21.03.2023

Interview with Anna M. Ambroziak, MD, Scientific Director of the Ophthalmology Center Świat Oka in Warsaw

Dr. Anna Ambroziak is an ophthalmologist specializing in eye diseases with 27 years of professional experience and an Assistant professor at the Faculty of Physics, University of Warsaw. Dr. Ambroziak is a member of the Polish Society of Ophthalmology (PTO) and the Society of Polish Ophthalmic Surgeons (SCOP). Dr. Ambroziak is also the Polish representative in the European Contact Society of Ophthalmologists (ECLSO), lecturer at the European Studies in Ophthalmic Optics and Optometry, and editor of the position paper of the Polish Expert Group of the Academy of Ocular Surfaces.

Dr. Ambroziak has more than 200 publications to her credit. She promotes the idea of interdisciplinary cooperation. She adheres to the philosophy of a holistic approach to the patient. Under her leadership, the Ophthalmic World Eye Center in Warsaw (Centrum Okulistyczne Świat Oka) has won the Health Ambassador Award for its expertise, experience and improvement in patients’ quality of life.

Based on the clinical studies conducted by Dr. Ambroziak, a therapeutic lens made of lotrafilcon A was registered by the US FDA. She is the winner of the ECLSO “Kersley Lecture” grand prize and the Medical University of Warsaw Scientific Award.

Dr. Anna M. Ambroziak

We present an interview with Dr. Anna Maria Ambroziak conducted by the Physical Optics and Biophotonics group at ICTER.

In recent years, the development of cooperation between ophthalmology and optometry in Poland has been noted. ICTER brings together specialists from the fields of optics, optometry, engineering, physics, biochemistry, mathematics to create specific tools and solutions that can translate into improved patient care. How do you think the collaboration of those involved in vision science has been changing in Poland over the past decades?

So, to begin with, a little bit of my personal memories, which will shed some light on the history of optometry in Poland. That is, a few words about how Optometry became the foundation of Ophthalmology in the country on the Vistula River.

In ’98, as a member of the Board of Directors of the Contact Lens Section of the Polish Ophthalmological Society, I organize a meeting, and a few months later a contactology symposium. That’s a little over a year after the first year of optometry postgraduates graduate from the K. Marcinkowski Medical University. The following years saw more conferences. Among the guests invited to the symposium were world-renowned optometrists, contactology experts – including Brian Holden, Lyndon Jones, Philip Morgan, Keith Edwards, Dwight Akerman, Brian Tompkins, Eric Papas and myself – a young ophthalmologist ready to change the world. Since the beginning of my career, I have been involved in the education and development of optometrists. I have been working at the University of Warsaw since 2011, for more than 10 years served as deputy editor-in-chief of the medical journal Contactology and Ophthalmic Optics. I took an active part in such events as the introduction of the world’s first silicone hydrogel lens to the Polish market. My love for contactology exploded suddenly and turned into a mature, fulfilling relationship. Scientific research on the effects of prolonged contact lens wear on the ocular surface became the subject of my doctoral dissertation defended with distinction at WUM. On the basis of clinical studies conducted by me, a therapeutic lens made of lotrafilcon A was registered by the US FDA.  To paraphrase a classic, it was worth looking at such a map of the world which includes utopia. For me, there was no dilemma, problem or division. The more I know, the more questions I ask and the more joyfully I share knowledge. In this natural environment of broadly understood vision care, we should work together to best serve each other and our patients. There is no room for divisions here, we are one compatible, integral creation and naturally work together.  For a wise scientist, the other person is an opportunity for development and cooperation, and if also for competition – it is only for the positive and constructive one. Years of work and creation of this ideal world have allowed us to raise new generations of specialists, these new generations work with each other and learn from each other. The Ophthalmic Center Świat Oka is a scientific and research & science clinic with modern training facilities, where optometry and medical students learn and work under the supervision of specialists, where clinical trials of drugs and technologies are carried out, and papers and publications are produced, including many on rules of procedure and ophthalmic-optometric cooperation. I strongly recommend this model. There is much work ahead of us, but let’s remember that changing the world should always start with ourselves. I have been supporting the development of Optometry in Poland since the beginning, working as an assistant professor at the Faculty of Physics at the University of Warsaw. In the academic environment of Warsaw, I was the first ophthalmologist to start teaching new generations of optometrists – teaching the younger generations at a proper level should be the primary goal for eye care specialists. I execute the plan according to which the Ophthalmologist and the Certified Optometrist work together on one level. This cooperation is not possible without the presence of scientists from the fields of optics, physics or mathematics, biology and chemistry. Education and Science is the future not only for this country, but for the whole world.

