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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., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Introduction: Many adverse occurrences in the eye have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. This is the first report of a patient with an unruptured retinal arterial macroaneurysm (RAM) who developed branch retinal artery occlusion (BRAO) one day after SARS-CoV-2 vaccination (BNT162b2 by Pfizer-BioNTech)., Patient Report: A 75-year-old man with a pertinent history of type-2 diabetes mellitus visited the hospital complaining of sudden visual loss in his right eye 1 day after receiving the fourth dose of the SARS-CoV-2 mRNA vaccine; his best-corrected visual acuity (BCVA) decreased from 1.0 to 0.7 (Snellen decimal). The patient had previously been diagnosed with an unruptured RAM and superior paracentral acute middle maculopathy in the same eye. Fundus examination showed increased sheathing of blood vessels. Indocyanine green showed a hyperfluorescent area suggestive of RAM on the right eye disc. Fluorescein angiography and optical coherence tomography angiography revealed arterial obstruction findings in the upper retinal area., Diagnosis and Intervention: The patient was diagnosed with BRAO with RAM and was followed up without any additional treatment. Follow-up examination after 4 months did not show any improvement in BCVA value., Conclusion: This case suggested that BRAO could develop after SARS-CoV-2 vaccination in patients with unruptured RAM; however, more research is required to investigate the causes., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The aim of this study was to examine the effects of foveal thickness (FT) fluctuation (FTF) on 2-year visual and morphological outcomes of eyes with central retinal vein occlusion (CRVO) undergoing anti-VEGF treatment for recurrent macular edema (ME) based on a pro re nata regimen., Design: Retrospective, observational case series., Participants: We analyzed 141 treatment-naive patients (141 eyes) with CRVO-ME at a multicenter retinal practice., Methods: We assessed FT using OCT at each study visit. Patients were divided into groups 0, 1, 2, and 3 according to increasing FTF., Main Outcome Measures: We evaluated the logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA), the length of the foveal ellipsoid zone (EZ) band defect measured using OCT, and the association of FTF with VA and EZ band defect length., Results: The mean baseline logMAR BCVA and FT were 0.65 ± 0.52 (Snellen equivalent range: 20/20-20/2000) and 661.1 ± 257.4 μm, respectively. The mean number of anti-VEGF injections administered was 5.6 ± 3.6. At the final examination, the mean logMAR BCVA and FT values were significantly improved relative to the baseline values (both P  < 0.01). During the observation, BCVA longitudinally improved in Groups 0 and 1, remained unchanged in Group 2, and worsened in Group 3. Likewise, the length of the foveal EZ band defect did not increase in Group 0; however, it gradually increased in Groups 1, 2, and 3. Foveal thickness fluctuation was significantly and positively associated with the logMAR BCVA and length of the foveal EZ band defect at the final examination ( P  < 0.01). The final logMAR BCVA of patients developing neovascular complications was 1.27 ± 0.72 (Snellen equivalent range: 20/50-counting fingers), which was significantly poorer than that of patients without complications ( P  < 0.001). There was no significant difference in the neovascular complication rate among the FTF groups ( P  = 0.106, Fisher exact test)., Conclusions: In eyes receiving anti-VEGF treatment for CRVO-ME, FTF can longitudinally impair the visual acuity and foveal photoreceptor status during the observation period, thus influencing the final outcomes. However, neovascular complications, which would also lead to a poor visual prognosis, may not be associated with FTF., Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article., (© 2023 by the American Academy of Ophthalmology.)

Purpose: The pathology of branch retinal vein occlusion (BRVO), a retinal circulatory disease, is related to monocular metamorphopsia-related vision impairment of the affected eyes, but the association of binocular metamorphopsia in such patients is unclear. This study aimed to examine the frequency of binocular metamorphopsia and its association with the clinical characteristics of patients with BRVO., Methods: A total of 87 patients who were treated for BRVO-associated macular edema (ME) were included in this study. At baseline and 1 and 3 months after the initiation of anti-vascular endothelial growth factor (VEGF) treatment, we quantified metamorphopsia in the affected eyes and binocular metamorphopsia using the M-CHARTS ® diagnostic tool., Results: At baseline, 53 and 7 patients had metamorphopsia in the affected eyes and binocular metamorphopsia, respectively. Although the visual acuity improved significantly after the initiation of anti-VEGF treatment, the mean M-CHARTS score in the affected eyes did not change from the baseline score. At 3 months, 9 patients showed binocular metamorphopsia; it was significantly associated with metamorphopsia in the affected eyes with a 95% confidence interval of 0.021-0.122 (β = 0.306, p = 0.006)., Conclusion: Metamorphopsia in the affected eyes can cause binocular metamorphopsia in patients with BRVO-ME., (© 2023. The Author(s).)

A higher serum vascular endothelial growth factor (VEGF) level can cause choroidal thickening in the choroid of patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. We aimed to determine whether fluctuations in serum VEGF levels affect choroidal vascular structures in patients with POEMS syndrome. This retrospective observational case series examined 17 left eyes of 17 patients with POEMS syndrome. Enhanced depth imaging optical coherence tomography (EDI-OCT) images were obtained, and serum VEGF levels were measured at baseline and 6 months after transplantation with dexamethasone (n = 6), thalidomide (n = 8), or lenalidomide (n = 3). EDI-OCT images were binarized using ImageJ software, and we calculated the areas of the whole choroid and the luminal and stromal areas. Subsequently, we determined whether the choroidal vascular structure had changed significantly between baseline and 6 months after treatment. Six months after treatment, serum VEGF levels and the whole choroid, luminal, and stromal areas had decreased significantly compared to the baseline values (all, P < 0.001). The mean luminal area to the whole choroidal area ratio at 6 months after treatment was 0.70 ± 0.03, which was significantly smaller than the ratio at baseline (0.72 ± 0.03; P < 0.001). Whole choroid and luminal area fluctuations were significantly positively correlated with fluctuations in serum VEGF levels (r = 0.626, P = 0.007 and r = 0.585, P = 0.014, respectively). Choroidal thickening induced by VEGF might be caused by increases in the choroidal vessel lumen area. These results may offer insights into the pathogenesis of POEMS syndrome and the role of serum VEGF in choroidal vascular structure, which may apply to other ocular diseases., (© 2023. The Author(s).)

