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We report a fascinating phenomenon that emerges when a surface is viewed through a tube held close to one eye, with the other eye open. The disk-shaped area seen through the tube looks strikingly brighter and, when viewed on a textured background, also of higher spatial contrast than the same surface area viewed without a tube. The effect is reminiscent of a spotlight illuminating the area under consideration. We call this the ‘tube effect’. The tube effect is one of the strongest contrast illusions known to us. It requires a matching luminance that is twice as high as the reference luminance seen through the tube. Brightness ratings increase linearly with the log of the background luminance. The effect (i) produces a dark afterimage, (ii) reverses in polarity with low ambient illumination, (iii) assumes the complementary colour of the illuminant, and (iv) persists with fully dilated pupils. Potential explanations include simultaneous contrast (due to the penumbra and dark inner walls of the tube) and veiling of the surround (due to local adaptation and a lower gain factor).

We summarize the performance of an AO-OCT system with reference arm phase shifting for complex conjugate artifactfree imaging of in vivo retinal structures. As a complex conjugate artifact removal (CCR) method we used a previously reported technique requiring constant phase shifts between consecutive A-scans. In our system these shifts were generated by continuous beam path-length changes from offsetting the pivot point of the scanning mirror placed in the system reference arm. In order to reconstruct the complex spectral fringe pattern we used Fourier transformation along the transverse axis and a filtering algorithm. The suppression ratio of mirror complex artifact images was assessed based on acquired in vivo CCR AO-OCT images. Finally, potential problems and limitations connected with this acquisition scheme and data processing algorithms are discussed.

PurposeThe purpose of this study is to evaluate the macular morphological changes associated with idiopathic epiretinal membrane (iERM) using high-resolution Fourier-domain optical coherence tomography (FD-OCT), as they correlate with visual acuity and microperimetry (MP-1).MethodsIn all, 24 eyes (19 subjects) with iERM were imaged prospectively using FD-OCT with axial resolution of 4.5 m and transverse resolution of 10 to 15 m. MP-1 and Stratus OCT were carried out in a subset of eyes.ResultsThe mean log of the minimum angle of resolution best-corrected visual acuity (BCVA) was 0.180.16 (range: 0.08 to 0.48, Snellen equivalent 20/15 1 to 20/60). ERM was visualized in all 24 eyes with FD-OCT and in 17 eyes (85%) of 20 eyes imaged with Stratus OCT. Although BCVA correlated with macular thickening in the central 1 mm sub-field of the Stratus ETDRS (P0.0005) and macular volume (central 3 mm area) on FD-OCT (P < 0.0001), macular thickening on thickness map and volume correlated poorly with decrease in macular sensitivity on MP-1 (P < 0.16). On FD-OCT, foveal morphological changes correlated best with decrease in BCVA, the strongest being central foveal thickness (P0.0001). Other significant changes included blurring of the foveal inner segment-outer segment (IS-OS) junction and/or Verhoeff's membrane, vitreal displacement of foveal outer nuclear layer and foveal detachment (P0.05). Foveal IS-OS junction disruption was seen in 25% of eyes on Stratus OCT but in none of the eyes on FD-OCT.ConclusionFD-OCT allowed improved visualization of ERM and associated foveal morphological changes that correlated best with BCVA. Macular thickening correlated weakly with decreased macular function as assessed by MP-1. © 2011 Macmillan Publishers Limited All rights reserved.

Inner and outer retinal morphology were quantified in vivo for 6 nonglaucomatous and 10 glaucomatous optic neuropathy patients. Custom, ultrahigh-resolution imaging modalities were used to evaluate segmented retinal layer thickness in 3D volumes (Fourier-domain optical coherence tomography), cone photoreceptor density (adaptive optics fundus camera), and the length of inner and outer segments of cone photoreceptors (adaptive optics-optical coherence tomography). Quantitative comparisons were made with age-matched controls, or by comparing affected and nonaffected retinal areas defined by changes in visual fields. The integrity of outer retinal layers on optical coherence tomography B-scans and density of cone photoreceptors were correlated with visual field sensitivity at corresponding retinal locations following reductions in inner retinal thickness. The photoreceptor outer segments were shorter and exhibited greater variability in retinal areas associated with visual field losses compared with normal or less affected areas of the same patient's visual field. These results demonstrate that nonglaucomatous and glaucomatous optic neuropathies are associated with outer retinal changes following long-term inner retinal pathology. © 2011 Macmillan Publishers Limited All rights reserved.

International audience; Previous studies have demonstrated an inverse relation between the size of the complete spatial summation area and ganglion cell density. We hypothesized that if this relation is dynamic, the spatial summation area at 6° nasal would expand to compensate for age-related losses of retinal ganglion cells but not in the fovea where age-related loss in ganglion cell density is not significant. This hypothesis was tested by measuring contrast thresholds with a series of Gabor patches varying in size. The spatial summation area was defined by the intersection of the segments of a two-branched, piece-wise linear function fitted to the data with slopes of -0.5 and 0 on a plot of log threshold vs. log area. Results demonstrate a 31% increase in the parafoveal spatial summation area in older observers with no significant age-related change in the fovea. The average foveal data show a significant increase in thresholds with age. Contrary to the foveal data, age comparisons of the parafoveal peak contrast thresholds display no significant difference below the summation area. Nevertheless, as expected from the increase in summation area, expressing the parafoveal thresholds as contrast energy reveals a significant difference for stimuli that are smaller than the maximal summation area.

