UHR OCT Research Articles

Ultra High-Resolution Anterior Segment Optical Coherence Tomography in the Evaluation of Anterior Corneal Dystrophies and Degenerations

To evaluate the clinical usefulness of a spectral-domain ultra high-resolution anterior segment optical coherence tomography (UHR OCT) in examination, diagnosis, and management of various anterior corneal dystrophies and degenerations. Noncomparative case series. Fifty-nine eyes of 38 consecutive patients were enrolled in the study and included 28 eyes of 14 patients with anterior corneal dystrophies, 21 eyes of 19 patients with anterior corneal degenerations or neoplasia, and 10 eyes of 5 patients with normal corneas. Subjects were imaged using a novel custom-built UHR OCT. Images were used to evaluate and describe the characteristics of anterior corneal dystrophies and degenerations. Nineteen patients underwent surgical management, and those histopathologic specimens were analyzed and correlated with the UHR OCT images. Comparison of clinical findings, UHR OCT images, and corresponding histopathologic specimens. The UHR OCT provided clear delineation of corneal anatomic features and pathologic corneal deposits in most cases. The characteristics and depth of these deposits are illustrated and can be localized to specific layers of the cornea. When available, there was significant correlation between UHR OCT images and histopathologic features, providing a noninvasive confirmation of the clinical diagnosis. Ultra high-resolution OCT is an innovative technique to perform in vivo optical biopsies and a promising research and clinical tool for the evaluation of corneal pathologic features in a noninvasive manner. The future use of this novel technology will evolve and increasingly is becoming a vital tool in the clinical and surgical management of corneal diseases.

Comparison of UHR-OCT versus Stratus-OCT for definition of early retinal changes after intravitreal Bevacizumab (Avastin®) application in patients with AMD

PURPOSE: To investigate and demonstrate early structural changes of the retina/pigmentepithelial/choriocapillaris (RPECC) complex before and 10 ± 3 days after intravitreal application of bevacizumab (Avastin®) in patients with neovascular age related macular degeneration (nAMD) by comparison of standard Stratus Optical Coherence Tomography (S-OCT) and Ultra High Resolution (UHR-OCT) imaging systems. METHODS: Six patients with nAMD were examined in a consecutive case series with UHR-OCT and Stratus OCT one day before and 10 ± 3 days after intravitreal application of 1.25 mg (0.125 ml) bevacizumab (Avastin®). Maximum central retinal thickness (CRT) was measured with the retinal thickness program and calliper measuring function of S-OCT and by the measuring tool of Adobe Photoshop 5.0 in UHR-OCT pictures. RESULTS: In three of six cases residual fluid after treatment was only visible with UHR-OCT but not with the S-OCT. A decrease of maximum CRT could be shown in all cases in UHR-OCT pictures but only in half of the cases (6/3) in S-OCT pictures. In 2/6 cases vitreoretinal adhesions were demonstrable with UHR-OCT but not seen with the S-OCT, irregularities in the photoreceptor layer could be revealed clearly by UHR-OCT in 2/6 cases. CONCLUSION: After anti-VEGF treatment, UHR–OCT gives more accurate information about residual fluid and intraretinal damage than S-OCT and offers more precise measurements of maximum CRT. These factors may influence further decision of therapy and give us a better explanation and correlation with unsatisfactory visual acuities than with the S-OCT.

Ultrahigh resolution optical coherence tomography of Barrett’s esophagus: preliminary descriptive clinical study correlating images with histology

Endoscopic ultrahigh resolution optical coherence tomography (UHR OCT) achieves an axial image resolution of approximately 5 microm, which is 2 - 3 times finer than standard endoscopic OCT imaging. This study investigated the capability of endoscopic UHR OCT for imaging patients with Barrett's esophagus. Fivty volunteers previously diagnosed with Barrett's esophagus underwent UHR OCT. Imaging was performed at 1.3 microm wavelengths with approximately 5 microm axial and approximately 15 microm transverse resolutions using a 1.8 mm/diameter linear-scanning catheter introduced through the accessory channel of a standard endoscope. OCT images were compared with endoscopic diagnosis and pinch biopsy histological appearances. UHR OCT images of normal esophagus, Barrett's esophagus, high grade dysplasia and esophageal adenocarcinoma were evaluated. UHR OCT images of the normal esophagus exhibited characteristic layered architecture with uniform epithelium, while images of Barrett's esophagus corresponded to crypt-like glandular structures. High grade dysplasia and esophageal adenocarcinoma images exhibited more heterogeneous structures corresponding to irregular, heterogeneous tissue morphology from distorted and cribriform or villiform glandular architecture. Fine features can be discerned more clearly with endoscopic UHR OCT. This study evaluated new endoscopic OCT technology and demonstrated the feasibility of carrying out UHR OCT imaging in conjunction with standard endoscopy for in vivo real-time imaging of Barrett's esophagus, dysplasia, and esophageal adenocarcinoma. A survey of normal and abnormal upper gastrointestinal tissues was performed using a research prototype OCT system with the highest axial resolution to date, and can serve as a baseline for future investigation.

