Liposomal Ozonated Oil Ensures a Further Reduction in the Microbial Load Before Intravitreal Injection: the "OPERA" Study.

INTRODUCTION: This was a prospective study to investigate the antimicrobial efficacy of a novel ophthalmic solution comprising ozonated sunflower oil in liposomes plus hypromellose in conjunction with liposomal foam (BlefOX), in patients undergoing intravitreal injection, in comparison to povidone iodine 5%. METHODS: The study employed a paired-eye design with n = 195 patients and a total of n = 390 eyes divided into two groups. Conjunctival swabs were collected from both eyes of each patient at baseline (T0-3 days before the injection). The study group underwent home therapy, which included instilling two drops of an isotonic ophthalmic solution containing 0.5% ozonated sunflower oil in liposomes plus hypromellose (Ozodrop) four times daily and applying liposomal foam twice daily to the eye undergoing intravitreal injections. In contrast, the control group (contralateral eyes) received treatment with povidone iodine 5%. This treatment regimen was maintained for 3 days. At T1 (10 min before injection), all patients instilled one drop of a topical solution of povidone iodine 5% into the conjunctival sac of both eyes. After 30 seconds had elapsed, a conjunctival swab was obtained for each eye in both study groups. RESULTS: The results, derived from conjunctival swabs, exhibited a significant reduction in the microbial load of the study group on both chocolate agar and blood agar (p ≤ 0.007). The study demonstrated that the combination of povidone iodine 5% + Ozodrop + BlefOX provides a greater reduction in microbial load than povidone iodine 5% alone on both chocolate agar (141 [72.31%] vs. 98 [50.26%], p < 0.0001) and blood agar (130 [66.67%] vs. 97 [49.74%], p = 0.0007). The combination of povidone iodine 5% + Ozodrop + BlefOX resulted in the killing of approximately 41% to 49% of bacteria compared to povidone iodine 5% alone on the chocolate agar and blood agar, respectively. CONCLUSIONS: Liposomal ozonated oil treatment, coupled with liposomal foam, in patients undergoing intravitreal injection led to a substantial reduction in conjunctival microbial load compared to eyes treated solely with povidone iodine 5%.

Calculated Drug Concentrations in Currently Available Intravitreal Therapies: Determination of Dilution Factor and Deviation From Recommended Doses.

In ophthalmology, intravitreal therapies are currently not personalized/customized and are not adjusted to the individual vitreous volume. With reference to the recently published calculation formula for a more accurate estimation of the vitreous body, we determined the dose of intravitreal medication for different vitreous volumes and compared them with the average volume. Using the axial length of the eye, the formula for the vitreous volume exact (VIVEX) can provide a more accurate indication of the vitreous volume in individual cases than an assumed standard volume of 4 mL. The concentration of active substances in small eyes may be twice as high as that in normal-sized emmetropic eyes. In contrast, large eyes may show less than half of the recommended drug concentration. The calculated concentrations of the investigated intravitreal drugs in small and large eyeballs showed impressive differences with large deviations from the recommended doses. Further systematic studies should follow to find out whether this has any impact on the effectiveness or side effects of the injected drugs.

Case report: heart failure related to intravitreal injection of anti-VEGF.

BACKGROUND: Intravitreal injection of anti-vascular endothelial growth factor is considered the first-line treatment for polypoidal choroidal vasculopathy. It has potential risks for circulatory system, which should be particularly carefully evaluated in older patients. In this case study, we aim to discuss the potential impact of this treatment regimen on cardiac health. CASE PRESENTATION: This case report describes an elderly patient with no prior history of heart disease who exhibited unexpected heart enlargement and dysfunction. Throughout the patient's hospital stay, various potential causes were investigated, leading to the hypothesis that a 10-year history of intravitreal injections of anti-vascular endothelial growth factor could be related to the observed clinical manifestations. The patient was advised to discontinue this treatment, and after a 2-month follow-up period, there was a gradual improvement in the patient's cardiac structure and function. CONCLUSION: This manuscript highlights the importance of conducting cardiac examinations before and after anti-vascular endothelial growth factor treatment, especially for individuals at risk of heart diseases like the elderly. It emphasizes the need to carefully weigh the benefits and risks of treatment regimens to ensure optimal therapeutic outcomes.

