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Background: Retinopathy of prematurity (ROP) is a significant cause of blindness in infants. Appropriate therapeutic intervention is essential because retinal detachment due to the progression of ROP is critical to visual function. The intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents has been increasingly applied to inhibit the development and progression of ROP. In this study, we compared the efficacy of single intravitreal bevacizumab (IVB) and ranibizumab (IVR) injections for the treatment of ROP. Methods: A total of 39 eyes in 21 patients with severe ROP and IVB (15 eyes of 8 patients) and IVR (24 eyes of 13 patients) were retrospectively reviewed. Patient background, the severity of ROP, and the percentage of cases in which ROP regressed without additional treatment were compared between the two groups. Results: Patient background and ROP severity were not significantly different between the two groups. Recurrence was observed in one eye of one patient in the IVB group, and thirteen eyes in seven patients in the IVR group required additional laser photocoagulation, which was significantly different in the two groups (p < 0.01, Fisher's exact test). In the IVR group, two eyes of two patients underwent vitreous surgery. Conclusion: Compared with IVR, IVB is likely to control the severity of ROP with a single treatment. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate anterior flare intensity (AFI) after intravitreal injection of brolucizumab (IVBr) in patients with diabetic macular edema (DME), and to identify the factors associated with the change of AFI after IVBr. Methods: This prospective multicenter study was conducted at five sites in Japan for patients with DME who underwent a single IVBr. AFI and central retinal thickness (CRT) were measured using a laser flare meter and spectral-domain optical coherence tomography, respectively, at weeks 0 and 6. Results: Sixty-five patients (phakia, 37 eyes; pseudophakia, 28 eyes) were enrolled. Six weeks after IVBr, CRT and best-corrected visual acuity significantly improved (p < 0.0001). AFI (p = 0.0003) and age (p = 0.0054) were significantly higher in patients with pseudophakic eyes than those with phakic eyes. The AFI of the phakic eyes decreased after IVBr (p = 0.043). As the AFI before injection is higher (p = 0.0363) and the age is lower (p = 0.0016), the AFI decreases after IVBr. There was a significant positive correlation between the rates of change in CRT and AFI (p = 0.024). Conclusion: After IVBr, AFI decreases in phakic eyes but not in pseudophakic eyes. The age, AFI and CRT before injection and changes of CRT are involved in the change in AFI after IVBr. [ABSTRACT FROM AUTHOR]

This multicenter study aimed to assess the short-term effectiveness and safety of faricimab in treatment-naïve patients with wet age-related macular degeneration (wAMD) in Japan. We retrospectively reviewed 63 eyes of 61 patients with wAMD, including types 1, 2, and 3 macular neovascularization as well as polypoidal choroidal vasculopathy (PCV). Patients received three consecutive monthly intravitreal injections of faricimab as loading therapy. Over these 3 months, visual acuity improved gradually compared to baseline. Moreover, the central foveal thickness decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). At 3 months after initiation of faricimab therapy, a dry macula (defined as absence of intraretinal or subretinal fluid) was achieved in 82% of the eyes. Complete regression of polypoidal lesions was observed in 52% of eyes with PCV. Subfoveal choroidal thickness also decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). Although retinal pigment epithelium tears developed in two eyes, there were no other ocular or systemic complications observed during the 3 months of loading therapy. In conclusion, loading therapy using faricimab resulted in improved visual acuity and retinal morphology in Japanese patients with wAMD without particular safety issues. [ABSTRACT FROM AUTHOR]

Purpose: To clarify recent trends in the use of intravitreal injections of anti-vascular endothelial growth factor (VEGF) in Japan. Study design: Retrospective cohort study. Methods: We used the DeSC database, a large-scale claims database for Japan, for entries between April 2014 and March 2021. We counted the number of anti-VEGF drug injections (aflibercept, ranibizumab, brolucizumab, and pegaptanib) administered every year, calculated the sex- and age-adjusted injection rates, and stratified these rates according to sex, age categories, anti-VEGF drugs, and diagnoses. We also calculated the number of injections administered within one year after the first injection according to the diagnoses. Results: In total, 164,451 cases of anti-VEGF injections were identified. The sex- and age-adjusted rates of anti-VEGF injections per 1000 person-years increased from 7.9 in 2014 to 16.1 in 2020. Men were approximately twice as likely to receive anti-VEGF injections than women. The 70–79, 80–89, and ≥90 age categories had the highest rates, accounting for approximately 80%. Neovascular age-related macular degeneration had the highest rate, accounting for 60–70% over the study period. Aflibercept was the most commonly used drug, accounting for approximately 80% over the study period. The average number of injections within one year after the first injection was 4.4 for neovascular age-related macular degeneration, 2.7 for branch retinal vein occlusion, 3.1 for central retinal vein occlusion, and 3.5 for diabetic macular edema in 2020. Conclusion: These findings can be used as a benchmark for the clinical practice of anti-VEGF therapy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the treatment outcomes of patients with neovascular age-related macular degeneration (nAMD) who initially received faricimab or aflibercept treatment using propensity score matching (PSM) to align patient backgrounds., Methods: Patients with treatment-naïve nAMD who received either faricimab or aflibercept for three consecutive monthly injections as the loading phase were enrolled in this study. In the 1:1 PSM, sex, age, best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and AMD subtypes in the pre-treatment state were selected as covariates. We examined the BCVA, CMT, CCT, and remaining fluid at 1-, 2-, and 3-month after the first injection., Results: After PSM, 43 eyes were included in the faricimab and aflibercept group each. Both groups showed significant improvements in BCVA, CMT, and CCT at 1-, 2-, and 3-month after the initial injection compared with baseline. Meanwhile, no significant differences were observed between the two groups at any time point regarding BCVA, CMT, and CCT. At 1-month, 18.6% of patients in the faricimab group and 41.9% in the aflibercept group demonstrated residual subretinal fluid or intraretinal fluid, with a significant difference between the groups (P = 0.03)., Conclusion: The BCVA improved after three loading injections of both faricimab and aflibercept. Faricimab may provide a favorable early treatment response in reducing subretinal fluid in a Japanese cohort., Competing Interests: Declarations. Ethical approval: The study was approved by the Institutional Review Board at Kyushu University, Fukuoka, Japan (REB #26–131) and adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants involved in the study. Conflict of interest: The authors declare that they have no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/purpose: Observation of choroidal thickness after anti-vascular endothelial growth factor (VEGF) therapy may be important for the ideal management of neovascular age-related macular degeneration (AMD). This study investigated changes in subfoveal choroidal thickness (SCT) during loading doses of intravitreal injections of brolucizumab in eyes with neovascular AMD. Methods: This study included 73 eyes of 72 patients with neovascular AMD at five university hospitals in Japan. All 73 eyes underwent three monthly 6.0 mg intravitreal injections of brolucizumab at baseline, 1 month, and 2 months. The SCT at 3 months was evaluated using optical coherence tomography. Results: The 73 eyes were classified into the treatment-naïve group (43 eyes) and the switched group (30 eyes) that were switched from other anti-VEGF treatments. After three intravitreal injections of brolucizumab, SCT significantly decreased from 236.5 ± 98.8 µm at baseline to 200.4 ± 98.3 µm at 3 months (percent of baseline 84.7%, P < 0.001) in the treatment-naïve group. In the switched group, SCT also significantly decreased from 229.0 ± 113.2 μm at baseline to 216.9 ± 110.2 μm at 3 months (percent of baseline 94.7%, P = 0.039), although the decrease was not as marked compared to that of the treatment-naïve group. Conclusion: Intravitreal injections of brolucizumab for neovascular AMD significantly reduced the SCT in both the treatment-naïve and switched groups. Brolucizumab may cause significant anatomic changes in the choroid, particularly in treatment-naïve AMD eyes, possibly more than that previously reported for other anti-VEGF agents. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the 2-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema (DME) in the YOSEMITE Japan subgroup., Study Design: YOSEMITE/RHINE (NCT03622580/NCT03622593) subgroup analysis: global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 faricimab trials., Methods: Patients were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W) and per treat-and-extend (T&E) dosing, or aflibercept 2.0 mg Q8W. Outcomes were assessed through year 2 for the YOSEMITE Japan subgroup (N = 60) and the pooled YOSEMITE/RHINE global cohort (N = 1891)., Results: In the YOSEMITE Japan subgroup, 21, 19, and 20 patients were randomized to faricimab Q8W, faricimab T&E, and aflibercept Q8W, respectively (632, 632, and 627 patients in the pooled YOSEMITE/RHINE cohort). Vision gains and anatomic improvements with faricimab at year 1 were maintained over 2 years and were generally consistent between groups. Mean best-corrected visual acuity changes from baseline at year 2 (weeks 92-100 average) for the YOSEMITE Japan subgroup were +12.5, +9.0, and +5.0 letters in the faricimab Q8W, faricimab T&E and aflibercept Q8W arms, respectively (+10.8, +10.4, and +10.3 letters in the pooled YOSEMITE/RHINE cohort). At week 96, 61.1% of the YOSEMITE Japan subgroup and 78.1% of the pooled YOSEMITE/RHINE cohort were on ≥ Q12W dosing. Faricimab was well-tolerated with a safety profile comparable with aflibercept., Conclusion: Faricimab up to Q16W offered durable vision gains and anatomic improvements up to 2 years in patients with DME in the YOSEMITE Japan subgroup. Outcomes were generally consistent with the pooled YOSEMITE/RHINE cohort., (© 2024. The Author(s).)

