Christian Simader | Medical University of Vienna (original) (raw)

Papers by Christian Simader

Research paper thumbnail of Published Online First

Evaluation of optical coherence tomography findings in age-related macular degeneration: a reprod... more Evaluation of optical coherence tomography findings in age-related macular degeneration: a reproducibility study of two independent reading centres

Research paper thumbnail of Reproducibility of Retinal Thickness Measurements across Spectral-Domain Optical Coherence Tomography Devices using Iowa Reference Algorithm

arXiv: Medical Physics, 2016

PURPOSE: Establishing and obtaining consistent quantitative indices of retinal thickness from a v... more PURPOSE: Establishing and obtaining consistent quantitative indices of retinal thickness from a variety of clinically used Spectral-Domain Optical Coherence Tomography scanners. DESIGN: Retinal images from five Spectral-Domain Optical Coherence Tomography scanners were used to determine total retinal thickness with scanner-specific correction factors establishing consistency of thickness measurement across devices. PARTICIPANTS: 55 Fovea-centered Spectral-Domain Optical Coherence Tomography volumes from eleven subjects were analyzed, obtained from Cirrus HD-OCT, RS-3000, Heidelberg Spectralis, RTVue and Topcon2000, seven subjects with retinal diseases and four normal controls. METHOD: The Iowa Reference Algorithm measured total retinal thickness. Nonlinear model of total retinal thickness measurement comparisons was derived and used for device-specific comparisons. Bland-Altman plots and pairwise predictive equations yielded pairwise scanner-specific differences. Mendel test determi...

Research paper thumbnail of Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration

Ophthalmology, 2018

Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL)... more Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. Design: (Pooled) analysis of cross-sectional data. Participants: 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. Methods: In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random-effect were used to estimate the associations. Main Outcome Measures: early, late or any AMD, phenotypic features of early AMD, lipid measurements. Results: HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). Conclusions: Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains a question to be answered.

Research paper thumbnail of The Decreasing Prevalence of Nonrefractive Visual Impairment in Older Europeans: A Meta-analysis of Published and Unpublished Data

Ophthalmology, Jan 13, 2018

To estimate the prevalence of nonrefractive visual impairment and blindness in European persons 5... more To estimate the prevalence of nonrefractive visual impairment and blindness in European persons 55 years of age and older. Few visual impairment and blindness prevalence estimates are available for the European population. In addition, many of the data collected in European population-based studies currently are unpublished and have not been included in previous estimates. Fourteen European population-based studies participating in the European Eye Epidemiology Consortium (n = 70 723) were included. Each study provided nonrefractive visual impairment and blindness prevalence estimates stratified by age (10-year strata) and gender. Nonrefractive visual impairment and blindness were defined as best-corrected visual acuity worse than 20/60 and 20/400 in the better eye, respectively. Using random effects meta-analysis, prevalence rates were estimated according to age, gender, geographical area, and period (1991-2006 and 2007-2012). Because no data were available for Central and Eastern ...

Research paper thumbnail of The Distribution of Leakage on Fluorescein Angiography in Diabetic Macular Edema: A New Approach to Its Etiology

Investigative Opthalmology & Visual Science, 2017

PURPOSE. To determine the distribution of leakage on fluorescein angiography (FA) and explore the... more PURPOSE. To determine the distribution of leakage on fluorescein angiography (FA) and explore the clinically protective role of astrocytes against damage to the inner blood retinal barrier (iBRB) in diabetic macular edema (DME). METHODS. A consecutive case series of 87 eyes of 87 patients with DME was included. We measured the leakage area in each field of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid on late-phase FA images. The normative thickness of the nerve fiber layer (NFL), in which the astrocytes are confined, was derived from a previous work using spectral-domain optical coherence tomography. We explored the difference in leakage areas in every two fields. Moreover, we investigated the correlation between the mean of the leakage area and the mean of thickness of the NFL in each ETDRS field. RESULTS. The leakage areas in the nasal, inferior, superior, and temporal fields were 2.34 mm 2 , 2.84 mm 2 , 3.03 mm 2 , and 3.96 mm 2. The difference in leakage area between each two fields was significant in all cases (P < 0.05) except between the inferior and superior fields (P ¼ 0.65). The temporal field was the only field that showed leakage in all 87 cases. The correlation between the leakage area and the thickness of the NFL in the ETDRS fields was negative and highly significant: r ¼ À0.96 (95% confidence interval À0.99 to À0.02). CONCLUSION. The distribution of leakage correlates inversely and statistically significantly with the thickness of the NFL, suggesting astrocytes in the NFL play a pivotal role in preventing damage to the iBRB and subsequent evolution of microaneurysms in DME. Moreover, fluid extravasation due to damage to the iBRB is expressed earlier in the temporal than in the other three fields.

