Old Problem in a New Guise: Retinal Pigment Epithelium Tear after Intravitreal Faricimab (Vabysmo®) Injection.
Ontology highlight
ABSTRACT:
SUBMITTER: Clemens CR
PROVIDER: S-EPMC10294021 | biostudies-literature | 2023 Jan-Dec
REPOSITORIES: biostudies-literature
Publications
Old Problem in a New Guise: Retinal Pigment Epithelium Tear after Intravitreal Faricimab (Vabysmo<sup>®</sup>) Injection.
Clemens Christoph R CR Alten Florian F Zimmermann Julian A JA Eter Nicole N
Case reports in ophthalmology 20230101 1
This case report describes a 78-year-old patient who developed a tear of the retinal pigment epithelium (RPE) during faricimab (Vabysmo<sup>®</sup>) therapy. After three consecutive intravitreal aflibercept (Eylea<sup>®</sup>) injections with persistent disease activity, therapy was switched to faricimab. The patient experienced a tear in the RPE 4 weeks postinjection. We report the first published case of RPE tear development after intravitreal faricimab injection in neovascular age-related mac ...[more]
Similar Datasets
Project description:Background and Objectives: Faricimab is a novel bispecific antibody with Fab regions inhibiting both vascular endothelial growth factor-A and angiopoietin-2. Therefore, this study aimed to obtain short-term outcomes of intravitreal injection of faricimab (IVF) for the treatment of diabetic macular edema (DME) in daily clinical practice. Materials and Methods: A retrospective review was carried out on consecutive patients with DME who had been treated with IVF and were followed up for at least 1 month. Outcome measures included changes in logMAR best-corrected visual acuity (logMAR BCVA), central retinal thickness (CRT), number of IVF administrations, and safety. Clinical outcomes were also compared between the treatment-naïve and switch groups. Results: A total of 21 consecutive DME eyes from 19 patients were identified. The mean number of IVFs was 1.6 ± 0.8 during the mean follow-up time of 5.5 months. The overall mean logMAR BCVA following IVF was 0.236, 0.204, 0.190, and 0.224 at baseline, 1, 3, and 6 months, respectively, without a significant change from baseline to 1 month (p = 0.176) or for 6 months (p = 0.923). The overall mean CRT (μm) following IVF was 400.6, 346.6, 342.1, and 327.5 at baseline, 1, 3, and 6 months, respectively. CRT significantly decreased from baseline to 1 month (p = 0.001) but did not reach a significant level over 6 months following IVF (p = 0.070). No significant difference in BCVA or CRT was observed between the treatment-naïve and switch groups. No serious safety concerns were noted. Conclusions: IVF for the treatment of DME may preserve visual acuity and improve macular thickness without serious safety concerns in the short term in a real-world clinical setting.
| S-EPMC10142035 | biostudies-literature
Project description:There is currently no available method to efficiently deliver proteins across the plasma membrane of photoreceptor or retinal pigment epithelium (RPE) cells in vivo. Thus, current clinical application of recombinant proteins in ophthalmology is limited to the use of proteins that perform their biological function extracellularly. The ability to traverse biological membranes would enable the mobilization of a significantly larger number of proteins with previously well characterized properties. Nucleolin is abundantly present on the surface of rapidly dividing cells including cancer cells. Surprisingly, nucleolin is also present on the surface of photoreceptor cell bodies. Here we investigated whether nucleolin can be utilized as a gateway for the delivery of proteins into retinal cells following intravitreal injection. AS1411 is a G-quartet aptamer capable of targeting nucleolin. Subsequent to intravitreal injection, fluorescently labeled AS1411 localized to various retinal cell types including the photoreceptors and RPE. AS1411 linked to streptavidin (a ∼50 kDa protein) via a biotin bridge enabled the uptake of Streptavidin into photoreceptors and RPE. AS1411-Streptavidin conjugate applied topically to the cornea allowed for uptake of the conjugate into the nucleus and cytoplasm of corneal endothelial cells. Clinical relevance of AS1411 as a delivery vehicle was strongly indicated by demonstration of the presence of cell surface nucleolin on the photoreceptors, inner neurons and ganglion cells of human retina. These data support exploration of AS1411 as a means of delivering therapeutic proteins to diseased retina.
