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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 investigate the relationship between changes in the optic disc size and color, cup-to-disc (C/D) ratio, and axial elongation in schoolchildren. Methods A prospective cohort study was performed in 75 right eyes of elementary school students for six years (from 8.5 to 14.5 years old). In the first and last year, all participants underwent optical axial length measurement and color fundus photography. The optic disc color was calculated by dividing the intensity of red by the sum of the intensity of red, green, and blue. The optic disc area was calculated by modifying the number of pixels according to Bennett’s formula. The C/D ratio was calculated by dividing the vertical cup diameter by vertical optic disc diameter. Wilcoxon signed rank test was used to compare these optic disc parameters and axial length in the first and last year. Results Mean axial length in the last year (24.82 mm) was significantly longer than that in the first year (23.34 mm). Likewise, the mean optic disc size was significantly smaller in the last year (41,946 pixels) than that in the first year (46,144 pixels). The mean optic disc color in the last year (0.49) was significantly more reddish than that in the first year (0.46), while the mean C/D ratio in last year (0.50) was significantly smaller than that in first year (0.52). Conclusions During the period from 8.5 years to 14.5 years of age, both the optic disc size and C/D ratio became smaller, while the color became more red.

ABSTRACT Aims/Introduction To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan. Materials and Methods Visually impaired patients with diabetes mellitus in Japan were divided into blind and low‐vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups. Results Among 408 visually impaired persons (blind group: 257, low‐vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low‐vision groups, respectively. Conclusions In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.

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 This study aimed to investigate the relationship between macular shape and idiopathic macular hole (MH) findings using an objective method. We present retrospective observational case series on patients with MH. The shape of the macular area was quantified using quadratic equations, and the ocular shape (OS) index was calculated. The correlation between the OS index and macular hole findings for each stage was evaluated. Pearson's correlation coefficient showed a significant correlation between the OS index and horizontal hole diameter (p = 0.044), bottom diameter (p = 0.006), and vertical bottom diameter (p = 0.024) in stage 2. For stage 4, there was a negative and significant correlation between the OS index and age (p = 0.037), and horizontal (p = 0.021) and vertical (p = 0.027) bottom diameter. Multiple regression analysis showed that the horizontal (p = 0.0070) and vertical (p = 0.031) bottom diameter and OS index were independently and positively correlated in stage 2. In stage 4, the OS index was independently and negatively correlated with the horizontal (p = 0.037) and vertical (p = 0.048) bottom diameter. The ocular shape of the macula affects MH findings, and its impact depends on its stage.

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.

ABSTRACT Aims/Introduction In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. Materials and Methods This is a real‐world clinical study including 1,552 patients with treatment‐naïve center‐involved DME. The patients were categorized into 4 categories by age at baseline (C1,

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

Abstract The purpose of this study was to investigate the effects of surgeon-related factors on the surgical outcome of pars plana vitrectomy (PPV) and scleral buckling (SB) surgery on eyes with a rhegmatogenous retinal detachment (RRD). This was a nationwide, multicenter, observational study of the data in the Japan-RD Registry. Registered cases that had undergone surgery for a RRD by 128 accredited surgeons in 26 institutions were studied. The surgeon-related factors that significantly affected surgical success and visual outcomes of simple RRD treated by PPV or SB at 6 months postoperatively were analyzed and compared. Among 3446 registered cases, 2533 cases met the inclusion criteria with 1896 in the PPV group and 637 cases in the SB group. The median total number of lifetime cases was 150 and the rate of surgeries/year was 22. Multivariate regression analyses showed that the number and rate of surgeries/year were not significantly associated with the surgical outcome in the PPV group. However, surgeons with a higher average annual number of surgeries had significantly better surgical outcomes in the SB group (P = 0.038). Analyses of a nationwide registry showed that SB but not PPV surgeries require sufficient experience and case numbers to acquire and maintain skills to treat RRDs successfully.

