Two-year outcomes of intravitreal brolucizumab for neovascular age-related macular degeneration: treat, extend, and stop-protocol.

PURPOSE: To investigate the real-world 2-year treatment outcomes of intravitreal brolucizumab (IVBr) for neovascular age-related macular degeneration (nAMD). METHODS: This multicenter, prospective, and interventional study included 53 eyes treated with brolucizumab from October 2020 to August 2021 at 3 institutions. A modified treat-and-extend (TAE) regimen with predefined discontinuation criteria was used. The mTAE regimen was discontinued if patients responded positively and achieved a treatment interval of 16 weeks twice with no sign of recurrence. The number of patients discontinuing TAE and the visual and anatomic changes at 1 and 2 years after the first IVBr were evaluated. RESULTS: Thirty-eight eyes from 38 patients (71%) completed the 2-year observation period and 7 eyes from 7 patients experienced intraocular inflammation (IOI). Of these 38 patients, 18 (47%) could discontinue the TAE at a median [interquartile range] of 13.1 [12.9-16.8] months after the first IVBr. Best-corrected visual acuity, central subfield retinal thickness, and central choroidal thickness were significantly improved compared with baseline at both 1 and 2 years after the first IVBr (all P < 0.001). An extension study revealed a 1-year recurrence rate of 5.6% (standard deviation, 5.4%) after TAE discontinuation. CONCLUSIONS: While IOI is a concern with brolucizumab, careful observation allows discontinuing the TAE regimen in patients treated with IVBr. Moreover, brolucizumab may reduce the risk of recurrence after treatment interruption. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry ( http://www.umin.ac.jp/ ; R000050688 UMIN 000044374).

Treat-and-Extend Versus Pro re nata Regimens of Ranibizumab and Aflibercept in Neovascular Age-Related Macular Degeneration: A Comparative Study from Routine Clinical Practice.

INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) is generally given using pro re nata or "treat-and-extend" (T&E) regimens for neovascular age-related macular degeneration (nAMD). Randomized clinical trials have reported that T&E is superior to Pro re nata (PRN), but results from clinical trials may not always be replicated in clinical practice. Real-world data comparing T&E and PRN regimens for nAMD are limited. The objective of this work was to report 24-month outcomes of PRN versus T&E regimens for ranibizumab and aflibercept to treat nAMD in routine clinical practice. METHODS: We conducted a retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project (FRB). Treatment-naïve eyes starting nAMD treatment with at least three injections using a T&E or PRN regimen were tracked by using the FRB. The primary outcome was the mean change in visual acuity (VA) measured by the number of letters read on a logarithm of the minimum angle of resolution chart at 2 years versus baseline. The secondary outcome was the number of injections at 2 years. RESULTS: From January 1, 2015 to January 31, 2019, 3313 eyes from 2948 patients with nAMD were included: 1243 eyes from 1065 patients were classified as PRN and 2070 eyes from 1935 patients started a T&E regimen. At 24 months, patients on the T&E regimen experienced significantly greater mean (95% confidence interval) improvement in VA than those on PRN (+ 4.2 [3.1, 5.2] vs. + 1.3 [0.1, 2.6] letters; p < 0.001), with more injections (14.9 standard deviation(SD) 4.3) vs. 9.8(SD 4.3); p < 0.001). CONCLUSIONS: Eyes treated with a T&E regimen had better VA outcomes from VEGF inhibitors than eyes treated PRN. This large real-world data assessment supports previous data from randomized clinical trials that the T&E regimen delivers better outcomes than PRN.

This study focused on comparing two methods of treating neovascular age-related macular degeneration, a common eye condition. The treatments used were ranibizumab and aflibercept. We looked at the reactive "pro re nata" method, where treatment is given sporadically and only when the condition reactivates, and the proactive "treat-and-extend" method, which aims to keep the disease inactive with the fewest treatments at regular intervals. The main aim was to determine which method provides the best vision outcomes over a 24-month period and the frequency of treatment required. We found that the treat-and-extend method resulted in a greater improvement in vision than the pro re nata method, although it did require more injections. This study highlights the effectiveness of the treat-and-extend method for neovascular age-related macular degeneration, suggesting it gets better outcomes despite requiring more injections.