Importance: There is no widespread effective treatment to halt the progression of retinitis pigmentosa. Consequently, adequate assessment and estimation of residual visual function are important clinically., Objective: To examine whether deep learning can accurately estimate the visual function of patients with retinitis pigmentosa by using ultra-widefield fundus images obtained on concurrent visits., Design, Setting, and Participants: Data for this multicenter, retrospective, cross-sectional study were collected between January 1, 2012, and December 31, 2018. This study included 695 consecutive patients with retinitis pigmentosa who were examined at 5 institutions. Each of the 3 types of input images-ultra-widefield pseudocolor images, ultra-widefield fundus autofluorescence images, and both ultra-widefield pseudocolor and fundus autofluorescence images-was paired with 1 of the 31 types of ensemble models constructed from 5 deep learning models (Visual Geometry Group-16, Residual Network-50, InceptionV3, DenseNet121, and EfficientNetB0). We used 848, 212, and 214 images for the training, validation, and testing data, respectively. All data from 1 institution were used for the independent testing data. Data analysis was performed from June 7, 2021, to December 5, 2022., Main Outcomes and Measures: The mean deviation on the Humphrey field analyzer, central retinal sensitivity, and best-corrected visual acuity were estimated. The image type-ensemble model combination that yielded the smallest mean absolute error was defined as the model with the best estimation accuracy. After removal of the bias of including both eyes with the generalized linear mixed model, correlations between the actual values of the testing data and the estimated values by the best accuracy model were examined by calculating standardized regression coefficients and P values., Results: The study included 1274 eyes of 695 patients. A total of 385 patients were female (55.4%), and the mean (SD) age was 53.9 (17.2) years. Among the 3 types of images, the model using ultra-widefield fundus autofluorescence images alone provided the best estimation accuracy for mean deviation, central sensitivity, and visual acuity. Standardized regression coefficients were 0.684 (95% CI, 0.567-0.802) for the mean deviation estimation, 0.697 (95% CI, 0.590-0.804) for the central sensitivity estimation, and 0.309 (95% CI, 0.187-0.430) for the visual acuity estimation (all P < .001)., Conclusions and Relevance: Results of this study suggest that the visual function estimation in patients with retinitis pigmentosa from ultra-widefield fundus autofluorescence images using deep learning might help assess disease progression objectively. Findings also suggest that deep learning models might monitor the progression of retinitis pigmentosa efficiently during follow-up.

Competing Interests: The authors declare that there are no conflicts of interests of this paper.

Anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) improves visual acuity. However, repeated injections during routine outpatient visits are required to maintain this effect. The recent sudden global outbreak of coronavirus disease 2019 (COVID-19) had a major impact on daily life, including medical care, such as the provision of VEGF therapy. We retrospectively investigated the relationship between the number of anti-VEGF injections for DME and the number of new COVID-19-positive patients at 23 centers in Japan. We also surveyed ophthalmologists regarding the impact of the COVID-19 pandemic on anti-VEGF therapy. In the third and fourth waves of the pandemic, when the number of infected patients increased, the number of injections significantly decreased. In the first, third, and fourth waves, the number of injections increased significantly during the last month of each wave. Approximately 60.9% of ophthalmologists reported that the number of injections decreased after the pandemic. Of the facilities, 52.2% extended the clinic visit intervals; however, there was no significant difference in the actual number of injections given between before and after the pandemic. Although the number of injections temporarily decreased, Japanese ophthalmologists maintained the total annual number of anti-VEGF injections for DME during the pandemic.

This study aimed to develop a diagnostic software system to evaluate the enlarged extraocular muscles (EEM) in patients with Graves' ophthalmopathy (GO) by a deep neural network.This prospective observational study involved 371 participants (199 EEM patients with GO and 172 controls with normal extraocular muscles) whose extraocular muscles were examined with orbital coronal computed tomography. When at least one rectus muscle (right or left superior, inferior, medial, or lateral) in the patients was 4.0 mm or larger, it was classified as an EEM patient with GO. We used 222 images of the data from patients as the training data, 74 images as the validation test data, and 75 images as the test data to "train" the deep neural network to judge the thickness of the extraocular muscles on computed tomography. We then validated the performance of the network. In the test data, the area under the curve was 0.946 (95% confidence interval (CI) 0.894-0.998), and receiver operating characteristic analysis demonstrated 92.5% (95% CI 0.796-0.984) sensitivity and 88.6% (95% CI 0.733-0.968) specificity. The results suggest that the deep learning system with the deep neural network can detect EEM in patients with GO., (© 2022. The Author(s).)

