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1.
Opt Lett ; 46(5): 1085-1088, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33649663

RESUMEN

Off-axis detection methods in adaptive optics (AO) ophthalmoscopy can enhance image contrast of translucent retinal structures such as cone inner segments and retinal ganglion cells. Here, we propose a 2D optical model showing that the phase contrast produced by these methods depends on the offset orientation. While one axis provides an asymmetric light distribution, hence high phase contrast, the perpendicular axis provides a symmetric one, thus substantially lower contrast. We support this model with in vivo human data acquired with a multi-offset AO scanning light ophthalmoscope. Then, using this finding, we provide a post-processing method, named spatial-frequency-based image reconstruction, to optimally combine images from different off-axis detector orientations, significantly increasing the structural cellular contrast of in vivo human retinal neurons such as cone inner segment, putative rods, and retinal ganglion cells.

2.
Signal Processing ; 1772020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32943806

RESUMEN

Advances in multimodal imaging have revolutionized diagnostic and treatment monitoring in ophthalmic practice. In multimodal ophthalmic imaging, geometric deformations are inevitable and they contain inherent deformations arising from heterogeneity in the optical characteristics of imaging devices and patient related factors. The registration of ophthalmic images under such conditions is challenging. We propose a novel technique that overcomes these challenges, using Laplacian feature, Hessian affine feature space and phase correlation, to register blue autofluorescence, near-infrared reflectance and color fundus photographs of the ocular posterior pole with high accuracy. Our validation analysis - that used current feature detection and extraction techniques (speed-up robust features (SURF), a concept of wind approach (KAZE), and fast retina keypoint (FREAK)), and quantitative measures (Sørensen-Dice coefficient, Jaccard index, and Kullback-Leibler divergence scores) - showed that our approach has significant merit in registering multimodal images when compared with a mix-and-match SURF-KAZE-FREAK benchmark approach. Similarly, our evaluation analysis that used a state-of-the-art qualitative measure - the mean registration error (MRE) - showed that the proposed approach is significantly better than the mix-and-match SURF-KAZE-FREAK benchmark approach, as well as a cutting edge image registration technique - Linear Stack Alignment with SIFT (scale-invariant feature transform) - in registering multimodal ophthalmic images.

3.
Sci Rep ; 10(1): 9561, 2020 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-32533046

RESUMEN

Retinal pigmented epithelial (RPE) cells are essential for maintaining normal visual function, especially in their role in the visual cycle, and are thought to be one of the first cell classes affected by age-related macular degeneration (AMD). Clinical imaging systems routinely evaluate the structure of the RPE at the tissue level, but cellular level information may provide valuable RPE biomarkers of health, aging and disease. In this exploratory study, participants were imaged with 795 nm excitation in adaptive optics scanning laser ophthalmoscopy (AOSLO) to observe the microstructure of the near-infrared autofluorescence (AO-IRAF) from the RPE layer in healthy retinas and patients with AMD. The expected hexagonal mosaic of RPE cells was only sometimes seen in normal eyes, while AMD patients exhibited highly variable patterns of altered AO-IRAF. In some participants, AO-IRAF structure corresponding to cones was observed, as we have demonstrated previously. In some AMD patients, marked alterations in the pattern of AO-IRAF could be seen even in areas where the RPE appeared relatively normal in clinical imaging modalities, such as spectral domain optical coherence tomography (SD-OCT). AO-IRAF imaging using AOSLO offers promise for better detection and understanding of early RPE changes in the course of AMD, potentially before clinical signs appear.

