Extended and adjustable field-of-view of variable interscan time analysis by ammonite-scanning swept-source optical coherence tomography angiography.

A novel scanning protocol, ammonite scan, is proposed for widefield optical coherence tomography angiography (OCTA) and relative retinal blood flow velocity imaging in the human retina using variable interscan time analysis (VISTA). A repeated circle scan using a 400 kHz swept-source was employed to achieve an interscan time of 1.28 ms. The center of the repeated circular scan continuously moved spirally towards the peripheral region, ensuring an extended and adjustable scan range while preserving the short interscan time. Image artifacts due to eye movement were eliminated via extra motion-correction processing using data redundancy. The relative blood flow velocity in superficial and deep plexus layers was calculated from the VISTA image, and their ratio was used to explore the microvascular flow parameter in the healthy human eye.

Birefringence-derived artifact in optical coherence tomography imaging of the lamina cribrosa in eyes with glaucoma.

We investigated birefringence-derived artifacts that potentially mimic focal defects of the lamina cribrosa (focal LC defects) in optical coherence tomography (OCT) imaging of eyes with glaucoma. This study included 74 eyes of 48 patients with glaucoma. Five horizontal line B-scan images of the optic disc were obtained using commercial swept-source OCT. From a dataset of prototype swept-source polarization-diversity OCT, we calculated the following types of OCT images: polarization-dependent, polarization-dependent attenuation-coefficient, polarization-independent, and polarization-independent attenuation-coefficient. We assessed the commercial OCT images for the presence of birefringence-derived artifacts by comparison with the polarization-diversity OCT images. Commercial OCT showed suggestive findings of focal LC defects in 17 of 74 eyes. Reevaluation using polarization-independent OCT revealed that the focal LC defects in one of 17 eyes (5.9%) were actually birefringence-derived artifacts. This study demonstrated the existence of birefringence-derived artifacts mimicking focal LC defects in commercial OCT imaging and indicated that polarization-diversity OCT is an effective tool to evaluate the presence of these artifacts.

Synthesizing the degree of polarization uniformity from non-polarization-sensitive optical coherence tomography signals using a neural network.

Degree of polarization uniformity (DOPU) imaging obtained by polarization-sensitive optical coherence tomography (PS-OCT) has the potential to provide biomarkers for retinal diseases. It highlights abnormalities in the retinal pigment epithelium that are not always clear in the OCT intensity images. However, a PS-OCT system is more complicated than conventional OCT. We present a neural-network-based approach to estimate the DOPU from standard OCT images. DOPU images were used to train a neural network to synthesize the DOPU from single-polarization-component OCT intensity images. DOPU images were then synthesized by the neural network, and the clinical findings from ground truth DOPU and synthesized DOPU were compared. There is a good agreement in the findings for RPE abnormalities: recall was 0.869 and precision was 0.920 for 20 cases with retinal diseases. In five cases of healthy volunteers, no abnormalities were found in either the synthesized or ground truth DOPU images. The proposed neural-network-based DOPU synthesis method demonstrates the potential of extending the features of retinal non-PS OCT.

Birefringence-derived scleral artifacts in optical coherence tomography images of eyes with pathologic myopia.

We investigated birefringence-derived scleral artifacts in optical coherence tomography (OCT) images of eyes with pathologic myopia. This study included 76 eyes of 42 patients with pathologic myopia. Five sets of OCT B-scan images of the macula were obtained using commercial swept-source OCT. A dataset of prototype swept-source polarization-diversity OCT images was used to identify polarization-dependent OCT images (i.e., complex averaging of OCT signals from two polarization channels) and polarization-independent OCT images (i.e., intensity averaging of two OCT signals). Polarization-dependent OCT images and commercial OCT images were assessed for the presence of birefringence-derived artifacts by comparison with polarization-independent OCT images. Both polarization-dependent OCT images and commercial OCT images contained scleral vessel artifacts. Scleral vessel artifacts were present in 46 of 76 eyes (60.5%) imaged by polarization-dependent OCT and 17 of 76 eyes (22.4%) imaged by commercial OCT. The proportion of images that showed scleral vessel artifacts was significantly greater among polarization-dependent OCT images than among commercial OCT images (P < 0.001). Additionally, polarization-dependent OCT images showed low-intensity band artifacts. This study demonstrated the existence of birefringence-derived scleral artifacts in commercial OCT images and indicated that polarization-diversity OCT is an effective tool to evaluate the presence of these artifacts.