Purpose: Branch retinal vein occlusion (BRVO) causes macular edema (ME), which can be controlled with anti-VEGF treatments. However, these treatments are not curative, necessitating additional anti-VEGF treatments at recurrence. Long-term results, optimal anti-VEGF treatment regimens, and the comprehensive effects of ME recurrence are largely unknown. Thus, we aimed to examine the effects of foveal thickness (FT) fluctuation (FTF) on the visual and morphologic outcomes of anti-VEGF treatments for BRVO-ME administered via a pro re nata regimen., Design: A retrospective, observational case series., Subjects: This study analyzed 309 treatment-naïve patients (309 eyes) with BRVO-ME between 2012 and 2021 at a multicenter retinal practice., Methods: The FT was assessed using OCT at each study visit., Main Outcome Measures: We evaluated the logarithm of the minimal angle of resolution (logMAR) best corrected visual acuity (BCVA) and the defect length of the foveal ellipsoid zone (EZ) band using OCT., Results: At baseline, the mean logMAR BCVA was 0.30 ± 0.30 and the mean FT was 503 ± 162 μm. The number of anti-VEGF injections for BRVO-ME was 5.8 ± 4.6 during the mean follow-up period (50.6 ± 22.2 months). At the final examination, the mean logMAR BCVA and FT values were significantly improved compared with those at the baseline. Multiple regression analyses showed that age, baseline logMAR BCVA, and FTF were significantly associated with the final logMAR BCVA (β = 0.20, 0.35, and 0.30, respectively). Foveal thickness fluctuation (divided into groups 0-3 in ascending order of FTF) was significantly associated with logMAR BCVA and the defect length of the foveal EZ band at the final examination. The defect lengths of the foveal EZ band were longitudinally shortened in groups 0 and 1 and were slightly prolonged in groups 2 and 3. The logMAR BCVA showed improvements in groups 0 and 1 and worsened slightly in groups 2 and 3., Conclusions: Foveal thickness fluctuation was significantly associated with visual acuity and foveal photoreceptor status. Thus, the morphologic and functional prognoses of eyes with BRVO may improve with the identification of the characteristics of eyes with greater FTF and consequently controlling the FTF more strictly., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Retinal arterial macroaneurysm shows rapid vision loss when rupture occurs; therefore, preventive photocoagulation should be considered, if necessary., Competing Interests: There are no conflicts of interest., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Purpose: To assess the performance of artificial intelligence in the automated classification of images taken with a tablet device of patients with blepharoptosis and subjects with normal eyelid., Methods: This is a prospective and observational study. A total of 1276 eyelid images (624 images from 347 blepharoptosis cases and 652 images from 367 normal controls) from 606 participants were analyzed. In order to obtain a sufficient number of images for analysis, 1 to 4 eyelid images were obtained from each participant. We developed a model by fully retraining the pre-trained MobileNetV2 convolutional neural network. Subsequently, we verified whether the automatic diagnosis of blepharoptosis was possible using the images. In addition, we visualized how the model captured the features of the test data with Score-CAM. k-fold cross-validation (k = 5) was adopted for splitting the training and validation. Sensitivity, specificity, and the area under the curve (AUC) of the receiver operating characteristic curve for detecting blepharoptosis were examined., Results: We found the model had a sensitivity of 83.0% (95% confidence interval [CI], 79.8-85.9) and a specificity of 82.5% (95% CI, 79.4-85.4). The accuracy of the validation data was 82.8%, and the AUC was 0.900 (95% CI, 0.882-0.917)., Conclusion: Artificial intelligence was able to classify with high accuracy images of blepharoptosis and normal eyelids taken using a tablet device. Thus, the diagnosis of blepharoptosis with a tablet device is possible at a high level of accuracy., Trial Registration: Date of registration: 2021-06-25., Trial Registration Number: UMIN000044660. Registration site: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000051004., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: In this paper, we report on 2 patients who developed branch retinal vein occlusion (BRVO) exacerbation 1 day after administration of the BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine., Patient Concerns: Case 1: A 71 year-old female developed vision loss in her left eye 1 day after receiving a second dose of the SARS-CoV-2 mRNA vaccine. This patient was diagnosed with temporal inferior BRVO and secondary macular edema (ME) in her left eye. ME resolved after 3 doses of intravitreal aflibercept (IVA). After treatment, no recurrence of ME was observed.Case 2: A 72 year-old man developed vision loss in his right eye 1 day after receiving the first dose of the SARS-CoV-2 mRNA vaccine. This patient was diagnosed with temporal superior BRVO in the right eye without ME. The patient was followed up and did not undergo any additional treatment., Diagnoses: Case1: Temporal superior BRVO and secondary ME were observed in the left eye. Her best-corrected visual acuity (BCVA) was 20/30.Case2: Temporal superior BRVO recurrence and secondary ME were observed in the right eye. BCVA was 20/25., Interventions: Case1: Additional dose of IVA was administered. Case2: Two times of Intravitreal ranibizumab was administered twice., Outcomes: Case1: Subsequently, ME resolved BCVA was 20/20. Case2: Subsequently, ME resolved BCVA was 20/25., Lessons: Both cases showed a possible association between SARS-CoV-2 vaccination and the exacerbation of BRVO., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: We assessed the ability of deep learning (DL) models to distinguish between tear meniscus of lacrimal duct obstruction (LDO) patients and normal subjects using anterior segment optical coherence tomography (ASOCT) images., Methods: The study included 117 ASOCT images (19 men and 98 women; mean age, 66.6 ± 13.6 years) from 101 LDO patients and 113 ASOCT images (29 men and 84 women; mean age, 38.3 ± 19.9 years) from 71 normal subjects. We trained to construct 9 single and 502 ensemble DL models with 9 different network structures, and calculated the area under the curve (AUC), sensitivity, and specificity to compare the distinguishing abilities of these single and ensemble DL models., Results: For the highest single DL model (DenseNet169), the AUC, sensitivity, and specificity for distinguishing LDO were 0.778, 64.6%, and 72.1%, respectively. For the highest ensemble DL model (VGG16, ResNet50, DenseNet121, DenseNet169, InceptionResNetV2, InceptionV3, and Xception), the AUC, sensitivity, and specificity for distinguishing LDO were 0.824, 84.8%, and 58.8%, respectively. The heat maps indicated that these DL models placed their focus on the tear meniscus region of the ASOCT images., Conclusion: The combination of DL and ASOCT images could distinguish between tear meniscus of LDO patients and normal subjects with a high level of accuracy. These results suggest that DL might be useful for automatic screening of patients for LDO.

