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Objective: This real-world retrospective case series evaluates the safety and efficacy of aflibercept 8 mg in patients diagnosed with neovascular age-related macular degeneration (nAMD)., Methods and Analyses: Treatment-naïve or treatment-experienced patients with nAMD receiving aflibercept 8 mg with at least 6 months of follow-up were assessed., Results: 40 eyes from 33 patients were included, of which 36/40 eyes were previously treated. The mean age of subjects is 79.84 years. At baseline, 29/36 eyes had intraretinal fluid (IRF)/subretinal fluid (SRF) at an average interval of 40.97 days, logMAR VA of 0.346, and average central subfield thickness (CST) of 341.53 µm. At final follow-up, average logMAR VA was 0.315 and average CST decreased by 39.39 µm, with an average number of days since last treatment of 52.9. Of the 32 eyes with IRF, SRF, or both at the time of switch, 12 eyes achieved anatomical quiescence without IRF/SRF after the first injection of aflibercept 8 mg, including three of four treatment-naive patients., Conclusions: This early case series suggests that patients treated with aflibercept 8 mg may achieve greater duration between treatments while preserving and, in some cases, improving visual acuity and anatomical outcomes in a real-world clinic setting. In this retrospective study, the patient population primarily consisted of treatment-experienced cases with recalcitrant disease or high treatment burdens, potentially using aflibercept 8 mg as salvage therapy. This selection bias limits generalisability to broader real-world populations. The small sample size precludes formal statistical conclusions. Multiple investigators made unstandardised treatment decisions based on individual clinical judgement, including whether to continue aflibercept 8 mg or revert to prior therapy, sometimes after just one injection., Competing Interests: Competing interests: DAE, FASRS, one of the authors of this paper also serves as Associates Editor of the journal., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Proliferative diabetic retinopathy (PDR) often leads to tractional retinal detachment and vitreous hemorrhage, requiring vitrectomy. Poor visual outcomes are commonly caused by macular edema and proliferative vitreous retinopathy after vitrectomy. Intravitreal dexamethasone implant has shown promise in improving visual function after vitrectomy for diabetic macular edema, but its role in vitrectomy for PDR treatment remains unexplored. This study aims to assess the effectiveness of vitrectomy combined with an intravitreal dexamethasone implant for PDR patients., Methods: We will design a single-mask, randomized controlled trial with 100 participants diagnosed with PDR requiring vitrectomy. Participants will be randomly assigned to either the Ozurdex (0.7 mg dexamethasone intravitreal implant) group or the control group. The dexamethasone implant group will undergo vitrectomy combined with 0.7 mg dexamethasone intravitreal implant, while the control group will undergo vitrectomy alone. A single surgeon will perform all the vitrectomy surgeries, and the choice of intravitreal dexamethasone implant treatment will be disclosed before the closure of scleral wounds. Primary and secondary outcomes will be assessed at baseline and at 4, 8, 12, and 24 weeks post-vitrectomy., Statistical Analysis: Statistical analysis will be conducted using R software. A p value 0.05 will be considered statistically significant. The analysis methods will include the following: visual acuity and OCT measurements will be analyzed using repeated measures analysis of variance (ANOVA) with two-tailed tests; rates of visual improvement, visual decline, postoperative vitreous hemorrhage, elevated intraocular pressure, and postoperative retinal detachment will be analyzed using chi-square tests with two-tailed tests. Logistic regression analysis will be used to analyze risk factors for poor visual prognosis, neovascular glaucoma development, and postoperative vitreous hemorrhage occurrence., Discussion: This protocol aims to enhance our understanding of the effects of combining an intravitreal Ozurdex 0.7 mg dexamethasone implant with vitrectomy on visual outcomes and macular morphology changes in treating late complications of PDR., Trial Registration: The trial was registered at the Chinese Clinical Trial Registry on May 11, 2022, with registration number ChiCTR2200059760., Competing Interests: Declarations. Ethics approval and consent to participate {24}: The study followed the tenets of the Declaration of Helsinki and the protocol and was approved by the Institutional Review Board of Beijing Tongren Hospital (TREC2022-KY063) on August 30, 2022. Patients were required to sign an informed consent form, and written informed consent was obtained from each participant. Consent for publication {32}: Not applicable. Competing interests {28}: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: This study aimed to evaluate the efficacy of a simple intravitreal injection of perfluoropropane (C 3 F 8 ) in treating unclosed idiopathic macular holes (IMHs) in patients who had previously undergone primary pars plana vitrectomy (PPV)., Methods: This study was a retrospective, observational clinical study. It included patients diagnosed with unclosed IMHs following primary PPV combined with internal limiting membrane peeling and air tamponade. Optical coherence tomography (OCT) performed 1 week after PPV revealed unclosed IMHs with the presence of the 'cuff' sign and intraretinal cysts. The following day, these patients received a simple intravitreal C 3 F 8 injection. Comprehensive evaluations, including best-corrected visual acuity (BCVA), indirect ophthalmoscopy, fundus photography, and OCT, were performed before PPV, 1 week after surgery, and at follow-up intervals of 1-3 months after the intravitreal gas injection., Results: The minimum linear diameter (MLD) of the macular holes (MHs) 1 week before C 3 F 8 injection was 335.1 ± 74.3 μm. Following C 3 F 8 tamponade, the closure rate of the MHs was 100%. The mean BCVA before C 3 F 8 tamponade was 0.68 ± 0.17 logMAR (20/100) after primary PPV, which improved to 0.48 ± 0.19 logMAR (20/63) after C 3 F 8 tamponade, showing a statistically significant difference (P = 0.01)., Conclusions: For patients with unclosed MHs after primary PPV, the presence of the 'cuff' sign on OCT suggests that retreatment can be effectively achieved through a simple intravitreal gas injection. This approach is straightforward, practical, and effective., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Tianjin Medical University Eye Hospital (2023KY(L)-25). Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: To analyse the impact on cost if faricimab is used as the first-line treatment for neovascular age-related macular degeneration (nAMD) compared to standard treatment with bevacizumab., Methods: Retrospective registry study including real-world data from the Swedish Macula Registry between 2017 and 2022. The observed number of injections and visits for bevacizumab during the first two years of treatment was used (n = 437 patients). Number of faricimab injections was obtained from published clinical trial data and unit costs mostly from publicly available Swedish sources. The provider cost included medication and visit cost and societal cost included additionally patient travel cost. Costs are presented in 2023 EUR., Results: The incremental societal cost of faricimab was 277 EUR per patient compared to bevacizumab in the base case. Medication cost was higher (1516 EUR) while visit cost (-1183 EUR) and patient travel cost (-56 EUR) were lower due to longer injection intervals. Faricimab was of similar cost as bevacizumab for patients residing far from the clinic. The faricimab injection interval and the number of bevacizumab injections were major drivers of uncertainty in the results., Conclusion: Faricimab represents a cost-effective alternative to bevacizumab for patients with nAMD in Sweden. Its extended treatment interval is particularly beneficial for patients living far from clinics, and if the real-life faricimab injection interval extends beyond 12 weeks. Our findings emphasize faricimab's potential to free up healthcare staff to treat a larger patient population with existing clinic resources., (© 2024 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Until recently, the standard care for retinopathy of prematurity (ROP) was destructive treatment of the peripheral avascular retina, most often using laser therapy. Now, intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have been included in recommendations for treatment-warranted ROP. The three anti-VEGF agents used to treat ROP are bevacizumab, ranibizumab, and aflibercept and clinical trials using, a variety of treatment strategies, have shown all three are efficacious and easy to administer. Intravitreal Bevacizumab is most used in the US, and ranibizumab has been approved for ROP use in Europe. In 2023, the FDA approved aflibercept for treatment of severe ROP. We summarize the clinical trial results and provide a side-by-side comparisons of the three drugs. Despite FDA approval of the use of aflibercept to treat ROP, there is a need for more research as the body of knowledge regarding this agent to treat ROP is limited., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: To evaluate the treatment outcomes of subthreshold micropulse laser (SMPL) with a wavelength of 670 nm (red) for treatment-naïve diabetic macular edema (DME)., Methods: A retrospective observational study which included 42 eyes in 34 patients diagnosed with treatment-naïve DME was conducted. Twenty-one eyes underwent red SMPL and the other 21 eyes underwent intravitreal injection of aflibercept (IVA) as initial treatment and were followed up for 12 months. Best-corrected visual acuity (BCVA), central retinal thickness (CRT) on optical coherence tomography (OCT), vessel density (VD), and foveal avascular zone area on OCT angiography (OCTA) were measured and compared between the two groups., Results: In the red SMPL group, the mean BCVA slightly improved from 0.29 ± 0.28 at baseline to 0.22 ± 0.29 at 12 months (p = 0.18), while the mean CRT significantly decreased from 472 ± 200 µm at baseline to 320 ± 136 µm at 12 months (p = 0.003). At 12 months from baseline, the mean change in BCVA and CRT were similar between the red SMPL and IVA groups (p = 0.79 and p = 0.31, respectively). No significant change was detected in OCTA parameters except for VD at the nasal section in the red SMPL group., Conclusion: Red SMPL for treatment-naïve DME maintained BCVA and significantly reduced CRT at 12 months. These treatment outcomes were equivalent to IVA in real-world settings, which tend to be inferior to clinical trials., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Assess 5-year all-cause mortality (ACM), hemorrhagic stroke, ischemic stroke, and myocardial infarction (MI) risks in nAMD patients receiving anti-VEGF injections compared with controls., Design: Population-based retrospective cohort study using a U.S. federated health research network, containing de-identified data of 96 million patients from 1/1/2003 to 3/6/2023., Participants: nAMD Patients with anti-VEGF injections. Controls included nAMD patients without anti-VEGF injections, non-exudative AMD patients, and patients without AMD., Methods: Patients were identified using nAMD ICD-10 and anti-VEGF CPT codes and matched for age, sex, and comorbidities. Five-year relative risk of ACM (RR 1 ), hemorrhagic stroke (RR 2 ), ischemic stroke (RR 3 ), and MI (RR 4 ) in nAMD patients receiving anti-VEGF injections were calculated., Results: A total of 27,609 nAMD patients (mean diagnosis age [SD], [78.2 (10.3)]) received anti-VEGF injections; 769 nAMD patients without injections (75.8 [12.2]), 27,599 non-exudative AMD patients (78.2 [10.3]), and 21,902 no-AMD patients (76.1 [10.5]) were identified. After matching, nAMD patients receiving injections did not show increased risk versus nAMD patients without injections (RR 1 , 0.66; 95% CI [0.53, 0.82]), (RR 2 , 1.00 [0.42, 2.38]), (RR 3 , 1.70 [0.92,3.13]), (RR 4 , 0.63 [0.33, 1.18]). No increased risk was found compared to non-exudative AMD patients (RR 1 , 0.99 [0.95, 1.03]), (RR 2 , 0.94 [0.83,1.07]), (RR 3 , 1.04 [0.96, 1.12]), (RR 4 , 0.99 [0.91, 1.08]). Increased risk for ACM was observed versus no-AMD patients (RR 1 , 1.21 [1.15, 1.27]), but no other differences were found (RR 2 , 0.81 [0.70, 0.93]), (RR 3 , 1.00 [0.92, 1.09]), (RR 4 , 0.986 [0.90, 1.09])., Conclusion: Anti-VEGF injections were not associated with major cardiovascular events in nAMD patients over 5 years., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: Subretinal hyperreflective material (SHRM) is a significant biomarker for poor visual outcomes in neovascular age-related macular degeneration (nAMD); however, its relationship with fibrosis and atrophy is not well understood. This study aims to evaluate the relationship between SHRM, atrophy, and fibrosis in eyes receiving antivascular endothelial growth factor therapy for nAMD., Methods: Post-hoc analysis of the 65 patients enrolled in the SEVEN-UP study, a multicenter cross-sectional study of patients originally enrolled in the ANCHOR and MARINA trials of ranibizumab. Color fundus photographs (CFP) were reviewed and manually segmented to define regions of atrophy and fibrosis. SHRM borders on OCT volume scans were manually delineated, and thickness measurements were computed and compared in corresponding regions of atrophy and fibrosis on the CFPs., Results: Of the 65 subjects, 51 eyes showed atrophy and/or fibrosis on CFP and were included in the final analysis. Both atrophy and fibrosis regions exhibited SHRM on OCT. The mean SHRM thickness on OCT was significantly greater in CFP-fibrosis regions (44.19 ± 46.95 μm) compared with CFP-atrophy regions (14.28 ± 13.35 μm; p < 0.001). Additionally, the average maximum height of SHRM in fibrotic regions (268.04 ± 130.05 μm) was significantly thicker than in atrophic regions (121.95 ± 51.17 μm; p < 0.001)., Conclusions: Although atrophy and fibrosis are thought to be different end-stage outcomes in eyes with nAMD, they both demonstrate SHRM on OCT; the main distinction being thickness. Given these similarities, these regions of nAMD-associated atrophy may be better-termed "atrosis" to distinguish these lesions from typical atrophy in the absence of neovascular disease., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD)., Design: Randomized, double-masked, multicenter, active-controlled, noninferiority phase II study., Participants: A total of 231 treatment-naive and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled., Methods: Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa, or 2 mg aflibercept groups. Participants in all groups received 3 initial monthly loading doses, followed by treatment every 8 weeks, with assessment every 4 weeks up to week 52., Main Outcome Measures: The primary end point was the mean best-corrected visual acuity (BCVA) change from baseline to week 36. The prespecified noninferiority margin was set as -5 letters (80% confidence interval [CI])., Results: Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, and +12.0 letters, respectively; least squares mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups., Conclusions: Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024. Published by Elsevier Inc.)