PurposeIn a previous cross-sectional study, we reported that the sexes can be distinguished using known factors obtained from color fundus photography (CFP). However, it is not clear how sex differences in fundus parameters appear across the human lifespan. Therefore, we conducted a cohort study to investigate sex determination based on fundus parameters in elementary school students.MethodsThis prospective observational longitudinal study investigated 109 right eyes of elementary school students over 4 years (age, 8.5 to 11.5 years). From each CFP, the tessellation fundus index was calculated as red/red + green + blue (R/[R+G+B]) using the mean value of red-green-blue intensity in eight locations around the optic disc and macular region. Optic disc area, ovality ratio, papillomacular angle, and retinal vessel angles and distances were quantified according to the data in our previous report. Using 54 fundus parameters, sex was predicted by L2 regularized binomial logistic regression for each grade.ResultsThe right eyes of 53 boys and 56 girls were analyzed. The discrimination accuracy rate significantly increased with age: 56.3% at 8.5 years, 46.1% at 9.5 years, 65.5% at 10.5 years and 73.1% at 11.5 years.ConclusionsThe accuracy of sex discrimination by fundus photography improved during a 3-year cohort study of elementary school students.

Vascular endothelial growth factor A (VEGF-A) plays pivotal roles in regulating tumor angiogenesis as well as physiological vascular function. The major VEGF-A isoforms, VEGF-A121 and VEGF-A165, in serum, plasma, and platelets have not been exactly evaluated due to the lack of the appropriate assay system. Antibodies against human VEGF-A121 and VEGF-A165 (hVEGF-A121 and hVEGF-A165) were successfully produced and Enzyme-Linked ImmunoSorbent Assay (ELISA) for hVEGF-A121 and hVEGF-A165 were separately created by these monoclonal antibodies. The measurement of recombinant hVEGF-A121 and hVEGF-A165 by the created ELISA showed no cross-reaction between hVEGF-A121 and hVEGF-A165 in conditioned media from HEK293 cells transfected with either hVEGF-A121 or hVEGF-A165 expression vector. The levels of VEGF-A121 and VEGF-A165 in serum, plasma, and platelets from 59 healthy volunteers proved that VEGF-A121 level was higher than VEGF-A165 in both plasma and serum in all the cases. VEGF-A121 or VEGF-A165 in serum represented higher level than that in plasma. In contrast, the level of VEGF-A165 was higher than VEGF-A121 in platelets. The newly developed ELISAs for hVEGF-A121 and hVEGF-A165 revealed different ratios of VEGF isoforms in serum, plasma, and platelets. Measuring these isoforms in combination provides useful information as biomarkers for diseases involving VEGF-A121 and VEGF-A165.

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 It is known that social factors affect the choice of treatments, and special attention has been paid to sex differences. The purpose of this study was to determine whether regional and sex differences exist in the treatment of rhegmatogenous retinal detachment (RD). We used Japan-RD Registry database of 2523 patients aged ≥ 40 years between February 2016 and March 2017 in 5 Japanese regions. Regional differences of patients’ perioperative factors were analyzed. The factors affecting the proportion of patients who underwent surgery within one week of the onset, defined as early-surgery, were examined by logistic regression. We observed regional differences in perioperative factors, especially in the use of phacovitrectomy, general anesthesia, and air-tamponade, which was higher in certain regions. (Fisher’s exact test, all P = 0.012) The proportion of early-surgery was significantly higher among men in Kyushu region (Odds ratio (OR) 1.83; 95% confidence interval (CI) 1.08–3.12; P = 0.02), and it was also significantly higher after adjusting for covariates (OR 1.89; 95% CI 1.06–3.42; P = 0.02). Regional and sex differences exist in the treatment of RD in Japan. Although there was no significant differences in the anatomical outcomes, women in certain regions of Japan are less likely to receive early surgical intervention for RD.

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 The purpose of this study was to compare the incidences of macular irregularities of elementary school (ES) and junior high school (JHS) students. This was a prospective cross-sectional observational study of 122 right eyes of 122 ES students (8–9 years) and 173 right eyes of 173 JHS students (12–13 years). Vertical cross-sectional images of the macula were obtained by optical coherence tomography. The eyes were classified based on the vertical symmetry of the posterior pole, and then sub-classified as convex-, flat-, concave-, or dome-shaped based on the direction of the curvature of the retinal pigment epithelium. One hundred and two eyes (83.6%) were placed in the symmetrical group in the ES students and 149 eyes (86.1%) in the JHS students. Twenty eyes (16.4%) were placed in the asymmetric groups in the ES students and 24 eyes (13.9%) in the JHS students. In symmetrical group, 78 and 118 eyes had a convex-shape (76.4 and 79.2%), followed by 22 and 29 eyes of dome-shaped group (21.6 and 19.4%) in ES and JHS students respectively. Because the incidences of the posterior pole shapes were not significantly different between the groups, it is likely that the macular irregularities develop before the age of ES.