Aims It is well established that glaucoma results in a thinning of the inner retina. To investigate whether the outer retina is also involved, ultrahigh-resolution retinal imaging techniques were utilised. Methods Eyes from 10 glaucoma patients (25–78 years old), were imaged using three research-grade instruments: (1) ultrahigh-resolution Fourier-domain optical coherence tomography (UHR-FD-OCT), (2) adaptive optics (AO) UHR-FD-OCT and (3) AO-flood illuminated fundus camera (AO-FC). UHR-FD-OCT and AO-UHR-FD-OCT B-scans were examined for any abnormalities in the retinal layers. On some patients, cone density measurements were made from the AO-FC en face images. Correlations between retinal structure and visual sensitivity were measured by Humphrey visual-field (VF) testing made at the corresponding retinal locations. Results All three in vivo imaging modalities revealed evidence of outer retinal changes along with the expected thinning of the inner retina in glaucomatous eyes with VF loss. AO-UHR-FD-OCT images identified the exact location of structural changes within the cone photoreceptor layer with the AO-FC en face images showing dark areas in the cone mosaic at the same retinal locations with reduced visual sensitivity. Conclusion Losses in cone density along with expected inner retinal changes were demonstrated in well-characterised glaucoma patients with VF loss.

Chromatic and achromatic components of 15 broadband surfaces were scaled by 15 younger (mean age = 21.3 yrs) and 15 older (mean age = 71.9 yrs) subjects. Colored surfaces were obtained from the OSA Uniform Color Scales and presented as 2°-diameter test stimuli that were freely viewed. Stimuli were presented in a grey (L = 0) ganzfeld-like hemisphere with an illuminant having a correlated color temperature of 6200 K. Five stimuli were presented at three lightness levels (L = −4, 0 and +4). Each lightness level included samples chosen so that one pair plotted approximately along a tritan axis in MacLeod-Boynton receptor-excitation space and another pair plotted on an axis of constant S-cone stimulation. The appearance of each test stimulus was scaled using the hue terms red, green, yellow and blue, and in terms of the proportion of overall chromatic content. The results indicate that hue names were used similarly for the two groups of subjects, however, older subjects perceived all stimuli as having less chromatic content than demonstrated by younger observers. Differences between the two age groups in perceived chromatic content of the test stimuli progressively increased as the lightness and luminance levels of the test stimuli decreased. Results obtained from control experiments suggest that this difference between the two age groups is not due to the influence of senile miosis or lenticular senescence leading to variations in the illuminances and spectral compositions of the test lights reaching the retina. © 1993 John Wiley & Sons, Inc.

Most of the high-order aberrations of the eye are not circularly symmetric. Hence, while it is well known that human vision is subject to cortically based orientation preference in cell tuning, the optics of the eye might also introduce some orientational anisotropy. We tested this idea by measuring contrast sensitivity at different orientations of sine-wave gratings when viewing through a closed-loop adaptive optics phoropter. Under aberration-corrected conditions, mean contrast sensitivity improved for all observers by a factor of 1.8× to 5×. The detectability of some orientations improved more than others. As expected, this orientation-specific effect varied between individuals. The sensitivity benefits were accurately predicted from MTF model simulations, demonstrating that the observed effects reflected the individual's pattern of high-order aberrations. In one observer, the orientation-specific effects were substantial: an improvement of 8× at one orientation and 2× in another orientation. The experiments confirm that, for conditions that are not diffraction limited, the optics of the eye introduce rotational asymmetry to the luminance distribution on the retina and that this impacts vision, inducing orientational anisotropy. These results suggest that the traditional view of meridional anisotropy having an entirely neural origin may be true for diffraction-limited pupils but that viewing through larger pupils introduces an additional orientation-specific optical component to this phenomenon.

Our lab has previously demonstrated losses in contrast sensitivity to low spatial frequencies under scotopic conditions with older adults. It is not clear, however, whether the temporal frequency of a stimulus alters the relation between age and the spatial contrast sensitivity function (sCSF) under scotopic conditions.A maximum-likelihood, two-alternative, temporal forced-choice QUEST procedure was used to measure threshold to spatially and temporally modulated stimuli in both young (mean = 26 years) and old (mean = 75 years) adults.In general, the shapes of the spatial and temporal CSFs were low-pass for both young and old observers; contrast sensitivity decreased at approximately the same rate with increasing spatial frequency and temporal frequency for both age groups, although the overall sensitivity of the old group was lower than that of the young group. The high-frequency resolution limit was lower for the old group compared to the young group.The differences in contrast sensitivity between the young and old groups suggest a uniform loss in sensitivity of the channels mediating spatial and temporal vision. Because of this loss, the spatial and temporal window of visibility for the older adults is compromised relative to the younger adults.

Exudative age-related macular degeneration (eAMD) is a leading cause of irreversible blindness in the elderly in the United States.1 The anatomy and growth patterns of choroidal neovascular membranes (CNVM) associated with eAMD have been studied in the past using either enucleated eyes or excised tissue from submacular surgery, in an attempt to understand the pathogenesis of this condition.2–14 These studies have demonstrated that CNVM comprises a dynamic proliferation of fibrovascular tissue through Bruch's membrane. Gass8 used enucleated eyes and classified the neovascular growth pattern as subretinal pigment epithelial (RPE) (type 1), subretinal (type 2), or combined. Several studies attempted to demonstrate a correlation between the angiographic classification of CNVM (classic versus occult) and the anatomic classification (type 1 vs. type 2). However, data on postmortem eyes are limited.10,11 Several groups have reported on clinicopathologic correlation using surgically removed CNVMs. These reports showed that classic CNVMs tend to exhibit either a combined or subretinal growth pattern while occult CNVMs tend to be composed of tissue that appeared to be from the sub-RPE space.12–14 However, tissue classification of surgically removed CNVMs can have limited accuracy since anatomy is disrupted, and incomplete excision of CNVM during surgery cannot be ruled out. With the emergence of optical coherence tomography (OCT), a new method for studying CNVM growth patterns in living subjects became available. OCT provides a noninvasive, nondestructive method of obtaining detailed anatomic data in vivo. A study using the commercially available time-domain OCT system Stratus OCT (Carl Zeiss Meditec, Inc., Dublin, CA) suggested that classic CNVM tends to be subretinal whereas occult CNVM tends to be sub-RPE.15,16 However, the Stratus OCT system that was used provides only six radial scans of the macula and has limited axial and transverse resolution. Thus, it is not possible to visualize the whole extent of the CNVM with this instrument. Fourier-domain OCT (Fd-OCT) systems are newer generation instruments that allow a reduction in image acquisition time by an additional factor of 20 to 40 when compared with the Stratus OCT. These modifications allow acquisition of rapid serial fine-cut B-scans of the macula in a single scanning sweep, so that the entire macula can be imaged and analyzed.17,18 The new Fd-OCT system has allowed detailed imaging of macular lesions that may be missed with the time-domain OCT system.17 There are several recent reports using Fd-OCT to image eyes with eAMD. These reports have concentrated on improved visualization of the retinal layers and drusen in eyes with eAMD before and after treatment with inhibitors of vascular endothelial growth factor when compared to the traditional time-domain OCT.19–23 One report describes volume measurements of CNVM before and after treatment but did not mention the growth pattern of CNVM.24 In this report, a high-resolution Fd-OCT system developed at our institution was used to image eyes with newly diagnosed eAMD to evaluate the usefulness of this instrument in visualizing CNVM and associated morphologic changes.

