I. Golbaz

Imaging of the Retinal Pigment Epithelium in Age-Related Macular Degeneration Using Polarization-Sensitive Optical Coherence Tomography

Purpose. Spectral-domain optical coherence tomography (SD-OCT) provides new insights into the understanding of age-related macular degeneration (AMD) but limited information on the nature of hyperreflective tissue at the level of the retinal pigment epithelium. Therefore, polarization-sensitive (PS) SD-OCT was used to identify and characterize typical RPE findings in AMD. Methods. Forty-four eyes of 44 patients with AMD were included in this prospective case series representing the entire AMD spectrum from drusen (n = 11), geographic atrophy (GA; n = 11), neovascular AMD (nAMD; n = 11) to fibrotic scars (n = 11). Imaging systems were used for comparative imaging. A PS-SD-OCT instrument was developed that was capable of recording intensity and polarization parameters simultaneously during a single scan. Results. In drusen, PS-SD-OCT identified a continuous RPE layer with focal elevations. Discrete RPE atrophy (RA) could be observed in two patients. In GA, the extension of the RA was significantly larger. Residual RPE islands could be detected within the atrophic zone. PS-SD-OCT identified multiple foci of RPE loss in patients with nAMD and allowed recognition of advanced RPE disease associated with choroidal neovascularization. Wide areas of RA containing residual spots of intact retinal pigment epithelium could be identified in fibrotic scars. Conclusions. PS-SD-OCT provided precise identification of retinal pigment epithelium in AMD. Recognition of these disease-specific RA patterns in dry and wet forms of AMD is of particular relevance to identify the status and progression of RPE disease and may help to better estimate the functional prognosis of AMD.

Influence of the vitreomacular interface on outcomes of ranibizumab therapy in neovascular age-related macular degeneration.

PURPOSE To investigate the influence of the vitreomacular interface (VMI) on the functional and anatomic efficacy of ranibizumab therapy in patients with neovascular age-related macular degeneration (AMD). DESIGN Subanalysis of a prospective, 12-month, multicenter, phase IIIb trial. PARTICIPANTS A total of 353 treatment-naïve patients with subfoveal choroidal neovascularization (CNV) receiving quarterly or monthly ranibizumab therapy. METHODS On monthly optical coherence tomography (OCT) scan sets, the VMI configuration was graded by a certified reading center into one of the following conditions: continuous posterior vitreoretinal attachment (PVA), vitreomacular adhesion (VMA), partial vitreous detachment without vitreomacular contact, or complete posterior vitreous detachment (PVD). Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measurements were performed at monthly intervals. Analysis included patients with a minimum of 10 OCT examinations, including baseline and month 12 (n = 251). After integration of the VMI configuration over 12 months, patients were divided into one of the following categories: PVD (n = 162), release of vitreomacular contact (RELEASE; n = 48), VMA (n = 37), or PVA (n = 4). General estimation equation analyses were applied to test for noninferiority of quarterly versus monthly treatment. MAIN OUTCOME MEASURES The BCVA and CRT changes at month 12. RESULTS Mean BCVA changes in letters were +4.7 (PVD), +3.2 (RELEASE), and -0.2 (VMA) in the quarterly regimen and +4.9 (PVD), +12.7 (RELEASE), and +7.5 (VMA) in the monthly regimen. No difference in therapeutic efficiency between monthly and quarterly intervention was found in eyes with PVD, and quarterly treatment was noninferior to monthly treatment (P = 0.001). However, monthly treatment was superior to quarterly treatment in the RELEASE (P = 0.008) and VMA (P = 0.043) groups. Mean CRT changes were -98 and -96 μm (PVD), -117 and -136 μm (RELEASE), and -93 and -87 μm (VMA) in the monthly and quarterly regimens, respectively, without statistically significant differences. CONCLUSIONS The configuration of the VMI seems to have an important effect on visual outcomes and need for retreatment. In patients with PVD, a lower treatment frequency may be feasible, whereas patients with RELEASE or VMA may benefit from intensive retreatment. These findings may serve as a basis for individualized treatment decisions in anti-angiogenic therapy of neovascular AMD and perhaps other indications.

