RESUMEN
Vascular endothelial growth factor receptor inhibitors (VEGFRis) improve cancer survival but are associated with treatment-limiting hypertension, often attributed to endothelial cell (EC) dysfunction. Using phosphoproteomic profiling of VEGFRi-treated ECs, drugs were screened for mitigators of VEGFRi-induced EC dysfunction and validated in primary aortic ECs, mice, and canine cancer patients. VEGFRi treatment significantly raised systolic blood pressure (SBP) and increased markers of endothelial and renal dysfunction in mice and canine cancer patients. α-Adrenergic-antagonists were identified as drugs that most oppose the VEGFRi proteomic signature. Doxazosin, one such α-antagonist, prevented EC dysfunction in murine, canine, and human aortic ECs. In mice with sorafenib-induced-hypertension, doxazosin mitigated EC dysfunction but not hypertension or glomerular endotheliosis, while lisinopril mitigated hypertension and glomerular endotheliosis without impacting EC function. Hence, reversing EC dysfunction was insufficient to mitigate VEGFRi-induced-hypertension in this mouse model. Canine cancer patients with VEGFRi-induced-hypertension were randomized to doxazosin or lisinopril and both agents significantly decreased SBP. The canine clinical trial supports safety and efficacy of doxazosin and lisinopril as antihypertensives for VEGFRi-induced-hypertension and the potential of trials in canines with spontaneous cancer to accelerate translation. The overall findings demonstrate the utility of phosphoproteomics to identify EC-protective agents to mitigate cardio-oncology side effects.
Asunto(s)
Doxazosina , Células Endoteliales , Hipertensión , Receptores de Factores de Crecimiento Endotelial Vascular , Animales , Perros , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Hipertensión/fisiopatología , Doxazosina/farmacología , Doxazosina/uso terapéutico , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Proteómica/métodos , Presión Sanguínea/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Lisinopril/farmacología , Lisinopril/uso terapéutico , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Sorafenib/farmacología , Sorafenib/uso terapéuticoRESUMEN
BACKGROUND: This study aimed to compare the regressive effects of aflibercept and faricimab on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration. METHODS: In total, 41 eyes of 40 patients diagnosed with type 1 macular neovascularization were retrospectively analyzed using multimodal imaging. Of these, 23 eyes were treated with intravitreal aflibercept injections (IVA group), and 18 eyes were treated with intravitreal faricimab (IVFa group), with 3 consecutive injections administered as loading dose therapy. Before treatment and at 1, 2, and 3 months after the first treatment, the maximum height (MH) and maximum diameter (MD) of the PED were measured using optical coherence tomography in each treatment group. RESULTS: In the IVA group, the MH at baseline (215 ± 177 µm) was reduced to 141 ± 150 (P = 0.06), 119 ± 150 (P < 0.01), and 107 ± 150 µm (P < 0.0001) at 1, 2, and 3 months after treatment, respectively. Similarly, in the IVFa group, the MH decreased from 240 ± 195 µm before treatment to 165 ± 170 µm (P = 0.24), 139 ± 142 µm (P < 0.05), and 117 ± 112 µm (P < 0.01) at 1, 2, and 3 months after treatment, respectively. The reduction at 2 and 3 months was significant in both treatments. The mean changes of MH from baseline were -108 ± 142 µm in the IVA group and -124 ± 112 µm in the IVFa group, with no significant difference (P = 0.21). In both groups, the MD did not regress significantly. CONCLUSIONS: The results suggested that the MH of the PED between the IVA and IVFa groups regressed similarly after each loading therapy.
