Bianca S. Gerendas

Three-dimensional automated choroidal volume assessment on standard spectral-domain optical coherence tomography and correlation with the level of diabetic macular edema.

PURPOSE To measure choroidal thickness on spectral-domain optical coherence tomography (SD OCT) images using automated algorithms and to correlate choroidal pathology with retinal changes attributable to diabetic macular edema (DME). DESIGN Post hoc analysis of multicenter clinical trial baseline data. METHODS SD OCT raster scans/fluorescein angiograms were obtained from 284 treatment-naïve eyes of 142 patients with clinically significant DME and from 20 controls. Three-dimensional (3D) SD OCT images were evaluated by a certified independent reading center analyzing retinal changes associated with diabetic retinopathy. Choroidal thicknesses were analyzed using a fully automated algorithm. Angiograms were assessed manually. Multiple endpoint correction according to Bonferroni-Holm was applied. Main outcome measures were average retinal/choroidal thickness on fovea-centered or peak of edema (thickest point of edema)-centered Early Treatment Diabetic Retinopathy Study grid, maximum area of leakage, and the correlation between retinal and choroidal thicknesses. RESULTS Total choroidal thickness is significantly reduced in DME (175 ± 23 μm; P = .0016) and nonedematous fellow eyes (177 ± 20 μm; P = .009) of patients compared with healthy control eyes (190 ± 23 μm). Retinal/choroidal thickness values showed no significant correlation (1-mm: P = .27, r(2) = 0.01; 3-mm: P = .96, r(2) < 0.0001; 6-mm: P = .42, r(2) = 0.006). No significant difference was found in the 1- or 3-mm circle of a retinal peak of edema-centered grid. All other measurements of choroidal/retinal thickness (DME vs healthy, DME vs peak of edema-centered, DME vs fellow, healthy vs fellow, peak of edema-centered vs healthy, peak of edema-centered vs fellow eyes) were compared but no statistically significant correlation was found. By tendency a thinner choroid correlates with larger retinal leakage areas. CONCLUSIONS Automated algorithms can be used to reliably assess choroidal thickness in eyes with DME. Choroidal thickness was generally reduced in patients with diabetes if DME is present in 1 eye; however, no correlation was found between choroidal/retinal pathologies, suggesting different pathogenetic pathways.

Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA)

Diabetic retinal disease is envisioned to become the plague of the coming decades with a steep increase of worldwide diabetes incidence followed by a substantial rise in retinal disease. Improvements in diagnostic and therapeutic care have to cope with this dilemma in a clinically and socioeconomically efficient manner. Laser treatment has found a less destructive competitor in pharmacological treatments. As a consequence of recent rigorous clinical trials, laser photocoagulation is no longer recommended for the treatment of diabetic macular edema (DME), and anti-vascular endothelial growth factor therapy has emerged as first-line therapy. Steroids have maintained a role in the management of chronically persistent DME. The paradigm shifts in therapy are accompanied by a substantial break-through in diagnostics. The following guidance for the management of DME has been composed from the best updated knowledge of leading experts in Europe and represents another volume in the series of EURETINA recommendations for the management of retinal disease.

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.

Correlation of 3-Dimensionally Quantified Intraretinal and Subretinal Fluid With Visual Acuity in Neovascular Age-Related Macular Degeneration

IMPORTANCE Robust and sensitive imaging biomarkers for visual function are an unmet medical need in the management of neovascular age-related macular degeneration. OBJECTIVE To determine the correlation of 3-dimensionally quantified intraretinal cystoid fluid (IRC) and subretinal fluid (SRF) with best-corrected visual acuity (BCVA) in treatment-naive neovascular age-related macular degeneration and during antiangiogenic therapy. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study between November 2009 and November 2011 at an institutional referral center and reading center of patients with treatment-naive subfoveal choroidal neovascularization receiving intravitreal ranibizumab or aflibercept over 12 months. All individual IRC and SRF lesions were manually delineated on each of the 128 B-scan sections of spectral-domain optical coherence tomographic volume scans at baseline and months 1, 6, and 12. Correlations were computed between the IRC and SRF parameters and the baseline BCVA, final BCVA, and BCVA change. A systematic parameter search was conducted to detect annotation-derived variables with best predictive value. An exponential model for BCVA change balancing for the ceiling effect was constructed. MAIN OUTCOMES AND MEASURES Goodness of fit of correlations between the IRC and SRF parameters and the baseline BCVA, final BCVA, and BCVA change. RESULTS Thirty-eight patients were included (25 female, 13 male; mean [SD] age at enrollment, 78.49 [8.23] years; mean [SD] BCVA score at baseline, 54 [16] Early Treatment Diabetic Retinopathy Study letters [Snellen equivalent approximately 20/160], with a gain to 63 [19] letters [Snellen equivalent approximately 20/100] at month 12). A total of 19,456 scans underwent complete quantification of IRC and SRF. The best correlation with BCVA at baseline was achieved using a coverage-based, foveal area-weighted IRC parameter (R2 = 0.59; P < .001). The same baseline parameter also predicted BCVA at 12 months (R2 = 0.21; P = .003). The BCVA gain correlated with IRC decrease in the exponential model (R2 = 0.40; P < .001) and linear model (R2 = 0.25; P = .002). No robust associations were found between SRF and baseline BCVA (R2 = 0.06; P = .14) or BCVA change (R2 = 0.14; P = .02). CONCLUSIONS AND RELEVANCE In this proof-of-principle study, IRC-derived morphometric variables correlated well with treatment-naive BCVA and BCVA outcomes in antiangiogenic therapy. While IRC reduction was associated with BCVA gains, some IRC-mediated neurosensory damage remained permanent.