Recurrence Rate during 5-Year Period after Suspension of Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration.

Purpose: To determine the recurrence rate of neovascular age-related macular degeneration (nAMD) during a 5-year period after the suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments. Methods: Thirty-four eyes of 34 nAMD patients who met the inclusion criteria and were treated by anti-VEGF drugs were studied. All met the treatment suspension criteria and were followed for 5 years after the suspension of the anti-VEGF treatment. Patients with a recurrence within one year were placed in Group A, and patients with a recurrence between 1 and 5 years were placed in Group B. The rate and time of a recurrence were analyzed using the Kaplan-Meier method. We also examined whether there were differences in the baseline factors of age, sex, subtype, treatment period, and treatment interval between Groups A and B. Results: Twenty-five of 34 eyes (73.5%) had a recurrence within 5 years of stopping the anti-VEGF treatments. Thirteen (52.0%) of the 25 eyes had a recurrence within 1 year, 4 (16.0%) eyes between 1 and 2 years, 4 (16.0%) eyes between 2 and 3 years, 2 (8%) between 3 and 4 years, and 2 eyes (8%) between 4 and 5 years. The baseline factors were not significantly different between Groups A and B. Conclusions: The results showed that the recurrence rate was highest within one year after the suspension of the anti-VEGF treatments, with a number of recurrences one year after the suspension. Clinicians should remember that nAMD may recur several years after the suspension of anti-VEGF treatments.

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

INTRODUCTION: 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). METHODS: This retrospective study included 17 eyes of 17 patients with refractory AMD treated with high-dose brolucizumab (12 mg/0.1 ml) for over 12 months. Patients initially received at least one anti-vascular endothelial growth factor (anti-VEGF) agent and were switched to standard-dose brolucizumab (6 mg/0.05 ml). Those who showed a suboptimal response to standard-dose treatment had their dosage of brolucizumab escalated. RESULTS: Visual acuity was maintained from 68.3 ± 3.4 letters to 70.7 ± 3.2 letters after 12 months of high-dose treatment (P = 0.128). Central subfield thickness was 343.7 ± 17.0 µm before high-dose treatment and 316.7 ± 18.5 µm at 12 months (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 ± 2.4 weeks to 10.2 ± 2.2 weeks after switching to standard-dose brolucizumab (P < 0.001) and was maintained at 13.5 ± 2.8 weeks after increasing the dose (P = 0.154). No severe ocular adverse events were observed. CONCLUSIONS: 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.

Comparison of One-Year Outcome of Intravitreal Aflibercept with or without Photodynamic Therapy for Polypoidal Choroidal Vasculopathy.

Background and Objectives: Our study compared the visual and anatomical outcomes of polypoidal choroidal vasculopathy (PCV) patients receiving intravitreal aflibercept (IVA) with or without photodynamic therapy (PDT) over 12 months. Materials and Methods: This retrospective study was performed for 60 eyes from 60 patients with treatment-naïve PCV. Thirty eyes were treated using IVA monotherapy (IVA group), and thirty eyes were treated using a combination of IVA with PDT (IVA/PDT group). The baseline characteristics, treatment outcomes, and retreatment rates were compared between the two groups over a one-year follow-up period. Results: The best-corrected visual acuity (BCVA) was found to have improved significantly in the IVA/PDT group at every 3-month visit. However, no significant BCVA improvement was observed in the IVA group. A significantly lower retreatment rate and higher dry macula rate were found in the IVA/PDT group than that in the IVA group. In the entire population of the study, a better baseline vision and younger age were associated with better final visual outcomes. Retreatment was associated with poor baseline BCVA and IVA monotherapy. Conclusions: The combination of IVA and PDT may offer superior visual improvement and a higher dry macula rate compared to IVA monotherapy in the treatment of PCV patients while requiring fewer retreatments over 12 months.