What are the most troublesome diagnostic limitations and needs of a modern ophthalmology center? If you could “conjure up” the equipment of your dreams, what would it diagnose (or what other function would it perform) and how?

Our tears are a vast, still tentatively explored, wealth of knowledge about our organisms enabling us the insight into more than just our genomics, and this is one of the directions I dream of.

Our brains are the realm where perception happens and where reality is created, and we can extend it using artificial intelligence; this is another important signpost for female and male wizard scientists.

The power of now shows, at the same time, a great need to monitor the progression and development of myopia. We know more and more about the effectiveness of the available solutions and are oriented towards polytherapies. We know more and more about new optical designs for eyeglasses and contact lenses, and about the long-standing results of meta-analyses of the use and clinical evaluation of these products. We are definitely vocal about the need to measure the axial length of the eyeball, the need to monitor and treat pre-myopia, and the impact of the pupil width on monitoring the development and progression of myopia. The power of now is also the power of creation, so we keep track of what science brings to practice. For example: Transplantation of embryonic human stem cells into the retinal pigment epithelium (RPE) is happening before our eyes – now in the cases of age-related macular degeneration, but soon in myopic maculopathy. The M1 molecule promotes the regeneration of retinal ganglion cell axons which means the potential to restore the activity of target neurons and thus restore visual function in cases of both maculopathy and neuropathy.

Do you think the demand for devices and techniques for visual system diagnostics will grow in the near future? Why?

The eyesight is the most important sense, but it is subject to a series of involutionary processes and the influence of exo- and endogenous factors. The increase in life expectancy has made the estimation numbers in epidemiology unequivocally indicate the imminent scale of the challenge. Returning to the example of myopia, we know that soon half of the world’s general population will be myopic and thus the number of myopia-related complications will increase, including the most serious and severe myopia-related maculopathy, which does not exclude the coincidence of age-related changes. Prevention based on modern, reproducible, minimally invasive and highly specific diagnostics is the basis of ophthalmology. In addition to the pandemic of myopia, often the same patients due to being overweight and obese add to a growing group of patients burdened with diabetes. In this group, the rise of maculopathy is also a critical challenge.

Online doctor consultations are already exploiting algorithm and data analyses today. Diagnostic tests and therapeutic regimens are becoming more precise, new previously unknown solutions and materials are being used. Technologies using virtual reality are already the foundation of our practice in vision therapy.

Artificial intelligence in the daily work of an eye care specialist involves much more than just monitoring fundus changes or the screening programs we are already familiar with nowadays and that are particularly advanced in the prevention of diabetic changes. The pandemic has brought us new challenges, new goals and new experiences.

Dr. Anna M. Ambroziak with a patient.

Are there eye diseases whose pathogenesis we have yet to understand?  Do they occur frequently – affect many people?

As I mentioned, the time of SARS-COV-2 is an acceleration of the development of the implementation of technological innovation and artificial intelligence in medicine. For us, this time is also the intersection of the myopia pandemic, diabetic eye syndrome and digital visual fatigue, with numerous challenges ahead.

The foundation of Science and Humanity is to develop and provide open-ended answers.

The pathogenesis of most ophthalmic conditions is based on genetic and environmental risk factors yet a shift in the importance of genotype versus phenotypic expression under the influence of external and internal causes of an individual definitely took place.

If we use the example of intelligence, as my “genetic masters” Prof. Ewa Bartnik and Prof. Wojciech Dragan say, when we analyze the entire population (from a newborn to the oldest person) the level of heritability of intelligence is 50%, and differences in the influence of genes on intelligence depend on the activity of the environment.

Genetic variances and environmental variances are constantly modifying our pathogenetic cocktails. If we analyze the non-modifiable and modifiable substrates, the last decades and years, in addition to the positive aspects such as extending our lifespan , and remember that age is the primary risk factor for diseases of all kinds, risk factors such as climate change, environmental pollution, changing educational and working conditions, food modifications, widespread consumption of excess calories, especially in the form of highly processed, sweetened products are now critical health challenges,  also for the organ of  the visual system.

Psychology and especially psychosomatics are also of increasing importance.

