The Institute for Safe Medication Practices and the American Society of Health-System Pharmacists have advocated for removing all injectable promethazine from inpatient and outpatient settings; however, this drug is still being used despite the risk for tissue necrosis, gangrene, and possible amputation when it inadvertently is given by the subcutaneous or intra-arterial route. This article describes alternative injectable medications that can be selected based on patient comorbidities, indications, and clinician experience.

• MeSH
• Injections, Subcutaneous MeSH
• Injections MeSH
• Humans MeSH
• Promethazine * administration & dosage   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability. The resin blend of polyethylene glycol diacrylate and N-vinylpyrrolidone, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photoinitiator, was used, mixed with IMQ nanocrystals in water. The final microneedle-patches had 36 cylindrical microneedles arranged in a square grid, measuring approximately 600 μm in height and 500 μm in diameter. They contained 5wt% IMQ, which is equivalent to a commercially available cream. The homogeneity of IMQ distribution in the matrix was higher for nanocrystals compared to usual crystalline form. The release of IMQ from the patches was determined ex vivo in natural skin and revealed a 48% increase in efficacy for nanocrystal formulations compared to the crystalline form of IMQ.

• MeSH
• Printing, Three-Dimensional * MeSH
• Administration, Cutaneous MeSH
• Imiquimod * chemistry   administration & dosage   MeSH
• Needles * MeSH
• Skin Absorption MeSH
• Skin metabolism   MeSH
• Microinjections instrumentation   MeSH
• Nanoparticles * chemistry   administration & dosage   MeSH
• Polyethylene Glycols chemistry   administration & dosage   MeSH
• Povidone chemistry   MeSH
• Solubility * MeSH
• Drug Delivery Systems instrumentation   MeSH
• Drug Liberation MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury. METHODS: This randomised, double-blind, placebo-controlled phase 2b clinical trial was done at 13 hospitals in the Czech Republic, Germany, Spain, and Switzerland. Patients aged 18-70 years with acute, complete or incomplete cervical spinal cord injury (neurological level of injury C1-C8) within 4-28 days of injury were eligible for inclusion. Participants were initially randomly assigned 1:1 to intrathecal treatment with 45 mg NG101 or placebo (phosphate-buffered saline); 18 months into the study, the ratio was adjusted to 3:1 to achieve a final distribution of 2:1 to improve enrolment and drug exposure. Randomisation was done using a centralised, computer-based randomisation system and was stratified according to nine distinct outcome categories with a validated upper extremity motor score (UEMS) prediction model based on clinical parameters at screening. Six intrathecal injections were administered every 5 days over 4 weeks, starting within 28 days of injury. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was change in UEMS at 6 months, analysed alongside safety in the full analysis set. The completed trial was registered at ClinicalTrials.gov, NCT03935321. FINDINGS: From May 20, 2019, to July 20, 2022, 463 patients with acute traumatic cervical spinal cord injury were screened, 334 were deemed ineligible and excluded, and 129 were randomly assigned to an intervention (80 patients in the NG101 group and 49 in the placebo group). The full analysis set comprised 78 patients from the NG101 group and 48 patients from the placebo group. 107 (85%) patients were male and 19 (15%) patients were female, with a median age of 51·5 years (IQR 30·0-60·0). Across all patients, the primary endpoint showed no significant difference between groups (with UEMS change at 6 months 1·37 [95% CI -1·44 to 4·18]; placebo group mean 19·20 [SD 11·78] at baseline and 30·91 [SD 15·49] at day 168; NG101 group mean 18·23 [SD 15·14] at baseline and 31·31 [19·54] at day 168). Treatment-related adverse events were similar between groups (nine in the NG101 group and six in the placebo group). 25 severe adverse events were reported: 18 in 11 (14%) patients in the NG101 group and seven in six (13%) patients in the placebo group. Although no treatment-related fatalities were reported in the NG101 group, one fatality not related to treatment occurred in the placebo group. Infections were the most common adverse event affecting 44 (92%) patients in the placebo group and 65 (83%) patients in the NG101 group. INTERPRETATION: NG101 did not improve UEMS in patients with acute spinal cord injury. Post-hoc subgroup analyses assessing UEMS and Spinal Cord Independence Measure of self-care in patients with motor-incomplete injury indicated potential beneficial effects that require investigation in future studies. FUNDING: EU program Horizon2020; Swiss State Secretariat for Education, Research and Innovation; Wings for Life; the Swiss Paraplegic Foundation; and the CeNeReg project of Wyss Zurich (University of Zurich and Eidgenössische Technische Hochschule Zurich).

• MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Cervical Cord * injuries   MeSH
• Cervical Vertebrae MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Nogo Proteins * MeSH
• Spinal Cord Injuries * drug therapy   MeSH
• Aged MeSH
• Injections, Spinal * MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

Ofatumumab představuje první plně humánní anti-CD20 monoklonální protilátku, vyvinutou pro subkutánní autoaplikaci v měsíčních intervalech. Je určen k terapii aktivní relabující-remitující RS (RR-RS) a u pacientů se známkami nepříznivé prognózy nemoci ho lze uplatnit v první linii léčby. V registračních klinických studiích prokázal jasnou superioritu oproti teriflunomidu a data z extenzí klinických hodnocení potvrzují jeho setrvalou účinnost, příznivý bezpečnostní profil i vysokou míru adherence pacientů k léčbě. Z pohledu pacienta se jedná o atraktivní možnost terapie vysoce účinným lékem s jednoduchou podkožní aplikací v domácím prostředí, bez nutnosti premedikace. Ofatumumab splňuje předpoklady moderní farmakoterapie a je jedním z průlomových přípravků, který může významně zlepšit prognózu pacientů s RR-RS.

Ofatumumab represents the first fully human anti-CD20 monoclonal antibody, developed for subcutaneous self-administration once a month. It is indicated for the treatment of active relapsing-remitting multiple sclerosis (RR-MS) and can be used as a first-line therapy in patients with negative prognostic factors suggestive of an unfavorable disease course. Ofatumumab demonstrated clear superiority over teriflunomide in registration clinical trials and long-term data from open-label extension studies which confirmed its sustained efficacy, favorable safety profile, and also a high level of patient compliance. From the patient‘s point of view, it is an attractive treatment option with a high-efficacy drug that is easy to administer via subcutaneous injection at home, requiring no premedication. Ofatumumab meets the requirements of modern pharmacotherapy and is one of the breakthrough drugs that can significantly improve the prognosis of patients with RR-MS.

• Keywords
• ofatumumab,
• MeSH
• Medication Adherence MeSH
• Antigens, CD20 adverse effects   therapeutic use   MeSH
• Antibodies, Monoclonal, Humanized * adverse effects   therapeutic use   MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Injections, Subcutaneous MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Multiple Sclerosis, Relapsing-Remitting drug therapy   MeSH
• Check Tag
• Humans MeSH

Okrelizumab je první monoklonální protilátka zamířená proti povrchovému znaku CD20 vyskytujícím se na subpopulaci B lymfocytů, která byla schválena pro léčbu roztroušené sklerózy. Doposud byla tato léčba dostupná pouze jako intravenózní forma s relativně dlouhou dobou podávání, byť vysokou účinností. Od července tohoto roku byla schválena její subkutánní forma, a to na základě studie OCARINA II, ve které participovalo i naše centrum. V tomto krátkém sdělení shrnujeme základní dosažené výsledky ze studie i naše vlastní zkušenosti s touto léčbou, jejíž subkutánní forma má potenciál odlehčit našim pacientům s dávkováním jednou za půl roku. Nová forma přichází i ve spojitosti se zajímavou technologií rekombinantní hyaluronidázy, která umožňuje podávání velkých objemů subkutánně, což byl donedávna limitující faktor subkutánních terapií obecně.

Ocrelizumab is the first monoclonal antibody targeting the CD20 surface marker found on a subpopulation of B lymphocytes, which has been approved for the treatment of multiple sclerosis. Until now, this treatment was only available as an intravenous form with a relatively long administration time, albeit with high efficacy. As of July this year, its subcutaneous form has been approved based on the OCARINA II study, in which our center also participated. In this brief report, we summarize the basic achieved results from the study as well as our own experiences with this treatment, whose subcutaneous form has the potential to ease the burden on our patients with dosing once every six months. The new form also comes with an interesting recombinant hyaluronidase technology that allows the administration of large volumes subcutaneously, which has been a limiting factor for subcutaneous therapies in general until recently.

• Keywords
• okrelizumab,
• MeSH
• Antigens, CD20 drug effects   MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   MeSH
• Injections, Subcutaneous * methods   MeSH
• Administration, Intravenous methods   MeSH
• Clinical Studies as Topic methods   MeSH
• Humans MeSH
• Multiple Sclerosis * drug therapy   MeSH
• Check Tag
• Humans MeSH