Bevacizumab and External Beam Radiation Therapy for Diffuse Choroidal Hemangioma in Sturge-Weber Syndrome: A Case Report.

Introduction: Sturge-Weber syndrome, a congenital vascular disorder, is associated with diffuse choroidal hemangiomas in which the current mainstay of treatment is radiation therapy, including external beam radiation therapy (EBRT). The purpose of this case report was to present a novel combination of treatments for diffuse choroidal hemangioma. Case Presentation: A 37-year-old man with a history of Sturge-Weber-associated glaucoma presented with an acute-onset decrease in vision in the right eye. Best-corrected visual acuity (BCVA) at the presentation was 20/400 in the right eye. Examination revealed a total macula-off, bullous, folded exudative retinal detachment and findings consistent with diffuse choroidal hemangioma. The patient was treated with a single injection of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agent bevacizumab and 10 fractions of EBRT of the right eye. Follow-up examination at 17 months demonstrated complete resolution of subretinal fluid and no evidence of choroidal elevation on B-scan. Final BCVA in the right eye was 20/1,000. Conclusion: This case uses simultaneous treatment with EBRT and bevacizumab in the treatment of diffuse choroidal hemangioma and associated exudative retinal detachment. Clinicians may use anti-VEGF agents early in the course of the disease in determining whether they may assist in preventing visual decline.

In Vitro Physicochemical and Pharmacokinetic Properties of Bevacizumab Dissolved in Silicone Oils Compared to Hydrogel-Substitutes and Porcine Vitreous Bodies.

Anti-VEGF agents, e.g., bevacizumab, are used in retinal surgery, while their interaction with silicone oils and novel hydrogels remains unclear. This study examines the in vitro pharmacokinetics of bevacizumab in silicone oil-filled eyes compared to various hydrogel replacements and the porcine vitreous body as well as its impact on the interface tension of silicone oils. An in vitro model filled with light or heavy silicone oil, porcine vitreous bodies, or hydrogels (alginate and polyethylene glycol (PEG)-based) was equilibrated with a balanced salt solution. Monitoring of bevacizumab in the aqueous phase was conducted for up to 24 h, and its effect on interfacial tension was studied. Significant differences in bevacizumab partitioning were observed across endotamponades after 24 h. In silicone oils, bevacizumab was found exclusively in the aqueous phase, while in the other endotamponades, it accumulated in the gel phase (96.1% in porcine vitreous body, 83.5% in alginate, and 27.6% in PEG-based hydrogel). Bevacizumab significantly reduced interfacial tension (40 to 8 mN/m), possibly enhancing silicone oil emulsification. The type of endotamponade heavily influenced the bevacizumab concentration in the aqueous. The vitreous body and replacement hydrogels likely serve as a drug reservoir, highlighting the need for in vivo studies to explore these interactions prior to clinical application.

Long-Term Stability, Sterility, And Cost-Effectiveness of 0.05% Chlorhexidine Gluconate as Antisepsis for Intravitreal Injection.

Purpose: Commercially available chlorhexidine gluconate (CHG) has a beyond-use date of 24 h. This study evaluated the stability and sterility of 0.05% CHG for 30 days after opening and compared its cost to povidone iodine (PI) for intravitreal injection antisepsis. Methods: 0.05% CHG was aliquoted into 1-mL syringes and stored at room temperature or refrigerated. Turbidity, pH, high-performance liquid chromatography (HPLC), and sterility testing were performed. A cost analysis was conducted. Results: 0.05% CHG remained stable for at least 30 days. All samples had measured turbidity <0.5 nephelometric turbidity units. The pH of all samples remained between 5.0 and 7.0. HPLC demonstrated CHG concentration at day 30 relative to day 0 of 98.52% ± 4.16% at room temperature and 99.99% ± 3.38% at 2°C -6°C. The cost per week to perform 150 injections using 0.05% CHG was $463.25 when opening a new bottle daily compared with $16.73 for 5% PI. This cost decreased to $23.16 when utilizing a bottle of CHG for 30 days. Conclusion: 0.05% CHG remains stable and sterile for at least 30 days after opening. The ability to use CHG for at least 30 days after its opening significantly decreases its utilization expense.

