Christopher Schütze

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.

Polarization sensitive optical coherence tomography of melanin provides intrinsic contrast based on depolarization

Polarization sensitive optical coherence tomography (PS-OCT) is a functional extension of OCT. In addition to imaging based on tissue reflectivity, PS-OCT also enables depth-resolved mapping of sample polarization properties such as phase-retardation, birefringent axis orientation, Stokes vectors, and degree of polarization uniformity (DOPU). In this study, PS-OCT was used to investigate the polarization properties of melanin. In-vitro measurements in samples with varying melanin concentrations revealed polarization scrambling, i.e. depolarization of backscattered light. Polarization scrambling in the PS-OCT images was more pronounced for higher melanin concentrations and correlated with the concentration of the melanin granules in the phantoms. Moreover, in-vivo PS-OCT was performed in the retinas of normal subjects and individuals with albinism. Unlike in the normal eye, polarization scrambling in the retinal pigment epithelium (RPE) was less pronounced or even not observable in PS-OCT images of albinos. These results indicate that the depolarizing appearance of pigmented structures like, for instance, the RPE is likely to be caused by the melanin granules contained in these cells.

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.

Progression of Retinal Pigment Epithelial Atrophy in Antiangiogenic Therapy of Neovascular Age-Related Macular Degeneration

Purpose To monitor retinal pigment epithelial (RPE) atrophy progression during antiangiogenic therapy of neovascular age-related macular degeneration (AMD) over 2 years using polarization-sensitive optical coherence tomography (OCT). Design Prospective interventional case series. Methods setting: Clinical practice. study population: Thirty patients (31 eyes) with treatment-naïve neovascular AMD. observation procedures: Standard intravitreal therapy (0.5 mg ranibizumab) was administered monthly during the first year and pro re nata (PRN; as-needed) during the second year. Spectral-domain (SD) OCT and polarization-sensitive OCT (selectively imaging the RPE) examinations were performed at baseline and at 1, 3, 6, 12, and 24 months using a standardized protocol. RPE-related changes were evaluated using a semi-automated polarization-sensitive OCT segmentation algorithm and correlated with SD OCT and fundus autofluorescence (FAF) findings. main outcome measures: RPE response, geographic atrophy (GA) progression. Results Atrophic RPE changes included RPE thinning, RPE porosity, focal RPE atrophy, and development of GA. Early RPE loss (ie, RPE porosity, focal atrophy) increased progressively during initial monthly treatment and remained stable during subsequent PRN-based therapy. GA developed in 61% of eyes at month 24. Mean GA area increased from 0.77 mm2 at 12 months to 1.10 mm2 (standard deviation = 1.09 mm2) at 24 months. Reactive accumulation of RPE-related material at the lesion borders increased until month 3 and subsequently decreased. Conclusions Progressive RPE atrophy and GA developed in the majority of eyes. RPE migration signifies certain RPE plasticity. Polarization-sensitive OCT specifically images RPE-related changes in neovascular AMD, contrary to conventional imaging methods. Polarization-sensitive OCT allows for precisely monitoring the sequence of RPE-related morphologic changes.

Association of Retinal Sensitivity and Morphology during Antiangiogenic Treatment of Retinal Vein Occlusion over One Year

PURPOSE Evaluation of the association between functional and anatomic retinal changes during anti-vascular endothelial growth factor (VEGF) therapy with bevacizumab (Avastin) in patients with cystoid macular edema secondary to retinal vein occlusion (RVO) using microperimetry and spectral domain optical coherence tomography (SD-OCT). DESIGN Prospective, uncontrolled study (EUDRACT NR-2005-003288-21). PARTICIPANTS Twenty-eight patients with cystoid macular edema secondary to RVO. METHODS Patients initially received 3 consecutive intravitreal injections of 1.25 mg bevacizumab at 4-week intervals. Further treatment was based on morphologic (OCT) and functional best-corrected visual acuity (BCVA) findings. During the 1-year follow-up, a rigorous standardized evaluation was performed monthly. Macular function was documented by microperimetry (Nidek, MP1 Microperimeter) and BCVA based on the Early Treatment in Diabetic Retinopathy Study (ETDRS). Morphologic parameters included central retinal thickness (CRT) as measured by conventional OCT (Stratus), and central subfield thickness (CST), mean retinal thickness (MRT), and retinal volume (RV) measured by SD-OCT. MAIN OUTCOME MEASURES Imaging of retinal morphology using OCT and SD-OCT and evaluation of retinal function assessed with microperimetry and ETDRS charts during 12 months of anti-VEGF treatment. RESULTS Within 6 months, the mean area of absolute scotoma was reduced from 21.4% of the central visual field to 6.4% and remained at this level until month 12 (7.4%). Mean BCVA improved from 51 to 66 letters on ETDRS charts. The CRT, CST, and MRT decreased significantly (P<0.002) and remained stable during the follow-up. The RV values did not improve significantly under therapy. Statistical analysis using a linear effects model revealed significant associations between the functional and morphologic outcomes, most notably between BCVA, macular sensitivity, CRT (Stratus OCT), CST, and MRT (Cirrus OCT) values. CONCLUSIONS Central retinal morphology, especially CRT and CST measured by conventional and SD-OCT, and retinal function improved significantly during treatment of RVO with a flexible dosing regimen of intravitreal bevacizumab. Functional (central visual acuity and visual field) and morphologic parameters (retinal thickness) were significantly related. These associations highlight the value of OCT imaging for assessing this disease entity.

