Joel S. Schuman

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.

Ultrahigh-resolution ophthalmic optical coherence tomography

Here we present new technology for optical coherence tomography (OCT) that enables ultrahigh-resolution, non-invasive in vivo ophthalmologic imaging of retinal and corneal morphology with an axial resolution of 2–3 μm. This resolution represents a significant advance in performance over the 10–15-μm resolution currently available in ophthalmic OCT systems and, to our knowledge, is the highest resolution for in vivo ophthalmologic imaging achieved to date. This resolution enables in vivo visualization of intraretinal and intra-corneal architectural morphology that had previously only been possible with histopathology. We demonstrate image processing and segmentation techniques for automatic identification and quantification of retinal morphology. Ultrahigh-resolution OCT promises to enhance early diagnosis and objective measurement for tracking progression of ocular diseases, as well as monitoring the efficacy of therapy.

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.

Detection of Macular Ganglion Cell Loss in Glaucoma by Fourier-Domain Optical Coherence Tomography

PURPOSE To map ganglion cell complex (GCC) thickness with high-speed Fourier-domain optical coherence tomography (FD-OCT) and compute novel macular parameters for glaucoma diagnosis. DESIGN Observational, cross-sectional study. PARTICIPANTS One hundred seventy-eight participants in the Advanced Imaging for Glaucoma Study, divided into 3 groups: 65 persons in the normal group, 78 in the perimetric glaucoma group (PG), and 52 in the preperimetric glaucoma group (PPG). METHODS The RTVue FD-OCT system was used to map the macula over a 7 x 6 mm region. The macular OCT images were exported for automatic segmentation using software we developed. The program measured macular retinal (MR) thickness and GCC thickness. The GCC was defined as the combination of nerve fiber, ganglion cell, and inner plexiform layers. Pattern analysis was applied to the GCC map and the diagnostic powers of pattern-based diagnostic parameters were investigated. Results were compared with time-domain (TD) Stratus OCT measurements of MR and circumpapillary nerve fiber layer (NFL) thickness. MAIN OUTCOME MEASURES Repeatability was assessed by intraclass correlation, pooled standard deviation, and coefficient of variation. Diagnostic power was assessed by the area under the receiver operator characteristic (AROC) curve. Measurements in the PG group were the primary measures of performance. RESULTS The FD-OCT measurements of MR and GCC averages had significantly better repeatability than TD-OCT measurements of MR and NFL averages. The FD-OCT GCC average had significantly (P = 0.02) higher diagnostic power (AROC = 0.90) than MR (AROC = 0.85 for both FD-OCT and TD-OCT) in differentiating between PG and normal. One GCC pattern parameter, global loss volume, had significantly higher AROC (0.92) than the overall average (P = 0.01). The diagnostic powers of the best GCC parameters were statistically equal to TD-OCT NFL average. CONCLUSIONS The higher speed and resolution of FD-OCT improved the repeatability of macular imaging compared with standard TD-OCT. Ganglion cell mapping and pattern analysis improved diagnostic power. The improved diagnostic power of macular GCC imaging is on par with, and complementary to, peripapillary NFL imaging. Macular imaging with FD-OCT is a useful method for glaucoma diagnosis and has potential for tracking glaucoma progression.

Optical Coherence Tomography Measurement of Macular and Nerve Fiber Layer Thickness in Normal and Glaucomatous Human Eyes

