Treatment Interval Research Articles

Matched-pair analysis of mCRPC patients receiving 177Lu-labeled PSMA-targeted radioligand therapy in a 4-week versus 6-week treatment interval

BackgroundThe optimal regimen for 177Lu-labeled prostate-specific membrane antigen-targeted radioligand therapy, including treatment intervals, remains under study, with evidence suggesting shorter intervals could benefit patients with high disease volume and rapid progression. This retrospective analysis evaluated treatment toxicity, PSA response, PSA-progression-free survival (PSA-PFS), and overall survival (OS) in matched cohorts of mCRPC patients receiving 177Lu-PSMA-RLT at 4-week versus 6-week intervals.ResultsA PSA response (PSA decline ≥ 50%) was achieved in 47.8% and 21.7% of patients in the 4-week and 6-week treatment interval groups, respectively (p = 0.12). There was a trend towards longer PSA-PFS in the 4-week group compared to the 6-week group (median PSA-PFS, 26.0 weeks vs. 18.0 weeks; HR 0.6; p = 0.2). Although not statistically significant, there was a trend towards shorter OS in the 4-week group compared to the 6-week group (median OS, 15.1 months vs. 18.4 months; HR 1.3; p = 0.5). The 4-week group had a significantly greater decrease in leucocyte and platelet counts compared to the 6-week group (38.5% vs. 18.2% and 26.7% vs. 10.7%; p = 0.047 and p = 0.02). Severe adverse events were modest in both groups.ConclusionsIntensifying treatment intervals from 6 weeks to 4 weeks showed some improvements in PSA response and PSA-PFS for mCRPC patients, but did not significantly affect OS. Additionally, bone marrow reserve was significantly reduced with the intensified regimen. Therefore, the overall benefit remains uncertain, and further prospective studies are needed to compare 4-week and 6-week intervals regarding toxicity, treatment response, and outcome.

Faricimab versus bevacizumab for neovascular age-related macular degeneration: Cost analysis based on real-world data from the Swedish Macula Registry.

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. 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. 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. 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.

Real-world six-month outcomes in patients switched to faricimab following partial response to anti-VEGF therapy for neovascular age-related macular degeneration and diabetic macular oedema.

Landmark studies reported on faricimab efficacy and safety predominantly in treatment naïve patients, but outcomes following switch from other anti-VEGF therapies are lacking. We evaluated patients switched to faricimab who hadpreviously shown a partial response to other anti-VEGF injections for neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). Retrospective study at the Oxford Eye Hospital. Patients switched to faricimab from January to April 2023 with six months follow-up were identified via electronic medical records. A total of 116 patients (151 eyes) were included. In 88 patients with nAMD (107 eyes), mean visual acuity remained stable: 62±17 ETDRS letters at baseline; 62±18 at six months (p > 0.05). Central subfield thickness (CST) reduced from 294 ± 73 μm to 270 ± 53 μm (p < 0.05) at six months. Subretinal or intraretinal fluid was present in 102 eyes (95%) at baseline and 75 eyes (70%) at follow-up (p < 0.05). Pigment epithelial detachment height decreased from 233 ± 134 μm to 188 ± 147 μm (p < 0.05). Mean treatment interval increased by 1.7 weeks (p < 0.05) and was extended in 61 eyes (57%) at six months. In 28 patients with DMO (44 eyes), visual acuity remained stable: 69 ± 15 letters at baseline; 70±15 at six months (p > 0.05). CST reduced from 355 ± 87 μm to 317 ± 82 μm (p < 0.05). Mean treatment interval increased by 1.4 weeks (p < 0.05) and was extended in 21 eyes (46%) by six months. Switching to faricimab in treatment resistant eyes led to improved anatomical response and extended treatment interval in a significant proportion of patients. Ongoing review of real-world data will inform longer-term outcomes of safety and effectiveness.