4.
JAMA Ophthalmol ; 137(6): 603-609, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30896765

RESUMEN

Importance: Targeting the early pathogenic steps in Stargardt disease type 1 (STGD1) is critical to advance our understanding of this condition and to develop potential therapies. Lipofuscin precursors may accumulate within photoreceptors, leading to photoreceptor damage and preceding retinal pigment epithelial (RPE) cell death. Fluorescence adaptive optics scanning light ophthalmoscopy can provide autofluorescence (AF) images in vivo with microscopic resolution to elucidate the cellular origin of AF abnormalities in STGD1. Objective: To study the spatial distribution of photoreceptor, RPE, and AF abnormalities in patients with STGD1 at a cellular level. Design, Setting, and Participants: Cross-sectional study using fluorescence adaptive optics scanning light ophthalmoscopy to compare the cones, rods, and RPE cells between 3 patients with STGD1 and 1 control individual. Imaging sessions were conducted at the University of Rochester. Further image analyses were performed at Beijing Tongren Eye Center and the University of Pittsburgh. Data were collected from August 2015 to February 2016, and analysis began in March 2016. Main Outcomes and Measures: Structural appearance of cones, rods, and AF structures at different retinal locations. Results: Two women and 1 man with macular atrophy phenotype of STGD1 and visual acuity loss ranging from 20/30 to 20/150 and 1 woman without STGD1 with 20/20 visual acuity were analyzed. Cone and rod spacing was increased in all 3 patients at all locations where photoreceptors were detectable; most cones had a dark appearance. Autofluorescence was low contrast but contained structures consistent with RPE cells in the periphery. In the transition zone peripheral to the foveal atrophic lesion, the structural pattern of AF was more consistent with photoreceptors than RPE cells. The microscopic AF was disrupted within areas of clinically detectable atrophy. Conclusions and Relevance: Adaptive optics high-resolution images of cones, rods, and RPE cells at the leading disease front of STGD1 macular atrophy show an AF pattern that appears to colocalize with photoreceptors or may result from a combination of AF signals from both RPE cells and photoreceptors. This in vivo observation is consistent with histologic reports of fluorescence arising from photoreceptors in STGD1. The detection of bisretinoid accumulation in the photoreceptors may represent an early pathologic step in STGD1 and can provide an in vivo imaging tool to act as a biomarker of disease progression.


Asunto(s)
Células Fotorreceptoras de Vertebrados/patología , Epitelio Pigmentado de la Retina/patología , Enfermedad de Stargardt/diagnóstico , Adulto , Estudios Transversales , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Masculino , Oftalmoscopía , Imagen Óptica , Óptica y Fotónica , Adulto Joven
5.
Biomed Opt Express ; 10(1): 66-82, 2019 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-30775083

RESUMEN

Progress is needed in developing animal models of photoreceptor degeneration and evaluating such models with longitudinal, noninvasive techniques. We employ confocal scanning laser ophthalmoscopy, optical coherence tomography (OCT) and high-resolution retinal imaging to noninvasively observe the retina of non-human primates with induced photoreceptor degeneration. Photoreceptors were imaged at the single-cell scale in three modalities of adaptive optics scanning light ophthalmoscopy: traditional confocal reflectance, indicative of waveguiding; a non-confocal offset aperture technique visualizing scattered light; and two-photon excited fluorescence, the time-varying signal of which, at 730 nm excitation, is representative of visual cycle function. Assessment of photoreceptor structure and function using these imaging modalities revealed a reduction in retinoid production in cone photoreceptor outer segments while inner segments appeared to remain present. Histology of one retina confirmed loss of outer segments and the presence of intact inner segments. This unique combination of imaging modalities can provide essential, clinically-relevant information on both the structural integrity and function of photoreceptors to not only validate models of photoreceptor degeneration but potentially evaluate the efficacy of future cell and gene-based therapies for vision restoration.