An accurate solid eye model (with volumetric retinal morphology) has many applications in the field of ophthalmology, including evaluation of ophthalmic instruments and optometry/ophthalmology training. We present a method that uses volumetric OCT retinal data sets to produce an anatomically correct representation of three-dimensional (3D) retinal layers. This information is exported to a laser scan system to re-create it within solid eye retinal morphology of the eye used in OCT testing. The solid optical model eye is constructed from PMMA acrylic, with equivalent optical power to that of the human eye (∼58D). Additionally we tested a water bath eye model from Eyetech Ltd. with a customized retina consisting of five layers of ∼60 μm thick biaxial polypropylene film and hot melt rubber adhesive. © 2010 SPIE.

We describe results of retinal imaging with a novel instrument that combines adaptive optics - Fourier-domain optical coherence tomography (AO-OCT) with an adaptive optics scanning laser ophthalmoscope (AO-SLO). One of the benefits of combining Fd-OCT with SLO includes automatic co-registration between the two imaging modalities and the potential for correcting lateral and transversal eye motion resulting in motion artifact-free volumetric retinal imaging. Additionally this allows for direct comparison between retinal structures that can be imaged with both modalities (e.g., photoreceptor mosaics or microvasculature maps). This dual imaging modality could provide insight into some retinal properties that could not be accessed by a single imaging system. Additionally, extension of OCT and SLO beyond structural imaging may open new avenues for diagnostics and testing in ophthalmology. In particular, non-invasive vasculature mapping with these modalities holds promise of replacing fluorescein angiography in vascular identification. Several new improvements of our system are described, including results of testing a novel 97-actuator deformable mirror and AO-SLO light intensity modulation. © 2010 SPIE.

We evaluated several, previously published, complex conjugate artifact removal methods and algorithms that have been proposed for Fourier domain optical coherence tomography (Fd-OCT). To ensure comparable conditions, only one OCT system was used, but with modified data acquisition schemes, depending on the requirements of each method/algorithm. This limited our evaluation to single spectrometer based Fd-OCT approaches. The suppression ratio of complex conjugate artifact images using a paperboard is assessed for all tested methods. Several other metrics are also used for comparison, including a list of additional hardware requirements (beyond standard Fd-OCT components) and data acquisition schemes. Finally, in vivo human finger pad and nail images are presented for comparison to the standard Fd- OCT images and full-range images. © 2010 Copyright SPIE - The International Society for Optical Engineering.

Neural contributions to the age-related reduction in spatial vision are incontrovertible. Whether there are differential age-related changes in the magnocellular (M) and parvocellular (P) pathways across the life span has not been tested extensively. We studied psychophysically the contrast gain signature of the M and P pathways for 13 younger and 13 older observers. Two separate paradigms thought to separate the M and P pathways based on their contrast gain (J. Pokorny & V. C. Smith, 1997) signature were used. A four-square array was presented as an increment or decrement on a background of 115 Td for 35 ms, with one test square presented at a slightly higher or lower retinal illumination. Using a four-alternative forced-choice procedure, the observer's task was to choose the unique square. The two paradigms differed only in the pretrial adaptation and inter-stimulus array. Data were fitted with models of contrast discrimination derived from the unique contrast gain signatures. The fitted models indicate a change in the discrimination functions with age for both the M and P pathways, revealing a shift in the contrast gain slope. Results indicate that both M and P pathways undergo age-related changes, but functional losses appear greater for the P pathway under the conditions tested.

Purpose—To describe a case of microcystoid maculopathy diagnosed by high-resolution Fourierdomain optical coherence tomography (Fd-OCT) in a patient treated with tamoxifen who had previously unexplained vision loss. Methods—Report of a case of a 66-year-old woman treated with tamoxifen for 4 years who had progressive unexplained vision loss in the left eye for 2 years. Results—Visual acuity was 20/25 in the right eye and 20/70 in the left eye. Findings of funduscopy and fluorescein angiography were unremarkable except for minimal pigment alteration in the macula in the left eye. Stratus OCT showed possible microcystoid changes in the fovea in both eyes. FdOCT revealed scattered intraretinal microcystoid changes and patches of focal loss of photoreceptors in the macula in both eyes with foveal involvement in the left eye. Full-field electroretinogram was normal. Multifocal electroretinogram showed some decreased response in the peripheral macula and borderline low foveal response in both eyes. Conclusion—Microcystoid maculopathy associated with tamoxifen use can be diagnosed by FdOCT in a normal appearing fundus. It can present as unexplained vision loss. Tamoxifen retinopathy is characterized by refractile deposits in the retina seen during funduscopy.1 Loss of central vision can occur and is thought to be secondary to cystoid macular edema observed by funduscopy and fluorescein angiography. 2 This report describes a case of microcystoid maculopathy diagnosed by high-resolution Fourier-domain optical coherence tomography (Fd-OCT) in a patient treated with tamoxifen who had previously unexplained vision loss.