Comparison of retinal thickness measurements and segmentation performance of four different spectral and time domain OCT devices in neovascular age-related macular degeneration

Aims: To evaluate the reliability of different optical coherence tomography (OCT) devices and scanning patterns in the assessment of retinal thickness and segmentation performance in neovascular age-related macular degeneration (nAMD). Methods: 28 eyes with nAMD and 10 healthy eyes were imaged using conventional time domain (TD) OCT as well as three spectral-domain (SD) OCT systems. Radial scans of 6 mm in size were compared between Stratus and Topcon OCT, in addition to raster scans of all three SD-OCT devices. Retinal thickness values were analysed. Results: Spectralis SD-OCT demonstrated the highest values of all OCT devices in central millimetre thickness (CMMT), and Topcon OCT raster scans showed the lowest values. Significant correlations could be found between the CMMT measurements of Cirrus and Spectralis OCT (r = 0.87). Analyses showed best segmentation for Cirrus and Spectralis SD-OCTs. Cirrus 200×200×1024 scans showed 4% and Stratus OCT 38% moderate or severe segmentation errors. Conclusion: Retinal thickness values were generally higher in SD-OCT analysis. Different performances of automatic retinal thickness analysis indicate the potential of different software algorithms to quantify retinal morphology in nAMD. Further development of current algorithms may improve quantification of retinal thickness detection in the future even further.

Quantification of the therapeutic response of intraretinal, subretinal, and subpigment epithelial compartments in exudative AMD during anti-VEGF therapy

PURPOSE To analyze the functional and morphologic effects of different ranibizumab treatment regimens on retinal and subretinal as well as sub-RPE compartments in neovascular age-related macular degeneration (nAMD) using spectral-domain optical coherence tomography (SD-OCT) and manual segmentation software. METHODS Twenty-seven eyes of 27 patients with nAMD were examined over a 12-month period. Two treatment arms received either monthly or quarterly administered intravitreal ranibizumab. Intraretinal, subretinal, and sub-RPE volume equivalents were delineated using manual segmentation software over a defined series of B-scans obtained by SD-OCT. The mean area in pixels was calculated for each compartment at each time interval. RESULTS SD-OCT and manual segmentation allowed for exact identification of intraretinal, subretinal and sub-RPE compartments and their responses to different treatment regimens. The loading dose demonstrated a corresponding treatment effect on all anatomic parameters. In contrast to the sub-RPE compartment, intraretinal fluid accumulation and subretinal fluid accumulation (SRFA) demonstrated an immediate response to ranibizumab therapy. The overall plasticity of the morphologic response declined over time. In general, SRFA demonstrated greater sensitivity for therapeutic effects and was more frequently associated with recurrent disease. CONCLUSIONS An exact quantification of fluid in different anatomic compartments based on SD-OCT imaging, using appropriate segmentation software systems, may be useful to determine optimal treatment and retreatment parameters and explains the lack of correlation of best-corrected visual acuity and conventional OCT values.

Time course of morphologic effects on different retinal compartments after ranibizumab therapy in age-related macular degeneration

PURPOSE To analyze the effect of ranibizumab therapy on retinal and subretinal compartments in age-related macular degeneration and to compare the time course of compartment specific effects to visual function. DESIGN Prospective noncomparative case series. PARTICIPANTS Fourteen patients with changes in 3 major compartments owing to neovascular age-related macular degeneration. METHODS Standard treatment with 3 monthly doses of intravitreal ranibizumab was performed. Eyes were examined at baseline and weeks 1, 4, and 12 using a standardized protocol. Manual segmentation was applied to all 128 B-scans contained in a macular raster scan (MRS). MAIN OUTCOME MEASURES Morphology and time course of different retinal and subretinal compartments. RESULTS High-definition optical coherence tomography and manual segmentation allowed for precise identification of volumes within individual compartments. All morphologic parameters responded positively to therapy, but demonstrated a specific time course. Subretinal fluid was identified as the most relevant factor for visual function, whereas changes in retinal and subpigment epithelial volumes did not correlate with the time course of functional rehabilitation. CONCLUSION Analysis of MRS identified a characteristic impact of therapy on retinal and subretinal morphology.

