Macular Telangiectasia type 2: multimodal assessment of retinal function and microstructure.

PURPOSE: To assess the impact of neurodegenerative morphologic alterations due to macular telangiectasia type 2 (MacTel) on microperimetry (MP) and multifocal electroretinography (mfERG). METHODS: Thirty-five eyes of 18 patients with MacTel were examined using spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), mfERG and MP. Software was used to match SD-OCT B-scans with the corresponding retinal sensitivity map and multifocal electroretinograms (mfERGs), thus enabling direct structure/function correlation. RESULTS: Loss of the ellipsoid zone (EZ) had the strongest negative association with retinal sensitivity (16.77 dB versus 4.58 dB, adj. p < 0.001) of all parameters examined, and a limited negative effect on mfERGs (0.32 SD versus -1.97 SD adj. p = 0.121). Ellipsoid zone (EZ) irregularity was associated with reduced MP values but preserved mfERGs. There was a significant association between areas of inner retinal hyporeflectivity and loss of MP sensitivity (adj. p < 0.001) but the reduction in sensitivity was less than in locations with EZ loss. Areas of mfERG abnormality showed similar sensitivity loss with either inner retinal hyporeflectivity or EZ loss (adj. p = 0.063). In areas with EZ loss alone, preservation of the external limiting membrane (ELM) was associated with higher MP values than in areas with additional ELM loss; the integrity of the ELM alone was not associated with changes either in MP or mfERG. Increased FAF was observed in 51% of eyes, mixed/reduced FAF in 40%, and no abnormality was detected in 9% of eyes. CONCLUSION: The data suggest both MP and mfERG to be useful non-invasive modalities for detecting localised macular dysfunction in MacTel. The findings suggest a different sensitivity of the two modalities to inner and outer retinal changes in macular function and are therefore complementary.

Ganglion cell layer thickening in well-controlled patients with type 1 diabetes: an early sign for diabetic retinopathy?

PURPOSE: To evaluate early changes in retinal layers using optical coherence tomography (OCT) in patients with long-standing type 1 diabetes (DM1) receiving intensified insulin therapy. METHODS: In a cross-sectional case-control study 150 patients with DM1 and 150 age- and sex-matched healthy control participants underwent OCT imaging. Scans of both eyes were analysed for different layers (NFL, GCL (+IPL), INL, outer layer complex (OLC, including OPL, ONL and ELM) and photoreceptors (PR)) in all subfields of an ETDRS grid. All analyses were performed semi-automatically using custom software by certified graders of the Vienna Reading Center. ANOVA models were used to compare the mean thickness of the layers between patients and controls. RESULTS: Six hundred eyes with 512 datapoints in 49 b-scans in each OCT were analysed. Mean thickness in patients/controls was 31.35 µm/30.65 µm (NFL, p = 0.0347), 76.7 µm/73.15 µm (GCL, p ≤ 0.0001), 36.29 µm/37.13 µm (INL, p = 0.0116), 114.34 µm/112.02 µm (OLC, p < 0.0001) and 44.71 µm/44.69 µm (PR, p = 0.9401). When evaluating the ETDRS subfields separately for clinically meaningful hypotheses, a significant swelling of the GCL in patients could be found uniformly and a central swelling for the OLC, whereas the distribution of NFL and INL thickening suggests that their statistical significance was not clinically relevant. CONCLUSION: These preliminary results demonstrate that preclinical retinal changes in patients with long-standing DM1 can be found by retinal layer evaluation. However, the changes are layer-specific, with significant thickening of the GCL and less so of the OLC suggesting a role as an early sign for diffuse swelling and the evolution of DME even in well-controlled diabetes.

Identification and Quantification of the Angiofibrotic Switch in Neovascular AMD.