Phase variance-based motion contrast imaging is demonstrated using a spectral domain optical coherence tomography system for the in vivo human retina. This contrast technique spatially identifies locations of motion within the retina primarily associated with vasculature. Histogrambased noise analysis of the motion contrast images was used to reduce the motion noise created by transverse eye motion. En face summation images created from the 3D motion contrast data are presented with segmentation of selected retinal layers to provide non-invasive vascular visualization comparable to currently used invasive angiographic imaging. This motion contrast technique has demonstrated the ability to visualize resolutionlimited vasculature independent of vessel orientation and flow velocity. © 2009 Optical Society of America.

Using high-resolution spectral-domain optical coherence tomography (SD-OCT) and adaptive optics (AO) imaging, photoreceptor damage in a patient with a central macular arteriovenous malformation (AVM) and otherwise unexplained progressive vision loss was demonstrated. This patient presented with a central scotoma, a macular AVM, and no evidence of macular edema, retinal hemorrhage, or subretinal fluid. Fluorescein angiography (FA) did not reveal leakage. Over 28 years, her vision progressively worsened from 20/25 to 20/400. Both time-domain OCT and FA did not reveal any significant retinal abnormality. However, high-resolution SD-OCT imaging revealed clear disorganization of the outer segments and focal photo-receptor disruption adjacent to the AVM. En face AO images further revealed loss of the photoreceptors in these regions. This case demonstrates the unique finding of progressive vision loss in a patient with a congenital retinal AVM, and how high-resolution imaging can detect structural changes of the retina in patients with otherwise unexplained vision loss.

The combination of adaptive optics (AO) technology with optical coherence tomography (OCT) instrumentation for imaging the retina has proven to be a valuable tool for clinicians and researchers in understanding the healthy and diseased eye. The micrometer-isotropic resolution achieved by such a system allows imaging of the retina at a cellular level, however imaging of some cell types remains elusive. Improvement in contrast rather than resolution is needed and can be achieved through better AO correction of wavefront aberration. A common tool for assessing and ultimately improving AO system performance is the development of an error budget. Specifically, this is a list of the magnitude of the constituent residual errors of an optical system so that resources can be directed towards efficient performance improvement. Here we present an error budget developed for the UC Davis AO-OCT instrument indicating that bandwidth and controller errors are the limiting errors of our AO system, which should be corrected first to improve performance. We also discuss the scaling of error sources for different subjects and the need to improve the robustness of the system by addressing subject variability. © 2009 Optical Society of America.

Imaging the structure and correlating it with the biochemical content of the retina holds promise for fundamental research and for clinical applications. Optical coherence tomography (OCT) is commonly used to image the 3D structure of the retina and while the added functionality of biochemical analysis afforded by Raman scattering could provide critical molecular signatures for clinicians and researchers, there are many technical challenges to combine these imaging modalities. We describe an OCT microscope for ex-vivo imaging combined with Raman spectroscopy capable of collecting morphological and molecular information about a sample simultaneously. We present our first results and discuss the challenges to further development of this dual-mode instrument and limitations for future in-vivo retinal imaging.

Exophytic retinal capillary hemangiomas (RCH) can be a diagnostic challenge in subjects without von Hippel-Lindau disease (VHL). This report of two cases describes the optical coherence tomographic (OCT) characteristics of RCH in two eyes of a subject with VHL and in one eye of an otherwise normal subject. Three different OCT instruments were used (Stratus, Cirrus and/or custom high resolution Fourier-domain OCT with 4.5 μm axial resolution) depending on availability. All instruments localized the tumor to the outer retina. A sharp border between the tumor and overlying inner retina was noted. The tumor bulged into the subretinal space and showed marked shadowing. Associated cystoid macular edema and sub-retinal fluid were noted. High-resolution Fourier-domain OCT showed a focal photoreceptor layer rip in the adjacent tumor-free macula in one eye with poor vision after treatment. OCT may be a useful tool in diagnosing RCH and studying associated morphologic changes.

Ultrahigh-resolution adaptive optics-optical coherence tomography (UHR-AO-OCT) instrumentation allowing monochromatic and chromatic aberration correction was used for volumetric in vivo retinal imaging of various retinal structures including the macula and optic nerve head (ONH). Novel visualization methods that simplify AO-OCT data viewing are presented, and include co-registration of AO-OCT volumes with fundus photography and stitching of multiple AO-OCT sub-volumes to create a large field of view (FOV) high-resolution volume. Additionally, we explored the utility of Interactive Science Publishing by linking all presented AO-OCT dataseis with the OSAISP software. © 2009 Optical Society of America.

We describe a novel instrument that combines adaptive optics - Fourier-domain optical coherence tomography (AO-OCT) with an adaptive optics scanning laser ophthalmoscope (AO-SLO). Both systems share a common AO sub-system and vertical scanner to permit simultaneous acquisition of retinal images from both OCT and SLO. One of the benefits of combining OCT with SLO includes automatic co-registration between the two imaging modalities and potential for correcting lateral and transversal eye motion resulting in motion artifact-free volumetric retinal imaging. Results of using this system for eye model imaging are presented. Feasibility for clinical application is briefly discussed as well as potential further improvements of the current system.

Imaging the structure and correlating it with the biochemical content of the retina holds promise for fundamental research and for clinical applications. Optical coherence tomography (OCT) is commonly used to image the 3D structure of the retina and while the added functionality of biochemical analysis afforded by Raman scattering could provide critical molecular signatures for clinicians and researchers, there are many technical challenges to combining these imaging modalities. We present an ex vivo OCT microscope combined with Raman spectroscopy capable of collecting morphological and molecular information about a sample simultaneously. The combined instrument will be used to investigate remaining technical challenges to combine these imaging modalities, such as the laser power levels needed to achieve a Raman signal above the noise level without damaging the sample.