Pro Re Nata brolucizumab for early onset and treatment-naïve diabetic macular edema: A prospective study.

OBJECTIVES: To determine the efficacy and safety of brolucizumab therapy administered on a pro re nata (PRN) basis without loading dose in treatment naïve patients with diabetic macular edema (DME) for 1 year follow-up. METHODS: Patients with recent DME (<6 months) received a mandatory brolucizumab injection at inclusion and other injections could be given on a PRN basis with an 8-week interval (between injections) at minimum. Rescue therapy with other anti-VEGF was possible in case of incomplete DME resolution after the second brolucizumab with a minimum of 1-month treatment free interval between 2 injections. The primary outcome measure was the change in (BCVA) at 12 months. Secondary outcome measures included the change in central subfield thickness (CST), the change in hard exudate surface area and microaneurysms at 1 year. RESULTS: A total of 53 patients were included. At 12 months, the mean (SD) number of injections was 2.6 (0.8) in addition to the first mandatory injection. The mean (SD) interval between 2 consecutive injections was 3.2 (1.4) months. The mean (SD) BCVA improved from 0.62 (0.1) logMAR to 0.40 (0.16) logMAR (p = 0.012). The mean CST reduced from 397.0 (47.2) µm to 224.5 (28.1) µm (p = 0.013). The hard exudate surface area decreased significantly (p = 0.012) as did microaneurysms (p = 0.02). Seven patients required at least 1 rescue therapy. No patients experienced intra-ocular inflammatory adverse events. CONCLUSION: Brolucizumab therapy for DME is a safe and effective modality for the treatment of recent DME and has the potential to reduce the number of injections.

Use of intravitreal antiviral injection during vitrectomy in the treatment of acute retinal necrosis: anatomic and visual outcomes.

PURPOSE: To investigate whether intravitreal antiviral injection (IAI) during vitrectomy reduces the postsurgical retinal detachment (RD) rate and improves the visual prognosis of patients with acute retinal necrosis (ARN). METHODS: This retrospective cohort study included ARN patients treated at a tertiary hospital between January 2013 and December 2020. Patients who underwent pars plana vitrectomy (PPV) alone or combined with intraoperative IAI were classified in PPV-only group and PPV + IAI group, respectively. The incidence of postsurgical RD and the best corrected visual acuity (BCVA) between the groups was compared. A multivariate Cox hazard analysis was employed to explore the risk factors of postsurgical RD. A multivariate logistic regression analysis was applied to assess the impact of intraoperative IAI on preventing severe vision loss (SVL). RESULTS: Fifty-seven eyes with ARN with a median follow-up of 18.5 months were included in the study. There was no significant association between intraoperative IAI during vitrectomy and a reduced risk of postsurgical RD (hazard ratio [HR], 2.65; 95% CI, 0.71-9.89) or SVL at the 6-month follow-up visit (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.25-3.35). Better baseline best-corrected visual acuity (BCVA) was identified to associate with a higher risk of postsurgical RD (HR, 0.33; 95% CI, 0.14-0.81) and a lower risk of SVL at 6 months (OR, 2.28; 95% CI, 1.10-4.89). CONCLUSION: We did not observe a significant effect of intraoperative IAI on the anatomic and visual outcomes of ARN patients in this study. Intraoperative IAI may not be a necessary treatment option for ARN patients who receive vitrectomy.

Short-Term Comparison of Switching to Brolucizumab or Faricimab from Aflibercept in Neovascular AMD Patients.

