Amirhossein Hariri

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.

Segmentation of the Geographic Atrophy in Spectral- Domain Optical Coherence Tomography and Fundus Autofluorescence Images

PURPOSE Geographic atrophy (GA) is the atrophic late-stage manifestation of age-related macular degeneration (AMD), which may result in severe vision loss and blindness. The purpose of this study was to develop a reliable, effective approach for GA segmentation in both spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) images using a level set-based approach and to compare the segmentation performance in the two modalities. METHODS To identify GA regions in SD-OCT images, three retinal surfaces were first segmented in volumetric SD-OCT images using a double-surface graph search scheme. A two-dimensional (2-D) partial OCT projection image was created from the segmented choroid layer. A level set approach was applied to segment the GA in the partial OCT projection image. In addition, the algorithm was applied to FAF images for the GA segmentation. Twenty randomly chosen macular SD-OCT (Zeiss Cirrus) volumes and 20 corresponding FAF (Heidelberg Spectralis) images were obtained from 20 subjects with GA. The algorithm-defined GA region was compared with consensus manual delineation performed by certified graders. RESULTS The mean Dice similarity coefficients (DSC) between the algorithm- and manually defined GA regions were 0.87 ± 0.09 in partial OCT projection images and 0.89 ± 0.07 in registered FAF images. The area correlations between them were 0.93 (P < 0.001) in partial OCT projection images and 0.99 (P < 0.001) in FAF images. The mean DSC between the algorithm-defined GA regions in the partial OCT projection and registered FAF images was 0.79 ± 0.12, and the area correlation was 0.96 (P < 0.001). CONCLUSIONS A level set approach was developed to segment GA regions in both SD-OCT and FAF images. This approach demonstrated good agreement between the algorithm- and manually defined GA regions within each single modality. The GA segmentation in FAF images performed better than in partial OCT projection images. Across the two modalities, the GA segmentation presented reasonable agreement.

COMPARISON OF MANUAL AND SEMIAUTOMATED FUNDUS AUTOFLUORESCENCE ANALYSIS OF MACULAR ATROPHY IN STARGARDT DISEASE PHENOTYPE.

Purpose: To evaluate manual and semiautomated grading techniques for assessing decreased fundus autofluorescence (DAF) in patients with Stargardt disease phenotype. Methods: Certified reading center graders performed manual and semiautomated (region finder—based) grading of confocal scanning laser ophthalmoscopy (cSLO) fundus autofluorescence (FAF) images for 41 eyes of 22 patients. Lesion types were defined based on the black level and sharpness of the border: definite decreased autofluorescence (DDAF), well, and poorly demarcated questionably decreased autofluorescence (WDQDAF, PDQDAF). Agreement in grading between the two methods and inter- and intra-grader agreement was assessed by kappa coefficients (&kgr;) and intraclass correlation coefficients (ICC). Results: The mean ± standard deviation (SD) area was 3.07 ± 3.02 mm2 for DDAF (n = 31), 1.53 ± 1.52 mm2 for WDQDAF (n = 9), and 6.94 ± 10.06 mm2 for PDQDAF (n = 17). The mean ± SD absolute difference in area between manual and semiautomated grading was 0.26 ± 0.28 mm2 for DDAF, 0.20 ± 0.26 mm2 for WDQDAF, and 4.05 ± 8.32 mm2 for PDQDAF. The ICC (95% confidence interval) for method comparison was 0.992 (0.984–0.996) for DDAF, 0.976 (0.922–0.993) for WDQDAF, and 0.648 (0.306–0.842) for PDQDAF. Inter- and intra-grader agreement in manual and semiautomated quantitative grading was better for DDAF (0.981–0.996) and WDQDAF (0.995–0.999) than for PDQDAF (0.715–0.993). Conclusion: Manual and semiautomated grading methods showed similar levels of reproducibility for assessing areas of decreased autofluorescence in patients with Stargardt disease phenotype. Excellent agreement and reproducibility were observed for well demarcated lesions.

Effect of angle of incidence on macular thickness and volume measurements obtained by spectral-domain optical coherence tomography.

PURPOSE Evaluation of the effect of angle of incidence on macular thickness and volume measurements obtained by spectral-domain optical coherence tomography (OCT). METHODS A total of 30 eyes from 15 healthy young subjects underwent macular cube volume scans (512 × 128 protocol) following dilation using the Cirrus spectral domain OCT. For each eye, scans were obtained by positioning the scanning beam in the center of the dilated pupil, as well as in four eccentric positions (approximately 3 mm from the center), superior, inferior, nasal, and temporal to the pupillary center, to create oblique angles of incidence between the light beam and retina. In all cases, the region scanned by the volume cube was centered on the fovea. Macular thickness and volume measurements were computed for volume scan acquisitions, and differences in values between eccentric scans and the central scan were analyzed. RESULTS Retinal thickness and volume values were observed to increase significantly in all subfields for all eccentrically-obtained scans compared to scans obtained through the center of the pupil. The mean increase in thickness for the various scan positions and subfields ranged from 3.76 to 11.38. Scans that were displaced temporally consistently showed the greatest increase in thickness and volume, whereas nasally positioned scans showed the least increase. The increase in retinal thickness for all subfields correlated significantly with angle of inclination or tilting of the retina. CONCLUSIONS Macular thickness and volume measurement results may be affected significantly by positioning of the scanning beam in the pupil and resultant angle of incidence on the retina. These findings suggest that care should be taken to position the scanning beam consistently in the center of the pupil to achieve reliable measurements.

