Ali S. Raza

Automated layer segmentation of macular OCT images using dual-scale gradient information

A novel automated boundary segmentation algorithm is proposed for fast and reliable quantification of nine intra-retinal boundaries in optical coherence tomography (OCT) images. The algorithm employs a two-step segmentation schema based on gradient information in dual scales, utilizing local and complementary global gradient information simultaneously. A shortest path search is applied to optimize the edge selection. The segmentation algorithm was validated with independent manual segmentation and a reproducibility study. It demonstrates high accuracy and reproducibility in segmenting normal 3D OCT volumes. The execution time is about 16 seconds per volume (480x512x128 voxels). The algorithm shows potential for quantifying images from diseased retinas as well.

Toward a clinical protocol for assessing rod, cone, and melanopsin contributions to the human pupil response.

PURPOSE. To better understand the relative contributions of rod, cone, and melanopsin to the human pupillary light reflex (PLR) and to determine the optimal conditions for assessing the health of the rod, cone, and melanopsin pathways with a relatively brief clinical protocol. METHODS. PLR was measured with an eye tracker, and stimuli were controlled with a Ganzfeld system. In experiment 1, 2.5 log cd/m(2) red (640 ± 10 nm) and blue (467 ± 17 nm) stimuli of various durations were presented after dark adaptation. In experiments 2 and 3, 1-second red and blue stimuli were presented at different intensity levels in the dark (experiment 2) or on a 0.78 log cd/m(2) blue background (experiment 3). Based on the results of experiments 1 to 3, a clinical protocol was designed and tested on healthy control subjects and patients with retinitis pigmentosa and Lebers congenital amaurosis. RESULTS. The duration for producing the optimal melanopsin-driven sustained pupil response after termination of an intense blue stimulus was 1 second. PLR rod- and melanopsin-driven components are best studied with low- and high-intensity flashes, respectively, presented in the dark (experiment 2). A blue background suppressed rod and melanopsin responses, making it easy to assess the cone contribution with a red flash (experiment 3). With the clinical protocol, robust melanopsin responses could be seen in patients with few or no contributions from the rods and cones. CONCLUSIONS. It is possible to assess the rod, cone, and melanopsin contributions to the PLR with blue flashes at two or three intensity levels in the dark and one red flash on a blue background.

Retinal Ganglion Cell Layer Thickness and Local Visual Field Sensitivity in Glaucoma

OBJECTIVE To compare loss in sensitivity measured using standard automated perimetry (SAP) with local retinal ganglion cell layer (RGC) thickness measured using frequency-domain optical coherence tomography in the macula of patients with glaucoma. METHODS To compare corresponding locations of RGC thickness with total deviation (TD) of 10-2 SAP for 14 patients with glaucoma and 19 controls, an experienced operator hand-corrected automatic segmentation of the combined RGC and inner plexiform layer (RGC+IPL) of 128 horizontal B-scans. To account for displacement of the RGC bodies around the fovea, the location of the SAP test points was adjusted to correspond to the location of the RGC bodies rather than to the photoreceptors, based on published histological findings. For analysis, RGC+IPL thickness vs SAP (TD) data were grouped into 5 eccentricities, from 3.4° to 9.7° radius on the retina with respect to the fovea. RESULTS The RGC+IPL thickness correlated well with SAP loss within approximately 7.2° of the fovea (Spearman ρ = 0.71-0.74). Agreement was worse (0.53-0.65) beyond 7.2°, where the normal RGC layer is relatively thin. A linear model relating RGC+IPL thickness to linear SAP loss provided a reasonable fit for eccentricities within 7.2°. CONCLUSION In the central 7.2°, local RGC+IPL thickness correlated well with local sensitivity loss in glaucoma when the data were adjusted for RGC displacement.

Evaluation of Inner Retinal Layers in Patients with Multiple Sclerosis or Neuromyelitis Optica Using Optical Coherence Tomography

PURPOSE To evaluate the thickness of the inner retinal layers in the macula using frequency-domain optical coherence tomography (fd-OCT) in patients with demyelinating diseases. DESIGN Cross-sectional study. PARTICIPANTS A total of 301 eyes of 176 subjects were evaluated. Subjects were divided in 5 different groups: controls, neuromyelitis optica (NMO), longitudinally extensive transverse myelitis (LETM), multiple sclerosis with a history of optic neuritis (MS-ON), and multiple sclerosis without a history of optic neuritis (MS non-ON). METHODS The individual layers from macular fd-OCT cube scans were segmented with an automated algorithm and then manually hand-corrected. For each scan, we determined the thickness of the retinal nerve fiber layer (RNFL), the combined retinal ganglion cell and inner plexiform layers (RGCL+), and the inner nuclear layer (INL). MAIN OUTCOME MEASURES Macular RNFL, RGCL+, and INL thickness. RESULTS The RNFL was significantly thinner than in controls for all patient groups (P ≤ 0.01). Macular RGCL+ thickness was significantly thinner than in controls for the NMO, MS-ON, and MS non-ON groups (P<0.001 for the 3 groups). The INL thickness was significantly thicker than in controls for the patients with NMO (P = 0.003) and LETM (P = 0.006) but not for those with MS-ON or MS non-ON. Although the RNFL and RGCL+ were not significantly different between the NMO and MS-ON groups, the patients with NMO had a significantly thicker INL than the patients with MS-ON (P = 0.02). CONCLUSIONS Macular RNFL and RGCL+ demonstrate axonal and neural loss in patients with MS, either with or without ON, and in patients with NMO. In addition, the INL thickening occurs in patients with NMO and patients with LETM, and study of this layer may hold promise for differentiating between NMO and MS.