Visual perception is another area being explored and tamed.

In a world of artificial intelligence, we still lack an integral view, and currently, all technologies absolutely require reason and humility, and human knowledge. Soon, refractive lens and corneal surgery will move toward modifying the cornea and implanting specific lenses that will adapt their optical properties to our visual requirements, varying lighting, different contrast and dynamic visual work distances. We are very privileged that such a huge technological leap has taken place before our eyes. Education, thanks to new tools and especially the use of the metaverse world, will also be decidedly friendlier.

We have shifted the boundaries of senior age and the age of 40-65 is called maturity and we increasingly speak of old age only after the age of 80.

We mature, develop, age, we are subject to involutionary changes and multiple factors from the day we are born and even throughout our fetal life. This applies to all structures of the eye, but especially significantly to the retina and lens, which processes known as presbyopia are associated with. Keep in mind that it is not a disease, but many conditions can accelerate and intensify this process.

The lens of the human eye is an intraocular structure whose main tasks are active participation in accommodation, refracting light and maintaining clarity. A normal lens, outside of fetal life, is devoid of blood vessels and nerves and is completely transparent. The lens of the eye is a unique structure, and its growth is caused by the addition of new cells inside the surrounding capsule. The new fibers become thickened and fuse with those previously formed. Older cells are not discarded or removed, but placed in its center. This is necessary to maintain the metabolic viability of the outer cortex (and thus the entire organ) and to produce the refractive properties necessary to focus images on the retina and reduce spherical aberration. With age, however, this brings undesirable consequences, including the development and progression of presbyopia.

Presbyopia is not a refractive defect, it is a peculiar indisposition of near vision manifested >40 years of age resulting from widespread involutionary processes. It is caused by physiological anatomical and functional changes occurring in the intraocular lens, especially its capsule, and functional changes in the ligamentous apparatus, resulting in decreasing amplitude of accommodation, i.e. reduced/insufficient ability to sharpen the image of close objects. Interestingly, the strength and work of the ciliary muscle is not affected, thus the full contraction and diastole of this muscle induces adequate changes in the tension of the ligamentous system, and only these forces are met with an altered susceptibility of the lens capsule and the lens itself to respond to a given accommodative stimulus. Such a condition calls for support, i.e. optical correction for nearsightedness. Its recommendation should not be delayed, as procrastination may result in causing symptoms of asthenopia and impaired nearsightedness in the future.

Let’s give our organ of the visual system the best possible correction, let’s use all possible solutions. Our brains like to be given tasks, they like to learn, and if we feed them properly, they will help us use more and more precise, higher resolution correction methods for years to come, as long as we make sure that the plasticity of our brain is preserved.

Dr. Anna M. Ambroziak talks with an invited expert during an interview series entitled “Let’s talk about sight” (#PorozmawiajmyoWzroku) at the Ophthalmology Center Świat Oka in Warsaw.

Can we guard against age-related retinal degeneration? What can we do in this area and, in your opinion, is such knowledge generally available?

The basis of ophthalmology is prevention and age-related maculopathy is a classic example of this. If we have a positive family history and other risk factors besides age, such as nicotinism, atherosclerosis, carbohydrate-lipid disorders, among others, then we should not delay screening and perform it systematically. Age-related macular degeneration (AMD) is the most common cause of so-called “practical blindness” in developed countries, occurring most often in people over 50. It is believed that the incidence of AMD will increase as a result of global population aging. AMD is a degenerative disease that destroys the retina in the place that is the most critical to the vision process – the macula, most often through atrophy of the pigment epithelium, choriocapillaries and photoreceptors and the development of pathological neovascularization. The pathogenetic mechanisms of the disease, described in detail, are indirectly responsible for its early and correct diagnosis. Knowledge of the processes that occur in aging tissues, as well as complex processes caused by external factors and genetic conditions, allow specialists to differentiate the degenerative changes that arise and classify them into different stages of disease development. A number of risk factors, which are divided into modifiable and non-modifiable ones, are subject to analysis both to assess the risk of the onset of the condition and its subsequent progression. Ongoing research on these factors is focusing the attention of specialists on their potential use in prevention and therapy. An interview based on these risk factors provides important information about the patient’s overall health and predisposition to develop maculopathy. In the diagnosis of AMD, there is no single rigid regimen of management, since the disease is not homogeneous and is characterized by a very wide spectrum of symptoms. Among the diagnostic methods described, imaging studies predominate, which can be divided into invasive studies – advanced vascular studies performed by ophthalmologists, and non-invasive studies – imaging degenerative changes, performed by both teams of specialists. Early diagnosis of age-related macular degeneration offers the possibility of preserving the patient’s normal visual function. The progression of untreated disease promotes the development of symptoms whose effects are irreversible.