Background and Objectives: In this study, our objective was to assess and compare the changes in visual and structural outcomes among patients with neovascular age-related macular degeneration (nAMD) who were switched from intravitreal aflibercept (IVA) to either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. Materials and Methods: This observational clinical study included 20 eyes of 20 patients switched to brolucizumab and 15 eyes of 14 patients switched to faricimab from aflibercept in eyes with nAMD. We measured the structural outcome (central macular thickness (CMT)) and the visual outcome (best-corrected visual acuity (BCVA); logMAR) as follows: just before the most recent IVA injection (B0), one month after the most recent IVA injection (B1), just before the first IVBr or IVF injection (A0), one month after (A1) and three months after (A3) the first IVBr or IVF injection. Results: BCVA showed significant improvement at A1 (0.25 ± 0.34) and at A3 (0.19 ± 0.24) compared to A0 (0.38 ± 0.35) in the IVBr group (p = 0.0156, p = 0.0166, respectively). CMT (µm) was significantly thinner at A1 (IVBr: 240.55 ± 51.82, IVF: 234.91 ± 47.29) and at A3 (IVBr: 243.21 ± 76.15, IVF: 250.50 ± 72.61) compared to at A0 (IVBr: 303.55 ± 79.18, IVF: 270.33 ± 77.62) in the IVBr group (A1: p = 0.0093, A3: p = 0.0026) and in the IVF group (A1: p = 0.0161, A3: p = 0.0093). There was no significant difference in BCVA and CMT improvement observed between two groups at any time point (p > 0.05 for all). Conclusions: Switching from aflibercept to either brolucizumab or faricimab has a significant anatomical effect in eyes with nAMD and both treatments appear to be effective short-term treatment options. There is a trend towards greater visual improvements and reductions in CMT with brolucizumab.

Unexpected Vision Loss following Six Intravitreal Injections for Neovascular Age-Related Macular Degeneration.

Introduction: We present a case of a patient with preceding vitreomacular traction (VMT) who developed a full-thickness macular hole (FTMH) following his sixth intravitreal aflibercept injection for the treatment of age-related macular degeneration and review the literature on risk factors and pathogenesis of this adverse event. Case Presentation: FTMH can occur after an extended number of repeat intravitreal injections in the setting of worsening vitreomacular adhesion or VMT. This patient's FTMH was successfully treated surgically in a timely manner, and additional injections were resumed safely. Conclusions: Patients with an unexpected decrease in vision after intravitreal injections should be reevaluated with optical coherence tomography to rule out alternative pathology including vitreomacular interface abnormalities. FTMH, if present, should be treated promptly to allow for resumption of therapy as needed and visual optimization.

Cardiovascular and cerebrovascular adverse events associated with intravitreal anti-vascular endothelial growth factor monoclonal antibodies: a World Health Organization pharmacovigilance study.

PURPOSE: To analyze cardiovascular and cerebrovascular adverse events (ADRs) after intravitreal anti-vascular endothelial growth factor (VEGF; aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment. SUBJECTS: VigiBase, a World Health Organization (WHO) global safety report database DESIGN: Pharmacovigilance study METHODS: The individual-case-safety reports (ICSR) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, 23,129 ADRs after intravitreal anti-VEGF therapy and 25,015,132 ADRs associated with any drug (full database). MAIN OUTCOME MEASURES: The reporting odds ratio (ROR) and information components (IC) were calculated, and the 95% lower credibility interval endpoint of the information component (IC025) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odd ratio (rOR). RESULTS: Compared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC025 0.75; ROR: 1.78 [95% CI 1.70-1.86]), angina pectoris (IC025 0.53; ROR: 1.61 [95% CI 1.47-1.77]), arrythemias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC025 >0, ROR>1), hypertension (IC025 2.22; ROR: 4.91 [95% CI 4.82-5.01]), and hypertensive crisis (IC025 1.97; ROR: 4.49 [95% CI 4.07-4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC025 4.34; ROR: 23.19 [95% CI 22.10-24.34]), carotid artery stenosis (IC025 1.85; ROR: 5.24 [95% CI 3.98-6.89]), cerebral hemorrhage (IC025 2.29; ROR: 5.38 [95% CI 5.03-5.76]), and subarachnoid hemorrhage (IC025 1.98; ROR: 4.81 [95% CI 4.14-5.6]). Inter-drug comparison indicated that compared to ranibizumab, patients with aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI 0.49-0.52]), atrial fibrillation (rOR 0.28 [95% CI 0.23-0.35]), cerebrovascular accident (rOR, 0.15 [95% CI 0.14-0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI 0.40-0.65]). CONCLUSIONS: In this pharmacovigilance case-noncase study, significantly increased reporting of cardiovascular and cerebrovascular ADRs were identified after intravitreal anti-VEGF treatment. While ranibizumab may exhibit superior systemic safety regarding its biological characteristics, it is crucial not to overlook the occurrence of cardiovascular and cerebrovascular ADRs considering its higher reporting rate than bevacizumab or aflibercept.