Short-Term Real-World Outcomes of Intensive Aflibercept Injection for Refractory Neovascular Age-Related Macular Degeneration.

Background: The aim of this study is to report short-term outcomes after the shortening of the treatment interval to 4 weeks with a treat-and-extend (TAE) regimen (Si4w) of aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 34 patients given aflibercept with a TAE regimen of a minimum of a 4-week interval when they had a limited response to bimonthly aflibercept. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared before and after Si4w. The resolution of subretinal and intraretinal fluid before and after Si4w was also examined. The risk factors associated with persistent fluid were analyzed. Results: The average treatment duration until initiation of Si4w was 57.82 ± 28.59 months, with an average of 23.64 ± 12.40 injections administered. The BCVA was not significantly improved after Si4w. The CMT decreased significantly from 427.91 ± 125.74 µm to 336.38 ± 121.67 µm at the third visit (p < 0.001). Eighteen eyes (52.9%) showed complete resolution, and twenty-three eyes (67.6%) experienced complete resolution at least once during the three visits. The duration of fluid before Si4w was significantly associated with complete resolution (p = 0.011). Conclusions: Si4w of aflibercept showed satisfactory anatomical outcomes with complete resolution of fluid in patients with a limited response to bimonthly aflibercept injections, and should be considered as a useful treatment option.

One-year outcomes and safety assessment of faricimab in treatment-naïve patients with neovascular age-related macular degeneration in Japan.

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

One-Year Anti-VEGF Therapy Outcomes in Diabetic Macular Edema Based on Treatment Intensity: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To compare 1-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal VEGF inhibitor injections were delivered. DESIGN: Cohort study. PARTICIPANTS: There were 2288 treatment-naive eyes with DME starting intravitreal VEGF inhibitor therapy from October 31, 2015 to October 31, 2021 from the Fight Retinal Blindness! international outcomes registry. METHODS: Eyes were grouped according to the proportion of visits at which an injection was received, Group A with less than the median of 67% (n = 1172) versus Group B with greater than the median (n = 1116). MAIN OUTCOME MEASURES: Mean visual acuity (VA) change after 12 months of treatment. RESULTS: The mean (95% confidence interval [CI]) VA change after 12 months of treatment was 3.6 (2.8-4.4) letters for eyes in Group A versus 5.2 (4.4-5.9) letters for eyes in Group B (P = 0.005). The mean (95% CI) central subfield thickness (CST) change was -69 (-76 to -61) µm and -85 (-92 to -78) µm for eyes in Group A versus Group B, respectively (P = 0.002). A moderate positive correlation was observed between the number of injections received over 12 months of treatment and the change in VA (P < 0.001). Additionally, eyes that received more injections had a moderately greater CST reduction. CONCLUSIONS: This registry analysis found that overall VA and anatomic outcomes tended to be better in DME eyes treated at a greater proportion of visits in the first year of intravitreal VEGF inhibitor therapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Factors Associated with Success of Switching to Faricimab for Neovascular Age-Related Macular Degeneration Refractory to Intravitreal Aflibercept.

We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals.

Preserving visual acuity: a compelling 12-year case study of controlling neovascular age-related macular degeneration.

