Boy Braaf

Phase-stabilized optical frequency domain imaging at 1-µm for the measurement of blood flow in the human choroid

In optical frequency domain imaging (OFDI) the measurement of interference fringes is not exactly reproducible due to small instabilities in the swept-source laser, the interferometer and the data-acquisition hardware. The resulting variation in wavenumber sampling makes phase-resolved detection and the removal of fixed-pattern noise challenging in OFDI. In this paper this problem is solved by a new post-processing method in which interference fringes are resampled to the exact same wavenumber space using a simultaneously recorded calibration signal. This method is implemented in a high-speed (100 kHz) high-resolution (6.5 µm) OFDI system at 1-µm and is used for the removal of fixed-pattern noise artifacts and for phase-resolved blood flow measurements in the human choroid. The system performed close to the shot-noise limit (<1dB) with a sensitivity of 99.1 dB for a 1.7 mW sample arm power. Suppression of fixed-pattern noise artifacts is shown up to 39.0 dB which effectively removes all artifacts from the OFDI-images. The clinical potential of the system is shown by the detection of choroidal blood flow in a healthy volunteer and the detection of tissue reperfusion in a patient after a retinal pigment epithelium and choroid transplantation.

Real-time eye motion correction in phase-resolved OCT angiography with tracking SLO

In phase-resolved OCT angiography blood flow is detected from phase changes in between A-scans that are obtained from the same location. In ophthalmology, this technique is vulnerable to eye motion. We address this problem by combining inter-B-scan phase-resolved OCT angiography with real-time eye tracking. A tracking scanning laser ophthalmoscope (TSLO) at 840 nm provided eye tracking functionality and was combined with a phase-stabilized optical frequency domain imaging (OFDI) system at 1040 nm. Real-time eye tracking corrected eye drift and prevented discontinuity artifacts from (micro)saccadic eye motion in OCT angiograms. This improved the OCT spot stability on the retina and consequently reduced the phase-noise, thereby enabling the detection of slower blood flows by extending the inter-B-scan time interval. In addition, eye tracking enabled the easy compounding of multiple data sets from the fovea of a healthy volunteer to create high-quality eye motion artifact-free angiograms. High-quality images are presented of two distinct layers of vasculature in the retina and the dense vasculature of the choroid. Additionally we present, for the first time, a phase-resolved OCT angiogram of the mesh-like network of the choriocapillaris containing typical pore openings.

Angiography of the retina and the choroid with phase-resolved OCT using interval-optimized backstitched B-scans

In conventional phase-resolved OCT blood flow is detected from phase changes between successive A-scans. Especially in high-speed OCT systems this results in a short evaluation time interval. This method is therefore often unable to visualize complete vascular networks since low flow velocities cause insufficient phase changes. This problem was solved by comparing B-scans instead of successive A-scans to enlarge the time interval. In this paper a detailed phase-noise analysis of our OCT system is presented in order to calculate the optimal time intervals for visualization of the vasculature of the human retina and choroid. High-resolution images of the vasculature of a healthy volunteer taken with various time intervals are presented to confirm this analysis. The imaging was performed with a backstitched B-scan in which pairs of small repeated B-scans are stitched together to independently control the time interval and the imaged lateral field size. A time interval of ≥ 2.5 ms was found effective to image the retinal vasculature down to the capillary level. The higher flow velocities of the choroid allowed a time interval of 0.64 ms to reveal its dense vasculature. Finally we analyzed depth-resolved histograms of volumetric phase-difference data to assess changes in amount of blood flow with depth. This analysis indicated different flow regimes in the retina and the choroid.

Real-time eye motion compensation for OCT imaging with tracking SLO

Fixational eye movements remain a major cause of artifacts in optical coherence tomography (OCT) images despite the increases in acquisition speeds. One approach to eliminate the eye motion is to stabilize the ophthalmic imaging system in real-time. This paper describes and quantifies the performance of a tracking OCT system, which combines a phase-stabilized optical frequency domain imaging (OFDI) system and an eye tracking scanning laser ophthalmoscope (TSLO). We show that active eye tracking minimizes artifacts caused by eye drift and micro saccades. The remaining tracking lock failures caused by blinks and large saccades generate a trigger signal which signals the OCT system to rescan corrupted B-scans. Residual motion artifacts in the OCT B-scans are reduced to 0.32 minutes of arc (~1.6 µm) in an in vivo human eye enabling acquisition of high quality images from the optic nerve head and lamina cribrosa pore structure.