Research paper thumbnail of Impact of B-Scan Averaging on Spectralis Optical Coherence Tomography Image Quality before and after Cataract Surgery

Journal of Ophthalmology, 2017

Background and Objective. To determine optimal image averaging settings for Spectralis optical co... more Background and Objective. To determine optimal image averaging settings for Spectralis optical coherence tomography (OCT) in patients with and without cataract. Study Design/Material and Methods. In a prospective study, the eyes were imaged before and after cataract surgery using seven different image averaging settings. Image quality was quantitatively evaluated using signal-to-noise ratio, distinction between retinal layer image intensity distributions, and retinal layer segmentation performance. Measures were compared pre- and postoperatively across different degrees of averaging. Results. 13 eyes of 13 patients were included and 1092 layer boundaries analyzed. Preoperatively, increasing image averaging led to a logarithmic growth in all image quality measures up to 96 frames. Postoperatively, increasing averaging beyond 16 images resulted in a plateau without further benefits to image quality. Averaging 16 frames postoperatively provided comparable image quality to 96 frames pre...

Research paper thumbnail of Stable registration of pathological 3D-OCT scans using retinal vessels

Proceedings of the Ophthalmic Medical Image Analysis First International Workshop, 2014

We propose a multiple scanner vendor registration method for pathological retinal 3D spectral dom... more We propose a multiple scanner vendor registration method for pathological retinal 3D spectral domain optical coherence tomography volumes based on Myronenko's Coherent Point Drift and our automated vessel shadow segmentation. Coherent point drift is applied to the segmented retinal vessel point sets used as landmarks to generate the registration parameters required. In contrast to other registration methods, our solution incorporates a landmark detection and extraction method that specifically limits the extraction of false positives and a registration method capable of handling any such noise in the landmark point sets. Our experiments show modified Hausdorff distance is reduced by a minimum of 91% between target and registered vessel point sets with at least 94% of bifurcations correctly overlapping based on ground truth, a significant improvement over current methods.

Research paper thumbnail of Multivendor Spectral-Domain Optical Coherence Tomography Dataset, Observer Annotation Performance Evaluation, and Standardized Evaluation Framework for Intraretinal Cystoid Fluid Segmentation

Journal of ophthalmology, 2016

Development of image analysis and machine learning methods for segmentation of clinically signifi... more Development of image analysis and machine learning methods for segmentation of clinically significant pathology in retinal spectral-domain optical coherence tomography (SD-OCT), used in disease detection and prediction, is limited due to the availability of expertly annotated reference data. Retinal segmentation methods use datasets that either are not publicly available, come from only one device, or use different evaluation methodologies making them difficult to compare. Thus we present and evaluate a multiple expert annotated reference dataset for the problem of intraretinal cystoid fluid (IRF) segmentation, a key indicator in exudative macular disease. In addition, a standardized framework for segmentation accuracy evaluation, applicable to other pathological structures, is presented. Integral to this work is the dataset used which must be fit for purpose for IRF segmentation algorithm training and testing. We describe here a multivendor dataset comprised of 30 scans. Each OCT s...

Research paper thumbnail of Choroidal thickness maps from spectral domain and swept source optical coherence tomography: algorithmic versus ground truth annotation

The British journal of ophthalmology, Jan 14, 2016

The purpose of the study was to create a standardised protocol for choroidal thickness measuremen... more The purpose of the study was to create a standardised protocol for choroidal thickness measurements and to determine whether choroidal thickness measurements made on images obtained by spectral domain optical coherence tomography (SD-OCT) and swept source (SS-) OCT from patients with healthy retina are interchangeable when performed manually or with an automatic algorithm. 36 grid cell measurements for choroidal thickness for each volumetric scan were obtained, which were measured for SD-OCT and SS-OCT with two methods on 18 eyes of healthy volunteers. Manual segmentation by experienced retinal graders from the Vienna Reading Center and automated segmentation on >6300 images of the choroid from both devices were statistically compared. Model-based comparison between SD-OCT/SS-OCT showed a systematic difference in choroidal thickness of 16.26±0.725 μm (p<0.001) for manual segmentation and 21.55±0.725 μm (p<0.001) for automated segmentation. Comparison of automated with manua...

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

JAMA Ophthalmology, 2016

IMPORTANCE Robust and sensitive imaging biomarkers for visual function are an unmet medical need ... more 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 (R 2 = 0.59; P < .001). The same baseline parameter also predicted BCVA at 12 months (R 2 = 0.21; P = .003). The BCVA gain correlated with IRC decrease in the exponential model (R 2 = 0.40; P < .001) and linear model (R 2 = 0.25; P = .002). No robust associations were found between SRF and baseline BCVA (R 2 = 0.06; P = .14) or BCVA change (R 2 = 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.

Research paper thumbnail of Differentiation of Diabetic Macular Edema From Pseudophakic Cystoid Macular Edema by Spectral-Domain Optical Coherence Tomography

Investigative ophthalmology & visual science, 2015

To differentiate diabetic macular edema (DME) from pseudophakic cystoid macular edema (PCME) base... more To differentiate diabetic macular edema (DME) from pseudophakic cystoid macular edema (PCME) based solely on spectral-domain optical coherence tomography (SD-OCT). This cross-sectional study included 134 participants: 49 with PCME, 60 with DME, and 25 with diabetic retinopathy (DR) and ME after cataract surgery. First, two unmasked experts classified the 25 DR patients after cataract surgery as either DME, PCME, or mixed-pattern based on SD-OCT and color-fundus photography. Then all 134 patients were divided into two datasets and graded by two masked readers according to a standardized reading-protocol. Accuracy of the masked readers to differentiate the diseases based on SD-OCT parameters was tested. Parallel to the masked readers, a computer-based algorithm was established using support vector machine (SVM) classifiers to automatically differentiate disease entities. The masked readers assigned 92.5% SD-OCT images to the correct clinical diagnose. The classifier-accuracy trained a...