INTRODUCTION: In neovascular age-related macular degeneration (nAMD) trials, anti-VEGF injection frequency decreases after the first year, while outcomes remain primarily related to the number of injections. To the best of our knowledge, there are no reports of maintaining the best corrected visual acuity (BCVA) for more than 7 years in extension studies. OBJECTIVE: To report a 12-year follow-up of a real-world case of nAMD where BCVA was preserved from declining. CASE DESCRIPTION: A 67-year-old Caucasian female presented to our department in June 2010 due to decreased vision in her left eye (LE) within the preceding months. Examination showed a BCVA of 85 letters (L) in the right eye (RE) and 35 L in the LE. Fundus examination showed drusen in the macula of both eyes. Macular edema, loss of the macular lutein pigment, macular hypo/hyperpigmentation were observed in the LE. A diagnosis of Type 2 choroidal neovascular membrane (CNV) in the LE was established and within two months a Type 1 CNV developed in the RE. She undergone 9 injections of bevacizumab (six) and ranibizumab (three) within the first year of treatment in the LE and seven injections of ranibizumab within the first year in the RE. RESULTS: The LE had a mean of 5.2 injections per year, and the RE had a mean of 7.5 injections per year, from 2010 to 2022. RE's BCVA dropped by 8L (85L to 77L) and central retinal thickness (CRT) increased by 16 µm (276 µm to 292 µm) while LE's BCVA increased by 28L (35L to 63L) and CRT decreased by 369 µm (680 µm to 311 µm), at the twelfth year. CONCLUSIONS: Although the final visual outcome depends on baseline BCVA and lesion type or size, the number of injections is paramount in preserving BCVA and achieving favorable functional outcomes in nAMD, even after 12 years of treatment.

Women's reproductive choice and (elective) egg freezing: is an extension of the storage limit missing a bigger issue?

Egg freezing can allow women to preserve their eggs to avoid age-related infertility. The UK's recent extension of elective egg freezing storage has been welcomed as a way of enhancing the reproductive choices of young women who wish to delay having children. In this paper, I explore the issue of enhancing women's reproductive choices, questioning whether there is a more significant aspect overlooked in egg freezing. While increasing storage limits expands reproductive choices for some women, focus on this extension alone, I argue, misses a fundamental issue with egg preservation that often remains ignored; the importance of effective information on egg freezing and the effect this has on women's reproductive choices. Ultimately, I highlight the crucial role of balanced information in enhancing women's choices regarding egg freezing and argue that focusing on extending and increasing provision may obscure this real opportunity to empower women and their authentic reproductive choices.

Treatment outcome of IDH1/2 wildtype CNS WHO grade 4 glioma histologically diagnosed as WHO grade II or III astrocytomas.

BACKGROUND: Isocitrate dehydrogenase (IDH)1/2 wildtype (wt) astrocytomas formerly classified as WHO grade II or III have significantly shorter PFS and OS than IDH mutated WHO grade 2 and 3 gliomas leading to a classification as CNS WHO grade 4. It is the aim of this study to evaluate differences in the treatment-related clinical course of these tumors as they are largely unknown. METHODS: Patients undergoing surgery (between 2016-2019 in six neurosurgical departments) for a histologically diagnosed WHO grade 2-3 IDH1/2-wt astrocytoma were retrospectively reviewed to assess progression free survival (PFS), overall survival (OS), and prognostic factors. RESULTS: This multi-center study included 157 patients (mean age 58 years (20-87 years); with 36.9% females). The predominant histology was anaplastic astrocytoma WHO grade 3 (78.3%), followed by diffuse astrocytoma WHO grade 2 (21.7%). Gross total resection (GTR) was achieved in 37.6%, subtotal resection (STR) in 28.7%, and biopsy was performed in 33.8%. The median PFS (12.5 months) and OS (27.0 months) did not differ between WHO grades. Both, GTR and STR significantly increased PFS (P < 0.01) and OS (P < 0.001) compared to biopsy. Treatment according to Stupp protocol was not associated with longer OS or PFS compared to chemotherapy or radiotherapy alone. EGFR amplification (P = 0.014) and TERT-promotor mutation (P = 0.042) were associated with shortened OS. MGMT-promoter methylation had no influence on treatment response. CONCLUSIONS: WHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors.

Relationships between Patient-Reported Outcome Measures and Clinical Measures in Naïve Neovascular Age-Related Macular Degeneration Patients Treated with Intravitreal Ranibizumab.