6.
Invest Ophthalmol Vis Sci ; 59(15): 5705-5716, 2018 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-30513531

RESUMEN

Purpose: To characterize in vivo morphometry and multispectral autofluorescence of the retinal pigment epithelial (RPE) cell mosaic and its relationship to cone cell topography across the macula. Methods: RPE cell morphometrics were computed in regularly spaced regions of interest (ROIs) from contiguous short-wavelength autofluorescence (SWAF) and photoreceptor reflectance images collected across the macula in one eye of 10 normal participants (23-65 years) by using adaptive optics scanning light ophthalmoscopy (AOSLO). Infrared autofluorescence (IRAF) images of the RPE were collected with AOSLO in seven normal participants (22-65 years), with participant overlap, and compared to SWAF quantitatively and qualitatively. Results: RPE cell statistics could be analyzed in 84% of SWAF ROIs. RPE cell density consistently decreased with eccentricity from the fovea (participant mean ± SD: 6026 ± 1590 cells/mm2 at fovea; 4552 ± 1370 cells/mm2 and 3757 ± 1290 cells/mm2 at 3.5 mm temporally and nasally, respectively). Mean cone-to-RPE cell ratio decreased rapidly from 16.6 at the foveal center to <5 by 1 mm. IRAF revealed cells in six of seven participants, in agreement with SWAF RPE cell size and location. Differences in cell fluorescent structure, contrast, and visibility beneath vasculature were observed between modalities. Conclusions: Improvements in AOSLO autofluorescence imaging permit efficient visualization of RPE cells with safe light exposures, allowing individual characterization of RPE cell morphometry that is variable between participants. The normative dataset and analysis of RPE cell IRAF and SWAF herein are essential for understanding microscopic characteristics of cell fluorescence and may assist in interpreting disease progression in RPE cells.


Asunto(s)
Células Fotorreceptoras Retinianas Conos/citología , Epitelio Pigmentado de la Retina/citología , Adulto , Anciano , Recuento de Células , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Mosaicismo , Oftalmoscopía/métodos , Imagen Óptica , Óptica y Fotónica , Epitelio Pigmentado de la Retina/diagnóstico por imagen , Tomografía de Coherencia Óptica , Adulto Joven
7.
Br J Ophthalmol ; 102(1): 136-141, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29074494

RESUMEN

PURPOSE: Several genes causing autosomal-dominant cone-rod dystrophy (AD-CRD) have been identified. However, the mechanisms by which genetic mutations lead to cellular loss in human disease remain poorly understood. Here we combine genotyping with high-resolution adaptive optics retinal imaging to elucidate the retinal phenotype at a cellular level in patients with AD-CRD harbouring a defect in the GUCA1A gene. METHODS: Nine affected members of a four-generation AD-CRD pedigree and three unaffected first-degree relatives underwent clinical examinations including visual acuity, fundus examination, Goldmann perimetry, spectral domain optical coherence tomography and electroretinography. Genome-wide scan followed by bidirectional sequencing was performed on all affected participants. High-resolution imaging using a custom adaptive optics scanning light ophthalmoscope (AOSLO) was performed for selected participants. RESULTS: Clinical evaluations showed a range of disease severity from normal fundus appearance in teenaged patients to pronounced macular atrophy in older patients. Molecular genetic testing showed a mutation in in GUCA1A segregating with disease. AOSLO imaging revealed that of the two teenage patients with mild disease, one had severe disruption of the photoreceptor mosaic while the other had a normal cone mosaic. CONCLUSIONS: AOSLO imaging demonstrated variability in the pattern of cone and rod cell loss between two teenage cousins with early AD-CRD, who had similar clinical features and had the identical disease-causing mutation in GUCA1A. This finding suggests that a mutation in GUCA1A does not lead to the same degree of AD-CRD in all patients. Modifying factors may mitigate or augment disease severity, leading to different retinal cellular phenotypes.