Adaptive optics (AO) and optical coherence tomography (OCT) are powerful imaging modalities that, when combined, can provide high-resolution (3.5 μm isotropic), 3-D images of the retina. The AO-OCT system at UC Davis has demonstrated the utility of this technology for microscopic, volumetric, in vivo retinal imaging. The current system uses an AOptix bimorph deformable mirror (DM) for low-order, high-stroke correction and a 140-actuator Boston Micromachines DM for high-order correction. Developments to improve performance or functionality of the instrument are on-going. Based on previous work in system characterization we have focused on improved AO control. We present preliminary results and remaining challenges for a newly implemented Fourier transform reconstructor (FTR). The previously reported error budget analysis is also reviewed and updated, with consideration of how to improve both the amount of residual error and the robustness of the system. Careful characterization of the AO system will lead to improved performance and inform the design of future systems.

We describe and compare two volume visualization methods for Optical Coherence Tomography (OCT) retinal data sets. One of these methods is CPU-slicing, which is previously reported and used in our visualization engine. The other is GPU-ray casting. Several metrics including image quality, performance, hardware limitations and perception are used to grade the abilities of each method. We also discuss how to combine these methods to make a scalable volume visualization system that supports advanced lighting and dynamic volumetric shadowing techniques on a broad range of hardware. The feasibility of each visualization method for clinical application as well as potential further improvements are discussed.

Purpose: To test the feasibility and applicability of a handheld probe for Fourier-domain optical coherence tomography (Fd-OCT) retinal imaging in infants and children. Methods: Thirty children ages 7 months to 9.9 years, with (10 of 30) or without (20 of 30) retinal pathology, were imaged with Fd-OCT. Imaging was performed under sedation in 10 of 30 children ages 7 months to 3.7 years. A high-resolution Fd-OCT system (axial resolution: 4.5 μm; acquisition speeds: 1000 A-scans/frame, 9 frames/second), constructed at the UC Davis Medical Center, in conjunction with a handheld scanner, was used for retinal imaging. Results: Useful images were obtained from all selected patients. Image acquisition was possible in a conscious state in children as young as 3 years of age. All children tolerated the tests well. The most challenging situation for young children was the lack of an internal fixation target and the moving scanning line, which usually distracted them from a steady fixation. Despite these problems, image quality was comparable with scans previously obtained from an adult population. Conclusions: The flexible handheld scanner in association with high acquisition speed and high-resolution Fd-OCT allows retinal imaging in infants and children. This technology provides high-resolution documentation of retinal structure in a pediatric population for the first time.{A figure is presented}. © 2009 American Association for Pediatric Ophthalmology and Strabismus.

Background: In severe necrotizing pancreatitis (SNP) systemic complications as pancreat it is associated lung injury (PALI) are crucial for morbidity and mortality. In the presented study we evaluated the role of chronic alcohol ingestion on the development of PALI. Methods: Wistar rats were fed for 6 weeks with either alcohol or control diet. This was followed by induction of SNP by intraductal bile salt followed by intravenous caerulein infusion for 6 hours. Control animals received Ringer’s solution. Hepatic microcirculation was assessed after 6 hours. Analyses of tissue and serum samples were performed after 12 hours in additional animals of each group. Results: SNP-related pancreatic tissue damage was not affected by preceeding alcohol exposure. In contrast, SNP was associated with increased pulmonary MPO-levels in alcohol fed animals indicating an increased pulmonary inflammatory damage. Furthermore, alcohol pretreatment revealed increased hepatic microcirculatory disturbances with an impairment of microperfusion and increased sticking leukocytes to control animals with SNP. Serum IL-6 levels were increased after both, alcohol pretreatment and induction of SNP. Highest levels were observed in alcohol fed SNP animals. Portal venous IL-6 levels were higher compared to systemic venous levels. Conclusion: Chronic alcohol exposure increases pulmonary inflammatory damage in experimental SNP. This may be explained by alcohol-related liver damage with a consecutive hepatic IL-6 release and does not seem to reflect a local pancreatic phenomenon.

PurposeTo describe a case of fine retinal striae visualized using an adaptive optics flood illuminated (AO-flood) fundus camera in a patient with vision loss from an idiopathic macular epiretinal membrane (ERM).MethodsA case report of a 48-year-old woman with recent vision loss from ERM imaged using an AO-flood fundus camera and high resolution Fourier-domain optical coherence tomography (Fd-OCT) before and 3 months after vitrectomy.ResultsVisual acuity improved from 20/70 to 20/20 after vitrectomy. Preoperative Fd-OCT showed severe cystoid macular edema with irregularities in the outer nuclear layer which consists of cell bodies of photoreceptors. Preoperative AO-flood en face images showed dark linear striae of approximately 10 μm width overlying the cone mosaic that improved following surgery, concurrent with improvement in visual acuity and morphologic changes on Fd-OCT.ConclusionMicrostructural changes within the retinal layers resulting from macular traction from ERM can be visualized using an AO-flood fundus camera and Fd-OCT. They can appear as fine linear striae in AO-flood en face images. Further studies are needed to correlate these changes with vision loss associated with this condition.

Objectives: To investigate retinal microstructure of patients affected with malattia leventinese (MLVT) and mutation in the EFEMP1 gene using high-resolution optical coherence tomography (OCT). Methods: Patients diagnosed with MLVT received a comprehensive eye exam, full-field and multifocal electroretinogram testing and imaging with a high-resolution Fourier domain OCT (Fd-OCT, UC Davis Medical Center, Davis, USA; axial resolution: 4.5 μm, acquisition speed: 9 frames s-1, 1000 A scans s-1) combined with a flexible scanning head (Bioptigen Inc. Durham, NC, USA). Results: Two related patients aged 30 and 60 years, with MLVT and identified c.R345W mutation in the EFEMP1 gene, were tested. Mother and daughter showed a variable phenotype with reduced vision function in the younger patient, whereas the mother had a 'form frustre'. Fd-OCT revealed extensive or focal sub-retinal pigment epithelium (RPE) deposits, separation of RPE and Bruch's membrane, and disruption of the photoreceptor outer and inner segment layers. No outer retinal changes were visible outside areas with sub-RPE deposits. Conclusion: Retinal structure in EFEMP1 retinal dystrophy is reflected by morphological changes within the RPE/Bruch's membrane complex with accumulation of sub-RPE material associated with disrupted photoreceptor integrity. The pattern of microstructural retinal abnormalities is similar but with a different extent in patients with variable phenotypes. © 2009 Macmillan Publishers Limited All rights reserved.