Purpose: The effects of coffee intake on the ratio of stromal and luminal components in the choroid and the underlying mechanism remain unclear. This prospective cross-sectional study aimed to explore how coffee intake affects the choroidal component ratio and circulation., Methods: Forty-nine right eyes of healthy adult volunteers were evaluated as the coffee intake group. Thirty-two right eyes of healthy volunteers served as the control group. The participants consumed 185 mL of coffee or water, respectively, and the systemic hemodynamics, enhanced-depth imaging optical coherence tomographic (EDI-OCT) images, and foveal mean blur rate (MBR), an indicator of blood flow velocity, were recorded at baseline and after coffee or water intake. The EDI-OCT images were binarized using ImageJ software, and subfoveal choroidal thickness (SCT) and whole, luminal, and stromal choroidal areas were calculated., Results: In the coffee intake group, significant decreases in SCT and luminal area peaked at 60 minutes after intake (both P < 0.001), whereas a significant increase in MBR peaked at 30 minutes (P < 0.001). No significant stromal area fluctuations were observed. SCT and luminal area fluctuations exhibited a significant positive correlation (r = 0.978, P < 0.001). Significant negative correlations of luminal area fluctuations with MBR fluctuations were observed by stepwise regression analysis (r = -0.220, P < 0.001). The control group exhibited no significant fluctuations., Conclusions: Coffee-induced choroidal thinning may result mainly from a reduction in the choroidal vessel lumen, and this vessel lumen reduction correlated with an increased choroidal blood flow velocity after coffee intake. These coffee-induced changes in choroidal component ratio and circulation should be considered when evaluating choroids.

A 61-year-old man presented with corneal perforation of 1.0 mm in diameter in his right eye caused by a metallic foreign body fragment. We used the "one-bite mini-keratoplasty" technique, which uses a cornea patch with a single host-graft-host suture to stop aqueous humor leakage. Postoperatively, the graft was completely epithelialized. The suture was removed and the use of soft contact lens was discontinued. Postoperative best-corrected visual acuity (BCVA) recovered to 180/200 and corneal astigmatism was 0.6 diopters. The postoperative course was unremarkable, but corneal perforation recurred due to an ocular contusion at 17 months. He was reoperated using the same technique. His BCVA was 160/200 and corneal astigmatism was 1.1 diopters after reoperation. Despite performing this surgical technique twice for corneal perforation, optimal visual function was maintained even after 2 years. For paracentral corneal perforations, our simple technique may reduce astigmatism and maintain high visual function.

Introduction: Neovascular glaucoma is characterized by neovascularization of the iris and anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may decrease intraocular pressure (IOP) and improve neovascularization. The VENERA study assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma., Methods: This was a 5-week, single-arm, nonrandomized, open-label, phase 3 study performed at 7 study sites in Japan that enrolled Japanese patients with anterior segment neovascularization and IOP > 25 mmHg who had not undergone (within 30 days prior), nor were imminently scheduled to undergo (within 8 days following) intraocular surgeries, including panretinal photocoagulation (PRP). Patients received background therapy plus 2 mg IVT-AFL at baseline. Background therapy with systemic IOP-lowering drugs was prohibited for 3 days before day 1 and until IOP evaluation at week 1. The primary endpoint was the change in IOP from baseline to week 1 and the secondary endpoint was the proportion of patients with an improvement of ≥ 1 grade of neovascularization of the angle (NVA) from baseline to week 1., Results: Sixteen patients received treatment (full analysis set); the per-protocol set comprised 15 patients. The mean IOP decreased from 34.1 mmHg at baseline to 25.8 mmHg at week 1 (mean change, -8.3 mmHg [95% confidence interval; CI -12.2 to -4.4; P = 0.0004]). At week 1, 81.3% of patients had an improvement in the grade of neovascularization of the iris (NVI) and 50.0% of patients had an improvement in NVA grade. The proportion of patients with controlled IOP (≤ 21 mmHg) was 43.8% (95% CI 19.8-70.1) at week 1, and increased to 56.3% at week 2 and 86.7% at week 5. The most common ocular treatment-emergent adverse event was eye pain, which occurred in 4 patients (25.0%)., Conclusions: IVT-AFL was associated with statistically significant and clinically meaningful IOP reductions, without concomitant use of systemic IOP-lowering drugs or PRP. The safety profile was consistent with the known safety profile of IVT-AFL. These findings supplement those from the previous VEGA study, and suggest that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma., Trial Registration: Clinicaltrials.gov identifier NCT03639675.

Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard treatment modality in various types of retinal diseases. However, endophthalmitis remains the most serious complication. Despite the lack of evidence that antibiotics prevent endophthalmitis, topical antibiotics are still used routinely in Japan. We conducted a retrospective multicenter study by analyzing records from patients who underwent IVI of anti-VEGF agents with or without antibiotic treatment. In the analysis of a total of 147,440 eyes, the incidence of endophthalmitis was 0.007%: 0.005% with no use of antibiotics, 0.009% with antibiotic pretreatment, 0.012% with posttreatment, and 0.005% with pre- and posttreatment. There was no statistically significant difference among the four groups (chi-square test, p = 0.57). Most facilities used masks, sterilized gloves, and drapes. Nine of the 10 eyes that developed endophthalmitis received topical antibiotics, and all infected eyes underwent IVI with aflibercept, not the prefilled syringe delivery system. In four patients who received multiple IVI, the detection of causative bacteria revealed resistance to used antibiotics. Data from this large population, treated with or without antibiotics, suggests that antibiotic prophylaxis does not reduce the rate of endophthalmitis after IVI.

