Technology. In a recent interview for Poland Weekly, ICTER head Prof. Maciej Wojtkowski described Jakub as one of the representatives of the group who are pioneering unprecedented solutions and highlighted that “these small miracles are done by them every day, when they finish one, they start a new challenge” which proves their exceptionality. Jakub deals with a field of science that arouses a lot of emotions, both positive and negative; it is a field so far little understood by the general public, but invariably associated with solutions of the future and modern technology. We are aware that lasers can be deadly weapons, but we also have an idea that they can be used for other purposes. We talk about one of these useful purposes of lasers with Jakub Bogusławski in an interview in which he tells us about the underpinnings of his work and introduces us to the image of a man who builds lasers for the benefit of society.

Jakub, you work at the International Centre for Translational Eye Research (ICTER) designing lasers, a rather unobvious connection, as it is difficult at first glance to find a common ground between these two worlds. So tell us, what do lasers and eyes have in common, and isn’t this combination destructive?

On the contrary. On the one hand, if we recall the lasers presented in movies and imagine the laser beam hitting the human eye, we become concerned that the organ would be irreparably damaged. However, let’s not succumb to the illusion of Hollywood fiction. Of course, lasers can be harmful to the human body at a high dose of energy. However, the development of science and a better understanding of the functioning of living organisms has allowed us to create conditions in which this type of energy is harmless and even proves useful. Examples include early diagnosis of eye diseases or developing new ophthalmic therapies.

So, to the question of what lasers and eyes have in common, the answer is that the contact of a laser light beam with the human eye can provide a lot of helpful information. How does this happen? The introduction of laser light into the eye, specifically into the retina and retinal pigment epithelium, results in fluorescence excitation. The fluorescence is emitted by naturally occurring fluorophores present in the eye. On its way out of the eye, the light is recorded using a highly sensitive photodetector, a photomultiplier. The optical system used here is called a scanning laser ophthalmoscope and is an entirely non-invasive and non-contact system. It first feeds light into the eye in the right way and then leads the light from the eye to the photodetector. The whole process is based on guiding light into and out of the eye, then the resulting data is processed in a computer, and we get an image that can then be analyzed and interpreted. The optical system is a bit similar to the OCT currently used in ophthalmologists’ offices. However, we only use a different light to excite and record the effects occurring in the eye. This phenomenon is called two-photon excited fluorescence.

Tell us what you do in your work.

I am a laser engineer, and I am involved in designing and developing new configurations of femtosecond lasers, that is, lasers that generate very short pulses of light. In the context of eye research, this property is beneficial because it solves the problem of lack of access to fluorophores in the retina and retinal pigment epithelium. The retina is at the back of the eye, and various fluorophores provide information about the functioning of that retina so that we can identify what changes occur there. The technical challenge is that those fluorophores can be stimulated using UV light because they absorb light in the range of these wavelengths. Nevertheless, such radiation cannot be shone into a person’s eye because it has high energy and would immediately destroy it. We have discovered that by using ultrashort infrared pulses, this problem can be solved by two-photon absorption, using two photons of half the energy, which is safe for the human eye. With this technology, we can safely bring this light into the eye and access those fluorophores that we could not access before. This is complementary information that, in other ways, no one could get in a way safe for human vision, at least at the moment. And this is precisely what femtosecond pulses are needed for, with adequately selected parameters: they must be calibrated in the right spectral range, very short, and with a specific repetition rate. Such lasers so far did not exist, they could not be bought, and we undertook to design and construct a special laser with precisely these parameters, which are optimal.

A whole group of people under the leadership of professor Grzegorz Soboń at the Wrocław University of Science and Technology was involved in constructing the first laser with the parameters mentioned above. Although I was not involved in the first stages, having joined the team in Wrocław more than a year ago, I am now engaged in the engineering and construction this type of system. All the components needed for the construction of this laser are commercially available; nevertheless, since it is a fiber laser, its construction is based on different types of optical fibers, which need to be adequately designed, and then combined to shape the radiation properly. It is a proprietary, high-precision, and high-tech art of engineering.

What values guide you in your scientific work?

I think it would be the usefulness. I want the things I do to be useful to someone, to create new opportunities, and to solve existing problems. What we are doing at ICTER is an excellent example because it is not art for art’s sake or science for science’s sake, but we have a specific problem to solve. Our goal is fundamental: to protect people’s eyesight, help diagnose eye diseases and develop new ophthalmic therapies.

