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Epiretinal membrane (ERM) foveoschisis is a recently proposed clinical entity. The purpose of this study was to compare the clinical characteristics and surgical outcomes of eyes with ERM foveoschisis to those of typical ERM. The medical records of all patients with ERM-related disorders examined between 2011 and 2020 were reviewed. ERM foveoschisis was defined by the clinical criteria proposed by an international panel of experts on ERMs. The background factors, clinical characteristics, and surgical outcomes of ERM foveoschisis were compared to those of typical ERM. Forty eyes with ERM foveoschisis were compared to 333 eyes with typical ERM. The percentage of women was significantly higher in the ERM foveoschisis group (92.5%) than in the typical ERM group (48.9%, p < 0.001). The central macular thickness (CMT) was significantly thinner in the ERM foveoschisis group (340 ± 110 μm) than in the typical ERM groups (476 ± 111 μm, p < 0.01). The degree of improvement in the best-corrected visual acuity (BCVA) three months after the surgery did not differ between the two groups (p = 0.59). These results suggest that the ERM foveoschisis is more likely to occur in women and that the prognosis after surgery is comparable to typical ERM.

Shin Asami, Masahiko Sugimoto, Hideyuki Tsukitome, Kumiko Kato, Hisashi Matsubara, Mineo Kondo Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Mie, JapanCorrespondence: Masahiko Sugimoto, Department of Ophthalmology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan, Tel +81-59-231-5027, Fax +81-59-231-3036, Email sugmochi@clin.medic.mie-u.ac.jpPurpose: To compare the therapeutic effects of anti-vascular endothelial growth factor (anti-VEGF) agents in eyes with macular edema associated with branch retinal vein occlusion (BRVO-ME) with glaucoma to those without glaucoma.Patients and Methods: This retrospective study was conducted using the medical records of Mie University Hospital from 2013 to 2017. Patients were recruited if they had received anti-VEGF agents for BRVO-ME treatment and included 30 patients (30 eyes) without glaucoma (G[-] group) and 27 patients (27 eyes) with glaucoma (G[+] group). The central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at 3 months after a single injection of anti-VEGF agents were compared between the two groups.Results: Before treatment, the mean±standard deviation of the CRT was 514.2± 117.3 μm for the G[-] group, which was not significantly different from that for the G[+] group (533.4± 171.4 μm). The CRT in the G[-] and G[+] groups significantly reduced to 321.1± 114.6 μm and 347.8± 134.7 μm, respectively, at 1 month after the injection and to 360.4± 159.5 μm and 352.4± 151.9 μm, respectively, at 3 months after the injection (P< 0.01 for each group). The difference in the degree of CRT reduction between the two groups was not significant. Before treatment, the BCVA was 0.42± 0.32 logMAR units in the G[-] group and 0.57± 0.33 logMAR units in the G[+] group, showing no significant difference. The BCVA in the G[-] and G[+] groups improved significantly to 0.27± 0.26 logMAR units and 0.34± 0.42 logMAR units, respectively, at 1 month, and to 0.18± 0.20 logMAR units and 0.39± 0.34 logMAR units, respectively, at 3 months (P< 0.01). The BCVA in the G[-] group was significantly better than that in the G[+] group at 3 months (P=0.02).Conclusion: The therapeutic response of anti-VEGF agents for BRVO-ME is affected by the presence of glaucoma.Keywords: anti-vascular endothelial growth factor treatment, branch retinal vein occlusion, glaucoma, macular edema

Purpose: To determine whether atrophy of the retinal pigment epithelium (RPE) in eyes with neovascular age-related macular degeneration (nAMD), which meets the criteria for the suspension of anti-vascular endothelial growth factor (anti-VEGF) treatment, is associated with anti-VEGF treatments. Methods: Twelve eyes of 12 patients with nAMD who began anti-VEGF treatment and were followed for 1 year after meeting the criteria for the suspension of anti-VEGF were studied. Six eyes of six patients were placed in the continuation group, and six eyes of six patients were placed in the suspension group. The RPE atrophic area at the time of the last anti-VEGF treatment was set as the baseline size and that at 12 months after the baseline (Month 12) was taken as the final size. A comparison of the expansion rate of RPE atrophy between the two groups was made by the square-root transformed differences. Results: The expansion rate of atrophy was 0.55 (0.43, 0.72) mm/year in the continuation group and 0.33 (0.15, 0.41) mm/year in the suspension group. This difference was not significant. (p = 0.29). Conclusions: Suspension of anti-VEGF treatments in eyes with nAMD does not alter the expansion rate of RPE atrophy.

Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

Purpose To investigate the outcomes of a suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments in the eyes with neovascular age-related macular degeneration (nAMD). Methods This was a retrospective study that examined eyes having no exudation for 48 weeks while undergoing intravitreal anti-VEGF injections every 12 to 16 weeks. The rate and time of recurrences, best-corrected visual acuity (BCVA), central subfield thickness (CST), number of visits, and reactivity to anti-VEGF were determined after the suspension of the anti-VEGF treatments. Results In 34 eyes of 34 patients, 17 eyes (50.0%) had a recurrence during the 24-month follow-up period. The median time of a recurrence was 10 months. The BCVA was maintained for 24 months after the suspension regardless of the development of any recurrences. In 41.7% of the eyes that resumed treatment, the duration of exudation suppression by the anti-VEGF therapy was shorter than 12 weeks during the 12 months after restarting the anti-VEGF treatments. There was a significant increase in the number of visits during the first year after beginning the suspension versus during the 1 year before the suspension (non-recurrence group; P = 0.007, recurrence group; P = 0.001). Conclusion Although one-half of the eyes had a recurrence within 24 months after a suspension of anti-VEGF treatment, the BCVA was maintained after a resumption of the anti-VEGF treatments. However, the number of hospital visits increases regardless of the recurrences and the lesion stability is altered by the anti-VEGF suspension. Clinicians should explain both the advantages and disadvantages of anti-VEGF suspension to nAMD patients.

To identify the eyes with macular edema (ME) due to a branch retinal vein occlusion (BRVO) that have good visual acuity during the continuous anti-vascular endothelial growth factor (anti-VEGF) treatment based on the patients’ clinical information and optical coherence tomography (OCT) images by using machine learning. Sixty-six eyes of 66 patients received 1 anti-VEGF injection followed by repeated injections in the pro re nata (PRN) regimen for 12 months. The patients were divided into two groups: those with and those without good vision during the 1-year experimental period. Handcraft features were defined from the OCT images at the time of the first resolution of the ME. Variables with a significant difference between the groups were used as explanatory variables. A classifier was created with handcrafted features based on a support vector machine (SVM) that adjusted parameters for increasing maximal precision. The age, best-corrected visual acuity (BCVA) at the baseline, BCVA at the first resolution of the ME, integrity and reflectivity of the external limiting membrane (ELM), the ellipsoid zone (EZ), and area of the outer segments of the photoreceptors were selected as explanatory variables. The classification performance was 0.806 for accuracy, 0.768 for precision, 0.772 for recall, and 0.752 for the F-measure. The use of the SVM of the patient’s clinical information and OCT images can be helpful for determining the prognosis of the BCVA during continued pro re nata anti-VEGF treatment in eyes with ME associated with BRVO.

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’s goal is to determine the accuracy of a linear classifier that predicts the prognosis of patients with macular edema (ME) due to a branch retinal vein occlusion during the maintenance phase of antivascular endothelial growth factor (anti-VEGF) therapy. The classifier was created using the clinical information and optical coherence tomographic (OCT) findings obtained up to the time of the first resolution of ME. In total, 66 eyes of 66 patients received an initial intravitreal injection of anti-VEGF followed by repeated injections with the pro re nata (PRN) regimen for 12 months. The patients were divided into two groups: those with and those without good vision during the PRN phase. The mean AUC of the classifier was 0.93, and the coefficients of the explanatory variables were: best-corrected visual acuity (BCVA) at baseline was 0.66, BCVA at first resolution of ME was 0.51, age was 0.21, the average brightness of the ellipsoid zone (EZ) was −0.12, the intactness of the external limiting membrane (ELM) was −0.14, the average brightness of the ELM was −0.17, the brightness value of EZ was −0.17, the area of the outer segments of the photoreceptors was −0.20, and the intactness of the EZ was −0.24. This algorithm predicted the prognosis over time for individual patients during the PRN phase.