Fiber-based polarization-sensitive OCT of the human retina with correction of system polarization distortions

In polarization-sensitive optical coherence tomography (PS-OCT) the use of single-mode fibers causes unpredictable polarization distortions which can result in increased noise levels and erroneous changes in calculated polarization parameters. In the current paper this problem is addressed by a new Jones matrix analysis method that measures and corrects system polarization distortions as a function of wavenumber by spectral analysis of the sample surface polarization state and deeper located birefringent tissue structures. This method was implemented on a passive-component depth-multiplexed swept-source PS-OCT system at 1040 nm which was theoretically modeled using Jones matrix calculus. High-resolution B-scan images are presented of the double-pass phase retardation, diattenuation, and relative optic axis orientation to show the benefits of the new analysis method for in vivo imaging of the human retina. The correction of system polarization distortions yielded reduced phase retardation noise, and better estimates of the diattenuation and the relative optic axis orientation in weakly birefringent tissues. The clinical potential of the system is shown by en face visualization of the phase retardation and optic axis orientation of the retinal nerve fiber layer in a healthy volunteer and a glaucoma patient with nerve fiber loss.

Forward ray tracing for image projection prediction and surface reconstruction in the evaluation of corneal topography systems

A forward ray tracing (FRT) model is presented to determine the exact image projection in a general corneal topography system. Consequently, the skew ray error in Placido-based topography is demonstrated. A quantitative analysis comparing FRT-based algorithms and Placido-based algorithms in reconstructing the front surface of the cornea shows that arc step algorithms are more sensitive to noise (imprecise). Furthermore, they are less accurate in determining corneal aberrations particularly the quadrafoil aberration. On the other hand, FRT-based algorithms are more accurate and more precise showing that point to point corneal topography is superior compared to its Placido-based counterpart.

Performance in specular reflection and slit-imaging corneal topography.

Purpose. Assessment of the relative performance in measuring corneal shape and corneal aberrations for two specular reflection topographers: Keratron Placido Ring Topographer, VU Topographer, and two slit-lamp imaging instruments: Orbscan II and Topcon SL-45 Scheimpflug. Methods. Corneal height maps of the anterior corneal surface were obtained from a group of 34 subjects with all four instruments; posterior corneal surface height maps were only obtained with the two slit-lamp imaging instruments. Corneal surface shapes are calculated in terms of radius of curvature and asphericity fitting an aspheric model. Wave aberrations for the anterior corneal surface and the total cornea are determined up to and including sixth order Zernike convention by means of ray tracing. Results. Clinical relevant differences were observed for radius of curvature of the anterior corneal surface, where the slit-imaging instruments measure higher values (mean difference = 0.05 mm, p < 0.05) and anterior corneal astigmatism for which the Orbscan II measures higher values than the VU Topographer [mean difference = 0.174 &mgr;m (0.134 Equivalent Diopters), p < 0.01]. Small significant differences were observed for asphericity and spherical aberration of the anterior corneal surface; however, these are not clinically relevant. Clinically relevant differences were also observed for posterior radius (difference = 0.135 mm p < 0.001), total corneal astigmatism (difference = 0.207 &mgr;m (0.159 Equivalent Diopters), p = 0.001), and central corneal thickness (CCT) (difference = −18.6 &mgr;m, p < 0.001). The differences found for total corneal coma and trefoil were not clinical relevant. Furthermore, the precision of the specular reflection topographers is superior to that of the slit-lamp instruments by at least a factor of two. Conclusions. For traditional spectacle and contact lens applications, the corneal topographers are interchangeable except for measuring anterior radius of curvature. However, for more modern techniques as customized corneal refractive surgery, the subtle differences (e.g., total corneal astigmatism and CCT) between the instruments are clinically relevant.