Motion Artefact Correction in Retinal Optical Coherence Tomography Using Local Symmetry

Patient movements during the acquisition of SD-OCT scans create substantial motion artefacts in the volumetric data that hinder registration and 3D analysis and can be mistaken for pathologies. In this paper we propose a method to correct these artefacts using a single volume scan while still retaining the overall shape of the retina. The method was quantitatively validated using a set of synthetic SD-OCT volumes and qualitatively by a group of trained OCT grading experts on 100 SD-OCT scans. Furthermore, we compared the motion compensation estimation by the proposed method with a hardware eye tracker on 100 SD-OCT volumes.

Spatio-Temporal Signatures to Predict Retinal Disease Recurrence

We propose a method to predict treatment response patterns based on spatio-temporal disease signatures extracted from longitudinal spectral domain optical coherence tomography (SD-OCT) images. We extract spatio-temporal disease signatures describing the underlying retinal structure and pathology by transforming total retinal thickness maps into a joint reference coordinate system. We formulate the prediction as a multi-variate sparse generalized linear model regression based on the aligned signatures. The algorithm predicts if and when recurrence of the disease will occur in the future. Experiments demonstrate that the model identifies predictive and interpretable features in the spatio-temporal signature. In initial experiments recurrence vs. non-recurrence is predicted with a ROC AuC of 0.99. Based on observed longitudinal morphology changes and a time-to-event based Cox regression model we predict the time to recurrence with a mean absolute error (MAE) of 1.25 months comparing favorably to elastic net regression (1.34 months), demonstrating the benefit of a spatio-temporal survival model.

Prediction of Anti-VEGF Treatment Requirements in Neovascular AMD Using a Machine Learning Approach

Purpose The purpose of this study was to predict low and high anti-VEGF injection requirements during a pro re nata (PRN) treatment, based on sets of optical coherence tomography (OCT) images acquired during the initiation phase in neovascular AMD. Methods Two-year clinical trial data of subjects receiving PRN ranibizumab according to protocol specified criteria in the HARBOR study after three initial monthly injections were included. OCT images were analyzed at baseline, month 1, and month 2. Quantitative spatio-temporal features computed from automated segmentation of retinal layers and fluid-filled regions were used to describe the macular microstructure. In addition, best-corrected visual acuity and demographic characteristics were included. Patients were grouped into low and high treatment categories based on first and third quartile, respectively. Random forest classification was used to learn and predict treatment categories and was evaluated with cross-validation. Results Of 317 evaluable subjects, 71 patients presented low (≤5), 176 medium, and 70 high (≥16) injection requirements during the PRN maintenance phase from month 3 to month 23. Classification of low and high treatment requirement subgroups demonstrated an area under the receiver operating characteristic curve of 0.7 and 0.77, respectively. The most relevant feature for prediction was subretinal fluid volume in the central 3 mm, with the highest predictive values at month 2. Conclusions We proposed and evaluated a machine learning methodology to predict anti-VEGF treatment needs from OCT scans taken during treatment initiation. The results of this pilot study are an important step toward image-guided prediction of treatment intervals in the management of neovascular AMD.

