C. Ahlers

Retinal pigment epithelium segmentation by polarization sensitive optical coherence tomography

We present a new method for identifying and segmenting the retinal pigment epithelium (RPE) in polarization sensitive optical coherence tomography (PS-OCT) images of the human retina. Contrary to previous, intensity based segmentation algorithms, our method uses an intrinsic tissue property of the RPE: its depolarizing, or polarization scrambling effect on backscattered light. Two different segmentation algorithms are presented and discussed: a simpler algorithm based on retardation data, and a more sophisticated algorithm based on local variations of the polarization state calculated from averaged Stokes vector elements. By using a state of the art spectral domain PS-OCT instrument, we demonstrate the method in healthy and diseased eyes.

Imaging of the Retinal Pigment Epithelium in Age-Related Macular Degeneration Using Polarization-Sensitive Optical Coherence Tomography

Purpose. Spectral-domain optical coherence tomography (SD-OCT) provides new insights into the understanding of age-related macular degeneration (AMD) but limited information on the nature of hyperreflective tissue at the level of the retinal pigment epithelium. Therefore, polarization-sensitive (PS) SD-OCT was used to identify and characterize typical RPE findings in AMD. Methods. Forty-four eyes of 44 patients with AMD were included in this prospective case series representing the entire AMD spectrum from drusen (n = 11), geographic atrophy (GA; n = 11), neovascular AMD (nAMD; n = 11) to fibrotic scars (n = 11). Imaging systems were used for comparative imaging. A PS-SD-OCT instrument was developed that was capable of recording intensity and polarization parameters simultaneously during a single scan. Results. In drusen, PS-SD-OCT identified a continuous RPE layer with focal elevations. Discrete RPE atrophy (RA) could be observed in two patients. In GA, the extension of the RA was significantly larger. Residual RPE islands could be detected within the atrophic zone. PS-SD-OCT identified multiple foci of RPE loss in patients with nAMD and allowed recognition of advanced RPE disease associated with choroidal neovascularization. Wide areas of RA containing residual spots of intact retinal pigment epithelium could be identified in fibrotic scars. Conclusions. PS-SD-OCT provided precise identification of retinal pigment epithelium in AMD. Recognition of these disease-specific RA patterns in dry and wet forms of AMD is of particular relevance to identify the status and progression of RPE disease and may help to better estimate the functional prognosis of AMD.

Automatic segmentation in three-dimensional analysis of fibrovascular pigmentepithelial detachment using high-definition optical coherence tomography

Background/aims: A limited number of scans compromise conventional optical coherence tomography (OCT) to track chorioretinal disease in its full extension. Failures in edge-detection algorithms falsify the results of retinal mapping even further. High-definition-OCT (HD-OCT) is based on raster scanning and was used to visualise the localisation and volume of intra- and sub-pigment-epithelial (RPE) changes in fibrovascular pigment epithelial detachments (fPED). Two different scanning patterns were evaluated. Methods: 22 eyes with fPED were imaged using a frequency-domain, high-speed prototype of the Cirrus™ HD-OCT. The axial resolution was 6 μm, and the scanning speed was 25 kA scans/s. Two different scanning patterns covering an area of 6×6 mm in the macular retina were compared. Three-dimensional topographic reconstructions and volume calculations were performed using MATLAB™-based automatic segmentation software. Results: Detailed information about layer-specific distribution of fluid accumulation and volumetric measurements can be obtained for retinal- and sub-RPE volumes. Both raster scans show a high correlation (p<0.01; R2>0.89) of measured values, that is PED volume/area, retinal volume and mean retinal thickness. Quality control of the automatic segmentation revealed reasonable results in over 90% of the examinations. Conclusion: Automatic segmentation allows for detailed quantitative and topographic analysis of the RPE and the overlying retina. In fPED, the 128×512 scanning-pattern shows mild advantages when compared with the 256×256 scan. Together with the ability for automatic segmentation, HD-OCT clearly improves the clinical monitoring of chorioretinal disease by adding relevant new parameters. HD-OCT is likely capable of enhancing the understanding of pathophysiology and benefits of treatment for current anti-CNV strategies in future.