Purpose: To evaluate 2-year efficacy, durability, and safety of faricimab in the TENAYA Japan subgroup and pooled global TENAYA/LUCERNE cohort of patients with neovascular age-related macular degeneration (nAMD)., Methods: Subgroup analysis of TENAYA/LUCERNE (NCT03823287/NCT03823300): phase III, multicentre, randomised, active comparator-controlled, double-masked, non-inferiority trials. Treatment-naïve patients aged ≥ 50 years with nAMD were randomised (1:1) to intravitreal faricimab (6.0 mg up to every 16 weeks [Q16W] after 4 initial Q4W doses) or aflibercept (2.0 mg Q8W after 3 initial Q4W doses). Outcomes were assessed through year 2 for the TENAYA Japan subgroup (N = 133) and global pooled TENAYA/LUCERNE cohort (N = 1329)., Results: Vision and anatomic improvements achieved with faricimab at year 1 were maintained over 2 years and were generally comparable between the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Adjusted mean best-corrected visual acuity (BCVA) change from baseline at year 2 for the TENAYA Japan subgroup and global pooled TENAYA/LUCERNE cohort was +7.1 (3.7-10.5) and +4.4 (3.2-5.5) letters in the faricimab arm, respectively, and +5.2 (1.9-8.6) and +4.3 (3.1-5.4) letters in the aflibercept arm, respectively. At week 112, the proportion of faricimab-treated patients on Q16W dosing was 61.0% and 63.1% in the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Faricimab was well tolerated through year 2., Conclusion: Year 2 TENAYA Japan subgroup findings for faricimab were generally consistent with the pooled global TENAYA/LUCERNE results in patients with nAMD. Vision and anatomical benefits with faricimab were similar to those with aflibercept but with fewer injections., (© 2024. The Author(s).)

This multicentre retrospective study evaluated the 1-year outcomes and safety profile of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Fifty-five patients (57 eyes) underwent loading therapy comprising three monthly faricimab injections. If dryness was achieved by the third month, subsequent treat-and-extend (TAE) follow-up continued at a minimum 8-week interval thereafter. If wet macula persisted at the third month, a fourth dose was administered, followed by the TAE regimen. After 1 year, improvements in visual acuity (0.44 ± 0.46 [baseline] to 0.34 ± 0.48; p < 0.01) and central foveal thickness (326 ± 149 [baseline] to 195 ± 82 μm; p < 0.0001) were significant. Dry macula, characterised by the absence of intraretinal or subretinal fluid, was achieved in 65% of cases. Treatment intervals varied, ranging from 8 to 16 weeks, with 44% of eyes extending to a 16-week interval, followed by 33% at 8 weeks, 16% at 12 weeks, 5% at 14 weeks, and 2% at 10 weeks. Notably, 50% of the polypoidal choroidal vasculopathy patients exhibited complete regression of polypoidal lesions between 12 and 15 months. Faricimab treatment in nAMD patients induced significant improvements in central vision and retinal morphology. Two cases of retinal pigment epithelial tears and one case of iritis were reported as ocular complications., (© 2024. The Author(s).)

Purpose: This study investigates the visual outcomes of neovascular age-related macular degeneration (nAMD) patients who developed intraocular inflammation (IOI) after intravitreal brolucizumab injection (IVBr)., Methods: We studied 285 eyes of 279 cases diagnosed with nAMD and focused on 18 eyes (6.3%) of 17 cases which developed IOI after IVBr. IVBr was performed either on the initial treatment or for switching of other anti-vascular endothelial growth factor agents during January 2020 to December 2021. We evaluated clinical features and the course of treatment of a 6-month follow-up after IOI occurred., Results: Of 17 cases, 9 cases were male, 8 cases were female. Baseline logarithm of the minimum angle of resolution(logMAR) best-corrected visual acuity (BCVA) was 0.36, BCVA before IOI occurred was 0.30, and BCVA when IOI occurred was 0.43. 16 eyes (88.9%) had symptoms such as visual loss or floaters when IOI occurred. On the other hand, the remaining 2 eyes (11.1%) had no symptoms. 11 eyes (61.1%) had only IOI, while the remaining 7 eyes (38.9%) had IOI and perivascular sheathing. Steroid sub-tenon injection was performed on 1 eye (5.6%), steroid eye drops were used in 11 eyes (61.1%), and 6 eyes (33.3%) were followed-up without treatment. Neovascular AMD recurred in 16 eyes (88.9%) after IOI occurred and were treated with aflibercept. VA at 3 and 6 months after IOI occurred were significantly improved to 0.34 and 0.30, respectively (P = 0.09 at 3 months and P = 0.02 at 6 months). The symptoms of patients were improved in all cases. We were able to stop steroid treatment in all cases., Conclusions: IOI occurred in 6.3% of nAMD patients after IVBr treatment. All of which showed significant improvement from logMAR of 0.43 to 0.30 with steroid treatment or without any treatment. We should consider the possibility of IOI after IVBr as a complication, however, they have a relatively good prognosis if treated at an early stage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hirono et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: We assessed the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti-vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database., Materials and Methods: This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti-VEGF agents after initiating SGLT2is or other antidiabetic drugs., Results: Among 2412 matched patients with DMO, the incidence rates of anti-VEGF agent injections were 230.1 per 1000 person-year in SGLT2i users and 228.4 times per 1000 person-year in non-users, respectively, and the risk ratio for events was unchanged in both groups. Sub-analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti-VEGF agent use [p = .027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.91]. SGLT2is reduced the risk for the first (p = .023, HR: 0.45, 95% CI: 0.22-0.91) and second (p = .021, HR: 0.39, 95% CI: 0.17-0.89) anti-VEGF agent injections., Conclusions: There was no difference in the risk ratio for the addition of anti-VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti-VEGF agent administration in patients with DMO requiring anti-VEGF therapy. Therefore, SGLT2i therapy may be a novel, non-invasive, low-cost adjunctive therapy for DMO requiring anti-VEGF therapy., (© 2024 John Wiley & Sons Ltd.)