Asunto(s)
Inhibidores de la Angiogénesis , Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Desprendimiento de Retina , Epitelio Pigmentado de la Retina , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Masculino , Femenino , Estudios Retrospectivos , Desprendimiento de Retina/tratamiento farmacológico , Desprendimiento de Retina/diagnóstico , Anciano , Tomografía de Coherencia Óptica/métodos , Inhibidores de la Angiogénesis/uso terapéutico , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/fisiopatología , Anciano de 80 o más Años , Persona de Mediana Edad , Angiografía con Fluoresceína , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
PURPOSE: To evaluate the structural characteristics and long-term visual outcomes in eyes impacted by macular edema as a consequence of retinal vein occlusion that has undergone effective treatment with anti-vascular endothelial growth factor therapy. METHODS: Inclusion criteria comprised 42 eyes of 41 patients, subjected to long-term follow-up, displaying resolved macular edema after a minimum of 5 years since the commencement of anti-vascular endothelial growth factor therapy. During the final visit, two experienced observers evaluated several qualitative parameters using spectral-domain optical coherence tomography, such as the integrity of the external limiting membrane, the state of the ellipsoid zone and retinal pigment epithelium, and the presence of disorganization of the retinal inner layers. In addition, a quantitative evaluation of the inner and outer retinal thicknesses was conducted for the purpose of topographical analysis. RESULTS: The most prominent qualitative correlation identified with best-corrected visual acuity during the final visit was connected to the presence of disorganization of the retinal inner layers ( P = 0.004) and the integrity of the external limiting membrane ( P = 0.015). In relation to quantitative aspects, a noteworthy correlation was noted between the visual acuity during the last visit and the parafoveal thickness in both the inner ( P = 0.003) and outer retina ( P = 0.018). CONCLUSION: In eyes where macular edema resulting from retinal vein occlusion has been successfully resolved with anti-vascular endothelial growth factor therapy, changes in the status of the external limiting membrane and the presence of disorganization of the retinal inner layers serve as valuable optical coherence tomography biomarkers, indicating prolonged visual outcomes.
Asunto(s)
Inhibidores de la Angiogénesis , Inyecciones Intravítreas , Edema Macular , Ranibizumab , Oclusión de la Vena Retiniana , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Humanos , Tomografía de Coherencia Óptica/métodos , Oclusión de la Vena Retiniana/tratamiento farmacológico , Oclusión de la Vena Retiniana/complicaciones , Oclusión de la Vena Retiniana/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Edema Macular/diagnóstico , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Masculino , Femenino , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Estudios de Seguimiento , Persona de Mediana Edad , Ranibizumab/administración & dosificación , Ranibizumab/uso terapéutico , Bevacizumab/uso terapéutico , Estudios Retrospectivos , Anciano de 80 o más Años , Biomarcadores , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Angiografía con Fluoresceína/métodosRESUMEN
PURPOSE: To understand factors affecting visual prognosis and the number of intravitreal antivascular endothelial growth factor (anti-VEGF) injections needed to stabilize wet age-related macular degeneration (AMD). METHODS: In this retrospective cohort, 119 treatment-naïve wet AMD patients were followed for two years. In patients with bilateral disease, the eye with worse best-corrected visual acuity (BCVA) or that received more intravitreal injections was recruited as the study eye. In all visits, BCVA was recorded, ophthalmological examination was performed including macular optical coherence tomography imaging. Twenty health status/lifestyle questions were asked to the patients via phone as potential risk factors. All patients received 3 loading doses of intravitreal bevacizumab injections and received repeat injections of aflibercept or ranibizumab when the eye had a new, active neovascular lesion. RESULTS: Patients who took regular micronutrition had similar visual outcome and injection numbers compared to the ones who did not. Patients with bilateral disease needed less intravitreal injections compared to unilateral AMD patients (p = 0.016) and women on hormone replacement therapy (HRT) required less injections compared to the women who were not (p = 0.024). Female patients had a mean gain of 2.7 letters while male patients lost 3.8 letters (p = 0.038). Wet AMD started at an earlier age in smokers (p = 0.002). Patients with a better education level presented earlier with better BCVA (p = 0.037). CONCLUSION: HRT and anti-VEGF injections to the fellow eye improved the prognosis of wet AMD, while male patients had slightly worse prognosis. Estrogen's protective effects and potential contribution in wet AMD needs further attention. Retrospectively registered: 2020/0622.