Extending field-of-view of retinal imaging by optical coherence tomography using convolutional Lissajous and slow scan patterns.

Optical coherence tomography (OCT) is a high-speed non-invasive cross-sectional imaging technique. Although its imaging speed is high, three-dimensional high-spatial-sampling-density imaging of in vivo tissues with a wide field-of-view (FOV) is challenging. We employed convolved Lissajous and slow circular scanning patterns to extend the FOV of retinal OCT imaging with a 1-µm, 100-kHz-sweep-rate swept-source OCT prototype system. Displacements of sampling points due to eye movements are corrected by post-processing based on a Lissajous scan. Wide FOV three-dimensional retinal imaging with high sampling density and motion correction is achieved. Three-dimensional structures obtained using repeated imaging sessions of a healthy volunteer and two patients showed good agreement. The demonstrated technique will extend the FOV of simple point-scanning OCT, such as commercial ophthalmic OCT devices, without sacrificing sampling density.

Evaluation of choroidal melanin-containing tissue in healthy Japanese subjects by polarization-sensitive optical coherence tomography.

In this study, the choroidal melanin content in healthy eyes was evaluated with polarization-sensitive optical coherence tomography (PS-OCT). We evaluated 105 healthy eyes of 105 Japanese subjects. The mean thickness of melanin-containing tissue in the choroid (thickness of MeCh) and the choroidal melanin occupancy rate within a 5-mm circular region from the foveal center were calculated using the degree of polarization uniformity obtained by PS-OCT and compared with the choroidal thickness, patient age, and axial length. To evaluate regional variations, the 5-mm circular region was divided into a center area and an outer ring area, and the outer ring area was further divided into four areas (nasal, temporal, superior, and inferior). The mean thickness of MeCh showed a significant positive correlation with the choroidal thickness. The mean choroidal melanin occupancy rate showed a significant positive correlation with age. The mean choroidal melanin occupancy rate of the center area was significantly larger than that of the outer ring area. The mean thickness of MeCh and choroidal melanin occupancy rate of the nasal area were significantly lower than those of other areas. The distribution of melanin-containing tissue in the choroid varies significantly with age and location.

Objective evaluation of choroidal melanin loss in patients with Vogt-Koyanagi-Harada disease using polarization-sensitive optical coherence tomography.

In this study, sunset glow fundus was evaluated in patients with Vogt-Koyanagi-Harada (VKH) disease using polarization-sensitive optical coherence tomography (PS-OCT). We evaluated 40 VKH eyes (20 patients) and 59 healthy eyes (59 age-matched controls). VKH eyes were divided into three groups according to color fundus images: sunset (17 eyes), potential sunset (13 eyes), and non-sunset (10 eyes). Choroidal melanin thickness (ChMeT) and the choroidal melanin thickness ratio (ChMeTratio) were calculated based on the degree of polarization uniformity from PS-OCT. ChMeT was significantly lower in sunset eyes than in non-sunset or control eyes (P = 0.003). The ChMeTratios of sunset or potential sunset eyes were significantly lower than those of non-sunset or control eyes (P = 0.04). Regional evaluation of ChMeT and the ChMeTratio showed that choroidal depigmentation predominantly occurred in the macula's outer ring area (P = 0.002). The areas under receiver operating characteristic curves discriminating combined sunset (sunset and potential sunset) from non-sunset eyes were 0.983 and 0.997 for ChMeT and the ChMeTratio, respectively. Time course evaluation of 12 eyes from disease onset showed that ChMeT and the ChMeTratio significantly decreased over time. PS-OCT may be useful for objectively evaluating choroidal depigmentation in patients with VKH disease.