Acetazolamide Therapy and Kidney Function in Persons with Non-albuminuric Diabetes Mellitus Type 1

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower the risk of kidney failure in persons with type 2 diabetes. The presumed mechanism of action is through greater delivery of sodium to the distal tubule, activation of tubuloglomerular feedback which lowers glomerular filtration rate (GFR) and intra-glomerular pressure. SGLT2is are not approved for use in persons with type 1 diabetes due to the risk of diabetic ketoacidosis. Acetazolamide, a proximal tubule diuretic, delivers more sodium to the distal nephron, and may activate tubuloglomerular feedback in a similar way to SGLT2is without a higher risk of diabetic ketoacidosis. The kidney effects and safety of acetazolamide in persons with type 1 diabetes have not been well studied. Methods: We conducted a dose-escalation trial to determine the effects of 3 dosages of oral acetazolamide (62.5mg, 125mg, and 250mg, all twice-daily) in 12 persons with type 1 diabetes. Participants were treated for 2 weeks followed by a 2-week washout before exposure to the next dosage level. Blood and urine chemistries, as well as iohexol measured GFR, were assessed before and after each treatment interval. We aimed to identify a dose that maximized measured GFR reductions while minimizing adverse effects. Results: The mean age was 46±17 years, 100% were White, and 75% were female. The mean measured GFR was 89±18ml/min/1.73m2 at baseline. Acetazolamide reduced measured GFR by 15% (95% CI 9, 21), 14% (95% CI 7, 21), and 15% (95% CI 10, 21) after 2 weeks at the 62.5mg, 125mg, and 250mg twice-daily dosage levels respectively. The measured GFR reduction was fully reversed after each 2-week washout. Serum bicarbonate was reduced by 2.3, 4.2 and 4.4 mEq/L with escalating doses, and no episodes of hypokalemia (&lt; 3.5 mEq/L) were observed. Conclusions: Among persons with type 1 diabetes and preserved kidney function, acetazolamide caused an acute, reversible reduction in measured GFR without effects on glucose metabolism.

Treatment regimens for optimising outcomes in patients with neovascular age-related macular degeneration.

Practice patterns for neovascular age-related macular degeneration (nAMD) have evolved from the landmark registration trials of vascular endothelial growth factor (VEGF) inhibitors. Non-monthly regimens like treat-and-extend (T&E) have become popular due to their effectiveness in clinical practice. T&E regimens attempt to limit the burden of visits and treatments by allowing progressively longer treatment intervals, but in so doing, are potentially associated with the expense of treating quiescent disease. This is acceptable to many patients and their ophthalmologists but can still be problematic in the real-world. Recent studies have further refined the T&E approach by allowing for quicker and longer extension of treatment intervals when less severe disease is detected. With newer drugs offering increased durability, a shift to longer regular intervals may emerge as a new practice pattern for VEGF inhibitor therapy. This review aims to consolidate the current literature on the most effective treatment patterns and update treatment guidelines based on options that are now available. It also summarises new aspects of nAMD management that may help to further refine current practice.

Baseline characteristics associated with the first year treatment interval of intravitreal faricimab in neovascular age-related macular degeneration (nAMD)

AimsTo identify baseline characteristics that best correlate to treatment interval for naive neovascular age-related macular degeneration patients treated with faricimab in the first year (Y1) of the TENAYA and LUCERNE...

Delays in Presentation, Diagnosis, and Treatment Among Patients With GI Cancer in Southwest Nigeria.

The incidence of GI cancers is increasing in sub-Saharan African countries. We described the oncological care pathway and assessed presentation, diagnosis, and treatment intervals and delays among patients with GI cancer who presented to the Obafemi Awolowo University Teaching Hospitals Complex in Ile-Ife, Nigeria. We analyzed data from 545 patients with GI cancer in the African Research Group for Oncology (ARGO) database. We defined presentation interval as the interval between symptom onset and presentation to tertiary hospital, diagnostic interval as between presentation and diagnosis, and treatment interval as between diagnosis and initiation of treatment. We considered >3 months, >1 month, and >1 month to be presentation, diagnosis, and treatment delays, respectively. We compared lengths of intervals using Mann-Whitney U tests and logistic regression. The most frequent cancer types were pancreatic (32%) and colorectal (28%). Most patients presented at stages III (38%) and IV (30%). The median presentation interval was 84 days (IQR, 56-191), and 49% presented after 3 months or longer. The median diagnosis and treatment intervals were 0 (IQR, 0-8) and 7 (IQR, 0-23) days, respectively. There was no relationship between age, sex, education, or distance to tertiary hospital and presentation delay, but patients with stage III to IV versus I to II had higher odds of presentation delay (odds ratio [OR], 1.68 [95% CI, 1.13 to 2.50]). Among patients with pancreatic cancer, older patients were less likely to have a diagnosis delay (OR, 0.50 [95% CI, 0.25 to 0.98]). About half of patients with GI cancer in Ile-Ife, Nigeria, did not present to tertiary hospitals until more than 90 days after noticing symptoms. Efforts are warranted to improve public knowledge of GI cancer symptoms and to strengthen health systems for prompt diagnosis and referral to specialty care.