Our objective was to evaluate changes in patient-reported outcome measures using the NEI-VFQ 25 questionnaire during a treat and extend regimen in naive neovascular Age-Related Macular Degeneration patients, and its correlation with anatomical and functional data. We conducted a prospective observational study. Patients underwent a treat and extend regimen with intravitreal ranibizumab for neovascular Age-Related Macular Degeneration. Initial response was evaluated at 4th month, and subsequently in every follow-up visit. If a clinical response was achieved, the injection interval was extended in two-week increments, up to a maximum of 12 weeks. Quality of life was assessed using the NEI-VFQ 25 questionnaire at baseline, 4th months, and 12th months. Patients were categorized as good or poor responders based on Best corrected visual acuity, central foveal thickness, intraretinal fluid, or subretinal fluid. Treatment with ranibizumab led to a significant improvement in quality of life, with a mean increase in NEI-VFQ 25 score of 4.27 points in the 12th month. No significant differences in improvement were observed between good and poor responders. Quality of life scores in neovascular Age-Related Macular Degeneration patients improved with intravitreal treatment regardless of the clinical response. The early response following the loading phase could indicate better quality of life after one year of treatment, with Best corrected visual acuity being the clinical parameter with the greatest influence on quality of life.

Optimizing Sensorless Control in PMSM Based on the SOGIFO-X Flux Observer Algorithm.

In the realm of sensorless control for a permanent magnet synchronous motor (PMSM), the flux observer algorithm is widely recognized. However, the estimation accuracy of rotor position is adversely impacted by the interference from DC bias and high-order harmonics. To address these issues, an advanced flux observation method, second-order generalized integrator flux observer extend (SOGIFO-X), is introduced in this paper. The study begins with a theoretical analysis to establish the relationship between flux observation error and rotor position error. The SOGIFO-X method, developed in this study, is compared with traditional methods such as the Low Pass Filter (LPF) and second-order generalized integrator flux observer (SOGIFO), employing mathematical rigor and Bode plot analysis. The emphasis is on the methodology and the general performance improvements SOGIFO-X offers over conventional methods. Simulations and experiments were conducted to assess the impact of SOGIFO-X on the steady-state and dynamic performances of sensorless control. Findings indicate that SOGIFO-X demonstrates significant enhancements in terms of reducing the reduced flux observation error, contributing to the advancement of position estimation accuracy and sensorless motor control technology.

One-year results of treat-and-extend regimen with intravitreal faricimab for treatment-naïve neovascular age-related macular degeneration.

PURPOSE: To evaluate 1-year outcomes of loading phase treatment followed by maintenance therapy using a treat-and-extend (TAE) regimen with intravitreal faricimab for neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective, interventional case series. METHODS: We retrospectively studied 40 eyes of 38 consecutive patients with treatment-naïve nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness, central choroidal thickness (CCT), total number of injections over 1 year, and intended injection interval at the last visit. RESULTS: Thirty eyes (75.0%) had completed the 1-year intravitreal faricimab treatment. Their BCVA showed significant improvement, with significant reductions in foveal thickness and CCT. The total number of injections during the 1-year treatment period was 6.6 ± 0.7. The intended injection interval at the last visit was 12.7 ± 3.3 weeks. Of the 10 eyes (25.0%) failing to complete the 1-year faricimab treatment, 1 eye developed intraocular inflammation after the loading phase treatment but showed no recurrence of exudative changes, and no further treatment was required. Moreover, 5 eyes switched to intravitreal brolucizumab injection due to persistent exudative changes with an 8-week interval of faricimab injections. The remaining 4 eyes either dropped out or the patient died. CONCLUSIONS: A loading phase treatment followed by a TAE regimen with intravitreal faricimab appears to be generally safe and effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, there might be cases in which exudative changes cannot be adequately controlled with injections of faricimab every 8 weeks in the maintenance phase.

Intravitreal anti-vascular endothelial growth factor and combined photodynamic therapy for pachychoroid neovasculopathy: long-term treatment outcomes.

