Yanling Ouyang

Diurnal variation of choroidal thickness in normal, healthy subjects measured by spectral domain optical coherence tomography.

PURPOSE To describe the pattern and magnitude of diurnal variation of choroidal thickness (CT), its relation to systemic and ocular factors, and to determine the intervisit reproducibility of diurnal patterns. METHODS A prospective study was conducted on 12 healthy volunteers who each underwent sequential ocular imaging on two separate days at five fixed, 2-hour time intervals. Spectral domain optical coherence tomography (OCT) with enhanced depth imaging and image tracking was performed using a standardized protocol. Choroidal and retinal thicknesses were independently assessed by two masked graders. CT diurnal variation was assessed using repeated-measures ANOVA. RESULTS A significant diurnal variation in CT was observed, with mean maximum CT of 372.2 μm, minimum of 340.6 μm (P < 0.001), and mean diurnal amplitude of 33.7 μm. Retinal thickness (mean, 235.0 μm) did not exhibit significant diurnal variation (P = 0.621). The amplitude of CT variation was significantly greater for subjects with thicker morning baseline CT compared with those with thin choroids (43.1 vs. 10.5 μm, P < 0.001). There were significant correlations between amplitude of CT and age (P = 0.032), axial length (P < 0.001), and spherical equivalent (P < 0.001). The change in CT also correlated with change in systolic blood pressure (P = 0.031). Comparing CT on two different days, a similar diurnal pattern was observed, with no significant difference between corresponding measurements at the same time points (P = 0.180). CONCLUSIONS There is significant diurnal variation of CT, with good intervisit reproducibility of diurnal patterns on two different days. The amplitude of variation varies with morning baseline CT, and is correlated with age, axial length, refractive error, and change in systolic blood pressure.

Optical coherence tomography-based observation of the natural history of drusenoid lesion in eyes with dry age-related macular degeneration.

PURPOSE To use spectral domain optical coherence tomography (SD-OCT) to investigate risk factors predictive for the development of atrophy of drusenoid lesions (DLs) (drusen and drusenoid pigment epithelium detachment) in eyes with non-neovascular age-related macular degeneration (NNVAMD). DESIGN Cohort study. PARTICIPANTS Forty-one eyes from 29 patients with NNVAMD. METHODS Patients with NNVAMD who underwent registered SD-OCT imaging over a minimum period of 6 months were reviewed. Drusenoid lesions that were accompanied by new atrophy onset at 6 months or last follow-up (FUL) were further analyzed. Detailed lesion change was described throughout the study period. Odds ratios (ORs) and risk for new local atrophy onset were calculated. MAIN OUTCOME MEASURES Drusenoid lesion features and longitudinal changes in features, including maximum lesion height, lesion diameter, lesion internal reflectivity, and presence and extent of overlying intraretinal hyperreflective foci (HRF). Subfoveal choroidal thickness (SFCT) and choroidal thickness (CT) were measured below each lesion. RESULTS A total of 543 individual DLs were identified at baseline, and 28 lesions developed during follow-up. The mean follow-up time was 21.3±8.6 months (range, 6-44 months). Some 3.2% of DLs (18/571) progressed to atrophy within 18.3 ± 9.5 months (range, 5-28 months) of the initial visit. Drusenoid lesions with heterogeneous internal reflectivity were significantly associated with new atrophy onset at 6 months (OR, 5.614; 95% confidence interval [CI], 1.277-24.673) and new atrophy onset at FUL (OR, 7.005; 95% CI, 2.300-21.337). Lesions with the presence of HRF were significant predictors of new atrophy onset at 6 months (OR, 30.161; 95% CI, 4.766-190.860) and FUL (OR, 11.211; 95% CI, 2.513-50.019). Lesions with a baseline maximum height >80 μm or CT ≤ 135 μm showed a positive association with the new atrophy onset at FUL (OR, 7.886; 95% CI, 2.105-29.538 and OR, 3.796; 95% CI, 1.154-12.481, respectively). CONCLUSIONS The presence of HRF overlying DLs, a heterogeneous internal reflectivity of these lesions, was found consistently to be predictive of local atrophy onset in the ensuing months. These findings provide further insight into the natural history of anatomic change occurring in patients with NNVAMD.

Detection of Cystoid Macular Edema with Three-Dimensional Optical Coherence Tomography versus Fluorescein Angiography

PURPOSE To compare the sensitivity and reproducibility of three-dimensional optical coherence tomography (3D-OCT) and fluorescein angiography (FA) for the detection of cystoid macular edema (CME). METHODS Data were retrospectively collected from all patients who underwent digital FA and 512 × 128 horizontal raster 3D-OCT scans on the same day in a retina subspecialty clinic. Images were reviewed independently by four reading center graders and adjudicated as a group to render a single result for each eye and each imaging modality. The κ statistic was used to determine the level of agreement between graders for each modality. The sensitivity of each imaging modality for CME detection was calculated by using the presence of CME on either modality as the ground truth; subgroup analysis was performed according to disease diagnosis and lens status. RESULTS Four hundred thirteen eyes of 207 patients were included in the analysis. Intergrader agreement was higher for 3D-OCT than for FA both before (κ(OCT) = 0.61, κ(FA) = 0.43) and after adjudication (κ(OCT) = 0.74, κ(FA) = 0.58).The sensitivity for detection of definite CME was higher for 3D-OCT (95%, 144/151 cases) than for FA (44%, 67/151 cases). Definite FA (+) 3D-OCT (-) CME was identified in 1 eye (0.2%), whereas definite FA (-) 3D-OCT (+) CME was identified in 40 eyes (10%). No significant associations between CME detection and lens examination or disease diagnosis were observed. CONCLUSIONS In this study, 3D-OCT was more sensitive and had better intergrader agreement than did FA for the detection of CME.

Semiautomated Segmentation of the Choroid in Spectral-Domain Optical Coherence Tomography Volume Scans

PURPOSE Changes in the choroid, in particular its thickness, are believed to be of importance in the pathophysiology of a number of retinal diseases. The purpose of this study was to adapt the graph search algorithm to semiautomatically identify the choroidal layer in spectral-domain optical coherence tomography (SD-OCT) volume scans and compare its performance to manual delineation. METHODS A graph-based multistage segmentation approach was used to identify the choroid, defined as the layer between the outer border of the RPE band and the choroid-sclera junction. Thirty randomly chosen macular SD-OCT (1024 × 37 × 496 voxels, Heidelberg Spectralis) volumes were obtained from 20 healthy subjects and 10 subjects with non-neovascular AMD. The positions of the choroidal borders and resultant thickness were compared with consensus manual delineation performed by two graders. For consistency of the statistical analysis, the left eyes were horizontally flipped in the x-direction. RESULTS The algorithm-defined position of the outer RPE border and choroid-sclera junction was consistent with the manual delineation, resulting in highly correlated choroidal thickness values with r = 0.91 to 0.93 for the healthy subjects and 0.94 for patients with non-neovascular AMD. Across all cases, the mean and absolute differences between the algorithm and manual segmentation for the outer RPE boundary was -0.74 ± 3.27 μm and 3.15 ± 3.07 μm; and for the choroid-sclera junction was -3.90 ± 15.93 μm and 21.39 ± 10.71 μm. CONCLUSIONS Excellent agreement was observed between the algorithm and manual choroidal segmentation in both normal eyes and those with non-neovascular AMD. The choroid was thinner in AMD eyes. Semiautomated choroidal thickness calculation may be useful for large-scale quantitative studies of the choroid.

Comparison of manually corrected retinal thickness measurements from multiple spectral-domain optical coherence tomography instruments

Background/aims To compare retinal thickness measurements from three different spectral domain optical coherence instruments when manual segmentation is employed to standardise retinal boundary locations. Methods 40 eyes of 21 healthy subjects were scanned on the Cirrus HD-OCT, Topcon 3D-OCT-2000 and Heidelberg Spectralis-OCT. Raw data were imported into custom grading software (3D-OCTOR). Manual segmentation was performed on every data set, and retinal thickness values in the foveal central subfield were computed. Results 37 eyes of 20 subjects were gradable on every machine. The average retinal thicknesses for these eyes were 236.7 μm (SD 20.1), 235.7 μm (SD 20.4) and 236.5 μm (SD 18.0) for the Cirrus, 3D-OCT-2000 and Spectralis, respectively. Comparing manual retinal thickness measurements between any two machines, the maximum difference was 18.2 μm. The mean absolute differences per eye between two machines were: 4.9 μm for Cirrus versus 3D-OCT-2000, 3.7 μm for Cirrus versus Spectralis and 4.4 μm for 3D-OCT-2000 versus Spectralis. Conclusions When a uniform position is used to locate the outer retinal boundary, the retinal thickness measurements derived from three different spectral domain optical coherence instruments devices are virtually identical. Manual correction may allow OCT-derived thickness measurements to be compared between devices in clinical trials and clinical research.

Different phenotypes of the appearance of the outer plexiform layer on optical coherence tomography

PurposeTo present a selected case series of different phenotypes of the normal outer plexiform layer (OPL) visualized by optical coherence tomography (OCT).MethodsFive cases were selected to represent the spectrum of appearances of the OPL in this case series. Categorical descriptions of each manifestation were then developed. Additional SD-OCT scans were obtained from a normal volunteer to further support the hypothesis.ResultsThe inner one-third of the OPL typically appears hyperreflective on OCT, while the outer two-thirds (Henle fiber layer) may have a more varied appearance. Six different phenotypes of Henle fiber layer reflectivity were noted in this series, and classified as: bright, columnar, dentate, delimited, indistinct, and dark. The brightness of the Henle fiber layer appears to depend on the geometric angle between the OCT light beam and the axonal fibers in this portion of the OPL. This angle appears to be a function of the natural orientation of the Henle fiber layer tissue (θN), the existence of subretinal pathology that alters the angle of the neurosensory retina (θP), and the tilt angle of the tissue on the B-scan (θT) due to decentered OCT acquisition.ConclusionsSince accurate interpretation of the OPL/ONL boundary is of vital importance to study the thickness of ONL, location of cystoid lesions, hyperreflective crescents over drusen, et al., our case series may aid better understanding of the OPL appearance in SD-OCT. In the absence of clear delineation, it may be most correct to refer to indistinct OPL and ONL together as the photoreceptor nuclear axonal complex (PNAC).

Clinical Significance of B-Scan Averaging With SD-OCT

Averaging multiple scans is a potential advantage of optical coherence tomography. The authors evaluate the qualitative benefits of B-scan averaging on the visualization of outer retinal structures. A retrospective analysis was performed on Cirrus OCT (Carl Zeiss Meditec, Dublin, CA) B-scans from 1 eye of 35 patients referred to the imaging unit who underwent three types of scan acquisitions: no averaging, 4× averaging, and 20× averaging. Masked assessment of quality was made using a qualitative scale of 0 (worst) to 3 according to the ability to identify structure, brightness, and continuity. Quality scores consistently improved with 4× averaging, but improved only slightly further with 20×. Averaging appeared to have a statistically significant beneficial effect for the assessment of the external limiting membrane and outer nuclear layer (P < .05), with no significant benefit for visualization of the retinal pigment epithelium and inner segment/outer segment junction. The benefits of oversampling or averaging B-scans for visualizing outer retinal substructures are apparent even when averaging relatively few frames. These findings may be helpful when designing acquisition protocols in clinical trials and clinical practice.

The Retinal Disease Screening Study: Prospective Comparison of Nonmydriatic Fundus Photography and Optical Coherence Tomography for Detection of Retinal Irregularities

PURPOSE To compare the sensitivity of volume scanning with optical coherence tomography (OCT) to nonmydriatic color fundus photography (FP) for the detection of retinal irregularities in asymptomatic populations. METHODS Asymptomatic subjects without known ocular disease were recruited over a 6-month period. For each eye, two undilated 45° fundus images and four undilated volume OCT image sets covering the macula and optic nerve were obtained. Color images were evaluated for irregularities both inside and outside the area covered by OCT. OCT image sets were evaluated for internal limiting membrane irregularities, abnormal retinal thickness, hyper/hyporeflective features, and photoreceptor/retinal pigment epithelium (RPE) irregularities. Detection sensitivities were compared and false-negative cases were analyzed. RESULTS A total of 284 eyes (144 subjects) were included, with a mean age of 38.1 years (range 18-77). Among 253 eyes (135 subjects) with gradable images from both FP and OCTs, the detection sensitivities for OCT were higher (96.2% infield and 85.7% in full field) than for FP (19.9% infield and 43.8% in full field) for all irregularities evaluated in the study (including epiretinal irregularities, abnormal retinal thickness, intraretinal hyperreflective/hyporeflective features, and photoreceptor/RPE irregularities). Overall, the presence of definite irregularities on either fundus imaging or OCT by eye in this asymptomatic population was 42.6% (121/284), with 39.4% (112/284) of eyes having RPE irregularities such as drusen. CONCLUSIONS For detection of a variety of retinal irregularities evaluated in the current study, volume OCT scanning was more sensitive than nonmydriatic retinal photography in our asymptomatic individuals. OCT detected clinically relevant disease features, such as subretinal fluid, that were missed by FP, and had a lower ungradable image rate. It is likely that OCT will be added to photography screening in the near future for chorioretinal disease.

Simple Estimation of Clinically Relevant Lesion Volumes Using Spectral Domain–Optical Coherence Tomography in Neovascular Age-Related Macular Degeneration

PURPOSE To evaluate simple methods of estimating the volume of clinically relevant features in neovascular age-related macular degeneration (NVAMD) using spectral domain-optical coherence tomography (SD-OCT). METHODS Using a database of NVAMD cases imaged with macular cube (512 A-scans × 128 B-scans) SD-OCT scans, the authors retrospectively selected visits where cystoid macular edema (CME), subretinal fluid (SRF), or pigment epithelial detachments (PEDs) were evident. Patients with single visits were analyzed in the cross-sectional analysis (CSA) and those with a baseline visit and three or more follow-up visits in the longitudinal analysis (LA). The volume of each feature was measured by manual grading using validated grading software. Simplified measurements for each feature included: number of B-scans or A-scans involved and maximum height. Automated measurements of total macular volume and foveal central subfield were also collected from each machine. Correlations were performed between the volumes measured with 3D-OCTOR, automated measurements, and the simplified measures. RESULTS Forty-five visits for 25 patients were included in this study: 26 cube scans from 26 eyes of 25 patients in the CSA and 24 scans from 5 eyes of 5 patients in the LA. The simplified measures that correlated best with manual grading in the CSA group were maximum lesion height for CME (r² value = 0.96) and B-scan count for SRF and PED volume (r² values of 0.88 and 0.70). In the LA group, intervisit differences were correlated. Change in B-scan count correlated well with change in SRF volume (r² = 0.97), whereas change in maximum height correlated with change in CME and PED volume (r² = 0.98 and 0.43, respectively). CONCLUSIONS These data suggest that simplified estimators of some NVAMD lesion volumes exist and are accessible by clinicians without the need for specialized software or time-consuming manual segmentation. These simple approaches could enhance quantitative disease monitoring strategies in clinical trials and clinical practice.

Acute severe visual decrease after photodynamic therapy with verteporfin: spectral-domain OCT features.

In this report, spectral-domain optical coherence tomography (OCT) was used to characterize the acute morphologic alterations that occur when photodynamic therapy with verteporfin results in an acute severe visual decrease. The clinical and imaging records of a patient with neovascular age-related macular degeneration who suffered this complication were reviewed. Using spectral-domain OCT, two relatively distinct subretinal fluid compartments were visualized: a sparsely hyperreflective pocket of subretinal fluid overlying the fibrovascular pigment epithelial detachment, consistent with fibrinous exudation, and a more homogeneously hyporeflective compartment at the periphery of the choroidal neovascular lesion, consistent with serous exudation. The higher axial resolution, and greater sensitivity, of spectral-domain OCT allows improved visualization of the subretinal space. As experience with spectral-domain OCT grows, new parameters will emerge-such as those related to subretinal fluid-that will facilitate improvements in both the qualitative and quantitative evaluation of macular disease.