Asunto(s)
Inhibidores de la Angiogénesis , Bevacizumab , Inyecciones Intravítreas , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Degeneración Macular Húmeda , Humanos , Masculino , Estudios Retrospectivos , Femenino , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/fisiopatología , Inhibidores de la Angiogénesis/administración & dosificación , Anciano , Ranibizumab/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/administración & dosificación , Bevacizumab/administración & dosificación , Tomografía de Coherencia Óptica/métodos , Pronóstico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano de 80 o más Años , Estudios de Seguimiento , Persona de Mediana Edad , Angiografía con Fluoresceína/métodosRESUMEN
This Viewpoint highlights the discrepancy between dosing and patient assessment schedules in clinical trials for 2 new intravitreal agents, faricimab, 6 mg, and aflibercept, 8 mg, to treat neovascular age-related macular degeneration.
Asunto(s)
Inhibidores de la Angiogénesis , Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Factor A de Crecimiento Endotelial Vascular , Humanos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/administración & dosificación , Inhibidores de la Angiogénesis/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/fisiología , Esquema de Medicación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Degeneración Macular Húmeda/tratamiento farmacológico , MasculinoRESUMEN
BACKGROUND: Colorectal cancer (CRC) treatment using time-saving and cost-effective targeted therapies with high selectivity and low toxicity drugs, is a great challenge. In primary investigations on Gallocin, as the most proposed factor in CRC pathogenesis caused by Streptococcus gallolyticus, it was surprisingly found that this bacteriocin has four α-helix structures and some anti-cancer sequences. OBJECTIVE: The aim of this study was to determine the ability of Gallocin-based anticancer peptides (ACPs) against epidermal growth factor receptor (EGFR) and vascular epidermal growth factor receptor (VEGFR) and the evaluation of their pharmacokinetic properties using bioinformatic approaches. METHODS: Support vector machine algorithm web-based tools were used for predicting ACPs. The physicochemical characteristics and the potential of anti-cancer activity of Gallocin-derived ACPs were determined by in silico tools. The 3D structure of predicted ACPs was modeled using modeling tools. The interactions between predicted ACPs and targets were investigated by molecular docking exercises. Then, the stability of ligand-receptor interactions was determined by molecular dynamic simulation. Finally, ADMET analysis was carried out to check the pharmacokinetic properties and toxicity of ACPs. RESULTS: Four amino acid sequences with anti-cancer potential were selected. Through molecular docking, Pep2, and Pep3 gained the best scores, more binding affinity, and strong attachments by the formation of reasonable H-bonds with both EGFR and VEGFR. Molecular simulation confirmed the stability of Pep3- EGFR. According to pharmacokinetic analysis, the ACPs were safe and truthful. CONCLUSION: Designed peptides can be nominated as drugs for CRC treatment. However, different in-vitro and in-vivo assessments are required to approve this claim.
Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Biología Computacional , Receptores ErbB , Péptidos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Péptidos/química , Péptidos/farmacología , Péptidos/síntesis química , Bacteriocinas/química , Bacteriocinas/farmacología , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Simulación del Acoplamiento Molecular , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacosRESUMEN
PURPOSE: Pathological angiogenesis and vascular instability are observed in diabetic retinopathy (DR), diabetic macular edema (DME), and wet age-related macular degeneration (wAMD). Many receptor tyrosine kinases (RTKs) including vascular endothelial growth factor receptors (VEGFRs) contribute to angiogenesis, whereas the RTK TIE2 is important for vascular stability. Pan-VEGFR tyrosine kinase inhibitors (TKIs) such as vorolanib, sunitinib, and axitinib are of therapeutic interest over current antibody treatments that target only one or two ligands. This study compared the anti-angiogenic potential of these TKIs. METHODS: A kinase HotSpot™ assay was conducted to identify TKIs inhibiting RTKs associated with angiogenesis and vascular stability. Half-maximal inhibitory concentration (IC50) for VEGFRs and TIE2 was determined for each TKI. In vitro angiogenesis inhibition was investigated using a human umbilical vein endothelial cell sprouting assay, and in vivo angiogenesis was studied using the chorioallantoic membrane assay. Melanin binding was assessed using a melanin-binding assay. Computer modeling was conducted to understand the TIE2-axitinib complex as well as interactions between vorolanib and VEGFRs. RESULTS: Vorolanib, sunitinib, and axitinib inhibited RTKs of interest in angiogenesis and exhibited pan-VEGFR inhibition. HotSpot™ assay and TIE2 IC50 values showed that only axitinib potently inhibited TIE2 (up to 89%). All three TKIs effectively inhibited angiogenesis in vitro. In vivo, TKIs were more effective at inhibiting VEGF-induced angiogenesis than the anti-VEGF antibody bevacizumab. Of the three TKIs, only sunitinib bound melanin. TKIs differ in their classification and binding to VEGFRs, which is important because type II inhibitors have greater selectivity than type I TKIs. CONCLUSIONS: Vorolanib, sunitinib, and axitinib exhibited pan-VEGFR inhibition and inhibited RTKs associated with pathological angiogenesis. Of the three TKIs, only axitinib potently inhibited TIE2 which is an undesired trait as TIE2 is essential for vascular stability. The findings support the use of vorolanib for therapeutic inhibition of angiogenesis observed in DR, DME, and wAMD.