PURPOSE: To examine the long-term visual outcomes after initial treatment with combined photodynamic therapy (PDT) or aflibercept treat-and-extend (TAE) monotherapy in patients with pachychoroid neovasculopathy (PNV). METHODS: Patients diagnosed with PNV, initially treated with PDT combined with anti-vascular endothelial growth factor (VEGF) or intravitreal aflibercept (IVA) monotherapy in the TAE protocol and followed up for at least 6 months, were included in the study. Medical records were retrospectively reviewed. Survival analysis was performed, in which deterioration in logMAR visual acuity by 0.1 or 0.3 is defined as "death." The annual number of treatments was also analyzed. Sub-analysis was performed on 33 patients diagnosed with PNV without polypoidal lesions. RESULTS: This study included 46 patients (23 in the initial combined PDT group and 23 in the IVA TAE group). Mean age, sex, mean baseline logMAR visual acuity, or duration of observation (3.6 ± 3.2 years vs. 3.1 ± 1.9 years) in both groups were comparable. As for visual outcome, no significant differences were found in survival analysis based on worsening of 0.1 or 0.3 logMAR (3-year survival; 26% vs. 26%, 91% vs. 90%, respectively). Meanwhile, the additional number of anti-VEGF injections per year was significantly lower in the initial combined PDT group than in the IVA TAE group (1.0 ± 1.3 vs. 4.1 ± 1.5, p < 0.0001). No significant differences were found in the number of additional PDTs per year (0.07 ± 0.20 vs. 0.02 ± 0.09, p = 0.27). Similar results were found in a sub-analysis of 33 patients without polyps. CONCLUSION: In the treatment of PNV, regardless of the presence of polyps, the long-term visual outcomes were similar between the initial combined PDT and IVA TAE monotherapy. However, the annual number of anti-VEGF injections was lower in the initial combined PDT group than in the aflibercept TAE group, whereas that of PDT was comparable.

Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration Beyond One Year of Treatment: AZURE, a Randomized Trial of Treat-and-Extend vs. Fixed Dosing.

INTRODUCTION: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year. METHODS: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52. RESULTS: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) µm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified. CONCLUSION: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540954.

Intravitreal faricimab for neovascular age-related macular degeneration previously treated with traditional anti-VEGF compounds: a real-world prospective study.

BACKGROUND/AIMS: To evaluate the efficacy, safety and durability of intravitreal faricimab in patients with neovascular age-related macular degeneration (nAMD) with unsatisfactory response to traditional anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: Single-centre, prospective cohort study of all consecutive patients with nAMD who were switched to intravitreal faricimab from intravitreal ranibizumab or aflibercept, due to unsatisfactory treatment response (maximal fluid-free interval ≤ 8 weeks). Intravitreal faricimab was administered with a loading dose of four 4-weekly injections, followed by an 8-week extension. A treat and extend (T&E) regime was adopted thereafter. Primary outcome was the difference between the maximal fluid-free interval achieved with faricimab, and the one achieved before the switch. Morpho-functional outcomes were also assessed. Secondary outcome was accordance with clinical management when applying faricimab pivotal trial criteria versus our real-world T&E protocol, measured as a proportion. RESULTS: Twenty-six eyes of 26 patients with a median age of 82 years (range 77-85) were included. Patients were followed for 30.2 weeks (range 26.3-33.1). Maximal fluid-free interval after switch to faricimab (Mdn = 6.0 weeks; IQR = 4-8) was longer than the maximum interval before the switch (Mdn = 4.0 weeks; IQR = 4-4), p < 0.001. Comparing real-world T&E protocol with pivotal trial criteria, 8 (30.8%) eyes received the same clinical management while 18 (69.2%) eyes were kept at a shorter interval when following our T&E protocol. No serious adverse events were recorded. CONCLUSIONS: Faricimab appears to increase the fluid-free interval and allow extension of dosing interval in patients with nAMD poorly responsive to traditional anti-VEGF drugs.

Two-Year Real-World Results for Aflibercept Using the Treat-and-Extend Regimen in Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

