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Abstract This study aims to develop a method to quantify choroidal vessels in normal eyes using wide-field optical coherence tomography (OCT) en-face images. The study included participants with normal eyes in whom wide-angle OCT images were acquired to generate planarized choroidal en-face and thickness map images. The images were segmented into central, midperipheral, and peripheral areas, and the midperipheral and peripheral areas were further segmented into supratemporal, infratemporal, supranasal, and infranasal sectors. The mean planarized choroidal-vessel density (p-CVD), planarized choroidal-vessel size (p-CVS), and choroidal thickness (CT) were calculated in each sector. Sex differences were analyzed using the Mann–Whitney U test. The study included 162 participants comprising 84 female (mean age, 43.5 years; axial length, 24.0 mm) and 78 male (mean age, 44.4 years; axial length, 24.2 mm) participants with no significant differences in demographics (P ≥ 0.107). Men had a higher mean p-CVD in all regions (P

Abstract Background To compare the one-year outcomes between intravitreal brolucizumab (IVBr) monotherapy and photodynamic therapy (PDT) as a second-line treatment in patients with polypoidal choroidal vasculopathy (PCV) who did not respond to first-line therapy. Methods This case–control study included eyes with PCV that do not respond to aflibercept or ranibizumab. The patients were retrospectively registered. We compared outcomes, including best-corrected visual acuity (BCVA), anatomical results, and the need for additional treatments, between IVBr and a combination therapy using PDT as second-line treatments for refractory PCV, after adjusting for potential confounders. We analyzed E-values to evaluate the robustness of the results against unmeasured confounders. Results Twenty-two eyes received IVBr, and twenty-four underwent PDT. No apparent differences were observed in BCVA and central macular thickness (CMT) changes from baseline between the groups (IVBr vs. PDT: BCVA, 0.01 ± 0.47 logMAR vs. 0.04 ± 0.18 logMAR, P-value = 0.756; CMT: − 36.3 ± 99.4 μm vs. − 114.7 ± 181.4 μm, P-value = 0.146). Only in the PDT group, five eyes (20.8%) did not require additional treatment after the second-line treatment, the adjusted odds ratio indicating no further treatment needed was 11.98 (95% confidence interval: 1.42–2070.07, P-value = 0.019). The E-value for the adjusted odds ratio was 23.44. Conclusions Both second-line treatments for PCV exhibited similar visual and anatomical outcomes. Only in the PDT-treated eyes were there some patients who did not require further treatment after second-line therapy.

Abstract To quantify the choroidal structures of normal eyes by optical coherence tomography (OCT)-based binarization and evaluate the relationships among age, refractive power, and ocular axial length. This was a retrospective observational study. One hundred and eighty nine eyes of 189 subjects without ocular diseases were examined by enhanced depth imaging (EDI)-OCT. A choroidal OCT horizontal image with a width of 1500 μm centered on the fovea was binarized. The lumen, stroma, and total choroidal area in the choriocapillaris (CC), Sattler’s layer (SL), and Haller's layer (HL) were measured, and the ratio of the luminal area to total choroidal area (L/C ratio) was calculated. Multiple regression analysis was performed for choroidal parameters in each choroidal layer and for age, refractive power, and ocular axial length. Multiple regression analysis showed that an older age was significantly correlated with a lower choroidal area and the L/C ratio in all choroidal layers (each P

The estimation of central choroidal thickness from colour fundus images can improve disease detection. We developed a deep learning method to estimate central choroidal thickness from colour fundus images at a single institution, using independent datasets from other institutions for validation. A total of 2,548 images from patients who underwent same-day optical coherence tomography examination and colour fundus imaging at the outpatient clinic of Jichi Medical University Hospital were retrospectively analysed. For validation, 393 images from three institutions were used. Patients with signs of subretinal haemorrhage, central serous detachment, retinal pigment epithelial detachment, and/or macular oedema were excluded. All other fundus photographs with a visible pigment epithelium were included. The main outcome measure was the standard deviation of 10-fold cross-validation. Validation was performed using the original algorithm and the algorithm after learning based on images from all institutions. The standard deviation of 10-fold cross-validation was 73 μm. The standard deviation for other institutions was reduced by re-learning. We describe the first application and validation of a deep learning approach for the estimation of central choroidal thickness from fundus images. This algorithm is expected to help graders judge choroidal thickening and thinning.