Chromatic induction was measured in terms of the wavelength of a central 1°, unique yellow field surrounded by annuli that varied in wavelength, area, contrast, and overall retinal illuminance. In the first experiment, a 1.3° surround was varied from approximately 470 to 670 nm, using an overall illuminance range from 0.5 to 4.0 log trolands. The illuminance contrast between the center and surround was 1.0 (i.e., isoluminant). The results indicated that the wavelength of unique yellow shifted in the direction of the wavelength of the surround at all intensities. The magnitude of the shift, however, decreased with increasing intensity for middle- and long-wavelength surrounds. The latter result was not expected from previous research. Experiment 2 tested the hypothesis that this might be due to a Bezold-Brucke effect in which the hue of the surround changes with increasing retinal illuminance. The relative influence of Bezold-Brucke hue shifts on chromatic induction was manipulated by changing surround area and luminance contrast. Results of this experiment were consistent with the hypothesis that changes in color appearance with increases in intensity may influence the magnitude of chromatic induction.

Membranoproliferative glomerulonephritis type II (MPGN type II)/dense deposit disease (DDD) is characterised by electron deposits within the lamina densa of the glomerular basement membrane. Systemic manifestation may include lipodystrophy and a retinopathy characterised by drusenoid deposits.1–3 MPGN type II is caused by overactivation of the alternative complement pathway (C3 Nephritic Factor, Factor H deficiency or functional defects) in the majority of cases.4 Recently, Factor H H402Y has been identified as a major-risk haplotype within the alternative complement pathway.5 In vivo microstructural identification and localisation of these retinal deposits in humans are …

Objectives: To elucidate the visual significance of the foveal pit by measuring foveal architecture and function and to reassess use of the term foveal hypoplasia (as visual acuity can vary among patients who lack a pit). Methods: We describe 4 patients who lack a foveal pit. Visual acuities ranged from 20/20 to 20/50. Stratus and Cirrus (Carl Zeiss Meditec, Dublin, California) optical coherence tomographs (OCXs) and multifocal electroretinograms were obtained. High-resolution retinal imaging on 2 of the participants was obtained by using a high-resolution Fourier-domain OCT and an adaptive optics flood-illuminated fundus camera. Results: No participants had a visible foveal pit with conventional OCT. Central widening of the outer nuclear layer and lengthening of cone outer segments were seen with high-resolution Fourier-domain OCT. Adaptive optics imaging showed normal cone diameters in the central 1° to 2°. Central multifocal electroretinogram responses were normal. Conclusions: We show that a foveal pit is not required for foveal cone specialization, anatomically or functionally. This helps to explain the potential for good acuity in the absence of a pit and raises questions about the visual role of the foveal pit. Because the term foveal hypoplasia commonly carries a negative functional implication, it may be more proper to call the anatomic lack of a pit fovea plana. ©2008 American Medical Association. All rights reserved.

Background:: New technology allows more precise definition of structural alterations of all retinal layers although it has not been used previously in cases of optic disc drusen. METHODS:: Using Stratus and Fourier domain (FD) optical coherence tomography (OCT) and adaptive optics (AO) through a flood-illuminated fundus camera, we studied the retinas of a patient with long-standing optic disc drusen and acute visual loss at high altitude attributed to ischemic optic neuropathy. RESULTS:: Stratus OCT and FD-OCT confirmed severe thinning of the retinal nerve fiber layer (RNFL). FD-OCT revealed disturbances in the photoreceptor layer heretofore not described in optic disc drusen patients. AO confirmed the FD-OCT findings in the photoreceptor layer and also showed reduced cone density at retinal locations associated with reduced visual sensitivity. CONCLUSIONS:: Based on this study, changes occur not only in the RNFL but also in the photoreceptor layer in optic nerve drusen complicated by ischemic optic neuropathy. This is the first reported application of FD-OCT and the AO to this condition. Such new imaging technology may in the future allow monitoring of disease progression more precisely and accurately. © 2008 Lippincott Williams & Wilkins.

We have developed an improved adaptive optics - optical coherence tomography (AO-OCT) system and evaluated its performance for in vivo imaging of normal and pathologic retina. The instrument provides unprecedented image quality at the retina with isotropic 3D resolution of 3.5 x 3.5 x 3.5 microm(3). Critical to the instrument's resolution is a customized achromatizing lens that corrects for the eye's longitudinal chromatic aberration and an ultra broadband light source (Delta lambda=112 nm lambda(0)= approximately 836 nm). The eye's transverse chromatic aberrations is modeled and predicted to be sufficiently small for the imaging conditions considered. The achromatizing lens was strategically placed at the light input of the AO-OCT sample arm. This location simplifies use of the achromatizing lens and allows straightforward implementation into existing OCT systems. Lateral resolution was achieved with an AO system that cascades two wavefront correctors, a large stroke bimorph deformable mirror (DM) and a micro-electromechanical system (MEMS) DM with a high number of actuators. This combination yielded diffraction-limited imaging in the eyes examined. An added benefit of the broadband light source is the reduction of speckle size in the axial dimension. Additionally, speckle contrast was reduced by averaging multiple B-scans of the same proximal patch of retina. The combination of improved micron-scale 3D resolution, and reduced speckle size and contrast were found to significantly improve visibility of microscopic structures in the retina.