Purpose: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan., Methods: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors., Results: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset., Conclusion: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.

Purpose: To assess the changes in intraocular pressure (IOP) after intravitreal aflibercept injections in Japanese patients with neovascular age-related macular degeneration (nAMD) complicated by glaucoma., Study Design: Retrospective observational study., Methods: We retrospectively reviewed 27 eyes of 25 Japanese patients diagnosed with nAMD complicated by glaucoma. The patients were treated with 2 mg/0.05 ml of aflibercept and followed for 52 weeks according to a treat-and-extend (TAE) regimen after 3 consecutive monthly injections. The IOP of each eye was measured at each visit using non-contact tonometry. IOP changes as well as additional glaucoma treatments during 52 weeks were recorded., Results: The mean of aflibercept injections was 8.3 ± 1.9. The mean IOP at baseline was 14.0 ± 3.1 mmHg, and the mean IOP after aflibercept therapy was 13.0 ± 2.4 mmHg at the final visit (P = 0.0463). No patients received additional glaucoma treatment of eye drops or surgery., Conclusion: Our results suggest that intravitreal aflibercept injections may be beneficial for patients with nAMD complicated by glaucoma., (© 2024. Japanese Ophthalmological Society.)

A new anti-vascular endothelial growth factor agent, brolucizumab, was approved by the United States Food and Drug Administration in 2019. We evaluated whether brolucizumab reduces the treatment burden of neovascular age-related macular degeneration (nAMD) after switching by examining 1-year treatment outcomes in a real-world setting. This retrospective single-institution study included 107 consecutive eyes with nAMD treated with brolucizumab. Among these eyes, 30 with treatment-naïve nAMD and 77 treated with other anti-VEGF agents for more than a year were included. All eyes were managed using a treat and extend (TAE) or modified TAE regimen. The last injection intervals at 52 weeks were 12.9 and 12.1 weeks in the treatment-naïve and switch therapy groups, respectively. Among switch therapy group patients whose pre-switch injection intervals were shorter than 120 days (n = 62 eyes), the injection interval was significantly longer after the switch than before, with a mean difference of 2.7 weeks (P < 0.0001). Intraocular inflammation events occurred in 2 and 7 treatment-naïve and switch therapy patients, respectively. In conclusion, brolucizumab might reduce the treatment burden in patients who required the injection of other anti-VEGF agents with a 120-day interval or shorter, despite a relatively high discontinuation rate due to intraocular inflammation., (© 2024. The Author(s).)

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., (© 2023. Japanese Ophthalmological Society.)

Purpose: To evaluate the 1-year efficacy, durability, and safety of faricimab versus aflibercept in patients with neovascular age-related macular degeneration (nAMD) enrolled in the Japan subgroup of the TENAYA trial., Study Design: TENAYA (NCT03823287) was a global, phase 3, multicenter, randomized, active comparator-controlled, double-masked, noninferiority, parallel-group, 112-week trial. After completion of global enrollment, additional patients were enrolled in the Japan extension of TENAYA., Methods: Treatment-naïve patients aged ≥ 50 years with nAMD were randomized (1:1) to intravitreal faricimab 6 mg up to every 16 weeks (Q16W) after 4 initial Q4W doses based on disease activity at weeks 20 and 24 or aflibercept 2 mg Q8W after 3 initial Q4W doses. Primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48. Anatomical/durability outcomes were assessed., Results: Overall, 133 patients were included in the TENAYA Japan subgroup analysis (faricimab, n = 66; aflibercept, n = 67). The adjusted mean (95% confidence interval) BCVA changes were + 7.1 (4.6‒9.7) and + 7.7 (5.2‒10.1) letters in the faricimab and aflibercept treatment groups, respectively. At week 48, 66.1%, 22.6%, and 11.3% of patients in the faricimab group were on Q16W, Q12W, Q8W and dosing intervals, respectively. Ocular adverse event rates were similar between treatment groups (faricimab, n = 14 [21.2%] versus aflibercept, n = 17 [25.4%])., Conclusion: The TENAYA Japan subgroup analysis showed that faricimab up to Q16W had sustained efficacy with an acceptable safety profile. These findings are consistent with the global TENAYA and LUCERNE findings., (© 2023. Japanese Ophthalmological Society.)

Purpose: To report the safety and effectiveness of intravitreal aflibercept (IVT-AFL) for diabetic macular edema (DME) in the real-world clinical practice setting in Japan., Methods: In this prospective, multicenter, observational, post-marketing surveillance, patients with DME newly receiving IVT-AFL were enrolled. During a 24-month follow-up, the primary outcome was the occurrence of safety events. Other pre-specified endpoints were effectiveness indicators, such as best-corrected visual acuity (BCVA), central retinal thickness, and injection frequency., Results: In total, 646 patients administered at least one IVT-AFL injection were included in the safety analysis. During the follow-up period, adverse events occurred in 42 patients (6.50%), whereas adverse drug reactions occurred in 12 (1.86%). In the 12 patients who had adverse drug reactions, seven events occurred in seven patients within the first month of the most recent injection. In addition, 622 patients were included in the effectiveness analysis set. The number of injections over 24 months was 3.6 ± 3.0 (mean ± standard deviation [SD]). BCVA (logarithm of the minimum angle of resolution) was 0.437 ± 0.362 (mean ± SD) (n = 622) at baseline and 0.321 ± 0.348 (n = 177) after 24 months of treatment with IVT-AFL. Central retinal thickness was 440.8 ± 134.2 μm (mean ± SD) (n = 444) at baseline and 355.5 ± 126.4 μm (n = 140) at 24 months., Conclusion: Routine administration of IVT-AFL for DME was not associated with new safety concerns, and BCVA outcomes were maintained over 24 months in the real-world setting. Nonetheless, patients in this real-world setting received fewer injections than those in clinical trials, suggesting that a margin for improvement exists in clinical practice., Trial Registration: ClinicalTrials.gov: NCT02425501., (© 2022. The Author(s).)

Purpose: To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a Japanese multicenter study., Study Design: Retrospective case control study METHODS: The subjects were 58 eyes of 57 patients with neovascular AMD (43 men and 14 women, mean age 74.6 years) of whom 43 eyes of 42 patients completed initial loading of 3 monthly IVBr injections and were followed for more than 3 months. Best-corrected visual acuity (BCVA) changes, anatomical outcomes, and complications were investigated., Results: Of the 43 eyes that completed loading doses, the AMD subtype was type 1 and type 2 macular neovascularization (MNV) in 51%, polypoidal choroidal vasculopathy (PCV) in 42%, and type 3 MNV in 7%. At 3 months after initiating treatment, BCVA significantly improved (P = 0.002) and central retinal thickness significantly decreased (P < 0.0001). At 3 months, complete retinal and subretinal fluid resolution was achieved in 91% of all eyes and complete regression of polypoidal lesions was achieved in 82% of PCV eyes. Iritis occurred in 8 eyes of 8 patients (14%), but resolved using topical or subtenon corticosteroid injection without visual loss in all cases., Conclusions: IVBr for treatment-naïve neovascular AMD was effective in the short-term, achieving significantly improved BCVA, good retinal fluid resolution, and a high rate of polypoidal lesion regression. However, iritis was noted in 14% of patients which may limit use of this drug., (© 2022. Japanese Ophthalmological Society.)