The Inner Segment/Outer Segment Border Seen on Optical Coherence Tomography Is Less Intense in Patients with Diminished Cone Function

UNLABELLED PURPOSE; The integrity of the inner segment ellipsoid (ISe) band, previously called the inner segment/outer segment (IS/OS) border, seen on optical coherence tomography (OCT) scans is of clinical significance. To better understand the influence of cones on the appearance of this band, the intensity of its signal in patients with diminished cone function was examined. METHODS Horizontal line scans through the fovea of 30 healthy controls, 10 patients with achromatopsia (A), and six with cone dystrophy (CD) were obtained with frequency domain (fd) OCT. The fdOCT borders were segmented with a computer-aided manual technique. The ISe was divided into regions 60.1 μm wide and 19.5 μm deep. The relative ISe intensity of each region was defined as its intensity divided by the intensity of a local region, which extended in depth from the choroid to the retinal ganglion cell/retinal nerve fiber layer. RESULTS Except for the central fovea, all patients had a clear ISe band across the region studied, ± 3 mm from the foveal center. However, the relative ISe intensity was significantly lower (P < 0.0001) in patients (A: 1.14 ± 0.14; CD: 1.27 ± 0.14), than in controls (1.61 ± 0.16). There were no differences in the relative intensity of the other retinal layers. CONCLUSIONS Although present, the intensity of this ISe band is lower in patients with diminished cone function than it is in healthy controls. This is consistent with the hypothesis that both rod and cone receptors must be absent or damaged for the ISe band to be missing.

Prevalence and Nature of Early Glaucomatous Defects in the Central 10° of the Visual Field

IMPORTANCE The macula is essential for visual functioning and is known to be affected even in early glaucoma. However, little is currently understood about the prevalence and nature of central vision loss in early glaucoma. OBJECTIVE To determine the prevalence and characteristics of visual field (VF) defects in the central 10° in glaucoma suspects and patients with mild glaucoma using a prospective design. DESIGN, SETTING, AND PARTICIPANTS This prospective observational cohort study was conducted at an outpatient glaucoma specialty clinic. One hundred eyes from 74 patients with glaucomatous optic neuropathy and a 24-2 VF with mean deviation better than -6 dB were prospectively studied and tested with a 10-2 test. MAIN OUTCOMES AND MEASURES Reliable: VF hemifields were classified as abnormal based on a cluster criterion, and abnormal 10-2 VFs were categorized based on the pattern of abnormal points: arcuatelike, widespread, or other. In addition, at each point of the 10-2 VF, the total deviation values were averaged across eyes and the number of abnormal points with total deviation values below a specific criterion level were calculated. RESULTS There appeared to be as many abnormal 10-2 hemifields (53%) as abnormal 24-2 hemifields (59%). Of the eyes with normal 24-2 hemifields, 16% were classified as abnormal when the 10-2 test was used. Of the abnormal 10-2 hemifields, 68%, 8%, and 25% were arcuatelike, widespread, and other, respectively. The average total deviation values and number of abnormal points plots revealed superior VF defects that were deeper and closer to fixation than those in the inferior VF. CONCLUSIONS AND RELEVANCE The 10-2 VF was abnormal in nearly as many hemifields as was the 24-2 VF, including some with normal 24-2 VF, suggesting that the 24-2 test is not optimal for detecting early damage of the macula. The pattern of the defects was in agreement with a recent model of macular damage.

Early glaucoma involves both deep local, and shallow widespread, retinal nerve fiber damage of the macular region.