Genome or prime editing has become a promising tool for the treatment of hereditary disorders affecting the inner retina, such as dominant optic neuropathies. In vivo delivery of gene editors, such as Cas9, is typically achieved using recombinant adeno-associated virus (rAAV) vectors, which have a broad range of cellular tropisms and are well tolerated following intravitreal administration. Owing to the large size of gene editing constructs and the limited carrying capacity of rAAV (<5.1 kb) it is unfortunately usually necessary to split therapeutic transgene cassettes across multiple co-administered vector genomes. While the efficiency with which multiple vector genomes recombine following cellular entry has been studied extensively, another potentially limiting factor is the likelihood of target cells (e.g. retinal ganglion cells) receiving two or more vectors containing genomes that correspond to the full-length expression cassette when recombined. In this study we examine the efficiency with which two or more vector genomes transduce various retinal cell types following intravitreal administration. rAAV2/2[MAX] vectors expressing individual fluorescent reporters (GFP, BFP or mCherry) were co-injected intravitreally singly or in combination (dual or triple), allowing the extent of co-transduction to be assessed through multimodal in vivo imaging, electroretinography, flow cytometry and post-mortem histology. We find that intravitreal co-administration of vectors containing multiple genomes is well tolerated - with no observed alterations in retinal thickness or ERG amplitudes - but that co-transduction efficiency decreases significantly with increasing genome number. As such co-transduction of multiple vectors may be a major bottleneck limiting gene editing of inherited disorders affecting the inner retina., Competing Interests: Declaration of interests The authors declare no conflicts of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Endophthalmitis is a blinding disease that may lead to permanent vision loss. The diagnosis of endophthalmitis relies on clinical findings. It is crucial to identify causative microorganisms in time for subsequent treatment and saving vision. For a long time, cultures of vitreous and/or aqueous humours have been the gold standard for the diagnosis of endophthalmitis. The development of modern molecular diagnostic techniques has brought new opportunities for identifying pathogens rapidly and improving sensitivity. Intravitreal antibiotic injection has the become standard treatment option for infectious endophthalmitis in clinical practice, however, the role and timing of pars plana vitrectomy remains controversial. Moreover, the development of new drugs for intravitreal injection and posterior segment drug delivery systems is expected to achieve the transition from invasive to non-invasive management. Thus, endophthalmitis is an ophthalmic emergency and timely diagnosis and treatment are crucial for preserving vision., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To assess the real-world outcome of best-corrected visual acuity after 2-year intervention for treatment-naive diabetic macular edema since the approval of anti-vascular endothelial growth factor therapy., Methods: A total of 1,780 treatment-naive eyes with diabetic macular edema for which intervention was initiated between 2015 and 2019, and which were followed for 2 years, were extracted from the longitudinal medical records of 37 retinal disease institutions in Japan. Interventions included anti-VEGF therapy, topical corticosteroid therapy, macular photocoagulation, and vitrectomy. The baseline and final best-corrected visual acuity, and the number and timing of interventions were recorded. Eyes were classified according to the year in which intervention was initiated., Results: Over a 2-year period, best-corrected visual acuity improved annually, finally reaching seven letters. The proportion of eyes in which good vision was maintained (best-corrected visual acuity >20/40) increased to 73.3% in the latest period. The administration of anti-VEGF therapy remained stable, accounting for approximately 90% of eyes. Notably, the proportion of eyes receiving anti-VEGF drugs as first-line treatment increased dramatically to approximately 80%., Conclusion: Anti-VEGF therapy has become the first-line treatment since the approval of anti-VEGF drugs for diabetic macular edema. These findings reflect the evolution of diabetic macular edema treatment and highlight the superiority of anti-VEGF therapy and its increased uptake over time., Competing Interests: The authors declare no conflicts of interest in association with the present study., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To report the safety and efficacy of brolucizumab (Beovu) 6 mg versus aflibercept (Eylea) 2 mg administered every 4 weeks in participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid after the week 52 up to week 104., Design: Multicenter, randomized, double-masked phase 3a study., Participants: Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-VEGF treatment)., Methods: Study eyes were randomized 2:1 to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks or until study termination., Main Outcome Measures: All available efficacy (analysis of noninferiority in mean best-corrected visual acuity [BCVA], central subfield thickness [CST], fluid-free status [no intraretinal fluid and no subretinal fluid]) and safety data up to study termination, including data up to week 104 for those participants who completed the study before its termination. All P values after week 52 were nominal and reflect observed data for the efficacy analyses., Results: Brolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in mean BCVA change from baseline to week 104 (least squares mean difference, -0.4 ETDRS letters; 95% confidence interval [CI], -3.7 to 3.0; P = 0.0169). The proportion of eyes with ≥15-letter loss was 6.2% for brolucizumab and 4.7% for aflibercept (P = 0.7762), and a greater proportion of eyes were fluid free at week 104 (52.5% brolucizumab vs. 28.2% aflibercept; 95% CI, 11.9-37.3; P < 0.001) in eyes treated with brolucizumab versus aflibercept. Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab versus 6.1% (0% and 0.6%) for aflibercept., Conclusions: Consistent with 52-week results, brolucizumab 6 mg every 4 weeks was noninferior in mean BCVA change, with anatomic outcomes superior to aflibercept 2 mg every 4 weeks from baseline to week 104 or study termination. The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab versus aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks after the loading regimen., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: The Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration (nAMD). Portal (NCT03683251) is evaluating long-term safety and tolerability of the PDS in patients with nAMD who completed the phase II Ladder (NCT02510794) or phase III Archway (NCT03677934) trials., Design: Multicenter, nonrandomized, open-label, extension clinical trial., Participants: All-PDS safety population (N = 555) comprises patients enrolled in Portal who completed Ladder or Archway. Because of data availability, efficacy population comprises Ladder-to-Portal patients only: patients who previously received PDS 10, 40, or 100 mg/mL pro re nata (as-needed [PRN]; n = 58, 62, and 59, respectively) or monthly intravitreal ranibizumab 0.5-mg injections (monthly ranibizumab; n = 41) in Ladder and subsequently enrolled in Portal., Methods: Ladder patients received PDS refill-exchanges PRN or monthly ranibizumab. Archway patients received PDS 100 mg/mL with fixed refill-exchanges every 24 weeks (Q24W) or monthly ranibizumab. Once enrolled in Portal, all patients receive PDS Q24W from day 1., Main Outcome Measures: Ocular adverse events of special interest (AESIs); changes from baseline in best-corrected visual acuity (BCVA) and center point thickness (CPT); supplemental ranibizumab treatment between refill-exchange procedures; and PDS Patient Preference Questionnaire results., Results: In the All-PDS safety population (mean follow-up, 111 weeks), 137 (24.7%) patients had ≥1 ocular AESI; most common were cataract (11.4%), vitreous hemorrhage (6.1%), and conjunctival thickening (bleb)/filtering bleb leak (6.3%). Endophthalmitis occurred in 11 of 555 (2.0%) patients. For Ladder-to-Portal patients previously treated with PDS 100 mg/mL or monthly ranibizumab, BCVA remained stable from baseline to month 48; mean (95% confidence interval) changes from baseline were 0.1 (-6.6 to 6.8; n = 31) and 2.3 (-9.4 to 14.1; n = 15) letters, respectively; CPT remained stable through month 48. Approximately 95% of patients did not need supplemental treatment before each refill-exchange for >2 years since Portal enrollment. Of Ladder-to-Portal previous monthly ranibizumab patients, 92% preferred the PDS over injections., Conclusions: Interim results from Portal suggest 4-year maintenance of visual/anatomic outcomes with PDS 100 mg/mL, with the PDS preferred to monthly injections. Long-term safety profile of the PDS is well characterized., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the incidence and factors associated with subretinal fluid (SRF) resolution during SRF-tolerating treatment in patients with neovascular age-related macular degeneration., Methods: This retrospective study included patients diagnosed with neovascular age-related macular degeneration who exhibited fovea-involving residual SRF persisting for at least 6 months during aflibercept treatment. Patients who showed SRF resolution despite maintaining the injection intervals were included in the resolution group, while those who exhibited persisting SRF throughout the study period were included in the nonresolution group. The incidence and associated factors of SRF resolution without reducing the injection interval were evaluated. Furthermore, the frequency of successfully extending the injection intervals while maintaining SRF resolution was identified., Results: In total, 65 patients with neovascular age-related macular degeneration were included (32 and 33 in the resolution and nonresolution groups, respectively). When compared with the nonresolution group, the resolution group showed a lower mean height of SRF (67.7 ± 33.4 vs. 109.9 ± 44.9 µ m, P < 0.001) and a lower maximum height of SRF (138.3 ± 88.6 vs. 176.2 ± 76.9 µ m, P = 0.034). In multivariate analysis, the mean SRF height ( P = 0.001), maximum SRF height ( P = 0.006), and interval of anti-vascular endothelial growth factor injections ( P = 0.023) were significantly associated with the resolution of SRF. In the resolution group, 14 patients (43.8%) successfully expanded the injection interval., Conclusion: During SRF-tolerating treatment for neovascular age-related macular degeneration, a substantial proportion of patients exhibited resolution of fluid without shortening the injection interval. Patients with lesser residual SRF during treatment were more likely to achieve fluid resolution. After SRF resolution, injection intervals can be extended in more than 40% of patients.