Asunto(s)
Distrofias de Conos y Bastones/genética , Electrorretinografía/instrumentación , Angiografía con Fluoresceína/instrumentación , Óptica y Fotónica , Tomografía de Coherencia Óptica/instrumentación , Agudeza Visual , Adolescente , Adulto , Anciano , Niño , Distrofias de Conos y Bastones/diagnóstico , Distrofias de Conos y Bastones/terapia , Diseño de Equipo , Femenino , Fondo de Ojo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Adulto Joven
8.
Ophthalmol Retina ; 2(2): 143-151, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-31047341

RESUMEN

PURPOSE: To demonstrate the validity of adaptive optics scanning laser ophthalmoscopy (AOSLO) imaging of the retina in human disease based on clinicopathologic correlation in a patient with cancer-associated retinopathy (CAR). DESIGN: Case report. PARTICIPANT: Sixty-four-year-old man with CAR. METHODS: Fundus photography, electroretinography, visual field testing, fundus autofluorescent imaging, spectral-domain OCT scans, AOSLO, and histopathologic analysis were performed. MAIN OUTCOME MEASURE: Comparison of AOSLO with histopathologic results. RESULTS: Changes in photoreceptor morphologic features were correlated highly between AOSLO and histopathologic results. CONCLUSIONS: We present a unique case where a patient with a rare and fatal disease, CAR, underwent AOSLO imaging during the course of the disease, and then shortly thereafter, postmortem histopathologic analysis of the eyes was carried out. This is the first report of use of AOSLO to elucidate further the retinal changes that occur in CAR and the first study to demonstrate correlation of AOSLO with histopathologic results in any human disease.


Asunto(s)
Carcinoma de Células Grandes/complicaciones , Neoplasias Pulmonares/complicaciones , Oftalmoscopía/métodos , Óptica y Fotónica , Síndromes Paraneoplásicos Oculares/patología , Células Fotorreceptoras Retinianas Conos/patología , Biopsia , Carcinoma de Células Grandes/diagnóstico , Diseño de Equipo , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Síndromes Paraneoplásicos Oculares/etiología , Reproducibilidad de los Resultados
9.
Biomed Opt Express ; 9(12): 5946-5961, 2018 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31065405

RESUMEN

We demonstrate near-infrared autofluorescence (NIRAF) imaging of retinal pigment epithelial (RPE) cells in vivo in healthy volunteers and patients using a 757 nm excitation source in adaptive optics scanning laser ophthalmoscopy (AOSLO). NIRAF excited at 757 nm and collected in an emission band from 778 to 810 nm produced a robust NIRAF signal, presumably arising from melanin, and revealed the typical hexagonal mosaic of RPE cells at most eccentricities imaged within the macula of normal eyes. Several patterns of altered NIRAF structure were seen in patients, including disruption of the NIRAF over a drusen, diffuse hyper NIRAF signal with loss of individual cell delineation in a case of non-neovascular age-related macular degeneration (AMD), and increased visibility of the RPE mosaic under an area showing loss of photoreceptors. In some participants, a superposed cone mosaic was clearly visible in the fluorescence channel at eccentricities between 2 and 6° from the fovea. This was reproducible in these participants and existed despite the use of emission filters with an optical attenuation density of 12 at the excitation wavelength, minimizing the possibility that this was due to bleed through of the excitation light. This cone signal may be a consequence of cone waveguiding on either the ingoing excitation light and/or the outgoing NIRAF emitted by fluorophores within the RPE and/or choroid and warrants further investigation. NIRAF imaging at 757 nm offers efficient signal excitation and detection, revealing structural alterations in retinal disease with good contrast and shows promise as a tool for monitoring future therapies at the level of single RPE cells.

10.
Proc Natl Acad Sci U S A ; 114(3): 586-591, 2017 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-28049835

RESUMEN

Although imaging of the living retina with adaptive optics scanning light ophthalmoscopy (AOSLO) provides microscopic access to individual cells, such as photoreceptors, retinal pigment epithelial cells, and blood cells in the retinal vasculature, other important cell classes, such as retinal ganglion cells, have proven much more challenging to image. The near transparency of inner retinal cells is advantageous for vision, as light must pass through them to reach the photoreceptors, but it has prevented them from being directly imaged in vivo. Here we show that the individual somas of neurons within the retinal ganglion cell (RGC) layer can be imaged with a modification of confocal AOSLO, in both monkeys and humans. Human images of RGC layer neurons did not match the quality of monkey images for several reasons, including safety concerns that limited the light levels permissible for human imaging. We also show that the same technique applied to the photoreceptor layer can resolve ambiguity about cone survival in age-related macular degeneration. The capability to noninvasively image RGC layer neurons in the living eye may one day allow for a better understanding of diseases, such as glaucoma, and accelerate the development of therapeutic strategies that aim to protect these cells. This method may also prove useful for imaging other structures, such as neurons in the brain.


