Usability of the SB11 Pre-filled Syringe (PFS) in Patients with Retinal Diseases.

INTRODUCTION: SB11 (Byooviz™; Samsung Bioepis Co., Ltd.) is a ranibizumab (Lucentis®; Genentech, Inc.) biosimilar targeting vascular endothelial growth factor A for the treatment of retinal diseases. The pre-filled syringe (PFS) presentation of SB11 offers an alternative administration method to the vial, with the potential for enhanced safety and efficient syringe preparation. The objective of this study was to assess the ability of healthcare professionals (HCPs) to follow the instructions for use to prepare and administer SB11 PFS intravitreal (IVT) injections to patients with neovascular age-related macular degeneration (nAMD) or macular edema secondary to retinal vein occlusion (RVO). METHODS: This study was an open-label, single-arm, single-dose clinical study to evaluate the usability of the SB11 PFS in patients with nAMD or macular edema secondary to RVO. Four HCPs prepared and administered 0.5 mg SB11 PFS IVT injections to 34 patients. Product use task completion (12 tasks in total) was assessed by independent observers. Safety was assessed up to 7 days after injection of the investigational product. RESULTS: A total of 34 patients were enrolled and completed the study. All 12 tasks were successfully completed in 34 (100%) patients without a use-related failure. Most patients (32 patients, 94.1%) experienced no adverse events (AEs), whereas 2 (5.9%) patients experienced three treatment-emergent AEs (TEAEs) which were mild to moderate in severity. There were no severe or serious TEAEs reported during the study. CONCLUSIONS: This study showed that HCPs were able to successfully prepare and administer the SB11 PFS via IVT injection. No unexpected safety issues were identified. The SB11 PFS is a promising alternative for therapeutic administration of SB11 in patients with retinal disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06176963; EudraCT number 2021-003566-12.

Biosimilar SB15 versus reference aflibercept in neovascular age-related macular degeneration: 1-year and switching results of a phase 3 clinical trial.

BACKGROUND/AIMS: To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD). DESIGN: Prospective, double-masked, randomised, phase 3 trial. METHODS: Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch's membrane). Additional endpoints included safety, PK and immunogenicity. RESULTS: Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (-2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were -119.2 µm and -132.4 µm for SB15/SB15 and -126.6 µm and -136.3 µm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 µm (-6.11 to 20.96); TRT: difference (95% CI)=3.9 µm (-18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (-2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups. CONCLUSIONS: Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.

Efficacy and Safety of the Aflibercept Biosimilar SB15 in Neovascular Age-Related Macular Degeneration: A Phase 3 Randomized Clinical Trial.

Importance: Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy. Objective: To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD). Design, Setting, and Participants: This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up. Intervention: Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56. Main Outcomes and Measures: The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity. Results: The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 µm vs AFL, -115.7 µm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable. Conclusions and Relevance: In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD. Trial Registration: ClinicalTrials.gov Identifier: NCT04450329.

The Impact of Robotic Fractionated Radiotherapy for Benign Tumors of Parasellar Region on the Eye Structure and Function.

PURPOSE: To evaluate the radiation effect of fractionated robotic radiotherapy of benign tumors located in the parasellar region on the anterior and posterior segments of the eye. METHODS: A prospective observational study based on the expanded ophthalmological examination. The pre-treatment baseline was used as a control for the post-radiotherapy follow-up examinations. The study group consists of 34 patients (68 eyes) irradiated using the CyberKnife system. There were ten patients with cavernous sinus meningioma, nine with pituitary adenoma, five with meningioma of the anterior and middle cranial fossa, five with meningioma in the region close to optic chiasm, three with craniopharyngioma, and two with meningioma of the orbit. All patients were treated using three fractions of 600-800 cGy. We assessed the impact of radiation on the eye based on changes in anatomical and functional features. The condition of the eye surface, central corneal thickness (CCT), endothelial cell density (ECD), lens densitometry, central macular thickness (CMT), and retinal nerve fiber layer (RNFL) were the anatomical features assessed. The functional tests were best-corrected visual acuity (BCVA), intraocular pressure (IOP), visual field (VF) and visual-evoked potentials (VEP). An ophthalmologic examination was performed before and 6, 12, 18, and 24 months after radiotherapy. RESULTS: We did not observe any significant changes in BCVA, IOP, CCT, CMT, VF, and VEP, nor in the slit-lamp examination during the two-years observation. We found a significant decrease in ECD at all follow-up measurements. The drop in ECD exceeded approximated age-related physiological loss. The reduction in ECD was not large enough to disrupt corneal function and thus affect vision. We also observed a statistically significant reduction of RNFL in all observation time points. However, there was no correlation between the dose delivered to the optic pathway and the decrease in RNFL thickness. The thinning of the RNFL was not significant enough to impair visual function. CONCLUSION: Fractionated robotic radiotherapy of the tumors located close to the optical pathway is safe and does not impair patient's vision. Minor changes found in optic nerve anatomy (RNFL thinning) might be related to radiation effect or tumor compression. The causal relation between low doses of radiation delivered to the cornea and the observed significant but slight decrease in ECD is uncertain. The observed changes did not cause visual disturbances perceivable by the patients.

Current Management Options in Irvine-Gass Syndrome: A Systemized Review.

