Michael R. Hee

Imaging of Macular Diseases with Optical Coherence Tomography

BACKGROUND/PURPOSE To assess the potential of a new diagnostic technique called optical coherence tomography for imaging macular disease. Optical coherence tomography is a novel noninvasive, noncontact imaging modality which produces high depth resolution (10 microns) cross-sectional tomographs of ocular tissue. It is analogous to ultrasound, except that optical rather than acoustic reflectivity is measured. METHODS Optical coherence tomography images of the macula were obtained in 51 eyes of 44 patients with selected macular diseases. Imaging is performed in a manner compatible with slit-lamp indirect biomicroscopy so that high-resolution optical tomography may be accomplished simultaneously with normal ophthalmic examination. The time-of-flight delay of light backscattered from different layers in the retina is determined using low-coherence interferometry. Cross-sectional tomographs of the retina profiling optical reflectivity versus distance into the tissue are obtained in 2.5 seconds and with a longitudinal resolution of 10 microns. RESULTS Correlation of fundus examination and fluorescein angiography with optical coherence tomography tomographs was demonstrated in 12 eyes with the following pathologies: full- and partial-thickness macular hole, epiretinal membrane, macular edema, intraretinal exudate, idiopathic central serous chorioretinopathy, and detachments of the pigment epithelium and neurosensory retina. CONCLUSION Optical coherence tomography is potentially a powerful tool for detecting and monitoring a variety of macular diseases, including macular edema, macular holes, and detachments of the neurosensory retina and pigment epithelium.

In vivo retinal imaging by optical coherence tomography

We describe what are to our knowledge the first in vivo measurements of human retinal structure with optical coherence tomography. These images represent the highest depth resolution in vivo retinal images to date. The tomographic system, image-processing techniques, and examples of high-resolution tomographs and their clinical relevance are discussed.

Topography of Diabetic Macular Edema with Optical Coherence Tomography

OBJECTIVE This study aimed to develop a protocol to screen and monitor patients with diabetic macular thickening using optical coherence tomography (OCT), a technique for high-resolution cross-sectional imaging of the retina. DESIGN A cross-sectional pilot study was conducted. PARTICIPANTS A total of 182 eyes of 107 patients with diabetic retinopathy, 55 eyes from 31 patients with diabetes but no ophthalmoscopic evidence of retinopathy, and 73 eyes from 41 healthy volunteers were studied. INTERVENTION Six optical coherence tomograms were obtained in a radial spoke pattern centered on the fovea. Retinal thickness was computed automatically from each tomogram at a total of 600 locations throughout the macula. Macular thickness was displayed geographically as a false-color topographic map and was reported numerically as averages in each of nine regions. MAIN OUTCOME MEASURES Correlation of OCT with slit-lamp biomicroscopy, fluorescein angiography, and visual acuity was measured. RESULTS Optical coherence tomography was able to quantify the development and resolution of both foveal and extrafoveal macular thickening. The mean +/- standard deviation foveal thickness was 174 +/- 18 microns in normal eyes, 179 +/- 17 microns in diabetic eyes without retinopathy, and 256 +/- 114 microns in eyes with nonproliferative diabetic retinopathy. Foveal thickness was highly correlated among left and right eyes of normal eyes (mean +/- standard deviation difference of 6 +/- 9 microns). Foveal thickness measured by OCT correlated with visual acuity (r2 = 0.79). A single diabetic eye with no slit-lamp evidence of retinopathy showed abnormal foveal thickening on OCT. CONCLUSIONS Optical coherence tomography was a useful technique for quantifying macular thickness in patients with diabetic macular edema. The topographic mapping protocol provided geographic information on macular thickness that was intuitive and objective.

Reproducibility of Nerve Fiber Layer Thickness Measurements Using Optical Coherence Tomography

PURPOSE Optical coherence tomography (OCT) is a new technology that uses near-infrared light in an interferometer to produce approximately 10-microns resolution cross-sectional images of the tissue of interest. The authors performed repeated quantitative assessment of nerve fiber layer thickness in individuals with normal and glaucomatous eyes, and they evaluated the reproducibility of these measurements. METHODS The authors studied 21 eyes of 21 subjects by OCT. Each subject underwent five repetitions of a series of scans on five separate occasions within a 1-month period. Each series consisted of three circular scans around the optic nerve head (diameters, 2.9, 3.4, and 4.5 mm). Each series was performed separately using internal (fixation with same eye being studied) and external (fixation with contralateral eye) fixation techniques. The eye studied and the sequence of testing were assigned randomly. RESULTS Internal fixation (IF), in general, provides a slightly higher degree of reproducibility than external fixation (EF). Reproducibility was better in a given eye on a given visit than from visit to visit. Reproducibility as measured by intraclass correlation coefficients were as follows: circle diameter (CD), 2.9 mm, 0.51/0.57 (normal/glaucoma) (IF), 0.43/0.54 (EF); CD, 3.4 mm, 0.56/0.52 (IF), 0.43/0.61 (EF); CD, 4.5 mm, 0.53/0.43 (IF), 0.42/0.49 (EF). CONCLUSIONS Nerve fiber layer thickness can be reproducibly measured using OCT. Internal is superior to external fixation; each circle diameter tested provides adequate reproducibility.

Optical coherence microscopy in scattering media.

We describe a novel technique, based on optical coherence tomography, for enhanced optical sectioning in confocal microscopy. Confocal imaging deep into highly scattering media is demonstrated and compared with the predictions of a single-backscatter theory.