To determine the characteristics and cause of the increase in the amplitude of flicker electroretinography (ERG) after cataract surgery.Prospective, observational clinical study.Thirty patients who underwent cataract surgery.Flicker ERGs were recorded with the RETeval system without mydriasis. The central macular thickness (CMT) was measured by OCT and the aqueous flare value (AFV) by laser flare-cell photometry. These examinations were performed before surgery and 1 day, 1 week, 1 month, 2 months, and 3 months after surgery. Linear regression analysis through the origin was used to compare the correlations between the relative changes in flicker ERG amplitudes and the changes in the CMT and AFV at different times after the surgery.The amplitude of flicker ERGs, CMT, and AFV.The mean amplitude of flicker ERGs increased significantly by 31% at 1 week after surgery (These results suggest that the increase in the amplitude of flicker ERGs after cataract surgery is a transient phenomenon that has a peak at 1 week after surgery. The increase of flicker ERG amplitude was associated with measures that are frequently used to evaluate postoperative inflammation.Proprietary or commercial disclosure may be found after the references.

To investigate potential clinical and multimodal imaging factors in central serous chorioretinopathy (CSC) recurrence.The study was performed at nine Japanese medical institutions for patients who had experienced an active CSC episode. Demographic data and medical history were reviewed retrospectively. Significant differences in chronic manifestation, leakage site, leakage point number, leakage intensity, choroidal hyperpermeability, central retinal thickness (CRT) and subfoveal choroidal thickness were analysed between the recurrence and non-recurrence groups.In total, 538 eyes (538 patients) diagnosed with CSC (402 men, 136 women; mean age: 53.4 ± 11.9 years) were enrolled. Among them, 253 eyes (47.0%) developed ≥1 recurrence (follow-up: 15.9 ± 13.5 months, range 3-86 months). Univariate and multivariate analyses indicated that a history of corticosteroid use (odds ratio [OR], 5.52; 95% confidence interval [CI], 1.39-21.92; p = 0.015), bilateral disease (OR, 3.94; 95% CI, 1.47-10.6; p = 0.007), chronic manifestations (OR, 7.12; 95% CI, 2.93-17.28; p 0.001), non-intense fluorescein leakage (OR, 3.34; 95% CI, 1.44-7.75; p = 0.005) and initial CRT (OR, 0.997; 95% CI, 0.993-0.999; p = 0.049) were significantly associated with CSC recurrence. Receiver operating characteristic curves were created, and the area under the curve for the multivariate logistic regression model of these five factors was 0.814.Patients with CSC who received corticosteroids and had bilateral disease, chronic manifestation, non-intense fluorescein leakage on fluorescein angiography or a relatively thinner CRT should be closely monitored to identify whether they are at high risk of recurrence.

The aim of this study was to determine the prevalence and progression of diabetic retinopathy (DR) with hyperglycemic disorders during pregnancy (HDPs) in Japan between 2013 and 2018 using two cohorts. The patients with HDPs were classified as those with pre-existing DM (pexD), gestational DM (GDM), and overt DM (ODM). Cohort 1 was obtained from the health claims database whose diseases were classified by the International Classification of Diseases-10. Cohort 2 was derived from a retrospective, multicenter analysis of the medical records of 225 patients from 10 ophthalmological institutions. In Cohort 1, there were 5268 patients with an HDP prevalence of 8.4%. Among them, 73 of 1139 patients had pexD (6.4%) and 61 of 4129 patients with GDM (1.5%) had DR; the overall prevalence of DR was 2.5%. In Cohort 2, 36 of 225 patients (16.0%) had DR, and 149 patients were followed at the early and late stages of pregnancy. Moreover, 10 of the 102 patients with pexD (9.8%) and two of five patients with ODM (40.0%) had a progression of DR. In conclusion, the prevalence and progression of DR in patients with pexD is lower than previously reported. More attention should be given to pexD and ODM.