Purpose: To compare the distribution of vortex vein ampulla (VVA) between pachychoroid spectrum disorder (PSD) and controls. Design: A single-center, case-control study. Participants: This study included 75 PSD, 35 fellow, and 65 control eyes. Methods: We quantified VVA distribution using a 3-dimensional reverse projection model corrected for image distortion. We investigated the distribution of major drainage veins (MDV), in which macular Haller's vessels directly influx. Main Outcome Measures: The mean distances from the optic disc to VVAs and the mean angles between VVAs and the fovea-disc line. Results: The PSD group had significantly fewer VVA in infranasal sector (PSD, fellow, control; 1.6 ± 0.6, 1.8 ± 0.6, 1.9 ± 0.6, respectively, P = 0.026). In supralateral sector, for PSD, fellows, and controls, the mean distances from the optic disc to VVAs were 14.1 ± 1.0 mm, 14.1 ± 1.1 mm, and 13.6 ± 1.4 mm, respectively, and were significantly farther in PSD than in controls (P = 0.023). The mean angles between VVAs and the fovea-disc line were 64.8 ± 5.9°, 66.4 ± 6.4°, and 61.7 ± 6.4°, respectively, and were significantly higher in PSD and fellows than in controls (P = 0.008). The mean distances from the optic disc to MDV in supratemporal sector were 14.1 ± 1.2 and 13.7 ± 1.2 in eyes whose Haller's vessels extended beyond the fovea-disc line (asymmetry), and those that did not, respectively, with the asymmetric eyes significantly farther (P = 0.016). Conclusions: The VVA position in supralateral sector was farther and higher in PSD than in controls, suggesting that the distribution of VVA may be associated with the development of PSD. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Objective Colour scanning laser ophthalmoscope (cSLO) offers several advantages, including improved image quality and better visualisation of the retinal structures compared with colour fundus photograph (CFP). This study aimed to identify whether cSLO could be used to predict systemic arterial stiffness.Methods and analysis We retrospectively analysed the data of 54 patients with 103 eyes. In addition to blood pressure and blood data, all patients had cardio-ankle vascular index (CAVI) measurements, as well as images of the fundus acquired using cSLO and CFP. We determined the retinal artery sclerosis (RAS) index from the colour of the retinal artery in cSLO images, the ratio of arterial to venous diameter (A/V ratio), and Scheie’s classification in CFP images. The correlation between each parameter and CAVI was examined using Spearman’s rank correlation coefficient, and the correlation between Scheie’s classification and CAVI was examined using Steel-Dowass tests.Results CAVI showed a significant positive correlation with the RAS index (r=0.679, p

Aim/backgroundTo aim of this study is to develop an artificial intelligence (AI) that aids in the thought process by providing retinal clinicians with clinically meaningful or abnormal findings rather than just a final diagnosis, i.e., a "wayfinding AI."MethodsSpectral domain optical coherence tomography B-scan images were classified into 189 normal and 111 diseased eyes. These were automatically segmented using a deep-learning based boundary-layer detection model. During segmentation, the AI model calculates the probability of the boundary surface of the layer for each A-scan. If this probability distribution is not biased toward a single point, layer detection is defined as ambiguous. This ambiguity was calculated using entropy, and a value referred to as the ambiguity index was calculated for each OCT image. The ability of the ambiguity index to classify normal and diseased images and the presence or absence of abnormalities in each layer of the retina were evaluated based on the area under the curve (AUC). A heatmap, i.e., an ambiguity-map, of each layer, that changes the color according to the ambiguity index value, was also created.ResultsThe ambiguity index of the overall retina of the normal and disease-affected images (mean ± SD) were 1.76 ± 0.10 and 2.06 ± 0.22, respectively, with a significant difference (p < 0.05). The AUC used to distinguish normal and disease-affected images using the ambiguity index was 0.93, and was 0.588 for the internal limiting membrane boundary, 0.902 for the nerve fiber layer/ganglion cell layer boundary, 0.920 for the inner plexiform layer/inner nuclear layer boundary, 0.882 for the outer plexiform layer/outer nuclear layer boundary, 0.926 for the ellipsoid zone line, and 0.866 for the retinal pigment epithelium/Bruch's membrane boundary. Three representative cases reveal the usefulness of an ambiguity map.ConclusionsThe present AI algorithm can pinpoint abnormal retinal lesions in OCT images, and its localization is known at a glance when using an ambiguity map. This will help diagnose the processes of clinicians as a wayfinding tool.

PurposeTo explore the effect of photodynamic therapy (PDT) on the choroid of medial area from optic disc and factors correlated with treatment outcomes, we evaluated choroidal changes using ultra-widefield optical coherence tomography (UWF-OCT) after PDT for central serous chorioretinopathy (CSC).MethodsIn this retrospective case-series, we included CSC patients who received a standard-dose of full-fluence PDT. UWF-OCT were examined at baseline and 3 months after treatment. We measured choroidal thickness (CT), classified into central, middle, and peripheral sectors. We examined CT changes after PDT by sectors and treatment outcome.ResultsTwenty-two eyes of 21 patients (20 males; mean age 58.7 ± 12.3 years) were included. CT reduction after PDT was significant in all sectors, including peripheral areas: supratemporal, 330.5 ± 90.6 μm vs. 237.0 ± 53.2 μm; infratemporal, 240.0 ± 89.4 μm vs. 209.9 ± 55.1 μm; supranasal, 237.7 ± 59.8 vs 209.3 ± 69.3 μm; infranasal, 172.6 ± 47.2 μm vs. 155.1 ± 38.2 μm (P < 0.001, for all). In patients with retinal fluid resolution, despite no apparent difference in baseline CT, there was more significant reduction after PDT in supratemporal and supranasal peripheral sectors, compared with patients without resolution: supratemporal, 41.9 ± 30.3 μm vs. -1.6 ± 22.7 μm; supranasal, 24.7 ± 15.3 μm vs. 8.5 ± 3.6 μm (P < 0.019, for both).ConclusionsWhole CT decreased after PDT, including in medial areas from optic disc. This may be associated with the treatment response of PDT for CSC.