Comparison of retinal thickness measurements and segmentation performance of four different spectral and time domain OCT devices in neovascular age-related macular degeneration

Aims: To evaluate the reliability of different optical coherence tomography (OCT) devices and scanning patterns in the assessment of retinal thickness and segmentation performance in neovascular age-related macular degeneration (nAMD). Methods: 28 eyes with nAMD and 10 healthy eyes were imaged using conventional time domain (TD) OCT as well as three spectral-domain (SD) OCT systems. Radial scans of 6 mm in size were compared between Stratus and Topcon OCT, in addition to raster scans of all three SD-OCT devices. Retinal thickness values were analysed. Results: Spectralis SD-OCT demonstrated the highest values of all OCT devices in central millimetre thickness (CMMT), and Topcon OCT raster scans showed the lowest values. Significant correlations could be found between the CMMT measurements of Cirrus and Spectralis OCT (r = 0.87). Analyses showed best segmentation for Cirrus and Spectralis SD-OCTs. Cirrus 200×200×1024 scans showed 4% and Stratus OCT 38% moderate or severe segmentation errors. Conclusion: Retinal thickness values were generally higher in SD-OCT analysis. Different performances of automatic retinal thickness analysis indicate the potential of different software algorithms to quantify retinal morphology in nAMD. Further development of current algorithms may improve quantification of retinal thickness detection in the future even further.

Imaging of the parafoveal capillary network and its integrity analysis using fractal dimension

Using a spectral domain OCT system, equipped with a broadband Ti:sapphire laser, we imaged the human retina with 5 µm x 1.3 µm transverse and axial resolution at acquisition rate of 100 kHz. Such imaging speed significantly reduces motion artifacts. Combined with the ultra-high resolution, this allows observing microscopic retinal details with high axial definition without the help of adaptive optics. In this work we apply our system to image the parafoveal capillary network. We demonstrate how already on the intensity level the parafoveal capillaries can be segmented by a simple structural high pass filtering algorithm. This data is then used to quantitatively characterize the capillary network of healthy and diseased eyes. We propose to use the fractal dimension as index for capillary integrity of pathologic disorders.

Performance of automated drusen detection by polarization-sensitive optical coherence tomography.

PURPOSE To estimate the potential of polarization-sensitive optical coherence tomography (PS-OCT) for quantitative assessment of drusen in patients with early age-related macular degeneration (AMD). METHODS Fifteen eyes from 13 patients presenting drusen consistent with Age-Related Eye Disease Study classifications (grades 2 and 3) were examined ophthalmoscopically, followed by fundus photography, autofluorescence imaging, and three-dimensional scanning using a PS-OCT. For the automated evaluation of drusen location, area, and volume, a novel segmentation algorithm was developed based on the polarization scrambling characteristics of the retinal pigment epithelium (RPE) and applied to each complete data set. Subsequently, the drusen in each individual B-scan were identified by two independent expert graders. Concordance between manual and automated segmentation results was analyzed. Errors in the automated segmentation performance were classified as nonsignificant, moderate, or severe. RESULTS. In all, 2355 individual drusen, with a mean of 157 drusen per eye, were analyzed. Of drusen seen in the individual B-scans, 91.4% were detected manually by both expert graders. The automated segmentation algorithm identified 96.5% of all drusen without significant error. The mean difference in manual and automated drusen area (mean, 4.65 mm(2)) was 0.150. The number of detected drusen was significantly higher with automated than that with manual segmentation. PS-OCT segmentation was generally superior to fundus photography (P < 0.001). Particularly in nondetected drusen, a large variability in drusen morphology was noted. CONCLUSIONS Automated drusen detection based on PS-OCT technology allows a fast and accurate determination of drusen location, number, and total area.

Quantification of the therapeutic response of intraretinal, subretinal, and subpigment epithelial compartments in exudative AMD during anti-VEGF therapy