AMD is an example of a disease in which a holistic view of the entire body is critical. The patient should therefore take full responsibility for his or her health and ensure proper diet and physical activity and not delay a visit to a specialist. Education level is insufficient in every dimension of our physical, mental and social well-being.

One of the world’s most popular imaging diagnostic techniques is optical tomography OCT. Recent research conducted at the International Centre for Translational Eye Research (ICTER) under the supervision of Professor Maciej Wojtkowski have allowed the development of an improved method called Spatio-Temporal Optical Coherence Tomography (STOC-T) that enables imaging of the retina with preserved high-resolution at any depth in the frontal section. The use of STOC-T for retinal imaging makes it possible to reconstruct the morphology of the cones in the human eye. From your point of view, why is retinal imaging important? Which diseases would imaging of the morphology of the cones be crucial for?

OCT is a widely used technology in ophthalmology and allows imaging of all structures of the eyeball, both anterior and posterior, but the greatest research and scientific achievement is in imaging the retina in the central, or macular, area.

Imaging of the morphology of the cones opens a kind of gateway to eternity by enabling anatomical and functional monitoring of photoreceptors that receive visual stimuli and thus informs the first changes leading to, and long before, the onset of maculopathy. It thus provides us with a range of variables for monitoring and modifying perceptual processes, including particularly promising prospects for detecting dementia-like changes and thus accurately assessing cognitive and executive functions.

The key to the future is to capture the state in which the physiological changes that occur in the aging process of eye tissues transform into pathologies.

Dr. Anna M. Ambroziak

For the diagnosis of retinal diseases, not only structural, but also functional changes are important. The group of functional methods includes a precise variant of visual field testing – microperimetry. A novel method is being developed at ICTER: two-photon microperimetry, which takes advantage of the two-photon vision effect occurring when the retina is illuminated by a femtosecond infrared laser pulse. Physics shows that the longer the wavelength of light, the weaker it scatters in the medium. Therefore, in your opinion, can the use of infrared for functional vision testing expand the applicability of microperimetry?

Absolutely yes.

Both in terms of screening in at-risk groups and the broad prevention of macular disease, as well as the standards of management of myopia and glycemic/diabetic disorders.

Comprehensive diagnostic measures performed by ophthalmologists and optometrists are the cornerstone of their daily practice. Complementary examinations performed by both teams are the basis for proper and early diagnosis of many diseases of the visual system and implementation of effective treatment. In the diagnosis of retinal diseases, the range of examinations is very wide and includes both invasive methods and increasingly popular non-invasive examinations, which are expanding the standards of ophthalmic-optometric examinations.

Our research shows that two-photon microperimetry has better repeatability than traditional microperimetry. In your opinion, could this be important for diagnosing eye diseases or tracking their progress?  If so, for which diseases in particular?

Absolutely yes.

Precise assessment of the progression of changes over time and high sensitivity and specificity of central perimetry parameters are the greatest challenges of current diagnostics.

Each of the broad spectrum of entities in the maculopathy family requires reproducible data, but myopic maculopathy should definitely be highlighted in this group.

Let’s return to imaging methods by staying with two-photon effects: we are also developing a two-photon variant of fluorescence scanning laser ophthalmoscopy. A standard fluorescence scanning ophthalmoscope (SLO) uses a beam from the visible range, with a wavelength of typically around 480 nm (blue). This wavelength allows to excite the fluorescence of lipofuscin deposits in the pigment epithelium, but not of pigments involved in visual cycle transformations, such as retinyl esters. They are excited with shorter wavelengths, absorbed in the cornea, so it is impossible to detect them with such a standard SLO. The two-photon variant of this device that we are developing at ICTER circumvents this limitation. Do you think this could be an interesting tool for ophthalmologists?

Absolutely yes for the third time. The two-photon effect, as in perimetry, totally changes the perspective and raises the level of reliability of the examinations carried out, which is particularly justified in combination with SLO technology, since it makes it possible to detect changes at the cellular level in the period before the formation of functional changes, such as perimetric changes.