Quantitative OCT Subanalysis of Eyes With Choroidal Neovascularization Switched From Multiple Injections of Bevacizumab or Ranibizumab to Intravitreal Aflibercept

BACKGROUND AND OBJECTIVE To assess the early therapeutic response after switching from multiple injections of bevacizumab or ranibizumab to aflibercept in eyes with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS SD-OCT scans of patients with neovascular AMD that was suboptimally responsive to multiple injections of bevacizumab or ranibizumab who were switched to aflibercept were analyzed. After segmenting these scans, the relevant volumes were computed and compared at the various time points by Students t test. RESULTS After switching to aflibercept, converse to the outcome of the last injection of bevacizumab or ranibizumab, statistically significant decreases of 0.32 mm(3) in neurosensory retinal volume, 0.08 mm(3) in subretinal fluid, and 0.56 mm(3) in pigment epithelial detachment were observed (P = .01, .04, and .001, respectively). The mean ETDRS visual acuity increased from 62 to 65 letters after switching (P = .04). These favorable outcomes were sustained after three monthly injections of the new drug. CONCLUSION Switching to aflibercept therapy in eyes with persistent fluid after multiple intravitreal injections of bevacizumab or ranibizumab was associated with an early reduction in all fluid compartments and improvement in visual acuity.

Predictors of Macular Atrophy Detected by Fundus Autofluorescence in Patients With Neovascular Age-Related Macular Degeneration After Long-Term Ranibizumab Treatment.

BACKGROUND AND OBJECTIVE To study the relationship between baseline morphologic characteristics of the choroidal neovascular (CNV) lesion and long-term development of macular atrophy in eyes with neovascular age-related macular degeneration (AMD) treated with ranibizumab (Lucentis; Genentech, South San Francisco, CA). PATIENTS AND METHODS Certified graders evaluated baseline and 7-year follow-up (SEVEN-UP study) images of 41 eyes from the MARINA/ANCHOR and HORIZON trials. Using GRADOR software and stepwise linear regression, graders correlated lesion characteristics on fluorescein angiography (FA) at both visits with areas of definite decreased autofluorescence (DDAF) on fundus autofluorescence (FAF) imaging at the SEVEN-UP visit. RESULTS Three of 41 eyes (7.3%) had macular atrophy on FA at baseline (mean ± standard deviation [SD] size: 0.29 mm(2) ± 1.50 mm(2)), 29 (70.7%) at SEVEN-UP (mean ± standard deviation [SD] area: 7.42 mm(2) ± 7.97 mm(2)). On FAF imaging at the SEVEN-UP visit, all 41 eyes (100%) had DDAF (mean ± SD size: 10.29 mm(2) ± 8.07 mm(2)). Variables significantly associated with area of DDAF at the SEVEN-UP visit were the area of leaking CNV lesion components (coefficient: 0.953; P < .001), the area of other lesion components (coefficient: 1.094; P = .038), and the area of retinal pigment epithelial (RPE) atrophy (coefficient: 1.334; P = .040) on baseline FA imaging. CONCLUSION The area of DDAF at more than 7 years after initiation of ranibizumab therapy was 35% larger than the original CNV lesion. The baseline area of leaking CNV and other components of the CNV lesion and the baseline area of RPE atrophy were important predictors of the area of definite decreased autofluorescence, presumably corresponding to areas of photoreceptor and RPE loss. The findings from this study may guide hypothesis generation for future AMD trials.

Multiple layer segmentation and analysis in three-dimensional spectral-domain optical coherence tomography volume scans

Abstract. Spectral-domain optical coherence tomography (SD-OCT) is a three-dimensional imaging technique that allows direct visualization of retinal morphology and architecture. The various retinal layers may be affected differentially by various diseases. An automated graph search algorithm is developed to sequentially segment 11 retinal surfaces in SD-OCT volumes using a three-stage approach. In stage 1, the four most easily discernible and/or distinct surfaces are identified in four-times-downsampled images and are used as a priori information to limit the graph search for the other surfaces in stage 2. Eleven surfaces were then detected in two-times-downsampled images in stage 2, and refined in the original images in stage 3 using the graph search integrating the estimated morphological shape models. Twenty macular SD-OCT volume scans from 20 normal subjects are used in this initial study. The overall mean and absolute mean differences in border positions between the automated and manual segmentation for the 11 surfaces are −0.20±0.53 voxels (−0.76±2.06  μm) and 0.82±0.64 voxels (3.19±2.46  μm), respectively. Intensity/reflectivity and thickness properties in various retinal layers are also investigated. This investigation in normal subjects may provide a comparative reference for subsequent adaptations in eyes with diseases.