Asunto(s)
Inhibidores de la Angiogénesis , Axitinib , Células Endoteliales de la Vena Umbilical Humana , Imidazoles , Indazoles , Indoles , Inhibidores de Proteínas Quinasas , Pirroles , Receptores de Factores de Crecimiento Endotelial Vascular , Sunitinib , Axitinib/farmacología , Humanos , Sunitinib/farmacología , Inhibidores de la Angiogénesis/farmacología , Imidazoles/farmacología , Pirroles/farmacología , Indoles/farmacología , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Indazoles/farmacología , Animales , Inhibidores de Proteínas Quinasas/farmacología , Receptor TIE-2/metabolismo , Receptor TIE-2/antagonistas & inhibidores , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismoRESUMEN
PURPOSE: To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept. METHODS: In this retrospective, single-center study, DME patients previously treated with at least 3 injections of aflibercept then switched to faricimab were enrolled. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline, at the time of the switch and at 6 months follow-up. At transition to faricimab, patients were categorized as "good visual responders" (≥ 5 letters from baseline) or "poor visual responders" (< 5 letters), and as "good anatomical responders" (any reduction in edema compared to baseline) or "poor anatomical responders" (no reduction or worsening of edema). Changes in BCVA and CST were recorded at 6 months after the switch to faricimab. RESULTS: 100 eyes of 100 patients (61 female, 61%) were switched to faricimab after a mean of 6.8 ± 3.3 aflibercept injections. At the 6 months follow-up, only "poor visual responders" (N = 62) demonstrated a meaningful increase in BCVA (Δswitch-6M = + 5 letters; P = 0.007), coupled with a reduction in CST (Δswitch-6M = - 67.9 µm; P = 0.004); participants with "poor anatomical response" upon transitioning exhibited a significant functional gain (Δswitch-6M = + 4.5 letters; p = 0.05) but limited CST enhancements (Δswitch-6M = - 95.1 µm; p = 0.05). CONCLUSIONS: Faricimab shows a positive impact on anatomical and functional metrics in DME cases refractory to aflibercept.