What are the available methods of keratoconus examination? What are their limitations?

First: genetics has entered diagnostics.

Second: imaging is giving us a new generation of tools with increasingly higher resolution and precision.

Corneal cone (Keratoconus, KC) is a bilateral, albeit asymmetric, condition that involves progressive thinning and convexity of the cornea, leading to irregular astigmatism. Keratoconus usually develops in the second or third decade of life. The condition affects all ethnic groups and both sexes. The prevalence and incidence rates of keratoconus can vary by geographic location and age of onset.

Approximately 73% (16 of 22) of human autosomal chromosomes are associated with KC , and 59% of these can be considered to show statistically significant associations (8 of 63). Studies suggest that it may be a polygenic disease, meaning that two or more affected genes are required for the development of keratoconus.

Keratoconus is a multifactorial disease and many genetic factors, along with various external factors, influence phenotypic expression and its development.

And what do we know from the Polish research I have been doing for many years?  That is, what do we know about the KC-related protein?

The ALDH3A1 protein is important in maintaining corneal physiology and protecting the eye from UV damage. However, no genome-wide association study has shown that the ALDH3A1 locus is associated with keratoconus. In this study, we investigated the potential role of ALDH3A1 variants as risk factors for the onset and severity of KC in a large group of Polish patients with keratoconus. In the first step, we analyzed the sequence of the coding region of ALDH3A1 in the KC subgroup. We then genotyped three selected ALDH3A1 variants in a larger group of KC patients (n=261) and healthy controls (n=317). We found that the minor A allele of rs1042183 is a risk factor for keratoconus in the dominant model. Genotypes of the rs2228100 variant appear to be associated with an earlier age of KC diagnosis in the Polish population (p=0.055 for the comparison of the three genotypes and p=0.022 for the dominant inheritance model). We showed that the rs1042183 variant in the ALDH3A1 gene is associated with predisposition to keratoconus in the Polish population. The allele frequency of ALDH3A1 variants associated with KC varies in different populations, which may be partly responsible for the difference in KC prevalence worldwide.

Early studies that diagnosed keratoconus were based mainly on symptoms seen on retinoscopy, non-standardized keratometry measurements and subjective assessment of clinical symptoms. Another diagnostic parameter is pachymetry, or corneal thickness assessment. We use different technologies and base the measurements on specific maps.

Until the development of technology and the advent of the ability to diagnose keratoconus with topography and high-resolution optical coherence tomography, information about corneal curvature was provided by keratometry.

Both pachymetry and keratometry are an essential part of the examination performed by an ophthalmologist or optometrist. The measurements obtained during the examination with an autorefractometer, should be the starting point of a comprehensive diagnosis.

Optical coherence tomography is a non-contact and non-invasive method of receiving and then processing an optical signal. It uses superluminescent diodes, which are a source of low-energy infrared light, to image high-resolution structures of the anterior segment of the eye. It is a Swept Source (SS-OCT) device that uses a long-wavelength light source with a central wavelength of 1310 nm and has a speed of 30,000 axial scans per second. The use of long-wavelength light, reduces unwanted scatter, and this results in a greater ability of the light to penetrate opaque structures, i.e. through the sclera or opaque cornea.

The device, performing qualitative analysis of the collected data, forms various types of tomographic and topographic maps of the anterior surface of the eye, the device generates a report respecting the percentage of similarity of the examined patient’s cornea to a typical cone eye model (ESI – Ectasia Screening Interpreted). Anterior corneal curvature and anterior and posterior astigmatism are significantly elevated in a person diagnosed with keratoconus; these parameters are not particularly useful in differentiating subclinical keratoconus from healthy eyes.

Epithelial criteria are the current diagnostic trend.

In daily practice, the usefulness of posterior corneal measurements continues to be emphasized, as changes in the posterior surface of the cornea can be one of the first clinically detectable signs of keratoconus. These measurements could not previously be obtained from traditional reflection-based topographers; they are measured using Scheimpflug imaging and anterior segment optical coherence tomography (AS OCT). By comparing topography maps taken over months and years, a trend curve of the condition is generated, e.g., the Cone Trend Analysis report, which is a key element in assessing the progression of keratoconus repression. A limitation, and thus a diagnostic challenge, is the detection of preclinical cases (pre-KC).

Dr. Anna M. Ambroziak and the Świat Oka Center in Warsaw.