| S-EPMC5334003 | biostudies-literature
Project description:ImportanceMonitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences in clinical trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance potential benefits and risks of these agents.ObjectiveTo provide descriptions of 3 initially culture-negative cases of acute, severe, posterior-segment IOI events occurring within the same month following intravitreal faricimab injections at a single institution.Design, setting, and participantsIn this case series, 3 patients manifesting acute, severe IOI following intravitreal injection of faricimab were identified between September 20, 2023, and October 20, 2023.ExposureFaricimab, 6 mg (0.05 mL of 120 mg/mL solution), for neovascular age-related macular degeneration among patients previously treated with aflibercept; 1 patient also had prior exposure to bevacizumab.Main outcomes and measuresVisual acuity, vitreous taps for bacterial or fungal cultures, and retinal imaging.ResultsAll 3 patients received intravitreal faricimab injections between September 20 and October 20, 2023, from 2 different lot numbers (expiration dates, July 2025) at 3 locations of 1 institution among 3 of 19 retina physicians. Visual acuities with correction were 20/63 OS for patient 1, 20/40 OD for patient 2, and 20/20 OS for patient 3 prior to injection. All 3 patients developed acute, severe inflammation involving the anterior and posterior segment within 3 to 4 days after injection, with visual acuities of hand motion OS, counting fingers OD, and hand motion OS, respectively. Two patients were continuing faricimab treatment while 1 patient was initiating faricimab treatment. All received intravitreal ceftazidime, 2.2 mg/0.1 mL, and vancomycin, 1 mg/0.1 mL, immediately following vitreous taps. All vitreous tap culture results were negative. One patient underwent vitrectomy 1 day following presentation. Intraoperative vitreous culture grew 1 colony of Staphylococcus epidermidis, judged a likely contaminant by infectious disease specialists. All symptoms resolved within 1 month; visual acuities with correction were 20/100 OS for patient 1, 20/50 OD for patient 2, and 20/30 OS for patient 3.Conclusions and relevanceIn this case series, 3 patients with acute, severe IOI within 1 month at 3 different locations among 3 ophthalmologists of 1 institution following intravitreal faricimab could represent some unknown storage or handling problem. However, this cluster suggests such inflammatory events may be more common than anticipated from faricimab trial reports, emphasizing the continued need for vigilance to detect and report such cases following regulatory approval.
| S-EPMC10905372 | biostudies-literature
Project description:IntroductionThis study investigates the early temporal changes in pigment epithelial detachment (PED) morphology following treatment with faricimab in patients with neovascular age-related macular degeneration (nAMD). Utilizing an artificial intelligence (AI)-assisted approach, we provide a detailed quantification and characterization of the dynamics of these morphological changes.MethodsA prospective observational study was conducted on 22 eyes from 22 treatment-naïve patients with nAMD-associated PED (presenting either type 1 or type 3 macular neovascularization). Participants were administered intravitreal faricimab (6 mg) at baseline and at days 30, 60, and 90. Comprehensive ophthalmic evaluations and spectral-domain optical coherence tomography (SD-OCT) imaging were conducted at baseline and at seven additional follow-up visits on days 1, 7, 14, 30, 60, 90, and 120. An AI-based automated segmentation algorithm was utilized to precisely quantify changes in PED volume, alongside intraretinal (IRF) and subretinal fluid (SRF) volumes, at each time point.ResultsTreatment with faricimab resulted in a significant reduction in mean PED volume, with an average decrease of 12% at day 1, 29% at day 7, 51% at day 14, 68% at day 30, 72% at day 60, 79% at day 90, and 84% at day 120 (p < 0.0001 for all time points). Similarly rapid and marked reductions were noted in both mean IRF (23.5% at day 1, 90.7% at day 14) and SRF (14.4% at day 1, 91.2% at day 14) volumes. The study also showed a statistically significant improvement in best-corrected visual acuity (BCVA) over the follow-up period, correlating with the reduction in PED volume.ConclusionFaricimab demonstrates early and significant efficacy in improving PED architecture in patients with nAMD. The rapid morphological improvements observed in this study suggest faricimab may represent a valid therapeutic option for PEDs associated with nAMD.