Wide-Range Calibration of Corneal Backscatter Analysis by In Vivo Confocal Microscopy

PURPOSE To report intra- and interinstrument calibration methods for corneal backscatter analysis by in vivo confocal microscopy. METHODS Applicability of two reference standards was evaluated for corneal backscatter calibration. Repeated measurements of four concentrations of AMCO Clear (GFS Chemicals, Inc., Powell, OH) suspension and three transparencies (26%, 49%, and 65%) of polymethylmethacrylate (PMMA) slabs were performed to assess image intensity acquisition in a wide backscatter range. Intra- and intersession repeatability and lot-to-lot variation were determined for both standards. The effect of light intensity (LI) variation on image intensity acquisition was evaluated by examination of PMMA slabs with nonreference (60% and 80%) and reference (72%) LIs. Both reference standards were implemented in the protocol. Intrainstrument calibration was verified by measuring three normal corneas with 60%, 72%, and 80% LIs. Interinstrument calibration was tested by measuring PMMA slabs on a second, similar confocal microscope. RESULTS AMCO Clear was used to express image intensity in absolute scatter units (SU), whereas the 49% transparent PMMA slab showed best repeatability, without image saturation, to adjust for LI variation. Intrainstrument calibration for LI variation reduced mean differences from -38.3% to 1.7% (60% LI) and from 33.9% to -0.6% (80% LI). The mean difference between similar microscopes decreased from 18.4% to 1.2%, after calibration of the second microscope. CONCLUSIONS Large interinstrument differences necessitate calibration of corneal backscatter measurements. With AMCO Clear suspension and PMMA slabs, standardization was achieved in a wide backscatter range corresponding to normal and opaque corneas. These methods can easily be applied in ophthalmic practice.

Parallel line scanning ophthalmoscope for retinal imaging

A parallel line scanning ophthalmoscope (PLSO) is presented using a digital micromirror device (DMD) for parallel confocal line imaging of the retina. The posterior part of the eye is illuminated using up to seven parallel lines, which were projected at 100 Hz. The DMD offers a high degree of parallelism in illuminating the retina compared to traditional scanning laser ophthalmoscope systems utilizing scanning mirrors. The system operated at the shot-noise limit with a signal-to-noise ratio of 28 for an optical power measured at the cornea of 100 μW. To demonstrate the imaging capabilities of the system, the macula and the optic nerve head of a healthy volunteer were imaged. Confocal images show good contrast and lateral resolution with a 10°×10° field of view.

Clinical Validation of Point-Source Corneal Topography in Keratoplasty

Purpose. To validate the clinical performance of point-source corneal topography (PCT) in postpenetrating keratoplasty (PKP) eyes and to compare it with conventional Placido-based topography. Methods. Corneal elevation maps of the anterior corneal surface were obtained from 20 post-PKP corneas using PCT (VU topographer, prototype; VU University Medical Center, Amsterdam, The Netherlands) and Placido-based topography (Keratron, Optikon 2000, Rome, Italy). Corneal surface parameters are calculated in terms of radius and asphericity. Corneal aberrations were characterized using standard Zernike convention. An artificial surface with quadrafoil feature (SUMIPRO, Almelo, The Netherlands) was measured and used as a reference to assess instrument performance compared with the gold standard. Results. The differences (mean ± std of PCT − Placido) found between the two types of topographers in measurements of post-PKP eyes are 0.02 ± 0.21 mm (p = 0.64) for radius of curvature, 0.14 ± 0.49 (p = 0.23) for asphericity, −0.19 ± 1.67 &mgr;m (p = 0.61) for corneal astigmatism, −0.25 ± 1.34 &mgr;m (p = 0.41) for corneal coma, 0.23 ± 0.82 &mgr;m (p = 0.23) for corneal trefoil, and 0.15 ± 0.28 &mgr;m (p = 0.02) for corneal quadrafoil. The PCT measured the artificial surface more accurate (rms error 0.16 &mgr;m; 0.12 eq. Dpt.) than the Placido-based topographer (rms error 1.50 &mgr;m; 1.15 eq. Dpt.). Conclusions. PCT is more accurate than Placido-based topography in measuring quadrafoil aberration.