Purpose: To evaluate the efficacy and safety of dexamethasone implantation in the supraciliary (SC) space, a novel and potential effective implantation site, compared to intravitreal (IV) application., Methods: This prospective study included 39 eyes of 38 patients with macular oedema (ME) who underwent SC and IV dexamethasone implantation (SC-DEX and IV-DEX). Patients were randomly assigned to treatment groups and followed for 3 months. Preoperative and postoperative assessments included maximum retinal thickness (MRT), change in central retinal thickness between consecutive visits (ΔCRT), intraocular pressure (IOP), and best corrected visual acuity (BCVA)., Results: Both SC-DEX and IV-DEX groups showed significant MRT reductions during at follow-up. In the SC group, MRT significantly decreased at 1st and 3rd months (p = 0.0002 for both), but not at 1st week (p = 0.2517). In the IV-DEX group, significant reductions in MRT were observed at all postoperative visits: 1st week (p = 0.0002), 1st month (p = 0.0004), and 3rd month (p = 0.0003). There were no significant differences in the change in ΔCRT between the SC-DEX and IV-DEX groups at any visit (p > 0.05). IOP did not show significant changes (p > 0.05). BCVA improved significantly in the SC group compared to the IV-DEX group during the first week (p = 0.014). No other perioperative or postoperative sight-threatening complications were noted in either group, including hypotony or endophthalmitis., Conclusion: SC-DEX shows promise as an alternative for managing ME, offering similar effectiveness to IV-DEX with safe profile. Further studies are needed to confirm its long-term safety and efficacy., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: To examine rates of submacular hemorrhage in patients undergoing anti-vascular endothelial growth factor (VEGF) injections, comparing rates between specific anti-VEGF agents., Design: Retrospective clinical cohort study., Methods: All patients in the database from January 2015 to November 2023 with a diagnosis of neovascular age-related macular degeneration and accompanying submacular hemorrhage (SMH). SMH prevalence and associated anti-VEGF injection type were analyzed in 140,915 eyes (of which 9107 had SMH) in a nationwide aggregated electronic health care database using chi-square test of proportion. Visual acuity (VA) data was assessed using 2-sample independent t-tests. The primary outcome was rate of SMH per injection type. Secondary datapoints examined were time between SMH diagnosis and last anti-VEGF injection, number of injections before SMH, treatment interval at time of SMH, VA before and at 12 months after SMH, eyes undergoing pars plana vitrectomy (PPV) within 30 days of SMH, and VA before PPV and at 12 months after PPV., Results: The last injection type in eyes with SMH was bevacizumab in 3430 (37.8%) eyes, brolucizumab-dbll in 46 (0.51%) eyes, aflibercept in 3221 (35.4%) eyes. Ranibizumab in 2246 (24.7%) eyes, and faricimab-svoa in 155 (1.7%) eyes. Rates of SMH were significantly higher (P ≤ .001) for last injection with bevacizumab compared to every other injection type. Rates of SMH were significantly lower (P = .0004) for last injection with faricimab-svoa or ranibizumab injections each had significantly shorter (mean and standard deviation 48.9 (27.9), P < .02; mean and standard deviation 59.6 (38.2), P = .003, respectively) mean time between SMH diagnosis and last injection than did patients undergoing any other injection. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type among all patients. The number of patients who underwent PPV were 52 (1.51%) for bevacizumab, 4 (8.7%) for brolucizumab-dbll, 58 (1.8%) for aflibercept, 41 (1.8%) for ranibizumab, and 3 (1.9%) for faricimab-svoa. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type in patients undergoing PPV., Conclusions: Faricimab may be more protective than other anti-VEGF injections against SMH in patients with neovascular age-related macular degeneration., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Due to its unique physiological structure and functions, the eye has received considerable attention in the field of adeno-associated virus (AAV) gene therapy. Inherited retinal degenerative diseases, which arise from pathogenic mutations in mRNA transcripts expressed in the eye's photoreceptor cells or retinal pigment epithelium (RPE), are the most common cause of vision loss. However, current retinal gene therapy mostly involves subretinal injection of therapeutic genes, which treats a limited area, entails retinal detachment, and requires sophisticated techniques. Intravitreal (IVT) injection provides an alternative method with less invasion and more convenience for retinal gene therapy. In the present study, we performed a directed evolution via DNA shuffling in RHO-GFP mice and identified a novel recombinant AAV vector (AAV-M04) suitable for IVT injection in the gene delivery of retinal tissue. Compared with AAV2, AAV9, and AAV2.7m8, AAV-M04 vector exhibited higher transduction efficiency in retinal ganglion cell line-5 (RGC-5) cells as well as in human embryonic stem cell derived retinal organoids. Importantly, when delivered via IVT injection in mice, the AAV-M04 vector also showed better delivery efficiency of transgene as indicated by the red fluorescence protein mScarlet. The red fluorescence was distributed in a wider retinal area of AAV-M04 injected mice, suggesting the potent retinal targeting of AAV-M04 vector. In addition, AAV-M04 qualities including the packaging efficiency, the thermal stability, and the capsid integrity were superior to controls, which were important in drug manufacture. In summary, we screened a novel AAV-M04 vector with great retinal-targeting via IVT injection, which provides the potential of AAV-M04 for effective gene therapy of retinal diseases., Competing Interests: Declaration of competing interests Fei Wu, Yixin Yu and Wei Peng are inventors on patent applications filed by Shanghai Langsheng Biotechnology Co., Ltd. related to novel AAV variant equences and in vivo functions. Fei Wu serves as the Senior Director of R&D Operations at Shanghai Langsheng Biotechnology Co., Ltd. All other authors declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Topic: To evaluate the efficacy and safety of anti-VEGF and panretinal photocoagulation (PRP) for the treatment of proliferative diabetic retinopathy (PDR). The outcomes examined are changes in best-corrected visual acuity (BCVA), neovascularization (NV), central macular thickness (CMT), and adverse outcomes., Clinical Relevance: Diabetic retinopathy is the leading cause of blindness in working-aged adults globally. At present, no consensus has been reached on the optimal choice for the treatment of PDR., Methods: Cochrane, Embase, PubMed, Scopus, Web of Science, and CiNAHL were searched for articles from their inception to June 2023 according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis. The review was registered prospectively with PROSPERO (CRD42023437778). Tool data analysis was performed using RevMan software version 5.4 (Review Manager [RevMan] [computer program], The Cochrane Collaboration, 2020). Randomized control trials (RCTs) of PDR patients treated with anti-VEGF, PRP, or a combination were included. Risk of bias was assessed using the Rob2 assessment tool (revised tool for risk of bias in randomized trials), and certainty of evidence was assessed with the Grading Recommendations Assessment, Development and Evaluation (GRADE) approach., Results: Nineteen studies were included, with 1361 patients (n = 1788 eyes) treated for PDR with either anti-VEGF (n = 274), PRP (n = 482), or combination (n = 320). Our results show more favorable BCVA outcomes with anti-VEGF compared with PRP at 3 months (mean difference [MD] = 2.35 letters; 95% confidence interval [CI], 1.18-3.52; I 2  = 0%) and 12 months follow-up (MD = 3.39 letters; 95% CI, 0.63-6.14; I 2  = 26%). Combination treatment showed better BCVA outcomes compared with PRP at 12 months (MD = 4.06 letters; 95% CI, 0.26-7.86; I 2  = 0%). Combination showed lower CMT at 3 months (MD = -33.10 μm; 95% CI, -40.12 to -26.08; I 2  = 25%) and 6 months (MD = -34.28 μm; 95% CI, -55.59 to -12.97; I 2  = 85%) compared with PRP, but CMT results were similar at 12 months. Complete regression of total NV (NVT) was more likely with anti-VEGF compared with PRP (odds ratio = 6.15; 95% CI, 1.39-27.15; I 2  = 80%). Posttreatment vitreous hemorrhage, vitrectomy, and increased intraocular pressure events were similar between the anti-VEGF and combination groups compared with PRP; however, macular edema results favored the anti-VEGF over the PRP group. Using the GRADE assessment, BCVA evidence was rated to be of moderate certainty, whereas CMT and NVT evidence certainty was rated as very low., Conclusion: Anti-VEGF and combination treatments could be regarded as alternative approaches to PRP alone in the management of PDR after engaging in a shared decision-making process based on patients' adherence, diabetic macular edema status, and preference. Limitations of this meta-analysis include the heterogeneity in participants' characteristics, treatment regimens, and outcome reporting between studies. Further RCTs should be conducted to compare the effectiveness of these treatments in the long term., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2025. Published by Elsevier Inc.)