INTRODUCTION: To evaluate the real-world efficacy of aflibercept using the treat-and-extend (TnE) regimen in treating neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), and to analyze biomarkers using optical coherence tomography (OCT) to predict treatment outcomes. METHODS: Patients diagnosed with nAMD or PCV who received an intravitreal injection of aflibercept following the TnE regimen for ≥ 2 years were retrospectively reviewed. Data on best-corrected visual acuity (BCVA), number of injections, treatment interval, and OCT biomarkers, including central macular thickness, presence of subretinal fluid (SRF), and serous pigmented epithelial detachment, were collected at baseline and at 3, 6, 12, 18, and 24 months after the first injection. RESULTS: A total of 43 patients were enrolled in this study, 24 of whom were diagnosed with nAMD and 19 with PCV. The BCVA in logMAR (mean ± standard deviation) improved from 0.75 ± 0.41 (baseline) to 0.60 ± 0.41 (P = 0.002) at 3 months after treatment initiation, and further improved to 0.66 ± 0.46 at 24 months (P = 0.137). The number of injections (mean ± standard deviation) within the 2-year treatment course was 10.95 ± 3.65. At month 24 of the TnE regimen, the treatment interval was extended to ≥ 16 weeks in 60.5% of all cases and to 78.9% of the PCV cases. After three loading injections, persistent subretinal fluid and intraretinal fluid were predictive of more frequent injections (P = 0.026) and poorer visual outcomes (P = 0.050), respectively. CONCLUSION: Aflibercept combined with a TnE regimen was effective in treating nAMD and PCV in a real-world setting. The treatment interval could be extended to ≥ 16 weeks in 60.5% of the cases after a 2-year treatment regimen. OCT can be used to predict the treatment course and visual outcomes.

Trans-Umbilical Lymphadenectomy Using an Articulating Bipolar Vessel-Sealing Device (TULAB) during Robotic Surgery for Gastric Cancer: Enhancing the Surgeon's Eye for Reduced-Port Robotic Gastrectomy.

BACKGROUND: Docking the scope and instruments through a multi-channel trocar has enabled reduced-port robotic distal gastrectomy (RRDG) for gastric cancer. To facilitate lymphadenectomy over the anatomical hindrances during RRDG, we recently introduced the Vessel Sealer Extend® (VSE) (Intuitive Surgical, Sunnyvale, CA, USA), a bipolar vessel-sealing device (BVSD) with an articulating jaw. METHODS: From May 2020 to August 2023, we performed RRDG to treat T1 gastric cancer. One endoscope arm and three instrument arms of the da Vinci® Xi Surgical System (Intuitive Surgical) were used. During the lymphadenectomy, the endoscope and VSE (Intuitive Surgical) were docked through a multi-channel trocar established on a trans-umbilical incision. Two Cardiere forceps were docked through cannulas established on each flank. A trans-umbilical lymphadenectomy using an articulating BVSD (TULAB) was then performed. RESULTS: A total of 42 patients underwent planned RRDG with the TULAB technique. The number of retrieved lymph nodes did not differ between the patients who underwent RRDG and those who underwent conventional laparoscopic distal gastrectomies (CLDG) (p = 0.362). There was no statistically significant difference in postoperative complications between the RRDG and CLDG group (p = 0.189). The mean time to first semi-fluid diet was shorter in the patients who underwent RRDG than CLDG (p = 0.030), and the incidence of postoperative ileus was lower in the RRDG group than the CLDG group (0% and 9.9%, respectively, p = 0.034). CONCLUSIONS: Despite use of fewer ports, RRDG with TULAB had similar outcomes to CLDG in terms of the incidence of postoperative morbidity and the number of harvested lymph nodes. Furthermore, by reducing the number of incisions, the incidence of the intra-abdominal adhesions can potentially be lowered when RRDG is used.

Investigation of satisfaction with short-term outcomes after switching to faricimab to treat neovascular age-related macular degeneration.

PURPOSE: To investigate the outcomes and patient satisfaction at 6-months' follow-up after switching to faricimab to treat neovascular age-related macular degeneration (nAMD) with a treat-and-extend (TAE) regimen. STUDY DESIGN: Retrospective observational study. METHODS: Forty-eight consecutive eyes (48 patients) were switched to faricimab to treat nAMD and followed for 6 months on a TAE regimen. The Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) was administered to patients 6 months after the switch. RESULTS: Best-corrected visual acuity (BCVA) was maintained 6 months after the switch, while the mean (± standard error) central foveal thickness 6 months after the switch (272 ± 14 µm) decreased significantly compared to the time of the switch (372 ± 20 µm) (p < 0.001). The interval between injections 6 months after the switch was 10.45 ± 0.44 weeks, a significant extension from 6.72 ± 0.34 weeks at the switch (p = 0.002). The MacTSQ total score (58.8 ± 1.7) in eyes with a BCVA of 20/40 and better 6 months after the switch was significantly higher compared to that in eyes with a BCVA worse than 20/40 (48.2 ± 1.5) (p < 0.001). The MacTSQ total score (56.8 ± 1.8) in eyes in which a 4 weeks extension of the injection interval was achieved was significantly higher than (49.5 ± 1.9) in eyes without (p < 0.001). CONCLUSION: Switching to faricimab with a TAE regimen seems to maintain the BCVA and extend the injection interval in patients with nAMD, resulting in enhanced satisfaction.