Asunto(s)
Inhibidores de la Angiogénesis , Retinopatía Diabética , Inyecciones Intravítreas , Edema Macular , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Femenino , Masculino , Estudios Retrospectivos , Edema Macular/tratamiento farmacológico , Edema Macular/diagnóstico , Edema Macular/etiología , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/complicaciones , Retinopatía Diabética/fisiopatología , Persona de Mediana Edad , Inhibidores de la Angiogénesis/administración & dosificación , Tomografía de Coherencia Óptica/métodos , Estudios de Seguimiento , Anciano , Resultado del Tratamiento , Sustitución de Medicamentos/métodos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
This review article explores the intricate correlation between growth factors and bone metastases, which play a crucial role in the development of several types of malignancies, namely breast, prostate, lung, and renal cancers. The focal point of our discussion is on crucial receptors for growth factors, including Epidermal Growth Factor Receptor (EGFR), Transforming Growth Factor-ß (TGFß), Vascular Endothelial Growth Factor Receptor (VEGFR), and Fibroblast Growth Factor Receptor (FGFR). These receptors, which are essential for cellular activities including growth, differentiation, and survival, have important involvement in the spread of cancer and the interactions between tumors and the bone environment. We discuss the underlying mechanisms of bone metastases, with a specific emphasis on the interaction between growth factor receptors and the bone microenvironment. EGFR signaling specifically enhances the process of osteoclast development and the formation of osteolytic lesions, especially in breast and lung malignancies. TGFß receptors have a role in both osteolytic and osteoblastic metastases by releasing TGFß, which attracts cancer cells and promotes bone remodeling. This is a crucial element in the spread of prostate cancer to the bones. The functions of FGFR and VEGFR in the processes of bone formation and tumor angiogenesis, respectively, highlight the complex and diverse nature of these interactions. The review emphasizes the possibility of targeted therapeutics targeting these receptors to interrupt the cycle of tumor development and bone degradation. Therapeutic approaches include focusing on the VEGF/VEGFR, EGF/EGFR, FGF/FGFR, and TGFß/TGFßR pathways. These include a variety of compounds, such as small molecule inhibitors and monoclonal antibodies, which have shown potential to interfere with tumor-induced alterations in bone. The text discusses clinical trials and preclinical models, offering insights into the effectiveness and constraints of various treatments. Ultimately, this study provides a succinct but thorough summary of the present knowledge and treatment strategies focused on growth factor receptors in bone metastases. This highlights the significance of comprehending the signaling of growth factor receptors in the microenvironment where tumors spread to the bones, as well as the possibility of using targeted therapies to enhance the results for cancer patients with bone metastases. The advancement of treating bone metastases hinges on the development of treatments that specifically target the intricate relationships between malignancies and bone.
Asunto(s)
Neoplasias Óseas , Humanos , Neoplasias Óseas/secundario , Neoplasias Óseas/metabolismo , Receptores de Factores de Crecimiento/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inhibidores , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/antagonistas & inhibidores , Animales , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
BACKGROUND: Macular retinoschisis (MRS) and myopic macular neovascularization (mMNV) are both potentially blinding complications of high myopia. In this case report, we highlight the progression of MRS after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for mMNV, as well as an extensive review of the literature on this topic. CASE DESCRIPTION: A 49-year-old woman presented with two weeks of recent onset blurring and metamorphopsia in her right eye. She had high myopia in both eyes (right eye - 20/60 with - 16D, left eye - 20/20 with - 13D). Slit-lamp ophthalmoscopy found a normal anterior segment in both eyes. On fundus examination, features of pathological myopia with posterior staphyloma and peripapillary atrophy were observed in both eyes. An active mMNV, as well as intraretinal fluid, minimal perifoveal inner and outer MRS, and focal posterior vitreous traction along the inferotemporal retinal arcade, were detected on optical coherence tomography (OCT) of the right eye. The patient received an intravitreal injection of Aflibercept (2 mg/0.05 ml). RESULTS: OCT scans at two- and four-month follow-up visits revealed regressed mMNV with a taut epiretinal membrane, progressive worsening of outer MRS, and the development of multiple perifoveal retinal detachment inferior to the fovea. Pars plana vitrectomy surgery was performed for the progressive MRS with good anatomical (resolved MRS) and functional outcome (maintained visual acuity at 20/60) at the last one-month post-surgery visit. CONCLUSION: Intravitreal anti-VEGF injections for mMNV can cause vitreoretinal interface changes, exacerbating MRS and causing visual deterioration. Vitrectomy for MRS could be one of several treatment options.
