Category: Image-guided Devices for Ophthalmic Care

For many years visual inspection of fundus photography [1] and examination of images acquired with optical coherence tomography (OCT) [2] have been used by ophthalmologists for eye disease diagnosis and monitoring therapy progress thanks to their ability to detect morphological changes in the retina. However, imaging the morphological manifestation of retinal diseases alone does not provide sufficient information on the loss of functionality of retinal neurons.

Over a decade ago, it was shown that optical coherence tomography (OCT) can detect small changes in the intensity of infrared light reflected from animal retinas in vitro [3,4] and in vivo [5] occurring after simultaneous stimulation with visible light. These findings laid the foundations for the development of optoretinography (ORG) [6], a method that measures photoreceptors’ response to light, thus giving a possibility for obtaining information about the functionality of retinal neurons.

At ICTER, we work on both ORG with a single pulse and flicker stimulation of the retina [7]. To acquire the ORG data, we use a Spatio-Temporal Optical Coherence-Tomography (STOC-T) [8] that records 3-D volumetric retina images within a few milliseconds each. After data processing, we extract the ORG signals by tracking subtle changes in the retina occurring between inner and outer photoreceptor junction (IS/OS) and the cone outer segment tips (COST). Fig. (a). presents the source of the ORG signal on an exemplary tomographic image of a human retina.

Exemplary results showing dark-adapted retinas’ responses to single pulse light stimulus are shown in Fig. (b) and (c). The (b) presents a spatially averaged ORG signal in function of time for uniformly distributed stimulus. The (c) shows the maximum amplitude of the ORG signal across imaged part of the retina surface in response to a projected pattern (letter E).

In the f-ORG experiments, which are the main subject of our works, a flickering light is used to stimulate the retina. First, such a study was performed by Schmoll et al. and measured photoreceptors’ response to a 5 Hz flicker [9], while, more recently, the group from Lübeck measured the response to different flicker frequencies (between 1 Hz and 6.6 Hz) [10].

Our f-ORG methodology allows for measuring retinas’ responses in a broader range of frequencies and mapping the photoreceptors’ response to a flickering light across the retinas’ surfaces. Exemplary results of measured frequency characteristics of the responses in four healthy human subjects are presented in Fig. (d). While an example of a spatially detected retina’s response to a DMD patterned stimulus with strips of light flickering at different frequencies is presented in Fig. (e).

Text: Sławomir Tomczewski, PhD, e-mail: stomczewski@ichf.edu.pl.

Team:

Sławomir Tomczewski, PhD

Piotr Węgrzyn, MSc

Dawid Borycki, PhD habil.

Egidijus Auksorius, PhD

Maciej Wielgo, MSc

Prof. Maciej Wojtkowski

Andrea Curatolo, PhD

Keywords: Optical Coherence Tomography, STOC-T, OCT, Optoretinography, Flicker ORG.

Publications:

1. V. J. Srinivasan, M. Wojtkowski, J. G. Fujimoto, and J. S. Duker, “In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography,” Opt. Lett. 31, 2308 (2006).
2. S. Tomczewski, P. Węgrzyn, D. Borycki, E. Auksorius, M. Wojtkowski, and A. Curatolo, “Light-adapted flicker optoretinograms captured with a spatio-temporal optical coherence-tomography (STOC-T) system,” Biomed. Opt. Express 13, 2186 (2022).
3. E. Auksorius, D. Borycki, P. Wegrzyn, B. L. Sikorski, K. Lizewski, I. Zickiene, M. Rapolu, K. Adomavicius, S. Tomczewski, and M. Wojtkowski, “Spatio-Temporal Optical Coherence Tomography provides full thickness imaging of the chorioretinal complex,” iScience 25, 105513 (2022).

The IMCUSTOMEYE project involves the cooperation of 10 partners, both academic and industrial, began in 2018. From day one, as a consortium, we have focused on developing new, non-invasive, imaging-based methods to change the paradigm in the diagnosis and treatment of various eye diseases.

