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Accurate assessment of corneal curvatures using frequency domain optical coherence tomography (OCT) with galvanometer scanners remains challenging due to the well-known scan field distortion. This paper presents an algorithm and software for correcting the distortion using only two simple measurements in which a readily available standard sphere is positioned in different depths in front of the OCT scanner. This offers a highly accessible and easily reproducible method for the field distortion correction (FDC). The correction was validated by measuring different spherical phantoms and conducting corneal curvature measurements of ex vivo porcine corneas using a commercial spectral-domain OCT system and a clinically approved swept-source OCT as a reference instrument. Thus, the error in radius measurements of spherical phantoms was reduced by >90 % and astigmatism by >80 % using FDC. In explanted porcine eyes, the error in astigmatism measurements with the Telesto was reduced by 75% for power and 70% for angle. The best fitting sphere radius was determined up to a deviation of 0.4% from the Anterion. This paper describes a correction algorithm for OCT immanent distortion that is applicable to any scanning OCT setup and enables precise corneal curvature measurements. The MATLAB software for the FDC is publicly available on GitHub.

Purpose: To investigate the most peripheral corneal nerve plexus using high-resolution micro-optical coherence tomography (µOCT) imaging and to assess µOCT's clinical potential as a screening tool for corneal and systemic diseases., Methods: An experimental high-resolution (1.5 × 1.5 × 1 µm) µOCT setup was applied for three-dimensional imaging of the subbasal nerve plexus in nonhuman primates (NHPs) and swine within 3 hours postmortem. Morphologic features of subbasal nerves in µOCT were compared to β3 tubulin-stained fluorescence confocal microscopy (FCM). Parameters such as nerve density, nerve distribution, and imaging repeatability were evaluated, using semiautomatic image analysis in form of a custom corneal surface segmentation algorithm and NeuronJ., Results: Swine and NHP corneas showed the species-specific nerve morphology in both imaging modalities. Most fibers showed a linear course, forming a highly parallel pattern, converging in a vortex with overall nerve densities varying between 9.51 and 24.24 mm/mm2. The repeatability of nerve density quantification of the µOCT scans as approximately 88% in multiple image recordings of the same cornea., Conclusions: Compared to the current gold standard of FCM, µOCT's larger field of view of currently 1 × 1 mm increases the conclusiveness of density measurements, which, coupled with µOCT's feature of not requiring direct contact, shows promise for future clinical application. The nerve density quantification may be relevant for screening for systemic disease (e.g., peripheral neuropathy)., Translational Relevance: Technological advances in OCT technology may enable a quick assessment of corneal nerve density, which could be valuable evaluating ophthalmic and systemic peripheral innervation.

Purpose: To image, track and map the nerve fiber distribution in excised rabbit corneas over the entire stromal thickness using micro-optical coherence tomography (µOCT) to develop a screening tool for early peripheral neuropathy., Methods: Excised rabbit corneas were consecutively imaged by a custom-designed µOCT prototype and a commercial laser scanning fluorescence confocal microscope. The µOCT images with a field of view of approximately 1 × 1 mm were recorded with axial and transverse resolutions of approximately 1 µm and approximately 4 µm, respectively. In the volumetric µOCT image data, network maps of hyper-reflective, branched structures traversing different stromal compartments were segmented using semiautomatic image processing algorithms. Furthermore, the same corneas received βIII-tubulin antibody immunostaining before digital confocal microscopy, and a comparison between µOCT image data and immunohistochemistry analysis was performed to validate the nerval origin of the tracked network structures., Results: Semiautomatic tracing of the nerves with a high range of different thicknesses was possible through the whole corneal volumes, creating a skeleton of the traced nerves. There was a good conformity between the hyper-reflective structures in the µOCT data and the stained nerval structures in the immunohistochemistry data., Conclusions: This article demonstrates nerval imaging and tracking as well as a spatial correlation between µOCT and a fluorescence corneal nerve standard for larger nerves throughout the full thickness of the cornea ex vivo., Translational Relevance: Owing to its advantageous properties, µOCT may become useful as a noncontact method for assessing nerval structures in humans to screen for early peripheral neuropathy., Competing Interests: Disclosure: C. Elhardt, None; C.M. Wertheimer, German Research Foundation Research Fellowship (F); A. Wartak, SPIE (The International Society for Optics and Photonics) Franz Hillenkamp Fellowship (F); J. Zhao, None; H.M. Leung, None; S.A. Kassumeh, None; B. Yin, None; G.J. Tearney, Vertex (F), CNUSA Biotech Holdings (F), Astra Zeneca (F), WayVector (F); R. Birngruber, None, (Copyright 2020 The Authors.)