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Inyecciones Intravítreas , Miopía Degenerativa , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Retinosquisis , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Femenino , Persona de Mediana Edad , Retinosquisis/diagnóstico , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Miopía Degenerativa/complicaciones , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/administración & dosificación , Progresión de la Enfermedad , Neovascularización Retiniana/tratamiento farmacológico , Neovascularización Retiniana/diagnóstico , Neovascularización Retiniana/inducido químicamente , Angiografía con FluoresceínaRESUMEN
"A journey of mixed emotions" is a quote that best describes the progress chart of vascular endothelial growth factor receptor (VEGFR) inhibitors as cancer therapeutics in the last decade. Exhilarated with the Food and Drug Administration (FDA) approvals of numerous VEGFR inhibitors coupled with the annoyance of encountering the complications associated with their use, drug discovery enthusiasts are on their toes with an unswerving determination to enhance the rate of translation of VEGFR inhibitors from preclinical to clinical stage. The recently crafted armory of VEGFR inhibitors is a testament to their growing dominance over other antiangiogenic therapies for cancer treatment. This review perspicuously underscores the earnest attempts of the researchers to extract the antiproliferative potential of VEGFR inhibitors through the design of mechanistically diverse structural assemblages. Moreover, this review encompasses sections on structural/molecular properties and physiological functions of VEGFR, FDA-approved VEGFR inhibitors, and hurdles restricting the activity range/clinical applicability of VEGFR targeting antitumor agents. In addition, tactics to overcome the limitations of VEGFR inhibitors are discussed. A clear-cut viewpoint transmitted through this compilation can provide practical directions to push the cart of VEGFR inhibitors to advanced-stage clinical investigations in diverse malignancies.
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Antineoplásicos , Neoplasias , Inhibidores de Proteínas Quinasas , Receptores de Factores de Crecimiento Endotelial Vascular , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Animales , Estructura MolecularRESUMEN
OBJECTIVES: Exploration into the use of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) inhibitors alongside programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has been undertaken for treating recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). We conducted a meta-analysis to provide a more precise assessment of the efficacy and safety of this integrated approach in managing R/M HNSCC. METHODS: A systematic exploration encompassing PubMed, Embase, the Cochrane Library, and Web of Science databases was undertaken to figure out relevant studies. It was attempted to analyze critical endpoints, such as overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) utilizing a random-effects model. RESULTS: Eleven studies, encompassing 413 patients, were analyzed. The combined data revealed an ORR of 41 % (95 % CI: 34-49 %), a DCR of 67 % (95 % CI: 51-83 %), a median PFS of 5.87 months (95 % CI: 3.90-7.85), and a median OS of 9.63 months (95 % CI: 6.78-12.49). Furthermore, the rates for 1-year PFS and OS were 45 % (95 % CI: 27-64 %) and 65 % (95 % CI: 49-81 %), respectively. The occurrence of grade 3 or higher adverse events related to the drugs was 20 % (95 % CI: 10-30 %). Subgroup analysis within the tyrosine kinase inhibitor (TKI) group revealed an ORR of 47 % (95 % CI: 39 %-55 %) and a DCR of 67 % (95 % CI: 46 %-88 %). CONCLUSIONS: In summary, combining VEGF/VEGFR inhibitors with PD-1/PD-L1 inhibitors shows considerable effectiveness with manageable side effects in cases with R/M HNSCC. SYSTEMATIC REVIEW REGISTRATION: Registered with the International Prospective Register of Systematic Reviews, identifier CRD42023486345.
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Receptores de Factores de Crecimiento Endotelial Vascular , Carcinoma de Células Escamosas de Cabeza y Cuello , Factor A de Crecimiento Endotelial Vascular , Humanos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Masculino , FemeninoRESUMEN
PURPOSE: This study compares the changes in the parameters of the anterior chamber of the eye using anterior segment optical coherence tomography (AS-OCT) in patients with a natural and artificial lens after treatment of neovascular age-related macular degeneration (nAMD) by multiple intravitreal injections (IVI) of anti-VEGF drugs. MATERIAL AND METHODS: The patients were divided into 2 groups: group 1 (control) included 30 patients (30 eyes) with a natural lens, group 2 - 30 patients (30 eyes) with an intraocular lens (IOL). AS-OCT was performed using the Revo NX tomograph (Optopol, Poland) to analyze anterior chamber depth (ACD) and the parameters of anterior chamber angle (ACA). Intraocular pressure (IOP) was measured with a contact tonometer ICare Pro. RESULTS: In patients with an IOL, the IOP level 1 minute after intravitreal injection (IVI) of an anti-VEGF drug was statistically lower than in the control group, on average by 17.8% during the first IVI and by 28.7% after 1 year of observation (p<0.001). ACD before treatment was statistically significantly higher in patients with IOL compared to patients of group 1 by an average of 39.3% (p<0.001). ACA from the nasal and temporal sides in the meridian 0°-180° before the start of treatment was statistically significantly wider in phakic patients than in the control group, by an average of 15.9±9.3° (p<0.001) and 16.9±8.2° (p<0.001), respectively. According to AS-OCT, there was no shift of the iris-lens diaphragm in patients with an IOL after multiple IVI of an anti-VEGF drug, in contrast to the control group. CONCLUSIONS: AS-OCT was used to determine for the first time the changes in the parameters of the anterior chamber of the eye in patients with a natural and artificial lens after multiple injections of an anti-VEGF drug in the treatment of nAMD.