What are the biggest challenges and most beautiful aspects of scientific work?

The biggest challenge for all scientists is to know what problem to tackle because the number of possibilities is enormous, and humanity already knows a great deal. Identifying a problem and defining it, then choosing whether this path we want to take makes sense, whether anyone needs it, whether it has a chance of succeeding, or whether it is worth pursuing, is perhaps the most challenging question. In particular, there are also huge costs along the way because this research is expensive, and many people are involved. Much time is devoted to it, and at the beginning, it is unclear whether it makes sense, whether it can be done, or whether it will not be a wasted effort. On the other hand, this can also lead to those most beautiful aspects of scientific work, because working on a scientific problem can go in such an unexpected direction. We can encounter a lot of surprises and unforeseen twists and turns. We can plan something for ourselves, and later it turns out we are somewhere else than we thought we would be. For a scientist, this is fascinating.

Tell us about your passions outside of work.

My biggest passion is food, which means both cooking and eating. I like to read books about cuisine and watch cooking shows. When I travel, I try to find out what is typical food in a particular place and why people eat it; it interests me. Besides, I also do sports of various kinds, such as running, hiking, biking, and water sports, especially windsurfing. I have participated in several marathons.

I see that your eyes have two different colors. What is the reason for this condition, and how do you feel about having such outstanding eyes? Did it influence your decision to do research specifically on eyesight?

Dr. Jakub Bogusławski. Photo: Dr. Karol Karnowski

This effect is called heterochromia, a genetic defect that occurs in less than 1% of the population, but it does not affect vision or have any effects other than the different colored irises. Occasionally someone will notice that one is green and the other brown, but most people do not react to my eyes at all. This condition did not influence my decision to work at ICTER. I am here by accident. I only deal with eyes because I deal with lasers, and the utility of lasers in the context of eye research led me to our centre. These lasers I am constructing could be useful for seeing something more in the human eye than we could see before.

What are your career plans for the next ten years?

First of all, I want the results of my work to be useful. I want to construct devices that will work and can be used by someone. I want these lasers to be able to do something good for society. I dream that the things I construct will be helpful and practically used. For example, the new fluorescence imaging of the eye, can be used clinically and get information that will help diagnose ocular diseases earlier. More broadly, I would like to look for new practical applications of these lasers that we can build because they are quite unique, so these features can be used somewhere it really makes sense. Such a laser is quite complicated, quite expensive, so I would like to find such applications that give enough new information and possibilities that it makes practical sense to use them.

At the moment, I plan to further develop my career in Poland, you can do research here at a very good level, and I feel good here. I have traveled abroad several times for scientific internships, including working at the University of California Irvine in Prof. Krzysztof Palczewski’s group, where we built a similar set-up to the one we have in Warsaw. Since there is an ophthalmology department, ophthalmic companies and doctors are working there, it is a good place to test this method on patients with eye diseases. Previously, I also trained in Stockholm at the Royal Institute of Technology KTH, Aalto University in Finland, and Helmholtz-Zentrum in Dresden. All of these visits involved the development of new types of lasers or developing femtosecond pulse shaping techniques.

I am just starting an NCN-funded grant in which my team of 3 and I will work on a new class of laser for two-photon excited fluorescence ophthalmoscopy. We want to develop a “smart” femtosecond laser that can adapt its parameters by itself to the object being imaged. The title of the grant is “Adaptive femtosecond pulse source for multiphoton fluorescence microscopy and ophthalmoscopy,” and the project will be carried out at the Wrocław University of Science and Technology. So the implementation of this grant is undoubtedly one of the plans for the next few years.

Thank you for this interview, Jakub. I am uplifted by your attitude and wish you good luck with all your plans.

Although he is developing laser technologies of the future that will shape the progress of ophthalmology, Dr. Jakub Bogusławski is a humble scientist. The greatest value that guides his work is utility directed at solving existing research problems. Through it, he shifts the hitherto existing boundaries of science. To Jakub and his teams from the Wrocław University of Science and Technology and ICTER, we owe the invention of lasers whose beams can be shone harmlessly into the human eye to gain crucial information for advancing the early diagnosis and developing new therapies for eye diseases.

The interview with Dr. Jakub Bogusławski was conducted by Dr. Anna Przybyło-Józefowicz

Photos: Dr. Karol Karnowski