Optical coherence tomography for optical biopsy : Properties and demonstration of vascular pathology

BACKGROUND Optical coherence tomography (OCT) is an recently developed medical diagnostic technology that uses back-reflected infrared light to perform in situ micron scale tomographic imaging. In this work, we investigate the ability of OCT to perform micron scale tomographic imaging of the internal microstructure of in vitro atherosclerotic plaques. METHODS AND RESULTS Aorta and relevant nonvascular tissue were obtained at autopsy. Two-dimensional cross-sectional imaging of the exposed surface of the arterial segments was performed in vitro with OCT. A 1300-nm wavelength, superluminescent diode light source was used that allows an axial spatial resolution of 20 microns. The signal-to-noise ratio was 109 dB. Images were displayed in gray scale or false color, Imaging was performed over 1.5 mm into heavily calcified tissue, and a high contrast was noted between lipid- and water-based constituents, making OCT attractive for intracoronary imaging. The 20-microns axial resolution of OCT allowed small structural details such as the width of intimal caps and the presence of fissures to be determined. The extent of lipid collections, which had a low backscattering intensity, also were well documented. CONCLUSIONS OCT represents a promising new technology for imaging vascular microstructure with a level of resolution not previously achieved with the use of other imaging modalities. It does not required direct contact with the vessel wall and can be performed with a catheter integrated with a relatively inexpensive optical fiber. The high contrast among tissue constituents, high resolution, and ability to penetrate heavily calcified tissue make OCT an attractive new imaging technology for intracoronary diagnostics.

Determination of the refractive index of highly scattering human tissue by optical coherence tomography.

We describe two new techniques, based on optical coherence tomography (OCT), for determining the refractive index of highly scattering human tissue. We obtained refractive indices of in vitro human tissue, using OCT to measure the physical and optical path lengths of the sample. We obtained measurements of the refractive index of in vitro and in vivo human tissue, using OCT to track the focal length shift that results from translating the focus along the optic axis within the tissue. The refractive indices of human skin, adipose, and muscle were measured and compared with previously published estimates.

Optical coherence tomography of age-related macular degeneration and choroidal neovascularization.

OBJECTIVE The authors used optical coherence tomography (OCT), a new technique for cross-sectional imaging of the retina, to morphologically study eyes with nonexudative and exudative age-related macular degeneration (AMD). In patients with untreated exudative AMD, OCT was compared with fluorescein angiography in the identification and classification of choroidal neovascularization (CNV). METHODS Optical coherence tomography imaging is analogous to ultrasound, except that the use of light rather than sound enables higher longitudinal resolution with a noncontact and noninvasive measurement. Optical coherence tomography was performed on 391 patients with the clinical diagnosis of AMD and was compared with conventional clinical examination to establish the cross-sectional morphology of different lesions and to develop a classification scheme for CNV. Optical coherence tomograms and fluorescein angiograms then were reviewed and correlated independently in 90 eyes of 86 patients who had exudative AMD without previous laser treatment. RESULTS Pigmentary changes, soft drusen, and detachments of the neurosensory retina and retinal pigment epithelium all had distinct presentations on OCT. Subretinal and intraretinal fluid caused changes in retinal thickness or elevation that could be quantified directly from the images. Choroidal neovascularization was evident in the tomograms as a thickening and fragmentation of a reflective layer, which corresponded to the retinal pigment epithelium and choriocapillaris. Changes in the reflection from this layer were observed during the progression of neovascularization, and after laser photocoagulation treatment. Classic CNV consistently presented with well-defined boundaries on OCT, whereas occult CNV had a variable cross-sectional appearance. CONCLUSIONS Optical coherence tomography was useful in quantitatively evaluating subretinal and intraretinal fluid, assessing possible subfoveal involvement of neovascularization, and in monitoring CNV before and after laser photocoagulation. Optical coherence tomography was unable to detect CNV beneath serous pigment epithelial detachments. Optical coherence tomography may have potential in accurately defining the boundaries in a subset of angiographically occult CNV.

HIGH-RESOLUTION OPTICAL COHERENCE TOMOGRAPHIC IMAGING USING A MODE-LOCKED TI:AL2O3 LASER SOURCE

A Kerr-lens mode-locked Ti:Al(2)O(3) oscillator, optimized for minimal coherence length, is demonstrated as a high-power source for high-resolution optical coherence tomographic imaging. Dispersion compensation and heterodyne noise rejection are demonstrated to yield in situ images of biological tissues with 3.7-mum resolution and 93-dB dynamic range.

Assessing atherosclerotic plaque morphology: comparison of optical coherence tomography and high frequency intravascular ultrasound.

BACKGROUND: OCT can image plaque microstructure at a level of resolution not previously demonstrated with other imaging techniques because it uses infrared light rather than acoustic waves. OBJECTIVES: To compare optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of in vitro atherosclerotic plaques. METHODS: Segments of abdominal aorta were obtained immediately before postmortem examination. Images of 20 sites from five patients were acquired with OCT (operating at an optical wavelength of 1300 nm which was delivered to the sample through an optical fibre) and a 30 MHz ultrasonic transducer. After imaging, the microstructure of the tissue was assessed by routine histological processing. RESULTS: OCT yielded superior structural information in all plaques examined. The mean (SEM) axial resolution of OCT and IVUS imaging was 16 (1) and 110 (7), respectively, as determined by the point spread function from a mirror. Furthermore, the dynamic range of OCT was 109 dB compared with 43 dB for IVUS imaging. CONCLUSIONS: OCT represents a promising new technology for intracoronary imaging because of its high resolution, broad dynamic range, and ability to be delivered through intravascular catheters.