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Inhibidores de la Angiogénesis , Segmento Anterior del Ojo , Presión Intraocular , Cristalino , Lentes Intraoculares , Degeneración Macular , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Factor A de Crecimiento Endotelial Vascular , Presión Intraocular/efectos de los fármacos , Segmento Anterior del Ojo/diagnóstico por imagen , Segmento Anterior del Ojo/efectos de los fármacos , Inyecciones Intravítreas , Tomografía de Coherencia Óptica , Degeneración Macular/tratamiento farmacológico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
Worldwide, cancer is a major public health concern. It is a well-acknowledged life-threatening disease. Despite numerous advances in the understanding of the genetic basis of cancer growth and progression, therapeutic challenges remain high. Human tumors exhibited mutation or overexpression of several tyrosine kinases (TK). The vascular endothelial growth factor receptor (VEGFR) is a TK family member and is well known for tumor growth and progression. Therefore, VEGF/VEGFR pathway inhibition is an appealing approach for cancer drug discovery. This review will discuss the structure-based optimization of thienopyrimidines incorporating the aryl urea moiety to develop scaffolds of potent anticancer activity via VEGFR inhibition published between 2013 and 2023. Increasing knowledge of probable scaffolds that can act as VEGFR inhibitors might spur the hunt for novel anticancer medications that are safer, more effective, or both.
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Antineoplásicos , Inhibidores de Proteínas Quinasas , Pirimidinas , Receptores de Factores de Crecimiento Endotelial Vascular , Urea , Humanos , Pirimidinas/farmacología , Pirimidinas/química , Pirimidinas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Urea/farmacología , Urea/química , Urea/análogos & derivados , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Relación Estructura-Actividad , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Estructura Molecular , AnimalesRESUMEN
On November 8, 2023, the FDA approved fruquintinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and if RAS wild-type and medically appropriate, an anti-EGFR therapy. Approval was based on Study FRESCO-2, a globally conducted, double-blind, placebo-controlled randomized trial. The primary endpoint was overall survival (OS). The key secondary endpoint was progression-free survival. A total of 691 patients were randomly assigned (461 and 230 into the fruquintinib and placebo arms, respectively). Fruquintinib provided a statistically significant improvement in OS with a hazard ratio (HR) of 0.66 [95% confidence interval (CI), 0.55, 0.80; P < 0.001]. The median OS was 7.4 months (95% CI, 6.7, 8.2) in the fruquintinib arm and 4.8 months (95% CI, 4.0, 5.8) for the placebo arm. Adverse events observed were generally consistent with the known safety profile associated with the inhibition of VEGFR. The results of FRESCO-2 were supported by the FRESCO study, a double-blind, single-country, placebo-controlled, randomized trial in patients with refractory mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. In FRESCO, the OS HR was 0.65 (95% CI, 0.51, 0.83; P < 0.001). FDA concluded that the totality of the evidence from FRESCO-2 and FRESCO supported an indication for patients with mCRC with prior treatment with fluoropyrimidine, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type and medically appropriate, an anti-EGFR therapy.