Cíl studie: zhodnocení účinnosti pneumatické vitreolýzy pro rozrušení vitreomakulární trakce (VMT) na vlastním souboru pacientů. Materiál a metodika: Prospektivní sledování 21 očí 18 pacientů s fokální VMT (šířka adheze < 1500 μm), kteří podstoupili intravitreální aplikaci 0,3 ml 100% perfluoropropanu v období od ledna 2015 do prosince 2020. Pacienti byli sledováni po dobu 90 dnů. Výsledky: Uvolnění VMT bylo dosaženo 28. den sledování u 15 očí z 21 (71,4 %), 90. den u 19 z 21 očí (90,5 %). Průměrná šíře adheze našich pacientů byla 382 μm (±212 μm). Průměrná nejlepší korigovaná zraková ostrost našeho souboru byla vstupně 0,77 (±0,21), po 28 dnech 0,74 (±0,30), po 3 měsících 0,82 (±0,21). Na konci sledovacího období jsme nepozorovali statisticky významné zlepšení zrakové ostrosti. U dvou očí se po aplikaci vytvořila makulární díra, která se ale spontánně uzavřela do 1 měsíce sledování, více komplikací jsme v souboru nepozorovali. Závěr: Pneumatická vitreolýza intravitreální injekcí plynu C3F8 představuje účinnou a levnou variantu řešení symptomatické vitreomakulární trakce. Výskyt závažných nežádoucích účinků v našem sledování byl výrazně nižší než u recentně publikovaných souborů. Metodu řešení je potřeba volit individuálně dle parametrů adheze, makulární díry a přidružených patologií oka.

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.

• Keywords
• perfluoropropan, vitreomakulární trakce, pneumatická vitreolýza,
• MeSH
• Fluorocarbons classification   therapeutic use   MeSH
• Intravitreal Injections classification   methods   MeSH
• Humans MeSH
• Vitreous Detachment * surgery   therapy   MeSH
• Ophthalmologic Surgical Procedures * classification   methods   MeSH
• Retinal Perforations surgery   classification   therapy   MeSH
• Prospective Studies MeSH
• Vitrectomy classification   methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH

BACKGROUND: Corticosteroids are among the few effective treatments for knee osteoarthritis, but short duration of action limits their utility. EP-104IAR, a long-acting formulation of fluticasone propionate for intra-articular injection, optimises the action of fluticasone propionate through novel diffusion-based extended-release technology. The SPRINGBOARD trial assessed the efficacy, safety, and pharmacokinetics of EP-104IAR in people with knee osteoarthritis. METHODS: SPRINGBOARD was a randomised, vehicle-controlled, double-blind, phase 2 trial done at 12 research sites in Denmark, Poland, and Czech Republic. We recruited adults aged 40 years or older with primary knee osteoarthritis (Kellgren-Lawrence grade 2-3) who reported Western Ontario and McMaster Universities Osteoarthritis Arthritis Index (WOMAC) pain scores of at least 4 and no more than 9 out of 10. Participants were randomly assigned (1:1) to receive one intra-articular dose of 25 mg EP-104IAR or vehicle control. Randomisation was done via interactive web-based access to a central predefined computer-generated list with block size of six (allocated by clinical site). Participants and assessors were masked to treatment allocation. Participants were followed up for 24 weeks. The primary outcome was the difference between groups in change in WOMAC pain score from baseline to week 12, analysed in all participants who were randomly assigned and received treatment. Safety, including laboratory analyses, and pharmacokinetics from quantification of fluticasone propionate in peripheral blood were assessed in all participants who received a dose of randomly assigned treatment. A person with lived experience of knee osteoarthritis was involved in study interpretation and writing of the report. This trial is registered with ClinicalTrials.gov, NCT04120402, and the EU Clinical Trials Register, EudraCT 2021-000859-39, and is complete. FINDINGS: Between Sept 10, 2021, and Nov 16, 2022, 1294 people were screened for eligibility, and 319 were randomly assigned to EP-104IAR (n=164) or vehicle control (n=155). One participant in the EP-104IAR group was excluded from all analyses because treatment was not administered due to an adverse event. 318 participants (135 [42%] male and 183 [58%] female, 315 [99%] White) received randomly assigned treatment and were included in the primary analysis and safety analysis (EP-104IAR, n=163; vehicle control, n=155). At week 12, least squares mean change in WOMAC pain score from baseline was -2·89 (95% CI -3·22 to -2·56) in the EP-104IAR group and -2·23 (-2·56 to -1·89) in the vehicle control group, with a between-group difference of -0·66 (-1·11 to -0·21; p=0·0044); a significant between-group difference persisted to week 14. 106 (65%) of 163 participants in the EP-104IAR group had one or more treatment-emergent adverse event compared with 89 (57%) of 155 participants in the vehicle control group. Effects on serum glucose and cortisol concentrations were minimal and transient. There were no treatment-emergent deaths or treatment-related serious adverse events. Plasma concentrations of fluticasone propionate showed a blunted initial peak with terminal half-life of approximately 18-20 weeks. INTERPRETATION: These phase 2 results suggest that EP-104IAR has the potential to offer clinically meaningful pain relief in knee osteoarthritis for an extended period of up to 14 weeks, longer than published data for currently marketed corticosteroids. There were minimal effects on glucose and cortisol, and stable fluticasone propionate concentrations in plasma. The safety and efficacy of EP-104IAR will be further evaluated in phase 3 trials, including the possibility of bilateral and repeat dosing with EP-104IAR. FUNDING: Eupraxia Pharmaceuticals. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