PURPOSE To evaluate the hypothesis that macular thickness correlates with the diagnosis of glaucoma. DESIGN Cross-sectional study. PARTICIPANTS We studied 367 subjects (534 eyes), including 166 eyes of 109 normal subjects, 83 eyes of 58 glaucoma suspects, 196 eyes of 132 early glaucoma patients, and 89 eyes of 68 advanced glaucoma patients. METHODS We used optical coherence tomography (OCT) to measure macular and nerve fiber layer (NFL) thickness and to analyze their correlation with each other and with glaucoma status. We used both the commercial and prototype OCT units and evaluated correspondence between measurements performed on the same eyes on the same days. MAIN OUTCOME MEASURE Macular and NFL thickness as measured by OCT. RESULTS All NFL parameters both in prototype and commercial OCT units were statistically significantly different comparing normal subjects and either early or advanced glaucoma (P < 0.001). Inner ring, outer ring, and mean macular thickness both in prototype and commercial OCT devices were found to be significantly different between normal subjects and advanced glaucomatous eyes (P < 0.001). The outer ring was the only macular parameter that could significantly differentiate between normal and early glaucoma with either the prototype or commercial OCT unit (P = 0.003, P = 0.008, respectively). The area under the receiver operator characteristic (AROC) curves comparing mean NFL thickness between normal and advanced glaucomatous eyes was 1.00 for both the prototype and commercial OCT devices for eyes scanned on both machines on the same day. The AROC comparing mean macular thickness in normal and advanced glaucomatous eyes scanned on both machines on the same day was 0.88 for the prototype OCT device and 0.80 for the commercial OCT. CONCLUSIONS Both macular and NFL thickness as measured by OCT showed statistically significant correlations with glaucoma, although NFL thickness showed a stronger association than macular thickness. There was good correspondence between findings using both the prototype and commercial OCT units. Macular and NFL thickness measurements made with OCT may have usefulness in the clinical assessment of glaucoma.

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.

Characterization of Epiretinal Membranes Using Optical Coherence Tomography

OBJECTIVE To evaluate optical coherence tomography (OCT), a novel noncontact and noninvasive imaging technique, for the diagnosis and quantitative characterization of epiretinal membranes. METHODS Optical coherence tomography is similar to an ultrasound B-scan, except that light rather than sound is used, which enables higher resolution. Over a 2-year period, OCT was used to examine 186 eyes of 160 patients who had a diagnosis of an epiretinal membrane. Optical coherence tomograms were correlated with visual acuity, slit-lamp biomicroscopy, fluorescein angiography, and funds photography. RESULTS Based on OCT, the epiretinal membrane was clearly separated from the retina with focal points of attachment in 49 eyes and globally adherent (no observed separation) in 125 eyes. Globally adherent membranes were associated with the following features: macular pseudohole (32 eyes), a difference in optical reflectivity between the membrane and retina (65 eyes), and/or a visible membrane tuft or edge (92 eyes). The membrane was undetectable on OCT in 12 eyes. The membrane thickness (mean +/- standard deviation) was 61 +/- 28 microns in the 169 eyes in which the thickness could be measured with OCT. Mean central macular thickness measured with OCT correlated with visual acuity (R2 = 0.73). CONCLUSION Optical coherence tomography was able to provide a structural assessment of the macula that was useful in the preoperative and postoperative evaluation of epiretinal membrane surgery. Quantitative measurements and the assessment of membrane adherence with OCT may be useful in characterizing the surgical prognosis of eyes with an epiretinal membrane.

Ultrahigh speed 1050nm swept source / Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second

We demonstrate ultrahigh speed swept source/Fourier domain ophthalmic OCT imaging using a short cavity swept laser at 100,000 - 400,000 axial scan rates. Several design configurations illustrate tradeoffs in imaging speed, sensitivity, axial resolution, and imaging depth. Variable rate A/D optical clocking is used to acquire linear-in-k OCT fringe data at 100 kHz axial scan rate with 5.3 um axial resolution in tissue. Fixed rate sampling at 1 GSPS achieves a 7.5mm imaging range in tissue with 6.0 um axial resolution at 100 kHz axial scan rate. A 200 kHz axial scan rate with 5.3 um axial resolution over 4mm imaging range is achieved by buffering the laser sweep. Dual spot OCT using two parallel interferometers achieves 400 kHz axial scan rate, almost 2X faster than previous 1050 nm ophthalmic results and 20X faster than current commercial instruments. Superior sensitivity roll-off performance is shown. Imaging is demonstrated in the human retina and anterior segment. Wide field 12x12 mm data sets include the macula and optic nerve head. Small area, high density imaging shows individual cone photoreceptors. The 7.5 mm imaging range configuration can show the cornea, iris, and anterior lens in a single image. These improvements in imaging speed and depth range provide important advantages for ophthalmic imaging. The ability to rapidly acquire 3D-OCT data over a wide field of view promises to simplify examination protocols. The ability to image fine structures can provide detailed information on focal pathologies. The large imaging range and improved image penetration at 1050 m wavelengths promises to improve performance for instrumentation which images both the retina and anterior eye. These advantages suggest that swept source OCT at 1050 nm wavelengths will play an important role in future ophthalmic instrumentation.