PurposeTo evaluate the clinical characteristics, treatment trends, and visual prognosis of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD) and retinal arterial macroaneurysm (RAM).MethodsThis retrospective study enrolled 187 Japanese patients with SMH at 10 institutions from 2015 to 2018. Medical records including SMH etiology, best-corrected visual acuity (BCVA), fundus photographs, optical coherence tomography images, and selected treatments were analyzed.ResultsMajor causes of SMH were typical nAMD (tnAMD) (18%), polypoidal choroidal vasculopathy (PCV) (50%) and RAM (29%). Age, male/female ratio, baseline BCVA, central retinal thickness, and involved retinal layers were significantly different between etiologies (all PConclusionsThe characteristics of, and treatment strategy for, SMH were different between the underlying diseases. Anti-vascular endothelial growth factor treatment with or without expansile gas was mainly chosen for SMH in tnAMD and PCV, whereas vitrectomy with gas was the most common treatment for RAM, and the higher rate for vitrectomy might result in the greater BCVA improvement in the RAM group than in the other groups. Final BCVA was better in PCV, RAM, and tnAMD, in that order, because patients with PCV were younger and had better baseline BCVA.

PurposeMyopia is a known risk factor of pigmentary glaucoma (PG), and the increased prevalence of myopia in Asian countries indicates that more cases of PG will likely develop soon. However, there are no diagnostic criteria for PG for Asians. Therefore, the purpose of this study is to determine the characteristics of PG in Japanese individuals and establish three diagnostic signs for PG.MethodsThis was a single-center, retrospective, case series study of glaucoma patients who visited the Kagoshima University Hospital between January 2015 and January 2020. The inclusion criteria were age ResultsTen eyes of 5 Japanese men and 10 eyes of 5 Japanese women were studied. Their age ranged from 13 to 46 years at the time of diagnosis. One eye had posterior corneal pigmentation and 6 eyes had pigmentation of the trabecular meshwork. None had mid peripheral iris transillumination defect. The Sampaolesi line, iris concavity, and midperipheral iris depigmentation were found in all patients except one patient who lacked the mid peripheral depigmentation. Two eyes had the pigment reversal sign, none had lens pigmentation, and 2 eyes had peripheral retinal degeneration.ConclusionThe presence of the Sampaolesi line, iris concavity, and midperipheral iris depigmentation may be appropriate signs for the diagnosis of PG in Asians.

Background: When scleral buckling is performed using a #240 encircling band anterior to the equator for rhegmatogenous retinal detachment, buckle migration may occur anteriorly, eroding the rectus muscle. There are few cases of buckle migration occurring simultaneously with buckle infection. Notably, most previous reports included inadequate data on the pathophysiology of buckle migration and did not include the Hess test and perioperative images. Case presentation: A 36-year-old man with a history of atopic dermatitis underwent scleral buckling for rhegmatogenous retinal detachment of the left eye with #287 and #240 encircling bands at Kagoshima University Hospital. Four years later, he developed discharge, redness, and diplopia of the left eye. He was then referred to our hospital because buckle infection was suspected. The buckle was partially visible on the lower nasal side. Optical coherence tomography of the anterior chamber revealed the buckle to be on the nasal side and overlying the medial rectus muscle. Buckle migration and infection in the left eye was diagnosed, and early buckle removal was recommended. Two weeks later, on the day before surgery, conjunctival melting progressed in the nasal and inferior areas, and the buckle was exposed to a greater extent. In the surgical video at the initial surgery, the silicone band was confirmed to pass under the four rectus muscles, specifically the inferior and medial rectus muscles. At the beginning of the second surgery, we confirmed that the buckles were over the inferior and medial rectus muscles. As far as could be observed after buckle removal, the inferior and medial rectus muscles were not present at the normal location. Postoperatively, ocular pain and discharge quickly resolved. The subjective symptoms of diplopia also improved, and the postoperative Hess chart showed an improved ocular movement in the upward and lateral directions. Conclusions: Buckle migration is a rare postoperative complication of scleral buckling; however, patients at risk of buckle migration, such as those with encircling scleral buckle anterior to the eyeball, should be monitored with caution. If a buckle infection develops, buckle migration may occur within a short period, and early buckle removal should be considered.