Purpose: We quantify volumetric changes of subretinal hyperreflective material (SHRM) and determine the conversion toward subretinal fibrosis, the angiofibrotic switch, under anti-VEGF therapy using polarization-sensitive optical coherence tomography (PS-OCT). Methods: A total of 50 eyes of 50 patients with treatment-naïve neovascular age-related macular degeneration (AMD) were included in this prospective observational study: 26 diagnosed with type 1 choroidal neovascularization (CNV), seven with type 2 CNV, 11 with mixed type CNV, three with a retinal angiomatous proliferation (RAP) lesion and three with a polypoidal choroidal vasculopathy (PCV). Patients were imaged at baseline and at the end of the loading phase (after treatment with three intravitreal anti-VEGF injections) using a PS-OCT system with a scanning angle of 30° × 30° and a scan pattern of 1024 × 250 A-scans. The device is capable of detecting fibrosis based on birefringence and the RPE based on depolarization. The volume of SHRM was quantified by manual delineation in each PS-OCT B-scan and interpolation between B-scans using proprietary reading center certified software. The occurrence of fibrosis detected by PS-OCT was compared to the clinical presentation of subretinal fibrosis. Results: Of 50 eyes, 28 had SHRM at baseline. Seven of these eyes had subretinal fibrosis within 3 months, six of which could be detected unambiguously based on PS-OCT imaging. SHRM thickness and volume at month 3 (P = 0.001 and P = 0.02) were significantly larger and the reduction of SHRM thickness and volume (P = 0.002 and P = 0.027) in response to therapy were significantly less pronounced in eyes with fibrosis. Conclusions: SHRM volume decreases significantly under anti-VEGF therapy. However, lesions unresponsive to therapy may progress to fibrosis as early as 3 months. Reduction in SHRM thickness may be a prognostic marker for treatment response.

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

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 mm2, 2.84 mm2, 3.03 mm2, and 3.96 mm2. 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 = 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 = -0.96 (95% confidence interval -0.99 to -0.02). 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.

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.

Evaluating the impact of vitreomacular adhesion on anti-VEGF therapy for retinal vein occlusion using machine learning.

Vitreomacular adhesion (VMA) represents a prognostic biomarker in the management of exudative macular disease using anti-vascular endothelial growth factor (VEGF) agents. However, manual evaluation of VMA in 3D optical coherence tomography (OCT) is laborious and data on its impact on therapy of retinal vein occlusion (RVO) are limited. The aim of this study was to (1) develop a fully automated segmentation algorithm for the posterior vitreous boundary and (2) to study the effect of VMA on anti-VEGF therapy for RVO. A combined machine learning/graph cut segmentation algorithm for the posterior vitreous boundary was designed and evaluated. 391 patients with central/branch RVO under standardized ranibizumab treatment for 6/12 months were included in a systematic post-hoc analysis. VMA (70%) was automatically differentiated from non-VMA (30%) using the developed method combined with unsupervised clustering. In this proof-of-principle study, eyes with VMA showed larger BCVA gains than non-VMA eyes (BRVO: 15 ± 12 vs. 11 ± 11 letters, p = 0.02; CRVO: 18 ± 14 vs. 9 ± 13 letters, p < 0.01) and received a similar number of retreatments. However, this association diminished after adjustment for baseline BCVA, also when using more fine-grained VMA classes. Our study illustrates that machine learning represents a promising path to assess imaging biomarkers in OCT.

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.

Geographic Atrophy and Foveal-Sparing Changes Related to Visual Acuity in Patients With Dry Age-Related Macular Degeneration Over Time.

PURPOSE: To correlate the area of geographic atrophy (GA) and residual foveal sparing (FS), and to identify the minimum FS and maximum GA area allowing sufficient visual acuity (VA) for daily tasks. DESIGN: Prospective cohort study. METHODS: Thirty-six eyes of 25 patients with GA and FS were followed for 18 months using spectral-domain optical coherence tomography and VA tests. Volume scans were imported into software enabling grading of areas in B-scans and computing of planimetric measurements in complete volume scans. Correlation of areas 1 (complete atrophy), 2 (FS in the central millimeter), and 3 (FS in the central 3 mm) with each other and with best-corrected VA (BCVA) were evaluated. RESULTS: Baseline means of areas 1, 2, and 3 were 6.15 mm2, 0.49 mm2, and 3.08 mm2, respectively. At 1 year, area 1 increased by a mean of 1.33 mm2, while areas 2 and 3 were decreased by 0.12 mm2 and 0.65 mm2, respectively. From baseline to 18 months and from visit to visit, all areas and BCVA changed progressively (P < .001). Significant thresholds in GA size and FS for achieving a BCVA ≥ 70 ETDRS letters were detected (area 1: ≤6 mm2; area 2: ≥0.48 mm2; and area 3: ≥3.28 mm2). CONCLUSION: GA and FS changed inversely over time. In general, FS highly correlated with BCVA, while GA progression correlated with the central 3-mm FS regression, but not with BCVA. A threshold in GA and FS area could be determined for BCVA necessary for daily activity.