Pneumatic Vitreolysis using C3F8 Gas in Treatment Naive Patients with Vitreomacular Traction.

PURPOSE: Evaluation of the effectiveness of pneumatic vitreolysis in disrupting vitreomacular traction in our own cohort of patients. METHODOLOGY: Prospective follow-up of 21 eyes of 18 patients with focal VMT (adhesion width < 1500 µm) who underwent intravitreal injection of 0.3 ml of 100% perfluoropropane between January 2015 and December 2020. The patients were observed for 90 days. RESULTS: Release of VMT was achieved on the 28th day of observation in 15 out of 21 eyes (71.4%), and by the 90th day in 19 out of 21 eyes (90.5%). The average width of adhesion in our patients was 382 µm (±212 µm). Average best corrected visual acuity in our cohort was initially 0.77 (±0.21), after 28 days 0.74 (±0.30), and after 3 months 0.82 (±0.21). At the end of the follow-up period, we did not observe a statistically significant improvement in vision. Macular holes developed in two eyes, but spontaneously closed within 1 month of observation, and no more complications were observed in the cohort. CONCLUSION: Pneumatic vitreolysis by intravitreal injection of C3F8 gas is an effective and inexpensive option for the management of symptomatic vitreomacular traction. The incidence of serious adverse events in our follow-up was significantly lower than in recently published series. The method of management should be selected individually according to the parameters of adhesion, macular hole and associated ocular pathologies.

Safety of intravitreally delivered AAV2 vector-mediated multi-characteristic opsin genetic construct in wild type beagle dogs.

BACKGROUND: A novel adeno-associated virus 2 (AAV2)-carried multi-characteristic opsin (MCO) (MCO-010) is undergoing several clinical trials as a novel therapeutic modality for the treatment of degenerative retinal diseases including retinitis pigmentosa and Stargardt disease. The present study aimed to determine the ocular and systemic safety of MCO-010 and the AAV2 vehicle in adult Beagle dogs following intravitreal (IVT) injection. METHODS: The current safety/toxicology studies spanning 13 weeks described here utilized well-documented techniques to assess the effects of IVT injection of MCO-010 up to 2.2 × 1011 genome copies (gc) per eye, or the AAV2 capsid (vehicle control) on gross behavioral and immunogenic changes, alterations in body weights, blood biochemistry, hematology, blood coagulation, gross necropsy lesions, organ weight changes and histopathology in the dogs (n = 4 per group; two males and two females per group). Immunohistochemical and functional electroretinogram studies were also conducted to determine MCO expression in the retina and determine any retinal toxicity associated with MCO-010. RESULTS: There were no significant deleterious effects of the MCO-010 (or the AAV2 at the tested doses) on any of the examined parameters, including the absence of any severe ocular or systemic adverse events. However, as expected, inflammation after IVT delivery of AAV2 and MCO-010 was observed in the conjunctivae of all groups of animals, although this self-resolved within 1 week post-injection. Quantitative immunohistochemical analyses of MCO-010-associated mCherry revealed successful delivery of the gene therapy within the inner retina. CONCLUSIONS: In summary, MCO-010 demonstrated a favorable safety profile when administered to the eyes of adult Beagle dogs of both sexes at dose levels up to 2.2 × 1011 gc per eye, with no adverse effects observed. This dose was identified as the No Observed Adverse Effect Level (i.e. NOAEL) and guided selection of safe doses for human clinical trials.