What fields will develop in the next 10 years? What are the biggest challenges for scientists in the field of optics, optometry, ophthalmology and for medical staff specializing in the diagnosis and treatment of eye disorders?

New optics and the use of artificial and augmented intelligence are among the trends, simultaneously, we know more and more about our brain and are pushing the limits of neuroregenerative abilities. Still, the most common cause of decreased visual acuity is uncorrected inaccuracy. The visual organ allows us to perceive stimuli from the surrounding world. Visual sensory fibers have the largest brain representation among our senses, the information transmitted through them, however, requires a very precise receptor. More than half of European adults are diagnosed with refractive errors (myopia≤-0.50, hyperopia ≥+0.75, astigmatism ≥0.75). Everyone over the age of 40, regardless of the type and level of non-massive refraction, needs nearsightedness-support, i.e. correction of presbyopia. Still, despite such modern tools, very often the visual defect is not corrected or is only partially corrected. According to estimates, at least one in two adults should use glasses or contact lenses or another form of correction, but this is not the case. This fact has strong economic implications, both individually and socially, and is a potential cause of decreased productivity and quality of life. I am pointing to significant differences in the assessment of most functions, from overall quality of vision to mental health.

Most of us believe that the primary symptom of an uncorrected vision defect is blurred vision. We see with our brains. The brain selects sharp images, and the eye, thanks to its ability to accommodate, can sharpen the image provided by the impulse. This explains in some cases the ability to read despite the lack of proper correction.

A patient with an uncorrected visual impairment subconsciously seizes the opportunity to minimize the discomfort of a blurry retinal image and squints. Narrowing the eyelid crevice restricts the access of rays that run off-axis through the optical system of the eye. Light rays that enter the receptors in the retina when the eyelids are closed run axially and have a much smaller effect on blurring the image than off-axis rays. By squinting, a person with a refractive defect makes the image they see clearer, but is still subject to the typical symptoms of asthenopia, which is a reaction of the visual system to increased visual effort caused by an uncorrected refractive defect, most often hyperopia and astigmatism. Other causes of asthenopia can be phoria, which is a misalignment disorder of binocular vision, convergence or accommodative disorders.

There are a number of mechanisms in the human visual system that offset the discomfort caused by visual defects or disorders of the visual system, including fusiform vergence or accommodations. These mechanisms can become impaired during illness, under stress or as a result of intensive visual work at close distances.

The discomforts associated with uncorrected or undercorrected visual impairment are usually not sudden in nature and do not cause ocular signs for a long time. Their occurrence is often read in terms of somatic disorders manifested, for example, by general fatigue, irritability, dizziness or headaches. We should discuss this with our patients. Adequate optimization of retinal and cerebral images expands the doors of perception and thus future possibilities for intraocular correction and neuroadaptation to modern optics.

Let us take care of the psyche and help the brain refine the senses.

My dream is education, education addressed to us – specialists, education of our patients, education of their families, education of officials and decision-makers. My dream is for patients to benefit and be aware of the need for prevention. I know this sounds like utopia to realists, but this is my reality, and I want to share it. We are the ones who create reality! If only we start with small steps, with small things, with examples, with ourselves and our own backyard and realize this ideal world. Just as in Świat Oka we showed the space for eye care professionals to work together. This is the only way we can change our reality. First of all, the environment! Our polluted world is the starting point for autoimmune diseases, and diseases on the spectrum are not only ophthalmic and ocular surface. Our contaminated air, water and soil and the lack of natural light for our young people, our children and teenagers means obesity and being overweight, it means myopia. These diseases already affect half the population of young people and their numbers are increasing dramatically. Psychosomatic diseases constitute now about 70-80% of diseases, autoimmune diseases similarly. The number of people requiring vision correction and vision therapy is similar and so few, far less than half, benefit from it. The majority of parents (more than 80%) believe, and this is us who is responsible for this educational error, that children only require vision control when they start going to school. Many still do not understand that a full Optometric and Ophthalmic examination is the basis, and we are not talking about any exceptionally high standards. At least two hours in natural light and dietary changes are the basis for holistic management of our patients of all ages. Digital eye fatigue along with disorders of the ocular surface, disorders of convergence, accommodation, with visual defects. including pseudo-short-sightedness simply require attentiveness, awareness of here and now, and willingness. No exceptional solutions or finances are needed there. Our dream for the present is for us to get examined and undergo corrections when needed. We will then be able to let our tired and irritated minds rest. The next step is modern diagnosis and treatment of ophthalmic conditions.