Impact of treat and extend criteria on proportions that can be extended after loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration: PRECISE Report 5.

To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD). Patients with nAMD initiated on the loading phase of three intravitreal doses of 2 mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response. The proportion of patients that qualify for interval extension based on different clinical trial criteria was also evaluated. A total of 722 patients with visual acuity (VA) and optical coherence tomography (OCT) scans done at all 4 visits were included. Of these 32.4% of eyes responded with complete macular fluid resolution after the first injection with no recurrence through the loading phase (super-responders) while 26.9% had persistent macular fluid in all 4 visits (true non-responders). The rest were considered suboptimal responders. Change in VA showed marked variations within each of these categories of fluid resolution. For extension of next treatment interval, if presence of any macular fluid at the post-loading visit is the only criteria considered, about 50% could be extended to 8 weeks. If both VA worsening by ≥5 letters and a > 25 μm increase in central sub-field thickness (CST)are considered, 90% will be eligible for interval extension. Clinical trial designs and pre-defined treatment extension/shortening criteria determine the proportion of patients requiring treatment in the post-loading visit. The short and long-term impact of interval extension immediate post-loading on visual outcome in clinical practice is unknown.

Submacular Hemorrhage Rates Following Anti-Vascular Endothelial Growth Factor Injections for Exudative Age-Related Macular Degeneration

Objective: To examine rates of submacular hemorrhage in patients undergoing anti-VEGF injections, comparing rates between specific anti-VEGF agents. Design: Retrospective clinical cohort study. Participants: All patients in the database from January 2015-November 2023 with a diagnosis of neovascular age-related macular degeneration (nAMD) and accompanying submacular hemorrhage (SMH). Methods: SMH prevalence and associated anti-VEGF injection type were analyzed in 140,915 eyes (of which 9,107 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 3,439 (37.8%) eyes, brolucizumab-dbII in 46 (0.51%) eyes, aflibercept in 3,221 (35.4%) eyes, ranibizumab in 2,246 (24.7%) eyes, and faricimab-svoa in 155 (1.7%) eyes. Rates of SMH were significantly higher (p≤0.001) for last injection with bevacizumab compared to every other injection type. Rates of SMH were significantly lower (p=0.0004) for last injection with faricimab-svoa compared to every other injection type. Patients receiving either faricimab-svoa or ranibizumab injections each had significantly shorter (mean and standard deviation (SD) 48.9 (27.9), p<0.02; mean and standard deviation (SD) 59.6 (38.2), p=0.003, 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-dbII, 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 nAMD.

SYNCHRONIZE: Real-World Retrospective Safety Analysis of Patients Treated with OnabotulinumtoxinA for More than One Therapeutic Indication.

OnabotulinumtoxinA (onabotA) is approved in the US for 12 therapeutic indications. Real-world data on onabotA multi-indication use are limited, often leading to delayed or reduced treatment. This study provides real-world evidence on the safety of onabotA when treating multiple indications concomitantly. SYNCHRONIZE was a multicenter, retrospective, chart-review study evaluating onabotA's safety for adults treated for ≥2 therapeutic indications within a 3-month period. The primary outcome was treatment-emergent adverse events (TEAEs) within 6 months post-treatment. A total of 279 patients were included. The most common concomitant indications treated were cervical dystonia and chronic migraine (43.4%). The average 3-month cumulative dose for multiple indications was 282.2 U. The treatment interval for multiple indications was ≤24 h for most patients (62.4%). Overall, 28.7% of patients reported ≥1 TEAE with no apparent trends in TEAEs and dose interval or cumulative dose. Reported TEAEs included UTI (5.7%), neck pain (5.0%), and headache (4.3%). No patient had a lack of effect according to clinical objective measurements. SYNCHRONIZE described the real-world safety of onabotA for patients treated concomitantly for ≥2 indications within a 3-month period. TEAEs were generally consistent with the known safety profiles of individual indications. No new safety signals were identified).

One-Year Real-World Outcomes of Intravitreal Faricimab for Previously Treated Neovascular Age-Related Macular Degeneration.