The lack of effective treatments for dry age-related macular degeneration (AMD) is in part due to a lack of a preclinical animal model that recapitulates features of the clinical state including macular retinal pigment epithelium (RPE) degeneration, also known as geographic atrophy (GA). A nonhuman primate model of GA was developed and its responsiveness to an approved treatment, avacincaptad pegol (ACP), a complement C5 inhibitor, was evaluated. Intravitreal (ivt) administration of sodium iodate (SI) into one eye of male Macaca fascicularis leads to retinal areas (mm 2 ) of hyper- or hypo-autofluorescence. Qualitative changes to the retinal structure over time were observed with spectral domain optical coherence tomography (OCT). Six days after SI administration, prior to treatment, mean (± SEM) GA of all eyes was 8.2 ± 1.8 mm 2 . Following randomization to treatment groups, either vehicle or ACP was ivt injected and treatment was continued every 4 weeks, for a total of four treatments. Sixteen weeks after SI administration, the GA area in vehicle-treated eyes was 18.9 ± 6.6 mm 2 , whereas GA in ACP-treated eyes was 11.4 ± 4.0 mm 2 , a reduction by about 36%. Increased, followed by decreased, overall macular thickness was observed with OCT over time following SI administration. Treatment with ACP did not change alter macular thickness thinning. Geographic atrophy-like lesions that expand over time are observed following SI administration. The current macaque model could be utilized to further explore the mechanism of dry AMD and to develop more novel therapeutics., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Objective: To assess the effect of the COVID-19 pandemic on injection intervals among patients treated for neovascular age-related macular degeneration., Design: Retrospective cohort study., Participants: Patients treated at a single practice using a treat-and-extend regimen with intravitreal aflibercept between December 2018 and April 2021., Methods: The primary outcome was the change in injection intervals. Secondary outcomes included differences in best-recorded visual acuity (BRVA) and central subfield thickness (CST). Associations were evaluated with linear mixed-effects modelling., Results: This study included 1839 injections from 185 eyes (141 patients). The median (interquartile range) injection intervals in the pre-COVID-19 and COVID-19 periods were 60 (42-70) and 70 (49-90) days, respectively. The pandemic was associated with a mean injection interval lengthening of 7.2 days (P < 0.001), a decrease in BRVA of 3.1 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and a reduction in CST of 14.7 μm (P = 0.003). The presence of exudative intraretinal fluid was associated with a reduction in treatment intervals of 11.1 days (P < 0.001), a reduction in BRVA of 1.9 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and an increase in CST of 52.4 μm (P < 0.001). The presence of subretinal fluid was associated with a reduction in treatment intervals of 8.5 days (P < 0.001) and an increase in CST of 21.6 μm (P < 0.001)., Conclusions: This real-world study estimated that the severe acute respiratory syndrome coronavirus 2 pandemic resulted in an injection extension of 7.2 days with associated decreases in BRVA and CST that are unlikely clinically significant on a population basis. This builds on evidence suggesting that long-term vascular endothelial growth factor suppression can facilitate meaningful interval extensions while maintaining visual acuity., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the effect and factors associated with the reactivation of retinopathy of prematurity (ROP) after intravitreal conbercept or aflibercept., Methods: We retrospectively reviewed the medical records of 176 eyes diagnosed with ROP and treated with anti-VEGF therapy between January 2018 and September 2022. The rate of reactivation and complications were assessed during the follow-up period. The factors of reactivation of ROP after intravitreal conbercept or aflibercept were analyzed on the basis of clinical factors and retinal parameters., Results: Reactivation of ROP occurred in 10 eyes (13.9%) after intravitreal conbercept and 13 eyes (12.5%) after intravitreal aflibercept (P = 0.79). The interval between injection and reactivation was significantly longer in the aflibercept group than in the conbercept group (15.50 ± 4.05 vs. 5.36 ± 0.50 weeks) (P < 0.001). The central retinal arteriolar equivalent (CRAE) of aggressive ROP was larger than that of type 1 prethreshold and threshold ROP before anti-VEGF therapy (P < 0.05). Zone I and stage 3 exhibited a positive correlation with the reactivation of retinopathy of prematurity (ROP) [odds ratio (OR) = 20.15, 5.02]. The changes in CRAE of pre-and post-therapy and gestational age were identified as potential protective factors for these outcomes (OR = 0.23, 0.49)., Conclusions: Conbercept and aflibercept are effective for treating ROP. Aflibercept resulted in longer treatment intervals compared to conbercept. Zone, stage, and gestational age were associated with the reactivation of ROP. CRAE was associated with not only the severity of ROP but also its reactivation. Additionally, it may be an objective indicator in the early indication and follow-up of ROP., Competing Interests: Declarations. Ethics approval and consent to participate: This study protocol was reviewed and approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University. Parents of each infant wrote informed consent before treatment. This research was carried out in line with a named standard. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Aims: To compare effectiveness of subconjunctival triamcinolone acetonide injections and intravitreal injections of dexamethasone 700 µg implants in reducing central macular thickness (CMT) in uveitic and postoperative macular oedema (ME)., Methods: We conducted an open-label, French multicentre randomised comparative trial with a logarithmic CMT non-inferiority margin set at 0.06. Patients were adults with non-infectious inflammatory ME, without any contraindication to the treatments. They were randomised 1:1 to receive either triamcinolone or dexamethasone. The primary endpoint was the difference in CMT among treated eyes between baseline and 2 months, measured with spectral-domain optical coherence tomography. Secondary outcomes included visual acuity, laser flare, vitreous haze, duration of action, tolerance to injections and adverse events., Results: Between January 2016 and January 2020, 106 patients were enrolled (54 in the triamcinolone group and 52 in the dexamethasone group). Subconjunctival triamcinolone injections seemed to be non-inferior to intravitreal dexamethasone injections, especially at month 3 (and nearly at month 1). Nevertheless, we could not demonstrate it, with a treatment effect at month 2 of 0.05 (0.01 ; 0.09) (p value=0.001). This was corroborated by post hoc analyses in the postoperative subgroup, for whom the non-inferiority was nearly demonstrated at month 2 with a treatment effect of 0.02 (-0.03 ; 0.08) (p=0.37). There was no significant difference in the occurrence of adverse effects., Conclusion: We could not demonstrate the non-inferiority of triamcinolone injections at month 2. Nevertheless, they showed some efficacity, particularly in treating postoperative ME, being as safe as dexamethasone injections, without any loss of chance if a therapeutic switch is necessary., Competing Interests: Competing interests: M-AV: data safety monitoring board member in Comité de Protection des Personnes—Ouest IV since september 2022. Payment for expert testimony by Institut National du Cancer in 2023. BB: grants/contracts with Horus Pharma, AbbVie/Allergan. Consulting fees by Horus Pharma, AbbVie/Allergan, Novartis, Active Biotech, Acelyrin, Roche. Advisory board for Genesight. ML: consulting fees/honoraria/payments for expert testimony by Alcon, Allergan, Bausch & Lomb, DMG, Dompe, Horus Pharma, MSD, Novartis, Quantel, Santen, Shire, Topivert, Théa. Support for attending meetings and/or travel by Bausch & Lomb, Novartis, Théa. M-BR: consulting fees/honoraria/support fort attending meetings by Allergan, Horus Pharma. KA: advisory board in uveitis for Horus Pharma. CChiquet : consulting fees for AbbVie, Amo, Horus Pharma, Théa. Advisory board for Horus Pharma. LK: consulting fees/honoraria by AbbVie, Alimera, Bayer, Novartis, Roche, Théa. Support for attending meetings and/or travel by AbbVie, Bayer, Novartis. Advisory board for Alimera, Bayer, Horus Pharma, Novartis. SB: honoraria by Abbvie, Horus Pharma, Novartis, Roche. Supporting for attending meetings and/or travel by Abbvie, Bayer, Roche. Advisory board for AbbVie, Bayer, Horus Pharma. CPC-G: grants/contracts for the institution with Bayer, Novartis. Consulting fees by AbbVie/Allergan, Alcon, Apellis Pharmaceuticals, Bayer, Horus Pharma, Novartis, Roche, Théa. Honoraria and support for attending meetings and/or travel by Allergan, Bayer, Novartis, Roche. MW: consulting fees/honoraria by AbbVie., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Purpose: Myopic choroidal neovascularization (CNV) is a common reason for visual impairment. This study investigated the clinical effects of repeated intravitreal injections of ranibizumab among patients with CNV secondary to pathologic myopia., Methods: This study involved a single-center, non-randomized clinical prospective cohort research design including 39 patients with myopic CNV and a control group of 10 patients with cataract. Plasma and aqueous humor samples were analyzed to compare cytokine concentrations between the two groups and assess changes after intravitreal ranibizumab injections. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were also monitored., Results: BCVA values and CMT varied significantly after intravitreal ranibizumab injections. The study group had significantly higher plasma concentrations of vascular endothelial growth factor (VEGF)-A and significantly lower epidermal growth factor (EGF) and angiopoietin-2 concentrations than the control group. Likewise, in the aqueous humor, the study group had significantly higher concentrations of fibroblast growth factor and significantly lower concentrations of EGF and VEGF-A than the control group. The average VEGF-A content decreased significantly after 1 and 2 months relative to the baseline. Mean VEGF-D and endoglin contents at two months were significantly reduced compared to the baseline and at 1 month. The average EGF contents were significantly higher at 2 months than the baseline., Conclusion: Ranibizumab could increase the BCVA and lower the CMT and cytokines involved in angiogenesis. This study contributes to further understanding the pathogenesis of myopic CNV and promoting new drug research and development for patients with this condition., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Consent to participate: Informed consent was obtained from all individual participants included in the study. This article does not contain any studies with animals performed by any of the authors., (© 2025. The Author(s).)