Abstract This study aimed to evaluate the usefulness of multicolor (MC) scanning laser ophthalmoscopy (MC-SLO) in detecting microaneurysm (MA) in eyes with diabetic retinopathy (DR). This was a retrospective cross-sectional study. Eyes with DR underwent fluorescein angiography (FA), MC-SLO, optical coherence tomography angiography (OCTA), and color fundus photography (CFP) were analyzed. The foveal region was cut in an 6 × 6 mm image and the number of MA in each image was counted by retina specialists to determine the sensitivity and positive predictive value. FA results were used as the ground standard. MAs were classified as those with early, late, or no dye leakage based on FA images. Fifty-four eyes of 35 patients with an average age of 64.5 ± 1.24 years were included. The sensitivity of MA detection was 37.3%, 15.3%, and 4.12% in MC-SLO, OCTA, and CFP, respectively (P

Abstract The purpose of this study was to determine the number and location of vortex vein ampullae (VVA) in normal eyes. This was an observational retrospective study. Montage images of one on-axis and two off-axis ultra-widefield images of 74 healthy eyes were enhanced, and reverse projected onto a 3D model eye. The number and distance between the optic disc to each VVA in the four sectors were compared. The significance of correlations between these values and age, sex, visual acuity, refractive error, and axial length was determined. The mean number of VVA was 8.10/eye with 1.84, 2.12, 2.19 and 1.95 in upper lateral, lower lateral, upper nasal, and lower nasal sectors, respectively. The mean number of VVA/eye was significantly greater in men at 8.43 than women at 7.76 (P = 0.025). The mean distance between the optic disc and VVA was 14.15 mm, and it was 14.04, 15.55, 13.29 and 13.66 mm in the upper lateral, lower lateral, upper nasal and lower nasal sectors, respectively (all P

Abstract Aims/Introduction To determine the current clinical preferences of anti‐vascular endothelial growth factor (VEGF) treatment protocols for diabetic macular edema (DME) in Japan. Materials and Methods This was a descriptive cross‐sectional study. Answers to a questionnaire consisting of 16 questions were obtained from 176 of 278 (63.3%) surveyed ophthalmologists. Results The results showed that 81.2% preferred intravitreal injections of anti‐VEGF antibodies as the first‐line therapy. The most important indicators for beginning anti‐VEGF therapy were: the best‐corrected visual acuity in 44.3% and the retinal thickness in 30.7%. In the loading phase, 53.4% preferred a single injection, and in the maintenance phase, 75.0% preferred the pro re nata regimen. Financial limitation (85.8%) was reported as the most important difficulty in the treatment. For combination therapy with anti‐VEGF treatment, panretinal photocoagulation, focal photocoagulations and a sub‐Tenon steroid injection were preferred. The contraindications for anti‐VEGF therapy were: prior cerebral infarction (72.7%). Regarding the use of both approved anti‐VEGF agents in Japan, ranibizumab and aflibercept, 39.8% doctors used them appropriately. Conclusions Our results present the current clinical preferences of anti‐VEGF treatment for DME in Japan. The best‐corrected visual acuity and the retinal thickness are important indicators to institute this therapy. The majority of the ophthalmologists use anti‐VEGF treatment as first‐line therapy and prefer the 1 + pro re nata regimen.

Abstract Purpose To compare the ability of ocular fundus images obtained by Spectralis MultiColor scanning laser ophthalmoscope (MC-SLO) to that obtained by conventional color fundus images (CF) in detecting non-glaucomatous nerve fiber layer defects (NFLDs). Methods A cross-sectional, retrospective study. Patients with retinal diseases who had ocular examination with both the MC-SLO and CF instruments at the Kagoshima University from December 2016 to February 2017 were studied. Eyes that had NFLDs with non-glaucomatous optic discs were analyzed. The visibility of the NFLDs was classified into three grades: grade 0, not visible; grade 1, barely visible; and grade 2, clearly visible. The NFLD grade for blue, green, and red scanning lights of the MC-SLO, merged images with three wavelengths and the color and red-free images were determined by two ophthalmologists. These scores were compared by Steel-Dwass tests. Results Thirty-one eyes of 26 patients with a mean age of 63.1 ± 11.2 years were studied. There were 14 eyes with diabetic retinopathy, 11 eyes with age-related macular degeneration, 3 eyes with a branch retinal vein occlusion, and 3 eyes with an epiretinal membrane/macular hole. Both the intra-rater (0.631–0.790) and inter-rater (0.637–0.733) agreements were good. NFLDs were detected by the blue wavelength in all cases and by green wavelength and merged wavelengths in 90.3% of the images. The mean NFLD grade was 1.58 ± 0.49 for blue light images, 1.13 ± 0.54 for green light images, 0.07 ± 0.24 for red light images, and 1.16 ± 0.56 for merged images. The NFLD score for blue wavelength was significantly higher than that for green and red wavelength images (P