Research paper thumbnail of Predictive Value of Retinal Morphologic Features for Visual Acuity Outcomes of Different Ranibizumab Treatment Regimens for Neovascular Age-Related Macular Degeneration

Ophthalmology, Jan 17, 2015

To establish the predictive value of defined retinal morphologic parameters on visual outcomes an... more To establish the predictive value of defined retinal morphologic parameters on visual outcomes and re-treatment needs in patients with neovascular age-related macular degeneration (nAMD) receiving ranibizumab treatment. Post hoc analysis of a prospective, 12-month, multicenter, phase IIIb trial. Three hundred fifty-three treatment-naïve patients with nAMD. Available data from 319 treatment-naïve patients receiving ranibizumab 0.3 mg monthly (frequent regimen; n = 102) or ranibizumab 0.3 or 0.5 mg quarterly (pooled 0.3/0.5 mg = infrequent regimen; n = 217) were analyzed to assess the correlations between baseline retinal morphologic parameters and best-corrected visual acuity (BCVA) change (structure-function correlations). The BCVA was measured at monthly visits. Optical coherence tomography scans were acquired monthly for quantitative measures of the central retinal thickness and qualitative assessment of retinal morphologic features. Assessed morphologic parameters included intrar...

Research paper thumbnail of Spatio-Temporal Signatures to Predict Retinal Disease Recurrence

Lecture Notes in Computer Science, 2015

We propose a method to predict treatment response patterns based on spatio-temporal disease signa... more 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.

Research paper thumbnail of Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy for Diabetic Macular Edema: A Meta-Analysis of Randomized Controlled Trials

PLoS ONE, 2014

Objective: To evaluate the relative efficacy of ranibizumab (RBZ) monotherapy or combined with la... more Objective: To evaluate the relative efficacy of ranibizumab (RBZ) monotherapy or combined with laser (RBZ + Laser) versus laser monotherapy for the treatment of diabetic macular edema (DME). Methods: A comprehensive literature search using PUBMED, ClinicalTrials.gov, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing RBZ or RBZ + Laser to laser monotherapy in patients with DME. Efficacy estimates were determined by comparing weighted mean differences (WMD) in the change of best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline, and the risk ratios (RR) for the proportions of patients with at least 15 letters change from baseline. Safety analysis estimated the RR of cardiac disorders at 6 to 12 months in RBZ therapy vs. laser monotherapy. Statistical analysis was performed using the RevMan 5.1 software. Results: Seven RCTs were selected for this meta-analysis, including 1749 patients (394 patients in the RBZ group, 642 patients in the RBZ + Laser group, and 713 patients in the laser group). RBZ and RBZ + Laser were superior to laser monotherapy in the mean change of BCVA and CMT from baseline (WMD55.65,

Research paper thumbnail of Motion Artefact Correction in Retinal Optical Coherence Tomography Using Local Symmetry

Lecture Notes in Computer Science, 2014

Patient movements during the acquisition of SD-OCT scans create substantial motion artefacts in t... more 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.

Research paper thumbnail of Impact of vitreomacular adhesion on ranibizumab mono- and combination therapy for neovascular age-related macular degeneration

American journal of ophthalmology, 2014

To investigate the influence of vitreomacular adhesion on the efficacy of pro re nata (PRN) ranib... more To investigate the influence of vitreomacular adhesion on the efficacy of pro re nata (PRN) ranibizumab monotherapy and verteporfin photodynamic therapy (PDT) combination therapy for neovascular age-related macular degeneration. Post hoc analysis of prospective randomized 12-month multicenter clinical trial data. Total of 255 treatment-naïve patients with subfoveal choroidal neovascularization. Assessment of the vitreomacular interface on monthly optical coherence tomography with division of patients into the following categories according to continuous 1-year grading: posterior vitreous detachment (n=154), dynamic release of vitreomacular adhesion (n=32), stable vitreomacular adhesion (n=51). Mean best-corrected visual acuity (BCVA) letter and central retinal thickness changes at month 12 in the vitreomacular interface groups. Mean BCVA changes at month 12 were +3.5 (posterior vitreous detachment), +4.3 (release of vitreomacular adhesion), and +6.3 (vitreomacular adhesion) in patie...

Research paper thumbnail of Efficacy and safety of intravitreal aflibercept injection in wet age-related macular degeneration: outcomes in the Japanese subgroup of the VIEW 2 study

The British journal of ophthalmology, 2015

To evaluate efficacy and safety of intravitreal aflibercept (IVT-AFL) in Japanese patients with w... more To evaluate efficacy and safety of intravitreal aflibercept (IVT-AFL) in Japanese patients with wet age-related macular degeneration (wAMD) from the VIEW 2 trial. In this double-masked study, patients were randomised to: 0.5 mg IVT-AFL every 4 weeks (0.5q4); 2 mg IVT-AFL every 4 weeks (2q4); 2 mg IVT-AFL every 8 weeks (2q8) after 3 monthly injections; or 0.5 mg ranibizumab every 4 weeks (Rq4). Main efficacy outcomes included vision maintenance and best-corrected visual acuity (BCVA) at week 52. At week 52, all Japanese patients in the IVT-AFL groups (n=70) maintained vision, compared with 96% of Japanese patients (n=23/24) treated with ranibizumab. Japanese patients in all treatment groups showed improvement in BCVA after treatment. The Rq4, 2q4 and 2q8 groups experienced similar gains in BCVA from baseline. The 0.5q4 group had higher gains due to an unexpected drop in BCVA between screening and baseline. Central retinal thickness and mean area of choroidal neovascularisation decrea...