Author(s): Choi, Stacey S; Zawadzki, Robert J; Keltner, John L; Werner, John S | Abstract: PurposeTo study the integrity of inner and outer retinal layers in patients with various types of optic neuropathy by using high-resolution imaging modalities.MethodsThree high-resolution imaging systems constructed at the University of California Davis were used to acquire retinal images from patients with optic neuropathy: (1) adaptive optics (AO)-flood-illuminated fundus camera, (2) high-resolution Fourier domain optical coherence tomography (FDOCT), and (3) adaptive optics-Fourier domain optical coherence tomography (AO-FDOCT). The AO fundus camera provides en face images of photoreceptors whereas cross-sectional images (B-scans) of the retina are obtained with both FDOCT and AO-FDOCT. From the volumetric FDOCT data sets, detailed thickness maps of a three-layer complex consisting of the nerve fiber (NF), ganglion cell (GC), and inner plexiform (IP) layers were created. The number of visible cones in the en face images of photoreceptors was then compared with visual sensitivity maps from Humphrey visual field (HVF; Carl Zeiss Meditec, Inc., Dublin, CA) testing, as well as FDOCT and AO-FDOCT images, including the thickness maps of the NF-GC-IP layer complex. Five types of optic neuropathy were studied: (1) optic neuritis with multiple sclerosis (MS), (2) idiopathic intracranial hypertension (pseudotumor cerebri), (3) nonarteritic anterior ischemic optic neuropathy (NAION), (4) optic nerve head drusen with NAION, and (5) systemic lupus erythematosus with MS and arthritis.ResultsWith permanent visual field loss and thinning of the NF-GC-IP layer complex, cone photoreceptors showed structural changes, making them less reflective, which caused the appearance of dark spaces in the en face images (hence, reduced number of visible cones) and indistinct outer retinal layers in OCT images. However, when the visual field loss was only transient, with a normal NF-GC-IP layer complex, there were no detectable abnormalities in cone photoreceptors (i.e., they were densely packed and had distinct photoreceptor layering in the OCT images).ConclusionsCone photoreceptors show structural changes when there is permanent damage to overlying inner retinal layers. There was a positive relation between the thickness of the three-layer inner retinal complex, visual sensitivity, and integrity of the cone mosaic.

Adaptive optics (AO) and optical coherence tomography (OCT) are powerful imaging modalities that, when combined, can provide high-resolution, 3-D images of the retina. The AO-OCT system at UC Davis has been under development for 2 years and has demonstrated the utility of this technology for microscopic, volumetric, in vivo retinal imaging. The current system uses a bimorph deformable mirror (DM) made by AOptix Technologies, Inc. for low-order, high-stroke correction and a 140-actuator mirco-electrical-mechanical-system (MEMS) DM made by Boston Micromachines Corporation for high-order correction. We present our on-going characterization of AO system performance. The AO-OCT system typically has residual wavefront error of 100 nm rms. The correctable error in the system is dominated by low-order error that we believe is introduced by aliasing in the control loop. Careful characterization of the AO system will lead to improved performance and inform the design of future systems.

Advances in Fourier-domain optical coherence tomography (Fd-OCT) permit visualization of three-dimensional morphology of in-vivo retinal structures in a way that promises to revolutionize clinical and experimental imaging of the retina. The relevance of these advances will be further increased by the recent introduction of several commercial Fd-OCT instruments that can be used in clinical practice. However, due to some inherent limitations of current Fd-OCT technology (e.g., lack of spectroscopic information, inability to measure fluorescent signals), it is important to co-register Fd-OCT data with images obtained by other clinical imaging modalities such as fundus cameras and fluorescence angiography to create a more complete interpretation and representation of structures imaged. The co-registration between different imaging platforms becomes even more important if small retinal changes are monitored for early detection and treatment. Despite advances in volume acquisition speed with FD-OCT, eye/head motion artifacts can be still seen on acquired data. Additionally high-sampling density, large field-of-view (FOV) Fd-OCT volumes may also be needed for comparison with conventional imaging. In standard Fd-OCT systems, higher sampling density and larger imaging FOV (with constant sampling densities) lead to longer acquisition time which further increases eye/head motion artifacts. To overcome those problems, we tested 3D stitching of multiple, smaller retinal volumes which can be acquired in a less time (reduction of motion artifacts) and/or when stitched create a larger FOV representation of the retina. Custom visualization software that makes possible manual co-registration and simultaneous visualization of volumetric Fd-OCT data sets is described. Volumetric visualizations of healthy retinas with corresponding fundus pictures are presented followed by examples of retinal volumes of high sampling density that are created from multiple "standard" Fd-OCT volumes.

We describe a compact MEMS-based adaptive optics (AO) optical coherence tomography (OCT) system with improved AO performance and ease of clinical use. A typical AO system consists of a Shack-Hartmann wavefront sensor and a deformable mirror that measures and corrects the ocular and system aberrations. Because of limitations on current deformable mirror technologies, the amount of real-time ocular-aberration compensation is restricted and small in previous AO-OCT instruments. In this instrument, we incorporate an optical apparatus to correct the spectacle aberrations of the patients such as myopia, hyperopia and astigmatism. This eliminates the tedious process of using trial lenses in clinical imaging. Different amount of spectacle aberration compensation was achieved by motorized stages and automated with the AO computer for ease of clinical use. In addition, the compact AO-OCT was optimized to have minimum system aberrations to reduce AO registration errors and improve AO performance.

Ultra-high isotropic resolution imaging of retinal structures was made possible with an adaptive optics system using dual deformable mirrors and a Fourier-domain optical coherence tomography (Fd-OCT) system with correction for longitudinal chromatic aberration. This system was used to image microscopic retinal structures of healthy as well as diseased retinas in vivo. The improved resolution and contrast enhanced visualization of morphological structures in the retina can be clearly seen. The benefits of this instrument are apparent from comparison of new images with those acquired using a previous generation AO-OCT instrument. Big change in the appearance of speckle field (reduction in speckle size) can be observed as well. Additionally, further improvements in volumetric data acquisition and image representation will be discussed. This includes creation of large Field of View (FOV) AO-OCT volume from multiple sub-volumes and its visualization. Also techniques and results of reducing speckle contrast by averaging multiple B-scans will be presented.