PURPOSE To better understand the nature of early glaucomatous damage of the macula by comparing the results from 10-2 visual fields, optical coherence tomography (OCT) macular cube scans, and OCT circumpapillary circle scans. METHODS One eye of each of 66 glaucoma patients or suspects, with a mean deviation (MD) on the 24-2 visual field (VF) test of better than -6 decibels (dB), was prospectively tested with 10-2 VFs and OCT macular cube and circumpapillary circle scans. Thickness and probability maps of the retinal ganglion cell plus inner plexiform (RGC+) layers were generated. A hemifield was considered abnormal if both the macular RGC+ and the 10-2 probability plots were abnormal (cluster criteria). The thickness plots of the circumpapillary retinal nerve fiber layer (RNFL) were analyzed in the context of a model that predicted the region of the disc associated with macular damage. RESULTS Twenty-seven hemifields (20 eyes) had abnormal 10-2 and RGC+ probability plots: 7 in upper VF/inferior retina, 6 in lower VF/superior retina, and 7 in both hemifields. Both shallow widespread and deep local thinning of the circumpapillary RNFL were observed. The local defects were more common and closer to fixation in the upper VF/inferior retina as predicted. CONCLUSIONS A model of glaucomatous damage of the macula predicted the location of both the widespread and local defects in the temporal and inferior disc quadrants. Optical coherence tomography scans of the circumpapillary RNFL and the macular RGC+ layer can aid in the identification of these defects and help in the interpretation of 24-2 and 10-2 VF tests.

Reliability of a computer-aided manual procedure for segmenting optical coherence tomography scans.

Purpose. To assess the within- and between-operator agreement of a computer-aided manual segmentation procedure for frequency-domain optical coherence tomography scans. Methods. Four individuals (segmenters) used a computer-aided manual procedure to mark the borders defining the layers analyzed in glaucoma studies. After training, they segmented two sets of scans, an Assessment Set and a Test Set. Each set had scans from 10 patients with glaucoma and 10 healthy controls. Based on an analysis of the Assessment Set, a set of guidelines was written. The Test Set was segmented twice with a ≥1 month separation. Various measures were used to compare test and retest (within-segmenter) variability and between-segmenter variability including concordance correlations between layer borders and the mean across scans (n = 20) of the mean of absolute differences between local border locations of individual scans, MEAN{mean( &Dgr;LBL )}. Results. Within-segmenter reliability was good. The mean concordance correlations values for an individual segmenter and a particular border ranged from 0.999 ± 0.000 to 0.978 ± 0.084. The MEAN{mean( &Dgr;LBL )} values ranged from 1.6 to 4.7 &mgr;m depending on border and segmenter. Similarly, between-segmenter agreement was good. The mean concordance correlations values for an individual segmenter and a particular border ranged from 0.999 ± 0.001 to 0.992 ± 0.023. The MEAN{mean( &Dgr;LBL )} values ranged from 1.9 to 4.0 &mgr;m depending on border and segmenter. The signed and unsigned average positions were considerably smaller than the MEAN{mean( &Dgr;LBL )} values for both within- and between-segmenter comparisons. Measures of within-segmenter variability were only slightly larger than those of between-segmenter variability. Conclusions. When human segmenters are trained, the within-and between-segmenter reliability of manual border segmentation is quite good. When expressed as a percentage of retinal layer thickness, the results suggest that manual segmentation provides a reliable measure of the thickness of layers typically measured in studies of glaucoma.

Automated segmentation of outer retinal layers in macular OCT images of patients with retinitis pigmentosa

To provide a tool for quantifying the effects of retinitis pigmentosa (RP) seen on spectral domain optical coherence tomography images, an automated layer segmentation algorithm was developed. This algorithm, based on dual-gradient information and a shortest path search strategy, delineates the inner limiting membrane and three outer retinal boundaries in optical coherence tomography images from RP patients. In addition, an automated inner segment (IS)/outer segment (OS) contour detection method based on the segmentation results is proposed to quantify the locus of points at which the OS thickness goes to zero in a 3D volume scan. The segmentation algorithm and the IS/OS contour were validated with manual segmentation data. The segmentation and IS/OS contour results on repeated measures showed good within-day repeatability, while the results on data acquired on average 22.5 months afterward demonstrated a possible means to follow disease progression. In particular, the automatically generated IS/OS contour provided a possible objective structural marker for RP progression.

On improving the use of OCT imaging for detecting glaucomatous damage

Aims To describe two approaches for improving the detection of glaucomatous damage seen with optical coherence tomography (OCT). Methods The two approaches described were: one, a visual analysis of the high-quality OCT circle scans and two, a comparison of local visual field sensitivity loss to local OCT retinal ganglion cell plus inner plexiform (RGC+) and retinal nerve fibre layer (RNFL) thinning. OCT images were obtained from glaucoma patients and suspects using a spectral domain OCT machine and commercially available scanning protocols. A high-quality peripapillary circle scan (average of 50), a three-dimensional (3D) scan of the optic disc, and a 3D scan of the macula were obtained. RGC+ and RNFL thickness and probability plots were generated from the 3D scans. Results A close visual analysis of a high-quality circle scan can help avoid both false positive and false negative errors. Similarly, to avoid these errors, the location of abnormal visual field points should be compared to regions of abnormal RGC+ and RNFL thickness. Conclusions To improve the sensitivity and specificity of OCT imaging, high-quality images should be visually scrutinised and topographical information from visual fields and OCT scans combined.