Graft cell expansion from hiPSC-RPE strip after transplantation in primate eyes with or without RPE damage.

Clinical studies using suspensions or sheets of human pluripotent cell-derived retinal pigment epithelial cells (hiPSC-RPE) have been conducted globally for diseases such as age-related macular degeneration. Despite being minimally invasive, cell suspension transplantation faces challenges in targeted cell delivery and frequent cell leakage. Conversely, although the RPE sheet ensures targeted delivery with correct cell polarity, it requires invasive surgery, and graft preparation is time-consuming. We previously reported hiPSC-RPE strips as a form of quick cell aggregate that allows for reliable cell delivery to the target area with minimal invasiveness. In this study, we used a microsecond pulse laser to create a local RPE ablation model in cynomolgus monkey eyes. The hiPSC-RPE strips were transplanted into the RPE-ablated and intact sites. The hiPSC-RPE strip stably survived in all transplanted monkey eyes. The expansion area of the RPE from the engrafted strip was larger at the RPE injury site than at the intact site with no tumorigenic growth. Histological observation showed a monolayer expansion of the transplanted RPE cells with the expression of MERTK apically and collagen type 4 basally. The hiPSC-RPE strip is considered a beneficial transplantation option for RPE cell therapy.

Percutaneous intravascular micro-axial blood pump: current state and perspective from engineering view.

The utilization of a minimally invasively placed catheter-mounted intravascular micro-axial flow blood pump (IMFBP) is increasing in the population with advanced heart failure. The current development of IMFBPs dates back around the 1990s, namely the Hemopump with a wire-drive system and the Valvopump with a direct-drive system. The wire-drive IMFBPs can use a brushless motor in an external console unit to transmit rotational force through the drive wire rotating the impeller inside the body. The direct-drive IMFBPs require an ultra-miniature and high-power brushless motor. Additionally, the direct-drive system necessitates a mechanism to protect against blood immersion into the motor. Therefore, the direct-drive IMFBPs can be categorized into two types of devices: those with seal mechanisms or those with sealless mechanisms using magnetically coupling. The IMFBPs can be classified into two groups depending on their purpose. One group is for cardiogenic shock following a heart attack or for use in high-risk percutaneous coronary intervention (PCI), and the other group serves the purpose of acute decompensated heart failure. Both direct-drive IMFBPs and wire-drive IMFBPs have their own advantages and disadvantages, and efforts are being made to develop and improve, and clinically implement them, leveraging their own strengths. In addition, there is a possibility that innovative new devices may be invented. For researchers in the field of artificial heart development, IMFBPs offer a new area of research and development, providing a novel treatment option for severe heart failure.

Drug combination of topical ripasudil and brimonidine enhances neuroprotection in a mouse model of optic nerve injury.

PURPOSE: To determine whether combination of topical ripasudil and brimonidine has more effective neuroprotection on retinal ganglion cells (RGCs) following injury to axons composing the optic nerve. METHODS: Topical ripasudil, brimonidine, or mixture of both drugs were administered to adult mice after optic nerve injury (ONI). The influence of drug conditions on RGC health were evaluated by the quantifications of surviving RGCs, phosphorylated p38 mitogen-activated protein kinase (phospho-p38), and expressions of trophic factors and proinflammatory mediators in the retina. RESULTS: Topical ripasudil and brimonidine suppressed ONI-induced RGC death respectively, and mixture of both drugs further stimulated RGC survival. Topical ripasudil and brimonidine suppressed ONI-induced phospho-p38 in the whole retina. In addition, topical ripasudil suppressed expression levels of TNFα, IL-1ß and monocyte chemotactic protein-1 (MCP-1), whereas topical brimonidine increased the expression level of basic fibroblast growth factor (bFGF). CONCLUSIONS: Combination of topical ripasudil and brimonidine may enhance RGC protection by modulating multiple signaling pathways in the retina.

A Case of Osteopetrosis with Orbital Inflammation Secondary to Maxillary Osteomyelitis.

Introduction: Osteopetrosis is a rare heritable disorder characterized by increased bone density resulting from osteoclast dysfunction. Major complications include bone fracture, osteomyelitis, anemia, and cranial nerve compression. Optic atrophy can occur due to compression of the optic nerve. Although osteomyelitis of the jaw is a common complication, it rarely occurs in the maxilla. Here, we report a case of a 74-year-old female with osteopetrosis who developed maxillary osteomyelitis, leading to orbital inflammation. Case Presentation: She was referred to our clinic for 2 months of ptosis and swelling of the left eyelid and temporal region. Previous imaging revealed a left intraorbital occupying lesion, but a biopsy of the temporal subcutaneous tissue did not provide a definitive diagnosis. After 7 months, she presented with severe temporal swelling and purulent discharge. Upon examination, maxillary osteomyelitis resulting from caries of the upper jaw was observed. Treatment with oral antibiotics, drainage of the temporal skin fistula, and regular cleaning of the maxillary drainage improved her symptoms. Conclusion: This is a rare case of maxillary osteomyelitis associated with osteopetrosis, causing orbital inflammation.