PurposeAbnormalities of the running pattern of choroidal vessel have been reported in eyes with pachychoroid diseases. However, it is difficult for clinicians to judge the running pattern with high reproducibility. Thus, the purpose of this study was to compare the degree of concordance of the running pattern of the choroidal vessels between that determined by artificial intelligence (AI) to that determined by experienced clinicians.MethodsThe running pattern of the choroidal vessels in en face images of Haller's layer of 413 normal and pachychoroid diseased eyes was classified as symmetrical or asymmetrical by human raters and by three supervised machine learning models; the support vector machine (SVM), Xception, and random forest models. The data from the human raters were used as the supervised data. The accuracy rates of the human raters and the certainty of AI's answers were compared using confidence scores (CSs).ResultsThe choroidal vascular running pattern could be determined by each AI model with an area under the curve better than 0.94. The random forest method was able to discriminate with the highest accuracy among the three AIs. In the CS analyses, the percentage of certainty was highest (66.4%) and that of uncertainty was lowest (6.1%) in the agreement group. On the other hand, the rate of uncertainty was highest (27.3%) in the disagreement group.ConclusionAI algorithm can automatically classify with ambiguous criteria the presence or absence of a symmetrical blood vessel running pattern of the choroid. The classification was as good as that of supervised humans in accuracy and reproducibility.

PURPOSE:The current study investigated differences in the peripapillary and macular choroidal areas between patients with primary open-angle glaucoma (POAG) and healthy controls because the choroid may potentially play a role in glaucoma pathophysiology. METHODS:We assessed 57 healthy controls and 42 POAG patients in a cross-sectional comparative study. We used enhanced depth imaging optical coherence tomography (EDI-OCT) and then converted the luminal and interstitial areas to binary images using the Niblack method to obtain peripapillary and macular choroidal images. The relationship between the choroidal area and demographic and ocular characteristics were determined with univariate and multivariate linear regression analysis. RESULTS:Regarding the peripapillary choroidal area, no significant differences were noted between healthy controls and POAG patients (1,836,336 ± 605,617 μm2 vs. 1,775,566 ± 477,317 μm2, respectively, P = 0.60). There were also no differences found for the macular choroidal area (controls: 347,220 ± 115,409 μm2, patients: 342,193 ± 104,356 μm2, P = 0.83). Multivariate regression analysis in the POAG patients revealed there was a significant relationship between the macular choroidal area and age (β = -0.525, P = 0.002) and axial length (β = -0.458, P = 0.005). In contrast, no correlation was found between peripapillary choroidal areas and various attributes in the POAG patients. CONCLUSIONS:EDI-OCT showed no differences in the peripapillary or macular choroidal area in healthy individuals compared to POAG patients.

The aim of this study was to assess the effect of wearing optical correction on the choroidal structure in eyes of children with anisohypermetropic amblyopia. This study was conducted at the Nara Medical University Hospital and at the Tokushima University Hospital. Twenty-nine anisohypermetropic amblyopic eyes and their fellow eyes of 29 amblyopic patients (mean age, 5.7 ± 1.7 years, range 3- to 8-years) and twenty eyes of 20 age-similar control children (4.9 ± 0.8 years, range 4- to 6-years) were studied. All patients wore optical correction and 15 patients had both optical correction and patching. The values at the baseline were compared to that at one year later. The binarization method was used to determine the total, luminal, and stromal areas of the choroid in the enhanced depth imaging optical coherence tomographic images. The best-corrected visual acuity (BCVA) of the amblyopic eyes was significantly improved after the one-year period. A large luminal area was characteristic of the amblyopic eye at the baseline, and it was significantly reduced after the optical treatment. The stromal area widened significantly in the amblyopic and fellow eyes after one year whereas there were no significant changes in the choroid of the control eyes after one year. After one-year of optical correction, the luminal/stromal ratios in the amblyopic and fellow eyes were decreased and were then not significantly different from that of the normal control eyes. There was a significant and positive correlation between the improvement of the BCVA and the stromal area at the baseline (r = 0.64, P = 0.001). Wearing corrective lenses on the amblyopic eyes improves the BCVA, and the choroidal structure of the amblyopic eye becomes closer to that of the control eyes. The narrowed luminal area is a specific response of the amblyopic eye associated with the correction of the refractive error. The larger stromal area in the amblyopic eyes at the baseline is a predictive factor for improvements of the BCVA.