Here, we examined prognostic factors for extremely poor visual outcomes in patients with central retinal vein occlusion (CRVO) in actual practices. We included 150 consecutive eyes with treatment-naïve acute CRVO from four different facilities and observed them for over 24 months. Macular edema (ME) was treated with one or three monthly anti-vascular endothelial growth factor injections (1 or 3 + pro re nata). According to the final Snellen visual acuity (VA), we divided the patients into very poor VA (< 20/200) and control (≥ 20/200) groups and examined risk factors for poor final visual outcomes. The baseline Snellen VA was hand motion to 20/13. The mean number of anti-VEGF injections for ME was 5.3 ± 3.7 during the follow-up period. In total, 49 (32.7%) patients exhibited a very poor final VA; this group comprised significantly older patients with a significantly poorer baseline VA (P < 0.01 for both) than the control group. Comorbid internal carotid artery disease and diabetic retinopathy were significantly associated with a poor final VA. In actual clinical practice, visual outcomes may be extremely poor despite ME treatment in certain patients with CRVO, with advanced age, poor baseline VA, and comorbid internal carotid artery disease and diabetic retinopathy being significant risk factors.

This study examined whether age and brachial-ankle pulse-wave velocity (baPWV) can be predicted with ultra-wide-field pseudo-color (UWPC) images using deep learning (DL). We examined 170 UWPC images of both eyes of 85 participants (40 men and 45 women, mean age: 57.5 ± 20.9 years). Three types of images were included (total, central, and peripheral) and analyzed by k-fold cross-validation (k = 5) using Visual Geometry Group-16. After bias was eliminated using the generalized linear mixed model, the standard regression coefficients (SRCs) between actual age and baPWV and predicted age and baPWV from the UWPC images by the neural network were calculated, and the prediction accuracies of the DL model for age and baPWV were examined. The SRC between actual age and predicted age by the neural network was 0.833 for all images, 0.818 for central images, and 0.649 for peripheral images (all P < 0.001) and between the actual baPWV and the predicted baPWV was 0.390 for total images, 0.419 for central images, and 0.312 for peripheral images (all P < 0.001). These results show the potential prediction capability of DL for age and vascular aging and could be useful for disease prevention and early treatment.

Purpose: To evaluate the ability of deep learning (DL) models to detect obstructive meibomian gland dysfunction (MGD) using in vivo laser confocal microscopy images., Methods: For this study, we included 137 images from 137 individuals with obstructive MGD (mean age, 49.9 ± 17.7 years; 44 men and 93 women) and 84 images from 84 individuals with normal meibomian glands (mean age, 53.3 ± 19.6 years; 29 men and 55 women). We constructed and trained 9 different network structures and used single and ensemble DL models and calculated the area under the curve, sensitivity, and specificity to compare the diagnostic abilities of the DL., Results: For the single DL model (the highest model; DenseNet-201), the area under the curve, sensitivity, and specificity for diagnosing obstructive MGD were 0.966%, 94.2%, and 82.1%, respectively, and for the ensemble DL model (the highest ensemble model; VGG16, DenseNet-169, DenseNet-201, and InceptionV3), 0.981%, 92.1%, and 98.8%, respectively., Conclusions: Our network combining DL and in vivo laser confocal microscopy learned to differentiate between images of healthy meibomian glands and images of obstructive MGD with a high level of accuracy that may allow for automatic obstructive MGD diagnoses in patients in the future.

This study examined and compared outcomes of deep learning (DL) in identifying swept-source optical coherence tomography (OCT) images without myopic macular lesions [i.e., no high myopia (nHM) vs. high myopia (HM)], and OCT images with myopic macular lesions [e.g., myopic choroidal neovascularization (mCNV) and retinoschisis (RS)]. A total of 910 SS-OCT images were included in the study as follows and analyzed by k-fold cross-validation (k = 5) using DL's renowned model, Visual Geometry Group-16: nHM, 146 images; HM, 531 images; mCNV, 122 images; and RS, 111 images (n = 910). The binary classification of OCT images with or without myopic macular lesions; the binary classification of HM images and images with myopic macular lesions (i.e., mCNV and RS images); and the ternary classification of HM, mCNV, and RS images were examined. Additionally, sensitivity, specificity, and the area under the curve (AUC) for the binary classifications as well as the correct answer rate for ternary classification were examined. The classification results of OCT images with or without myopic macular lesions were as follows: AUC, 0.970; sensitivity, 90.6%; specificity, 94.2%. The classification results of HM images and images with myopic macular lesions were as follows: AUC, 1.000; sensitivity, 100.0%; specificity, 100.0%. The correct answer rate in the ternary classification of HM images, mCNV images, and RS images were as follows: HM images, 96.5%; mCNV images, 77.9%; and RS, 67.6% with mean, 88.9%.Using noninvasive, easy-to-obtain swept-source OCT images, the DL model was able to classify OCT images without myopic macular lesions and OCT images with myopic macular lesions such as mCNV and RS with high accuracy. The study results suggest the possibility of conducting highly accurate screening of ocular diseases using artificial intelligence, which may improve the prevention of blindness and reduce workloads for ophthalmologists., Competing Interests: The authors have declared that no competing interests exist.