Correction of hyperopia requires an increase of the refractive power by steepening of the corneal surface. Present refractive surgical techniques based on corneal ablation (LASIK) or intrastromal lenticule extraction (SMILE) are problematic due to epithelial regrowth. Recently, it was shown that correction of low hyperopia can be achieved by implanting intracorneal inlays or allogeneic lenticules. We demonstrate a steepening of the anterior corneal surface after injection of a transparent, liquid filler material into a laser-dissected intrastromal pocket. We performed the study on ex-vivo porcine eyes. The increase of the refractive power was evaluated by optical coherence tomography (OCT). For a circular pocket, injection of 1 μl filler material increased the refractive power by +4.5 diopters. An astigmatism correction is possible when ellipsoidal intrastromal pockets are created. Injection of 2 μl filler material into an ellipsoidal pocket increased the refractive power by +10.9  dpt on the short and +5.1  dpt on the long axis. OCT will enable to monitor the refractive change during filler injection and is thus a promising technique for real-time dosimetry.

Optical coherence tomography angiography (OCTA) provides in-vivo images of microvascular perfusion in high resolution. For its application to basic and clinical research, an automatic and robust quantification of the capillary architecture is mandatory. Only this makes it possible to reliably analyze large amounts of image data, to establish biomarkers, and to monitor disease developments. However, due to its optical properties, OCTA images of skin often suffer from a poor signal-to-noise ratio and contain imaging artifacts. Previous work on automatic vessel segmentation in OCTA mostly focuses on retinal and cerebral vasculature. Its applicability to skin and, furthermore, its robustness against imaging artifacts had not been systematically evaluated. We propose a segmentation method that improves the quality of vascular quantification in OCTA images even if corrupted by imaging artifacts. Both the combination of image processing methods and the choice of their parameters are systematically optimized to match the manual labeling of an expert for OCTA images of skin. The efficacy of this optimization-based vessel segmentation is further demonstrated on sample images as well as by a reduced error of derived quantitative vascular network characteristics.

Aberration-corrected imaging of human photoreceptor cells, whether hardware or software based, presently requires a complex and expensive setup. Here we use a simple and inexpensive off-axis full-field time-domain optical coherence tomography (OCT) approach to acquire volumetric data of an in vivo human retina. Full volumetric data are recorded in 1.3 s. After computationally correcting for aberrations, single photoreceptor cells were visualized. In addition, the numerical correction of ametropia is demonstrated. Our implementation of full-field optical coherence tomography combines a low technical complexity with the possibility for computational image correction.

With a simple setup, mainly composed of a low coherence light source and a camera, full-field optical coherence tomography (FF-OCT) allows volumetric tissue imaging. However, fringe washout constrains its use in retinal imaging. Here, we present a novel motion-insensitive approach to FF-OCT, which introduces path-length differences between the reference and the sample light in neighboring pixels using an off-axis reference beam. The temporal carrier frequency in scanned time-domain OCT is replaced by a spatial carrier frequency. Volumetric in-vivo FF-OCT measurements of the human retina were acquired in only 1.3 s, comparable to the acquisition times of current clinically used OCT devices.

Optical coherence tomography (OCT) has been increasingly used for imaging pulmonary alveoli. Only a few studies, however, have quantified individual alveolar areas, and the validity of alveolar volumes represented within OCT images has not been shown. To validate quantitative measurements of alveoli from OCT images, we compared the cross-sectional area, perimeter, volume, and surface area of matched subpleural alveoli from microcomputed tomography (micro-CT) and OCT images of fixed air-filled swine samples. The relative change in size between different alveoli was extremely well correlated (r>0.9, P<0.0001), but OCT images underestimated absolute sizes compared to micro-CT by 27% (area), 7% (perimeter), 46% (volume), and 25% (surface area) on average. We hypothesized that the differences resulted from refraction at the tissue-air interfaces and developed a ray-tracing model that approximates the reconstructed alveolar size within OCT images. Using this model and OCT measurements of the refractive index for lung tissue (1.41 for fresh, 1.53 for fixed), we derived equations to obtain absolute size measurements of superellipse and circular alveoli with the use of predictive correction factors. These methods and results should enable the quantification of alveolar sizes from OCT images in vivo.