PurposeTo investigate retinal vessel shift (RVS) and its association with axial length (AL) elongation in junior high school students.MethodsTotal 161 eyes of 161 healthy junior high school students were prospectively studied. Optical AL and anterior chamber depth (ACD) measurements, and fundus photography were performed in the first and third grades. Eyes of subjects in the first and third grade that had perfect matching among all the retinal vessels were allocated to the RVS(-) group, otherwise allocated to the RVS(+) group. In the RVS(+) group, the peripapillary retinal arteries angle (PRAA) was measured for quantitative analysis of RVS; the angle between the major retinal arteries. The variables related to PRAA were identified using model selection with the corrected Akaike information criterion.ResultsForty-two eyes (26.1%) were allocated to the RVS(+) group. There were seven patterns in the RVS of those in the RVS(+) group, including clockwise shift in the supra temporal area (5 eyes), infra temporal area (7 eyes), and nasal area (9 eyes); anticlockwise shift in the supra temporal area (7 eyes), infra temporal area (5 eyes), and nasal area (2 eyes); and distal shift in the temporal area (7 eyes). The optimal model for the PRAA narrowing included larger AL and body weight in the first grade, and greater AL elongation.ConclusionVarious (seven) RVS patterns were observed in about 25% of the junior high school students within two years. RVS was associated with AL elongation, and useful to reveal the mechanism of myopic retinal stretch.

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.

PurposeIntravitreal anti-VEGF injection (IVI) is administered before vitrectomy to assist management of proliferative diabetic retinopathy (PDR)-related complications. In the clinical setting, retinal surgeons determine the use of preoperative IVI based on individual criteria. In this study, we investigated factors related to the potential bias of retinal surgeons in using IVI prior to vitrectomy for PDR-related complications, and evaluated the real-world outcomes of surgeon-determined preoperative IVI.MethodsMedical records of 409 eyes of 409 patients who underwent 25-gauge vitrectomy for PDR complications at seven Japanese centers (22 surgeons) were retrospectively reviewed. Ocular factors, demographic and general clinical factors, surgical procedures, and postoperative complications were compared between IVI group (patients who received preoperative IVI; 87 eyes, 21.3%) and non-IVI group (patients who did not receive preoperative IVI; 322 eyes, 78.7%). In addition, baseline HbA1c in IVI group and non-IVI group was compared between eyes with and without postoperative complications.ResultsAt baseline, IVI group was younger (PConclusionsIn this multicenter real-world clinical study, younger age and presence of NVG and TRD were identified as potential biases in using IVI before vitrectomy for PDR complications. Eyes that received preoperative IVI had more intraoperative retinal breaks requiring tamponade than eyes not receiving IVI, but postoperative outcome was not different between the two groups.

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

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.

Abstract Background The purpose of this study is to determine whether the lifestyle and body stature are significantly associated with the axial length (AL) of the eyes of Japanese third grade students. Methods A prospective, cross sectional, observational study was performed on 122 third grade students consisting of 61 boys and 61 girls ages 8 to 9 years. The AL, body height, body weight, and body mass index (BMI) were measured. The lifestyle was determined by activities such as the daily duration of indoor studying, television viewing, use of computers and smart phones, outdoor activity time, bed time, Japanese or Western dietary habits, and parental myopia were investigated by a questionnaire with three or five grade levels. The relationship between AL and the questionnaire variables were analyzed by Spearman’s correlation analyses. Results Westernized dietary habits (r = −0.24, P = 0.01), duration of computer and smart phone use (r = 0.24, P = 0.008), parental myopia (r = 0.39, P

Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively examined the bacterial endophthalmitis characteristics of 314 Japanese patients and performed statistics using these clinical data. Older patients, with significantly more severe clinical symptoms, were prevalent in the ExE group compared with the EnE group. However, the final best-corrected visual acuity (BCVA) was not significantly different between the ExE and EnE groups. Bacteria isolated from patients were not associated with age, sex, or presence of eye symptoms. Genus Streptococcus, Streptococcus pneumoniae, and Enterococcus were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye pain, bacterial identification, and poor BCVA at baseline were risk factors for final visual impairment.