This study assessed the efficacy, durability, and safety of faricimab in patients with neovascular age-related macular degeneration (nAMD), previously treated with aflibercept or ranibizumab with unsatisfactory results. This was a single-center, prospective cohort study of all consecutive patients with nAMD switched to intravitreally administered faricimab from traditional anti-vascular endothelial growth factor (anti-VEGF) treatments between September 2022 and April 2023 because of unsatisfactory response (maximal fluid-free interval ≤ 8weeks). Faricimab was administered with a loading dose of four 4-weekly injections, followed by a treat-and-extend regimen. The primary outcome measures were maximum fluid-free interval after the switch and last assigned treatment interval. Secondary outcome measures included best-corrected visual acuity (BCVA) and structural optical coherence tomography parameters. Thirty-three eyes of 33 patients were included. Patients were followed for a median of 72weeks [interquartile range 61, 76]. Median maximum fluid-free treatment interval after switch to faricimab and the last assigned interval were significantly longer than before the switch (7 vs. 4weeks, p < 0.001 and 8 vs. 5weeks, p < 0.001, respectively). Significant improvements in central subfield thickness (353 vs. 281µm), macular volume (2.46 vs. 2.16mm3), and pigment epithelial detachment height (198 vs. 150µm) were observed (all p < 0.001). BCVA remained stable at 0.4 versus 0.3logMAR before switch (p = 0.190). One eye (3%) developed intraocular inflammation and one eye (3%) developed a retinal pigment epithelium tear. Faricimab improved anatomical outcomes and allowed longer treatment intervals in patients with nAMD previously treated with other anti-VEGF therapies with unsatisfactory response, reducing treatment burden. A favorable safety profile was observed.

ThP5.12 - Safety of emergency laparoscopic cholecystectomy in the treatment of gall stone disease: A single centre observational study from a District General Hospital

Abstract Aim To evaluate the safety of emergency laparoscopic cholecystectomy in the treatment of gallstone disease. Methods This was a retrospective, single-centre observational study of 267 patients who were admitted with abdominal pain due to a gallstone related pathology during June 2021 to June 2022. The parameters studied were age, gender, duration of symptoms, previous admissions, investigations, imaging, conservative or surgical treatment, emergency surgery or elective interval surgery, utilisation of dedicated "hot gallbladder list", re-admissions, and re-operations. Results Out of the 267 patients, 163 were female and 104 were male. The median age was 61 with the age ranging from 20 to 96. The median duration of symptoms was 2 days before admission. First-time admissions were 226 and re-admissions were 41. Ultrasound, CT and MRI were done on 188, 123 and 64 patients respectively. 178 patients were diagnosed to have acute calculous cholecystitis, 51 patients had acute gallstone pancreatitis and 38 had biliary colic due to lithiasis. 172 patients were treated with surgery of which 104 were operated on during the same admission, 20 in readmission and 48 as an interval elective surgery. Of the 124 emergency operations, 37 were performed on the dedicated "hot gallbladder list" and 87 were performed on the emergency CEPOD list. 2 patients were re-operated due to post-operative complications. 95 patients were managed conservatively. Conclusions Emergency laparoscopic cholecystectomy is a safe option when performed by experienced surgeons. A dedicated "hot gall bladder list" provides a safe and effective way to reduce the disease burden.

Switch to faricimab after initial treatment with aflibercept in eyes with neovascular age-related macular degeneration

PurposeTo investigate the efficacy and outcomes of switching neovascular age-related macular degeneration (nAMD) patients from aflibercept to faricimab, focusing on visual acuity, retinal fluid management, and treatment intervals. The primary aim was to assess the early outcomes in nAMD patients refractory to aflibercept and explore faricimab’s potential as a longer-lasting therapeutic alternative.MethodsA single-center retrospective study was conducted on 50 refractory nAMD patients at Cleveland Clinic Abu Dhabi from September 2022–May 2023. Patients were switched from aflibercept to faricimab, having met specific criteria for refractory nAMD. The study analyzed best-corrected visual acuity (BCVA), central subfield thickness (CST), and fluid changes post-switch, using Optical Coherence Tomography (OCT).ResultsAfter three faricimab injections, significant reductions in CST were observed, with a notable decrease in retinal fluid. The mean BCVA remained stable throughout the study period. Although there was a decrease in the maximum pigment epithelial detachment (PED) height, it was not statistically significant. Treatment intervals post-switch showed that the majority of patients maintained or extended their treatment intervals, with a significant proportion achieving resolution of intraretinal fluid (IRF) and subretinal fluid (SRF).ConclusionsSwitching to faricimab from aflibercept in refractory nAMD patients led to significant improvements in retinal fluid management and CST, with stable BCVA outcomes. Faricimab presents a promising alternative for patients requiring frequent aflibercept injections, potentially offering a more manageable treatment regimen with extended dosing intervals. This study highlights the need for personalized therapeutic strategies in nAMD treatment, though further research is necessary to optimize treatment switches.

