Ferdinand Schlanitz

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.

Drusen volume development over time and its relevance to the course of age-related macular degeneration

Aims To quantify the change in drusen volume over time and identify its prognostic value for individual risk assessment. Methods A prospective observational study over a minimum of 3 years and maximum of 5 years and follow-up examination every 3 months was conducted at the ophthalmology department of the Medical University of Vienna. 109 patients presenting early and intermediate age-related macular degeneration (AMD) were included, of which 30 patients concluded a regular follow-up for at least 3 years. 50 eyes of 30 patients were imaged every 3 months using spectral-domain and polarisation-sensitive optical coherence tomography (OCT). Drusen volume was measured using an automated algorithm. Data of a 6-month follow-up were segmented manually by expert graders. Results Gradings from 24 000 individual B-scans showed solid correlation between manual and automated segmentation with an initial mean drusen volume of 0.17 mm3. The increase in drusen volume was shown to be comparable among all eyes, and a model for long-term drusen volume development could be fitted as a cubic polynomial function and an R2=0.955. Spontaneous drusen regression was observed in 22 of 50 eyes. In this group, four eyes developed choroidal neovascularisation and three geographic atrophy. Conclusions Drusen volume increase over time can be described by a cubic function. Spontaneous regression appears to precede conversion to advanced AMD. OCT might be a promising tool for predicting the individual risk of progression of AMD.

Identification of Drusen Characteristics in Age-Related Macular Degeneration by Polarization-Sensitive Optical Coherence Tomography.

Purpose To describe qualitative characteristics of drusen in eyes with nonadvanced age-related macular degeneration (AMD) using polarization-sensitive optical coherence tomography (OCT). Design Cross-sectional study. Methods Twenty-five eyes of 25 patients with early to intermediate (nonadvanced) AMD were imaged with polarization-sensitive OCT using macular volume scans. All individual drusen in each B-scan were manually delineated by experts certified by a reading center and graded for 6 different morphologic characteristics based on a defined classification scheme, including the presence of internal depolarizing structures and associated depolarizing foci. With the use of a custom-made software, the central B-scan of each individual druse was selected and used to analyze its location, diameter, and characteristics and assess the prevalence of the different features and relations between them. Results Using the macular volume scans, 6224 individual drusen could be identified, including their position within the retina, their characteristics, and their association with any pigmentary alterations. The most common drusen type was a convex-shaped druse with homogeneous medium internal reflectivity and no depolarizing contents (55.3% of drusen). A total of 30.5% of the drusen exhibited internal depolarizing material; 0.3% presented overlying hyperreflective foci, and in 54.5% the foci were also depolarizing. Significant correlations were found between the diameter of the drusen and their distribution throughout the retina, shape, homogeneity of internal reflectivity, presence of internal depolarizing characteristics, and presence of overlying foci (P < .001 each). Significant relations were found between reflectivity, homogeneity, and polarization-sensitive internal characteristics (P < .001). Conclusions Polarization-sensitive OCT reveals characteristic morphologic features of different druse types highlighting the pathophysiological spectrum of early to intermediate AMD.

Detection and analysis of hard exudates by polarization-sensitive optical coherence tomography in patients with diabetic maculopathy.

PURPOSE To image and analyze hard exudates (HEs) and their precursors in patients with diabetic macular edema (DME) by using polarization-sensitive optical coherence tomography (PS-OCT). METHODS Twenty-two eyes of 16 patients with DME were imaged by using color fundus photography (CF) and PS-OCT. In PS-OCT, HEs were automatically detected by their distinct polarization-scrambling qualities. Color fundus images were manually graded for the presence of HEs by two masked graders and correlated with the corresponding PS-OCT HE maps: corresponding images were overlaid and an identical grid of 128 × 128 fields was used for correlation of detected HEs. RESULTS In all eyes, HEs were present owing to DME. Agreement of a pixel-to-pixel analysis of HEs in CF images was 0.72 (Cohens κ) between graders and 0.44 between graders and automated detection by PS-OCT. Mean ± SD detection of HEs was significantly higher in PS-OCT than in manual grading (1180.5 ± 1009.8 fields versus 828.8 ± 695.0 fields; P = 0.02). The higher detection rate of PS-OCT was confirmed by a linear regression analysis with a slope of β = 1.18 (r = 0.81). CONCLUSIONS PS-OCT enables not only two-dimensional imaging of the extent of HEs, as in CF, but also allows tissue-specific, three-dimensional imaging of HEs throughout retinal layers, based on their distinct polarization-scrambling characteristics. The higher detection rate in PS-OCT images indicates an increased sensitivity of PS-OCT imaging over conventional CF.

Machine Learning of the Progression of Intermediate Age-Related Macular Degeneration Based on OCT Imaging

Purpose To develop a data-driven interpretable predictive model of incoming drusen regression as a sign of disease activity and identify optical coherence tomography (OCT) biomarkers associated with its risk in intermediate age-related macular degeneration (AMD). Methods Patients with AMD were observed every 3 months, using Spectralis OCT imaging, for a minimum duration of 12 months and up to a period of 60 months. Segmentation of drusen and the overlying layers was obtained using a graph-theoretic method, and the hyperreflective foci were segmented using a voxel classification method. Automated image analysis steps were then applied to identify and characterize individual drusen at baseline, and their development was monitored at every follow-up visit. Finally, a machine learning method based on a sparse Cox proportional hazard regression was developed to estimate a risk score and predict the incoming regression of individual drusen. Results The predictive model was trained and evaluated on a longitudinal dataset of 61 eyes from 38 patients using cross-validation. The mean follow-up time was 37.8 ± 13.8 months. A total of 944 drusen were identified at baseline, out of which 249 (26%) regressed during follow-up. The prediction performance was evaluated as area under the curve (AUC) for different time periods. Prediction within the first 2 years achieved an AUC of 0.75. Conclusions The predictive model proposed in this study represents a promising step toward image-guided prediction of AMD progression. Machine learning is expected to accelerate and contribute to the development of new therapeutics that delay the progression of AMD.

