Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema: The INSIGHT Randomized Clinical Trial.

Importance: Biosimilars may be lower-cost alternatives to originator biologic products, potentially offering expanded access or reduced economic burden, but have not been evaluated with aflibercept in diabetic macular edema (DME). Objective: To compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME. Design, Setting, and Participants: This was a double-masked, randomized clinical trial that included participants at 77 centers across the US, Europe, Japan, and India. Included in the analysis were individuals 18 years and older with type 1 or type 2 diabetes with central DME and best-corrected visual acuity (BCVA) letter score of 73 to 38 in the study eye using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Study data were analyzed from October to December 2021. Interventions: Formulations of MYL-1701P (0.5-mg vial) or reference aflibercept every 4 weeks for 5 consecutive intravitreal injections, followed by every 8 weeks through week 52. Main Outcomes and Measures: The primary outcome was the adjusted difference in least squares mean (SE) change from baseline BCVA letter score at week 8 with an equivalence margin of -3 to +3 letters. Secondary outcomes included change in central subfield thickness (CST), BCVA, number of injections over 52 weeks, incidence of adverse events (AEs), and antidrug antibodies (ADAs). Results: A total of 355 participants (mean [SD] age, 62.2 [9.2] years; 216 male [60.8%]) were randomized to MYL-1701P (179 participants [50.4%]) and aflibercept (176 participants [49.6%]). At week 8, mean (SE) change in BCVA was 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups. The adjusted mean difference of 0.04 letters (90% CI, -1.16 to 1.24 letters) met the primary outcome. At week 8, mean (SE) change in CST was -112 (7) µm vs -124 (7) µm in the MYL-1701P vs aflibercept groups (adjusted mean difference, 12 µm; 90% CI, -3 to 26 µm). The incidence of treatment-emergent AEs in the MYL-1701P and aflibercept arms were ocular (30.9% [55 of 178] vs 29.5% [52 of 176]), serious ocular (0.6% [1 of 178] vs 1.1% [2 of 176]), nonocular (65.2% [116 of 178] vs 65.3% [115 of 176]), and serious nonocular (16.9% [30 of 178] vs 11.9% [21 of 176]). The mean (SD) total number of injections was 8.4 (2.1) vs 8.7 (1.8) in the MYL-1701P vs aflibercept groups. The incidence of treatment-induced or treatment-boosted ADAs was 2.8% (5 of 177) vs 5.7% (10 of 176) in the MYL-1701P vs aflibercept arms. Conclusions and Relevance: MYL-1701P demonstrated clinical equivalence in regard to efficacy, with comparable safety and immunogenicity, to reference aflibercept. These findings support use of MLY-1701P as an alternative to reference aflibercept. Trial Registration: ClinicalTrials.gov Identifier: NCT03610646.

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.

Efficacy and Safety of Biosimilar FYB201 Compared with Ranibizumab in Neovascular Age-Related Macular Degeneration.

PURPOSE: This trial was conducted to investigate the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in patients with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration (nAMD). DESIGN: This was a prospective, multicenter, evaluation-masked, parallel-group, 48-week, phase III randomized study. PARTICIPANTS: A total of 477 patients were randomly assigned to receive FYB201 (n = 238) or reference ranibizumab (n = 239). METHODS: Patients received FYB201 or reference ranibizumab 0.5 mg by intravitreal (IVT) injection in the study eye every 4 weeks. MAIN OUTCOME MEASURES: The primary end point was change from baseline in best-corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks before the third monthly IVT injection. Biosimilarity of FYB201 to its originator was assessed via a 2-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters. RESULTS: The BCVA improved in both groups, with a mean improvement of +5.1 (FYB201) and +5.6 (reference ranibizumab) ETDRS letters at week 8. The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was -0.4 ETDRS letters with a 90% confidence interval (CI) of -1.6 to 0.9. Primary end point was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups. CONCLUSIONS: FYB201 is biosimilar to reference ranibizumab in terms of clinical efficacy and ocular and systemic safety in the treatment of patients with nAMD.

The relationship between pre-pregnancy BMI, gestational weight gain and neonatal birth weight: a retrospective cohort study.