Abstract This study was conducted to investigate the size and shape of the foveal avascular zone (FAZ) determined by optical coherence tomography angiography (OCTA) and the relationship of the size and shape to the clinical findings in normal subjects. This was a cross-sectional study with seventy eyes of 70 volunteers. The size of the superficial FAZs were assessed by its area, length of perimeter, and Feret’s diameter, and the shape by the circularity, axial ratio, roundness, and solidity. The correlations between each parameter and the clinical findings were statistically determined. The coefficients of variation (CV) of the parameters of FAZ size were higher than that of the parameters of FAZ shape. The refractive error and axial length were significantly correlated with area-related factors. The central macular thickness (CMT) was significantly correlated with all parameters. Although the CMT was a critical factor that was significantly correlated with the size and shape characteristics of the FAZ, the shape might be a better factor for characterizing the FAZ than the size because of the low CV of shape-related factors and the characteristics are less affected by the other ocular factors.

PurposeTo evaluate changes in the macula and peripapillary choroidal area at one year after trabeculectomy in order to determine the effect of intraocular pressure (IOP) changes.MethodsThis prospective longitudinal study examined 30 eyes of 30 patients with glaucoma that was uncontrolled by medical therapy. At 1 day before and at 1 year after the trabeculectomy surgery, macular and peripapillary choroidal images were recorded by enhanced depth imaging optical coherence tomography (EDI-OCT). Luminal and interstitial areas were converted to binary images using the Niblack method. Factors influencing the macular choroidal and peripapillary area were examined by multivariate analysis.ResultsAfter trabeculectomy, the mean IOP was 10.8±3.2 mmHg compared to 17.8±7.2 mmHg at baseline (P < 0.001). The total macular choroidal area after the surgery increased from 317,735±77,380 to 338,120±90,700 μm2, while the interstitial area increased from 108,598±24,502 to 119,172±31,495 μm2 (all P < 0.05). The total peripapillary choroidal area after the surgery also increased from 1,557,487±431,798 to 1,650,253±466,672 μm2, while the interstitial area increased from 689,891±149,476 to 751,816±162,457 μm2 (all P < 0.05). However, there were no significant differences observed in the luminal area before and after the surgery. A decrease in the IOP was among the factors associated with the changes in the peripapillary choroidal area.ConclusionsIOP reductions after trabeculectomy led to increases in the macular and peripapillary choroidal areas for at least 1 year postoperative. Increases in the interstitial areas were the primary reason for observed changes in the choroidal area after trabeculectomy.

The purpose of this study is to determine the factors related to anxiety and depression in patients with retinitis pigmentosa (RP). The status of anxiety and depression was determined in RP patients with the Hospital Anxiety and Depression Scale (HADS) questionnaire which consisted of subscales for HADS-anxiety (HADS-A) and HADS-depression (HADS-D). The vision-specific quality of life (VSQOL) was assessed with the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ25). The correlations between the HADS-A or HADS-D scores and vision-related clinical parameters such as the best-corrected visual acuity (BCVA), Functional Acuity Score, Functional Field Score, Functional Vision Score, the NEI- VFQ25 subscale score were determined. The socioeconomic status, such as the work status and membership in the RP society, was investigated to determine the factors related to the HADS-A and HADS-D scores. One hundred and twelve RP patients (46 men and 66 women) with mean age of 60.7±15.4 (standard deviation) years were studied. The HADS-A score was not significantly correlated with any visual functions but was significantly correlated with the general health condition (r = -0.34, P

PURPOSE:To evaluate normal and normal-tension glaucoma (NTG) eyes for differences in peripapillary and macular choroidal area measurements. METHODS:This cross-sectional comparative study enrolled 52 normal subjects and 35 NTG patients. Peripapillary and macular choroidal images were recorded by enhanced depth imaging optical coherence tomography (EDI-OCT), with conversion of the luminal and interstitial areas to binary images performed using the Niblack method. RESULTS:While there was a significant difference between normal subjects and NTG patients for the peripapillary choroidal area (1,853,672 ± 626,501 μm2 vs. 1,606,448 ± 418,214 μm2, P = 0.047), there were no significant differences between the normal subjects and NTG patients observed for the macular choroidal area (345,365 ± 119,248 μm2 vs. 316,442 ± 85,732 μm2, P = 0.23). In the NTG patients, multivariate regression analysis demonstrated a correlation between the macular choroidal area and the axial length (β = -0.345, P = 0.04). Furthermore, there was also a significant correlation between the peripapillary choroidal area and the age of the NTG patients (β = -0.469, P = 0.004). In addition, there was no relationship between the glaucoma severity and the peripapillary and macular choroidal areas in the NTG patients. CONCLUSIONS:There was no correlation between the peripapillary choroidal area and glaucoma severity in NTG patients, even though the area was smaller in these patients.

