Polarization-sensitive imaging with simultaneous bright- and dark-field optical coherence tomography.

We present a polarization-sensitive (PS) extension for bright- and dark-field (BRAD) optical coherence tomography imaging. Using a few-mode fiber detection scheme, the light backscattered at different angles is separated, and the BRAD images of tissue scattering are generated. A calibration method to correct for the fiber birefringence is proposed. Since particle scattering profiles are polarization dependent, a PS detection extends the capabilities for investigating the scattering properties of biological tissues. Both phantoms consisting of different-sized microparticles and a brain tissue specimen were imaged to validate the system performance and demonstrate the complementary image contrast.

IMAGING OF VITELLIFORM MACULAR LESIONS USING POLARIZATION-SENSITIVE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To examine the involvement of the retinal pigment epithelium (RPE) in the presence of vitelliform macular lesions (VML) in Best vitelliform macular dystrophy (BVMD), autosomal recessive bestrophinopathy, and adult-onset vitelliform macular degeneration using polarization-sensitive optical coherence tomography (PS-OCT). METHODS: A total of 35 eyes of 18 patients were imaged using a PS-OCT system and blue light fundus autofluorescence imaging. Pathogenic mutations in the BEST1 gene, 3 of which were new, were detected in all patients with BVMD and autosomal recessive bestrophinopathy. RESULTS: Polarization-sensitive optical coherence tomography showed a characteristic pattern in all three diseases with nondepolarizing material in the subretinal space consistent with the yellowish VML seen on funduscopy with a visible RPE line below it. A focal RPE thickening was seen in 26 eyes under or at the edge of the VML. Retinal pigment epithelium thickness outside the VML was normal or mildly thinned in patients with BVMD and adult-onset vitelliform macular degeneration but was diffusely thinned or atrophic in patients with autosomal recessive bestrophinopathy. Patients with autosomal recessive bestrophinopathy showed sub-RPE fibrosis alongside the subretinal VML. Polarization-sensitive optical coherence tomography was more reliable in assessing the localization and the integrity of the RPE than spectral domain OCT alone. On spectral domain OCT, identification of the RPE was not possible in 19.4% of eyes. Polarization-sensitive optical coherence tomography allowed for definite identification of the location of VML in respect to the RPE in all eyes, since it provides a tissue-specific contrast. CONCLUSION: Polarization-sensitive optical coherence tomography confirms in vivo the subretinal location of VML and is useful in the assessment of RPE integrity.

Optical coherence tomography in Optics Express [Invited].

Optical coherence tomography (OCT) is one of the most successful technologies in the history of biomedical optics. Optics Express played an important role in communicating groundbreaking technological achievements in the field of OCT, and, conversely, OCT papers are among the most frequently cited papers published in Optics Express. On the occasion of the 20th anniversary of the journal, this review analyzes the reasons for the success of OCT papers in Optics Express and discusses possible motivations for researchers to submit some of their best OCT papers to the journal.

Retinal pigment epithelium findings in patients with albinism using wide-field polarization-sensitive optical coherence tomography.

PURPOSE: To investigate pigmentation characteristics of the retinal pigment epithelium (RPE) in patients with albinism using wide-field polarization-sensitive optical coherence tomography compared with intensity-based spectral domain optical coherence tomography and fundus autofluorescence imaging. METHODS: Five patients (10 eyes) with previously genetically diagnosed albinism and 5 healthy control subjects (10 eyes) were imaged by a wide-field polarization-sensitive optical coherence tomography system (scan angle: 40 × 40° on the retina), sensitive to melanin contained in the RPE, based on the polarization state of backscattered light. Conventional intensity-based spectral domain optical coherence tomography and fundus autofluorescence examinations were performed. Retinal pigment epithelium-pigmentation was analyzed qualitatively and quantitatively based on depolarization assessed by polarization-sensitive optical coherence tomography. RESULTS: This study revealed strong evidence of polarization-sensitive optical coherence tomography to specifically image melanin in the RPE. Depolarization of light backscattered by the RPE in patients with albinism was reduced compared with normal subjects. Heterogeneous RPE-specific depolarization characteristics were observed in patients with albinism. Reduction of depolarization observed in the light backscattered by the RPE in patients with albinism corresponds to expected decrease of RPE pigmentation. The degree of depigmentation of the RPE is possibly associated with visual acuity. Findings suggest that different albinism genotypes result in heterogeneous levels of RPE pigmentation. CONCLUSION: Polarization-sensitive optical coherence tomography showed a heterogeneous appearance of RPE pigmentation in patients with albinism depending on different genotypes.