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.

Automated Fovea Detection in Spectral Domain Optical Coherence Tomography Scans of Exudative Macular Disease.

In macular spectral domain optical coherence tomography (SD-OCT) volumes, detection of the foveal center is required for accurate and reproducible follow-up studies, structure function correlation, and measurement grid positioning. However, disease can cause severe obscuring or deformation of the fovea, thus presenting a major challenge in automated detection. We propose a fully automated fovea detection algorithm to extract the fovea position in SD-OCT volumes of eyes with exudative maculopathy. The fovea is classified into 3 main appearances to both specify the detection algorithm used and reduce computational complexity. Based on foveal type classification, the fovea position is computed based on retinal nerve fiber layer thickness. Mean absolute distance between system and clinical expert annotated fovea positions from a dataset comprised of 240 SD-OCT volumes was 162.3 µm in cystoid macular edema and 262 µm in nAMD. The presented method has cross-vendor functionality, while demonstrating accurate and reliable performance close to typical expert interobserver agreement. The automatically detected fovea positions may be used as landmarks for intra- and cross-patient registration and to create a joint reference frame for extraction of spatiotemporal features in "big data." Furthermore, reliable analyses of retinal thickness, as well as retinal structure function correlation, may be facilitated.

A novel benchmark model for intelligent annotation of spectral-domain optical coherence tomography scans using the example of cyst annotation.

BACKGROUND AND OBJECTIVES: The lack of benchmark data in computational ophthalmology contributes to the challenging task of applying disease assessment and evaluate performance of machine learning based methods on retinal spectral domain optical coherence tomography (SD-OCT) scans. Presented here is a general framework for constructing a benchmark dataset for retinal image processing tasks such as cyst, vessel, and subretinal fluid segmentation and as a result, a benchmark dataset for cyst segmentation has been developed. METHOD: First, a dataset captured by different SD-OCT vendors with different numbers of scans and pathology qualities are selected. Then a robust and intelligent method is used to evaluate performance of readers, partitioning the dataset into subsets. Subsets are then assigned to complementary readers for annotation with respect to a novel confidence based annotation protocol. Finally, reader annotations are combined based on their performance to generate final annotations. RESULT: The generated benchmark dataset for cyst segmentation comprises 26 SD-OCT scans with differing cyst qualities, collected from 4 different SD-OCT vendors to cover a wide variety of data. The dataset is partitioned into three subsets which are annotated by complementary readers based on a confidence based annotation protocol. Experimental results show annotations of complementary readers are combined efficiently with respect to their performance, generating accurate annotations. CONCLUSION: Our results facilitate the process of generating benchmark datasets. Moreover the generated benchmark data set for cyst segmentation can be used reliably to train and test machine learning based methods.

Choroidal Line Scan Measurements in Swept-Source Optical Coherence Tomography as Surrogates for Volumetric Thickness Assessment.

PURPOSE: To compare choroidal thickness of different areas on swept-source optical coherence tomography (SSOCT) line and cube scans for their interchangeable use. DESIGN: Validity analysis. METHODS: SSOCT line and cube scans were obtained from 21 patients with various choroidal thicknesses. Subfoveal center point choroidal thickness, mean central millimeter choroidal thickness, and mean 6-mm-area choroidal thicknesses were obtained from both eyes by 2 independent graders in a reading center setting. Cross-correlations were performed using Passing and Bablok regression models. A 95% confidence interval of slope that included 1 was considered to indicate no significant difference. Average choroidal thickness of center point, Early Treatment Diabetic Retinopathy Study grid subfields, and total grid area of 6 mm on both scans and the correlation between different areas served as main outcome measures. RESULTS: No significant difference between line scans/corresponding subfields of cube scans (outer nasal 0.92-1.11, inner nasal 0.88-1.06, central 0.94-1.11, inner temporal 0.95-1.12, outer temporal 0.93-1.17). No significant difference between subfoveal center point measurement/mean of choroidal thickness in the central millimeter of cube scans (0.89-1.08). Significant difference of subfoveal center point measurement or mean of central millimeter area of cube scans to entire 6-mm area of cube scans (1.01-1.53 and 1.03-1.38). CONCLUSIONS: Measurements on a single SSOCT horizontal line scan can represent the entire choroid but subfoveal center point measurements are only indicative for the central millimeter area. There is a consistent overestimation of choroidal thickness when trying to estimate overall choroidal thickness from any central measurement.

