Tilman Otto’s research while affiliated with Heidelberg Engineering and other places

Purpose: To assess the impact of working distance (WD) on optical distortion in optical coherence tomography (OCT) imaging and to evaluate the effectiveness of optical distortion correction in achieving consistent retinal Bruch's membrane (BM) layer curvature, regardless of variations in WD. Methods: Ten subjects underwent OCT imaging with four serial macular volume scans, each employing distinct WD settings adjusted by balancing the sample and reference arm of the OCT interferometer (eye length settings changed). Either of two types of 30° standard objectives (SOs) was used. A ray tracing model was used to correct optical distortion, and BM layer curvature (represented as the second derivative of the curve) was measured. Linear mixed effects (LME) modeling was used to analyze factors associated with BM layer curvature, both before and after distortion correction. Results: WD exhibited significant associations with axial length (β = -1.35, P < 0.001), SO type (P < 0.001), and eye length settings (P < 0.001). After optical distortion correction, the mean ± SD BM layer curvature significantly increased from 16.80 ± 10.08 µm-1 to 49.31 ± 7.50 µm-1 (P < 0.001). The LME model showed a significant positive association between BM layer curvature and WD (β = 1.94, P < 0.001). After distortion correction, the percentage change in BM layer curvature due to a 1-mm WD alteration decreased from 9.75% to 0.25%. Conclusions: Correcting optical distortion in OCT imaging significantly mitigates the influence of WD on BM layer curvature, enabling a more accurate analysis of posterior eye morphology, especially when variations in WD are unavoidable.

Purpose: Optical coherence tomography (OCT) representations in clinical practice are static and do not allow for a dynamic visualization and quantification of blood flow. This study aims to present a method to analyze retinal blood flow dynamics using time-resolved structural OCT. Methods: We developed novel imaging protocols to acquire video-rate time-resolved OCT B-scans (1024 × 496 pixels, 10 degrees field of view) at four different sensor integration times (integration time of 44.8 µs at a nominal A-scan rate of 20 kHz, 22.4 µs at 40 kHz, 11.2 µs at 85 kHz, and 7.24 µs at 125 kHz). The vessel centers were manually annotated for each B-scan and surrounding subvolumes were extracted. We used a velocity model based on signal-to-noise ratio (SNR) drops due to fringe washout to calculate blood flow velocity profiles in vessels within five optic disc diameters of the optic disc rim. Results: Time-resolved dynamic structural OCT revealed pulsatile SNR changes in the analyzed vessels and allowed the calculation of potential blood flow velocities at all integration times. Fringe washout was stronger in acquisitions with longer integration times; however, the ratio of the average SNR to the peak SNR inside the vessel was similar across all integration times. Conclusions: We demonstrated the feasibility of estimating blood flow profiles based on fringe washout analysis, showing pulsatile dynamics in vessels close to the optic nerve head using structural OCT. Time-resolved dynamic OCT has the potential to uncover valuable blood flow information in clinical settings.

Purpose: Optical coherence tomography (OCT) representations in clinical practice are static and do not allow for a dynamic visualisation and quantification of blood flow. This study aims to present a method to analyse retinal blood flow dynamics using time-resolved structural optical coherence tomography (OCT). Methods: We developed novel imaging protocols to acquire video-rate time-resolved OCT B-scans (1024 x 496 pixels, 10 degrees field of view) at four different sensor integration times (integration time of 44.8 μs at a nominal A-scan rate of 20 kHz, 22.4 μs at 40 kHz, 11.2 μs at 85 kHz, 7.24 μs at 125 kHz). The vessel centres were manually annotated for each B-scan and surrounding subvolumes were extracted. We used a velocity model based on signal-to-noise ratio (SNR) drops due to fringe washout to calculate blood flow velocity profiles in vessels within five optic disc diameters of the optic disc rim. Results: Time-resolved dynamic structural OCT revealed pulsatile SNR changes in the analysed vessels and allowed the calculation of potential blood flow velocities at all integration times. Fringe washout was stronger in acquisitions with longer integration times; however, the ratio of the average SNR to the peak SNR inside the vessel was similar across all integration times. Conclusions: We demonstrated the feasibility of estimating blood flow profiles based on fringe washout analysis, showing pulsatile dynamics in vessels close to the optic nerve head using structural OCT. Time-resolved dynamic OCT has the potential to uncover valuable blood flow information in clinical settings.

Purpose: To evaluate the degenerative findings including cistern formation in the premacular vitreous using optical coherence tomography (OCT). Methods: A novel enhanced vitreous imaging method by which 4 A-scans at each position were averaged prior to the Fourier transform increased the image quality per frame so that subsequent image registration for averaging could occur. Analysis of B-scans and volume rendered images of eyes in subjects of various ages was performed. Results: There were 43 eyes of 23 subjects ranging in age from 23 - 68 years. The texture in the vitreous images suggests specific orientations of the vitreous fibers in the macular region; there were fibers circumferential to the retina immediately anterior to the premacular bursa. The pattern of the vitreous fibers seemed less well defined internal to the zone of circumferential fibers. In younger eyes, there were striations oriented in a roughly inferior to superior direction in this zone. In older eyes there were striations in the same orientation but actually were alternating zones of vitreous synchysis and syneresis. In these same eyes numerous cisterns appeared at various levels in the vitreous gel. With extensive vitreous condensation and synchysis, definition of the premacular bursa was lost. Conclusions: With this novel method of enhanced vitreous imaging, the vitreous appeared to have stereotypic patterns of degeneration. The formation of vitreous syneresis and synchysis may be related to organization architecture of the vitreous, including the pattern of vitreous collagen deposition, and the effects of eye motion through decades of time.

