Binocular metamorphopsia in patients with branch retinal vein occlusion: a multi-center study.

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 (ß = 0.306, p = 0.006). CONCLUSION: Metamorphopsia in the affected eyes can cause binocular metamorphopsia in patients with BRVO-ME.

Developing an iOS application that uses machine learning for the automated diagnosis of blepharoptosis.

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_view.cgi?recptno=R000051004.

Automatic screening of tear meniscus from lacrimal duct obstructions using anterior segment optical coherence tomography images by deep learning.

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.

Changes of choroidal structure and circulation after water drinking test in normal eyes.

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.

MORPHOLOGIC CHARACTERISTICS OF MACULAR HOLE AND MACULAR HOLE RETINAL DETACHMENT ASSOCIATED WITH EXTREME MYOPIA.

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.

Comparison between support vector machine and deep learning, machine-learning technologies for detecting epiretinal membrane using 3D-OCT.

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.

Usability and reproducibility of tear meniscus values generated via swept-source optical coherence tomography and the slit lamp with a graticule method.

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.

Correlation between optic nerve head circulation and visual function before and after anti-VEGF therapy for central retinal vein occlusion: prospective, interventional case series.

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.

Foveal Thickness Fluctuations in Anti-VEGF Treatment for Central Retinal Vein Occlusion.

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.

Characterization of the visually impaired patients with diabetes mellitus in Japan.

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.

Alterations in choroidal vascular structures due to serum levels of vascular endothelial growth factor in patients with POEMS syndrome.

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.

Branch retinal artery occlusion with unruptured retinal arterial macroaneurysm post-SARS-CoV-2 vaccination: A case report.

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.

Estimation of Visual Function Using Deep Learning From Ultra-Widefield Fundus Images of Eyes With Retinitis Pigmentosa.

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.

Need of preventive photocoagulation for retinal arterial macroaneurysm with retinal hemorrhage.

Retinal arterial macroaneurysm shows rapid vision loss when rupture occurs; therefore, preventive photocoagulation should be considered, if necessary.

Branch retinal vein occlusion post severe acute respiratory syndrome coronavirus 2 vaccination.

In this article, we report two patients who experienced the first onset of branch retinal vein occlusion (BRVO) 3 days after the administration of the BNT162b2 (Pfizer-BioNTech) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Case 1: A 50-year-old woman without any history of retinal disease developed vision loss in her right eye 3 days after receiving the first dose of the SARS-CoV-2 mRNA vaccine. Case 2: A 56-year-old woman without any history of retinal disease developed vision loss in her right eye 3 days after receiving the first dose of the SARS-CoV-2 mRNA vaccine. Case 1: Temporal superior BRVO and secondary macular edema (ME) were observed in the patient's right eye. Her best-corrected visual acuity (BCVA) was 20/25. Case 2: Temporal inferior BRVO and secondary ME were observed in the patient's right eye. Her BCVA was 13/20. Case 1: Three doses of intravitreal ranibizumab (IVR) were administered. Case 2: Three doses of IVR were administered. Case 1: ME resolved and BCVA improved to 20/20. Case 2: ME resolved and BCVA improved to 20/20. Both the cases showed a possible association between the SARS-CoV-2 vaccination and the first onset of BRVO.

Automated detection of enlarged extraocular muscle in Graves' ophthalmopathy with computed tomography and deep neural network.

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.

Foveal Thickness Fluctuation in Anti-VEGF Treatment for Branch Retinal Vein Occlusion: A Long-term Study.

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 (ß = 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.

Impact of the COVID-19 Pandemic on Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema in Japan.

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.

A Case of Paracentral Corneal Perforation Treated with One-Bite Mini-Keratoplasty.

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.

Efficacy and Safety of Intravitreal Aflibercept Injection in Japanese Patients with Neovascular Glaucoma: Outcomes from the VENERA Study.

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.