Purpose: To compare the anatomical and visual outcomes in eyes with submacular hemorrhage (SMH) treated with a combination of ranibizumab (RBZ) either innovator or biosimilar (Razumab) and intravitreal perfluoropropane gas (C 3 F 8 )., Methods: Treatment naïve neovascular age related macular degeneration (n-AMD) patients with SMH were retrospectively analyzed. Patients received either innovator or biosimilar RBZ (3 loading doses followed by pro re nata regimen) and single injection of intravitreal C 3 F 8 . Optical coherence tomography (OCT) was performed at baseline, 1, 3 and 6 months. Changes in best corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 6 months. P value ≤ 0.05 was considered statistically significant., Results: A total of 67 eyes (35 and 32 eyes in innovator and biosimilar group respectively) were analyzed. BCVA improved from 1.15 ± 0.19 to 0.51 ± 0.23 logarithm of minimum angle of resolution (logMAR) in innovator RBZ group (p < 0.001) and from 1.17 ± 0.15 to 0.53 ± 0.20 logMAR in biosimilar RBZ group (p < 0.001). Similarly, mean CMT showed significant reduction in both groups at 6 months (innovator RBZ: 609.5 ± 50.1 μm to 254.3 ± 20.3 μm, p < 0.001; biosimilar RBZ: 602.3 ± 58.9 μm to 251.8 ± 22.3 μm, p < 0.001). Intergroup comparisons between innovator and biosimilar RBZ showed no differences in either BCVA or CMT at all time points (all p values > 0.05). Mean number of intravitreal injections was marginally higher in innovator group compared to biosimilar RBZ (4.37 ± 0.49 vs. 4.22 ± 0.42; p = 0.18)., Conclusion: Biosimilar RBZ may act as a viable alternative to innovator RBZ to treat SMH with comparable anatomical and visual outcomes at 6 months., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by ethics committee of Disha Eye Hospitals, Kolkata, India Hospital. (Reg. number ECR/846/Inst/WB/2016/RR-19: EC-2023-31) The study was conducted in accordance with the tenets of the Helsinki Declaration. All patients gave informed consent before undergoing intravitreal injections. Consent for publication: not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: To report a case of intraocular inflammation (IOI) after intravitreal injection of aflibercept 8 mg for treatment-refractory neovascular age-related macular degeneration., Case Presentation: An 80-year-old man with diabetes mellitus had neovascular age-related macular degeneration refractory to treatment with aflibercept 2 mg. Despite ten injections of faricimab, the exudation remained, and we switched to brolucizumab, which resulted in a mild IOI. The IOI improved with only topical steroids, and we switched back to aflibercept 2 mg for the exudation. However, the exudation remained, and we decided to switch to aflibercept 8 mg after careful discussion with the patient. Two weeks later, he experienced minor ocular pain and photophobia. One month later, although a dry macula was achieved, severe visual impairment occurred due to anterior chamber inflammation, retinal vasculitis, and retinal vascular occlusion. We diagnosed the severe IOI following aflibercept 8 mg and immediately started steroid eye drops and a sub-Tenon injection of triamcinolone acetonide. Although the inflammation resolved, his visual acuity did not improve., Conclusions: This case demonstrated a potential dose-dependent inflammatory response following aflibercept 8 mg, which did not occur with aflibercept 2 mg in patients with a history of intraocular inflammation., Competing Interests: Declarations. Ethics approval and consent to participate: This retrospective study was conducted in accordance with the tenets of the Declaration of Helsinki. The institutional review board at Tokyo Women’s Medical University School of Medicine approved the study, which included OCT observation of eyes with macular and retinal disorders, observational study of age-related macular degeneration, and similar disorders. Consent for publication: The patients have consented to the submission of this case report to the journal for publication. Written informed consent was obtained for all presented case details and accompanying images. Competing interests: The authors declare no competing interests. The author(s) have made the following disclosure(s): funding statement: Dr. Hashiya receives lecturing and travel fees from Senju Pharmaceutical, Chugai Pharmaceutical, Kowa, Novartis Pharma, and AMO. Dr. Maruko receives lecturing and travel fees from Bayer Pharmaceuticals, Novartis Pharma, Japan Alcon, Santen, Senju Pharmaceutical, Topcon, Chugai Pharmaceutical, Canon, Nidek, and Nikon. He holds a patent. Dr. Miyaguchi has nothing to disclose. Dr. Ruka Maruko receives lecturing and travel fees from Chugai Pharmaceutical and Kyowa Kirin. Dr. Hasegawa receives lecturing and travel fees from Novartis Pharma, Alcon Pharma, Santen, Kowa, Senju Pharmaceutical, R.E. Medical, Nikon Health Care Japan, JFC Sales Plan, Otsuka Pharmaceutical, and Japan Beringer Ingelheim. Dr. Iida receives grants from Nidek, Topcon, Santen, Novartis Pharma, Senju Pharmaceutical, Japan Alcon, HOYA, and AMO, consultant fees from Bayer Pharmaceuticals, Novartis Pharma, Chugai Pharmaceutical, Japan Beringer Ingelheim, and Janssen Pharma, and received lecturing and travel fees from Bayer Pharmaceuticals, Novartis Pharma, Japan Alcon, Santen, Senju Pharmaceutical, Topcon, Chugai Pharmaceutical, Canon, Nidek, Otsuka Pharmaceutical, Nikon, and Kyowa Kirin. He holds a patent., (© 2024. The Author(s).)

Bleb-like retinal detachment (BLRD) in posterior zone 1 retinopathy of prematurity (ROP) presents a significant therapeutic challenge and is associated with a guarded visual prognosis. We present a case of a female infant born preterm with a birth weight of 1100 g. Examination revealed bilateral stage 4 aggressive ROP in posterior zone 1 with BLRD. Given the extent of retinal detachment, a combination of bilateral intravitreal bevacizumab injection, followed by lens-sparing vitrectomy surgery was performed. The baby tolerated the procedures well. The initial postoperative course was uneventful, and the child showed good anatomical and visual success. Through this case, we aim to discuss the risk factors associated with BLRD in ROP, the specific treatment challenges encountered and the potential treatment outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Purpose: To report a rare case of a Coats-like response developing after vitreoretinal surgery for proliferative diabetic retinopathy (PDR) and its successful management with retinal laser photocoagulation and adjunctive intravitreal steroids., Case Description: A 52-year-old woman with a five-year history of type 2 diabetes mellitus and hypertension presented with decreased vision in the left eye (counting fingers at 1 m). Examination revealed high-risk PDR in both eyes, with a subtotal macula-off combined retinal detachment in the left eye. The patient underwent pan retinal photocoagulation for the right eye and vitreoretinal surgery with silicone oil tamponade for the left eye. Postoperatively, the retina remained attached, but progressive increase in hard exudates in the inferotemporal quadrant was noted in the left eye. Wide-field fluorescein angiography showed temporal capillary dropout and leakage corresponding to the exudates, consistent with a Coats-like response., Results: Silicone oil removal combined with targeted endolaser photocoagulation and intravitreal triamcinolone acetonide injection resulted in a complete resolution of the subretinal lipid exudation. Two weeks postoperatively, the retina remained well-attached, but best-corrected visual acuity declined to 6/60 due to posterior subcapsular cataract progression. Optical coherence tomography confirmed the resolution of subretinal lipid exudation, and the patient was advised to undergo cataract surgery., Conclusion: This case highlights the occurrence of a Coats-like response following vitreoretinal surgery for PDR, potentially triggered by retinal ischemia and surgical inflammation. Timely intervention with laser photocoagulation, and adjunctive intravitreal corticosteroids can effectively manage such responses., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: To evaluate the efficacy and safety of intravitreal injections of 4 mg (high dose) of aflibercept in treatment-naive patients with neovascular AMD(nAMD) with treat and extend(TREX) dosing regimens, and to determine the frequency of injections., Methods: In this interventional, retrospective study a total of 15 eyes of 14 patients (eight female and 9 male) with nAMD were included. All patients were examined and OCT imaging was performed at the time of initial presentation, on the day of each injection and at subsequent follow-up visits. Each eye received intravitreal injections of 4 mg/0.1 mL aflibercept at the dose of every 4 weeks for three months (loading phase) after that 4 mg high dose of aflibercept was applied as the TREX regime. The eyes with a minimum follow-up time of 12 months are included., Results: The mean age of the patients was 74.9 ± 7.3(61-85) years and the mean follow-up time was 20.33 ± 8.7(12-34) months. Total number of injections were 9.3 ± 3.0 (5-14) during the follow-up period. A statistically significant increase was found in terms of best-corrected visual acuity and central macular thickness between mean baseline values and at 1, 3, 6, 12 months, and the final examination(p < 0.05 for each comparison). No complication was observed during follow-up., Conclusions: High-dose Aflibercept of 4 mg/0.1 mL application with the TREX regimen was found to be efficient and safe. High-dose may also help to reduce the frequency of injections and visits in the follow-up period in eyes with nAMD. Prospective studies with large series are warranted., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The study followed the tenets of the Declaration of Helsinki and was approved by the ethics committee of University of Acibadem., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)