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

American journal of ophthalmology, 2014

To measure choroidal thickness on spectral-domain optical coherence tomography (SD OCT) images us... more 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). Post hoc analysis of multicenter clinical trial baseline data. 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 c...

Research paper thumbnail of Patient-reported visual function outcomes improve after ranibizumab treatment in patients with vision impairment due to diabetic macular edema: randomized clinical trial

; for the RESTORE Study Group IMPORTANCE Few data are available on relative changes in vision-rel... more ; for the RESTORE Study Group IMPORTANCE Few data are available on relative changes in vision-related function after treatment for diabetic macular edema (DME). OBJECTIVE To determine the impact of intravitreal ranibizumab, 0.5 mg, compared with laser on patient-reported visual function. DESIGN Phase 3, randomized, double-masked, 12-month study (RESTORE). SETTING Outpatient retina practices in Australia, Canada, and Europe. PARTICIPANTS Patients 18 years or older with type 1 or 2 diabetes mellitus and visual impairment due to DME. INTERVENTIONS Patients were randomized to ranibizumab plus sham laser (n = 116), ranibizumab plus laser (n = 118), or sham injections plus laser (n = 111). Ranibizumab and sham injections were given for 3 consecutive months then as needed; laser or sham laser treatment was given at baseline then as needed. MAIN OUTCOMES AND MEASURES National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) scores at 0, 3, and 12 months for patients receiving 1 or more study treatments with 1 or more postbaseline NEI VFQ-25 assessments and last observation carried forward for missing data. RESULTS Mean baseline NEI VFQ-25 composite scores were 72.8, 73.5, and 74.1 in the ranibizumab, laser, and ranibizumab plus laser groups, respectively. At 12 months, the mean composite scores (95% CIs) improved by 5.0 (ranibizumab vs laser, 2.6 to 7.4; P = .01 vs laser) and 5.4 (ranibizumab plus laser vs laser alone, 3.3 to 7.4; P = .004 vs laser) from baseline in the ranibizumab and ranibizumab plus laser groups, respectively, compared with 0.6 (−1.8 to 3.0) for the laser group. Near activities scores improved by 9.0 (ranibizumab vs laser, 5.0 to 13.0; P = .01) and 9.1 (ranibizumab plus laser vs laser, 5.6 to 12.6; P = .006) compared with 1.1 (−3.0 to 5.2) for the laser group, whereas distance activities scores improved by 5.3 (ranibizumab vs laser, 1.8 to 8.9; P = .04) and 5.6 (ranibizumab plus laser vs laser, 2.3 to 9.0; P = .03) compared with 0.4 (−3.1 to 3.8) for the laser group. Patients with better baseline visual acuity or lower central retinal thickness had greater improvements with ranibizumab treatment compared with laser in composite and some subscale scores compared with patients with worse visual acuity or higher central retinal thickness. CONCLUSIONS AND RELEVANCE These data provide vision-related, patient-reported outcome evidence that mirrors visual acuity outcomes and supports benefits from ranibizumab or ranibizumab plus laser treatment for patients with DME and characteristics similar to those enrolled in this randomized clinical trial. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00687804

Research paper thumbnail of A Longitudinal Comparison of Spectral-Domain Optical Coherence Tomography and Fundus Autofluorescence in Geographic Atrophy

American Journal of Ophthalmology, 2014

To identify reliable criteria based on spectral-domain optical coherence tomography (SD OCT) to m... more To identify reliable criteria based on spectral-domain optical coherence tomography (SD OCT) to monitor disease progression in geographic atrophy attributable to age-related macular degeneration (AMD) compared with lesion size determination based on fundus autofluorescence (FAF). Prospective longitudinal observational study. setting: Institutional. study population: A total of 48 eyes in 24 patients with geographic atrophy. observation procedures: Eyes with geographic atrophy were included and examined at baseline and at months 3, 6, 9, and 12. At each study visit best-corrected visual acuity (BCVA), FAF, and SD OCT imaging were performed. FAF images were analyzed using the region overlay device. Planimetric measurements in SD OCT, including alterations or loss of outer retinal layers and the RPE, as well as choroidal signal enhancement, were performed with the OCT Toolkit. main outcome measures: Areas of interest in patients with geographic atrophy measured from baseline to month 12 by SD OCT compared with the area of atrophy measured by FAF. Geographic atrophy lesion size increased from 8.88 mm² to 11.22 mm² based on quantitative FAF evaluation. Linear regression analysis demonstrated that results similar to FAF planimetry for determining lesion progression can be obtained by measuring the areas of outer plexiform layer thinning (adjusted R(2) = 0.93), external limiting membrane loss (adjusted R(2) = 0.89), or choroidal signal enhancement (R(2) = 0.93) by SD OCT. SD OCT allows morphologic markers of disease progression to be identified in geographic atrophy and may improve understanding of the pathophysiology of atrophic AMD.