Minimum distance mapping using three-dimensional optical coherence tomography for glaucoma diagnosis

Objective imaging of the optic nerve structure has become central to the management of patients with glaucoma. There is an urgent need in diagnosis and staging for reliable objective precursors and markers. Three-dimensional ultrahigh-resolution frequency domain optical coherence tomography (3D UHR OCT) holds particular promise in this respect since it enables volumetric assessment of intraretinal layers including tomographic data for the retinal nerve fiber layer (RNFL) and optic nerve head. The integrated analysis of this information and the resolution advantage has enabled the development of more informative indices of axonal damage in glaucoma compared with measurements of RNFL thickness and cup-to-disc ratio provided by commercial OCT devices. The potential for UHR OCT in enabling the combined analysis of tomographic and volumetric data on retinal structure is explored. A novel parameter was developed; the three-dimensional minimal distance as the optical correlate of true retinal nerve fiber layer thickness around the optic nerve head region. For the purposes of this pilot study, we present data from a normal subject and from two patients with characteristic optic nerve and retinal nerve fiber layer changes secondary to glaucoma.

ULTRAHIGH RESOLUTION OPTICAL COHERENCE TOMOGRAPHY OF MACULAR HOLES

To evaluate ultrahigh resolution optical coherence tomography (UHR OCT) for visualization of intraretinal layers, especially the photoreceptor inner segment and outer segment layers, in eyes with macular holes and after surgical intervention. An UHR OCT system based on a titanium:sapphire laser was used, enabling in vivo cross-sectional retinal imaging with 3-micro m axial resolution. Typical, representative tomograms of 5 of 48 eyes from 36 patients demonstrated the potential of UHR OCT to detect morphologic changes in different stages of full-thickness macular holes and changes induced by surgical intervention. UHR OCT could detect subtle intraretinal changes in macular hole formation. Unprecedented visualization of photoreceptor impairment was achieved that appeared to be more extensive than the hole itself. Postoperatively, clinically closed holes showed restoration of the photoreceptor inner and outer segment layers of various extents, with residual disease in some eyes. In macular holes, UHR OCT allows for detection of even small morphologic changes of the retinal layers, especially the photoreceptor inner and outer segment layers. Therefore, it also represents a superior method to monitor the effect of surgical interventions. Preoperative photoreceptor impairment and the degree of postoperative restoration could possibly be associated with visual function. Hence, UHR OCT could lead to better understanding of macular hole pathogenesis and to more accurate disease prognosis.

Ultrahigh-Resolution Optical Coherence Tomography in Patients with Decreased Visual Acuity after Retinal Detachment Repair

To assess microstructural changes in the retina that may explain incomplete visual recovery after anatomically successful repair of rhegmatogenous retinal detachments (RD) using ultrahigh-resolution optical coherence tomography (UHR OCT). Retrospective observational case series. Seventeen patients with decreased visual acuity after RD repair. Twelve patients had macula-involving and 5 had macula-sparing RDs. The UHR OCT prototype capable of approximately 3 mum axial resolution was developed for clinical use. The UHR OCT images through the center of the fovea in 17 patients with visual complaints after RD surgery were obtained. Patients were either postoperative patients from the New England Eye Center or tertiary referrals. Baseline visual acuity, preoperative lens status, location of retinal detachment, macular involvement, and postoperative visual acuity were recorded. The UHR OCT images after RD repair. The UHR OCT images were obtained 1 to 84 months (median, 5 months) postoperatively. The mean preoperative logarithm of the minimum angle of resolution (logMAR) visual acuity was 1.37 (Snellen equivalent, 20/390). The mean postoperative logMAR visual acuity was 0.48 (Snellen equivalent, 20/60). Anatomical abnormalities that were detected included distortion of the photoreceptor inner/outer segments (IS/OS) junction in 14 of 17 patients (82%), epiretinal membranes in 10 of 17 patients (59%), residual subretinal fluid in 3 of 17 patients (18%), and cystoid macular edema in 2 of 17 patients (12%). Of the 5 patients with preoperative macula-on detachments, 4 had distortion of the outer retina after RD repair. The higher resolution of UHR OCT facilitates imaging of the IS/OS junction. Therefore, UHR OCT is able to confirm prior histopathologic findings that damage to photoreceptor outer segments may occur as a consequence of retinal detachment. This may explain poor postoperative visual acuity in eyes with anatomically successful repair.