Purpose: To compare the efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy (PCV) over 96 weeks in the HAWK study., Design: HAWK was a global, 2-year, randomised, double-masked, multicentre phase III trial in participants with neovascular age-related macular degeneration., Methods: Of the Japanese participants with PCV, 39 received brolucizumab 6 mg and 30 received aflibercept 2 mg. After 3 monthly loading doses, brolucizumab-treated eyes received an injection every 12 weeks (q12w) but were adjusted to q8w if disease activity was detected. Aflibercept-treated eyes received fixed q8w dosing. Mean change in best-corrected visual acuity (BCVA), the proportion of participants on q12w, retinal thickness, retinal fluid changes and safety were assessed to Week 96., Results: Mean change in BCVA (early treatment diabetic retinopathy study (ETDRS) letters) from baseline to week 48/week 96 was+10.4/+11.4 for brolucizumab and +11.6/+11.1 for aflibercept. For brolucizumab-treated eyes, the probability of only q12w dosing after loading through week 48 was 76%, and 68% through week 96. Fluid resolution was greater with brolucizumab than aflibercept: respective proportions of eyes with intraretinal fluid and/or subretinal fluid were 7.7% and 30% at week 48% and 12.8% and 16.7% at week 96. Brolucizumab exhibited an overall well-tolerated safety profile despite a higher rate of intraocular inflammation compared with aflibercept., Conclusion: In Japanese eyes with PCV, brolucizumab q12w/q8w monotherapy resulted in robust and consistent BCVA gains that were comparable to q8w aflibercept dosing. Anatomical outcomes favoured brolucizumab over aflibercept, with 76% of brolucizumab participants maintained on q12w dosing after loading to week 48., Competing Interests: Competing interests: Glenn Jaffe and Jordi Mones are members of the Brolucizumab Safety Review Committee. Y. Ogura: Consultant for Novartis, Bayer Holding, Alcon Japan, Wakamoto Pharmaceuticals, HOYA Corporation, Astellas Pharma, Senju Pharmaceutical, Boehringer Ingelheim, Chengdu Kanghong Biotechnology, Kyoto Drug Discovery & Development; Lecture fees—Santen Pharmaceuticals, KOWA, Novartis, Bayer Holding, TOPCON, NIKON Healthcare Japan, Sanwa KagakuG. J. Jaffe: Consultant for Novartis, Eyepoint, Iveric, Neurotech, RegeneronG. Cheung: Consultant for Novartis, Bayer, Roche, Boehringer-Ingelheim, Topcon, Samsung; Lecture fees - Topcon, Novartis, Bayer; Grant—ZeissG. T. Kokame: Consultant for Regeneron, Bayer, Genentech, Bausch and Lomb, Santen, Iveric, Allergan Zeiss; Speaker for Regeneron, Bayer, Second Sight, Bausch & Lomb, Salutaris Medical Devices, Zeiss; Research Support from Genentech, Regeneron, Salutaris Medical DevicesT. Iida: Consultant for Novartis, Bayer Healthcare Pharmaceuticals, Tyugai; Lecture fees and grant support—Nidek, Inc., Santen, Inc., Senju Pharmaceutical Co., Ltd, Alcon Laboratories, Inc, Novartis, Bayer Healthcare Pharmaceuticals; Grant support; Topcon Medical Systems Inc. K. Takahashi: Consultant for Novartis, Bayer, Kyowa Kirin, Santen, Allergan Japan, Lecture fees from Novartis, Bayer, Santen, SenjyuW. K. Lee: Consultant for Novartis, Bayer, Allergan, Santen, Boehringer-Ingelheim, Roche; Lecture fee from Novartis, Bayer, AllerganA. Chang: Consultant for Novartis, Bayer, Allergan, Roche, AlconJ. Monés: Consultant/Advisor for Novartis, Alcon, Bayer, Iveric Bio, Notal Vision, Roche, Cellcure, Lineage and Reneuron; Financial Interests: Iveric Bio, Notal Vision; Lecture Fees from Novartis, Roche and Ophthotech; Trial grants from Novartis, Bayer, Roche and IvericD. D’Souza, G. Weissgerber, K. Gedif: Employees of Novartis Pharma AGA. Koh: Consultant for Novartis, Bayer, Allergan, Carl Zeiss Meditec, and Heidelberg Engineering., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pro re nata (PRN) regimen using anti-vascular endothelial growth factor (VEGF) agent is popular for the treatment of diabetic macular edema (DME). We investigated the influence of waiting time (WT) and interval between the date of recurrence of edema and re-injection on treatment efficacy. Methods: This retrospective study conducted at 7 sites in Japan enrolled patients who received intravitreal injection of ranibizumab (IVR) and aflibercept (IVA) in 1+PRN regimen. Enrolled patients were divided into 2 groups: prompt group (less than 1 week) and deferred group (3 weeks or more). Central retinal thickness (CRT) and best corrected visual acuity (BCVA) were measured every month for 1 year. Results: CRT in the deferred group was significantly higher than that in the prompt group at 2, 5, 6, 7, and 12 months (p < 0.05). BCVA in the prompt group was significantly better than that in the deferred group at 7, 10, and 12 months (p < 0.05). Conclusion: The prompt group was superior in anatomical and functional improvement of DME in anti-VEGF therapy than the deferred group. Our data suggests that shorter WT is recommended for better visual prognosis in the treatment for DME. [ABSTRACT FROM AUTHOR]

Purpose: The MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis., Methods: This was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients' psychological status using the Hospital Anxiety and Depression Scale (HADS)., Results: The mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was - 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080)., Conclusion: MERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement., (© 2021. The Author(s).)

Purpose: We investigated 10-year changes in baseline best-corrected visual acuity (BCVA), as well as functional and anatomical changes at 1 and 2 years after initial treatment, in eyes with treatment-naïve neovascular age-related macular degeneration (nAMD)., Methods: This retrospective, multicenter, case series reviewed patients with treatment-naïve nAMD who underwent initial treatment from 2006 to 2015, using photodynamic therapy (PDT), anti-vascular endothelial growth factor (VEGF), or a combination of PDT and anti-VEGF. BCVA and central retinal subfield thickness (CRST), were measured at baseline and at 1 or 2 years of follow-up., Results: In total, 3096 eyes of 3096 patients were included from 14 hospitals. Mean BCVA at baseline became significantly better over the 10-year study period (P < 0.001). BCVA at 1 year significantly improved from baseline in patients who underwent initial treatment from 2009 to 2015 (P = 0.001, 2009; P = 0.004, 2010; P = 0.01, 2011; P < 0.001, 2012-2015). BCVA at 2 years significantly improved from baseline in patients who underwent initial treatment from 2012 to 2015 (P < 0.001, 2012; P < 0.001, 2013-2015). CRST at 1 year decreased significantly from CRST at baseline, each year from 2006 to 2015 (P < 0.001, 2006-2015). CRST at 2 years decreased significantly from CRST at baseline, each year from 2006 to 2015 (P = 0.03, 2006; P < 0.001, 2007-2015)., Conclusion: Baseline BCVA with treatment-naïve nAMD tended to become better during the study period. BCVA at 1 year improved in the era of anti-VEGF; BCVA at 2 years improved in patients who underwent initial treatment in 2012 or later; and CRST decreased in each year during the study period.