We aimed to assess the ability of deep learning (DL) and support vector machine (SVM) to detect a nonperfusion area (NPA) caused by retinal vein occlusion (RVO) with optical coherence tomography angiography (OCTA) images. The study included 322 OCTA images (normal: 148; NPA owing to RVO: 174 [128 branch RVO images and 46 central RVO images]). Training to construct the DL model using deep convolutional neural network (DNN) algorithms was provided using OCTA images. The SVM used a scikit-learn library with a radial basis function kernel. The area under the curve (AUC), sensitivity and specificity for detecting an NPA were examined. We compared the diagnostic ability (sensitivity, specificity and average required time) between the DNN, SVM and seven ophthalmologists. Heat maps were generated. With regard to the DNN, the mean AUC, sensitivity, specificity and average required time for distinguishing RVO OCTA images with an NPA from normal OCTA images were 0.986, 93.7%, 97.3% and 176.9 s, respectively. With regard to SVM, the mean AUC, sensitivity, and specificity were 0.880, 79.3%, and 81.1%, respectively. With regard to the seven ophthalmologists, the mean AUC, sensitivity, specificity and average required time were 0.962, 90.8%, 89.2%, and 700.6 s, respectively. The DNN focused on the foveal avascular zone and NPA in heat maps. The performance of the DNN was significantly better than that of SVM in all parameters (p < 0.01, all) and that of the ophthalmologists in AUC and specificity (p < 0.01, all). The combination of DL and OCTA images had high accuracy for the detection of an NPA, and it might be useful in clinical practice and retinal screening., Competing Interests: The funder, Rist Incorporated, provided support in the form of salary for author HE. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Purpose: To determine whether water drinking test (WDT) alters choroidal structure using binarization of enhanced depth imaging optical coherence tomographic (EDI-OCT) images., Methods: We performed a prospective study of 57 eyes of 57 normal subjects. The intraocular pressure (IOP), EDI-OCT images, and laser speckle flowgraphic images were recorded at baseline, and at 15, 30, 45, and 120 min after the WDT. The EDI-OCT images were converted to binary images using ImageJ software, and we examined luminal area, interstitial area, whole choroidal area, the ratio of luminal area to whole choroidal area (L/W ratio), subfoveal choroidal thickness (SCT), and central retinal thickness (CRT)., Results: The luminal area, L/W ratio, whole choroidal area, and IOP were significantly increased 30 min after water drinking; levels returned to the baseline at 120 min. No significant changes were found in the CRT and interstitial area. The fluctuations in the SCT after water intake were significantly correlated with those in the L/W ratio and luminal area but not with those of the interstitial area. The choroidal blood flow velocity was significantly decreased at 30 min. Fluctuations in the luminal area, L/W ratio, and whole choroidal area were significantly correlated with IOP fluctuations., Conclusions: The changes in the SCT after water drinking were mainly due to the changes in the choroidal vascular space. Dilatations of the choroidal vessels after water drinking may lead to choroidal thickening and subsequent IOP elevation. These findings should be considered in the evaluation of choroidal structure in patients with retinal disease.

Purpose: In this study, we compared deep learning (DL) with support vector machine (SVM), both of which use three-dimensional optical coherence tomography (3D-OCT) images for detecting epiretinal membrane (ERM)., Methods: In total, 529 3D-OCT images from the Tsukazaki hospital ophthalmology database (184 non-ERM subjects and 205 ERM patients) were assessed; 80% of the images were divided for training, and 20% for test as follows: 423 training (non-ERM 245, ERM 178) and 106 test (non-ERM 59, ERM 47) images. Using the 423 training images, a model was created with deep convolutional neural network and SVM, and the test data were evaluated., Results: The DL model's sensitivity was 97.6% [95% confidence interval (CI), 87.7-99.9%] and specificity was 98.0% (95% CI, 89.7-99.9%), and the area under the curve (AUC) was 0.993 (95% CI, 0.993-0.994). In contrast, the SVM model's sensitivity was 97.6% (95% CI, 87.7-99.9%), specificity was 94.2% (95% CI, 84.0-98.7%), and AUC was 0.988 (95% CI, 0.987-0.988)., Conclusion: DL model is better than SVM model in detecting ERM by using 3D-OCT images.

Purpose: To investigate the surgical results and morphologic characteristics of macular hole (MH) and macular hole retinal detachment (MHRD) associated with extreme myopia., Methods: We retrospectively reviewed consecutive cases with axial length ≥28 mm who were treated with pars plana vitrectomy for MH or MHRD. The choroidal and scleral thickness at the fovea, presence of dome-shaped macula, and the height of posterior staphyloma 3 mm from the fovea were measured from postoperative optical coherence tomography images., Results: Significant improvement in visual acuity was obtained postoperatively in both MH (16 eyes; 15 patients) and MHRD (19 eyes; 18 patients) groups (P < 0.05). Final MH closure rate was not significantly different between the groups (MH: 15/16, MHRD: 14/19, P = 0.19). Axial length was not significantly different between the groups (MH: 30.5 ± 1.5 mm, MHRD: 29.6 ± 1.3 mm, P = 0.098). Eyes with MH had significantly greater choroidal thickness (MH: 61.9 ± 66.0 μm, MHRD: 24.1 ± 19.8 μm, P = 0.045), greater scleral thickness (MH: 294 ± 77 μm, MHRD: 232 ± 89 μm, P = 0.008), higher frequency of dome-shaped macula (MH: 6/16, MHRD: 1/19, P = 0.032), and lower staphyloma height (MH: 190 ± 113 μm, MHRD: 401 ± 156 μm, P < 0.001)., Conclusion: Surgical outcomes were generally favorable. The pathogenetic differences between the two conditions may be attributable to differences with respect to eye morphology.