Eye screening programs are still needed both in developing countries and here in the center of Europe, where preventive care in ophthalmology still does not happen realistically.

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Interview questions prepared by: Marta Mikuła-Zdańkowska, PhD and Oliwia Kaczkoś, MSc.

Expert supervision: senior researcher Katarzyna Komar, PhD.

Additional contribution: Anna Salamończyk.

THE INTERVIEW WAS REALIZED BY THE MEMBERS OF THE PHYSICAL OPTICS AND BIOPHOTONICS GROUP LED BY PROF. MACIEJ WOJTKOWSKI, HEAD OF ICTER.

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.

26.10.2022

How to improve microendoscopes? New probe design brings promises to improve biomedical imaging – paper in IEEE Photonics Journal by Karol Karnowski, PhD

Microendoscopes are the cornerstone of modern medical diagnostics – they allow us to see what we could not even describe two decades ago. The technology is constantly improving, with ICTER scientists contributing to the development of the probes.

Microendoscopes using fiber optics are becoming increasingly important imaging tools, but they have physical limitations. They are essential for applications that require a long working distance, high resolution, and a minimum probe diameter. The research paper titled “Superior imaging performance of all-fiber, two- focusing-element microendoscopes,” by Dr. Karol Karnowski of ICTER, Dr. Gavrielle Untracht of the Technical University of Denmark (DTU), Dr. Michael Hackmann of the University of Western Australia (UWA), Onur Cetinkaya of ICTER and Prof. David Sampson of the University of Surrey, sheds new light on modern microendoscopes. It is noteworthy that the research work started while the authors worked in the same research group at UWA.

In it, the researchers showed that endoscopic imaging probes, particularly those for so-called side viewing, combining fiber-optic (GRIN) and spherical lenses, offer excellent performance over the entire range of numerical apertures and open the way to a broader range of imaging applications. In the publication, the performance of endoscopic imaging probes is comparable to commonly used single focusing element probes.

Photo: Karol Karnowski

What are microendoscopes?

Miniature fiber-optic probes, or micro-endoscopes, allow imaging of tissue microstructures deep into the specimen or patient. Endoscopic Optical Coherence Tomography (OCT) is particularly promising. It is suitable for volumetric imaging of external tissues and the interior of organs (e.g., the upper respiratory tract, gastrointestinal tract, or lung tubules).

Three main ranges of fiber optic probes can be distinguished. Studies of large, hollow organs (such as those above the upper respiratory tract) require the largest imaging depth ranges (up to 15 mm or more from the probe surface), which can usually be achieved with low-resolution Gaussian beams (spot size in focus in the range of 30-100 μm). The intermediate resolution range (10-30 μm) is helpful for broader applications, such as imaging the esophagus, smaller airways, blood vessels, bladder, ovaries, or ear canal. The biggest challenge is obtaining beams with a resolution better than 10 μm, potentially helpful for animal model studies.

Photo: Karol Karnowski

When developing a probe, one must be mindful of design parameters’ trade-offs and their impact on imaging performance. Optical systems with a large numerical aperture (high resolution) tend to have a shorter working distance (WD). In addition, better resolution and longer working distance are more difficult to achieve as the probe diameter is reduced. This can be particularly problematic for side viewing probes – a greater minimum working distance is required compared to their forward imaging counterparts. Suppose the probe is encased in a catheter or needle. In that case, this increases the required minimum working distance – in many cases, this is the limiting factor in minimum achievable resolution or probe diameter.

It’s worth noting that engineers are usually interested in minimizing the probe diameter for reduced perturbation to the sample and patient comfort. A smaller probe means a more flexible catheter and, therefore, better tolerance of the test by the patient. Thus, one of the best solutions is using monolithic fiber optic probes, whose diameter is limited by the thickness of the optical fibers. Such probes are characterized by ease of fabrication, thanks to fiber-optic welding technology, which avoids the need for tedious alignment and bonding (usually gluing) of individual micro-optical components.