Large-field high-speed polarization sensitive spectral domain OCT and its applications in ophthalmology

We present a novel spectral domain polarization sensitive OCT system (PS-OCT) that operates at an A-scan rate of 70 kHz and supports scan angles of up to 40° × 40°. The high-speed imaging allows the acquisition of up to 1024 × 250 A-scans per 3D scan, which, together with the large field of view, considerably increases the informative value of the images. To demonstrate the excellent performance of the new PS-OCT system, we imaged several healthy volunteers and patients with various diseases such as glaucoma, AMD, Stargardt’s disease, and albinism. The results are compared with clinically established methods such as scanning laser polarimetry and autofluorescence.

Lesion Size Detection in Geographic Atrophy by Polarization-Sensitive Optical Coherence Tomography and Correlation to Conventional Imaging Techniques

PURPOSE To investigate the reproducibility of automated lesion size detection in patients with geographic atrophy (GA) using polarization-sensitive spectral-domain optical coherence tomography (PS-OCT) and to compare findings with scanning laser ophthalmoscopy (SLO), fundus autofluorescence (FAF), and intensity-based spectral-domain OCT (SD-OCT). METHODS Twenty-nine eyes of 22 patients with GA were examined by PS-OCT, selectively identifying the retinal pigment epithelium (RPE). A novel segmentation algorithm was applied, automatically detecting and quantifying areas of RPE atrophy. The reproducibility of the algorithm was assessed, and lesion sizes were correlated with manually delineated SLO, FAF, and intensity-based SD-OCT images to validate the clinical applicability of PS-OCT in GA evaluation. RESULTS Mean GA lesion size of all patients was 5.28 mm(2) (SD: 4.92) in PS-OCT. Mean variability of individual repeatability measurements was 0.83 mm(2) (minimum: 0.05; maximum: 3.65). Mean coefficient of variation was 0.07 (min: 0.01; max: 0.19). Mean GA area in SLO (Spectralis OCT) was 5.15 mm(2) (SD: 4.72) and 2.5% smaller than in PS-OCT (P = 0.9, Pearson correlation coefficient = 0.98, P < 0.01). Mean GA area in intensity-based SD-OCT pseudo-SLO images (Cirrus OCT) was 5.14 mm(2) (SD: 4.67) and 2.7% smaller than in PS-OCT (P = 0.9, Pearson correlation coefficient = 0.98, P < 0.01). Mean GA area of all eyes measured 5.41 mm(2) (SD: 4.75) in FAF, deviating by 2.4% from PS-OCT results (P = 0.89, Pearson correlation coefficient = 0.99, P < 0.01). CONCLUSIONS PS-OCT demonstrated high reproducibility of GA lesion size determination. Results correlated well with SLO, FAF, and intensity-based SD-OCT fundus imaging. PS-OCT may therefore be a valuable and specific imaging modality for automated GA lesion size determination in scientific studies and clinical practice.

Performance of OCT segmentation procedures to assess morphology and extension in geographic atrophy

Purpose:  Investigating segmentation procedures and morphological findings in time domain (TD) and current spectral domain (SD) optical coherence tomography (OCT) devices in patients with geographic atrophy (GA).

Evaluation of segmentation procedures using spectral domain optical coherence tomography in exudative age-related macular degeneration.

Purpose: The purpose of this study was to evaluate standardized automated segmentation procedures of spectral domain optical coherence tomography (SD-OCT) in imaging of age-related macular degeneration. Methods: Twenty-nine eyes of 29 patients with neovascular age-related macular degeneration were included. Three groups were assigned, according to the predominant localization of extravasated fluid in the intra-, subretinal, and subretinal pigment epithelium (RPE) compartment. Automated segmentation procedures were evaluated in B scans of 512 × 128 × 1024 and 200 × 200 × 1024 scan patterns using SD-OCT (Cirrus). Alignment errors at the internal limiting membrane, actual RPE, and extrapolation of the physiologic RPE (RPE fit) were graded using a standardized classification system. Results: The rate of severe alignment failures was 56% and 41% for the 512 × 128 and the 200 × 200 raster pattern, respectively. Internal limiting membrane and actual RPE boundaries were most correctly delineated in the 200 × 200 raster pattern. Retinal pigment epithelium fit alignment was generally poor in 50% of scans. Retinal thickness values defined by internal limiting membrane and actual RPE segmentation were 90% accurate and not compromised by RPE fit misalignment. Subretinal fluid was demarcated most reliably. Alignment errors may occur together with a large spectrum of morphologic alterations. Conclusion: Automated algorithms of SD-OCT demonstrate a substantial rate of alignment failures in the assessment of exudative age-related macular degeneration pathologies, which are usually associated with misinterpretation of boundaries at the (sub) RPE level.