Automated inter-device 3D OCT image registration using deep learning and retinal layer segmentation.

Optical coherence tomography (OCT) is the most widely used imaging modality in ophthalmology. There are multiple variations of OCT imaging capable of producing complementary information. Thus, registering these complementary volumes is desirable in order to combine their information. In this work, we propose a novel automated pipeline to register OCT images produced by different devices. This pipeline is based on two steps: a multi-modal 2D en-face registration based on deep learning, and a Z-axis (axial axis) registration based on the retinal layer segmentation. We evaluate our method using data from a Heidelberg Spectralis and an experimental PS-OCT device. The empirical results demonstrated high-quality registrations, with mean errors of approximately 46 µm for the 2D registration and 9.59 µm for the Z-axis registration. These registrations may help in multiple clinical applications such as the validation of layer segmentations among others.

Phase retardation and corneal sublayer thickness repeatability using ultrahigh-resolution polarization-sensitive OCT.

PURPOSE: To assess phase retardation and corneal sublayer thickness repeatability using ultrahigh-resolution polarization-sensitive optical coherence tomography (PS-OCT). SETTING: Narayana Nethralaya Eye Hospital, Bangalore. DESIGN: Observational. METHODS: In this study, all eyes were imaged using a custom-built ultrahigh-resolution PS-OCT and high-resolution hybrid OCT (MS-39). The repeatability of phase retardation en face maps and corneal sublayer thickness profiles was evaluated. The reflectivity and phase retardation were calculated from the 2 orthogonal polarization channels to generate en face maps of phase retardation and corneal sublayer thicknesses. 3 consecutive measurements of all participants were acquired for each eye. For each measurement, the participant was asked to sit back and was realigned again. The repeatability was assessed using the intraclass correlation coefficient (ICC). RESULTS: The study included 20 healthy eyes of 20 participants. The phase retardation en face maps showed preferential arrangement of collagen fibrils with least retardation in the apex and maximum retardation in the periphery. The phase retardation showed excellent repeatability (ICC >0.95) in all zones. The Bowman layer and stromal layer thicknesses were measured with excellent repeatability (ICC >0.93 and >0.99, respectively). Significant differences ( P < .05) in stromal layer thickness were observed between MS-39 and PS-OCT. The repeatability of epithelial thickness measurements was better with PS-OCT than MS-39. CONCLUSIONS: The combinational assessment of corneal birefringence and sublayer thicknesses shows the advanced potential of ultrahigh-resolution PS-OCT in routine clinical practice over current OCT devices.

Characteristics of Henle's fiber layer in healthy and glaucoma eyes assessed by polarization-sensitive optical coherence tomography.

Using conventional optical coherence tomography (OCT), it is difficult to image Henle fibers (HF) due to their low backscattering potential. However, fibrous structures exhibit form birefringence, which can be exploited to visualize the presence of HF by polarization-sensitive (PS) OCT. We found a slight asymmetry in the retardation pattern of HF in the fovea region that can be associated with the asymmetric decrease of cone density with eccentricity from the fovea. We introduce a new measure based on a PS-OCT assessment of optic axis orientation to estimate the presence of HF at various eccentricities from the fovea in a large cohort of 150 healthy subjects. By comparing a healthy age-matched sub-group (N = 87) to a cohort of 64 early-stage glaucoma patients, we found no significant difference in HF extension but a slightly decreased retardation at about 2° to 7.5° eccentricity from the fovea in the glaucoma patients. This potentially indicates that glaucoma affects this neuronal tissue at an early state.

Lens based adaptive optics scanning laser ophthalmoscope.

We present an alternative approach for an adaptive optics scanning laser ophthalmoscope (AO-SLO). In contrast to other commonly used AO-SLO instruments, the imaging optics consist of lenses. Images of the fovea region of 5 healthy volunteers are recorded. The system is capable to resolve human foveal cones in 3 out of 5 healthy volunteers. Additionally, we investigated the capability of the system to support larger scanning angles (up to 5°) on the retina. Finally, in order to demonstrate the performance of the instrument images of rod photoreceptors are presented.