Efficacy and Durability of Faricimab in Naïve Eyes with Neovascular Age-Related Macular Degeneration

Introduction: The aim of the study was to evaluate functional and anatomical changes in patients with neovascular age-related macular degeneration (nAMD) treated with a loading dose of faricimab intravitreal injections (IVIs). Methods: Eighteen eyes of 18 patients with active macular neovascularization and nAMD were enrolled at the Ophthalmology Clinic of University G. D’Annunzio, Chieti-Pescara, Italy. All patients were scheduled for faricimab IVI as per label. Enrolled patients underwent complete ophthalmic evaluation, including optical coherence tomography, fluorescein angiography, and indocyanine green angiography. All measurements were evaluated at baseline (T0) and then monthly up to week 20 (T4). Main outcome measures were changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachments (PEDs) presence and maximum height (PED-MH), intraretinal fluid (IRF) presence, subfoveal subretinal fluid (SSRF) presence and thickness. Results: BCVA improved and CMT reduced significantly during follow-up (p < 0.001). In addition, SFCT decreased significantly (p = 0.031). Between T0 and T4, SSRF presence reduced from 55.6 to 16.7% (p = 0.045); IRF presence changed from 50 to 22.2%, respectively (p = 0.074). PED-MH was reduced in 58.8% of patients at T4. At week 20, 72.3% of patients were in the q12/q16 interval. Conclusion: Faricimab showed efficacy in the treatment of naïve nAMD patients with an improvement of anatomical and functional parameters and a treatment interval after the loading phase equal or greater than 12 weeks in the majority of patients.

Long-Term Management of Post-Stroke Spasticity with Botulinum Toxin: A Retrospective Study.

Stroke-induced spasticity is a prevalent condition affecting stroke survivors, significantly impacting their quality of life. Botulinum Toxin A injections are widely used for its management, yet the long-term effects and optimal management strategies remain uncertain. This retrospective study analyzed medical records of 95 chronic stroke patients undergoing long-term BoNT-A treatment for spasticity. Demographic data, treatment duration, dosage variability, and dropout rates were assessed over a period ranging from 2 to 14 years. The study revealed a notable extension of the interval between BoNT-A injections throughout the treatment duration. Dropout rates peaked during the initial 5 years of treatment, perhaps due to perceived treatment ineffectiveness. Additionally, a trend of escalating dosage was observed across all groups, indicating a potential rise in the severity of spasticity or changes in treatment response over time. BoNT-A injections emerged as the predominant treatment choice for managing post-stroke spasticity. The delayed initiation of BoNT-A treatment underscores the need for heightened awareness among healthcare providers to recognize and manage spasticity promptly post-stroke. Patients' expectations and treatment goals should be clearly defined to optimize treatment adherence, while the observed escalation in dosage and treatment intervals emphasizes the dynamic nature of spasticity and underscores the importance of monitoring long-term treatment outcomes.

High-Dose Brolucizumab for Refractory Neovascular Age-Related Macular Degeneration Resistant to Standard-Dose Brolucizumab.

The aim of this study was to evaluate the efficacy and safety of escalating the dosage of intravitreal brolucizumab in patients with refractory neovascular age-related macular degeneration (AMD). This retrospective study included 17 eyes of 17 patients with refractory AMD treated with high-dose brolucizumab (12mg/0.1ml) for over 12months. Patients initially received at least one anti-vascular endothelial growth factor (anti-VEGF) agent and were switched to standard-dose brolucizumab (6mg/0.05ml). Those who showed a suboptimal response to standard-dose treatment had their dosage of brolucizumab escalated. Visual acuity was maintained from 68.3 ± 3.4 letters to 70.7 ± 3.2 letters after 12months of high-dose treatment (P = 0.128). Central subfield thickness was 343.7 ± 17.0μm before high-dose treatment and 316.7 ± 18.5μm at 12months (P = 0.083). The proportions of patients with subretinal fluid and serous pigment epithelial detachment significantly decreased from 82.4% to 41.2% and from 52.9% to 17.6%, respectively, after high-dose treatment (P = 0.039 and P = 0.031, respectively). The treatment interval extended from 7.2 ± 2.4weeks to 10.2 ± 2.2weeks after switching to standard-dose brolucizumab (P < 0.001) and was maintained at 13.5 ± 2.8weeks after increasing the dose (P = 0.154). No severe ocular adverse events were observed. High-dose brolucizumab was effective in patients who did not respond to standard-dose brolucizumab after switching from previous anti-VEGF agents. Increasing the dosage could offer sustained disease control and reduce the treatment burden for patients with refractory AMD.