Irvine-Gass syndrome (IGS) remains one of the most common complications following uneventful cataract surgery. In most cases, macular edema (ME) in IGS is benign, self-limiting, and resolves spontaneously without visual impairment; however, persistent edema and refractory cases may occur and potentially deteriorate visual function. Despite the relatively high prevalence of IGS, no solid management guidelines exist. We searched the PUBMED database for randomized clinical trials (RCT) or case series of at least 10 cases published since 2000 evaluating different treatment strategies in patients with cystoid macular edema (CME). The search revealed 28 papers that fulfilled the inclusion criteria with only seven RCTs. The scarceness of material makes it impossible to formulate strong recommendations for the treatment of IGS. Clinical practice and theoretical background support topical non-steroidal anti-inflammatory drugs (NSAIDs) as the first-line therapy. Invasive procedures, such as periocular steroids, intravitreal corticosteroids, and anti-vascular endothelial growth factor (anti-VEGF), are usually applied in prolonged or refractory cases. Results of novel applications of subthreshold micropulse laser (SML) are also promising and should be studied carefully in terms of the safety profile and cost effectiveness. Early initiation of invasive treatment for providing better functional results must be examined in further research.

Ocular Complications Following Autologous Fat Injections into Facial Area: Case Report of a Recovery from Visual Loss After Ophthalmic Artery Occlusion and a Review of the Literature.

With the increase in popularity of the use of cosmetic fillers in plastic and esthetic surgery, the possibility of severe ocular complications should not be neglected. Of the fillers used, autologous fat is the most common to cause permanent visual deterioration, one of the most severe complications associated with the use of cosmetic fillers. Here we present the first report of a complete recovery of visual acuity from an instance of visual loss with no light perception caused by ophthalmic artery occlusion of the right eye following autologous fat injection in the facial area. Immediate ophthalmological intervention and comprehensive therapy with prostaglandins and vinpocetine made it possible to restore retinal perfusion and achieve complete recovery of visual acuity. Awareness of the iatrogenic artery occlusions associated with facial fillers and the need for immediate treatment should be popularized among injectors to prevent devastating consequences, such as permanent vision loss. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Neuromarkers of anxiety and depression in a patient after neuro-ophthalmic surgery of the meningioma - effect of individually-tailored tDCS and neurofeedback.

UNLABELLED: The aim of the study was to evaluate the effectiveness of individually tailored anodal tDCs/ neurofeedback protocol for the reduction of post-operative depression after a neuroophtalmological operation of the meningioma. The neuromarkers in Quantitative EEG (QEEG) and Event-related potentials (ERPs) were utilized in the construction of protocol and evaluation. CASE DESCRIPTION: A 45-year-old female after successful neuro-ophthalmic surgery of the meningioma, complained of severe pain and anxiety, difficulties with sleeping, attention and memory problems, as well as inability to continue working in her given profession. Neuropsychological testing showed lack of cognitive disturbances and post-operative depression. Two working hypotheses were tested to find neuromarkers of depression and anxiety. In line with the 'depression hypothesis' a frontal alpha asymmetry pattern was found in the patient, and in line with the 'anxiety' hypothesis an increased left temporal P1 wave in response to visual stimuli was found in ERPs. A specific alpha asymmetry neurofeedback protocol combined with an anodal tDCS was suggested. Twenty sessions of individually-tailored anodal tDCs/ neurofeedback protocol were performed. The QEEG frontal asymmetry pattern and the excessive temporal P1 wave were normalized after the intervention. CONCLUSIONS: The patient recovered from post-operative depression and returned to work after 20 sessions of the combined neurofeedback/tDCS protocol. Specific patterns of QEEG and ERPs serve as neuromarkers for constructing the protocol and for monitoring the results of intervention.

The effect of the selected factors on corneal endothelial cell loss following phacoemulsification.

INTRODUCTION: Corneal endothelium is a single layer of cells, which do not regenerate. Damage to the endothelium can take place in the course of certain diseases and after intraocular operations. When the number of endothelial cells decreases, corneal decompensation can occur. Pre- and postoperative measurement of the number of the corneal endothelial cells can help assess the degree of corneal damage during the surgery. PURPOSE: To compare the effect of various factors, such as: sex, age, corneal incision, intraocular pressure, cataract density, visual acuity and surgeon's experience on corneal endothelial cell loss following uneventful phacoemulsification. MATERIAL AND METHODS: 365 patients (114 men and 251 women aged 19 to 91 years) undergoing phacoemulsification were examined preoperatively and postoperatively at 4 weeks. 68 eyes underwent phacoemulsification through a 1.8 mm microincision and 297 eyes through a standard 2.75 mm incision. Patients were operated on by four surgeons. RESULTS: There was a significant difference in the postoperative endothelial cell loss relative to the degree of cataract hardness (p < 0.001). Endothelial cell loss was significantly higher in patients aged 71 and above than in the remaining age groups. Significant differences in the postoperative endothelial cell loss were observed in relation to the clear corneal incision size (p < 0.01). Preoperative best corrected visual acuity influenced the postoperative endothelial cell loss in a statistically significant way (p < 0.05). Endothelial cell loss was strongly influenced by the surgeon's experience. CONCLUSIONS: Surgeon's experience, hardness of cataract, type of corneal incision, age and preoperative visual acuity influenced endothelial cell loss at 4 weeks following uneventful phacoemulsification, however such factors as sex and intraocular pressure showed no statistically significant influence on corneal endothelial cell loss.