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Changes in Retinal and Choroidal Vascularity in Eyes with Acute Central Serous Chorioretinopathy Using Optical Coherence Tomography Angiography

Background To compare the vascular changes of superficial capillary layer (SCP) and deep capillary layer (DCP) in retina and choriocapillary layer in eyes with acute central serous chorioretinopathy (CSCR) by optical coherence tomography angiography (OCTA) between at baseline and 3 months. Prospective case series; Twelve patients (12 eyes) with acute CSCR at the baseline and 3 months were included. All patients underwent comprehensive ophthalmic examinations. Subfoveal choroidal thickness (SFCT) and central macular thickness (CMT) were evaluated by swept domain optical coherence tomography (SD-OCT). The foveal avascular zone (FAZ), the microvascular morphology and density of SCP and DCP, and the choroicapillary morphology were assessed by OCTA and Image J software.

Haller's layer and choroidal thickness. 3 Fundus autofluorescence (FAF) could reflect RPE function state and allow a non-invasive detection of a series of alterations at different phases and types of CSCR. 4,5 Fluorescein fundus angiography (FFA) indicates the origin of leakage of acute CSCR. 6 In spite of not compulsiveness for the diagnosis of CSCR, but FFA is helpful to confirm the diagnosis and provides a guide for possible photodynamic therapy of eccentric leaks. 7 Indocyanine green angiography (ICGA) has become the gold standard of the visualization of the choroidal vasculature and CNV complicating CSCR. 8  Optical coherence tomography angiography (OCTA) is a new-noninvasive imaging modality that allows the visualization of blood flow of retina and choroicapillary, appling to evaluate retinal vascular disease. 9-11 Signal strength detected by OCTA is positively correlated with blood perfusion. 12 Recently, several studies used OCTA to assess the presence of CNV in CSCR with variable and noncomparable results. 13,14 However, less research focus on the microvascular changes of retina and choroicapillary in eyes with acute CSCR. 15 Because serous retinal detachments resolve spontaneously within three months in most acute CSCR episodes, 1 the ideal timing for interventions still remains to be determined. Moreover, it can further supply more morphological informations for exploring the mechanisms of acute CSCR.
On account of the previous research about the structure changes of retina and choroid by OCT, the aim of this study is to further explore the microvascular changes of retina and choriocapillary in eyes with aute CSCR by OCTA during the process of self-resolve.

Methods
This was a prospective case series studies. 12 consecutive patients with acute CSCR were SD-OCT was performed as previous mode, as well as the evaluation of CMT. 16 The subfoveal choroidal thickness (SFCT) was measured using enhanced-depth imaging scans as the axial distance from the RPE to the sclera interface. All images were obtained by two independent well-trained operators.
Observers assessed the OCTA data using the best-quality 3 × 3-mm scan and controlled the corrected segmentation for the 12 patients before reporting the data. Vascular retinal layers were divided into the SCP, DCP, outer retina and choroicapillary layers (CC) by OCTA. The FAZ and density of the macula were assessed using flow density map software Angio-Analytics (Optovue RTVue XR 100 Avanti). The density of choroicapillary was assessed by Image J software. Whole-image data were used to measure the microvascular densities in the SCP and DCP layers.

Statistical Analysis
Visual acuity were incorporation into logarithm of the minimum angle of resolution (logMAR) for statistical analysis. Quantitative data (mean BCVA, CMT, vascular density of SCP, DCP and choroicapillary layer, FAZ areas of the SCP) were compared between at baseline and 3 months by the Mann-Whitney test using IBM SPSS Statistics v19 (SPSS Inc., Chicago, IL, USA). Significance was defined as P < 0.05.

Results
A total of 12 eyes in 12 patients (8 men and 4 women) were included in the study. The demographic characteristics of the patients are listed in Table 1 The FAZ areas of the SCP were (0.33±0.11)mm 2 at baseline and (0.32±0.92)mm 2 at 3 months (p=0.915) in acute CSCR eyes using OCTA software. The mean vessel density value of SCP, DCP and CC were evaluated by OCTA and Image J software respectively (shown in Table 2). The morphology of SCP, DCP and CC was presented by OCTA , comparing the microvascular changes, and the extent and range of angiectasis at baseline and 3 months. (shown in Figure 1  The changes of microvascular density in different layers are diverse not only among various retinal diseases, but also the progress or efficacy of disease. [22][23][24][25] For example, the extend of photoreceptor damage is related to the blood flow density of DCP in diabetic retinopathy. 24,25 Moreover, another publication showed reduced microvascular density of SCP and the increased density of DCP in adult-onset foveomacular vitelliform dystrophy. 23 At present, rare study is focus on the microvascular density in SCP, DCP and CC in acute CSCR episodes without treatment. Nelis et al 27 compared 16 eyes with acute CSCR with contralateral eyes and normal eye, resulting in the much more density of SCP and much smaller of FAZ in eyes with acute CSCR than the contralateral and normal eyes. However, the higher density of DCP in 12 eyes with acute CSCR at 3 months compared with eyes at initial visit, but no significant differene in density and FAZ of SCP between at baseline and at 3months. At the same time, in spite of completely absorption of subretinal fluid, the photoreceptor layer need longer time to recovery. We could identify the disruption of IS/OS by en -face imaging, which is related with the visual acuity.
Elevation of RPE by OCT was found in 19-68% in acute CSCR patients, 3  Availability of data and materials Transcripts from this study are available for sharing upon request; however, all identifying and confidential information of the participants will be removed.

Consent for publication Not Applicable
Competing interests All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
Funding This work was supported by funding from the National Natural Science Foundation for Young Scholars of China (81300781). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.     The range of photoreceptor disruption at picture A was larger than the one of it at picture C. OCT and OCTA imaging of flat PED in 2 females by the model of 3mm×3mm OCTA.
A and E presented locally high signal and peripheral low signal of choriocapillary layer at baseline.B showed remodeling choriodal neovascularization at 3 months.
F manifested much high signal and less low signal at 3 month than at baseline.