Asunto(s)
Oftalmoscopía/métodos , Células Ganglionares de la Retina/citología , Animales , Femenino , Glaucoma/diagnóstico por imagen , Humanos , Macaca fascicularis/anatomía & histología , Macaca mulatta/anatomía & histología , Degeneración Macular/diagnóstico por imagen , Degeneración Macular/patología , Masculino , Fenómenos Ópticos , Células Fotorreceptoras Retinianas Conos/citología , Especificidad de la Especie
11.
Biomed Opt Express ; 6(8): 2864, 2015 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-26309750

RESUMEN

This publisher's note amends the author list and Acknowledgments of a recent publication [Biomed. Opt. Express6, 2120 (2015)].[This corrects the article on p. 2120 in vol. 6, PMID: 26114033.].

12.
JAMA Ophthalmol ; 133(10): 1198-203, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26247787

RESUMEN

IMPORTANCE: Stargardt disease (STGD1) is characterized by macular atrophy and flecks in the retinal pigment epithelium. The causative ABCA4 gene encodes a protein localizing to photoreceptor outer segments. The pathologic steps by which ABCA4 mutations lead to clinically detectable retinal pigment epithelium changes remain unclear. We investigated early STGD1 using adaptive optics scanning light ophthalmoscopy. OBSERVATIONS: Adaptive optics scanning light ophthalmoscopy imaging of 2 brothers with early STGD1 and their unaffected parents was compared with conventional imaging. Cone and rod spacing were increased in both patients (P < .001) with a dark cone appearance. No foveal cones were detected in the older brother. In the younger brother, foveal cones were enlarged with low density (peak cone density, 48.3 × 103 cones/mm2). The ratio of cone to rod spacing was increased in both patients, with greater divergence from normal approaching the foveal center, indicating that cone loss predominates centrally and rod loss increases peripherally. Both parents had normal photoreceptor mosaics. Genetic testing revealed 3 disease-causing mutations. CONCLUSIONS AND RELEVANCE: This study provides in vivo images of rods and cones in STGD1. Although the primary clinical features of STGD1 are retinal pigment epithelial lesions, adaptive optics scanning light ophthalmoscopy reveals increased cone and rod spacing in areas that appear normal in conventional images, suggesting that photoreceptor loss precedes clinically detectable retinal pigment epithelial disease in STGD1.


Asunto(s)
Degeneración Macular/congénito , Células Fotorreceptoras de Vertebrados/patología , Transportadoras de Casetes de Unión a ATP/genética , Femenino , Humanos , Degeneración Macular/diagnóstico , Degeneración Macular/genética , Masculino , Mutación , Oftalmoscopía/métodos , Linaje , Enfermedad de Stargardt , Tomografía de Coherencia Óptica , Agudeza Visual
13.
Biomed Opt Express ; 6(6): 2120-37, 2015 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-26114033