Aim: To investigate and compare the efficacy of two machine-learning technologies with deep-learning (DL) and support vector machine (SVM) for the detection of branch retinal vein occlusion (BRVO) using ultrawide-field fundus images., Methods: This study included 237 images from 236 patients with BRVO with a mean±standard deviation of age 66.3±10.6y and 229 images from 176 non-BRVO healthy subjects with a mean age of 64.9±9.4y. Training was conducted using a deep convolutional neural network using ultrawide-field fundus images to construct the DL model. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) were calculated to compare the diagnostic abilities of the DL and SVM models., Results: For the DL model, the sensitivity, specificity, PPV, NPV and AUC for diagnosing BRVO was 94.0% (95%CI: 93.8%-98.8%), 97.0% (95%CI: 89.7%-96.4%), 96.5% (95%CI: 94.3%-98.7%), 93.2% (95%CI: 90.5%-96.0%) and 0.976 (95%CI: 0.960-0.993), respectively. In contrast, for the SVM model, these values were 80.5% (95%CI: 77.8%-87.9%), 84.3% (95%CI: 75.8%-86.1%), 83.5% (95%CI: 78.4%-88.6%), 75.2% (95%CI: 72.1%-78.3%) and 0.857 (95%CI: 0.811-0.903), respectively. The DL model outperformed the SVM model in all the aforementioned parameters ( P <0.001)., Conclusion: These results indicate that the combination of the DL model and ultrawide-field fundus ophthalmoscopy may distinguish between healthy and BRVO eyes with a high level of accuracy. The proposed combination may be used for automatically diagnosing BRVO in patients residing in remote areas lacking access to an ophthalmic medical center.

The aim of this study is to assess the performance of two machine-learning technologies, namely, deep learning (DL) and support vector machine (SVM) algorithms, for detecting central retinal vein occlusion (CRVO) in ultrawide-field fundus images. Images from 125 CRVO patients ( n =125 images) and 202 non-CRVO normal subjects ( n =238 images) were included in this study. Training to construct the DL model using deep convolutional neural network algorithms was provided using ultrawide-field fundus images. The SVM uses scikit-learn library with a radial basis function kernel. The diagnostic abilities of DL and the SVM were compared by assessing their sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic curve for CRVO. For diagnosing CRVO, the DL model had a sensitivity of 98.4% (95% confidence interval (CI), 94.3-99.8%) and a specificity of 97.9% (95% CI, 94.6-99.1%) with an AUC of 0.989 (95% CI, 0.980-0.999). In contrast, the SVM model had a sensitivity of 84.0% (95% CI, 76.3-89.3%) and a specificity of 87.5% (95% CI, 82.7-91.1%) with an AUC of 0.895 (95% CI, 0.859-0.931). Thus, the DL model outperformed the SVM model in all indices assessed ( P < 0.001 for all). Our data suggest that a DL model derived using ultrawide-field fundus images could distinguish between normal and CRVO images with a high level of accuracy and that automatic CRVO detection in ultrawide-field fundus ophthalmoscopy is possible. This proposed DL-based model can also be used in ultrawide-field fundus ophthalmoscopy to accurately diagnose CRVO and improve medical care in remote locations where it is difficult for patients to attend an ophthalmic medical center.

Aim: To investigate the changes in the choroidal thickness in healthy pediatric children in a longitudinal study, and to determine the ocular and systemic parameters that were significantly correlated with the changes in the choroidal thickness., Methods: This study included 64 eyes of 34 healthy Japanese children with a mean age (±SD) of 4.4 (±0.4)y (range, 3.6-5.8y) at baseline. Swept-source optical coherence tomography (SS-OCT) was used to record images of the retina and choroid at the baseline and after a mean follow-up period of about 1.5y. The 3D raster scan protocol was used to construct the choroidal thickness map. Mean choroidal thickness was calculated for each of the nine sectors of the Early Treatment Diabetic Retinopathy Study grid. Best-corrected visual acuity, axial length, body height, and weight were also measured. Changes in measurements were defined as the baseline values subtracted from the values at the final visit. A generalized estimating equation was used to eliminate the effect of within-subject intereye correlations., Results: The mean central choroidal thickness was significantly reduced during the follow-up period (baseline, 301.8±8.6 µm; final visit, 286.6±8.0 µm, P <0.001). The decrease in the choroidal thickness was greatest in the central sector, followed by the sectors of the inner and outer rings. The inner and outer rings had diameters of 1 to 3 mm and 3 to 6 mm, respectively. The changes in the choroidal thickness in the central, inner ring, and outer ring sectors were significantly and negatively correlated with the age, baseline body height, baseline body weight, and elongation of the axial length., Conclusion: These results indicate that the choroidal thickness among preschool-aged Japanese children decreased significantly during the follow-up period. The choroidal thinning is significantly associated with the elongation of axial length. These characteristics should be considered in the evaluation of choroidal thickness in younger children with retinochoroidal disorders.