Research paper thumbnail of Published Online First

Evaluation of optical coherence tomography findings in age-related macular degeneration: a reprod... more Evaluation of optical coherence tomography findings in age-related macular degeneration: a reproducibility study of two independent reading centres

Research paper thumbnail of Reproducibility of Retinal Thickness Measurements across Spectral-Domain Optical Coherence Tomography Devices using Iowa Reference Algorithm

arXiv: Medical Physics, 2016

PURPOSE: Establishing and obtaining consistent quantitative indices of retinal thickness from a v... more PURPOSE: Establishing and obtaining consistent quantitative indices of retinal thickness from a variety of clinically used Spectral-Domain Optical Coherence Tomography scanners. DESIGN: Retinal images from five Spectral-Domain Optical Coherence Tomography scanners were used to determine total retinal thickness with scanner-specific correction factors establishing consistency of thickness measurement across devices. PARTICIPANTS: 55 Fovea-centered Spectral-Domain Optical Coherence Tomography volumes from eleven subjects were analyzed, obtained from Cirrus HD-OCT, RS-3000, Heidelberg Spectralis, RTVue and Topcon2000, seven subjects with retinal diseases and four normal controls. METHOD: The Iowa Reference Algorithm measured total retinal thickness. Nonlinear model of total retinal thickness measurement comparisons was derived and used for device-specific comparisons. Bland-Altman plots and pairwise predictive equations yielded pairwise scanner-specific differences. Mendel test determi...

Research paper thumbnail of Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration

Ophthalmology, 2018

Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL)... more Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. Design: (Pooled) analysis of cross-sectional data. Participants: 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. Methods: In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random-effect were used to estimate the associations. Main Outcome Measures: early, late or any AMD, phenotypic features of early AMD, lipid measurements. Results: HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). Conclusions: Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains a question to be answered.

Research paper thumbnail of The Decreasing Prevalence of Nonrefractive Visual Impairment in Older Europeans: A Meta-analysis of Published and Unpublished Data

Ophthalmology, Jan 13, 2018

To estimate the prevalence of nonrefractive visual impairment and blindness in European persons 5... more To estimate the prevalence of nonrefractive visual impairment and blindness in European persons 55 years of age and older. Few visual impairment and blindness prevalence estimates are available for the European population. In addition, many of the data collected in European population-based studies currently are unpublished and have not been included in previous estimates. Fourteen European population-based studies participating in the European Eye Epidemiology Consortium (n = 70 723) were included. Each study provided nonrefractive visual impairment and blindness prevalence estimates stratified by age (10-year strata) and gender. Nonrefractive visual impairment and blindness were defined as best-corrected visual acuity worse than 20/60 and 20/400 in the better eye, respectively. Using random effects meta-analysis, prevalence rates were estimated according to age, gender, geographical area, and period (1991-2006 and 2007-2012). Because no data were available for Central and Eastern ...

Research paper thumbnail of The Distribution of Leakage on Fluorescein Angiography in Diabetic Macular Edema: A New Approach to Its Etiology

Investigative Opthalmology & Visual Science, 2017

PURPOSE. To determine the distribution of leakage on fluorescein angiography (FA) and explore the... more PURPOSE. To determine the distribution of leakage on fluorescein angiography (FA) and explore the clinically protective role of astrocytes against damage to the inner blood retinal barrier (iBRB) in diabetic macular edema (DME). METHODS. A consecutive case series of 87 eyes of 87 patients with DME was included. We measured the leakage area in each field of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid on late-phase FA images. The normative thickness of the nerve fiber layer (NFL), in which the astrocytes are confined, was derived from a previous work using spectral-domain optical coherence tomography. We explored the difference in leakage areas in every two fields. Moreover, we investigated the correlation between the mean of the leakage area and the mean of thickness of the NFL in each ETDRS field. RESULTS. The leakage areas in the nasal, inferior, superior, and temporal fields were 2.34 mm 2 , 2.84 mm 2 , 3.03 mm 2 , and 3.96 mm 2. The difference in leakage area between each two fields was significant in all cases (P < 0.05) except between the inferior and superior fields (P ¼ 0.65). The temporal field was the only field that showed leakage in all 87 cases. The correlation between the leakage area and the thickness of the NFL in the ETDRS fields was negative and highly significant: r ¼ À0.96 (95% confidence interval À0.99 to À0.02). CONCLUSION. The distribution of leakage correlates inversely and statistically significantly with the thickness of the NFL, suggesting astrocytes in the NFL play a pivotal role in preventing damage to the iBRB and subsequent evolution of microaneurysms in DME. Moreover, fluid extravasation due to damage to the iBRB is expressed earlier in the temporal than in the other three fields.

Research paper thumbnail of Impact of B-Scan Averaging on Spectralis Optical Coherence Tomography Image Quality before and after Cataract Surgery

Journal of Ophthalmology, 2017

Background and Objective. To determine optimal image averaging settings for Spectralis optical co... more Background and Objective. To determine optimal image averaging settings for Spectralis optical coherence tomography (OCT) in patients with and without cataract. Study Design/Material and Methods. In a prospective study, the eyes were imaged before and after cataract surgery using seven different image averaging settings. Image quality was quantitatively evaluated using signal-to-noise ratio, distinction between retinal layer image intensity distributions, and retinal layer segmentation performance. Measures were compared pre- and postoperatively across different degrees of averaging. Results. 13 eyes of 13 patients were included and 1092 layer boundaries analyzed. Preoperatively, increasing image averaging led to a logarithmic growth in all image quality measures up to 96 frames. Postoperatively, increasing averaging beyond 16 images resulted in a plateau without further benefits to image quality. Averaging 16 frames postoperatively provided comparable image quality to 96 frames pre...