RESUMEN

Here we demonstrate a new imaging system that addresses several major problems limiting the clinical utility of conventional adaptive optics scanning light ophthalmoscopy (AOSLO), including its small field of view (FOV), reliance on patient fixation for targeting imaging, and substantial post-processing time. We previously showed an efficient image based eye tracking method for real-time optical stabilization and image registration in AOSLO. However, in patients with poor fixation, eye motion causes the FOV to drift substantially, causing this approach to fail. We solve that problem here by tracking eye motion at multiple spatial scales simultaneously by optically and electronically integrating a wide FOV SLO (WFSLO) with an AOSLO. This multi-scale approach, implemented with fast tip/tilt mirrors, has a large stabilization range of ± 5.6°. Our method consists of three stages implemented in parallel: 1) coarse optical stabilization driven by a WFSLO image, 2) fine optical stabilization driven by an AOSLO image, and 3) sub-pixel digital registration of the AOSLO image. We evaluated system performance in normal eyes and diseased eyes with poor fixation. Residual image motion with incremental compensation after each stage was: 1) ~2-3 arc minutes, (arcmin) 2) ~0.5-0.8 arcmin and, 3) ~0.05-0.07 arcmin, for normal eyes. Performance in eyes with poor fixation was: 1) ~3-5 arcmin, 2) ~0.7-1.1 arcmin and 3) ~0.07-0.14 arcmin. We demonstrate that this system is capable of reducing image motion by a factor of ~400, on average. This new optical design provides additional benefits for clinical imaging, including a steering subsystem for AOSLO that can be guided by the WFSLO to target specific regions of interest such as retinal pathology and real-time averaging of registered images to eliminate image post-processing.

14.
Opt Lett ; 40(1): 85-8, 2015 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-25531615

RESUMEN

Sinusoidal rectification (i.e., desinusoiding) is necessary for scanning imaging systems and is typically achieved by calculating a rectification transform from a calibration image such as a regular grid. This approach is susceptible to error due to electronic or mechanical instability that can alter the phase of the imaging window with respect to the calibration transform. Here, we show a calibration-free rectification method implemented from live video of a scanning light ophthalmoscope (SLO) with or without adaptive optics (AO). This approach, which capitalizes on positional differences in the images obtained in the forward and backward scan directions, dynamically keeps the imaging window in phase with the motion of the sinusoidal resonant scanner, preventing errors from signal drift over time. A benefit of this approach is that it allows the light power across the field-of-view (FOV) to be modulated inversely to achieve uniform irradiance on the retina, a feature desirable for functional imaging methods and light safety in SLOs.


Asunto(s)
Oftalmoscopía/métodos , Fenómenos Ópticos , Retina , Calibración , Humanos
15.
Biomed Opt Express ; 5(9): 3174-91, 2014 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-25401030

RESUMEN

Eye motion is a major impediment to the efficient acquisition of high resolution retinal images with the adaptive optics (AO) scanning light ophthalmoscope (AOSLO). Here we demonstrate a solution to this problem by implementing both optical stabilization and digital image registration in an AOSLO. We replaced the slow scanning mirror with a two-axis tip/tilt mirror for the dual functions of slow scanning and optical stabilization. Closed-loop optical stabilization reduced the amplitude of eye-movement related-image motion by a factor of 10-15. The residual RMS error after optical stabilization alone was on the order of the size of foveal cones: ~1.66-2.56 µm or ~0.34-0.53 arcmin with typical fixational eye motion for normal observers. The full implementation, with real-time digital image registration, corrected the residual eye motion after optical stabilization with an accuracy of ~0.20-0.25 µm or ~0.04-0.05 arcmin RMS, which to our knowledge is more accurate than any method previously reported.