Sensorless astigmatism correction using a variable cross-cylinder for high lateral resolution optical coherence tomography in a human retina.

High lateral resolution (∼5µm) optical coherence tomography (OCT) that employs a variable cross-cylinder (VCC) to compensate for astigmatism is presented for visualizing minute structures of the human retina. The VCC and its sensorless optimization process enable ocular astigmatism correction of up to -5.0 diopter within a few seconds. VCC correction has been proven to increase the signal-to-noise ratio and lateral resolution using a model eye. This process is also validated using the human eye by visualizing the capillary network and human cone mosaic. The proposed method is applicable to existing OCT, making high lateral resolution OCT practical in clinical settings.

Accurately motion-corrected Lissajous OCT with multi-type image registration.

Passive motion correction methods for optical coherence tomography (OCT) use image registration to estimate eye movements. To improve motion correction, a multi-image cross-correlation that employs spatial features in different image types is introduced. Lateral motion correction using en face OCT and OCT-A projections on Lissajous-scanned OCT data is applied. Motion correction using OCT-A projection of whole depth and OCT amplitude, OCT logarithmic intensity, and OCT maximum intensity projections were evaluated in retinal imaging with 76 patients. The proposed method was compared with motion correction using OCT-A projection of whole depth. The comparison shows improvements in the image quality of motion-corrected superficial OCT-A images and image registration.

Evaluation of retinal pigment epithelium changes in serous pigment epithelial detachment in age-related macular degeneration.

The purpose of this study was to quantitatively evaluate retinal pigment epithelium (RPE) changes in serous pigment epithelial detachment (PED) among patients with age-related macular degeneration by means of prototype multi-contrast optical coherence tomography (OCT), which is capable of simultaneous collection of OCT angiography, polarization-sensitive OCT, and standard OCT images. We evaluated 26 eyes of 21 patients with serous PED. RPE-melanin OCT images were calculated from the multi-contrast OCT dataset and compared with near-infrared autofluorescence images. An active RPE lesion was defined as an area of thickened RPE-melanin (≥ 70 µm; RPE70) on RPE-melanin OCT. Each PED area was divided into peak and slope regions. RPE70 area ratios were compared with the maximum PED height, PED area, PED volume, and slope area ratio (area of slope region/area of whole PED). RPE-melanin OCT images were consistent with near-infrared autofluorescence images. The RPE70 area ratio in the slope region was significantly negatively correlated with the slope area ratio. Development of active RPE lesions in the slope region was correlated with the PED configuration. Multi-contrast OCT is useful for objective evaluation of changes in the RPE in patients with age-related macular degeneration.

Evaluation of focal damage in the retinal pigment epithelium layer in serous retinal pigment epithelium detachment.

The purpose of this study was to evaluate focal damage in the retinal pigment epithelium (RPE) layer in serous retinal pigment epithelium detachment (PED) with multi-contrast optical coherence tomography (OCT), which is capable of simultaneous measurement of OCT angiography, polarization-sensitive OCT and standard OCT images. We evaluated 37 eyes with age-related macular degeneration that had serous PED. Focal RPE damage was indicated by hyper-transmission beneath the RPE-Bruch's membrane band in standard OCT images. Distribution of RPE melanin was calculated using the dataset from multi-contrast OCT. Twenty-four points with hyper-transmission were detected in 21 of the 37 eyes. Standard OCT images failed to show disruption of the RPE-Bruch's membrane band at 5 of the 24 hyper-transmission points. Conversely, multi-contrast OCT images clearly showed melanin defects in the RPE-Bruch's membrane band at all points. Areas of melanin defects with disruption of the RPE-Bruch's membrane band were significantly larger than those without disruption. The volume of intraretinal hyper-reflective foci was significantly larger in eyes with hyper-transmission than that in eyes without hyper-transmission. Multi-contrast OCT is more sensitive than standard OCT for displaying changes at the RPE-Bruch's membrane band when there are small areas of RPE damage.