Objective: To evaluate the morphologic changes in the macula of subjects with repaired macula-off retinal detachment (RD) using high-resolution Fourier-domain optical coherence tomography (FD OCT) and to perform functional correlation in a subset of patients using microperimetry (MP-1). Design: Prospective observational case series. Participants: Seventeen eyes from 17 subjects who had undergone anatomically successful repair for macula-off, rhegmatogenous RD at least 3 months earlier and without visually significant maculopathy on funduscopy. Methods: FD OCT with axial and transverse resolution of 4.5 μm and 10 to 15 μm, respectively, was used to obtain rapid serial B-scans of the macula, which were compared with that from Stratus OCT. The FD OCT B-scans were used to create a 3-dimensional volume, from which en face C-scans were created. Among 11 patients, MP-1 was performed to correlate morphologic changes with visual function. Main Outcome Measures: Stratus OCT scans, FD OCT scans, and MP-1 data. Results: Stratus OCT and FD OCT images of the macula were obtained 3 to 30 months (mean 7 months) postoperatively in all eyes. Although Stratus OCT revealed photoreceptor disruption in 2 eyes (12%), FD OCT showed photoreceptor disruption in 13 eyes (76%). This difference was statistically significant (P

PURPOSE: To study the anatomic details of retinal angiomatous proliferation (RAP) in patients with age-related macular degeneration (AMD) using high-resolution Fourier-domain optical coherence tomography (Fd-OCT) and its three-dimensional reconstructions. METHODS: A Fd-OCT instrument was used to image five patients clinically diagnosed with RAP. A series of 100 raster-scanned B-scans centered over the macula was registered and rendered as a three-dimensional volume. These retinal structures were analyzed for anatomic details of the RAP lesions. RESULTS: The RAP lesion could be identified within the retina on Fd-OCT in all five cases. Fd-OCT images of the first four cases revealed areas of intraretinal neovascularization (IRN) in the deep retina adjacent to a pigment epithelial detachment (PED). There was neovascular proliferation anteriorly and posteriorly through a break in the retinal pigment epithelium (RPE). In three of the four cases, Bruch membrane remained intact. There was no identifiable choroidal neovascularization (CNV). The fifth case had both subretinal and sub-RPE neovascular membranes without a PED. CONCLUSION: Fd-OCT provides unprecedented in vivo detail of the anatomy of RAP lesions that nearly resembles histologic specimens. This study suggests that the initial neovascular process in RAP can originate either within the retina or in the sub-RPE space. © The Ophthalmic Communications Society, Inc.

A fast and efficient method for quantifying photoreceptor density in images obtained with an en-face flood-illuminated adaptive optics (AO) imaging system is described. To improve accuracy of cone counting, en-face images are analyzed over extended areas. This is achieved with two separate semiautomated algorithms: (1) a montaging algorithm that joins retinal images with overlapping common features without edge effects and (2) a cone density measurement algorithm that counts the individual cones in the montaged image. The accuracy of the cone density measurement algorithm is high, with >97% agreement for a simulated retinal image (of known density, with low contrast) and for AO images from normal eyes when compared with previously reported histological data. Our algorithms do not require spatial regularity in cone packing and are, therefore, useful for counting cones in diseased retinas, as demonstrated for eyes with Stargardt's macular dystrophy and retinitis pigmentosa. © 2007 Optical Society of America.

Color appearance remains remarkably stable in the aging visual system despite large changes in the spectral distribution of the retinal stimulus and losses in chromatic sensitivity (P. B. Delahunt, J. L. Hardy, K. Okajima, & J. S. Werner, 2005; J. S. Werner, 1996). This stability could reflect adaptive adjustments in peripheral or central chromatic mechanisms that compensate for sensitivity losses in senescence. We asked whether similar compensatory adjustments play a role in maintaining spatial vision--and whether the adaptation itself shows changes with aging-by examining the effects of adaptation on judgments of image focus. Perceptual aftereffects following adaptation to a uniform field and blurred or sharpened images were compared between younger adults and older observers. Subjects adapted to a sequence of blurred or sharpened images for 120 s, and a two-alternative forced-choice staircase task was used to vary the filter exponent of the test to define the subjective point of best focus. There was a small but significant difference between younger and older observers in the level perceived as best focused in all three adaptation conditions, possibly reflecting differences in the ambient blur level the groups are routinely exposed to. However, the magnitude of the blur aftereffect did not differ between the two age groups. These results suggest that although there may be small differences in the long-term adaptation to blur, younger and older observers do not differ in the strength of adaptation to transient changes in blur. The neural processes mediating adaptation to blur thus appear to remain largely intact with aging.

Ultrahigh axial resolution in adaptive optics - optical coherence tomography (AO-OCT) is fundamentally limited by the intrinsic chromatic aberrations of the human eye. Variation in refractive index of the ocular media with wavelength causes the spectral content of broadband light sources to focus at different depths in the retina for light entering the eye and at the imaging detector for light exiting. This effect has not been previously reported for ultrahigh-resolution OCT (without AO) likely because the effect is masked by the relatively long depth of focus dictated by the small pupils used in these systems. With AO, the pupil size is much larger and depth of focus substantially narrower. As such the chromatic aberrations of the eye can counteract the lateral resolution benefit of AO when used with broadband light sources. To more fully tap the potential of AO-OCT, compensation of the eye's chromatic and monochromatic aberrations must occur concurrently. One solution is to insert an achromatizing lens in front of the eye whose chromatic aberrations are equal but opposite in sign to that of the eye. In this paper we evaluate the efficacy of a novel design that uses a custom achromatizing lens placed near the fiber collimating optic. AO-OCT images are acquired on several subjects with and without the achromatizing lens and in combination with two light sources of different spectral width. The combination of the achromatizing lens and broadband light source yielded the sharpest images of the retina and the smallest speckle.

Two deformable mirrors (2DM) were used in an adaptive optics - optical coherence tomography (AO-OCT) system to image in vivo microscopic retinal structures of healthy and diseased retinas. As a result, multiple morphological structures not previously seen in vivo have been visualized. Among those presented are three-dimensional representations of the fovea and optic nerve head (ONH), revealing cellular structures and micro-vasculature. Drusen in macular degeneration and photoreceptor dystrophies are also presented. Different methods for displaying volumetric AO-OCT data to facilitate visualization of certain morphological details are compared.