OBJECTIVES: Maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) have a meaningful impact on pregnancy and perinatal outcomes. The first aim of the study was to analyze the association between pre-pregnancy BMI and the prevalence of small for gestational age (SGA) and large for gestational age (LGA) outcomes. The second aim was to assess the relation- ship between pre-pregnancy BMI combined with gestational weight gain (GWG) and the prevalence of SGA and LGA measurements. MATERIAL AND METHODS: The retrospective cohort study was conducted at Jagiellonian University Hospital in Cracow, Po- land from 2016 to 2017. During this time there were 2,123 deliveries. Patients with chronic diseases, multiple pregnancies, fetal defects and incomplete data were excluded. Finally, 474 cases were enrolled. Patients were divided into BMI groups (underweight, normal, overweight and obese) and into GWG groups (inadequate, adequate, excessive). Relationships between maternal BMI, GWG and newborn weight were examined. RESULTS: There was no statistically significant association between maternal pre-pregnancy BMI and prevalence of SGA measurements. However, underweight women with inadequate GWG showed a higher risk to bear SGA babies (OR 5.2, 95% CI 1.57-17.18). Obese women with adequate GWG had higher risk of bearing LGA newborns (OR 5.48, 95% CI 1.15-26.13). High BMI correlated with excessive GWG (overweight: OR 3.0, 95% CI 1.84-3.87; obese OR 2.45, 95% CI 1.1-5.48). CONCLUSIONS: There is a considerable risk of giving birth to a SGA newborn for underweight women with inadequate GWG. There is a statistically significant association between maternal obesity and LGA outcomes. Our study shows that redefining the risks of abnormal neonatal weight considering both pre-pregnancy BMI and gestational weight gain can be useful in providing effective prevention during pregnancy.

The influence of medical education level on the Jagiellonian University Collegium Medicum medical students' knowledge concerning oral hormonal contraceptive pills.

In December 2014 the authors carried out a research among Jagiellonian University Collegium Medicum medical students in a form of a questionnaire which consisted of two parts: personal information and multiple choice test concerning student's knowledge on OCPs. It showed that the level of medical education, defined as the year of study, increases student's knowledge about oral hormonal contraceptive pills. New program of study introduced from academic year 2012/2013 gives students wider knowledge on OCPs at earlier stage of education. Factors as female sex, usage of OCPs by student or his partner, positive attitude towards recommending OCPs to future patients show positive correlation with student's knowledge.

Management of diffuse choroidal hemangioma in Sturge-Weber syndrome with Ruthenium-106 plaque radiotherapy.

PURPOSE: To evaluate Ruthenium-106 plaque radiotherapy in the treatment of diffuse choroidal hemangioma (DCH) associated with serous retinal detachment. METHODS: A retrospective analysis was performed in five patients treated for DCH associated with Sturge-Weber syndrome (SWS). In all cases, Ruthenium-106 plaque therapy with a target apex dose of 30.98-47.36 Gy (mean:38.9 Gy) was performed. The outcomes of treatment were regression of DCH, assessed by B-scan ultrasonography; resolution of serous retinal detachment, measured by B-scan ultrasonography and optical coherence tomography (OCT); changes in best corrected visual acuity (BCVA) and the development of radiation-related complications. All investigations were repeated 3 months after treatment and then at six monthly intervals within 22-122 months (mean: 62 months) of follow-up. RESULTS: The initial BCVA of the affected eyes ranged from counting fingers at 1 m to 0.1 by the Snellen chart. Mean tumor basal diameter was 16.7 mm (range: 13.8 to 18.5 mm) and mean tumor thickness was 4.4 mm (range: 2.4 to 5.8 mm). Tumor regression was found in all cases with the prompt resolution of subretinal fluid. In three patients, BCVA improved and in two it remained stable. During the follow-up period, in one case secondary glaucoma was treated with transscleral cyclophotocoagulation, and in another case, recurrence of the hemangioma was treated with repeated Ruthenium-106 plaque irradiation and transpupillary therapy. CONCLUSION: Ruthenium-106 plaque radiotherapy is an effective and safe treatment option for DCH associated with SWS. Brachytherapy led to tumor regression and resolution of serous retinal detachments, and visual stabilization was achieved in most cases.

[Photodynamic therapy in a patient with chronic central serous chorioretinopathy--a case report]. / Terapia fotodynamiczna u chorego na przewlekla centralna surowicza chorioretinopatie--opis przypadku.

PURPOSE: The aim of the study was to evaluate the efficacy of photodynamic therapy as the treatment of chronic central serous chorioretinopathy. MATERIAL AND METHODS: A 59-year-old man was referred to the Department of Ophthalmology and Ocular Oncology, Jagiellonian University in Cracow with a complaint of recurrent visual acuity impairment in his left eye, which he had noticed for the first time three years earlier. The complete ophthalmic examination was extended by the additional diagnostic procedures of optical coherence tomography and fluorescein angiography and the patient was diagnosed with chronic central serous chorioretinopathy. He was eligible for the photodynamic therapy with a full dose of verteporfin, which was performed. The patient was subsequently re-assessed at 3 and 6 months following treatment completion. During the follow up assessment the amount of subretinal fluid on fundus examination and the best-corrected visual acuity (Snellen) were evaluated. The follow up optical coherence tomography was also performed. RESULTS: Six months after photodynamic therapy the subretinal fluid resolved completely, the distance best-corrected visual acuity improved from 0.2 to 0.5 and the near best-corrected visual acuity from 2.25 to 0.5. No treatment-induced adverse effects were observed. CONCLUSION: The photodynamic therapy may be effective in the management of selected cases with chronic central serous chorioretinopathy. central serous chorioretinopathy, photodynamic therapy.