PURPOSE:To investigate the correlation between geographic filling delays in the choriocapillaris using indocyanine green angiography (ICGA) images and dilated vortex veins in central serous chorioretinopathy (CSC). DESIGN:Observational case series. PARTICIPANTS:Thirty-two eyes of 32 patients, 21 with acute and 11 with chronic CSC. METHODS:Digital ICGA and fluorescein angiography (FA), with videoangiography, and swept-source optical coherence tomography (SS-OCT) for B-scan and en-face choroidal imaging were performed. Overlapping of the filling delay areas in the choriocapillaris in the early-phase ICGA images and the region of dilated vortex veins in the en-face images were analyzed. The consistency of both areas was graded as follows. Grade 3: filling delay area is entirely involved in the dilated vortex vein region. Grade 2: 50% or more of filling delay area overlaps with the dilated vortex vein region. Grade 1: less than 50% of filling delay area overlaps with the dilated vortex vein region. Grade 0: no tendency for overlapping of two areas. We evaluated the asymmetry of upper and lower vortex veins in en-face images of the Haller layer. Using the binarization method, we quantified the luminal and stromal areas of the choroid. The ratios of the Haller layer area and luminal areas in the Haller layer to total choroidal area were examined. RESULTS:The consistency of overlapping of the two areas was grade 2.62 ± 0.49 in acute CSC and grade 1.55 ± 0.78 in chronic CSC (p = 0.0005). Asymmetry of upper and lower vortex veins was seen in 17 of 22 eyes (81%) with acute CSC and 6 of 11 eyes (54.5%) with chronic CSC (p = 0.114). Central choroidal thickness was 411 ± 79 μm in acute CSC and 326 ± 64 μm in chronic CSC (p = 0.004). In the posterior fundus with a 4500 μm diameter, the ratio of the Haller layer area to total choroidal area was 63.7 ± 8.6% in acute CSC and 57.1 ± 7.9% in chronic CSC (p = 0.047). The ratio of the luminal area in the Haller layer area to total choroidal area was 46.9 ± 7.6% in acute CSC and 40.0 ± 6.9% in chronic CSC (p = 0.014). CONCLUSION:Filling delay areas in the choriocapillaris and dilated vortex vein regions showed marked overlapping in acute CSC. Increased choroidal thickness was attributed to dilated vortex veins. These findings suggest that the blood flow into the choriocapillaris is delayed as a result of congestion of the dominant vortex veins that supply this geographic area. CSC may be a disease characterized by vortex vein congestion that develops in eyes with asymmetric vortex veins.

PURPOSE:To investigate changes of the macular and peripapillary choroidal areas after trabeculectomy. METHODS:This prospective and interventional study examined 74 eyes of 74 patients with glaucoma uncontrolled by medical therapy. Enhanced depth imaging optical coherence tomography (EDI-OCT) recorded macular and peripapillary choroidal images at 1 day before trabeculectomy and at 2 weeks after surgery. The Niblack method was used to covert luminal and interstitial areas to binary images. RESULTS:At baseline, the mean intraocular pressure (IOP) was 17.6±6.3 mmHg, while it was 6.5±2.9 mmHg after trabeculectomy (P < 0.001). Increases were observed for the macular choroidal area after the surgery, with the total area increasing from 317,853±95,728 μm2 to 368,597±104,393 μm2, while the luminal area increased from 210,355±73,650 μm2 to 249,464±77,195 μm2, and the interstitial area increased from 107,498±27,613 μm2 to 119,133±31,811 μm2 (all P < 0.001). Increases were also observed after the surgery for the peripapillary choroidal area, with the total area increasing from 1,629,440±460,429 μm2 to 1,974,289±500,496 μm2, while the luminal area increased from 920,141±328,690 μm2 to 1,179,843±357,601 μm2, and the interstitial area increased from 709,299±153,179 μm2 to 794,446±169,029 μm2 (all P < 0.001). There was a significant increase in the ratio of the luminal to choroidal area in the macular area (67.2%) and in the peripapillary area (59.1%). Factors associated with the changes in the peripapillary choroidal area included decreases in the diastolic blood pressure and IOP. CONCLUSIONS:A reduction in the IOP after trabeculectomy led to increases in the macular and peripapillary choroidal areas. Observed changes in the choroidal area after trabeculectomy are primarily due to increases in the luminal areas.

To determine the structural changes of the choroid in eyes with central serous chorioretinopathy (CSC) by enhanced depth imaging optical coherence tomography (EDI-OCT).A retrospective comparative study was performed at two academic institutions. Forty eyes with CSC, their fellow eyes, and 40 eyes of age-matched controls were studied. Subfoveal cross sectional EDI-OCT images were recorded, and the hypo reflective and hyperreflective areas of the inner and outer choroid in the EDI-OCT images were separately measured. The images were analyzed by a binarization method to determine the sizes of the hyporeflective and hyperreflective areas.In the inner choroid, the hyperreflective area was significantly larger in the CSC eyes (35,640±10,229 μm2) than the fellow eyes (22,908±8,522 μm2) and the control eyes (20,630±8,128 μm2; P