• MeSH
• Osteoarthritis, Knee * drug therapy   MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Fluticasone * administration & dosage   pharmacokinetics   therapeutic use   adverse effects   MeSH
• Injections, Intra-Articular MeSH
• Delayed-Action Preparations MeSH
• Middle Aged MeSH
• Humans MeSH
• Pain Measurement MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• Czech Republic MeSH
• Denmark MeSH
• Poland MeSH

Injekční aplikace výplňového materiálu zejména do oblasti obličeje jsou populární estetickou procedurou, která se využívá k obnovení objemu, zlepšení kontur a vyhlazení vrásek. Za nejbezpečnější je považována kyselina hyaluronová, ale i ta nese riziko vzniku vaskulárních komplikací. Tyto komplikace mohou být závažné a vést k ischemii, nekróze tkání nebo dokonce slepotě či centrální mozkové příhodě. Tento článek se zaměřuje na identifikaci rizik spojených s vaskulárními komplikacemi při aplikaci dermálních výplní a na strategie pro jejich prevenci a řešení.

The application of filler material, particularly in the facial area, is a popular aesthetic procedure used to restore volume, improve contours and smooth wrinkles. Hyaluronic acid is considered the safest option, but it too carries the risk of vascular complications. These complications can be severe and lead to ischemia, tissue necrosis, or even blindness or stroke. This article focuses on identifying the risks associated with vascular complications associated with dermal filler application and strategies for prevention and management.

• MeSH
• Retinal Artery pathology   MeSH
• Dermal Fillers adverse effects   MeSH
• Hyaluronoglucosaminidase * pharmacology   adverse effects   MeSH
• Injections, Subcutaneous adverse effects   MeSH
• Hyaluronic Acid adverse effects   MeSH
• Humans MeSH
• Vascular Diseases * chemically induced   pathology   prevention & control   therapy   MeSH
• Drug-Related Side Effects and Adverse Reactions pathology   prevention & control   therapy   MeSH
• Eye Manifestations MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

PURPOSE: Subretinal (SR) injection in porcine models is a promising avenue for preclinical evaluation of cell and gene therapies. Targeting of the subretinal fluid compartment (bleb) is critical to the procedure, especially if treatment of the cone-rich area centralis is required (i.e., visual streak [VS] in pigs). To our knowledge, this study is the first to investigate the influence of injection site placement on VS involvement in the pig eye. METHODS: We performed 23-gauge pars plana vitrectomy followed by SR injection in 41 eyes of 21 animals (Sus scrofa domesticus). In 27 eyes (65.9%), the injection site was placed superior to the VS, and in 14 eyes (34.1%) it was placed inferior to it. Using intraoperative imaging, blebs were classified based on their propagation behavior relative to the VS. RESULTS: In 79% of cases, blebs from inferior injection sites developed away from the VS, exhibiting a mean ± SEM vertical anisotropy (AP) of 0.67 ± 0.11. In contrast, blebs from superior injection sites tended to develop toward the VS with an AP of 1.27 ± 0.18 (P = 0.0070). Blebs developed away from the VS in only 41% of injections (P = 0.0212). Inferior blebs were orientated close to 0° (horizontal), whereas superior blebs displayed varied orientations with a mean angle of 56° (P = 0.0008). CONCLUSIONS: Bleb propagation was anisotropic (i.e., directionally biased) and dependent on injection site placement. Superior injection sites led to superior VS detachment. Morphological analysis suggested increased adhesion forces at the VS and superior vascular arcades. This study will aid the planning of surgeries for targeted subretinal delivery in pig models.

• MeSH
• Genetic Therapy * methods   MeSH
• Injections, Intraocular MeSH
• Disease Models, Animal * MeSH
• Swine MeSH
• Retina MeSH
• Subretinal Fluid metabolism   MeSH
• Sus scrofa MeSH
• Vitrectomy * methods   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

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.

• MeSH
• Biosimilar Pharmaceuticals * therapeutic use   adverse effects   MeSH
• Diabetic Retinopathy * drug therapy   diagnosis   physiopathology   MeSH
• Double-Blind Method MeSH
• Angiogenesis Inhibitors * administration & dosage   therapeutic use   adverse effects   MeSH
• Intravitreal Injections * MeSH
• Middle Aged MeSH
• Humans MeSH
• Macular Edema * drug therapy   physiopathology   diagnosis   MeSH
• Tomography, Optical Coherence MeSH
• Receptors, Vascular Endothelial Growth Factor * administration & dosage   MeSH
• Recombinant Fusion Proteins * therapeutic use   administration & dosage   MeSH
• Aged MeSH
• Vascular Endothelial Growth Factor A antagonists & inhibitors   MeSH
• Treatment Outcome MeSH
• Visual Acuity * physiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH