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The purpose of the study was to evaluate the retinal blood flow in patients with acute central serous chorioretinopathy (CSC) over an observational period of 1 month using swept-source optical coherence tomography (SS-OCTA), focusing especially on changes in the area of subretinal fluid (A-SRF). We correlated these findings with conventional indocyanine green angiography (ICGA). ICGA and SS-OCTA images were collected and analyzed of 12 eyes of 12 patients. The A-SRF was annotated and a qualitative analysis of choriocapillaris, the vessel density (VD) and perfusion density (PD) of the retinal superficial capillary plexus (SCP) and the deep capillary plexus (DCP) was performed in A-SRF and the unaffected remaining area (RA). The VD and PD in the DCP were statistically significantly lower in A-SRF than in the RA at baseline. (VD: p = 0.014; PD: p = 0.036). After 1 month, there was a statistically significant difference in the VD and PD of the DCP (VD: p = 0.015; PD: p = 0.014), and for the PD of the SCP between the A-SRF and the RA (p = 0.015), with lower values in the A-SRF. We found low perfused areas in choriocapillaris corresponding to hypofluorescent areas on ICGA. In conclusion there is a difference in VD and VD of the DCP in the area of SRF in acute CSC. These alterations may lead to a chronic change in the microvasculature and potentially to morphological changes.

Purpose: The coupling between neural activity and blood flow is a physiological key principle of ocular blood flow regulation. The current study was performed to investigate whether Laser speckle flowgraphy (LSFG), a commercially available technique for measuring blood flow, is capable to assess flicker-induced haemodynamic changes in the retinal and optic nerve head (ONH) circulation., Methods: Twenty healthy subjects were included in this cross sectional study. A commercial LSFG instrument was used to measure blood flow at the ONH as well as in retinal vessels before and during stimulation with flickering light. Mean blur rate (MBR), a measure of relative blood flow velocity, was obtained for the ONH and relative flow volume (RFV) a measure of relative blood flow of the respective retinal vessels., Results: Stimulation with flicker light increased ONH MBR by +17.5%±6.6% (p<0.01). In retinal arteries, flicker stimulation led an increase of +23.8±10.0% (p<0.05) in total RFV. For retinal veins, an increase of +23.1%±11.0 (p<0.05) in total RFV was observed during stimulation. A higher response was observed in nasal RFV compared to temporal RFV in retinal arteries (nasal: +28.9%±20.0%; temporal: +20.4%±17.6%, p<0.05) and veins (nasal: +28.3%±19.6%; temporal +17.8%±18.9%, p<0.05)., Conclusion: As shown previously with other techniques, flicker stimulation leads to an increase in retinal and optic nerve head blood flow. Our results indicate that LSFG is an appropriate method for the quantification of retinal and ONH blood flow during visual stimulation and may be used as a non-invasive, easy to use tool to assess neuro-vascular coupling in humans., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To describe qualitative characteristics of drusen in eyes with nonadvanced age-related macular degeneration (AMD) using polarization-sensitive optical coherence tomography (OCT)., Design: Cross-sectional study., Methods: Twenty-five eyes of 25 patients with early to intermediate (nonadvanced) AMD were imaged with polarization-sensitive OCT using macular volume scans. All individual drusen in each B-scan were manually delineated by experts certified by a reading center and graded for 6 different morphologic characteristics based on a defined classification scheme, including the presence of internal depolarizing structures and associated depolarizing foci. With the use of a custom-made software, the central B-scan of each individual druse was selected and used to analyze its location, diameter, and characteristics and assess the prevalence of the different features and relations between them., Results: Using the macular volume scans, 6224 individual drusen could be identified, including their position within the retina, their characteristics, and their association with any pigmentary alterations. The most common drusen type was a convex-shaped druse with homogeneous medium internal reflectivity and no depolarizing contents (55.3% of drusen). A total of 30.5% of the drusen exhibited internal depolarizing material; 0.3% presented overlying hyperreflective foci, and in 54.5% the foci were also depolarizing. Significant correlations were found between the diameter of the drusen and their distribution throughout the retina, shape, homogeneity of internal reflectivity, presence of internal depolarizing characteristics, and presence of overlying foci (P < .001 each). Significant relations were found between reflectivity, homogeneity, and polarization-sensitive internal characteristics (P < .001)., Conclusions: Polarization-sensitive OCT reveals characteristic morphologic features of different druse types highlighting the pathophysiological spectrum of early to intermediate AMD., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: To identify the effects of anti-angiogenic therapy in neovascular age-related macular degeneration (AMD) in respect to morphologic type and time course and to identify prognostic factors for visual outcome on the basis of standardized optical coherence tomography (OCT) analysis., Design: Subanalysis of a prospective, 12-month, multicenter, phase IIIb trial (Efficacy and Safety of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration [EXCITE])., Participants: A total of 353 treatment-naïve patients with subfoveal choroidal neovascularization (CNV) receiving quarterly or monthly ranibizumab therapy., Methods: Patients were randomized to receive 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised a loading phase of 3 consecutive monthly injections followed by a 9-month maintenance phase of monthly or quarterly injections. Best-corrected visual acuity (BCVA) was measured using the Early Treatment Diabetic Retinopathy Study protocol, and retinal morphology was assessed by Stratus OCT (Carl Zeiss Meditec, Dublin, CA). Imaging data were evaluated by certified examiners of the Vienna Reading Center using a standardized protocol., Main Outcome Measures: The BCVA was measured using ETDRS charts and retinal morphology was assessed by OCT., Results: During the loading phase, there was a significant correlation between a reduction in central retinal thickness and an increase in BCVA (P < 0.001), which decreased during the maintenance phase in all treatment arms. The proportion of patients showing retinal morphologic changes, such as intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment epithelial detachments (PEDs), decreased significantly in all groups (P < 0.001), more intensively in the 0.5 mg quarterly than in both 0.3 mg groups. Intraretinal cysts resolved most rapidly followed by SRF, whereas PED decreased at a slower rate and intensity. Patients with IRC at baseline had lower BCVA levels that remained lower over the entire study period, whereas recurrence of IRC during follow-up showed no additional negative effect on function. Baseline SRF had no effect on visual recovery; however, recurrence of SRF during follow-up showed a tendency for an additional negative effect on function (P = 0.06). Baseline PED showed a negative influence on visual outcome only in combination with IRC and SRF., Conclusions: There is a distinct response pattern and time course of morphologic parameters associated with anti-vascular endothelial growth factor therapy in neovascular AMD. Specific alterations, such as IRC, SRF, and PED, as baseline or follow-up features are significantly influencing the potential for visual gain., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify the morphologic changes secondary to macular grid photocoagulation in diabetic macular edema in vivo using spectral domain optical coherence tomography., Methods: In this prospective cohort study, 13 consecutive patients with vision loss because of clinically significant macular edema associated with diabetes mellitus Type 2 underwent grid laser treatment (PASCAL). Best-corrected visual acuity, Spectralis optical coherence tomography, infrared fundus imaging, and biomicroscopy were performed at baseline, Day 1, Week 1, and Months 1, 2, and 3 after treatment. Fluorescein angiography was performed at baseline and at 3 months., Results: Mean central 1-mm thickness decreased significantly from 438 ± 123 μm (mean ± SD) at baseline to 391 ± 111 μm (P < 0.05) at 3 months with a nonsignificant trend of best-corrected visual acuity improvement. A wipeout of the photoreceptor layer and the inner segment/outer segment line together with an alteration of the overlaying outer nuclear layer and external limiting membrane was seen at Day 1. The lesion was reduced to a focal hyperreflective deposit on the retinal pigment epithelium boundary. In 55% of lesions, the external limiting membrane as well as the previously interrupted inner segment/outer segment line revealed intact continuity at Month 3. In some areas, repair was incomplete indicated by a focal condensation interrupting the inner segment/outer segment line in the lesion center., Conclusion: In vivo imaging of morphologic lesion repair in human eyes after PASCAL grid laser of diabetic macular edema demonstrates progressive restoration of the external limiting membrane and inner segment/outer segment integrity as previously described in animal models.

Purpose: We evaluated the morphologic changes in retinal structure after laser photocoagulation using supra- and subthreshold laser fluence., Methods: In a prospective cohort study 10 consecutive patients received scatter laser photocoagulation. Treatment was performed using a semiautomated patterned scanning laser system. In a study area adjacent to the temporal vessel arcades, 2 × 2 pattern laser spots were applied with halving the flux of the laser power in a stepwise manner starting from a power producing a typical grayish lesion. The study areas then were imaged on days one, three, and seven, and on months one, two, three, and six using color fundus photography, autofluorescence (AF), infrared (IR) imaging, and spectral domain optical coherence tomography (SD-OCT)., Results: The starting threshold power lesions each were visible on color fundus photography, IR, and AF in all patients, and showed characteristic changes on OCT throughout the follow-up period. The halved flux laser burns (first step) were undetectable ophthalmoscopically during the laser session, but during the follow-up always were detectable on IR and AF images, and sometimes on fundus photography. On OCT they showed changes similar to the suprathreshold laser scars, but were much smaller in diameter, and in some instances an inward migration of the photoreceptor layer was observed., Conclusions: Subthreshold laser burns with halved energy flux produced similar morphologic changes in the retina as threshold power, but with a smaller size. They induced less collateral damage to the neuroretina, and permit a level of reorganization in the outer retina. (ClinicalTrials.gov number, NCT00682240.).

Purpose: To compare different spectral domain optical coherence tomography devices regarding retinal thickness values in patients with diabetic macular edema and to correlate the results with conventional time domain Stratus OCT data., Methods: Thirty eyes of 30 consecutive patients with diabetic macular edema were included into a prospective study. The macula was examined by Spectralis HRA+OCT, Cirrus HD-OCT, 3D OCT-1000, and Stratus OCT. The procedures' sequence was performed by a single experienced technician in a randomized fashion according to a computer-generated list. In each eye, foveal thickness, foveal volume, and total macular volume were measured automatically. Intraclass correlation, coefficients of variance, and coefficients of repeatability were calculated., Results: Foveal thickness differed between the particular devices with a mean ± SD ranging from 359.97 ± 105.84 μm to 437.70 ± 115.84 μm. Correlation between the different OCT devices resulted in r > 0.7 (Pearson), and intraclass correlation was >0.9. Agreement of measurements was assessed showing a mean difference of foveal thickness values ranging from 19.2 μm to 77.7 μm (P < 0.05) and coefficients of repeatability ranging from 37.7 μm to 87.4 μm., Conclusion: While intradevice reproducibility is satisfactory, retinal thickness and volume measurements should not be used interchangeably because measurements differed significantly between systems. The lack of interdevice agreement seems to be related to the different segmentation algorithm of thickness measurement and should be considered because it may strongly influence treatment decisions and conclusions.

Purpose: The aim of this study was to correlate different types of retinal morphologic alterations secondary to diabetic macular disease with their characteristic impact on retinal function., Methods: In the present cross-sectional study, 26 eyes of 26 diabetic patients with clinically significant macular edema were examined. All patients underwent complete standardized ophthalmologic examination, including SD-OCT and microperimetry. Microperimetric values were projected over the scanning laser ophthalmoscope image of the OCT device, allowing direct correlation of functional and morphologic parameters. Results over all 1066 individual areas were analyzed using a general linear model., Results: All the characteristic morphologic alterations demonstrated a significant effect on retinal function (P < 0.0002), except for outer nuclear layer (ONL) hyporeflectivity and small ONL cysts. Large ONL cysts (>220 μm) and serous retinal detachment had the greatest estimated negative effect on retinal sensitivity (-3.86 and -3.66 dB), followed by medium-sized ONL cysts, hard exudates associated with an extinction of the scan signal, and inner nuclear layer cysts., Conclusions: In diabetic macular edema, serous retinal detachment and large ONL cysts are the two morphologic changes with the greatest negative impact on retinal function.

Purpose: To image the ultrastructural morphology of retinal laser effects and their healing response in vivo using spectral domain optical coherence tomography (SD-OCT)., Design: Prospective, interventional study., Participants: Ten patients undergoing panretinal photocoagulation for proliferative diabetic retinopathy., Methods: Panretinal photocoagulation (PRP) was performed using a semiautomated patterned scanning laser system providing a raster of effects with homogenous intensity. Retinal morphology and localization of effects owing to laser-tissue interaction were imaged at 1 day, 1 week, and at monthly intervals for 6 months. The characteristic, specific structural changes during the healing process were followed over time using an SD-OCT device (Spectralis OCT) allowing for high-resolution raster scanning of the entire lesion pattern with identification of identical retinal sites (tracking modality)., Main Outcome Measures: Retinal morphology and localization of effects of photocoagulation on SD-OCT images., Results: At day 1 after PRP, the photocoagulation effects were sharply delineated from the surrounding unaffected retina and all spots seemed to be identical in size and location. The area of tissue destruction was confined to the outer retinal layers, extending from the outer nuclear layer (ONL) to the retinal pigment epithelium (RPE). At 1 week, images showed a progressive loss of the affected outer retinal layers, namely, the ONL and the outer plexiform layer. Concomitant distortion of the inner nuclear and plexiform layers generated a pattern of "archways" between adjacent laser spots. The photoreceptor layers (PRL) seemed to be eliminated in the photocoagulated area, particularly at the borders of each lesion. The lesion center contained a condensed RPE and PRL segment. The ONL recovered partially, but the PRL inner and outer segments remained absent. During the long-term follow-up, RPE cells migrated to the center of the lesion, forming a hyperplastic scar., Conclusions: The characteristic morphology of retinal photocoagulation effects in vivo and over time was identified for the first time in human eyes using SD-OCT. The OCT imaging demonstrated a well-defined reproducible area of destruction confined to the outer retinal layers. Healing proceeded as the condensation of the RPE and PRL in the lesion center., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze immediate in vivo intraretinal morphologic changes secondary to standardized grid photocoagulation using spectral domain optical coherence tomography (SD OCT)., Design: Prospective clinical trial., Participants: Thirteen consecutive patients with treatment-naïve clinically significant diabetic macular edema (DME)., Methods: Before and 1 day after standardized grid photocoagulation using the PASCAL system (Pattern Scan Laser, OptiMedica Corporation, Santa Clara, CA), Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) examinations based on an eye-tracking system, infrared fundus imaging, color fundus photography, and biomicroscopy were performed. A standardized visual acuity assessment (Early Treatment Diabetic Retinopathy Study protocol) and fluorescein angiography were performed at baseline., Main Outcome Measures: Morphologic changes secondary to grid laser treatment., Results: One day after laser therapy, immediate morphologic alterations of only the outer retinal layers, that is, the retinal pigment epithelium (RPE), the photoreceptor layer (PRL), and the outer nuclear layer (ONL), were observed. The shape of the laser-induced lesions did not show a sagittal alteration pattern throughout all 3 of the layers, however, but rather seemed to follow an oblique pathway throughout the ONL, changing direction at the level of the external limiting membrane and proceeding sagittally through the PRL and RPE. These morphologic changes also induced biometric changes, such as a decrease in central retinal thickness combined with local thickening at the lesion site, especially in the PRL., Conclusions: Spectral domain optical coherence tomography provides new insight into the immediate morphologic changes after laser treatment using the PASCAL laser system. Standardized grid photocoagulation induces characteristic homogenous alteration in the neurosensoric retinal layers. Biometric changes, indicating an immediate effect, were observed within 1 day after treatment., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To correlate leakage patterns in fluorescein angiography (FA) images and retinal morphologic features in high-definition optical coherence tomography (HD OCT) images in diabetic macular edema., Design: Prospective pilot study and case series., Participants: Nine consecutive patients (10 eyes) with diabetic macular edema., Methods: All patients were examined using FA (HRA 2; Heidelberg Engineering) and HD OCT (Carl Zeiss Meditec; resolution, 512x128 pixels, 5.8x5.8 mm, and high-resolution scans consisting of 4096 A scans) on the same day. Using Adobe Photoshop (CS2 Version 9.0; Adobe Systems Incorporated, San Jose, CA) a grid containing 15x7 fields was superimposed on the HD OCT en face image and a late-phase FA image according to retinal landmarks. In each patient, a standardized analysis of 105 subfields was performed to provide a characterization of the type of vascular leakage in FA and the associated retinal morphologic changes in corresponding locations., Main Outcome Measures: Angiographic leakage type and structural alteration in retinal morphologic features in OCT., Results: There was a high consistency between FA and OCT in the petaloid pattern of hyperfluorescence that correlated with the presence of large cystic spaces in the outer nuclear layer (ONL) and the outer plexiform layer (OPL) with or without subretinal fluid in 30.4% and 69.6% of graded fields, respectively. A honeycomblike pattern of hyperfluorescence was associated with swelling and cystic spaces in ONL, OPL, the inner nuclear, and the inner plexiform layer in 71.4% of graded fields. Diffuse patterns of hyperfluorescence did not correlate with characteristic retinal changes in HD OCT, but rather showed diversity in the type of morphologic alteration. The presence of central fluid pooling, such as subretinal fluid, could be identified only by HD OCT and not by FA., Conclusions: In the examined patients, a petaloid pattern and a honeycomb pattern of hyperfluorescence observed in FA were found to correlate to characteristic changes in HD OCT, whereas a diffuse leakage pattern was associated with nonuniform changes in retinal morphologic features., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.