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

Optical coherence tomography (OCT) has made it possible for clinicians to measure the peripapillary choroidal thickness (ppCT) noninvasively in various ocular diseases. However, the ocular factors associated with the ppCT have not been conclusively determined. The purpose of this study was to determine the relationship between the local ppCT and the axial length, optic disc tilt, and the angle of the papillo-macular position (PMP) in healthy eyes. This was a prospective, observational cross-sectional study of 119 right eyes of 119 healthy Japanese volunteers. The ppCT was manually measured at eight sectors around the optic disc using the B-scan images of the Topcon 3D OCT RNFL 3.4 mm circle scan. The trajectory of the retinal pigment epithelium in the B-scan image was fitted to a sine curve using ImageJ, and the amplitude of the sine curve was used to determine the degree of the optic disc tilt. The PMP angle was determined in the color fundus photographs. The relationships between the ppCT and the axial length, the optic disc tilt, and PMP angle were determined by Spearman and multiple correlation analyses. The mean age was 25.8 ± 3.9 years and the mean axial length was 25.5 ± 1.4 mm. The ppCT was significantly and negatively associated with the axial length (R = -0.43 to -0.24, P

The location of the peaks of the circumpapillary retinal nerve fiber layer (cpRNFL) thickness is affected by several ocular parameters. In this study, we have generated equations that can determine the peaks of the cpRNFL. This study was a prospective, observational, cross sectional study of 118 healthy right eyes. The axial length, optic disc tilt, superiortemporal (ST)- and inferiortemporal (IT)-peaks of the cpRNFL thickness, and angles of the ST and IT retinal arteries (RA) and veins (RV) were determined. The correlations between the location of the ST- and IT-peaks and ocular structural parameters and the sex, body height and weight were calculated. The best fit equations to generate the location of the ST/IT-peaks were determined using corrected-Akaike Information Criteria. The location of the ST-peak was 0.72+(0.40 x ST-RA)+(0.27 x ST-RV)+(0.14 x height)-(0.47 x papillo-macular-position)-(0.11 x disc tilt) with a coefficient of correlation of 0.61 (P

Tessellated fundus is found as common and early-phase characteristic of myopic eyes and their locations are varied among patients. However, the relationship between their locations and morphological parameters of the eyes is still unknown. The purpose is this study is to determine the locations of the tessellations in the ocular fundus of young healthy eyes, and to determine relationships between their locations and morphological parameters of the eyes. This is a prospective observational cross sectional study of 126 eyes of 126 healthy volunteers (mean age 26.0±4.1 years). The eyes were classified into eight groups based on the location of the tessellations; no tessellation, temporal, infra-temporal, inferior, nasal, peripapillary, whole retina, and unclassified tessellations. The degree of optic disc tilt was quantified using a sine curve fitting program on the optical coherence tomographic circle scan images. The correlations between each tessellation location and the axial length, area of the optic disc plus conus (AOC), and optic disc tilt were determined. Forty-four eyes were place in the no tessellation group, 12 eyes in the temporal, 21 eyes in the infra-temporal, 9 eyes in the inferior, 8 eyes in the nasal, 15 eyes in the peripapillary, 11 eyes in the whole, and 6 eyes in the unclassified groups. The differences in the axial lengths between the no tessellation group and the infra-temporal groups were significant. A significant difference was found in the AOC between the no tessellation and the inferior, infra-temporal, and peripapilalry groups. A significant difference was found in the optic disc tilt between the no tessellation and infra-temporal groups (P