Comparison of penetration depth in choroidal imaging using swept source vs spectral domain optical coherence tomography

PurposeTo compare signal penetration depth and deep structure-visualization of swept source (SS) and spectral domain (SD)-optical coherence tomography (OCT) with and without enhanced depth imaging (EDI) and B-scan averaging modes.MethodsVolume scans were obtained from 20 eyes of healthy volunteers by DRI OCT-1, Spectralis using EDI and B-scan averaging, and Cirrus HD-OCT. The signal penetration depth was measured as the distance between the retinal pigment epithelium and the deepest visible anatomical structure at the foveal center. Visibility and contrast of the choroidoscleral junction and of vascular details within the choroid were assessed across the entire volume using an ordinal scoring scale. Outcome measures were compared using paired t-test and rank-sum test.ResultsThe mean signal penetration depth was 498±114 μm for Spectralis, 491±85 μm for DRI OCT-1, and 123±65 μm for Cirrus; P=0.9708 Spectralis vs DRI OCT-1, P<0.0001 Spectralis vs Cirrus, and P<0.0001 DRI OCT-1 vs Cirrus. Mean ranks for visibility and contrast of the choroidoscleral junction were 3.83 for Spectralis, 3.98 for DRI OCT-1, and 2.00 for Cirrus; and 3.45 for Spectralis, 2.93 for DRI OCT-1, and 1.58 for Cirrus. Mean ranks for visibility and contrast of vascular details were 3.73 (Spectralis), 3.70 (DRI OCT-1), and 2.23 (Cirrus); and 3.53 (Spectralis), 2.05 (DRI OCT-1), and 1.98 (Cirrus).ConclusionSignal penetration depths are similar for SS-OCT and SD-OCT using EDI and frame averaging, and statistically significantly lower without EDI/averaging. Both SD-OCT using EDI/frame averaging and SS-OCT offer excellent visualization capabilities for volumetric imaging of the choroidoscleral interface.

Quantitative comparison of macular segmentation performance using identical retinal regions across multiple spectral-domain optical coherence tomography instruments.

Purpose Comparison of optical coherence tomography (OCT) segmentation performance regarding technical accuracy and clinical relevance. Methods 29 eyes were imaged prospectively with Spectralis (Sp), Cirrus (Ci), 3D-OCT 2000 (3D) and RS-3000 (RS) OCTs. Raw data were evaluated in validated custom software. A 1 mm diameter subfield, centred on the fovea, was investigated to compare identical regions for each case. Segmentation errors were corrected on each B-scan enclosed in this subfield. Proportions of wrongly segmented A-scans were noted for inner and outer retinal boundaries. Centre point thickness (CPT) and central macular thickness (CMT) were compared before and after correction. Results Segmentation errors occurred in 77% and affected on average 29% of A-scans, resulting in mean differences of 24/13 µm (CPT/CMT). The incidence of segmentation errors was 48% (Sp), 79% (Ci), 86% (3D) and 93% (RS), p<0.001. Mean proportions of A-scans with wrong outer retinal boundary were 30% (Sp), 9% (Ci), 23% (3D) and 10% (RS), p=0.006; proportions for the inner retinal boundary were 11% (Sp), 12% (Ci), 6% (3D) and 21% (RS), p=0.034. Mean deviations in CPT/CMT were 41/28 µm (Sp), 17/11 µm (Ci), 30/13 µm (3D) and 18/8 µm (RS), p=0.409/0.477. Conclusions By comparison of identical regions, substantial differences were detected between the tested OCT devices regarding technical accuracy and clinical impact. Spectralis showed lowest error incidence but highest error impact.

Retinal Pigment Epithelial Features in Central Serous Chorioretinopathy Identified by Polarization-Sensitive Optical Coherence Tomography

PURPOSE To determine the subclinical RPE lesions detected by tissue selective polarization-sensitive optical coherence tomography (PS-OCT) in eyes with central serous chorioretinopathy (CSC) and to compare PS-OCT findings to current imaging standards. METHODS In this prospective observational case series, individuals with unilateral or bilateral active CSC were imaged using PS-OCT at baseline and after resolution of serous retinal detachment. Features seen on PS-OCT were compared with corresponding lesions as seen on conventional, intensity-based spectral-domain OCT (SD-OCT), fluorescein angiography, and indocyanine green angiography (ICGA). Features of RPE evaluated by PS-OCT were as follows: area and volume of pigment epithelium detachment (PED), presence of RPE aggregations, RPE skip lesions, RPE thickening, and RPE atrophy. RESULTS Twenty-five study eyes and 23 fellow eyes of 25 participants (2 women, 23 men; mean age ± standard deviation = 40.5 ± 7.4 years) were included and followed for 6.1 ± 3 months. Study eyes and fellow eyes with recurrent CSC showed more RPE abnormalities in PS-OCT than eyes with acute CSC, which correlated well with lesions in ICGA. Closure of the leakage site was observed only in eight (32%) eyes after resolution of subretinal fluid (SRF). All study eyes showed widespread RPE aggregates and 23 (92%) eyes showed RPE skip lesions after resolution of SRF. CONCLUSIONS Features of RPE indicative of previous episodes of CSC detected by PS-OCT correspond well to choroidal lesions in ICGA. In addition, noninvasive PS-OCT imaging enables detection of RPE microrips and aggregations invisible to clinical examination or SD-OCT, thus providing valuable information about disease processes in vivo.