We conducted a study to correlate the retinal temperature rise during photocoagulation to the afterward detected tissue effect in optical coherence tomography (OCT). 504 photocoagulation lesions were examined in 20 patients. The retinal temperature increase was determined in real-time during treatment based on thermoelastic tissue expansion which was probed by repetitively applied ns laser pulses. The tissue effect was examined on fundus images and OCT images of individualized lesions. We discerned seven characteristic morphological OCT lesion classes. Their validity was confirmed by increasing visibility and diameters. Mean peak temperatures at the end of irradiation ranged from approx. 60 °C to beyond 100 °C, depending on burn intensity., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: It is unclear whether anti-VEGF monotherapy in age-related macular degeneration (AMD) achieves morphologic CNV regression or only stops further CNV growth. In this study, spectral domain-optical coherence tomography (SD-OCT) was used to image CNV structure before and after anti-VEGF treatment., Methods: Out of 107 consecutive patients, a prospective CNV evaluation was possible in 78 of them. Newly diagnosed CNV (classic CNV: n = 16; occult CNV: n = 54; minimal classic CNV: n = 8) due to AMD was imaged before and 4 weeks after anti-VEGF upload in three intravitreal injections of ranibizumab. Qualitative (structural changes) and quantitative measurements (diameter and thickness) of the CNV were obtained from the OCT images., Results: Classic CNV components were observed above the RPE/photoreceptor complex, whereas occult CNVs stayed below. Of all postoperative OCTs, 59% revealed complete dry retinal structures, 27% showed reduced edema, and 14% showed edema remaining unchanged. Mean macular thickness decreased significantly from 427 to 303 microm (P = 0.000). Qualitatively, overall CNV architecture appeared to be unchanged in 78%, was reduced in thickness in 18%, and became larger in 4%. Quantitatively, in all CNV subtypes, the diameter of the CNV lesions (preoperative, 2813 microm; postoperative, 2804 microm) did not change after treatment (classic CNV: P = 0.390; occult CNV: P = 0.405, minimal classic CNV: P = 0.092) independent of postoperative retinal edema. The overall thickness of the lesion, however, was reduced from 205 to 175 microm (P = 0.000). Thickness reduction was significantly enhanced especially in CNV with classic components (n = 24; 252 to 197 microm; P = 0.000; reduction, 22%), whereas reduction was smaller but also significant in occult CNV (183 to 164 microm; P = 0.003; reduction, 10%)., Conclusions: With SD-OCT, CNV size can be two-dimensionally determined and followed up after intravitreal anti-VEGF treatment. In only 4% of CNV was enlargement observed, whereas in 78%, CNV architecture appeared qualitatively unchanged, independent of retinal edema. Quantitative measurements underlined stable CNV diameters for all subtypes but revealed significant reduction of thickness especially for classic CNV components. In this series, ranibizumab monotherapy was able to morphologically stop further CNV growth but, in most patients, did not lead to a major regression of CNV, especially of its occult components.

Purpose: Investigation of slit-lamp-adapted 1310-nm optical coherence tomography (OCT) as an in vivo imaging device in the postoperative course of glaucoma surgery., Methods: Postoperative images of filtering blebs and deep sclerectomies and their healing processes were qualitatively evaluated with a slit-lamp-adapted anterior segment OCT (AS-OCT; Heidelberg Engineering, Heidelberg, Germany) in 28 patients. Ophthalmologic examinations included slit-lamp examination, applanation tonometry, and slit-lamp photography. The OCT scans were qualitatively correlated with the morphologic and functional outcome of the filtering bleb., Results: 1310-nm OCT was able to demonstrate the internal structure and the dimensions of filtering blebs, as well as the scleral flap and the deep sclerectomy location including Descemet membrane. Functioning filtering blebs showed a low OCT signal, small fluid-filled cysts, superficial microcystic layer, and a slack internal texture. High internal reflectivity indicated an earlier scarring of the filtering bleb. Nonfunctioning filtering blebs delivered a high OCT signal, no or few cysts, and a dense internal texture. These different OCT patterns correlated with the clinical outcome., Conclusions: Slit-lamp-adapted 1310-nm OCT allowed the noncontact observation and documentation of the postoperative healing course of filtering blebs after glaucoma surgery. Internal structures of the filtering bleb and deep sclerectomies could be visualized. Functioning and dysfunctioning filtering blebs delivered different OCT pattern and correlated with the clinical outcome. This could be a new way to assess the postoperative healing process with the possibility of earlier intervention in cases of impending scarring.

We tested a 1310-nm optical coherence tomograph coupled with a beam splitter on the front lens of an operating microscope for intraoperative, noncontact visualization of anterior segment procedures. This new modification of optical coherence tomography technology allows intraoperative, high-resolution, cross-sectional imaging and pachymetry of the cornea and sclera during anterior segment surgery. It is particularly helpful for lamellar dissection techniques such as deep anterior lamellar keratoplasty and trabeculectomy.