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.

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.

Anti-VEGF Treatment Strategies for 3 Subtypes of Neovascular Age-Related Macular Degeneration in a Clinical Setting: A Multicenter Cohort Study in Japan.

PURPOSE: Neovascular age-related macular degeneration (nAMD) is classified into typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). This study investigated clinical features of the 3 subtypes and visual outcome associated with treatment regimens in a large cohort of patients with nAMD in a clinical setting. DESIGN: Retrospective multicenter cohort study. PARTICIPANTS: Five hundred patients with treatment-naive nAMD (268 tAMD, 200 PCV, and 32 RAP) initiated with anti-VEGF agents and followed for 1 year. METHODS: Medical records were reviewed to extract demographic data, best-corrected visual acuity at baseline and 1 year after treatment initiation, spectral-domain OCT findings, baseline fellow eye condition, systemic factors, treatment strategies, and number of intravitreal injections in the first year. MAIN OUTCOME MEASURES: Primary outcome measures were anti-VEGF treatment strategy (ranibizumab or aflibercept, anti-VEGF regimen, concomitant photodynamic therapy, drug switch), best-corrected visual acuity at 1 year, and factors associated with visual acuity. RESULTS: Patients with RAP were significantly older, were more commonly women, and had more macular lesions in fellow eye than patients with tAMD and PCV. Smoking history and diabetes prevalence were not different among the 3 subtypes. Frequencies of subretinal fluid were higher and intraretinal fluid were lower in tAMD and PCV than in RAP, whereas serous pigment epithelial detachment and subretinal hemorrhage were higher in PCV than in tAMD and RAP. Choice of anti-VEGF agents and treatment regimens did not differ among 3 subtypes. The aflibercept-to-ranibizumab ratio was approximately 7:3. The mean number of injections in 1 year was 5.3 ± 2.4 in nAMD overall, which was significantly less in pro re nata (PRN) than in treat and extend (TAE) regardless of the anti-VEGF agent. Best-corrected visual acuity improved in all 3 subtypes, although it was not significant in patients with RAP. CONCLUSIONS: This clinical study demonstrates that treatment regimens were similar in 3 subtypes and aflibercept was used in 70% of all patients. Approximately 5 injections were given in the first year regardless of the anti-VEGF agent, which was significantly less in PRN regimen than in TAE. Visual acuity improvement was observed after 1-year anti-VEGF therapy in all 3 subtypes, but was not significant in RAP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

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.

Subtype prevalence and baseline visual acuity by age in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective multicenter case series. METHODS: We reviewed the records of patients with treatment-naïve nAMD who underwent initial treatment in 14 institutions in Japan sometime during the period from 2006 to 2015. In patients in whom both eyes were treated, only the eye treated first was included for analysis. The patients were stratified by age for the analysis. RESULTS: In total, 3096 eyes were included. The overall prevalence of subtypes was as follows: typical AMD, 52.6%; polypoidal choroidal vasculopathy (PCV), 42.8%; retinal angiomatous proliferation (RAP), 4.6%. The number of eyes in each age group was as follows: younger than 60 years, 199; 60s, 747; 70s, 1308; 80s, 784; 90 years or older, 58. The prevalence of typical AMD in each age group was 51.8%, 48.1%, 52.1%, 57.7%, and 55.2%, respectively. The prevalence of PCV was 46.7%, 49.1%, 44.7%, 34.4%, and 19.0%, respectively. The prevalence of RAP was 1.5%, 2.8%, 3.2%, 7.9%, and 25.9%, respectively. The prevalence of PCV decreased with age, whilst that of RAP increased. The prevalence of RAP was higher than that of PCV in patients aged 90 years or older. The mean baseline BCVA (logMAR) was 0.53. In each age group, the mean baseline BCVA was 0.35, 0.45, 0.54, 0.62, and 0.88, respectively. The mean logMAR BCVA at baseline significantly worsened with age (P < 0.001). CONCLUSION: The prevalence of nAMD subtypes differed according to age in Japanese patients. The baseline BCVA worsened with age.

Efficacy, durability, and safety of faricimab with extended dosing up to every 16 weeks in Japanese patients with diabetic macular edema: 1-year results from the Japan subgroup of the phase 3 YOSEMITE trial.