Automated measurement of choroidal thickness in the human eye by polarization sensitive optical coherence tomography.

We present a new method to automatically segment the thickness of the choroid in the human eye by polarization sensitive optical coherence tomography (PS-OCT). A swept source PS-OCT instrument operating at a center wavelength of 1040 nm is used. The segmentation method is based entirely on intrinsic, tissue specific polarization contrast mechanisms. In a first step, the anterior boundary of the choroid, the retinal pigment epithelium, is segmented based on depolarization. In a second step, the choroid-sclera interface is found by using the birefringence of the sclera. The method is demonstrated in five healthy eyes. The mean repeatability (standard deviation) of thickness measurement was found to be 18.3 µm.

Morphologic characteristics of idiopathic juxtafoveal telangiectasia using spectral-domain and polarization-sensitive optical coherence tomography.

PURPOSE: Idiopathic juxtafoveal telangiectasia (IJT) is characteristically associated with pigmentary changes. Polarization-sensitive spectral-domain optical coherence tomography (PS-SD-OCT) enables imaging of the retinal pigment epithelium (RPE) and similar melanin-containing structures based on specific polarization properties. This study examined IJT with the latest-generation SD-OCT and PS-SD-OCT, identifying pathophysiologically relevant characteristics of the retinal layers and RPE. METHODS: Twenty-two eyes of 12 patients with IJT were examined by PS-SD-OCT, with special focus on RPE detection and segmentation. Furthermore, SD-OCT technology (Cirrus, Spectralis, and 3D-OCT-1000) was applied. Characteristics of the retinal layers and RPE were evaluated. A classification system based on OCT characteristics of IJT was suggested. RESULTS: Polarization-sensitive spectral-domain optical coherence tomography together with SD-OCT identified characteristic patterns of IJT, used to classify eyes into three distinct groups. Group 1 (5 eyes) revealed discrete alterations in the inner retinal layers; group 2 (12 eyes) showed irregularities of the junction between the inner and outer photoreceptor segments with outer retinal atrophy but an intact RPE. Group 3 (5 eyes) revealed RPE irregularities and loss in addition to intraretinal alterations and photoreceptor abnormalities. CONCLUSION: This study described characteristic morphologic changes in IJT based on PS-SD-OCT and SD-OCT. Morphologic changes were classified, possibly leading to an OCT-based grading scheme. The intensity images of SD-OCT verified intraretinal and photoreceptor irregularities in great detail, whereas PS-SD-OCT additionally showed RPE alterations.

High-speed retinal imaging with polarization-sensitive OCT at 1040 nm.

PURPOSE: To demonstrate the ability of a new high-speed polarization-sensitive optical coherence tomography (PS-OCT) system for retinal imaging at 1040 nm. METHODS: A new polarization-sensitive swept source OCT system in the 1 µm wavelength range is used to image the retina of healthy volunteers. The instrument is operated at an A-scan rate of 100 kHz which is about three times faster than previously reported PS-OCT instruments in this wavelength region. The increased imaging speed can be used to record densely sampled volumes of the retina. Moreover, it enables averaging of several B-scans recorded at the same location to obtain high-definition B-scans without the use of an eye tracker. RESULTS: Polarization-sensitive images of healthy volunteers clearly show the retinal pigment epithelium as a depolarizing layer. In addition, the good tissue penetration of the system allows the visualization of the sclera, which is highly birefringent and therefore shows increased image contrast with PS-OCT. CONCLUSIONS: PS-OCT in the 1 µm wavelength region shows similar polarization effects as in the 840 nm wavelength range. The high speed enables averaging of several B-scans to obtain high-definition polarization-sensitive images. The new system provides excellent penetration depth into the choroid and sclera.

Farewell editorial.

Biomedical Optics Express Editor-in-Chief Christoph K. Hitzenberger and Deputy Editor Adam Gibson share some final remarks as they prepare to end their editorial terms on 31 December 2021.

Automatic retinal nerve fiber bundle tracing based on large field of view polarization sensitive OCT data.