Photo: Karol Karnowski

Different types of microendoscopes

The most popular designs of fiber-optic imaging probes are those based on two types of focusing elements: GRIN fiber probes (GFP – GRIN fiber probes) and ball lens probes (BLP – ball lens probes). GRIN probes are easy to make, and their GRIN refractive power is not lost when the refractive index of the surrounding medium is close to that of the fiber used. Commercially available GRIN fibers limit achievable designs. High resolution is tough to achieve with GRIN fibers with small core diameters.

For lateral viewing probes, the curved surface of the fiber (and potentially the catheter) introduces distortion that can adversely affect imaging quality. Spherical BLP probes will not have this problem, but a sphere bigger than the fiber diameter is often required to achieve a resolution comparable to GFP probes. The focusing power of a BLP probe depends on the refractive index of the surrounding medium, which is an important issue when working in a medium with close or near biological samples.

One solution to improve the performance of probes is to use multiple light focusing elements, similar to the design of lenses with a long working distance. Studies have shown that combining numerous light-focusing elements provides better results for many imaging purposes. Probes with multiple focusing elements can achieve better resolution with smaller diameters while offering longer working distances without sacrificing resolution.

How do we improve the probes?

In their latest work, researchers led by Dr. Karnowski have shown that probes with two focusing elements using both GRIN segments and spherical lenses – called GRIN-ball-lens probes (GBLP) – significantly improve the performance of monolithic fiber optic probes. Their first modeling results have already been shown at conferences in 2018 and 2019. GBP probes were compared to the most commonly used GFP and BLP probes and showed performance benefits, especially for applications requiring longer operating distances, better resolution, and small size.

For intuitive visualization of probe performance, the researchers introduced a novel way to comprehensively present simulation results, especially useful when more than two variables are used. Analysis of the effect of GRIN fiber length and spherical lens size led to two interesting conclusions: for optimal results, the range of GRIN fiber length can be kept in the field of 0.25-0.4 pitch length (so-called pitch length); even if the working distance (WD) gain is not so significant for GBLP probes with high numerical aperture, the authors showed that the same or better performance in terms of working distance is achieved for a search with twice the diameter. Moreover, the novel GBLP probes offer higher resolution compared to BLP probes.

Photo: Bartłomiej A. Bałamut

The paper’s conclusion reads:

We have demonstrated the potential of GBLP probe design for applications with increased working distance, significant for lateral imaging probes, with a highly reduced impact of the refractive index of the probe’s environment and a significantly smaller size compared to BLP or GFP probes. These advantages make GBLP probes a tool worth considering for many imaging applications in biological and biomedical research, particularly for projects requiring micro endoscopes.

Author of the press release: Marcin Powęska

Note: The first results from “GRIN-ball-lens probes (GBLP)” modeling have already been shown at the 2018 and 2019 conferences:

– Karol Karnowski, Gavrielle R. Untracht, Michael J. Hackmann, Mingze Yang, Onur Cetinkaya, David D. Sampson, “Versatile, all-fiber, side viewing imaging probe for applications in catheter-based optical coherence tomography,” Photonics West, San Francisco, USA, Feb 2019, oral presentation;

– K. Karnowski, G. Untracht, M. Hackmann, M. Yang, O. Cetinkaya, and D. D. Sampson, “Versatile, monolithic imaging probes for catheter-based OCT,” 15th Conference on Optics Within Life Sciences, Rottnest Island, Australia, Nov. 2018, poster presentation.

The team responsible for these results started at the University of Western Australia (UWA), and work has now been completed within the following institutions: the Institute of Physical Chemistry, Polish Academy of Sciences and the University of Surrey, one of the authors only remaining at UWA.

Photos by: Karol Karnowski, PhD and Bartłomiej A. Bałamut, MSc

Photographers’ comment: One of the key components of the developed probes is a spherical surface on the tip of the fiber. In the photos, we used the imaging capabilities of such spherical elements (glass sphere).

Cited paper: K. Karnowski, G. Untracht, M. Hackmann, O. Cetinkaya and D. Sampson, “Superior Imaging Performance of All-Fiber, Two-Focusing-Element Microendoscopes,” in IEEE Photonics Journal, vol. 14, no. 5, pp. 1-10, Oct. 2022, Art no. 7152210, doi: 10.1109/JPHOT.2022.3203219.

Funding sources:

  • Polish National Agency for Academic Exchange (NAWA) through the Polish Returns Program
  • University of Western Australia IPRS  
  • Rank Prize Covid Fund 
  • Australian Research Council  
  • University of Surrey 
Photo: Karol Karnowski
DOI Number:
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

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