16.
Invest Ophthalmol Vis Sci ; 55(6): 3929-38, 2014 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-24845640

RESUMEN

PURPOSE: Many retinal imaging instruments use infrared wavelengths to reduce the risk of light damage. However, we have discovered that exposure to infrared illumination causes a long-lasting reduction in infrared autofluorescence (IRAF). We have characterized the dependence of this effect on radiant exposure and investigated its origin. METHODS: A scanning laser ophthalmoscope was used to obtain IRAF images from two macaques before and after exposure to 790-nm light (15-450 J/cm(2)). Exposures were performed with either raster-scanning or uniform illumination. Infrared autofluorescence images also were obtained in two humans exposed to 790-nm light in a separate study. Humans were assessed with direct ophthalmoscopy, Goldmann visual fields, multifocal ERG, and photopic microperimetry to determine whether these measures revealed any effects in the exposed locations. RESULTS: A significant decrease in IRAF after exposure to infrared light was seen in both monkeys and humans. In monkeys, the magnitude of this reduction increased with retinal radiant exposure. Partial recovery was seen at 1 month, with full recovery within 21 months. Consistent with a photochemical origin, IRAF decreases caused by either raster-scanning or uniform illumination were not significantly different. We were unable to detect any effect of the light exposure with any measure other than IRAF imaging. We cannot exclude the possibility that changes could be detected with more sensitive tests or longer follow-up. CONCLUSIONS: This long-lasting effect of infrared illumination in both humans and monkeys occurs at exposure levels four to five times below current safety limits. The photochemical basis for this phenomenon remains unknown.


Asunto(s)
Angiografía con Fluoresceína , Rayos Infrarrojos/efectos adversos , Imagen Óptica , Traumatismos Experimentales por Radiación/etiología , Retina/efectos de la radiación , Enfermedades de la Retina/etiología , Animales , Electrorretinografía , Femenino , Lipofuscina/metabolismo , Macaca fascicularis , Macaca mulatta , Masculino , Concentración Máxima Admisible , Oftalmoscopía , Traumatismos Experimentales por Radiación/diagnóstico , Traumatismos Experimentales por Radiación/metabolismo , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Pruebas del Campo Visual , Campos Visuales
17.
Biomed Opt Express ; 4(11): 2527-39, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24298413

RESUMEN

Morgan and colleagues demonstrated that the RPE cell mosaic can be resolved in the living human eye non-invasively by imaging the short-wavelength autofluorescence using an adaptive optics (AO) ophthalmoscope. This method, based on the assumption that all subjects have the same longitudinal chromatic aberration (LCA) correction, has proved difficult to use in diseased eyes, and in particular those affected by age-related macular degeneration (AMD). In this work, we improve Morgan's method by accounting for chromatic aberration variations by optimizing the confocal aperture axial and transverse placement through an automated iterative maximization of image intensity. The increase in image intensity after algorithmic aperture placement varied depending upon patient and aperture position prior to optimization but increases as large as a factor of 10 were observed. When using a confocal aperture of 3.4 Airy disks in diameter, images were obtained using retinal radiant exposures of less than 2.44 J/cm(2), which is ~22 times below the current ANSI maximum permissible exposure. RPE cell morphologies that were strikingly similar to those seen in postmortem histological studies were observed in AMD eyes, even in areas where the pattern of fluorescence appeared normal in commercial fundus autofluorescence (FAF) images. This new method can be used to study RPE morphology in AMD and other diseases, providing a powerful tool for understanding disease pathogenesis and progression, and offering a new means to assess the efficacy of treatments designed to restore RPE health.

18.
J Opt Soc Am A Opt Image Sci Vis ; 30(12): 2595-604, 2013 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-24323021

RESUMEN

Adaptive optics (AO) imaging methods allow the histological characteristics of retinal cell mosaics, such as photoreceptors and retinal pigment epithelium (RPE) cells, to be studied in vivo. The high-resolution images obtained with ophthalmic AO imaging devices are rich with information that is difficult and/or tedious to quantify using manual methods. Thus, robust, automated analysis tools that can provide reproducible quantitative information about the cellular mosaics under examination are required. Automated algorithms have been developed to detect the position of individual photoreceptor cells; however, most of these methods are not well suited for characterizing the RPE mosaic. We have developed an algorithm for RPE cell segmentation and show its performance here on simulated and real fluorescence AO images of the RPE mosaic. Algorithm performance was compared to manual cell identification and yielded better than 91% correspondence. This method can be used to segment RPE cells for morphometric analysis of the RPE mosaic and speed the analysis of both healthy and diseased RPE mosaics.