Purpose: To evaluate the efficacy and safety of intravitreal aflibercept (IVT-AFL) versus IVT-AFL plus rescue photodynamic therapy (IVT-AFL + rPDT) in the subgroup of Japanese patients with polypoidal choroidal vasculopathy (PCV) enrolled in the PLANET study., Study Design: A 96-week, double-masked, sham-controlled phase-3b/4 randomized clinical trial conducted at multiple centers from May 2014 to August 2016., Patients and Methods: Patients with PCV (BCVA 73-24 ETDRS letters [20/40-20/320 Snellen]) received 3 initial monthly doses of IVT-AFL 2 mg. At week 12, the patients were randomly assigned 1:1 to IVT-AFL + sham PDT or IVT-AFL + rPDT. Patients not requiring rescue received IVT-AFL every 8 weeks; those requiring rescue received IVT-AFL monthly plus sham/active PDT. Following week 52, the treatment intervals could be extended > 8 weeks., Results: The baseline demographics for the 159 Japanese patients were balanced. At week 96, the mean BCVA change was + 9.7 (IVT-AFL) versus + 9.5 letters (IVT-AFL + rPDT) (least-squares mean difference of - 0.3; 95% CI, - 3.7 to 3.1); the mean central subfield thickness reduction was - 148.0 µm versus - 145.9 µm. Overall, 17.1% of the patients required rescue PDT. At week 96, 25.0% (IVT-AFL) and 37.9% (IVT-AFL + rPDT) of the patients had complete polyp regression; 84.1% (IVT-AFL) and 88.4% (IVT-AFL + rPDT) of the patients had no evidence of active polyps. The mean number of injections (weeks 52-96) were 4.6 (IVT-AFL) and 4.5 (IVT-AFL + rPDT). Overall, 36.0% (IVT-AFL) and 33.8% (IVT-AFL + rPDT) of the patients experienced ocular treatment-emergent adverse events., Conclusion: IVT-AFL monotherapy was efficacious for the treatment of Japanese patients with PCV, and the addition of rescue PDT did not show additional benefits.

Purpose: To describe treatment patterns in patients diagnosed with neovascular age-related macular degeneration (nAMD), retinal vein occlusion (RVO), or diabetic macular edema (DME), newly-treated with anti-vascular endothelial growth factor (anti-VEGF) agents as recorded in the Japanese Medical Data Center (JMDC) database., Study Design: This non-interventional, descriptive, retrospective, observational cohort study included insured Japanese patients aged ≥ 21 and ≤ 75 years at index date (anti-VEGF treatment initiation)., Methods: Patients with minimum one claim in JMDC database with a diagnosis code for nAMD, RVO, or DME between October 2007-May 2015 and with minimum of one claim for anti-VEGF agents on or after the date of diagnosis were included. Frequency and proportion of claims submitted for anti-VEGF injections were assessed during 12 months post-index date., Results: The median (interquartile range) number of claims for anti-VEGF injections during 12 months post-index date were 3 (1, 4) for nAMD (n = 255), 2 (1, 3) for RVO (n = 223) and 2 (1, 4) for DME (n = 125) patients. Frequencies of nAMD, RVO and DME patients with one or more claims for a retinal disease treatment other than an anti-VEGF agent were 4 (1.57%), 59 (26.46%) and 68 (54.40%) during the 12 months pre-index date and 21 (8.24%), 85 (38.12%) and 62 (49.60%) in the 12 months post-index date, respectively., Conclusions: The median number of anti-VEGF injections per patient was lower than those reported in clinical trials. Although various pre- and concomitant treatments were used in RVO and DME, anti-VEGF monotherapy was the first-line treatment in > 90% of nAMD patients.

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.

Introduction: Neovascular glaucoma is characterized by neovascularization of the iris and the anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may improve intraocular pressure (IOP) and neovascularization., Methods: The VEGA trial assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma in a 13-week, randomized, double-masked, sham-controlled, phase 3 study performed at multiple sites in Japan that enrolled patients with anterior segment neovascularization and IOP > 25 mmHg. Patients received background therapy plus IVT-AFL (2 mg) or sham injection at baseline. Patients were re-treated if presenting with IOP > 21 mmHg and incomplete regression of iris neovascularization, receiving additional sham or IVT-AFL injections at week 1 and IVT-AFL injections at weeks 5 and/or 9. Double-masking was maintained throughout. The primary endpoint was change in IOP from baseline to week 1., Results: Fifty-four patients were randomly assigned (full analysis set); the per-protocol set comprised 52 patients. At week 1, the least squares mean change in IOP was -9.9 mmHg for IVT-AFL versus -5.0 mmHg for sham [full analysis set: difference -4.9 mmHg (95% confidence interval -10.2 to 0.3; P = 0.06); per-protocol set: -5.5 mmHg (95% CI -10.8 to -0.2; P = 0.04)]. At week 1, a greater proportion of patients administered IVT-AFL versus sham achieved IOP ≤ 21 mmHg and had improved neovascularization grades. Patients in the sham group who met re-treatment criteria and received IVT-AFL at week 1 [n = 22 (81.5%)] had an additional mean IOP decrease of 9.2 mmHg by week 2, and the proportion with improvement in neovascularization grades increased from 11.5% to 69.2%. Increases in the proportion of patients with improved neovascularization grades and the proportion who achieved IOP control (≤ 21 mmHg) were also observed by week 2 in this group. Overall, 77.8% and 74.1% of patients treated with IVT-AFL and sham/IVT-AFL, respectively, received a single IVT-AFL injection. The most common ocular treatment-emergent adverse event was punctate keratitis (9.3%: 7.4% and 11.1% in the IVT-AFL and sham/IVT-AFL groups, respectively)., Conclusions: IVT-AFL was associated with clinically meaningful improvements in IOP control, indicating that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma., Trial Registration: Clinicaltrials.gov identifier, NCT02396316.

Given the success in stabilizing vision with current anti-vascular endothelial growth factor (VEGF) options, one main target for future anti-VEGF drug development includes creating medications with longer durations of action. Achieving this goal will decrease the number of overall injections and follow-up visits required to ensure better patient compliance. The smallest anti-VEGF created so far is brolucizumab (Beovu; Novartis). It is a 26-kDa IgG single-chain antibody fragment that delivers 11 times more anti-VEGF per injection than aflibercept. Brolucizumab was approved by the U.S. Food and Drug Administration (FDA) in late 2019 for the treatment of wet age-related macular degeneration, and has been also approved for the same indication in Japan and the European Union in 2020. In this article, we compare brolucizumab to current FDA-approved anti-VEGF treatments, address the studies associated with brolucizumab, discuss brolucizumab's side effects, and conclude with recommendations., (Copyright 2020 Clarivate Analytics.)