Multimodal Imaging of Cotton Wool Spots in Branch Retinal Vein Occlusion.

PURPOSE: To describe and follow cotton wool spots (CWS) in branch retinal vein occlusion (BRVO) using multimodal imaging. METHODS: In this prospective cohort study including 24 patients with new-onset BRVO, CWS were described and analyzed in color fundus photography (CF), spectral domain optical coherence tomography (SD-OCT), infrared (IR) and fluorescein angiography (FA) every 3 months for 3 years. The CWS area on SD-OCT and CF was evaluated using OCT-Tool-Kit software: CWS were marked in each single OCT B-scan and the software calculated the area by interpolation. RESULTS: 29 central CWS lesions were found. 100% of these CWS were visible on SD-OCT, 100% on FA and 86.2% on IR imaging, but only 65.5% on CF imaging. CWS were visible for 12.4 ± 7.5 months on SD-OCT, for 4.4 ± 3 months and 4.3 ± 3.4 months on CF and on IR, respectively, and for 17.5 ± 7.1 months on FA. The evaluated CWS area on SD-OCT was larger than on CF (0.26 ± 0.17 mm(2) vs. 0.13 ± 0.1 mm(2), p < 0.0001). The CWS area on SD-OCT and surrounding pathology such as intraretinal cysts, avascular zones and intraretinal hemorrhage were predictive for how long CWS remained visible (r(2) = 0.497, p < 0.002). CONCLUSIONS: The lifetime and presentation of CWS in BRVO seem comparable to other diseases. SD-OCT shows a higher sensitivity for detecting CWS compared to CF. The duration of visibility of CWS varies among different image modalities and depends on the surrounding pathology and the CWS size.

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.

Detection and Differentiation of Intraretinal Hemorrhage in Spectral Domain Optical Coherence Tomography.

PURPOSE: The purpose of this study was to classify and detect intraretinal hemorrhage (IRH) in spectral domain optical coherence tomography (SD-OCT). METHODS: Initially the presentation of IRH in BRVO-patients in SD-OCT was described by one reader comparing color-fundus (CF) and SD-OCT using dedicated software. Based on these established characteristics, the presence and the severity of IRH in SD-OCT and CF were assessed by two other masked readers and the inter-device and the inter-observer agreement were evaluated. Further the area of IRH was compared. RESULTS: About 895 single B-scans of 24 eyes were analyzed. About 61% of SD-OCT scans and 46% of the CF-images were graded for the presence of IRH (concordance: 73%, inter-device agreement: k = 0.5). However, subdivided into previously established severity levels of dense (CF: 21.3% versus SD-OCT: 34.7%, k = 0.2), flame-like (CF: 15.5% versus SD-OCT: 45.5%, k = 0.3), and dot-like (CF: 32% versus SD-OCT: 24.4%, k = 0.2) IRH, the inter-device agreement was weak. The inter-observer agreement was strong with k = 0.9 for SD-OCT and k = 0.8 for CF. The mean area of IRH detected on SD-OCT was significantly greater than on CF (SD-OCT: 11.5 ± 4.3 mm(2) versus CF: 8.1 ± 5.5 mm(2), p = 0.008). CONCLUSIONS: IRH seems to be detectable on SD-OCT; however, the previously established severity grading agreed weakly with that assessed by CF.

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.

A quantitative approach to identify morphological features relevant for visual function in ranibizumab therapy of neovascular AMD.