Dual pathway inhibition with faricimab for previously treated neovascular age-related macular degeneration and diabetic macular oedema: guidance from a UK panel of retina specialists.

Some eyes with neovascular age-related macular degeneration (nAMD) and centre-involving diabetic macular oedema (DMO) fail to respond sufficiently or lose response over time to standard of care intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. This paper explores clinical scenarios for switching to dual action angiopoietin-2 (Ang-2)/VEGF-A inhibitor faricimab (Vabysmo, Roche Products Limited) in previously anti-VEGF-treated patients. A national steering group meeting of UK retina specialists was held in London on 27 October 2023. Clinician practice and experience were reviewed together with pivotal clinical trial data and early findings from real-world settings. Roche Products Limited facilitated and funded the meeting. While there is no standardised protocol for identifying suboptimal response, the authors review relevant clinical biomarkers of disease activity used in routine clinical practice to determine patient response and guide treatment decisions. Common reasons identified for considering a change of treatment were lack of efficacy demonstrated by suboptimal anatomic or visual improvement and insufficient durability of response. The panel outline strategies for switching to faricimab among eligible patients with a prior anti-VEGF treatment history, with initial monthly loading doses or maintaining the previous treatment interval before attempting to extend, that may be integrated into current treat-and-extend (T&E) clinical pathways for treating patients with nAMD and DMO. General considerations for switching between treatments are also reviewed. Clinicians may consider a treatment switch to faricimab in nAMD and DMO patients who have suboptimal disease control or insufficient durability of response on initial anti-VEGF therapy.

Effect of vibratory probe compaction method on bearing capacity of loess investigated via random finite element analysis

Probabilistic analyses using random fields are increasingly performed in geotechnical fields; however, they focus on random fields in natural soils. Comparatively, few studies have been conducted regarding random field variations in improved ground. An innovative technique for treating loess–the pneumatic vibratory probe compaction method is used in this study. The effects of different construction techniques on the spatial variability of improved ground and bearing capacity are investigated by varying the pneumatic injection pressure and treatment interval. To determine the posteriori parameter of the effective friction angle of a loess random field, Bayes' theorem and the transitional Markov chain Monte Carlo algorithm are applied. Subsequently, a random finite element analysis is performed. Based on the results, the maximum increase in bearing capacity and the minimum dispersion are achieved at a jet pressure of 0.6 MPa under a treatment interval of 1.4 m. Furthermore, the probability of failure is reduced to the lowest possible level.

Real-World Efficacy of Intravitreal Faricimab for Diabetic Macular Edema: A Systematic Review.

Diabetic macular edema (DME) is a prevalent exudative maculopathy, and anti-vascular endothelial growth factor (anti-VEGF) therapy is the first-line choice for treatment. Faricimab, a novel anti-VEGF and anti-angiopoietin-2 bispecific agent, has recently been approved for the treatment of DME. In this study, we systematically reviewed the real-world evidence of the efficacy of faricimab for the treatment of DME. We searched 11 databases for eligible studies. Study selection and data extraction were made independently by two authors in duplicate. Eligible studies were reviewed qualitatively. We identified 10 eligible studies that summarized data from a total of 6054 eyes with a mean follow-up of between 55 days and 12 months. Five studies reported outcomes in a population of both treatment-naïve and previously treated eyes, and five studies reported outcomes exclusively in relation to eyes that were previously treated. Faricimab improved the best-corrected visual acuity and macular thickness. The extension of the treatment interval was possible in 61-81% of treatment-naïve eyes and 36-78% of previously treated eyes. Faricimab for DME yields clinical outcomes similar to those known from previous anti-VEGF treatments but with extended treatment intervals, thus lowering the burden of therapy for patients. Long-term real-world studies are warranted.

The Role of Botulinum Toxin A Neuromodulator in the Management of Synkinesis in Facial Palsy.

Facial palsy describes the denervation of the facial nerve leading to difficulty in facial animation and expression. Facial synkinesis is the result of complex pathological nerve regeneration following damage to the facial nerve axons. Synkinesis in facial palsy can be managed using facial neuromuscular rehabilitation, botulinum toxin neuromodulators, and surgical treatment options. Botulinum toxin A can be used as an adjunct to other treatment options to manage synkinesis. This article will explore the role of botulinum toxin A in the management of synkinesis in facial palsy including the clinical assessment, injection location (muscles targeted), dosages, treatment interval, and long-term results. It will also include surgical management options.