To determine the effects of dynamic exercise on the circulation and the luminal and stromal areas of the choroid in normal eyes.This was a prospective interventional study of 38 eyes of 38 normal subjects enrolled by invitation. The systolic and diastolic blood pressures, heart rate, intraocularpressure, mean ocular perfusion pressure (MOPP), choroidal blood velocity, and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded before, and immediately after mild dynamic exercise. The same measurements were recorded after 10 min of rest. The choroidal blood velocity was measured bylaser speckle flowgraphy, and the mean blur rate was used for the evaluations. The horizontal EDI-OCT images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), total cross sectional choroidal area, luminal areas, stromal areas, and the ratio of luminal area to total choroidal area (L/C ratio) were determined from these images.The systolic and diastolic blood pressures, heart rate, MOPP, and the mean blur rate were significantly increased immediately after the exercise and significantly decreased 10 minutes after the exercise. There wereno significant changes in the mean CCT, the mean total choroidal area, the mean luminal and stromal areas, and the mean L/C ratio after the exercise.Our results suggest that a rest period is needed before measurements of blood flow velocity but not necessary for the EDI-OCT imaging to determine the choroidal thickness and area.

[This corrects the article DOI: 10.1371/journal.pone.0164672.].

PURPOSE:To compare the choroidal structure of the subfoveal area in the eyes of children with anisohypermetropic amblyopia to that of the fellow eyes and to age-matched controls using a binarization method of the images obtained by enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS:This study was performed at Nara Medical University Hospital, Tokushima University Hospital, and Kagoshima University Hospital, Japan. Forty amblyopic eyes with anisohypermetropic amblyopia and their fellow eyes (5.9 ± 2.1 years, mean ± standard deviation), and 103 age-matched controls (6.7 ± 2.4 years) were studied. The control eyes were divided into myopic, emmetropic, and hyperopic eyes. The total choroidal area, luminal area and stromal area of the subfoveal choroid were measured by the binarization method. The luminal/stromal ratio and the axial length of the amblyopic eyes were compared to that of the control eyes. RESULTS:The total choroidal area in the amblyopic eyes was significantly larger than that of the fellow eyes (P = 0.005). The luminal/stromal ratio was significantly larger in the amblyopic eyes than that of the fellow eyes (P

To determine the structural changes in the choroid after half-dose photodynamic therapy (hPDT) in eyes with chronic central serous chorioretinopathy (CSC).This was a retrospective interventional study of 29 eyes of 29 patients who underwent hPDT for chronic CSC with serous retinal detachment (SRD) and were followed for ≥3 months. Enhanced depth imaging optical coherence tomographic (EDI-OCT) images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), the cross sectional subfoveal choroidal area, the hyporeflective and hyperreflective areas of the inner, outer, and whole choroid were determined at the baseline, and at 1, 3, and 12 months after the hPDT.The SRDs were resolved in 26 (89.7%) eyes at 3 months after the hPDT. The mean CCT (P = 0.001), the total choroidal area (P = 0.001), and the hypo-reflective area (P = 0.003) of the whole choroid were significantly decreased from the baseline at 3 months. The hyperreflective area of whole choroid was not significantly changed during the study period (P = 0.083). The hyperreflective but not the hyporeflective area of the inner choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively). The hyporeflective but not the hyperreflective area of the outer choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively).The hyperreflective area of the inner choroid and hyporeflective area of the outer choroid were significantly decreased after hPDT for chronic CSC. Because the hyperreflective and hyporeflective area correspond to the choroidal stroma and vessels, respectively, the decreased CCT and subfoveal choroidal area after hPDT may be attributed to a decrease in the exudative changes in the inner choroidal stroma and the reduction of the dilation of the outer choroidal vessels.

PURPOSE:To determine whether the width of the retinal artery (RA) trajectory was associated with the presence of a macular hole (MH). METHODS:A retrospective cross sectional case-control study was performed. The fundus photographs were rotated 90 degrees, and the coordinates of the best fit curve of the RA trajectory were determined automatically based on these plots using the ImageJ program. The converted coordinates were fit to a second degree polynomial (ax2/100 + bx + c) equation. The width and steepness of the RA trajectory, "a", of the eyes with a MH eye were compared to that of the fellow eyes. RESULTS:One hundred and ten eyes of 55 consecutive patients (30 women) with a unilateral MH and healthy fellow eyes were analyzed. The mean age was 64.9 years (range 47-81 years). The constant 'a' was significantly smaller in eyes with a MH than that of the fellow eyes (0.379 ± 0.094 vs 0.416 ± 0.121, P = 0.001, paired t test), indicating that the RA trajectory was wider in the MH eyes than in the fellow eyes. There was a significant correlation between the axial length and 'a' of the RA trajectory in the MH eyes (R = 0.273, P = 0.044) and in the fellow eyes (R = 0.356, P = 0.008; Spearman's rank correlation coefficient). CONCLUSIONS:Because eyes with a MH have a significantly wider and flatter RA trajectory, there may be greater traction on the fovea which is located between the RA arches. The causative role of this finding is still unclear.