A technique to accurately estimate trajectories of retinal nerve fiber bundles (RNFB) in a large field of view (FOV) image covering 45° is described. The method utilizes stitched projections of polarization-sensitive optical coherence tomography (PS-OCT) data, as well as a mathematical model of average RNFB trajectories as prior. The fully automatic process was applied to data recorded in healthy subjects and glaucoma patients and automatically detected individual RNFB trajectories are compared to manual traces.

Quantitative assessment of depolarization by the retinal pigment epithelium in healthy and glaucoma subjects measured over a large field of view.

We present measurements of depolarization introduced by the retinal pigment epithelium (RPE) over a 45° field of view using polarization sensitive optical coherence tomography. A detailed spatial distribution analysis of depolarization caused by the RPE is presented in a total of 153 subjects including both healthy and diseased eyes. Age and sex related differences in the depolarizing character of the RPE are investigated.

Birefringent Properties of the Peripapillary Retinal Nerve Fiber Layer in Healthy and Glaucoma Subjects Analyzed by Polarization-Sensitive OCT.

Purpose: To study the circumpapillary retinal nerve fiber layer (RNFL) birefringence (BIR) of early glaucoma and age-matched healthy eyes using polarization-sensitive optical coherence tomography (PS-OCT). Methods: In this prospective cross-sectional study, we compared virtual circular PS-OCT B-scans with a diameter of 3.5 mm centered on the optic disc (OD) acquired with a PS-OCT prototype (860 nm center wavelength). Early glaucoma was defined by the glaucomatous appearance of the OD and a pathologic visual field test with a mean deviation (MD) better than -6 dB. The main outcome parameters were BIR, RNFL-thickness (RNFL-T), and phase retardation (RET). The BIR value at each virtual A-scan position was the quotient of the RET measured at the inner segment/outer segment junction divided by the RNFL-T. Results: The dataset comprised 49 early glaucoma patients (mean ± standard deviation [SD]: 64 ± 10 years) and 49 healthy control subjects (61 ± 9 years). Glaucomatous eyes showed a statistically significant lower BIR globally (mean ± SD: 0.108 ± 0.008°/µm vs. 0.112 ± 0.009°/µm, P = 0.033), superiorly (0.116 ± 0.017°/µm vs. 0.126 ± 0.013°/µm, P = 0.0001), and inferiorly (0.112 ± 0.011°/µm vs. 0.121 ± 0.011°/µm, P < 0.0001), and increased BIR in the temporal quadrant (0.088 ± 0.015°/µm vs. 0.078 ± 0.014°/µm, P = 0.0001) compared to healthy eyes. Conclusions: We report a reduced BIR of the RNFL in early perimetric glaucoma, which can be interpreted as a sign of loss or change of intracellular microtubules and may contribute to a better understanding of early disease development. Prospective longitudinal studies are needed to determine whether BIR is altered in pre-perimetric human glaucoma before RNFL-T decline.

Mapping of corneal birefringence in thin and asymmetric keratoconus corneas with ultrahigh-resolution polarization-sensitive OCT.

PURPOSE: To evaluate phase retardation (PR) across healthy eyes and eyes with thin corneas (<500 µm) and with asymmetric and bilateral keratoconus (KC). SETTING: Narayana Nethralaya Eye Hospital, Bangalore, India. DESIGN: Observational cross-sectional. METHODS: There were 4 eye groups: healthy eyes (Group 1; n = 10 eyes), eyes with thin corneas and no clinical disease (Group 2; n = 10 eyes), eyes with asymmetric KC (Group 3; n = 5 eyes), and eyes with clinical KC (Group 4; n = 15 eyes). All eyes were imaged with polarization-sensitive optical coherence tomography (PS-OCT), MS-39, and Corvis-ST. Using PS-OCT, PR was analyzed in annular regions. The anterior (A-E) and Bowman (E-B) wavefront aberrations, epithelial Zernike indices (EZI), total corneal thickness, Corvis biomechanical index (CBI), total biomechanical index (TBI), and Belin-Ambrósio overall deviation index (BAD-D) were analyzed. RESULTS: Only CBI, TBI, BAD-D, A-E and E-B aberrations, EZI, and total corneal thickness distributions of Groups 1 (n =10), 2 (n =10), and 3 (n =5) were similar ( P > .05) but not CCT ( P < .05). PR distributions clearly showed that the eyes in Groups 1, 2, and 3 had a normal corneal birefringence unlike Group 4 (n = 10) eyes ( P < .05). The PR map was similar to the preferred orientations of collagen fibers seen in X-ray diffraction ex vivo studies of corneal stroma. CONCLUSIONS: PR distributions may eliminate the uncertainty associated with the stromal status of thin and asymmetric KC corneas. Group 2 and 3 eyes appeared as healthy because of normal corneal birefringence at the time of imaging, but a longitudinal follow-up of these eyes with PS-OCT may assist in early detection of onset of disease.