Humanin (HN) is a small mitochondrial-encoded peptide with neuroprotective properties. We have recently shown protection of retinal pigmented epithelium (RPE) cells by HN in oxidative stress; however, the effect of HN on endoplasmic reticulum (ER) stress has not been evaluated in any cell type. Our aim here was to study the effect of HN on ER stress-induced apoptosis in RPE cells with a specific focus on ER-mitochondrial cross-talk. Dose dependent effects of ER stressors (tunicamycin (TM), brefeldin A, and thapsigargin) were studied after 12 hr of treatment in confluent primary human RPE cells with or without 12 hr of HN pretreatment (1-20 μg/mL). All three ER stressors induced RPE cell apoptosis in a dose dependent manner. HN pretreatment significantly decreased the number of apoptotic cells with all three ER stressors in a dose dependent manner. HN pretreatment similarly protected U-251 glioma cells from TM-induced apoptosis in a dose dependent manner. HN pretreatment significantly attenuated activation of caspase 3 and ER stress-specific caspase 4 induced by TM. TM treatment increased mitochondrial superoxide production, and HN co-treatment resulted in a decrease in mitochondrial superoxide compared to TM treatment alone. We further showed that depleted mitochondrial glutathione (GSH) levels induced by TM were restored with HN co-treatment. No significant changes were found for the expression of several antioxidant enzymes between TM and TM plus HN groups except for the expression of glutamylcysteine ligase catalytic subunit (GCLC), the rate limiting enzyme required for GSH biosynthesis, which is upregulated with TM and TM+HN treatment. These results demonstrate that ER stress promotes mitochondrial alterations in RPE that lead to apoptosis. We further show that HN has a protective effect against ER stress-induced apoptosis by restoring mitochondrial GSH. Thus, HN should be further evaluated for its therapeutic potential in disorders linked to ER stress.

The purpose of this study was to develop a method of quantifying the degree of optic disc tilt in normal eyes. This was a prospective, observational cross sectional study of 126 right eyes of 126 healthy volunteers. The optic disc tilt was determined from the circular peripapillary optical coherence tomographic (OCT) scan images. The course of the retinal pigment epithelium (RPE) layer in the peripapillary cross sectional scan images was fit to a sine wave curve, and the amplitude of the sine curve was used to reflect the degree of the optic disc tilt in the optical axis. The repeatability of the amplitude determinations was calculated. The correlation between the amplitude and the ovality ratio of the optic disc was determined. The correlation between the amplitude and the body height was also calculated. The mean amplitude was 36.6 ± 17.5 pixels, which was significantly and inversely correlated with the ovality ratio of the optic disc (R = -0.59, P < 0.001). The intra-rater and inter-rater correlation coefficients of the amplitude were significant high (P < 0.001, both). The amplitude was significantly and inversely correlated with the body height (R = -0.38, P < 0.001), but not with the axial length. In conclusion, a sine wave function can be used to describe the course of the RPE in the circumpapillary OCT images. The results indicate that the amplitude of the sine wave can be used to represent the degree of optic disc tilt. Thus, the sine wave analyses can be used as a quantifiable and repeatable method to determine the optic disc tilt.

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

Background/aims To determine the incidence and causative pathogens of endophthalmitis after vitrectomy during strict face mask wearing in the COVID-19 period. Methods This was a retrospective multicentre study including 31 ophthalmological institutions of the Japanese Retina and Vitreous Society or Japan-Clinical Retina Study group. Patients who had undergone vitrectomy during 2019, the pre-COVID-19 period, and from July 2020 to June 2021, the COVID-mask period, were studied. The results of cataract surgery were used as a control. The total number of vitrectomies and the total number of postoperative endophthalmitis were determined. Then, the differences in the incidence of postoperative endophthalmitis between the preCOVID-19 period and the COVID-mask period, and the type of pathogens causing the endophthalmitis were studied. Results The incidence of postvitrectomy endophthalmitis was significantly lower in the preCOVID-19 period with 16 568 surgeries and 18 endophthalmitis cases (0.11%) than in the COVID-mask period of 14 929 surgeries and 31 endophthalmitis cases (0.21%; p=0.031, OR=1.913, 95% CI 1.078 to 3.394). In the pre-COVID-19 period, 4 of the 18 eyes were culture positive, and all were of the Staphylococcus family. In the COVID-mask period, 9 of the 31 eyes were culture positive, and 4 cases were related to oral commensals including Streptococcus spp, which are reportedly very rare in endophthalmitis after vitrectomy. Conclusions It is necessary for physicians to be aware of the higher incidence of postvitrectomy endophthalmitis during the COVID-mask period, and to treat their patients appropriately. [ABSTRACT FROM AUTHOR]