Purpose: The lateral resolution of an optical coherence tomography (OCT) instrument was considered to be equal to the illumination spot size on the retina. To evaluate the potential lateral resolution of the Spectralis OCT, an instrument calculated to have a 14 µm resolution. Methods: The lateral point spread function (PSF) was evaluated using diamond abrasive powder 0 to 1 µm in diameter in silicone elastomer and a validated target with 800 nm FeO particles in urethane. The amplitude transfer function was calculated from human OCT images. Finally, resolution was measured using the 1951 USAF target. Results: Measurement of the lateral PSF from 1215 diamond particle images yielded a full-width half maximum (FWHM) to be 5.11 µm and for 732 FeO particles, 4.9 µm. From the amplitude transfer function, the FWHM of the diffraction limited PSF was calculated to be 5.0 µm. The USAF target imaging showed a lateral resolution of 4.6 µm. Conclusions: Although a calculation of the spot size of the illumination beam was reported in the past as the lateral resolution of the OCT instrument, the actual lateral resolution is better by a factor of at least 2.5 times. The clinically used A-scan spacing was derived from the calculated, and not the true resolution, and results in under sampling. This set of findings likely apply to all commercial clinical instruments. Translational relevance: The scan density parameters of past and present commercial OCT instruments were based on earlier translational concepts, which now appear to have been incorrect.

Purpose: To describe imaging produced by machine learning-based segmentation of high-resolution optical coherence tomography imaging of the intermediate capillary plexus and deep capillary plexus, layers of vessels not imaged well by dye-based angiography. Methods: Three healthy subjects with no ocular problems were imaged with spectral domain optical coherence tomography using an instrument with a scanning speed of 85,000 A-scans per second and 3 µm axial optical resolution. A random forest segmentation strategy was used to segment the intermediate capillary plexus and deep capillary plexus. The depth-resolved imaging data was visualized with the help of volume rendering. Results: The high-resolution optical coherence tomography showed the intermediate capillary plexus and deep capillary plexus at the outer borders of the inner nuclear layer. These vessels could be visualized with unprecedented detail in three dimensions. There were multiple bridging vessels connecting to the whorl-like patterns of capillary mesh of the deep capillary plexus, a feature only previously imaged in histologic evaluation of excised eyes. Conclusion: High-resolution optical coherence tomography, machine learning, and advanced image display techniques have wide relevancy in studying the retina in health and disease. Application of this approach has provided images of the deeper vascular layers of the eye that approximate histologic imaging, but noninvasively.

Glaucoma is the leading cause of irreversible blindness worldwide, with an increasing prevalence. The complexity of the disease has been a major challenge in moving the field forward with regard to both pathophysiological insight and treatment. In this context, discussing possible outcome measures in glaucoma trials is of utmost importance and clinical relevance. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "New Technologies for Outcome Measures in Retina and Glaucoma," addressing both functional and structural outcomes, as well as translational hot topics in glaucoma and retina research. In conjunction with the published literature, this review summarizes the meeting focusing on glaucoma.

Since the first scanning laser ophthalmoscope (SLO) was introduced in the early 1980s, this imaging technique has been adapted and optimized for various clinical applications based on different contrast mechanism. Reflectance imaging, where the back scattered light is detected, is widely used for eye tracking and as reference image for OCT applications. But also the reflectance modality itself has several important diagnostic applications: laser scanning tomography (SLT), imaging with different laser wavelengths (Multicolor contrast) and others. Fluorescence imaging channels with different excitation wavelengths were introduced to SLOs for angiography, i.e. for the visualization of the vascular system after intravenously injecting an appropriate dye, as well as for autofluorescence imaging of endogenous fluorophores within the retina. This chapter gives an introduction to the history of SLO technology and a general overview on its clinical applications. In the following sections the focus is directed on one distinct clinical application for each of the major imaging modalities: reflectance, angiography and autofluorescence. First, the assessment of the optic nerve head for glaucoma diagnostic by means of laser scanning tomography is presented, before in the third section the clinical aspect of wide field SLO angiography is discussed. Finally, an introduction to quantitative autofluorescence (qAF) is given, a new research tool, which is used to measure the accumulation of lipofuscin within the retinal pigment epithelium (RPE) for normal subjects and for patients with macular dystrophies.

Novel diagnostic tools to measure retinal function and structure are rapidly being developed and introduced into clinical use. Opportunities exist to use these informative and robust measures as endpoints for clinical trials to determine efficacy and to monitor safety of therapeutic interventions. In order to inform researchers and clinician-scientists about these new diagnostic tools, a workshop was organized by the European Vision Institute. Invited speakers highlighted the recent advances in state-of-the-art technologies for outcome measures in the field of retina. This review highlights the workshop's presentations in the context of published literature.