Dual inhibition of the angiopoietin (Ang)/Tie and vascular endothelial growth factor (VEGF) signalling pathways in patients with retinal diseases, such as neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DME), may induce greater vascular stability and contribute to increased treatment efficacy and durability compared with treatments that only target the VEGF pathway. Faricimab, a bispecific intravitreal agent that inhibits both VEGF and Ang-2, is the first injectable ophthalmic drug to achieve treatment intervals of up to 16 weeks in Phase 3 studies for nAMD and DME while exhibiting improvements in visual acuity and retinal thickness. Data from real-world studies have supported the safety, visual and anatomic benefits and durability of faricimab, even in patients who were previously treated with other intravitreal agents. These evidence-based expert recommendations from a panel of retina specialists consolidate current evidence with clinical experience for the optimal use of faricimab in patients with nAMD or DME, with a focus on switching from an anti-VEGF agent to faricimab., Competing Interests: Competing interests: DTW has received consulting fees from AbbVie, Alcon, Apellis, Astellas, Bausch Health, Bayer, Biogen, Hoffmann-La Roche, Novartis, Regeneron, Ripple Therapeutics and Zeiss and has received grants/research support from Bayer, Hoffmann-La Roche and Novartis. SA has been a consultant for Hoffmann-La Roche, Bayer, Novartis and Apobiologix and a speaker for Hoffmann-La Roche. DM has been an advisor for Alcon, Apellis, Bayer, Hoffmann-La Roche, Novartis, Novo Nordisk and Preceyes and has received research support from Alcon, Apellis, Bayer, Ionis, Janssen, Opthea, RegenXBio, Preceyes and Hoffmann-La Roche. SS has been a consultant to Novartis, Bayer, Biogen and Hoffman-La Roche and has received research funding from Novartis and Bayer. DY has received honoraria from Hoffmann-La Roche, Bayer, Novartis and Apellis and has received research grants from Hoffmann-La Roche and Alimera Sciences., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Autophagic dysfunction-induced deterioration of the retinal microenvironment drives the progression of wet age-related macular degeneration (wAMD). The efficacy of single-target anti-VEGF antibodies in treating wAMD has long been suboptimal due to the intricate interplay between autophagy dysfunction, oxidative stress, and angiogenesis. Here, we introduce an intravitreal hydrogel depot, named Rab&Rapa-M@G, consisting of rapamycin-loaded microemulsion (Rapa-M, an mTOR inhibitor), ranibizumab (anti-VEGF antibody), and a thermosensitive hydrogel matrix. A single intravitreal injection of Rab&Rapa-M@G can sustainably deliver Rapa-M and ranibizumab to the retinal pigment epithelium for at least 14 days. This formulation significantly improves retinal autophagic flux homeostasis and reduces oxidative stress injury in wAMD mice by modulating the AMPK/mTOR/HIF-1α/VEGF and AMPK/ROS/HO-1/VEGF pathways. Consequently, it synergistically disrupts the "autophagic dysfunction-oxidative stress-angiogenesis" loop, leading to a remarkable reduction in choroidal neovascularization area and retinal damage compared to ranibizumab alone. Notably, the sequential administration of ranibizumab and Rab&Rapa-M@G further enhances the overall anti-wAMD efficacy, achieved through sequential delivery of Rab and Rapa, allowing for a more precise grasp of the treatment window. In conclusion, this hydrogel depot design, with its sequential and sustained delivery of mTOR inhibitors and anti-VEGF antibodies, offers a promising strategy for multi-target synergistic therapy in wAMD., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024. Published by Elsevier B.V.)

Central serous chorioretinopathy (CSC) is a known side effect of systemic steroid therapy. The role of intravitreal steroids in causing CSC is controversial. We present two cases of acute CSC that developed after intravitreal steroid injections. One was a case of diabetic macular oedema; another was a case of branch retinal vein occlusion-related macular oedema. Both cases showed complete resolution of cystoid oedema after intravitreal triamcinolone acetonide injection, but there was a progressive increase in neurosensory detachment (NSD), leading to a suspicion of CSC. Fundus fluorescein angiography confirmed the diagnosis. The first case was treated with focal laser, and the second one was treated with oral eplerenone. There was complete resolution of NSD in both cases. This report adds to the evidence that intravitreal steroids can indeed cause acute CSC. A high index of suspicion for CSC should be maintained in cases where NSD increases following intravitreal steroid administration., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: This case report describes a rare case of Coats disease in adult female patient with preserved vision after intravitreal Aflibercept injection and laser photocoagulation., Case Presentation: A female patient of Asian Palestinian descent, aged 20, exhibited a progressive and painless deterioration in the vision of her left eye over a period of two weeks. She exhibited no additional ocular symptoms. Prior to her presentation, she had no notable medical history and her vision was normal in both eyes. Inferotemporal telangiectasia, sausage-like blood vessels with perivascular sheathing in the peripheral fundus, extensive exudate involving the macula, severe macular edema, and localized inferotemporal exudative retinal detachment were observed upon examination of the posterior segment of her left eye. Following this, optical coherence tomography (OCT) identified subretinal exudate, intraretinal and subretinal fluid. After establishing the diagnosis of stage 3 Coats' disease, the patient was treated with intravitreal Aflibercept (Eylea) injections and sectoral laser photocagulation. The third injection resulted in the absence of intraretinal and subretinal fluid by OCT, but the subretinal exudate remained unresolved. One month subsequent to the previous injection, FFA guided sectoral laser photoagulation was applied to the inferiotemporal ischemic area. The patient was subsequently monitored monthly, and her vision improved. Five months after treatment, her vision has improved to 0.7 (6/8.7) and she has remained stable ever since. At present, the patient is undergoing routine outpatient follow-up., Conclusion: Coats disease is an idiopathic, progressive disease that mostly affects male infants, yet adult cases have been documented. Our case and the existing body of literature indicate that adult individuals have a favorable visual prognosis in the small proportion of cases where this occurs. It appeared that the implementation of intravitreal therapies and increased use of lasers led to enhanced visual outcomes. It is recommended to perform lifelong follow-up to monitor for recurrences and complications., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was not sought for the present study because it is not reporting research findings. Consent for publication: Written informed consents for publication were obtained from the patient. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: This study aimed to identify a novel recombinant adeno-associated virus (rAAV) capsid variant that can widely transfect the deep retina through intravitreal injection and to assess their effectiveness and safety in gene delivery., Methods: By adopting the sequences of various cell-penetrating peptides and inserting them into the capsid modification region of AAV2, we generated several novel variants. The green fluorescent protein (GFP)-carrying variants were screened following intravitreal injection. Gene therapy experiments were conducted via intravitreal injection of rd1 mice. We validated the therapeutic effects utilizing the pupillary light reflex and visual cliff test. Assessment of retinal structure and Pde6b gene levels in rd1 mice after gene therapy further was confirmed through transcriptome sequencing to validate the gene therapy efficacy., Results: We observed enhanced transduction and penetration efficiency of the AAV variant AAV2.CPP.21 after intravitreal injection which can target all layers of the retinas. Normal doses of AAV2.CPP.21 administered via intravitreal injection achieved effective gene therapy for retinitis pigmentosa in rd1 mice, with no increased risk of transgenic leakage in peripheral organs., Conclusions: Our study identified another new, safe, and efficient AAV vector for gene therapy via intravitreal injection for retinal diseases. This new vector holds promise for clinical application and improvement of the efficacy of gene therapy for inherited retinal diseases.

Purpose: Alteration of visual acuity in wet age-related macular degeneration (AMD) is mostly driven by vascular endothelial growth factor A (VEGF-A)-induced edema from leaky newly forming blood vessels below the retina layers. To date, all therapies aimed at alleviation of this process have relied on inhibition of VEGF-A activity. Although effective in preventing vascular leak and edema, this approach also leads to the loss of normal vasculature and multiple related side effects., Methods: We have developed an alternative strategy that uses anti-syndecan-2 polyclonal antibody (anti-Sdc2 pAb) to block VEGF-A-induced permeability without interfering with other VEGF-A activities. The effect of anti-Sdc2 pAb therapy was assessed in vitro using a transendothelial electrical resistance (TEER) assay, as well as staining of the endothelial cell junction, and in vivo in the laser-induced choroidal neovascularization (CNV) model., Results: Anti-Sdc2 pAb blocked VEGF-A-induced permeability in vitro, and both local intravitreal injections and systemic intravenous treatments with anti-Sdc2 pAb were as effective as intravitreal anti-VEGF therapy in reducing edema, size of retinal lesions, and local inflammation in this model. Post-injury neovascularization was not affected by treatment with anti-Sdc2 pAb., Conclusions: These findings indicate that anti-Sdc2 pAb therapy can be an effective alternative to anti-VEGF-A approaches for suppression of edema and to prevent retinal lesions in wet neovascular AMD (nAMD)., Translational Relevance: Intravitreal anti-Sdc2 treatment may avoid side effects observed with the long-term anti-VEGF therapy, and systemic treatment with an anti-Sdc2 pAb antibody can address the issues associated with repeated intravitreal injections.

Purpose: To report the effect of anti-vascular endothelial growth factor inhibitor on fovea-involving cystoid macular edema in a patient with Birdshot chorioretinopathy., Methods: A 42-year-old male patient presented to our hospital with bilateral posterior uveitis with retinal vasculitis, cystoid macular edema, and optic disk edema. He was diagnosed with birdshot chorioretinopathy based on clinical appearance and tissue type HLA-A29., Results: The patient underwent vitrectomy in the right eye without any change in visual acuity. Retinal leakage was reduced by oral prednisolone, which could not be tapered below 50 mg per day without relapse. Oral prednisolone, topical dexamethasone, and subtenon Kenalog were associated with intraocular pressure rise in both eyes. Hence, his uveitis responded to steroids, but there was no detectable effect of any steroid-sparing immunomodulatory drugs. The patient had been on oral prednisolone 50 mg for five years when it was decided to attempt intravitreal vascular endothelial growth factor inhibitor injection therapy. The anti-vascular endothelial growth factor therapy diminished cystoid macular edema in the fovea and improved the visual acuity., Conclusion: Here, we report for the first time the long-term outcomes of anti-vascular endothelial growth factor injections on fovea-involving cystoid macular edema in Birdshot chorioretinopathy to keep steroid at the minimal possible doses and preserve a satisfying visual acuity level.