| S-EPMC11408430 | biostudies-literature
Project description:BackgroundFaricimab is a novel anti-vascular endothelial growth factor agent, used to treat patients with neovascular age-related macular degeneration (nAMD). This study assessed efficacy and safety of faricimab in previously treated eyes.MethodsThis retrospective study included previously treated nAMD patients who had received at least three faricimab injections. Baseline data were collected from February 2023 to September 2023, and follow-up data were collected until April 2024. The patients were divided into two cohorts: (1) the "Loaded" cohort, which received four weekly injections prior to treatment extension, and (2) the "Interval-Matched" cohort, which continued on the same treatment interval as their previous regimen. Efficacy was evaluated based on the primary outcome measures: central subfield thickness (CST), the presence of macular fluid, and visual outcomes. Safety was assessed through the secondary outcome measure of adverse event reporting.ResultTwo hundred thirty-seven participants (297 eyes) were included with a mean age of 80.7 ± 7 years, 44% were males. 2,237 faricimab injections were administered (7.5 ± 1.9 per eye). In the loaded cohort, CST decreased from 315.1 ± 86.0 µm to 288.0 ± 63.6 µm (p < 0.001). The percentage of dry macula increased from 11.0% to 42.5% (p < 0.001). Vision changed from 67.9 ± 12.3 to 69.3 ± 13.4 letters (p = 0.002), and the injection interval extended from 5.3 ± 1.3 to 6.4 ± 2.1 weeks (p < 0.001). For the interval-matched cohort, CST decreased from 302.8 ± 57.4 µm to 291.2 ± 62.6 µm (p = 0.001). The percentage of dry macula increased from 22.5% to 47.7% (p < 0.001). Vision changed from 65.9 ± 13.8 to 65.0 ± 17.1 letters (p = 0.613), and the injection interval extended from 6.6 ± 2.8 to 7.9 ± 3.2 weeks (p < 0.001). 68 (28.7%) adverse events were reported, of which 9 (3.8%) were serious.ConclusionFaricimab showed beneficial anatomical response with stable vision, and less injections. The loaded cohort exhibited superior outcomes but needed more injections.
| S-EPMC11892307 | biostudies-literature
Project description: Not available
| S-EPMC8343317 | biostudies-literature
Project description:BackgroundIntravitreal injection (IVI) of antibody biologics is a key treatment approach in ophthalmology. Pharmaceutical compounding and storage of prefilled syringes for IVI must take place without impairing the structure and function of the biologics. This study investigated the effect of withdrawing and storing the therapeutic antibody faricimab (Vabysmo, Roche, Basel, Switzerland) in the Zero Residual silicone oil-free, 0.2-mL syringe (SJJ Solutions, The Hague, the Netherlands).MethodsTo assess the effect of syringe withdrawal on faricimab, we compared samples from syringes prepared at day 0 with samples taken directly from faricimab vials. To assess the effect of syringe storage on faricimab, we kept prefilled syringes in the dark at 4 oC for 7, 14, or 37 days and compared samples from these syringes with day 0. We measured protein concentration (with spectrophotometry), stability and integrity (with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size-exclusion chromatography (SEC), and melting temperature (Tm)), as well as binding of faricimab to its cognate antigens: vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2) (with enzyme-linked immunosorbent assay (ELISA)).ResultsFaricimab migrated in line with its expected molecular mass under both reducing and non-reducing conditions for all time points when analyzed with SDS-PAGE, without any sign of degradation products or aggregation. The SEC elution profiles were identical for all time points. There were slight variations in Tm for different time points compared to day 0 but without consistent relationship with storage time. ELISA did not detect differences in VEGF-A or Ang-2 binding between time points, and faricimab did not bind the neonatal Fc receptor.ConclusionsWithdrawal and storage of faricimab in syringes for up to day 37 did not impair the structure and bi-specific binding properties of the therapeutic antibody.