POB group’s researchers, were tasked with constructing a compact, low-cost device to measure 3D dynamic corneal deformation of the human eye. As it is in life, and especially in physics, we had to make some compromises with respect to the prototype being constructed. Even if full three-dimensional imaging of a corneal deformation process lasting only 20 ms is possible, it would require considerable complication of the measurement system and generate unacceptable costs. We proposed an intermediate solution of simultaneous measurements at multiple points on the cornea, including the center of the cornea and 4 pairs of points placed opposite along 4 directions (horizontal, vertical and corresponding directions rotated by 45 degrees). This approach made it possible to prepare a prototype compact system to be placed in an eye clinic. In addition, we preliminarily verified the possibility of both further miniaturization of the system and the potential for a significant reduction in manufacturing costs.

Our clinical prototype has not only survived the 300+ kilometer trip to the clinic in Bydgoszcz, Poland, but has also measured more than 100 eyes to date. It is worth noting that the prototype has been prepared from the hardware and software side in such a way that it could be successfully operated by eye clinic staff.

To analyze the data, we extract temporal corneal deformation for each spot. The biomechanical asymmetry can be assessed by comparison of opposite spots. To provide more intuitive presentation of the results, we introduced “asymmetry vector” that can be plotted for any deformation parameter (e.g., displacements amplitudes, deformation area, deformation slopes). For each pair of opposite spots, we create a vector pointing towards spot with higher value of selected parameter with a magnitude given by the differences of values for both spots in pair.

Having vectors for all 4 pairs of spots we can calculate overall vector to show global effect. This approach was applied already to some of our early clinical data to show differences in biomechanical asymmetry between healthy and keratoconus corneas (presented here for displacement amplitude and area).

Text: Dr. Karol Karnowski

TEAM:

Karol Karnowski, PhD

Jadwiga Milkiewicz, MSc

Angela Pachacz, Eng

Onur Cetinkaya, BEng

Rafał Pietruch, Eng

Andrea Curatolo, PhD

Prof. Maciej Wojtkowski

Publications:

1. D. Alonso-Caneiro, K. Karnowski, B. Kaluzny, A. Kowalczyk, and M. Wojtkowski, “Assessment of corneal dynamics with high-speed swept source Optical Coherence Tomography combined with an air puff system”, Optics Express, Vol. 19, Issue 15, pp. 14188-14199 (2011)
2. S. Marcos, C. Dorronsoro, K. Karnowski, M. Wojtkowski, „Corneal biomechanics From Theory to Practice: OCT with air puff stimulus”, Kugler Publications 2016, edited by C.J. Roberts, J. Liu
3. K. Karnowski, E. Maczynska, M. Nowakowski, B. Kaluzny, I. Grulkowski, M. Wojtkowski, “Impact of diurnal IOP variations on the dynamic corneal hysteresis measured with air-puff swept-source OCT”, Photonics Letters of Poland, (2018)
4. E. Maczynska, K. Karnowski, K. Szulzycki, M. Malinowska, H. Dolezyczek, A. Cichanski, M. Wojtkowski, B. Kaluzny and I. Grulkowski, “Assessment of the influence of viscoelasticity of cornea in animal ex vivo model using air-puff optical coherence tomography and corneal hysteresis”, J Biophotonics, 2019; 12:e201800154 (2019)
5. A. Curatolo, J. S. Birkenfeld, E. Martinez-Enriquez, J. A. Germann, G. Muralidharan, J. Palací, D. Pascual, A. Eliasy, A. Abass, J. Solarski, K. Karnowski, Maciej Wojtkowski, Ahmed Elsheikh, and Susana Marcos, “Multi-meridian corneal imaging of air-puff induced deformation for improved detection of biomechanical abnormalities,” Biomed. Opt. Express 11, 6337-6355 (2020)