Background/aims: To investigate real-world outcomes for best-corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve, centr-involving diabetic macular oedema (DME)., Methods: Retrospective analysis of longitudinal medical records obtained from 27 institutions specialising in retinal diseases in Japan. A total of 2049 eyes with treatment-naïve DME commencing intervention between 2010 and 2015 who were followed for 2 years were eligible. Interventions for DME included anti-vascular endothelial growth factor (VEGF) therapy, local corticosteroid therapy, macular photocoagulation and vitrectomy. Baseline and final BCVA (logMAR) were assessed. Eyes were classified by the treatment pattern, depending on whether anti-VEGF therapy was used, into an anti-VEGF monotherapy group (group A), a combination therapy group (group B) and a group without anti-VEGF therapy (group C)., Results: The mean 2-year improvement of BCVA was -0.04±0.40 and final BCVA of >20/40 was obtained in 46.3% of eyes. Based on the treatment pattern, there were 427 eyes (20.9%) in group A, 807 eyes (39.4%) in group B and 815 eyes (39.8%) in group C. Mean improvement of BCVA was -0.09±0.39, -0.02±0.40 and -0.05±0.39, and the percentage of eyes with final BCVA of >20/40 was 49.4%, 38.9%, and 52.0%, respectively., Conclusion: Following 2-year real-world management of treatment-naïve DME in Japan, BCVA improved by 2 letters. Eyes treated by anti-VEGF monotherapy showed a better visual prognosis than eyes receiving combination therapy. Despite treatment for DME being selected by specialists in consideration of medical and social factors, a satisfactory visual prognosis was not obtained, but final BCVA remained >20/40 in half of all eyes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To evaluate the three-year outcome after intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD)., Methods: Forty-nine treatment-naïve nAMD patients (50 eyes) were enrolled in this prospective study. The eyes received IAI at two-month intervals in the first year. The treatment regimen was changed to IAI based on a treat-and-extend approach in the second and third years., Results: Twenty-nine eyes of 28 patients were successfully followed up over 36 months. The nAMD subtypes included 15 eyes with typical AMD and 14 eyes with polypoidal choroidal vasculopathy. The number of IAIs performed over the 3 years was 17.2 ± 3.1 (mean ± standard deviation). The mean logMAR, which was 0.42 at baseline, improved to 0.19 (P = 0.001) at 12 months, and 0.26 (P = 0.049) at 36 months. The central retinal thickness (CRT) was 329 ± 120 μm at baseline, 151 ± 38 μm (P < 0.001) at 12 months, and 143 ± 61 μm (P < 0.001) at 36 months. The mean subfoveal choroidal thickness (SFCT) was 288 ± 97 μm at baseline, 243 ± 82 μm (P < 0.001) at 12 months, and 208 ± 63 μm (P < 0.01) at 36 months. The changes in logMAR, CRT, and SFCT over the study period did not differ between typical AMD and PCV., Conclusion: Long-term aflibercept injection can achieve visual improvement and reduce the thickness of the retina and choroid in nAMD. Morphological improvement of these tissues may not be sufficient to sustain earlier visual improvement over the long-term.

Purpose: To evaluate the development and rate of growth in macular atrophy after intravitreal injections of aflibercept (IVAs) for neovascular age-related macular degeneration (AMD) over a 2-year period., Study Design: Retrospective, interventional, consecutive case series., Methods: This study included 94 eyes of 92 patients with treatment-naïve AMD involving the foveal center treated with IVAs at 3 university hospitals in Japan. The patients underwent IVAs bimonthly after 3 initial monthly doses in the first year. The protocol was converted to a treat-and-extend regimen in the second year. The incidence and growth rate of macular atrophy were quantified based on hypoautofluorescence detected by fundus autofluorescence images. Additionally, possible background factors related to the development and rate of growth of macular atrophy were investigated., Results: Of 94 eyes, 39 (41.5%) had typical AMD and 55 (58.5%) had polypoidal choroidal vasculopathy. Ten eyes (10.6%) had macular atrophy at the baseline. Of the remaining 84 eyes, 14 (16.7%) had developed new macular atrophy at 2 years, the square root of the growth rate of atrophy was 0.52 mm/year. In multivariate analyses, a poorer best-corrected visual acuity (P = 0.01) and the presence of intraretinal fluid (P = 0.04) at baseline were found to be the independent predictors for the development of macular atrophy. No factors were found that were significantly related to the growth rate of the macular atrophy., Conclusions: Our study determined the incidence and rate of growth of macular atrophy after IVAs for neovascular AMD in clinical settings. Eyes with vision reduction and intraretinal fluid at the baseline develop macular atrophy more frequently after IVAs for neovascular AMD.

Purpose: The purpose of this study was to evaluate neurodevelopmental outcomes in 18-month old (corrected age) preterm infants who received an intravitreal bevacizumab (IVB) injection for the treatment of type 1 retinopathy of prematurity (ROP)., Methods: In this ten-year retrospective study, we reviewed the medical records of patients who underwent ROP screening at Kyushu University Hospital. Among the patients who received IVB or laser photocoagulation (LPC) for the treatment of type 1 ROP, we included infants whose neurodevelopmental examination (the Kyoto Scale of Psychological Development [KSPD]) results at 18 months corrected age were available. Then, the effect of IVB on the developmental quotient (DQ) in each KSPD domain (Postural-Movement, Cognitive-Adaptive, or Language-Social domain) or the overall DQ was investigated by performing linear regression analysis., Results: Out of the 513 patients reviewed, 53 were included in the study. IVB and LPC were performed for 14 and 39 patients, respectively. Administration of IVB was significantly associated with neurodevelopmental delay in the Language-Social domain (p = 0.01). The observed association remained even after adjusting for gestational age and birth weight (p = 0.03)., Conclusions: Administration of IVB may introduce a risk of developmental impairment of interpersonal relationships, socializations, and/or verbal abilities of preterm children. We recommended that preterm infants who received IVB undergo a neurodevelopmental reassessment during their school years or in adulthood., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate vision-related quality of life (QoL) in wet age-related macular degeneration (wAMD) patients receiving intravitreal aflibercept (IVT-AFL)., Study Design: Prospective, observational Japanese postmarketing surveillance study., Methods: All decisions were made by the treating physician. QoL was assessed using the 25-item National Eye Institute-Visual Functioning Questionnaire (NEI-VFQ-25) composite score administered at baseline, 6 months, and 12 months (primary assessment). Secondary assessments included NEI-VFQ-25 subscale scores, resource use, and best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution [logMAR])., Results: In total, 576 patients (baseline), 555 patients (6 months), and 446 patients (12 months) were included. The mean (SD) number of IVT-AFL injections was 3.5 (1.2) at 6 months and 4.6 (2.2) at 12 months. The mean (SD) improvement from baseline in the NEI-VFQ-25 composite score was 3.1 (11.1) at 6 months and 2.7 (12.3) at 12 months (P < .0001). For the NEI-VFQ-25 subscale scores, the mean change was ≥ 4 (minimally important difference) for general vision, near vision, and mental health at 6 months, and for general vision and mental health at 12 months (all P < .0001). A significant improvement from baseline was found in mean BCVA (logMAR) at 6 months (-0.1) and 12 months (-0.1) (P < .0001). The mean change from baseline in the NEI-VFQ-25 scores was greatest in patients with improved BCVA (gain of ≤ -0.3 logMAR units or ≥ 15 letters) after treatment., Conclusion: IVT-AFL was associated with significant improvements in QoL and visual acuity in Japanese patients with wAMD in a real-world setting.