Identification of Optical Density Ratios in Subretinal Fluid as a Clinically Relevant Biomarker in Exudative Macular Disease

PURPOSE To investigate the potential role of optical density ratios (ODRs) obtained from subretinal fluid analysis in exudative macular disease and to identify the predictive role of ODRs under therapy in comparison to conventional morphometric measurements (CMMs). METHODS Fifteen patients with neovascular age-related macular degeneration (nAMD) and 15 with acute central serous chorioretinopathy (CSC) were included in this prospective comparative and interventional case series. High-definition optical coherence tomography (SD-OCT) was performed according to a standardized protocol. nAMD patients received a standard treatment consisting of three monthly doses of intravitreous ranibizumab. Best corrected visual acuity (BCVA) was assessed at baseline (BSL) and weeks 2, 4, and 12. SD-OCT parameters were compared between CSC and nAMD at baseline. Predictive factors for functional recovery under ranibizumab treatment were identified in patients with nAMD. RESULTS ODR showed highly significant differences between CSC and nAMD, whereas it was not possible to differentiate between these diseases on the basis of CMM. During follow-up, CMM correlated with BCVA at BSL only, whereas ODR showed a significant correlation with BCVA at week 4 and 12 during antiangiogenic therapy. CONCLUSIONS Results suggest that CMM may correlate with BCVA at BSL, but has limited predictive value regarding recovery of visual function. Most interesting, ODR correlated with BCVA under therapy and was the only parameter that was pathognomic for nAMD in contrast to CSC in this study. ODR may reflect the status of the blood-retina barrier and may be used for pathophysiologic differentiation and prognostic purposes in exudative macular disease.

Alterations of intraretinal layers in acute central serous chorioretinopathy

Purpose:  Optical coherence tomography (OCT) is restricted by its low scanning speed and limited resolution. High‐definition raster‐scanning OCT (HD‐OCT) was used to evaluate changes in retinal microstructure in patients with acute central serous chorioretinopathy (CSCR) and to find new morphological features.

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

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

[The role of Stratus OCT in anti-VEGF therapy. Qualitative and quantitative assessment of neovascular AMD].

BACKGROUND The evaluation of OCT3 during anti-VEGF therapy. METHODS A total of 29 patients with choroidal neovascularization secondary to AMD received 3 intravitreal injections of ranibizumab. OCT examination and visual acuity testing (ETDRS) were performed before therapy onset, after 1 week and after 1, 2 and 3 months. RESULTS The central retinal thickness (CRT) was assessed correctly by OCT in 128 out of 145 measurements. There was a distinct (84%) but not significant correlation between decrease in central retinal thickness and increase in visual acuity. Incorrect retinal layer segmentation and inadequate CRT measurements were a significant technical limitation. CONCLUSION During anti-VEGF therapy, OCT allows documentation and quantification of morphologic retinal changes and in most cases also for an estimation of functional improvement.

[Three-dimensional imaging in central serous chorioretinopathy].

BACKGROUND Conventional optical coherence tomography (OCT) has brought new insights to retinal diagnostics, but it is restricted due to its low scanning speed and limited resolution. In this study, high-resolution raster scanning OCT (HR-OCT) was used to identify typical changes in central serous chorioretinopathy (CSC). METHODS Fifteen consecutive patients with acute CSC were imaged using HR-OCT with an axial image resolution of 6 mum. The scanned area measured 6x6 mm2. Three-dimensional (3D) evaluation was performed using various analysing programmes. RESULTS Topographic changes in CSC could be visualised with 3D reconstructions in all locations. Retinal thickness was measured with the automatic segmentation mode and quantified precisely. Results were presented in 2D and 3D maps. En-face imaging as a modality to present an integrative overview showed specific alterations in CSC. CONCLUSION HR-OCT was able to provide essential additional information about CSC when combined with appropriate analysing programmes, allowing the identification of typical differences. Aside from precise volumetric measurements, exact localisation of pathological deviations could be achieved.