Idiopathic Juxtafoveal Retinal Telangiectasis: New Findings by Ultrahigh-Resolution Optical Coherence Tomography

To investigate the capabilities of ultrahigh-resolution optical coherence tomography (UHR OCT); to compare with the commercially available OCT standard-resolution system, StratusOCT, for imaging of idiopathic juxtafoveal retinal telangiectasis (IJT); and to demonstrate that UHR OCT provides additional information on disease morphology, pathogenesis, and management. Retrospective, observational, interventional case series. Nineteen eyes of 10 patients diagnosed with IJT in at least one eye. All patients were imaged with UHR OCT and StratusOCT at the same visit. A subset of patients was also imaged before and after treatment of IJT. Ultrahigh- and standard-resolution cross-sectional tomograms of IJT pathology. Using both standard- and ultrahigh-resolution OCT, we identified the following features of IJT: (1) a lack of correlation between retinal thickening on OCT and leakage on fluorescein angiography, (2) loss and disruption of the photoreceptor layer, (3) cystlike structures in the foveola and within internal retinal layers such as the inner nuclear or ganglion cell layers, (4) a unique internal limiting membrane draping across the foveola related to an underlying loss of tissue, (5) intraretinal neovascularization near the fovea, and (6) central intraretinal deposits and plaques. In 63% of cases, the presence of abnormal vessels and a discontinuity of the photoreceptor layer correlated with visual acuity. Ultrahigh-resolution OCT improves visualization of the retinal pathology associated with IJT and allows identification of new features associated with it. Some of these features, such as discontinuity of the photoreceptor layer, are revealed only by UHR OCT.

Ultrahigh Resolution Optical Coherence Tomography In Macular Dystrophy

To visualize and investigate intraretinal changes in macular dystrophies with ultrahigh resolution optical coherence tomography (UHR OCT). Prospective observational case series. setting: Department of Ophthalmology and Center for Biomedical Engineering and Physics, Christian Doppler Laboratory, Medical University of Vienna, Vienna, Austria. patients: Thirteen patients (23 eyes) with adult-onset foveomacular vitelliform dystrophy (AOFVD) and 14 patients (27 eyes) with Stargardt's disease (SD) or fundus flavimaculatus (FF). Imaging using a compact, new generation UHR OCT system, achieving considerably improved visualization of intraretinal layers, especially the photoreceptor layer. main outcome measures: UHR OCT tomograms visualizing intraretinal differences in morphology of AOFVD and SD/FF as location and extension of deposits and loss of photoreceptors. Central foveal thickness defined as distance between internal limiting membrane and photoreceptors/retinal pigment epithelium interface. Patients with AOFVD had a mostly intact photoreceptor layer, a central foveal thickness of 142 +/- 23 microm as well as subretinal deposits. Patients with SD generally had a diffuse degenerative change with a visible reduction in thickness of all intraretinal layers, resulting in a corresponding reduction of central foveal thickness (94 +/- 38 microm) and central loss of photoreceptors (PRs). Comparative central foveal thickness of patients with AOFVD and SD/FF was significantly different (P < .001). Patients with FF had pigment epithelial deposits and paracentral focal photoreceptor loss. UHR OCT is a clinically feasible tool for examining intraretinal changes, in particular photoreceptor atrophy in macular dystrophies and, therefore, has the potential to be an adequate imaging system for monitoring the course of disease.

Three-dimensional adaptive optics ultrahigh-resolution optical coherence tomography using a liquid crystal spatial light modulator

A liquid crystal programmable phase modulator (PPM) is used as correcting device in an adaptive optics system for three-dimensional ultrahigh-resolution optical coherence tomography (UHR OCT). The feasibility of the PPM to correct high order aberrations even when using polychromatic light is studied, showing potential for future clinical use. Volumetric UHR OCT of the living retina, obtained with up 25,000 A-scans/s and high resolution enables visualization of retinal features that might correspond to groups of terminal bars of photoreceptors at the external limiting membrane.