Acute retinal necrosis--a case report.

We present a case of acute retinal necrosis (ARN) which is a rare but devastating and rapidly progressive viral retinitis. It is caused mainly by Herpes simplex virus (HSV) or Varicella zoster virus (VZV) (2), but also Cytomegalovirus (CMV) and Epstein-Barr virus infections may be aethiological factors of ARN. A 17-year-old male patient was referred with history of painful sudden worsening of visual acuity in the left eye and the presence of floaters in the visual field of the right eye. Based on the ophthalmological examination the diagnosis of bilateral ARN was established. Aqueous humor aspirates were analyzed using polymerase chain reaction (PCR) for Herpes simplex virus (HSV), Varicella zoster virus (VZV), Cytomegalovirus (CMV) and Epstein-Baar virus (EBV). PCR confirmed the presence of Varicella zoster virus in aqueous humor samples. Prompt systemic antiviral therapy combined with steroids was initiated. Since a rapid and accurate diagnosis is crucial for prompt administration of antiviral therapy, PCR-based analysis of intraocular fluids orovides a valuable tool in the establishina an etiologic factor in patients with retinitis caused by herpesvirus.

[Acute posterior multifocal placoid pigment epitheliopathy (APMPPE)--a therapeutic dilemma]. / Ostra tylna wieloogniskowa plackowata epiteliopatia barwnikowa--dylematy terapeutyczne.

PURPOSE: To present a rare idiopathic inflammation of the posterior segment of the eye - acute posterior multifocal placoid pigment epitheliopathy (APMPPE). MATERIAL AND METHODS: A 17 years old male patient was referred to the Department of Ophthalmology of Medical College, Jagiellonian University in Krakow with the diagnosis of bilateral choroiditis of unknown etiology. The patient underwent the basic ophthalmological examination followed by fluorescein (FA) and indocyanine green (ICGA) angiography. Laboratory testing for Lyme disease, sarcoidosis and syphilis, as well as genetic testing, to determine the presence of HLA antigen complex, were performed RESULTS: Based on the outcomes of performed investigations the definitive diagnosis of APMPPE was established. Systemic steroidotherapy was initiated due to rapid progression of the inflammatory changes, progression of the central visual field changes and profound visual acuity deterioration. CONCLUSIONS: APMPPE is a rare, inflammatory and idiopathic eye disease with no clear indications for pharmacological therapy. However decision about necessity and sort of pharmacological therapy should be taken under consideration individually for each patient. ostra tylna wieloogniskowa plackowata epiteliopatia barwnikowa, steroidoterapia. acute posterior multifocal placoid pigment epitheliopathy, steroidotherapy.

A case of choroidal metastasis in a male breast cancer.

PURPOSE: We present a case of male patient under therapy due to breast cancer with choroid metastasis and exudative retinal detachment in right eye. MATERIAL AND METHODS: A 59 years old male patient was referred with diagnosis of intraocular tumor in right eye Three years ago radical right-side mastectomy was performed (T2N1M0). The medical history revealed that the patient was under chemo- and hormontherapy due to right breast cancer with lungs, liver and mediastinum metastases. Based on the ophthalmological examination the diagnosis of intraocular tumor was established--choroidal metastasis with exudative retinal detachment. Due to tumor size and general dissemination external beam irradiation of tumor was performed. CONCLUSIONS: The majority of choroidal metastases in males are secondary to lung carcinoma, however in differential diagnosis it is necessary to consider also rare cases of breast carcinoma metastases. Treatment strategy should be considered individual depending on size, localization, presence of metastases to other organs and general condition of the patient.

[Guidance for the treatment of neovascular age-related macular degeneration (AMD)]. / Wspólczesne metody leczenia wysiekowej postaci zwyrodnienia plamki zwiazanego z wiekiem (AMD).

BACKGROUND: Neovascular age-related macular degeneration (AMD) is becoming an increasing socio-medical problem as the proportion of the aged population is continuously increasing. However, new researches in the pathogenesis of the disease offer the opportunity to develop more effective therapies of AMD. AIM: This article will focus on the options in the management of neovascular age-related macular degeneration and recent therapeutic options. RESULTS: The recent development of anti-VEGF (vascular endothelial growth factor) substances for use in clinical routine has markedly improved the prognosis of patients with neovascular AMD. Intravitreal treatment with substances targeting all isotypes of Vascular Endothelial Growth Factor (VEGF), for the first time results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like photodynamic therapy (PDT) potentially offers a reduction of re-treatment frequency and long-term maintenance of the treatment benefit. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. CONCLUSION: Nevertheless, the growing number of novel therapeutic options will have to provide proof of concept in randomized controlled clinical trials.