Baseline predictors for subretinal fibrosis in neovascular age-related macular degeneration.

To find baseline predictors for subretinal fibrosis (SF) in neovascular age-related macular degeneration (nAMD). Forty-five eyes of 45 participants with treatment-naïve nAMD were consecutively enrolled and treated according to a standardized treat-and-extend protocol. Spectral-domain optical coherence tomography (OCT), color fundus photography and fluorescein angiography as well as novel imaging modalities polarization-sensitive OCT and OCT angiography (OCTA) were performed to detect SF after 1 year and find baseline predictors for SF development. Baseline OCTA scans were evaluated for quantitative features such as lesion area, vessel area, vessel junctions, vessel length, vessel endpoints and mean lacunarity. Additionally, the type of macular neovascularization, the presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material (SHRM), retinal hemorrhage as well as best-corrected visual acuity (BCVA) were evaluated. After 12 months 8 eyes (18%) developed SF. Eyes with SF had worse baseline BCVA (p = .001) and a higher prevalence of IRF (p = .014) and SHRM at baseline (p = .017). There was no significant difference in any of the evaluated quantitative OCTA parameters (p > .05) between eyes with and without SF. There were no quantitative baseline microvascular predictors for SF in our study. Low baseline BCVA, the presence of IRF and SHRM, however, are easily identifiable baseline parameters indicating increased risk.

Visualization of microvasculature by dual-beam phase-resolved Doppler optical coherence tomography.

We present a dual-beam Doppler optical coherence tomography system for visualizing the microvasculature within the retina. The sample arm beams from two identical spectral domain optical coherence tomography (SD-OCT) systems are combined such that there is a small horizontal offset between them at the retina. Thereby we record two tomograms which are slightly separated in time. Phase-resolved Doppler analysis is performed between these two data sets. This system allows blood capillary imaging with high flow sensitivity and variable velocity range. To demonstrate the performance of our system we present images of the microvascular network around the fovea and around the optic nerve head of the human eye.

Speckle noise reduction in high speed polarization sensitive spectral domain optical coherence tomography.

We present a high speed polarization sensitive spectral domain optical coherence tomography system based on polarization maintaining fibers and two high speed CMOS line scan cameras capable of retinal imaging with up to 128 k A-lines/s. This high imaging speed strongly reduces motion artifacts and therefore averaging of several B-scans is possible, which strongly reduces speckle noise and improves image quality. We present several methods for averaging retardation and optic axis orientation, the best one providing a 5 fold noise reduction. Furthermore, a novel scheme of calculating images of degree of polarization uniformity is presented. We quantitatively compare the noise reduction depending on the number of averaged frames and discuss the limits of frame numbers that can usefully be averaged.

Temporal phase evolution OCT for measurement of tissue deformation in the human retina in-vivo.

We demonstrate the use of temporal phase evolution (TPE-) OCT methods to evaluate retinal tissue deformation in-vivo over time periods of several seconds. A custom built spectral domain (SD)-OCT system with an integrated retinal tracker, ensuring stable imaging with sub-speckle precision, was used for imaging. TPE-OCT measures and images phase differences between an initial reference B-scan and each of the subsequent B-scans of the evaluated temporal sequence. In order to demonstrate the precision and repeatability of the measurements, retinal nerve fiber (RNF) tissue deformations induced by retinal vessels pulsating with the heartbeat were analyzed in several healthy subjects. We show TPE maps (M-scans of phase evolution as a function of position along B-scan trace vs. time) of wrapped phase data and corresponding deformation maps in selected regions of the RNF layer (RNFL) over the course of several cardiac cycles. A reproducible phase pattern is seen at each heartbeat cycle for all imaged volunteers. RNF tissue deformations near arteries and veins up to ∼ 1.6 µm were obtained with an average precision for a single pixel of about 30 nm. Differences of motion induced by arteries and veins are also investigated.