Comparison of Ultrahigh- and Standard-Resolution Optical Coherence Tomography for Imaging Macular Pathology

To compare ultrahigh-resolution optical coherence tomography (UHR OCT) with standard-resolution OCT for imaging macular diseases, develop baselines for interpreting OCT images, and identify situations where UHR OCT can provide additional information on disease morphology. Cross-sectional study. One thousand two eyes of 555 patients with different macular diseases including macular hole, macular edema, central serous chorioretinopathy, age-related macular degeneration (AMD), choroidal neovascularization, epiretinal membrane, retinal pigment epithelium (RPE) detachment, and retinitis pigmentosa. A UHR ophthalmic OCT system that achieves 3-microm axial image resolution was developed for imaging in the ophthalmology clinic. Comparative studies were performed with both UHR OCT and standard 10-microm-resolution OCT. Standard scanning protocols of 6 radial 6-mm scans through the fovea were obtained with both systems. Ultrahigh-resolution OCT and standard-resolution OCT images were correlated with standard ophthalmic examination techniques (dilated ophthalmoscopy, fluorescein angiography, indocyanine green angiograms) to assess morphological information contained in the images. Ultrahigh-resolution and standard-resolution OCT images of macular pathologies. Correlations of UHR OCT images, standard-resolution images, fundus examination, and/or fluorescein angiography were demonstrated in full-thickness macular hole, central serous chorioretinopathy, macular edema, AMD, RPE detachment, epiretinal membrane, vitreal macular traction, and retinitis pigmentosa. Ultrahigh-resolution OCT and standard-resolution OCT exhibited comparable performance in differentiating thicker retinal layers, such as the retinal nerve fiber, inner and outer plexiform, and inner and outer nuclear. Ultrahigh-resolution OCT had improved performance differentiating finer structures or structures with lower contrast, such as the ganglion cell layer and external limiting membrane. Ultrahigh-resolution OCT confirmed the interpretation of features, such as the boundary between the photoreceptor inner and outer segments, which is also visible in standard-resolution OCT. The improved resolution of UHR OCT is especially advantageous in assessing photoreceptor morphology. Ultrahigh-resolution OCT enhances the visualization of intraretinal architectural morphology relative to standard-resolution OCT. Ultrahigh-resolution OCT images can provide a baseline for defining the interpretation of standard-resolution images, thus enhancing the clinical utility of standard OCT imaging. In addition, UHR OCT can provide additional information on macular disease morphology that promises to improve understanding of disease progression and management.

Three-Dimensional Ultrahigh-Resolution Optical Coherence Tomography of Macular Diseases

To demonstrate a new generation of three-dimensional (3-D) ultrahigh-resolution optical coherence tomography (UHR OCT) technology for visualization of macular diseases. One hundred forty eyes with a distinct disease in each of the posterior pole compartments were examined with 3-D UHR OCT. 3-D imaging was performed with a high axial resolution of 3 mum with a compact, commercially available, ultra-broad-bandwidth (160 nm) titanium:sapphire laser at a video rate of up to 25 B-scans/s. Each tomogram consisted of 1024 x 1024 pixels, resulting in 25 megavoxels/s. 3-D UHR OCT offers high-precision 3-D visualization of macular diseases at all structural levels. The UHR modality allows identification of the contour of the hyaloid membrane, tractive forces of epiretinal membranes, and changes within the inner limiting membrane. The system provides quality 3-D images of the topographic dynamics of traction lines from the retinal surface down to the level of the photoreceptor segments. Intraretinal diseases are identified by their specific location in different layers of the neurosensory ultrastructure. Photoreceptor inner and outer segments are clearly delineated in configuration and size, with a characteristic peak in the subfoveal area. The microarchitecture of choroidal neovascularization is distinctly imaged, related leakage can be identified, and the volume can be quantified. High-speed UHR OCT offers unprecedented, realistic, 3-D imaging of ocular diseases at all epi-, intra- and subretinal levels. A complete 3-D data set of the macular layers allows a comprehensive analysis of focal and diffuse diseases, as well as identification of dynamic pathomechanisms.