Purpose: To investigate the usability and the reproducibility of the tear meniscus values via swept-source optical coherence tomography (SS-OCT) and the conventional slit lamp microscope method with a graticule., Methods: The right eye was examined in 90 healthy adult subjects who were grouped according to age (group 1: 20-39 years; group 2: 40-59 years; group 3: ≥60 years). The tear meniscus height (TMH) and tear meniscus area were measured using SS-OCT and TMH by the slit lamp microscope method. The reproducibility of each method was calculated using intraclass correlation coefficients (ICCs) in additionally enrolled 30 healthy young subjects. We also evaluated TMH at 3 mm from the corneal center in both temporal and nasal directions using SS-OCT., Results: The mean of the TMH values measured by SS-OCT was significantly higher than those measured by the slit lamp method (328 vs. 212 μm, P < 0.001, respectively). High reproducibility was observed for each method (ICC > 0.75 for both). No statistically significant differences were found in TMH among the age groups using both SS-OCT and slit lamp methods (P = 0.985, 0.380, respectively). TMH values at both sides of the corneal center were significantly smaller than those at the corneal center (P < 0.0001)., Conclusions: TMH values obtained by the slit lamp method were lower than those obtained by SS-OCT. However, both methods yielded highly reproducible TMH measurements, suggesting that they are clinically useful. Tear meniscus values did not vary by age but by measurement points in our cohort.

Background: To determine the correlation between the optic nerve head (ONH) circulation determined by laser speckle flowgraphy and the best-corrected visual acuity or retinal sensitivity before and after intravitreal bevacizumab or ranibizumab for central retinal vein occlusion., Methods: Thirty-one eyes of 31 patients were treated with intravitreal bevacizumab or ranibizumab for macular edema due to a central retinal vein occlusion. The blood flow in the large vessels on the ONH, the best-corrected visual acuity, and retinal sensitivity were measured at the baseline, and at 1, 3, and 6 months after treatment. The arteriovenous passage time on fluorescein angiography was determined. The venous tortuosity index was calculated on color fundus photograph by dividing the length of the tortuous retinal vein by the chord length of the same segment. The blood flow was represented by the mean blur rate (MBR) determined by laser speckle flowgraphy. To exclude the influence of systemic circulation and blood flow in the ONH tissue, the corrected MBR was calculated as MBR of ONH vessel area - MBR of ONH tissue area in the affected eye divided by the vascular MBR - tissue MBR in the unaffected eye. Pearson's correlation tests were used to determine the significance of correlations between the MBR and the best-corrected visual acuity, retinal sensitivity, arteriovenous passage time, or venous tortuosity index., Results: At the baseline, the corrected MBR was significantly correlated with the arteriovenous passage time and venous tortuosity index (r = -0.807, P < 0.001; r = -0.716, P < 0.001; respectively). The corrected MBR was significantly correlated with the best-corrected visual acuity and retinal sensitivity at the baseline, and at 1, 3, and 6 months (all P < 0.050). The corrected MBR at the baseline was significantly correlated with the best-corrected visual acuity at 6 months (r = -0.651, P < 0.001) and retinal sensitivity at 6 months (r = 0.485, P = 0.005)., Conclusions: The pre-treatment blood flow velocity of ONH can be used as a predictive factor for the best-corrected visual acuity and retinal sensitivity after anti-VEGF therapy for central retinal vein occlusion., Trial Registration Number: UMIN000009072. Date of registration: 10/15/2012.

Purpose: We evaluated the choroidal thickness and volume in healthy pediatric individuals by swept-source optical coherence tomography (SS-OCT) and compared the findings to those of adults., Methods: We examined 100 eyes of 100 healthy pediatric volunteers (3-15 years) and 83 eyes of 83 healthy adult volunteers (24-87 years) by SS-OCT with a tunable long wavelength laser source. The three-dimensional raster scan protocol was used to construct a choroidal thickness map. When the built-in software delineated an erroneous chorioscleral border in the B-scan images, manual segmentation was used., Results: The central choroidal thickness and volume within a 1.0-mm circle were significantly larger in the children (260.4 ± 57.2 μm, 0.205 ± 0.045 mm(3)) than in the adults (206.1 ± 72.5 μm, 0.160 ± 0.056 mm(3), both P < 0.0001). In the children, the mean choroidal thickness of the nasal area was significantly thinner than that of all other areas (P < 0.005). Pediatric choroidal thinning with increasing age in the central area was faster than that in the outer areas. Stepwise regression analysis showed that the axial length and body mass index had the highest correlation with the choroidal thickness (R(2) = 0.313, P < 0.0001)., Conclusions: The macular choroidal thickness and volume in the pediatric individuals were significantly larger than those in the adults. The pediatric choroidal thinning with increasing age is more rapid in the central area. Pediatric choroidal thickness is associated with several systemic or ocular parameters, especially the axial length and body mass index. These differences should be remembered when the choroidal thickness is evaluated in pediatric patients with retinochoroidal diseases.

Purpose: We investigated by in vivo confocal microscopy alterations in the subepithelial nerve plexus in different types of herpes simplex keratitis (HSK)., Methods: Seventeen patients (seven women and ten men, mean age 63.9 years) with a history of HSK were classified into three groups according to the classification of Herpetic Keratitis Infection Research Group. Slit-lamp examinations, corneal sensitivity measurements, and corneal in vivo confocal microscopy examinations [Rostock Corneal Module attached to the Heidelberg Retina Tomograph II (HRT II-RCM)] were performed., Results: Among the 17 cases, three were classified as epithelial type, ten as stromal type, and four as endothelial type HSK. The average corneal sensitivities were 11.41 ± 9.46 mm in the affected eyes and 43.24 ± 12.2 mm in controls. Decreases in three parameters in the affected eyes (long nerve-fiber density, nerve-branch density, nerve thickness) were statistically significant compared with controls. Decreases in the three parameters were more remarkable in the epithelial and stromal types than in the endothelial type., Conclusion: The morphology of the corneal subepithelial nerve plexus may get gradually destroyed along with recurrent episodes of epithelial and stromal HSK. However, the destruction does not seem remarkable in the endothelial type of HSK, suggesting the possibility of a different route of virus recruitment in this type.