Research paper thumbnail of Stable registration of pathological 3D-OCT scans using retinal vessels

Proceedings of the Ophthalmic Medical Image Analysis First International Workshop, 2014

We propose a multiple scanner vendor registration method for pathological retinal 3D spectral dom... more We propose a multiple scanner vendor registration method for pathological retinal 3D spectral domain optical coherence tomography volumes based on Myronenko's Coherent Point Drift and our automated vessel shadow segmentation. Coherent point drift is applied to the segmented retinal vessel point sets used as landmarks to generate the registration parameters required. In contrast to other registration methods, our solution incorporates a landmark detection and extraction method that specifically limits the extraction of false positives and a registration method capable of handling any such noise in the landmark point sets. Our experiments show modified Hausdorff distance is reduced by a minimum of 91% between target and registered vessel point sets with at least 94% of bifurcations correctly overlapping based on ground truth, a significant improvement over current methods.

Research paper thumbnail of Multivendor Spectral-Domain Optical Coherence Tomography Dataset, Observer Annotation Performance Evaluation, and Standardized Evaluation Framework for Intraretinal Cystoid Fluid Segmentation

Journal of ophthalmology, 2016

Development of image analysis and machine learning methods for segmentation of clinically signifi... more Development of image analysis and machine learning methods for segmentation of clinically significant pathology in retinal spectral-domain optical coherence tomography (SD-OCT), used in disease detection and prediction, is limited due to the availability of expertly annotated reference data. Retinal segmentation methods use datasets that either are not publicly available, come from only one device, or use different evaluation methodologies making them difficult to compare. Thus we present and evaluate a multiple expert annotated reference dataset for the problem of intraretinal cystoid fluid (IRF) segmentation, a key indicator in exudative macular disease. In addition, a standardized framework for segmentation accuracy evaluation, applicable to other pathological structures, is presented. Integral to this work is the dataset used which must be fit for purpose for IRF segmentation algorithm training and testing. We describe here a multivendor dataset comprised of 30 scans. Each OCT s...

Research paper thumbnail of Choroidal thickness maps from spectral domain and swept source optical coherence tomography: algorithmic versus ground truth annotation

The British journal of ophthalmology, Jan 14, 2016

The purpose of the study was to create a standardised protocol for choroidal thickness measuremen... more The purpose of the study was to create a standardised protocol for choroidal thickness measurements and to determine whether choroidal thickness measurements made on images obtained by spectral domain optical coherence tomography (SD-OCT) and swept source (SS-) OCT from patients with healthy retina are interchangeable when performed manually or with an automatic algorithm. 36 grid cell measurements for choroidal thickness for each volumetric scan were obtained, which were measured for SD-OCT and SS-OCT with two methods on 18 eyes of healthy volunteers. Manual segmentation by experienced retinal graders from the Vienna Reading Center and automated segmentation on >6300 images of the choroid from both devices were statistically compared. Model-based comparison between SD-OCT/SS-OCT showed a systematic difference in choroidal thickness of 16.26±0.725 μm (p<0.001) for manual segmentation and 21.55±0.725 μm (p<0.001) for automated segmentation. Comparison of automated with manua...

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

JAMA Ophthalmology, 2016

IMPORTANCE Robust and sensitive imaging biomarkers for visual function are an unmet medical need ... more 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 (R 2 = 0.59; P < .001). The same baseline parameter also predicted BCVA at 12 months (R 2 = 0.21; P = .003). The BCVA gain correlated with IRC decrease in the exponential model (R 2 = 0.40; P < .001) and linear model (R 2 = 0.25; P = .002). No robust associations were found between SRF and baseline BCVA (R 2 = 0.06; P = .14) or BCVA change (R 2 = 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.

Research paper thumbnail of Differentiation of Diabetic Macular Edema From Pseudophakic Cystoid Macular Edema by Spectral-Domain Optical Coherence Tomography

Investigative ophthalmology & visual science, 2015

To differentiate diabetic macular edema (DME) from pseudophakic cystoid macular edema (PCME) base... more To differentiate diabetic macular edema (DME) from pseudophakic cystoid macular edema (PCME) based solely on spectral-domain optical coherence tomography (SD-OCT). This cross-sectional study included 134 participants: 49 with PCME, 60 with DME, and 25 with diabetic retinopathy (DR) and ME after cataract surgery. First, two unmasked experts classified the 25 DR patients after cataract surgery as either DME, PCME, or mixed-pattern based on SD-OCT and color-fundus photography. Then all 134 patients were divided into two datasets and graded by two masked readers according to a standardized reading-protocol. Accuracy of the masked readers to differentiate the diseases based on SD-OCT parameters was tested. Parallel to the masked readers, a computer-based algorithm was established using support vector machine (SVM) classifiers to automatically differentiate disease entities. The masked readers assigned 92.5% SD-OCT images to the correct clinical diagnose. The classifier-accuracy trained a...