PURPOSE: To quantitatively analyze morphological features in eyes with neovascular AMD (nAMD) at baseline, after 12 months, and after 24 months of intravitreal ranibizumab treatment and to perform a structure/function correlation. METHODS: Eyes with treatment-naïve nAMD were treated with intravitreal ranibizumab according to a standardized dosing regimen over 2 years and followed continuously in a prospective study design. The central foveal area of 1000 µm (horizontal)×960 µm (vertical) of spectral-domain optical coherence tomography (SD-OCT) volume scans was evaluated quantitatively (using proprietary software) for the following pathologies: alteration of the external limiting membrane (ELM), alteration of the ellipsoid zone, subretinal fluid, pigment epithelium detachment, drusen, intraretinal cysts, subretinal mass, and subretinal pigment epithelium mass. The total area of each pathology was calculated in mm2 at baseline and after 1 and 2 years of ranibizumab therapy and correlated with BCVA results. RESULTS: In total, 480 central SD-OCT scans of 20 consecutive patients were evaluated. In the multivariate regression analysis, the area of ELM alteration, the area of intraretinal cysts, and foveal retinal thickness were significant variables influencing visual acuity at baseline (R=-0.827; R2=0.684; P<0.001). The area of ELM alteration was the only significant factor to be directly associated with visual acuity at 12 months (R=-0.846; R2=0.716; P<0.001) and 24 months (R=-0.778; R2=0.606; P<0.001). CONCLUSIONS: The integrity of the ELM appears to be the most important feature correlating with visual acuity in native nAMD as well as nAMD treated with intravitreal ranibizumab at each time interval, but not prospectively. In general, no significant predictors for an individual gain or loss in mid- (12 months) or long-term BCVA results (24 months) were found by OCT.

A longitudinal comparison of spectral-domain optical coherence tomography and fundus autofluorescence in geographic atrophy.

PURPOSE: 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). DESIGN: Prospective longitudinal observational study. METHODS: 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. RESULTS: 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. CONCLUSIONS: SD OCT allows morphologic markers of disease progression to be identified in geographic atrophy and may improve understanding of the pathophysiology of atrophic 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 mm(2)), 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.

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). METHODS: This cross-sectional study applied optical-coherence-tomography over a 12×12 fovea-centered field in 50 patients with ICME and mapped the extent of fluid-filled spaces in various retinal layers, of subretinal-fluid and of diffuse-edema. Regression analysis examined effect of planimetric fluid-distribution on best-corrected-visual-acuity (BCVA) and mean microperimetric-sensitivity. RESULTS: BCVA decreased with increasing central-neuroretinal-thickness (r= 0.52, p= 0.001), total central-retinal-thickness, including subneuroretinal-fluid (r= 0.41, p= 0.006), total cystoid-and-diffuse edema-area (r= 0.35, p= 0.036) and cystoid inner-nuclear-layer area (r= 0.39, p= 0.02). Mean retinal-sensitivity decreased with increasing diffuse edema-area (r= -0.86, p<0.0001), total cystoid-and-diffuse edema-area (r= -0.54, p= 0.001), cystoid inner-nuclear-layer area (r= -0.46, p= 0.008) and cystoid ganglion-cell-layer area (r= -0.6, p=0.049), central-neuroretinal-thickness (r= -0.42, p= 0.028) and total central-retinal-thickness (r= -0.34, p= 0.039). In multivariate-analyses BCVA was best described by central-neuroretinal-thickness, duration of edema, total cystoid-and-diffuse edema-area and cystoid inner-nuclear-layer area (R(2) = 0.5, p= 0.002). Mean retinal-sensitivity was best described by diffuse edema-area, total cystoid-and-diffuse edema-area and central-neuroretinal-thickness (R(2) = 0.75, p< 0.0001). Subretinal-fluid area and cystoid outer-nuclear/Henle's layer area had no effect on either BCVA or microperimetry. CONCLUSIONS: Thickening of the neurosensory-fovea, not subfoveal-fluid, had major impact on both BCVA and retinal-sensitivity. The extent of edema in inner retinal layers also had major impact on both of these two functional parameters. Visual-impairment seems to differ depending on the layers involved, thus different types of fluid accumulation may potentially be given varying treatment priorities.