Evaluation of Retinal Pigment Epithelium Layer Change in Vogt-Koyanagi-Harada Disease With Multicontrast Optical Coherence Tomography.

Purpose: Clinical evaluation of retinal pigment epithelium (RPE) change is important for the therapeutic management of chronic Vogt-Koyanagi-Harada (VKH) disease. We evaluated long-term change in the RPE layer in VKH disease, using near-infrared (NIR; 817 nm) images and autofluorescence images at 488 nm (short-wavelength [SW]-AF) and 785 nm (NIR-AF), and compared those images with images from multicontrast optical coherence tomography (MC-OCT). MC-OCT is capable of simultaneous measurement of OCT angiography, polarization-sensitive OCT, and standard OCT. Methods: We evaluated 24 eyes of 12 patients with chronic VKH disease. RPE changes were assessed using NIR, NIR-AF, SW-AF, and MC-OCT imaging performed from 6 to 48 months after disease onset. RPE-melanin-specific contrast OCT images were calculated using the dataset from MC-OCT. Results: Granular hyper NIR-AF lesions were observed in 8 of 24 eyes (33%). Eyes with granular hyper NIR-AF lesions showed a sunset glow fundus appearance significantly more frequently than did eyes without such lesions (P < 0.0001). MC-OCT imaging confirmed that there was melanin accumulation at the RPE-Bruch's membrane band at the location of granular hyper NIR-AF lesions. Granular hyper NIR-AF lesions were unclear in SW-AF and color fundus images, but clearly detectable in NIR images. Areas of hyper NIR-AF lesions gradually decreased over time. Conclusions: Melanin accumulation in the RPE layer at the location of granular hyper NIR-AF lesions was confirmed with MC-OCT imaging. Long-term follow-up showed the reversible nature of this accumulation. MC-OCT is useful for the evaluation of change at the RPE layer in chronic VKH disease.

Clinical prototype of pigment and flow imaging optical coherence tomography for posterior eye investigation.

Measurements of the randomness of polarization (RP) obtained using polarization-sensitive optical coherence tomography (PS-OCT) are applied in several applications, and RP is attractive for posterior eye imaging. The addition of RP without retardation requires a minimal extension to standard OCT; therefore, we developed a prototype OCT system with a simplified scheme for RP measurement. A compact polarization-diversity receiver module is the only required hardware extension to a standard OCT system. All components were packed into the retinal scanning head. The degree-of-polarization uniformity and complex-decorrelation based OCT angiography were calculated using noise-corrected algorithms that accounted for the depth-dependent noise power. The structure, melanin, and blood flow distribution imaging of in vivo human eyes were demonstrated. Pathological eye imaging shows potential applications for combinations of these contrasts.

Quantitative analysis of polarization-controlled tip-enhanced Raman imaging through the evaluation of the tip dipole.

Polarization analysis in tip-enhanced Raman spectroscopy (TERS) is of tremendous advantage, as it allows one to study highly directional intrinsic properties of a sample at the nanoscale. However, neither evaluation nor control of the polarization properties of near-field light in TERS is as straightforward as in usual far-field illumination, because of the random metallic nanostructure attached to the tip apex. In this study, we have developed a method to successfully analyze the polarization of near-field light in TERS from the scattering pattern produced by the induced dipole in the metallic tip. Under dipole approximation, we measured the image of the dipole at a plane away from the focal plane, where the information about the direction of the dipole oscillation was intact. The direction of the dipole oscillation was determined from the defocused pattern, and then the polarization of near-field light was evaluated from the oscillation direction by calculating the intensity distribution of near-field light through Green's function. After evaluating the polarization of some fabricated tips, we used those tips to measure TERS images from single-walled carbon nanotubes and confirmed that the contrast of the TERS image depended on the oscillation direction of the dipole, which were also found in excellent agreement with the calculated TERS images, verifying that the polarization of the near-field was quantitatively estimated by our technique. Our technique would lead to better quantitative analysis in TERS imaging with consideration of polarization impact, giving a better understanding of the behavior of nanomaterials.