PURPOSE: To evaluate efficacy, durability, and safety of faricimab in Japanese patients with diabetic macular edema (DME). STUDY DESIGN: Subgroup analysis of 2 global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 trials (YOSEMITE, NCT03622580; RHINE, NCT03622593). METHODS: Patients with DME were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W through week 100. Primary endpoint was best-corrected visual acuity (BCVA) change from baseline at 1 year, averaged over weeks 48, 52, and 56. This is the first time 1-year outcomes between Japanese patients (only enrolled into YOSEMITE) and the pooled YOSEMITE/RHINE cohort (N = 1891) have been compared. RESULTS: The YOSEMITE Japan subgroup included 60 patients randomized to faricimab Q8W (n = 21), faricimab PTI (n = 19), or aflibercept Q8W (n = 20). Consistent with global results, the adjusted mean (95.04% confidence interval) BCVA change at 1 year in the Japan subgroup was comparable with faricimab Q8W (+11.1 [7.6-14.6] letters), faricimab PTI (+8.1 [4.4-11.7] letters), and aflibercept Q8W (+6.9 [3.3-10.5] letters). At week 52, 13 (72%) patients in the faricimab PTI arm achieved ≥ Q12W dosing, including 7 (39%) patients receiving Q16W dosing. Anatomic improvements with faricimab were generally consistent between the Japan subgroup and pooled YOSEMITE/RHINE cohort. Faricimab was well tolerated; no new or unexpected safety signals were identified. CONCLUSION: Consistent with global results, faricimab up to Q16W offered durable vision gains and improved anatomic and disease-specific outcomes among Japanese patients with DME.

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.

Risk Factors for Legal Blindness in 237 Japanese Patients with Exogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential risk factors for visual prognosis in Japanese patients with exogenous endophthalmitis. METHODS: In this retrospective observational multicenter cohort study, risk factors for legal blindness at 12 weeks after treatment initiation were evaluated based on patient characteristics, initial BCVA, causative events, pathogens, ocular symptoms, duration from symptom onset to initial treatment, and selected treatments. RESULTS: Overall, 23.1% of eyes developed legal blindness. The six risk factors for legal blindness were presence of eye pain, pathogen identification, poor BCVA at the initial visit, longer duration from symptom onset to initial treatment, type of causative event, and type of causative pathogen. Regarding the type of causative pathogen, coagulase-negative staphylococci was associated with a better visual impairment outcome. CONCLUSION: Exogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatment, as well as other advances in medical knowledge and technology.

Risk Factors for Legal Blindness in 77 Japanese Patients with Endogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential predictive factors for visual prognosis in Japanese patients with endogenous endophthalmitis. DESIGN: Retrospective observational multicenter cohort study. METHODS: We examined the characteristics of 77 Japanese patients with endogenous endophthalmitis and performed statistical analyses of these real-world data. The primary endpoint was the identification of factors associated with visual prognosis. We examined differences between patients in the better vision and legal blindness groups at 12 weeks after treatment initiation. RESULTS: The five risk factors for visual impairment at 12 weeks after treatment initiation were presence of pressure injuries, severe clinical symptoms (presence of eye pain and ciliary injection), pathogen identification, and poor best-corrected visual acuity at baseline. Staphylococcus aureus and fungus were associated with a better visual impairment outcome. CONCLUSIONS: Endogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatments, as well as other advances in medical knowledge and technology.

Development and initial performance of a miniature axial flow blood pump using magnetic fluid shaft seal.

In this study, we developed a new catheter-mounted micro-axial flow blood pump (MFBP) using a new miniature magnetic fluid shaft seal (MFSS). The prototype of the catheter-mounted MFBP had a maximum diameter of 8 mm and a length of 50 mm. The new MFSS composed a neodymium magnet ring, an iron ring, and a magnetic fluid particularly designed for the MFSS. The new MFSS had outer and inner diameters of 4.0 mm and 2.6 mm, respectively, and a length of 3.0 mm. The sealing pressure of the MFSS was calculated to be 432 mmHg using FEM (Finite Element Method) result; therefore, the MFSS had sufficient sealing pressure for the catheter-mounted MFBP. The friction loss of the MFSS included the friction owing to the viscosity of the magnetic fluid and the magnetic force between the iron ring and ring magnet. The total friction loss of the MFSS was 0.08-0.09 W in the pump operational speed range from 22,000 to 35,000 rpm. From the in vitro experimental results, the catheter-mounted MFBP using the MFSS had a pump output of 3 L/min. against a differential pressure of 60 mmHg, and the pump characteristics of the MFBP were almost the same as those of Impella 5.0.