Purpose: To investigate the effects of faricimab, a bispecific antibody targeting VEGF and Ang-2 (thus increasing Tie-2 activity), in patients with CSC based on a recent genetic study that implicated Tie-2 signaling in CSC pathophysiology., Design: A retrospective interventional multicenter case series., Methods: We included patients with chronic CSC (persistent or recurrent SRF for ≥6 months) who received at least one faricimab 6 mg injection between January 1 2022, and April 1 2024,. Study sites included Massachusetts Eye and Ear and University of California San Francisco. Patients with evidence of a choroidal neovascular membrane on color photos, optical coherence tomography (OCT) and/or fluorescein angiography were excluded. 16 eyes (15 patients) met the inclusion criteria. The median central macular thickness at each visit from 52 weeks before to 52 weeks after the first faricimab injection was calculated using automated Heidelberg Spectralis ETDRS subfield measurements., Results: Prior to treatment with faricimab, CSC had been diagnosed a median of 4.1 years (range 0.9-8) earlier and SRF (and intraretinal fluid [IRF] in a subset) had been continuously present for a median of 30 weeks (range 9-257). Decreases in macular thickness were observed in 14/16 eyes after the first faricimab injection and in 14/16 eyes in the full follow-up period compared with prior, 10 of which experienced complete resolution of SRF following the start of the first series of injections at a median of 4 weeks (range 2-25). One eye worsened after the second injection. The median improvement in macular thickness was 40 μm [range -3 to 89.5] (P = .0007). Upon review of OCT images, reductions in macular thickness were consistent with reductions in SRF and/or IRF. Visual acuity improved by 2 lines or more in 6/16 eyes., Conclusions: In a retrospective case series of patients with chronic CSC and longstanding SRF, we observed improvement in macular thickness after intravitreal faricimab. While the small number of patients and variable natural history of CSC preclude definitive conclusions, a randomized controlled trial seems warranted., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To compare the incidence, type, interval for reactivation, and structural outcomes in infants with aggressive retinopathy of prematurity (A-ROP) treated with ranibizumab or bevacizumab., Method: It is a single-center, retrospective, consecutive, case series. We included infants with A-ROP which were initially treated with either intravitreal ranibizumab (IVR, 0.25 mg) or intravitreal bevacizumab (IVB, 0.625 mg) between January 2017 and December 2023. The infants were followed up for reactivation. The demographic and clinical data were collected. The time, zone, type of reactivation, its treatment, type of final structural outcome, and factors associated with reactivation were analyzed., Results: One hundred eight among the 322 infants with A-ROP were included in the study. Fifty-five received IVR, while 53 received IVB. Infants treated with IVR had higher incidence of reactivation (92.7% vs 52.8%, P < 0.001) at an earlier interval than IVB (7.7 weeks vs 12.8 weeks, P < 0.001). Infants treated with IVR had approximately 3.3 times higher possibility of reactivation than those treated with IVB. Three infants (5.9%) in the IVR group and five (9.4%) in the IVB group attained complete vascularization of the retina ( P = 0.72). More infants treated with IVB had regression with a persistent avascular retina (PAR) than IVR (52.8% vs 15.7%, P < 0.001). Infants in the IVB group had 10 times higher possibility of regression with PAR., Conclusion: Infants of A-ROP treated with IVR have a higher incidence and earlier reactivation, while those treated with IVB have less incidence and delayed reactivation, albeit with a higher possibility of regression with a PAR., (Copyright © 2024 Indian Journal of Ophthalmology.)

Purpose: This study aims to quantify the volume of intraretinal fluid (IRF), subretinal fluid (SRF), and subretinal pigment epithelium (sub-RPE) fluid in treatment-naïve Type 3 macular neovascularization (MNV) eyes with age-related macular degeneration (AMD) and to investigate the correlation of these fluid volumes with visual acuity (VA) outcomes at baseline and following antivascular endothelial growth factor (VEGF) treatment., Design: Retrospective, clinical cohort study., Methods: In this study, we analyzed patients diagnosed with exudative AMD and treatment-naïve Type 3 MNV undergoing a loading dose of anti-VEGF therapy. Using a validated deep-learning segmentation strategy, we processed optical coherence tomography (OCT) B-scans to segment and quantify IRF (i.e., both in the inner and outer retina), SRF, and sub-RPE fluid volumes at baseline. The study correlated baseline fluid volumes with baseline and short-term VA outcomes postloading dose of anti-VEGF injections., Results: Forty-six eyes from 46 patients were included in this study. Visual acuity was 0.51 ± 0.30 LogMAR at baseline and 0.33 ± 0.20 LogMAR after the loading dose of anti-VEGF (P = .001). Visual acuity at the follow-up visit was 0.40 ± 0.17 LogMAR in patients with no complete resolution of retinal fluid and 0.31 ± 0.20 LogMAR in eyes without retinal fluid after treatment (P = .225). In the multivariable analysis, the IRF volume in the inner retina (P = .032) and the distance of the MNV from the fovea (P = .037) were predictors of visual acuity at baseline. The baseline IRF volume in the inner retina also predicted the visual acuity at follow-up (P = .023)., Conclusion: The present study highlights the fluid volume in the inner retina as a crucial predictor of short-term visual outcomes in Type 3 MNV, underscoring the detrimental effect of IRF on neuroretinal structures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the world and anti-vascular endothelial growth factor (VEGF) injections have been the standard of care for the wet/neovascular variant since 2004. Currently, there are conflicting reports regarding its effect on the choroid, which supplies outer retina with oxygen and other nutrients. We synthesize available information of anti-VEGF on choroidal thickness (CT) in treatment-naïve typical neovascular AMD patients during the initial 12-week loading phase. We found 43 studies involving 1901 eyes from 1878 patients were included. Meta-analysis of 35 studies reporting CT at baseline and after 12 weeks suggested a significant decrease in CT with anti-VEGF treatment. A greater mean change with aflibercept compared to ranibizumab was found in subgroup analyses of sub-foveal CT in types 1 and 2 macular neovascularization. The long-term consequences of reduced CT in neovascular AMD remain unclear and require further targeted studies., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the 12-month outcomes of ziv-aflibercept for neovascular age-related macular degeneration (nAMD) in eyes previously treated with aflibercept., Methods: Retrospective chart review of patients with nAMD previously treated with aflibercept for at least 12 months and subsequently transitioned to ziv-aflibercept between January 1, 2019, and December 31, 2022, for a period of at least 12 months. Participants were identified, and their clinical and imaging information was extracted from our electronic health records system. Data on best corrected visual acuity (BCVA), intraocular pressure, injection intervals, central retinal thickness (CRT), volume cube presence of subretinal fluid (SRF), and intraretinal fluid (IRF) were obtained. Main outcome measures included changes in BCVA, injection intervals, CRT, SRF, and IRF before and after 12 months of ziv-aflibercept treatment., Results: Fifty-four eyes of 44 patients were included in the study. After 12 months of ziv-aflibercept treatment, BCVA decreased by 0.84 ETDRS letters (P = 0.424) compared to BCVA at the last visit prior to conversion from aflibercept. Injection intervals decreased by 1.18 weeks (P = 0.489). CRT significantly decreased by 15.66 µm (P = 0.005). SRF was present initially in 31.5% of eyes and decreased to 22.2% (P = 0.125). IRF was present initially in 42.6% of eyes and decreased to 35.2% (P = 0.219)., Conclusion: Ziv-aflibercept demonstrated effectiveness in maintaining treatment outcomes in nAMD eyes previously treated with aflibercept. The treatment was well-tolerated with no reported adverse events. Ziv-aflibercept may be a cost-effective alternative and a potential solution to the financial burden associated with conventional anti-VEGF agents., (Copyright © 2024 Indian Journal of Ophthalmology.)

Objective: To compare the efficacy of brolucizumab and aflibercept treatment in reducing the maximum thickness of pigment epithelial detachments (PEDs) and sub-retinal pigment epithelium (sub-RPE) fluid in patients with neovascular age-related macular degeneration in the HAWK and HARRIER studies., Design: HAWK and HARRIER were 96-week, prospective, randomized, double-masked, controlled, multicenter studies., Participants: A total of 1775 patients across 11 countries were included in the HAWK study, and 1048 patients across 29 countries were included in the HARRIER study., Intervention: After 3 monthly loading doses, brolucizumab-treated eyes received injections every 12 weeks or every 8 weeks if disease activity (DA) was detected. Aflibercept-treated eyes received fixed 8-week dosing., Main Outcome Measures: Maximum thickness of PEDs and sub-RPE fluid across the macula were assessed at baseline through week 96 in the brolucizumab- and aflibercept-treated patients and in the patient subgroups with DA at week 16 (matched in terms of injection number and treatment interval)., Results: At week 96, there were greater mean percentage reductions from baseline in maximum thickness of both PEDs and sub-RPE fluid in brolucizumab-treated patients vs. aflibercept-treated patients (PED: 19.7% [n = 336] vs. 11.9% [n = 335] in HAWK; 29.5% [n = 364] vs. 18.3% [n = 361] in HARRIER. Sub-RPE fluid: 75.4% vs. 57.3% in HAWK; 86.0% vs. 76.3% in HARRIER). A similar trend in mean percentage reductions was observed in patients with DA at week 16., Conclusions: This analysis shows that brolucizumab achieved greater reductions in PEDs and sub-RPE fluid thickness than aflibercept in HAWK and HARRIER., Trial Registration: ClinicalTrials.gov Identifiers: NCT02307682 (HAWK) and NCT02434328 (HARRIER)., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the duration of vascular endothelial growth factor (VEGF) suppression in the aqueous humor of macaque eyes after intravitreal faricimab (IVF) injection. Methods: Faricimab (6 mg/50 µL) was injected into the vitreous cavity of the right eye of 6 macaques. Aqueous humor samples (150 μL) were collected from both eyes immediately before injection and on days 1, 3, 7, 14, 21, 28, 42, 56, 84, and 112 after injection. The VEGF concentrations in the aqueous humor were measured using an enzyme-linked immunosorbent assay. Results: The VEGF was undetectable until 4 weeks after IVF injection in 4 eyes and until 6 weeks in the remaining 2 eyes. The mean duration of complete VEGF suppression was 4.7 weeks (range, 4-6 weeks). The VEGF concentration did not decrease in the aqueous humor of the non-injected fellow eyes. Conclusions: Faricimab effectively suppressed the VEGF concentrations in the aqueous humor of macaques for an average of 4.7 weeks after a single intravitreal injection. It did not reduce the VEGF concentrations in the aqueous humor of the fellow eyes.

Purpose: To describe the patient characteristics and clinical course of severe intraocular inflammation (IOI) following intravitreal injection (IVT) of faricimab., Design: Retrospective case series., Methods: Case series at a single French academic center (Dijon University Hospital) where 263 patients were treated with faricimab IVT between January 9, 2024 and May 7, 2024., Results: Over the 4-month period, a total of 1659 eyes (1338 patients) received anti-vascular endothelial growth factor (anti-VEGF) IVTs for a total of 3510 IVTs, of which 343 eyes (263 patients) received faricimab IVTs for a total of 971 IVTs. Overall, 6 pretreated eyes with neovascular age-related macular degeneration that were switched to faricimab developed severe unilateral IOI following faricimab IVT (1/162 injections [0.62%]), including 5 eyes presenting with a severe anterior and intermediate uveitis mimicking infectious endophthalmitis. All eyes were normotensive and presented with mild to moderate pain and predominantly moderate vitritis, associated with granulomatous keratic precipitates in 2 eyes and nonocclusive vasculitis in one eye. The clinical presentation, sterile vitreous sample culture, and rapid improvement with treatment made the diagnosis of infectious endophthalmitis unlikely. Four patients out of 6 did not recover their pre-IOI visual acuity, with an average visual loss of +0.2 logMAR. Two patients had positive antinuclear antibodies, including one with a history of cutaneous lupus., Conclusions: In this case series, we reported 6 cases of severe IOI after intravitreal faricimab over 4 months in a single French center with an estimated incidence rate of 0.6% per injection. Future real-world data will contribute to a better evaluation of the epidemiology of this rare inflammatory adverse event related to intravitreal faricimab., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To present a case of a patient with bilateral wet age-related macular degeneration who was unilaterally treated with intravitreal aflibercept injections (IAIs) and the disease status in the fellow eye ameliorated after an IAI., Methods: Retrospective case report., Results: A 72-year-old woman was diagnosed with wet and dry age-related macular degeneration in her right eye and left eye, respectively. In the right eye, treatment strategy comprised three monthly IAIs, followed by reinjections according to need, whereas optical coherence tomography scans were performed before IAIs. One month after the second IAI, subretinal fluid developed in the left eye. One week later, an IAI was applied in the right eye; 2 days later, the disease status in the left eye was assessed by fluorescein angiography and optical coherence tomography. Surprisingly, in the left eye, subretinal fluid completely resolved and fluorescein angiography did not detect leakage, highlighting the absence of an active choroidal neovascularization. The short interval between IAI and the resolution of exudative phenomena in the other eye is suggestive of a beneficial effect in the contralateral eye., Conclusion: In this article, we showed that an IAI had an effect to the fellow untreated eye. Our observation is consistent with active aflibercept in the systemic circulation. To the best of our knowledge, no other report in the literature has demonstrated this effect of aflibercept in wet age-related macular degeneration.

Objective: To evaluate in a real-world setting an intravitreal clindamycin treatment protocol for ocular toxoplasmosis., Methods: This was a single-center, retrospective review with a 6-month follow-up. Our protocol proposed an IVT of clindamycin as first-line treatment, and management was chosen according to the patient's status (past medical history of ocular toxoplasmosis or not). We evaluated the gain in best corrected visual acuity (BCVA) at 6months, the therapeutic burden and anatomical outcomes., Results: The study included 38 eyes of 38 patients. The 6-month follow-up was reached for 23 patients. In the whole cohort, 6 patients experienced one recurrence, and one patient had two recurrences (mean time to recurrence 65±36days), for a total number of 46 occurrences. BCVA gain was 0.24±0.49 logMAR (P-value 0.023). Cicatrization of the chorioretinal lesion was obtained with a mean number of 1.3 (62/46) IVT of clindamycin (1 to 4 IVTs per patient per episode) and a mean time between 2 IVT for the same occurrence of 15.9±8.5days. The percentage of occurrences resolved with a single IVT was 67% (31/46). Oral corticosteroid therapy was started in 26 patients (68%). We demonstrated no adverse effects of IVT, except for one patient who developed a retinal detachment., Conclusion: Our study shows the efficacy and tolerance of our intravitreal treatment protocol with clindamycin for ocular toxoplasmosis., Competing Interests: Déclaration de liens d’intérêts Les auteurs déclarent ne pas avoir de liens d’intérêts., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Aims: To investigate the efficacy and safety of intravitreal Dexamethasone implant (DEX-I) therapy in the treatment of diabetic macular edema (DME) refractory to intravitreal bevacizumab (IVB)., Material and Methods: This retrospective and cross-sectional study included 37 eyes of 37 patients who received 3 loading doses of IVB injections for DME with no response and underwent DEX-I implant. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurements and central foveal thickness (CFT) measured by spectral domain optical coherence tomography (SD-OCT) were recorded and compared before DEX-I, at the first week, first, second, third and sixth months. Duration of DME, glycated hemoglobin (HbA1c) levels, DME types and lens status (phakic, pseudophakic) were also recorded., Results: The mean age of the patients was 61.14 ±8.69 years (59.5% male, 40.5% female). 35.1% of the patients had cystoid macular edema, 64.9% had diffuse macular edema and 73 % were phakic and 27% were pseudophakic. BCVA, CFT and IOP values before DEX-I injection were 0.78 ±0.16 LogMAR, 493.73 ±107.6 µm and 13.05 ±2.59 mmHg, respectively. At 6 months after DEX-I, BCVA, CFT and IOP values were 0.64 ±0.11 LogMAR, 397.35 ±59.72 µm and 16.3 ±2.51 mmHg, respectively. In all follow-ups, there was a significant improvement in BCVA, a significant decrease in CFT and a significant increase in IOP compared to pre-injection. Ocular hypertension was observed in 0.8 % of patients and progression of cataract progression in 1% of patients after treatment., Conclusion: DEX-I therapy is an effective and safe treatment option for DME refractory to IVB treatment.

We evaluate the pharmacokinetics, safety, and optimal dosages of intravitreal agents in silicone oil (SO)-filled eyes, addressing challenges in administering such therapies. We assessed the pharmacological properties and safety profiles of intravitreal drugs in SO-filled eyes, deriving conclusions and guidance from available literature and expert consensus. Preclinical data suggest comparable half-lives of anti-vascular endothelial growth factoragents in SO-filled eyes, but clinical evidence is mainly from case reports and small series. Available research prioritizes standard dosages, particularly for bevacizumab (1.25 mg), supported by stronger evidence than aflibercept (2 mg) or ranibizumab (0.5 mg). Intravitreal steroids, especially dexamethasone at 0.7 mg, show efficacy and safety, while evidence for fluocinolone acetonide at 0.19 mg is limited. Intravitreal methotrexate has been reported at the dosage of 250-400 μg, with keratitis as the primary expected side effect. Case reports indicate tolerability of standard dosages of antivirals (foscarnet 1.2-2.4 mg/0.1 mL, ganciclovir 4 mg/0.1 mL) and the antibiotic combination piperacillin/tazobactam (250 μg/0.1 mL). We offer guidance based on current, but limited, literature. Standard dosage of intravitreal agents should be carefully considered, along with close monitoring for potential side effects, which should be discussed with patients., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe a case of full thickness macular hole after intravitreal brolucizumab injection in neovascular age-related macular degeneration, which has not been reported to date., Case Description: A 65-year-old male patient received brolucizumab intravitreal injection therapy for neovascular macular degeneration of the right eye. He received multiple intravitreal anti-VEGF injections on a pro re nata regimen and developed a full thickness macular hole., Outcome: Surgical treatment was performed with pars plana vitrectomy of the right eye. Full thickness macular hole was successfully treated., Conclusion: Although a full thickness macular hole following intravitreal brolucizumab injection is an uncommon complication, it requires caution., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The management of intermediate and posterior uveitis poses a significant challenge of achieving adequate drug concentrations in the posterior segment over the chronic nature of the disease. Systemic agents seldom reach effective drug levels, and even with low maintenance or tapering doses, it is hard to avoid systemic toxicity. The use of intravitreal and periocular injections is often unable to prevent recurrences due to their short half-life. Since the emergence of intravitreal implants (Vitrasert, Retisert), it has become possible to circumvent these therapeutic challenges. A detailed review in the PubMed index yielded 155 articles, of which 22 were analyzed based on exclusion criteria. A recent shift from surgically sutured to minimally invasive injectable implants mainly indicated for noninfectious uveitis is evident from the literature. This review article also provides insights into dexamethasone (Ozurdex) and recent fluocinolone acetonide (Yutiq, Iluvien) implants with particular emphasis on their improved safety and efficacy. Dexamethasone implants favor the therapeutic goal of prevention of recurrences, whereas the use of fluocinolone implants helps to attain better visual outcomes due to their longer duration of action. Thus, the review provides recent literature supporting the role and indication of sustained release intravitreal implants in the management of noninfectious intermediate and posterior uveitis., (Copyright © 2024 Indian Journal of Ophthalmology.)