Research paper thumbnail of Predictive Value of Retinal Morphologic Features for Visual Acuity Outcomes of Different Ranibizumab Treatment Regimens for Neovascular Age-Related Macular Degeneration

Ophthalmology, Jan 17, 2015

To establish the predictive value of defined retinal morphologic parameters on visual outcomes an... more To establish the predictive value of defined retinal morphologic parameters on visual outcomes and re-treatment needs in patients with neovascular age-related macular degeneration (nAMD) receiving ranibizumab treatment. Post hoc analysis of a prospective, 12-month, multicenter, phase IIIb trial. Three hundred fifty-three treatment-naïve patients with nAMD. Available data from 319 treatment-naïve patients receiving ranibizumab 0.3 mg monthly (frequent regimen; n = 102) or ranibizumab 0.3 or 0.5 mg quarterly (pooled 0.3/0.5 mg = infrequent regimen; n = 217) were analyzed to assess the correlations between baseline retinal morphologic parameters and best-corrected visual acuity (BCVA) change (structure-function correlations). The BCVA was measured at monthly visits. Optical coherence tomography scans were acquired monthly for quantitative measures of the central retinal thickness and qualitative assessment of retinal morphologic features. Assessed morphologic parameters included intrar...

Research paper thumbnail of Spatio-Temporal Signatures to Predict Retinal Disease Recurrence

Lecture Notes in Computer Science, 2015

We propose a method to predict treatment response patterns based on spatio-temporal disease signa... more 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.

Research paper thumbnail of Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy for Diabetic Macular Edema: A Meta-Analysis of Randomized Controlled Trials

PLoS ONE, 2014

Objective: To evaluate the relative efficacy of ranibizumab (RBZ) monotherapy or combined with la... more Objective: To evaluate the relative efficacy of ranibizumab (RBZ) monotherapy or combined with laser (RBZ + Laser) versus laser monotherapy for the treatment of diabetic macular edema (DME). Methods: A comprehensive literature search using PUBMED, ClinicalTrials.gov, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing RBZ or RBZ + Laser to laser monotherapy in patients with DME. Efficacy estimates were determined by comparing weighted mean differences (WMD) in the change of best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline, and the risk ratios (RR) for the proportions of patients with at least 15 letters change from baseline. Safety analysis estimated the RR of cardiac disorders at 6 to 12 months in RBZ therapy vs. laser monotherapy. Statistical analysis was performed using the RevMan 5.1 software. Results: Seven RCTs were selected for this meta-analysis, including 1749 patients (394 patients in the RBZ group, 642 patients in the RBZ + Laser group, and 713 patients in the laser group). RBZ and RBZ + Laser were superior to laser monotherapy in the mean change of BCVA and CMT from baseline (WMD55.65,

Research paper thumbnail of Motion Artefact Correction in Retinal Optical Coherence Tomography Using Local Symmetry

Lecture Notes in Computer Science, 2014

Patient movements during the acquisition of SD-OCT scans create substantial motion artefacts in t... more 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.

Research paper thumbnail of Impact of vitreomacular adhesion on ranibizumab mono- and combination therapy for neovascular age-related macular degeneration

American journal of ophthalmology, 2014

To investigate the influence of vitreomacular adhesion on the efficacy of pro re nata (PRN) ranib... more To investigate the influence of vitreomacular adhesion on the efficacy of pro re nata (PRN) ranibizumab monotherapy and verteporfin photodynamic therapy (PDT) combination therapy for neovascular age-related macular degeneration. Post hoc analysis of prospective randomized 12-month multicenter clinical trial data. Total of 255 treatment-naïve patients with subfoveal choroidal neovascularization. Assessment of the vitreomacular interface on monthly optical coherence tomography with division of patients into the following categories according to continuous 1-year grading: posterior vitreous detachment (n=154), dynamic release of vitreomacular adhesion (n=32), stable vitreomacular adhesion (n=51). Mean best-corrected visual acuity (BCVA) letter and central retinal thickness changes at month 12 in the vitreomacular interface groups. Mean BCVA changes at month 12 were +3.5 (posterior vitreous detachment), +4.3 (release of vitreomacular adhesion), and +6.3 (vitreomacular adhesion) in patie...

Research paper thumbnail of Efficacy and safety of intravitreal aflibercept injection in wet age-related macular degeneration: outcomes in the Japanese subgroup of the VIEW 2 study

The British journal of ophthalmology, 2015

To evaluate efficacy and safety of intravitreal aflibercept (IVT-AFL) in Japanese patients with w... more To evaluate efficacy and safety of intravitreal aflibercept (IVT-AFL) in Japanese patients with wet age-related macular degeneration (wAMD) from the VIEW 2 trial. In this double-masked study, patients were randomised to: 0.5 mg IVT-AFL every 4 weeks (0.5q4); 2 mg IVT-AFL every 4 weeks (2q4); 2 mg IVT-AFL every 8 weeks (2q8) after 3 monthly injections; or 0.5 mg ranibizumab every 4 weeks (Rq4). Main efficacy outcomes included vision maintenance and best-corrected visual acuity (BCVA) at week 52. At week 52, all Japanese patients in the IVT-AFL groups (n=70) maintained vision, compared with 96% of Japanese patients (n=23/24) treated with ranibizumab. Japanese patients in all treatment groups showed improvement in BCVA after treatment. The Rq4, 2q4 and 2q8 groups experienced similar gains in BCVA from baseline. The 0.5q4 group had higher gains due to an unexpected drop in BCVA between screening and baseline. Central retinal thickness and mean area of choroidal neovascularisation decrea...