Optical coherence tomographic correlates of angiographic subtypes of occult choroidal neovascularization.

PURPOSE To compare the optical coherence tomographic (OCT) correlates of two previously described angiographic subtypes of occult choroidal neovascularization (CNV). METHODS We retrospectively analyzed 17 consecutive patients with previously untreated occult CNV who underwent both fluorescein angiography (FA) and volume spectral domain (SD)-OCT imaging on the same visit. Planimetric grading was performed on the FA images by certified reading center graders to precisely outline the boundaries of the fibrovascular pigment epithelial detachment (FVPED) and/or late leakage of undetermined source (LLUS) components of occult CNV for each case. In the SD-OCT images, the outer retinal pigment epithelial (RPE) and inner choroidal boundaries were manually segmented on all B-scans to generate a PED thickness map. Fluorescein angiography images were manually registered with the OCT fundus image, and the PED thickness was correlated with the angiographic lesion component present at each corresponding point in the fundus. RESULTS Point-to-point correlations revealed that PED thickness was significantly different in areas of FVPED versus areas of LLUS. Whereas the mean PED thickness in areas of FVPED was 196.1 ± 120.36 μm, it was only 38.42 ± 8.14 μm in areas of LLUS (P = 0.003). Normalized internal reflectivity in areas of FVPED was lower than in areas of LLUS (0.12 ± 0.11 vs. 0.24 ± 0.07; P = 0.03). The integrity or continuity of the overlying RPE band on OCT, however, did not appear to differ between areas of LLUS and FVPED (P = 0.33). CONCLUSIONS Although LLUS and FVPED appear to be distinct angiographic subtypes of CNV, the major difference between the two is the height of the RPE elevation and the internal reflectivity, with areas of LLUS representing much shallower RPE elevations with brighter mean internal reflectivity.

Automated multilayer segmentation and characterization in 3D spectral-domain optical coherence tomography images

Spectral-domain optical coherence tomography (SD-OCT) is a 3-D imaging technique, allowing direct visualization of retinal morphology and architecture. The various layers of the retina may be affected differentially by various diseases. In this study, an automated graph-based multilayer approach was developed to sequentially segment eleven retinal surfaces including the inner retinal bands to the outer retinal bands in normal SD-OCT volume scans at three different stages. For stage 1, the four most detectable and/or distinct surfaces were identified in the four-times-downsampled images and were used as a priori positional information to limit the graph search for other surfaces at stage 2. Eleven surfaces were then detected in the two-times-downsampled images at stage 2, and refined in the original image space at stage 3 using the graph search integrating the estimated morphological shape models. Twenty macular SD-OCT (Heidelberg Spectralis) volume scans from 20 normal subjects (one eye per subject) were used in this study. The overall mean and absolute mean differences in border positions between the automated and manual segmentation for all 11 segmented surfaces were -0.20 ± 0.53 voxels (-0.76 ± 2.06 μm) and 0.82 ± 0.64 voxels (3.19 ± 2.46 μm). Intensity and thickness properties in the resultant retinal layers were investigated. This investigation in normal subjects may provide a comparative reference for subsequent investigations in eyes with disease.

Three-dimensional choroidal segmentation in spectral OCT volumes using optic disc prior information

Recently, much attention has been focused on determining the role of the peripapillary choroid - the layer between the outer retinal pigment epithelium (RPE)/Bruchs membrane (BM) and choroid-sclera (C-S) junction, whether primary or secondary in the pathogenesis of glaucoma. However, the automated choroidal segmentation in spectral-domain optical coherence tomography (SD-OCT) images of optic nerve head (ONH) has not been reported probably due to the fact that the presence of the BM opening (BMO, corresponding to the optic disc) can deflect the choroidal segmentation from its correct position. The purpose of this study is to develop a 3D graph-based approach to identify the 3D choroidal layer in ONH-centered SD-OCT images using the BMO prior information. More specifically, an initial 3D choroidal segmentation was first performed using the 3D graph search algorithm. Note that varying surface interaction constraints based on the choroidal morphological model were applied. To assist the choroidal segmentation, two other surfaces of internal limiting membrane and innerouter segment junction were also segmented. Based on the segmented layer between the RPE/BM and C-S junction, a 2D projection map was created. The BMO in the projection map was detected by a 2D graph search. The pre-defined BMO information was then incorporated into the surface interaction constraints of the 3D graph search to obtain more accurate choroidal segmentation. Twenty SD-OCT images from 20 healthy subjects were used. The mean differences of the choroidal borders between the algorithm and manual segmentation were at a sub-voxel level, indicating a high level segmentation accuracy.