Alessio Montuoro

A Systematic Comparison of Spectral-Domain Optical Coherence Tomography and Fundus Autofluorescence in Patients with Geographic Atrophy

PURPOSE To evaluate spectral-domain optical coherence tomography (SD-OCT) in providing reliable and reproducible parameters for grading geographic atrophy (GA) compared with fundus autofluorescence (FAF) images acquired by confocal scanning laser ophthalmoscopy (cSLO). DESIGN Prospective observational study. PARTICIPANTS A total of 81 eyes of 42 patients with GA. METHODS Patients with atrophic age-related macular degeneration (AMD) were enrolled on the basis of total GA lesion size ranging from 0.5 to 7 disc areas and best-corrected visual acuity of at least 20/200. A novel combined cSLO-SD-OCT system (Spectralis HRA-OCT, Heidelberg Engineering, Heidelberg, Germany) was used to grade foveal involvement and to manually measure disease extent at the level of the outer neurosensory layers and retinal pigment epithelium (RPE) at the site of GA lesions. Two readers of the Vienna Reading Center graded all obtained volume stacks (20×20 degrees), and the results were correlated to FAF. MAIN OUTCOME MEASURES Choroidal signal enhancements and alterations of the RPE, external limiting membrane (ELM), and outer plexiform layer by SD-OCT. These parameters were compared with the lesion measured with severely decreased FAF. RESULTS Foveal involvement or sparing was definitely identified in 75 of 81 eyes based on SD-OCT by both graders (inter-grader agreement: κ=0.6, P < 0.01). In FAF, inter-grader agreement regarding foveal involvement was lower (48/81 eyes, inter-grader agreement: κ=0.3, P < 0.01). Severely decreased FAF was measured over a mean area of 8.97 mm(2) for grader 1 (G1) and 9.54 mm(2) for grader 2 (G2), consistent with the mean SD-OCT quantification of the sub-RPE choroidal signal enhancement (8.9 mm(2) [G1] -9.4 mm(2) [G2]) and ELM loss with 8.7 mm(2) (G1) -10.2 mm(2) (G2). In contrast, complete morphologic absence of the RPE layer by SD-OCT was significantly smaller than the GA size in FAF (R(2)=0.400). Inter-reader agreement was highest regarding complete choroidal signal enhancement (0.98) and ELM loss (0.98). CONCLUSIONS Absence of FAF in GA lesions is consistent with morphologic RPE loss or advanced RPE disruption and is associated with alterations of the outer retinal layers as identified by SD-OCT. Lesion size is precisely determinable by SD-OCT, and foveal involvement is more accurate by SD-OCT than by FAF.

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.

A systematic correlation of morphology and function using spectral domain optical coherence tomography and microperimetry in patients with geographic atrophy

Aims This study has been designed to describe the functional impact of distinct pathologies within the retinal layers in patients with geographic atrophy (GA) by means of a point-to-point correlation between optical coherence tomography (OCT) and microperimetry. Methods Retinal morphology and function of 23 patients suffering from GA of the retinal pigment epithelium (RPE) have been investigated using the Spectralis OCT (Heidelberg Engineering) and the MP1 microperimeter (Nidek Technologies). The point-to-point overlay of morphology and function has been done using proprietary software, allowing OCT image grading to define distinct alterations of the neurosensory retina, the RPE and the choroid. By overlaying the retinal sensitivity map on the OCT data set, retinal layer alterations could be evaluated regarding their impact on visual function. Results A total of 1005 stimulation points in the lesion area in 2107 spectral domain OCT B-scans were graded in 43 eyes of 23 patients (mean best corrected visual acuity=20/70). Retinal sensitivity decreases with an increasing number of morphological alterations graded (p<10−13). Alterations of the RPE and the external limiting membrane (p<0.02) were associated with absolute scotomas. Furthermore, the loss of the external limiting membrane as the largest area of morphological alteration among our patients with GA (mean area=5.65 mm2), had a significant impact (p<10−4) on sensitivity (−1.3 dB). Conclusions Mapping retinal sensitivity to distinct retinal pathologies revealed outer retinal layers, in addition to the RPE, as significant for sensitivity loss. Therefore in GA the RPE loss and the alteration of outer retinal layers should be analysed, which could also provide insight into lesion progression.

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.

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.

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.

Visual acuity and microperimetric mapping of lesion area in eyes with inflammatory cystoid macular oedema

Purpose:  To evaluate the effect of fluid accumulation on local visual function in inflammatory cystoid‐macular‐edema (ICME).

Joint retinal layer and fluid segmentation in OCT scans of eyes with severe macular edema using unsupervised representation and auto-context

Modern optical coherence tomography (OCT) devices used in ophthalmology acquire steadily increasing amounts of imaging data. Thus, reliable automated quantitative analysis of OCT images is considered to be of utmost importance. Current automated retinal OCT layer segmentation methods work reliably on healthy or mildly diseased retinas, but struggle with the complex interaction of the layers with fluid accumulations in macular edema. In this work, we present a fully automated 3D method which is able to segment all the retinal layers and fluid-filled regions simultaneously, exploiting their mutual interaction to improve the overall segmentation results. The machine learning based method combines unsupervised feature representation and heterogeneous spatial context with a graph-theoretic surface segmentation. The method was extensively evaluated on manual annotations of 20,000 OCT B-scans from 100 scans of patients and on a publicly available data set consisting of 110 annotated B-scans from 10 patients, all with severe macular edema, yielding an overall mean Dice coefficient of 0.76 and 0.78, respectively.

Systematic correlation of morphologic alterations and retinal function in eyes with uveitis-associated cystoid macular oedema during development, resolution and relapse.

Purpose To evaluate morphological changes due to uveitis-associated cystoid macular oedema (uvCME) and their impact on central retinal sensitivity (CRS) before and after intravitreal triamcinolone-acetonide (IVTA). Methods 28 eyes with uvCME were examined with microperimetry and spectral-domain optical-coherence-tomography (SD-OCT) before and after IVTA. Microperimetry-maps were superimposed on SD-OCT and morphological-alterations were correlated point to point with CRS and followed-up for 3 months. The effects of morphological-alterations on CRS over time were evaluated with a linear mixed-model. Results Mean-CRS increased significantly after IVTA (p=0.009). Proportion of cysts correlated negatively with corresponding CRS (estimate/95% CI −3.8dB/−6.6 to −0.9, p=0.011). Proportion of diffuse macular-oedema (DifME) had no significant effect on mean-CRS (−0.76dB/−4.9 to 3.3, p=0.71). The proportion of serous retinal detachment (SRD) had a borderline significant effect on mean-CRS (−9.5dB/−19.1 to 0.1, p=0.052), however the initial presence of SRD at baseline had no significant negative effect on mean-CRS (−1.3dB/−4.9 to 2.3, p=0.46). Patients with epiretinal-membrane showed lower mean-CRS than patients without (−3.3dB/−6.5 to −0.008, p=0.05). The lowest percentage of morphological-alterations was achieved 30 days post IVTA concordant to best visual-acuity (logMAR 0.16±0.26), while best mean-CRS was achieved 90 days post IVTA (16.9±1.8dB). Fixation-stability showed no significant improvement. Conclusions UvCME Morphological-alterations were associated with specific CRS-decreases. DifME showed no significant- and SRD only a borderline effect on mean-CRS, which implicates that their presence should be considered when interpreting SD-OCT and making treatment-decisions.