PURPOSE: To determine by objective methods the minimum number of spectral-domain optical coherence tomographic (SD-OCT) images to average to obtain the clearest retinal image. METHODS: SD-OCT Images were obtained from 9 healthy eyes and also from a phantom eye model. The SD-OCT images were obtained by averaging 1, 5, 20, 60, and 100 B-scan images. The reflectivity (mean gray value) of the different retinal layers was evaluated in these images. The image quality was evaluated by the size of the standard deviations (SDs) and the contrast-to-noise ratios (CNRs). A phantom eye model made by TiO2 silicone plates was also examined. RESULTS: The SDs decreased significantly when the number of images averaged increased from 1 to 5 and also from 5 to 20 (P

Asymmetrical secretion of vascular endothelial growth factor (VEGF) by retinal pigment epithelial (RPE) cells in situ is critical for maintaining the homeostasis of the retina and choroid. VEGF is also involved in the development and progression of age-related macular degeneration (AMD). We studied the effect of tumor necrosis factor-α (TNF-α) on the secretion of VEGF in polarized and non-polarized RPE cells (P-RPE cells and N-RPE cells, respectively) in culture and in situ in rats. A subretinal injection of TNF-α caused a decrease in VEGF expression and choroidal atrophy. Porcine RPE cells were seeded on Transwell™ filters, and their maturation and polarization were confirmed by the asymmetrical VEGF secretion and trans electrical resistance. Exposure to TNF-α decreased the VEGF secretion in P-RPE cells but increased it in N-RPE cells in culture. TNF-α inactivated JNK in P-RPE cells but activated it in N-RPE cells, and TNF-α activated NF-κB in P-RPE cells but not in N-RPE cells. Inhibition of NF-κB activated JNK in both types of RPE cells indicating crosstalk between JNK and NF-κB. TNF-α induced the inhibitory effects of NF-κB on JNK in P-RPE cells because NF-κB is continuously inactivated. In N-RPE cells, however, it was not evident because NF-κB was already activated. The basic activation pattern of JNK and NF-κB and their crosstalk led to opposing responses of RPE cells to TNF-α. These results suggest that VEGF secretion under inflammatory conditions depends on cellular polarization, and the TNF-α-induced VEGF down-regulation may result in choroidal atrophy in polarized physiological RPE cells. TNF-α-induced VEGF up-regulation may cause neovascularization by non-polarized or non-physiological RPE cells.

Photoreceptor degeneration is the most critical cause of visual impairment in age-related macular degeneration (AMD). In neovascular form of AMD, severe photoreceptor loss develops with subretinal hemorrhage due to choroidal neovascularization (CNV), growth of abnormal blood vessels from choroidal circulation. However, the detailed mechanisms of this process remain elusive. Here we demonstrate that neovascular AMD with subretinal hemorrhage accompanies a significant increase in extracellular ATP, and that extracellular ATP initiates neurodegenerative processes through specific ligation of Purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7; P2X7 receptor). Increased extracellular ATP levels were found in the vitreous samples of AMD patients with subretinal hemorrhage compared to control vitreous samples. Extravascular blood induced a massive release of ATP and photoreceptor cell apoptosis in co-culture with primary retinal cells. Photoreceptor cell apoptosis accompanied mitochondrial apoptotic pathways, namely activation of caspase-9 and translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei, as well as TUNEL-detectable DNA fragmentation. These hallmarks of photoreceptor cell apoptosis were prevented by brilliant blue G (BBG), a selective P2RX7 antagonist, which is an approved adjuvant in ocular surgery. Finally, in a mouse model of subretinal hemorrhage, photoreceptor cells degenerated through BBG-inhibitable apoptosis, suggesting that ligation of P2RX7 by extracellular ATP may accelerate photoreceptor cell apoptosis in AMD with subretinal hemorrhage. Our results indicate a novel mechanism that could involve neuronal cell death not only in AMD but also in hemorrhagic disorders in the CNS and encourage the potential application of BBG as a neuroprotective therapy.

This paper aims to evaluate the efficacy of intravitreal ultrasound (US) irradiation for green fluorescent protein (GFP) plasmid transfer into the rabbit retina using a miniature US transducer. Intravitreal US irradiation was performed by a slight modification of the transconjunctival sutureless vitrectomy system utilizing a small probe. After vitrectomy, the US probe was inserted through a scleral incision. A mixture of GFP plasmid (50 μL) and bubble liposomes (BLs; 50 μL) was injected into the vitreous cavity, and US was generated to the retina using a SonoPore 4000. The control group was not exposed to US. After 72 h, the gene-transfer efficiency was quantified by counting the number of GFP-positive cells. The retinas that received plasmid, BL, and US showed a significant increase in the number (average ± SEM) of GFP-positive cells (32±4.9; n=7; P