| S-EPMC10631190 | biostudies-literature
Project description:PurposeThe intravitreal injection volume is known to vary with plunger alignment and the speed of injection. We investigated the role that syringe stopper deformation plays in allowing excess volumes to be injected into the eye and the potential for the vitreous humor to become incarcerated when excess force is released within the eye.DesignExperimental study.MethodsAflibercept prefilled syringes (PFSs), ranibizumab PFSs, and 1-ml tuberculin (TB) syringes were subjected to increasing injection force to assess the extent to which each design allowed for excess volumes to be expelled after the stopper reached the bottom of the syringe barrel (i.e., after the 50-μl dose was expelled).Main outcome measuresAdditional volume expelled with stopper deformation.ResultsSyringe stoppers are capable of deformation into the dead space when additional force is applied. This allows for progressively greater medication doses to be administered. At an additional force of 3.92 N after the syringe stopper came in contact with the bottom of the syringe barrel, the aflibercept PFSs, ranibizumab PFSs, and 1-ml TB syringes dispensed an additional 17.2%, 11.4%, and 0.8% higher volume than the intended volume of 50 μl, respectively. Upon release of this force, a proportional volume was observed to be drawn back into the needle.ConclusionsThe intravitreal injection volume varies with the force applied to fully depressed syringes because of syringe stopper deformation. We advise that performing forceful intravitreal injections be avoided to prevent excessive dosing of medication. We also caution that pressure applied to the plunger during intravitreal injections not be released while the needle is in the vitreous cavity to guard against vitreous incarceration, which could lead to retinal tear formation or detachment.
| S-EPMC9754977 | biostudies-literature
Project description:IntroductionIntravitreal injection of therapeutic medications has become one of the most commonly performed procedures in ophthalmology. Over the past decade, a number of guidelines have been published that recommend proper techniques to increase the safety of intravitreal injections. In this course, we teach and practice the skills necessary to perform safe intravitreal injections.MethodsThe course was developed for first-year ophthalmology residents and was designed to be delivered in one 2-hour session. Associated materials include guidelines for faculty facilitators and residents to prepare them for safe intravitreal injection of therapeutic medications. Also included are a slide presentation, wet-lab practice guidelines, and an evaluation form.ResultsLearner response has been universally very positive. Residents (N = 15) have reported that structured lectures with practice in the wet lab improved their skill for intravitreal injection of therapeutic medication.DiscussionOverall, we found that our curriculum improved learner knowledge about safe intravitreal injections and learners' self-assessed confidence in the three objectives of the curriculum.
| S-EPMC6440421 | biostudies-literature
Project description:PurposeTo characterize faricimab ocular and systemic pharmacokinetics (PK) in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) and to assess the effect of faricimab ocular exposure on clinical endpoints.MethodsA population PK (popPK) model was developed using pooled data from phase 1 to 3 studies in patients with nAMD/DME. The dataset included 1095 faricimab aqueous humor (AH) concentrations from 284 patients and 8372 faricimab plasma concentrations from 2246 patients.ResultsFollowing intravitreal administration, faricimab PK was accurately described by a linear three-compartment model with sequential vitreous humor (VH), AH, and plasma compartments. Faricimab VH elimination to AH is the slowest process, with an estimated half-life (t1/2) of 7.5 days. Due to flip-flop kinetics, plasma, AH, and VH concentrations declined in parallel. Disease had no effect on faricimab PK. Plasma exposure was ∼6000-fold lower than VH exposure. Age, anti-drug antibodies, body weight, and sex statistically significantly influenced PK parameters but had no clinically meaningful effect on ocular and systemic exposure. VH t1/2 alone could not explain faricimab dosing frequency. Exposure-response analyses showed similar gains in best-corrected visual acuity across faricimab exposure ranges and dosing regimens.ConclusionsFaricimab ocular and systemic pharmacokinetics were quantified and accurately described by the popPK model, developed using a large dataset from patients with nAMD/DME. Exposure-response analyses suggest that faricimab phase 3 dosing algorithms are appropriate to select the most suitable dosing regimen.Translational relevanceThe popPK analysis suggested that faricimab dosing frequency was influenced by several factors and not by VH t1/2 alone.
| S-EPMC11563007 | biostudies-literature