Retinal pigment epithelial features indicative of neovascular progression in age-related macular degeneration

Background/aims To identify characteristic retinal pigment epithelium (RPE) changes in fellow eyes of patients with neovascular age-related macular degeneration (nAMD) using polarisation-sensitive optical coherence tomography (PS-OCT). Methods Thirty-one fellow eyes of 31 patients with unilateral nAMD were evaluated in this cohort study of a prospective interventional trial. PS-OCT as well as conventional imaging including spectral-domain (SD)-OCT and fluorescein angiography (FA) were performed using a standardised protocol. Monitoring visits were performed continuously at 1-month intervals. Morphological RPE features associated with the development of choroidal neovascularisation (CNV) were systematically analysed. Results Mean follow-up was 29 months (±17, SD). Thirteen (42%) of 31 eyes developed de novo CNV: 9 eyes type I CNV, 2 eyes type II CNV, 2 eyes a retinal angiomatous proliferation lesion. RPE thickening and reticular pseudodrusen (RPD) were observed significantly more often in eyes that developed CNV than in eyes without CNV development (p<0.01). Monthly increase in drusen volume was higher in the CNV group with a median increase of +2.2% in area and +2.9% in volume compared with +0.8% and +0.6% in the non-progressing group. RPE migration within the neurosensory retina and at the level of the RPE resulting in RPE thickening was seen topographically and chronologically associated with CNV development. Conclusions Conversion to CNV is associated with RPE-related changes such as RPE migration, RPE thickening, drusen volume or the presence of RPD. Early detection of these features may allow more efficient screening in risk eyes and timely vision-preserving treatment in eyes developing neovascular disease.

SPECTRAL DOMAIN-OPTICAL COHERENCE TOMOGRAPHY IMAGE CONTRAST AND BACKGROUND COLOR SETTINGS INFLUENCE IDENTIFICATION OF RETINAL STRUCTURES.

Purpose: To evaluate image contrast and color setting on assessment of retinal structures and morphology in spectral-domain optical coherence tomography. Methods: Two hundred and forty-eight Spectralis spectral-domain optical coherence tomography B-scans of 62 patients were analyzed by 4 readers. B-scans were extracted in 4 settings: W + N = white background with black image at normal contrast 9; W + H = white background with black image at maximum contrast 16; B + N = black background with white image at normal contrast 12; B + H = black background with white image at maximum contrast 16. Readers analyzed the images to identify morphologic features. Interreader correlation was calculated. Differences between Fleiss-kappa correlation coefficients were examined using bootstrap method. Any setting with significantly higher correlation coefficient was deemed superior for evaluating specific features. Results: Correlation coefficients differed among settings. No single setting was superior for all respective spectral-domain optical coherence tomography parameters (P = 0.3773). Some variables showed no differences among settings. Hard exudates and subretinal fluid were best seen with B + H (&kgr; = 0.46, P = 0.0237 and &kgr; = 0.78, P = 0.002). Microaneurysms were best seen with W + N (&kgr; = 0.56, P = 0.025). Vitreomacular interface, enhanced transmission signal, and epiretinal membrane were best identified using all color/contrast settings together (&kgr; = 0.44, P = 0.042, &kgr; = 0.57, P = 0.01, and &kgr; = 0.62, P ⩽ 0.0001). Conclusion: Contrast and background affect the evaluation of retinal structures on spectral-domain optical coherence tomography images. No single setting was superior for all features, though certain changes were best seen with specific settings.

Impact of drusen and drusenoid retinal pigment epithelium elevation size and structure on the integrity of the retinal pigment epithelium layer

Purpose To evaluate the impact of drusen size and structure on retinal pigment epithelium (RPE) and photoreceptor layers in eyes with early to intermediate age-related macular degeneration (AMD) using polarisation-sensitive optical coherence tomography (OCT). Design Retrospective investigation of an observational cross-sectional study. Participants Patients with early to intermediate AMD. Methods Twenty-five eyes of 25 patients with drusen were imaged with polarisation-sensitive OCT using macular volume scans. Each scan was manually graded for six distinct drusen characteristics and the integrity of both the overlying RPE and photoreceptor layer. The central scan of each single druse, as well as its diameter and location, were selected for statistical calculations. Results A total number of 5933 individual drusen including their adjacent RPE and photoreceptor layer were evaluated. 41.3% of all drusen demonstrated an intact overlying RPE; in 28.1% the RPE layer was irregular, but continuous. In 30.6%, the RPE layer signal was discontinuous above the area of drusen. The level of RPE alteration was significantly related to shape (p<0.001), internal reflectivity (p<0.001) and homogeneity (p<0.001) of the drusen and their diameter, with a higher probability for larger drusen to have a discontinuous RPE (OR 3.2, p<0.001). The number of drusen showing overlying foci or an altered photoreceptor layer was too small to be conclusive, but showed a trend towards an altered RPE if present. Conclusions Polarisation-sensitive OCT reveals a correlation between specific drusen characteristics and the integrity of the overlying RPE layer. Drusen diameter and configuration were significantly associated with RPE loss.