Purpose: To assess the real-world 5-year treatment outcomes of ranibizumab therapy in Japanese patients with neovascular age-related macular degeneration (AMD)., Methods: This was a retrospective, observational, and open-label effectiveness study that included 295 eyes. The participants were patients with treatment-naïve neovascular AMD who received intravitreal ranibizumab (IVR) monthly injection at least three times as the loading phase, followed by further injections as needed (pro re nata (PRN)) and follow-up assessments for 5 years. Outcomes were determined at least 5 years after the first ranibizumab injection., Results: Mean logMAR best-corrected visual acuity (BCVA) at baseline was 0.52. The mean BCVA significantly improved after three loading injections; however, it declined gradually. The BCVA at 1 year was significantly better than the baseline BCVA, whereas the 3-year, 4-year, and 5-year BCVA values were significantly lower than the baseline values. The average central foveal thickness improved significantly from 366 ± 125 μm to 268 ± 134 μm (p < 0.0001). Macular atrophy was significantly more likely to occur in cases with classic choroidal neovascularization (CNV) than in cases with other AMD (p = 0.01)., Conclusions: IVR is well tolerated in eyes with AMD. However, a PRN regimen for AMD may have limited real-world effectiveness for long-term maintenance of improved visual acuity. Macular atrophy may occur more frequently in classic CNV. To maintain good vision, IVR treatment should be started earlier and performed continuously.

Purpose: To evaluate the efficacy and safety of intravitreal aflibercept injection (IAI) in Japanese patients with diabetic macular edema (DME)., Methods: VIVID-DME was a Phase 3 study comprising patients with DME randomized 1:1:1 to IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 4 weeks until Week 16 then 8-week dosing (2q8), and laser. A total of 403 patients (76 Japanese) were included in this study. VIVID-Japan (72; all Japanese patients) was a nonrandomized, open-label study comprising Japanese patients with DME receiving IAI 2q4 until Week 16, then 2q8. Primary efficacy endpoint (Week 52) of VIVID-DME was mean change from baseline in best-corrected visual acuity; VIVID-Japan evaluated safety and tolerability., Results: Mean change in best-corrected visual acuity (letters) for 2q4, 2q8, and laser groups was +10.6, +10.9, and +1.2 and +9.8, +9.5, and +1.1 in the non-Japanese and Japanese populations of VIVID-DME, respectively. In VIVID-Japan, it was +9.3 for IAI 2q8. Intravitreal aflibercept injection also provided consistently greater benefits for anatomical outcomes versus laser. Adverse events were consistent with the known safety profile of IAI., Conclusion: In Japanese patients with DME, IAI treatment was superior to laser for visual and anatomical outcomes and resulted in efficacy and safety outcomes similar to those in a non-Japanese patient population.

Aims: To estimate the impact of anti-vascular endothelial growth factor (VEGF) agents on visual impairment and blindness avoided in patients with diabetic macular edema (DME) and on associated patient and caregiver productivity loss in Japan., Methods: This study compared the impact of current care (estimated at 53.8% utilization of anti-VEGF agents using current data) with that of hypothetical care (characterized by a higher utilization of anti-VEGF agents [80.0%], as estimated by an expert panel) of DME patients. A population-based Markov model (two-eye approach) simulated visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) transitions over 5 years with DME treatments (intravitreal aflibercept, ranibizumab, and triamcinolone acetonide, and grid/focal laser) in patients with DME. Patient and caregiver productivity loss was determined using the human capital method., Results: In total, 570,000 DME patients were included in the model over 5 years. Increased utilization of anti-VEGF agents resulted in 6,659 fewer cases of severe visual impairment (SVI; 26-35 ETDRS letters) or blindness (0-25 ETDRS letters) compared with the current care approach (26,023 vs 32,682 cases; 20.38% reduction) over this period. Increased utilization of anti-VEGF agents also contributed to productivity loss savings of ¥12.58 billion (US $115.64 million) (i.e., 17.01%) at the end of year 5. The total overall saving over 5 years was ¥45.83 billion (US $421.27 million) (13.45%)., Limitations: Few Japanese data were available, and assumptions were made for some inputs. Vision changes dependent on the function of both eyes were not studied. Only intravitreal (not sub-Tenon's) injections of triamcinolone were considered in this model. Direct costs were not considered., Conclusions: Increased utilization of anti-VEGF agents can reduce SVI and legal blindness in patients with DME in Japan. This would also be associated with substantial savings in patient and caregiver productivity loss.

Objectives: The aim of this study was to obtain real-world clinical data on the safety and efficacy of ranibizumab treatment for myopic choroidal neovascularization (CNV) due to pathologic myopia., Methods: This was a prospective, observational, post-marketing surveillance study in ranibizumab-naive Japanese patients with myopic CNV. Patients who initiated ranibizumab treatment were registered and prospectively observed over 12 months. Safety endpoints were the incidence of ocular and non-ocular adverse drug reactions (ADRs) and serious adverse events (SAEs). The efficacy endpoint included the average change in best-corrected visual acuity (BCVA) in logarithm of the minimal angle of resolution (logMAR) units (logMAR BCVA) from baseline to the last observation., Results: Three hundred and eighteen patients were included in the safety analysis population. Of these 79.9% were female and the mean age was 65.5 years. The incidences of SAEs and ADRs were 0.6 and 0.3%, respectively. A total of 268 patients (84.0%) completed the 12-month study period. The mean (±SD) and median number of ranibizumab injections were 2.0 ± 1.5 and 1.0 during the 12-month study period, respectively. The number of ranibizumab injections received was one in 52.2% of patients and less than or equal to three in 89.2%. The mean change in logMAR BCVA from baseline to month 12 was -0.193, and the mean logMAR BCVA improved from 0.517 to 0.319 between baseline and month 12., Conclusions: This study showed that ranibizumab is generally well tolerated, and that a minimum number of injections were necessary to produce a therapeutic effect in Japanese myopic CNV patients in a real-world setting.

Purpose: To evaluate the efficacy and safety of ranibizumab 0.5 mg in Japanese patients with visual impairment due to macular oedema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) and to support the applicability of the phase III results from Caucasian to Japanese populations., Methods: This is a 3-month, open-label, single-arm, multicentre, phase III study. Thirty-one patients (15 BRVO and 16 CRVO) aged ≥18 years with a best-corrected visual acuity (BCVA) letter score of 19-73 (BRVO) or 24-73 (CRVO) were included. The primary end-point was the mean average change in BCVA from baseline to month 1 through month 3 after three consecutive monthly intravitreal injections of ranibizumab 0.5 mg. Secondary end-points were mean change in BCVA and central subfield thickness (CSFT), categorized BCVA, and safety over 3 months., Results: At month 3, the mean average change in BCVA improved substantially from baseline for BRVO (11.3 letters, p = 0.001) and CRVO (6.7 letters, p = 0.019). The mean BCVA improved (12.8 and 9.1 letters) and the mean CSFT decreased (212.5 and 442.1 μm) from baseline to month 3. At month 3, 26.7% (BRVO) and 31.3% (CRVO) of the patients had a gain of ≥15 letters from baseline. Safety findings in this study were similar to those reported in the previous clinical trials., Conclusion: Ranibizumab was effective in improving BCVA and was well tolerated in Japanese patients with BRVO and CRVO. The findings from this study were consistent with those reported in the Caucasian population., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the results of a 3-year follow-up of intravitreal pegaptanib sodium injection as maintenance therapy for the treatment of neovascular age-related macular degeneration (AMD) in Japanese patients., Methods: In this prospective, uncontrolled interventional study, 20 eyes of 19 patients with treatment-naïve AMD who had received 3 consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab as the induction treatment and had shown clinical/anatomical improvement were enrolled. An intravitreal injection of 0.3 mg/0.09 mL pegaptanib sodium was administered as the maintenance therapy every 6 weeks. Booster treatments using ranibizumab were allowed if clinical deterioration was judged to be present. The primary outcome measures were the best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) as evaluated using spectral-domain optical coherence tomography., Results: Sixteen of the 20 eyes (80 %) were assessed at the 3-year follow-up. The mean logMAR BCVA improved significantly from 0.56 ± 0.31 before the induction treatment to 0.24 ± 0.25 at baseline (P < 0.001) and was well maintained at 156 weeks (0.25 ± 0.28, P = 0.938). Moreover, the mean CFT also decreased significantly from 346 ± 111 μm before the induction treatment to 232 ± 54 μm at baseline (P < 0.001) and was well preserved at 156 weeks (210 ± 59 μm, P = 0.278). Thirteen eyes (81.3 %) received an unscheduled booster treatment, and no severe systemic or ocular side effects occurred during follow-up., Conclusion: Intravitreal pegaptanib sodium injection as the maintenance therapy was effective in stabilizing the vision of patients with AMD in whom induction treatment led to improved BCVA, as evaluated at the 3-year follow-up.