Asunto(s)
Células Epiteliales/fisiología , Epitelio Pigmentado de la Retina/patología , Algoritmos , Animales , Automatización , Simulación por Computador , Fluorescencia , Humanos , Procesamiento de Imagen Asistido por Computador , Luz , Macaca , Microscopía Fluorescente/métodos , Distribución Normal , Oftalmoscopía/métodos , Óptica y Fotónica , Epitelio Pigmentado de la Retina/citología
19.
PLoS One ; 8(2): e57956, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23469117

RESUMEN

Carriers of blue cone monochromacy have fewer cone photoreceptors than normal. Here we examine how this disruption at the level of the retina affects visual function and cortical organization in these individuals. Visual resolution and contrast sensitivity was measured at the preferred retinal locus of fixation and visual resolution was tested at two eccentric locations (2.5° and 8°) with spectacle correction only. Adaptive optics corrected resolution acuity and cone spacing were simultaneously measured at several locations within the central fovea with adaptive optics scanning laser ophthalmoscopy (AOSLO). Fixation stability was assessed by extracting eye motion data from AOSLO videos. Retinotopic mapping using fMRI was carried out to estimate the area of early cortical regions, including that of the foveal confluence. Without adaptive optics correction, BCM carriers appeared to have normal visual function, with normal contrast sensitivity and visual resolution, but with AO-correction, visual resolution was significantly worse than normal. This resolution deficit is not explained by cone loss alone and is suggestive of an associated loss of retinal ganglion cells. However, despite evidence suggesting a reduction in the number of retinal ganglion cells, retinotopic mapping showed no reduction in the cortical area of the foveal confluence. These results suggest that ganglion cell density may not govern the foveal overrepresentation in the cortex. We propose that it is not the number of afferents, but rather the content of the information relayed to the cortex from the retina across the visual field that governs cortical magnification, as under normal viewing conditions this information is similar in both BCM carriers and normal controls.


Asunto(s)
Defectos de la Visión Cromática/patología , Defectos de la Visión Cromática/fisiopatología , Corteza Visual/patología , Corteza Visual/fisiopatología , Adulto , Recuento de Células , Color , Femenino , Fóvea Central/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Células Ganglionares de la Retina/patología , Agudeza Visual
20.
J Vis ; 10(12): 11, 2010 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-21047743

RESUMEN

The visual benefit of correcting high-order aberrations may not be fully realized due to neural mechanisms that compensate for the aberrations of the eye. We examined the extent to which these neural mechanisms might be susceptible to perceptual learning in an adaptive optics (AO)-corrected test of visual resolution. Visual resolution was measured in an adaptive optics scanning laser ophthalmoscope (AOSLO) in 3 conditions: (1) low-order correction (defocus and astigmatism) without AO, (2) 3-mm pupil with AO correction, and (3) 5.81-mm pupil with AO correction. Measurements were made on both eyes in all three conditions before training. Subjects underwent 5 days of monocular training in both AO-corrected conditions and were retested in all three conditions in both eyes after training. The range of minimum angle of resolution (MAR) for each condition was: (1) without AO: 0.53-0.95 arcmin, (2) AO 3-mm pupil: 0.33-0.6 arcmin, and (3) AO 5.81-mm pupil: 0.36-0.56 arcmin. AO correction provided an immediate and significant improvement in visual resolution. There was no significant difference in resolution when correcting aberrations over a 5.81-mm pupil versus a 3-mm pupil. Training on this task provided a minimal improvement in performance. Adaptation to aberrations did not hinder AO correction from providing an immediate visual benefit.


Asunto(s)
Astigmatismo/fisiopatología , Astigmatismo/terapia , Emetropía/fisiología , Aprendizaje/fisiología , Agudeza Visual/fisiología , Anteojos , Humanos , Miopía/fisiopatología , Miopía/terapia , Oftalmoscopía/métodos , Psicofísica , Pupila/fisiología , Visión Monocular/fisiología , Percepción Visual/fisiología
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