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.

Effect of foveal morphology on visual acuity in 4-6-year-old children with retinopathy of prematurity: a J-CREST study.

Laser therapy is the most effective treatment considered for retinopathy of prematurity (ROP). We compared the foveal morphology of the retina in eyes with a history of ROP to that of full-term children. This cross-sectional comparative study included 74 patients with a history of ROP, aged 4-6 years. Among them, 41 underwent laser treatment for ROP. The clinical findings and retinal morphology in these patients were compared to that of 33 patients who had spontaneous ROP regression and 30 age-matched full-term controls. All the patients with ROP had 20/40 or better best-corrected visual acuity (BCVA). The foveal thickness was significantly thicker in laser-treated ROP eyes than in regressed ROP eyes and controls. The outer nuclear layer was significantly thicker, and the inner segment (IS) of the photoreceptors and the inner retinal layer were significantly thicker in the laser-treated ROP eyes than that in the control eyes. In the patients with ROP and controls, better BCVA was associated positively with deeper foveal depression, which was associated with a later gestational age. Our results suggest that prematurity and laser treatment affect the foveal morphology and BCVA.

Differences in clinical characteristics and treatment outcomes of submacular hemorrhage caused by age-related macular degeneration and retinal macroaneurysms: A multicenter survey from the Japan Clinical Retina Study (J-CREST) group.

PURPOSE: To 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). METHODS: This 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. RESULTS: Major 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 P<0.0001). Treatment with anti-vascular endothelial growth factor drugs with and without intravitreal gas injection was chosen for half of eyes in the tnAMD and PCV groups, whereas vitrectomy was performed in 83.7% of eyes with RAM. The final BCVA improved significantly from baseline in the PCV and RAM groups (P = 0.0009, P<0.0001) and final BCVA was significantly better in the PCV group at a level similar to the other groups (P = 0.0007, P = 0.0008). BCVA improvement from baseline was significantly greater in the RAM group compared with the tnAMD (P = 0.0152) and PCV (P = 0.017) groups. Multivariate analysis revealed better final BCVA was significantly associated with younger age (P = 0.0054), better baseline BCVA (P = 0.0021), RAM subtype (P = 0.0446), and no tnAMD (P = 0.001). CONCLUSIONS: The 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.

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.

Visual prognosis of submacular hemorrhage secondary to age-related macular degeneration: A retrospective multicenter survey.

PURPOSE: To investigate the clinical features, treatment options, and visual outcomes of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD). DESIGN: A retrospective, observational case series. METHODS: Setting: Multicenter institutional setting. Patient Population: A total of 127 patients (127 eyes; 88 men, 39 women; (mean age, 74.2 years)) diagnosed with AMD-associated SMHs exceeding 2 disc diameters involving the fovea. Observation: The AMD types, previous treatments, treatment options, anatomic findings, and best-corrected visual acuity (BCVA) were assessed. Main Outcome Measures: Clinical features, treatment options, and visual outcomes of SMHs secondary to nAMD. RESULTS: Thirty-two eyes had typical AMD, 94 eyes polypoidal choroidal vasculopathy (PCV), and one eye retinal angiomatous proliferation. Eighty-five eyes were treatment-naïve; 42 eyes were treated previously: anti-vascular endothelial growth factor (VEGF) therapy (n = 26), photodynamic therapy (n = 3), and combined therapy (n = 13). Treatment of SMHs included vitrectomy (36 eyes), pneumatic displacement (49 eyes), and anti-VEGF monotherapy (42 eyes). The final BCVA improved significantly in treatment-naïve cases from 0.86 to 0.62 logarithm of the minimal angle of resolution (logMAR) unit (Snellen equivalent from 20/145 to 20/83) and from 0.80 to 0.56 (Snellen equivalent from 20/126 to 20/73) in PCV cases. Meanwhile, the BCVA logMAR values improved from 1.15 to 0.75 (Snellen equivalent from 20/283 to 20/112) and from 0.87 to 0.63 (Snellen equivalent from 20/148 to 20/85) in eyes that underwent vitrectomy or pneumatic displacement, respectively. In eyes with BCVAs between 20/133 to 20/40 at SMH onset, the final VA in the pneumatic displacement group was better than in the anti-VEGF monotherapy group. One eye had a retinal detachment and 1 eye had a macular hole in the vitrectomy group, and 5 eyes had a vitreous hemorrhage in the pneumatic displacement group. CONCLUSIONS: The recommended treatment for SMHs secondary to nAMD exceeding 2 disc area and with BCVA below 20/40 is vitrectomy or pneumatic displacement for visual improvement.