Improving urban ecosystem holistic sustainability of municipal solid waste-to-energy strategy using extended exergy accounting analysis.

Waste-to-energy technologies play a crucial role in integrated waste management strategies to reduce waste mass and volume, disinfect the waste, and recover energy; different technologies have advantages and disadvantages in treating municipal solid waste under urban conditions. This paper applies the extended exergy accounting method to develop an analytical framework to identify the optimal waste-to-energy strategy from an urban ecosystem holistic sustainability perspective. In the analytical framework, urban ecosystem costs and revenues are formulated as a multi-criteria cost-benefit quantitative model. The urban ecosystem cost is divided into five categories, and the urban ecosystem revenues consist of direct and indirect parts. The direct part is the chemical exergy of the waste-to-energy plants produced product, and the indirect part includes equivalent exergy content of power generation substitution, human health risk elimination, disamenity impact removal and environmental degradation avoidance. Proposing an indicator system to evaluate the waste-to-energy strategy impact on the sustainability of the urban ecosystems and social, economic and environmental sub-ecosystem. Detailed analysis of food waste treatment scenarios of a food center in Singapore was done as a case study to illustrate this analytical framework. Base scenario is current practice that food waste disposal in incineration plant. Anaerobic digestion and gasification are proposed as potential technological solutions for on-site food waste treatment in scenario I and II respectively. In different scenarios, the urban ecosystem costs are estimated to be 71,536.01, 61,854.87 and 74,190.34MJ/year respectively, and the urban ecosystem revenues are estimated to be 135,312.66, 405,442.53 and 298,426.81MJ/year respectively. We show that the scenario where food waste is treated by anaerobic digestion outperforms both the base scenario and scenario II in terms of urban ecosystem costs and revenues, technical energy conversion efficiency, contribution to urban ecosystem holistic sustainability, and natural, social, and economic subsystems improvement, making it the optimal municipal solid waste-to-energy strategy choice.

Predictors of stoppage and recurrence of choroidal neovascularization with a Treat- Extend-Stop protocol: 4-year follow-up.

OBJECTIVE: To analyze the long-term results of treatment of active age-related macular degeneration (AMD) with anti-vascular endothelial growth factor (VEGF) agents using the treat-extend-stop (TES) approach, defining predictive factors for stoppage of the treatment and recurrences in a real-world setting. METHODS: Data from 191 eyes treated with intravitreal injections for choroidal neovascularization due to AMD were retrospectively reviewed. Changes in best-corrected visual acuity (BCVA) and membrane activity (optical coherence tomography) were recorded and evaluated over a 48-month follow-up. Logistic regression analysis was used to determine predictors of treatment stoppage and recurrences after stoppage. RESULTS: BCVA improvement was found in 70.5% of eyes at 48 months, and remaining signs of activity in 27.9%. Disease inactivity was achieved in 69 eyes (31.9%), with a relapse of the membrane in 29 of these eyes (42.0%). Significant independent predictors of treatment stoppage were found: no foveal membrane, inactive membrane at 12, 24, 36 and 48 months, extension interval>8 weeks at 12 and 24 months,>15 injections at 24 months, and baseline BCVA>61 letters. Concerning recurrent membranes, only the presence of membrane activity at 36 months and baseline BCVA>61 letters were independent predictors. CONCLUSIONS: Anti-VEGF treatment of AMD using the TES protocol allows for successful visual restoration in most patients, with more likely disease inactivity in those eyes with better baseline BCVA, maintaining signs of membrane inactivity during the first two years of follow-up and requiring fewer injections.