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

American journal of ophthalmology, 2014

To measure choroidal thickness on spectral-domain optical coherence tomography (SD OCT) images us... more 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). Post hoc analysis of multicenter clinical trial baseline data. 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 c...

Research paper thumbnail of Patient-reported visual function outcomes improve after ranibizumab treatment in patients with vision impairment due to diabetic macular edema: randomized clinical trial

; for the RESTORE Study Group IMPORTANCE Few data are available on relative changes in vision-rel... more ; for the RESTORE Study Group IMPORTANCE Few data are available on relative changes in vision-related function after treatment for diabetic macular edema (DME). OBJECTIVE To determine the impact of intravitreal ranibizumab, 0.5 mg, compared with laser on patient-reported visual function. DESIGN Phase 3, randomized, double-masked, 12-month study (RESTORE). SETTING Outpatient retina practices in Australia, Canada, and Europe. PARTICIPANTS Patients 18 years or older with type 1 or 2 diabetes mellitus and visual impairment due to DME. INTERVENTIONS Patients were randomized to ranibizumab plus sham laser (n = 116), ranibizumab plus laser (n = 118), or sham injections plus laser (n = 111). Ranibizumab and sham injections were given for 3 consecutive months then as needed; laser or sham laser treatment was given at baseline then as needed. MAIN OUTCOMES AND MEASURES National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) scores at 0, 3, and 12 months for patients receiving 1 or more study treatments with 1 or more postbaseline NEI VFQ-25 assessments and last observation carried forward for missing data. RESULTS Mean baseline NEI VFQ-25 composite scores were 72.8, 73.5, and 74.1 in the ranibizumab, laser, and ranibizumab plus laser groups, respectively. At 12 months, the mean composite scores (95% CIs) improved by 5.0 (ranibizumab vs laser, 2.6 to 7.4; P = .01 vs laser) and 5.4 (ranibizumab plus laser vs laser alone, 3.3 to 7.4; P = .004 vs laser) from baseline in the ranibizumab and ranibizumab plus laser groups, respectively, compared with 0.6 (−1.8 to 3.0) for the laser group. Near activities scores improved by 9.0 (ranibizumab vs laser, 5.0 to 13.0; P = .01) and 9.1 (ranibizumab plus laser vs laser, 5.6 to 12.6; P = .006) compared with 1.1 (−3.0 to 5.2) for the laser group, whereas distance activities scores improved by 5.3 (ranibizumab vs laser, 1.8 to 8.9; P = .04) and 5.6 (ranibizumab plus laser vs laser, 2.3 to 9.0; P = .03) compared with 0.4 (−3.1 to 3.8) for the laser group. Patients with better baseline visual acuity or lower central retinal thickness had greater improvements with ranibizumab treatment compared with laser in composite and some subscale scores compared with patients with worse visual acuity or higher central retinal thickness. CONCLUSIONS AND RELEVANCE These data provide vision-related, patient-reported outcome evidence that mirrors visual acuity outcomes and supports benefits from ranibizumab or ranibizumab plus laser treatment for patients with DME and characteristics similar to those enrolled in this randomized clinical trial. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00687804

Research paper thumbnail of A Longitudinal Comparison of Spectral-Domain Optical Coherence Tomography and Fundus Autofluorescence in Geographic Atrophy

American Journal of Ophthalmology, 2014

To identify reliable criteria based on spectral-domain optical coherence tomography (SD OCT) to m... more To identify reliable criteria based on spectral-domain optical coherence tomography (SD OCT) to monitor disease progression in geographic atrophy attributable to age-related macular degeneration (AMD) compared with lesion size determination based on fundus autofluorescence (FAF). Prospective longitudinal observational study. setting: Institutional. study population: A total of 48 eyes in 24 patients with geographic atrophy. observation procedures: Eyes with geographic atrophy were included and examined at baseline and at months 3, 6, 9, and 12. At each study visit best-corrected visual acuity (BCVA), FAF, and SD OCT imaging were performed. FAF images were analyzed using the region overlay device. Planimetric measurements in SD OCT, including alterations or loss of outer retinal layers and the RPE, as well as choroidal signal enhancement, were performed with the OCT Toolkit. main outcome measures: Areas of interest in patients with geographic atrophy measured from baseline to month 12 by SD OCT compared with the area of atrophy measured by FAF. Geographic atrophy lesion size increased from 8.88 mm² to 11.22 mm² based on quantitative FAF evaluation. Linear regression analysis demonstrated that results similar to FAF planimetry for determining lesion progression can be obtained by measuring the areas of outer plexiform layer thinning (adjusted R(2) = 0.93), external limiting membrane loss (adjusted R(2) = 0.89), or choroidal signal enhancement (R(2) = 0.93) by SD OCT. SD OCT allows morphologic markers of disease progression to be identified in geographic atrophy and may improve understanding of the pathophysiology of atrophic AMD.