Intraocular lens–capsular bag imaging with ultrahigh-resolution optical coherence tomography

To compare in vitro ultrahigh-resolution optical coherence tomography (UHR OCT) cross-sectional images of the pseudophakic human autopsy eye with histology to evaluate the potential of this imaging technique for enhanced visualization of the anterior segment, especially the capsular bag, intraocular lens (IOL), and posterior capsule opacification (PCO) formation after cataract surgery.Department of Medical Physics and Department of Ophthalmology, University of Vienna, Vienna, Austria, and Department of Oral and Maxillofacial Surgery Institute of Dentistry, University of Turku, Turku, Finland.Ultrahigh-resolution OCT images were acquired from 7 pseudophakic human autopsy eyes using 1.4 microm axial x 3.0 microm transverse resolution. The axial resolution with UHR OCT is 1.4 microm compared to 10.0 microm with the commercially available OCT. Plastic-embedded histologic sections were obtained in precise alignment with the OCT tomograms.Ultrahigh-resolution OCT cross-sectional tomograms corresponded to the histologic sections. With the wavelength used (800 nm), the anterior and posterior capsules, area of lens epithelial cell growth and extracellular matrix proliferation, and IOL could be clearly visualized. The extent of capsular bag adhesion to the IOL could be detected, as well as the amount of PCO formation.The improved resolution makes UHR OCT a powerful tool in anterior segment imaging and evaluation of the capacity of IOL materials and models to induce capsular bag adhesion. Ultrahigh-resolution OCT may also help in determining the area of origin of PCO after cataract surgery.

Imaging ex vivo healthy and pathological human brain tissue with ultra-high-resolution optical coherence tomography

The ability of ultra-high-resolution optical coherence tomography (UHR OCT) to discriminate between healthy and pathological human brain tissue is examined by imaging ex vivo tissue morphology of various brain biopsies. Micrometer-scale OCT resolution (0.9x2 microm, axialxlateral) is achieved in biological tissue by interfacing a state-of-the-art Ti:Al2O3 laser (lambda(c)=800 nm, delta lambda=260 nm, and P(out)=120 mW exfiber) to a free-space OCT system utilizing dynamic focusing. UHR OCT images are acquired from both healthy brain tissue and various types of brain tumors including fibrous, athypical, and transitional meningioma and ganglioglioma. A comparison of the tomograms with standard hematoxylin and eosin (H&E) stained histological sections of the imaged biopsies demonstrates the ability of UHR OCT to visualize and identify morphological features such as microcalcifications (>20 microm), enlarged nuclei of tumor cells (approximately 8 to 15 microm), small cysts, and blood vessels, which are characteristic of neuropathologies and normally absent in healthy brain tissue.

Methodological advancements. Ultrahigh-resolution OCT

Development of ultrabroad bandwidth light sources has recently enabled significant improvement of ophthalmic axial OCT imaging resolution, demonstrating the potential of ultrahigh resolution OCT (UHR OCT) to perform noninvasive optical biopsy, i.e., the in vivo visualization of microstructural morphology in situ, which had previously only been possible with histopathology. Therefore, UHR OCT allows detection of intraretinal changes that can be used for diagnosis of retinal disease in its early stages when treatment is most effective and irreversible damage can be prevented or delayed. Furthermore, it may provide a better understanding of the pathogenesis of several macular pathologies as well as contribute to the development of new therapy approaches. Future developments of ophthalmic OCT include high speed, three-dimensional retinal imaging, combining adaptive optics and UHR OCT, spatially resolved spectroscopic OCT, functional imaging, and OCT imaging with enhanced penetration into the choroid by employing novel wavelength regions.

Advances in broad bandwidth light sources for ultrahigh resolution optical coherence tomography

Novel ultra-broad bandwidth light sources enabling unprecedented sub-2 µm axial resolution over the 400 nm–1700 nm wavelength range have been developed and evaluated with respect to their feasibility for clinical ultrahigh resolution optical coherence tomography (UHR OCT) applications. The state-of-the-art light sources described here include a compact Kerr lens mode locked Ti:sapphire laser (λc = 785 nm, Δλ = 260 nm, Pout = 50 mW) and different nonlinear fibre-based light sources with spectral bandwidths (at full width at half maximum) up to 350 nm at λc = 1130 nm and 470 nm at λc = 1375 nm. In vitro UHR OCT imaging is demonstrated at multiple wavelengths in human cancer cells, animal ganglion cells as well as in neuropathologic and ophthalmic biopsies in order to compare and optimize UHR OCT image contrast, resolution and penetration depth.