Background/aims: To evaluate efficacy and safety of intravitreal aflibercept (IVT-AFL) in Japanese patients with wet age-related macular degeneration (wAMD) from the VIEW 2 trial., Methods: In this double-masked study, patients were randomised to: 0.5 mg IVT-AFL every 4 weeks (0.5q4); 2 mg IVT-AFL every 4 weeks (2q4); 2 mg IVT-AFL every 8 weeks (2q8) after 3 monthly injections; or 0.5 mg ranibizumab every 4 weeks (Rq4). Main efficacy outcomes included vision maintenance and best-corrected visual acuity (BCVA) at week 52., Results: At week 52, all Japanese patients in the IVT-AFL groups (n=70) maintained vision, compared with 96% of Japanese patients (n=23/24) treated with ranibizumab. Japanese patients in all treatment groups showed improvement in BCVA after treatment. The Rq4, 2q4 and 2q8 groups experienced similar gains in BCVA from baseline. The 0.5q4 group had higher gains due to an unexpected drop in BCVA between screening and baseline. Central retinal thickness and mean area of choroidal neovascularisation decreased in all treatment groups with similar magnitude. Ocular treatment-emergent adverse events were balanced across treatment groups., Conclusions: IVT-AFL was effective and well tolerated in Japanese patients. Outcomes in this population were consistent with those in the overall VIEW 2 population., Trial Registration Number: NCT00637377., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Several retinal ischemic diseases can cause neovascular glaucoma (NVG). Trabeculectomy with mitomycin C (MMC) is a relatively better treatment modality in the management of eyes with NVG than other glaucoma surgeries. The aim of this study was to investigate the factors that may influence the outcome of trabeculectomy with MMC for NVG., Methods: Forty-nine NVG eyes from 43 patients (26 males and 17 females) underwent primary trabeculectomy with MMC. The mean follow-up period was 16.8 ± 8.1 months (range, 6 to 34 months). Twenty-one eyes of 21 patients received intravitreal bevacizumab (IVB) 3.6 ± 1.8 days before trabeculectomy with MMC. A Kaplan-Meier survival-curve analysis was used to summarize the cumulative probability of success. We examined the relationship between the surgical outcome and the following surgical factors: gender, age, history of panretinal photocoagulation, history of cataract surgery, history of vitrectomy, preoperative IVB, NVG in the fellow eye, and postoperative complications (hyphema, choroidal detachment, and formation of fibrin) by multivariate analysis., Results: The survival rate was 83.7% after 6 months, 70.9% after 12 months, and 60.8% after 24 months. The Kaplan-Meier survival curves showed no significant difference in the survival rate between the eyes with preoperative IVB (n = 21) and the eyes without preoperative IVB (n = 28) (p = 0.14). The multiple logistic regression analysis showed that postoperative hyphema (odds ratio, 6.54; 95% confidence interval, 1.41 to 35.97) was significantly associated with the surgical outcome (p = 0.02)., Conclusions: Postoperative hyphema was significantly correlated with the outcome of trabeculectomy for NVG. There was no significant association between preoperative IVB and postoperative hyphema or the results of trabeculectomy.

Purpose: To explore the efficacy and safety of pegaptanib sodium as maintenance therapy in Japanese patients with neovascular, age-related macular degeneration (AMD) after induction therapy (LEVEL-J study)., Methods: A multi-center, prospective study was conducted at 21 medical institutions between 2009 and 2011. Of Japanese neovascular AMD patients with choroidal neovascularization who showed improvement in visual acuity (VA) with induction therapy, those who were scheduled for intravitreal injections of pegaptanib as maintenance therapy were recruited. LogMAR VA was assessed. Booster treatment (unscheduled treatment with other agents) was allowed during the study period if symptoms were judged to have worsened. Safety was assessed by monitoring adverse events and intraocular pressure (IOP)., Results: Of 75 patients included in the analysis, 80 % completed the 54-week study period. Their mean age was 74.7 ± 6.9 years, and 54 patients (72.0 %) were men. The mean number of pegaptanib injections was 5.7 ± 2.6. Booster treatment was not required in 40 eyes (53.3 %). Mean logMAR VA was 0.61 ± 0.31 before induction therapy, 0.26 ± 0.24 before maintenance therapy, and 0.29 ± 0.28 at 54 weeks. No notable change in VA was observed during maintenance therapy. Adverse events were reported in 4 patients (5.3 %), including increased intraocular pressure, cancer, gallstones and recurrence of breast cancer, but mean IOP remained stable during maintenance therapy., Conclusions: The results of this exploratory study suggest that maintenance therapy with pegaptanib is potentially an effective and well-tolerated option in Japanese patients with neovascular AMD in whom induction therapy has been successful.

Purpose: To determine the 2-year results of intravitreal bevacizumab in highly myopic eyes with choroidal neovascularization (CNV)., Methods: An open-label, consecutive, interventional case series. Seventy-five eyes of 69 consecutive Japanese patients with either subfoveal or nonsubfoveal myopic CNVs were studied. The eyes were treated with intravitreal bevacizumab and followed-up for at least 2 years. The best-corrected visual acuities at the baseline in eyes with subfoveal CNV were compared with that in eyes with nonsubfoveal CNV at 2 years after the intravitreal bevacizumab., Results: The difference between the mean best-corrected visual acuity at the baseline and that at 2 years in eyes with a subfoveal CNV was not significant. However, the mean best-corrected visual acuity in eyes with nonsubfoveal CNV was significantly improved from 0.53 ± 0.36 logarithm of the minimal angle of resolution units (Snellen 20/66) before intravitreal bevacizumab to 0.29 ± 0.36 logMAR units (Snellen 20/40) (P < 0.001) 2 years after intravitreal bevacizumab. The incidence of chorioretinal atrophy after 2 years was 3 of 49 (6.1%) in eyes with nonsubfoveal CNV and 21 of 26 (80.8%) in eyes with which subfoveal CNV (P < 0.001). Furthermore, the chorioretinal atrophy area with nonsubfoveal CNV was 0.05 ± 0.21 mm, which was also significantly smaller than that of subfoveal CNV at 1.76 ± 1.60 mm (P < 0.001)., Conclusion: Intravitreal bevacizumab is a good treatment for eyes with nonsubfoveal CNV; however, another treatment is necessary for eyes with a subfoveally located CNV.