PURPOSE To analyze the functional and morphologic effects of different ranibizumab treatment regimens on retinal and subretinal as well as sub-RPE compartments in neovascular age-related macular degeneration (nAMD) using spectral-domain optical coherence tomography (SD-OCT) and manual segmentation software. METHODS Twenty-seven eyes of 27 patients with nAMD were examined over a 12-month period. Two treatment arms received either monthly or quarterly administered intravitreal ranibizumab. Intraretinal, subretinal, and sub-RPE volume equivalents were delineated using manual segmentation software over a defined series of B-scans obtained by SD-OCT. The mean area in pixels was calculated for each compartment at each time interval. RESULTS SD-OCT and manual segmentation allowed for exact identification of intraretinal, subretinal and sub-RPE compartments and their responses to different treatment regimens. The loading dose demonstrated a corresponding treatment effect on all anatomic parameters. In contrast to the sub-RPE compartment, intraretinal fluid accumulation and subretinal fluid accumulation (SRFA) demonstrated an immediate response to ranibizumab therapy. The overall plasticity of the morphologic response declined over time. In general, SRFA demonstrated greater sensitivity for therapeutic effects and was more frequently associated with recurrent disease. CONCLUSIONS An exact quantification of fluid in different anatomic compartments based on SD-OCT imaging, using appropriate segmentation software systems, may be useful to determine optimal treatment and retreatment parameters and explains the lack of correlation of best-corrected visual acuity and conventional OCT values.

Time course of morphologic effects on different retinal compartments after ranibizumab therapy in age-related macular degeneration

PURPOSE To analyze the effect of ranibizumab therapy on retinal and subretinal compartments in age-related macular degeneration and to compare the time course of compartment specific effects to visual function. DESIGN Prospective noncomparative case series. PARTICIPANTS Fourteen patients with changes in 3 major compartments owing to neovascular age-related macular degeneration. METHODS Standard treatment with 3 monthly doses of intravitreal ranibizumab was performed. Eyes were examined at baseline and weeks 1, 4, and 12 using a standardized protocol. Manual segmentation was applied to all 128 B-scans contained in a macular raster scan (MRS). MAIN OUTCOME MEASURES Morphology and time course of different retinal and subretinal compartments. RESULTS High-definition optical coherence tomography and manual segmentation allowed for precise identification of volumes within individual compartments. All morphologic parameters responded positively to therapy, but demonstrated a specific time course. Subretinal fluid was identified as the most relevant factor for visual function, whereas changes in retinal and subpigment epithelial volumes did not correlate with the time course of functional rehabilitation. CONCLUSION Analysis of MRS identified a characteristic impact of therapy on retinal and subretinal morphology.

Morphological and functional analysis of the loading regimen with intravitreal ranibizumab in neovascular age-related macular degeneration

Aim To quantify and correlate the morphological and functional effects of the recommended loading regimen with intravitreal ranibizumab in neovascular age-related macular degeneration (AMD). Methods In a prospective, interventional clinical trial, 29 consecutive patients (29 eyes) with choroidal neovascularisation secondary to AMD received three initial monthly intravitreal injections of ranibizumab. During this loading regimen, best corrected visual acuity (BCVA) and microperimetry (MP) testing, as well as optical coherence tomography and fluorescein angiography (FA), were performed using a standardised protocol and the results correlated. Results Significant morphological and functional therapeutic effects were observed as early as 1 week following the first treatment. Throughout the loading-dose period, central retinal thickness, including intraretinal cysts and subretinal fluid, decreased fast and significantly (p<0.01); pigment epithelial detachment resolved less rapidly. The mean leakage area by FA decreased (p<0.01) and retinal function (BCVA and MP) increased significantly (both p<0.01). However, the change in morphology and function was only significant between baseline and week 1. There was no significant additional morphological or functional benefit following the second and third injection. Conclusion The initial administration of intravitreal ranibizumab in neovascular AMD induced a significant effect on intra- and subretinal fluid and visual function; subsequent injections had a less pronounced effect. It remains to be determined whether this loading regimen should be mandatory in all patients or if a single dose regimen would lead to a comparable functional and morphological retinal improvement.

Three-dimensional polarization sensitive OCT imaging and interactive display of the human retina

Polarization sensitive OCT has recently been shown to provide tissue specific contrast, enabling direct identification of retinal layers based on the intrinsic properties of their interaction with light. However, the capabilities of displaying and analyzing 3D datasets in scientific publications were rather limited. Within the framework of the Interactive Science Publishing project, we present new ways of displaying and analyzing 3D sets of various polarization parameters recorded in healthy and diseased human retinas. These datasets can be interactively explored by the reader. Furthermore, we provide data of the 3D distribution of backscattered Stokes vectors to allow the reader to develop and test their own data processing algorithms.