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.

The effect of intravitreal cidofovir injection on end-stage glaucoma in dogs: a retrospective study of 153 eyes.

OBJECTIVE: To evaluate the long-term efficacy, prognostic factors, and complications of intravitreal cidofovir injection in dogs with end-stage glaucoma. ANIMALS: 130 client-owned dogs. METHODS: Medical records of dogs that underwent intravitreal cidofovir injections were reviewed. A minimum follow-up period of 6 months was required as the inclusion criterion. Signalment, type of glaucoma, preinjection intraocular pressure (IOP), types of applied glaucoma eye drop, coexisting ocular diseases, outcomes, and complications were recorded. Success was defined as IOP of ≤ 25 mm Hg at the 2-week recheck that remained to the 6-month recheck. RESULTS: The overall success rate of intravitreal cidofovir injection was 91.5% (140/153). The success rate of a single injection was 69.3% (106/153), of a second injection was 59.5% (25/42), of a third injection was 42.9% (6/14), of a fourth injection was 33.3% (2/6), and of a fifth injection was 50.0% (1/2). Intraocular pressures at 6 months after injection were relatively higher when the injection was repeated, fewer types of glaucoma eye drop were applied prior to the injection, and cataract stages were advanced at the time of injection (P < .05). The most common complications were phthisis bulbi (42.5%), cataract progression (30.1%), and intraocular hemorrhage (16.3%). Six eyes were enucleated, and 3 were enucleated due to corneal perforation. CLINICAL RELEVANCE: Intravitreal cidofovir injection had a high long-term success rate in lowering IOP in dogs with end-stage glaucoma.

Efficacy of anti-VEGF intravitreal injection in traumatic submacular hemorrhage: a retrospective study.

OBJECTIVE: In this study we investigated the efficacy of short-term intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) in treating traumatic submacular hemorrhage. METHODS: A total of 115 patients were diagnosed with submacular hemorrhage between 2018 and 2022 at Shenzhen Eye Hospital. In a retrospective analysis, we examined 13 of these patients who presented with submacular hemorrhage and choroidal rupture due to ocular trauma. Eight patients were treated with intravitreal anti-VEGF injection and 5 with oral drugs. We systematically analyzed changes in their ocular conditions pre and post-treatment. The evaluations encompassed best-corrected visual acuity (BCVA), optical coherence tomography, fundus fluorescein angiography, and retinal imaging. RESULTS: The 13 patients diagnosed with submacular hemorrhage comprised of 10 males and 3 female, with their age ranging between 27 and 64 years, with an average age of 38.1 years (standard deviation [SD]: 11.27). A statistically significant reduction in central foveal thickness (CFT) was observed following intravitreal injections of anti-VEGF drugs (P = 0.03). In control group, the CFT was reduced without statistical significance (P = 0.10). The BCVA of the patients in treatment group improved significantly from 1.15 (SD: 0.62. Range: 0.4-2) to 0.63 (SD: 0.59. Range: 0.1-1.6), indicating an average increase of 4.13 lines (SD: 3.36. Range: 0-9) as measured by the visual acuity test using an eye chart (P = 0.01). The difference between baseline visual acuity and final visual acuity was not statistically significant in control group (P = 0.51). CONCLUSION: Short-term administration of anti-VEGF drugs exhibited significant efficacy in reducing submacular hemorrhage following ocular trauma and enhancing visual acuity.