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Benzofuranos , Neoplasias Colorrectales , Aprobación de Drogas , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estados Unidos , Benzofuranos/uso terapéutico , Benzofuranos/efectos adversos , Benzofuranos/administración & dosificación , Adulto , Método Doble Ciego , Quinazolinas/uso terapéutico , Metástasis de la Neoplasia , United States Food and Drug Administration , Anciano de 80 o más Años , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Resistencia a Antineoplásicos/efectos de los fármacosRESUMEN
Importance: There is no systemic therapy for recurrent or metastatic adenoid cystic carcinoma (ACC) approved by the US Food and Drug Administration. Objective: To examine the efficacy, safety, and tolerability of vascular endothelial growth factor receptor (VEGFR) inhibitors in recurrent or metastatic ACC. Data Sources: PubMed, Embase, and Cochrane Library were systematically searched for studies of VEGFR inhibitors in recurrent or metastatic ACC from database inception to August 31, 2023. Study Selection: Inclusion criteria were prospective clinical trials of recurrent or metastatic ACC treated with VEGFR inhibitors, reporting at least 1 outcome of interest specifically for ACC. Of 1963 identified studies, 17 (0.9%) met inclusion criteria. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline was followed to extract data. Data were pooled using a random-effects generalized linear mixed model with 95% CIs. Main Outcomes and Measures: The primary efficacy outcome was best overall response to VEGFR inhibitors, including objective response, stable disease, or progressive disease (PD). Safety and tolerability outcomes included incidence of grade 3 or higher adverse events, rates of exit from trial due to PD or drug-related toxic effects, and dose reduction rate (DRR). Results: A total of 17 studies comprising 560 patients with recurrent or metastatic ACC treated with 10 VEGFR inhibitors were included. The objective response rate was 6% (95% CI, 3%-12%; I2 = 71%) and stable disease was the most frequent best overall response (82%; 95% CI, 74%-87%; I2 = 67%). The 6-month disease control (defined as objective response and stable disease) rate was 54% (95% CI, 45%-62%; I2 = 52%). The rate of grade 3 or higher adverse events was 53% (95% CI, 42%-64%; I2 = 81%) and of DRR was 59% (95% CI, 40%-76%). Most patients (57%; 95% CI, 44%-70%; I2 = 83%) continued therapy until PD; 21% (95% CI, 15%-28%; I2 = 62%) of patients suspended therapy for toxic effects. In subgroup analysis by specific VEGFR inhibitor, the objective response rate was 14% (95% CI, 7%-25%; I2 = 0%), stable disease rate was 76% (95% CI, 63%-85%; I2 = 0%), proportion treated until PD was 61% (95% CI, 14%-94%; I2 = 94%), and DRR was 78% (95% CI, 66%-87%; I2 = 39%) with lenvatinib. Corresponding axitinib results were objective response rate of 8% (95% CI, 4%-15%; I2 = 0%) and stable disease rate of 85% (95% CI, 72%-92%; I2 = 69%), with 73% (95% CI, 63%-82%; I2 = 0%) of patients treated until PD, and the DRR was 22% (95% CI, 12%-38%; I2 = 77%). Rivoceranib had the highest objective response rate (24%; 95% CI, 7%-57%) but high heterogeneity among studies (I2 = 95%) and the lowest rate of patients who continued therapy until PD (35%; 95% CI, 20%-55%; I2 = 90%). Conclusions and Relevance: This systematic review and meta-analysis found that VEGFR inhibitors were associated with high rates of disease stabilization in recurrent or metastatic ACC. Of 10 included VEGFR inhibitors, lenvatinib and axitinib were associated with the best combined and consistent efficacy, safety, and tolerability profiles, substantiating their inclusion in treatment guidelines.
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Carcinoma Adenoide Quístico , Recurrencia Local de Neoplasia , Receptores de Factores de Crecimiento Endotelial Vascular , Humanos , Carcinoma Adenoide Quístico/tratamiento farmacológico , Carcinoma Adenoide Quístico/secundario , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Recurrencia Local de Neoplasia/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Metástasis de la NeoplasiaRESUMEN
PURPOSE: To compare 1-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal VEGF inhibitor injections were delivered. DESIGN: Cohort study. PARTICIPANTS: There were 2288 treatment-naive eyes with DME starting intravitreal VEGF inhibitor therapy from October 31, 2015 to October 31, 2021 from the Fight Retinal Blindness! international outcomes registry. METHODS: Eyes were grouped according to the proportion of visits at which an injection was received, Group A with less than the median of 67% (n = 1172) versus Group B with greater than the median (n = 1116). MAIN OUTCOME MEASURES: Mean visual acuity (VA) change after 12 months of treatment. RESULTS: The mean (95% confidence interval [CI]) VA change after 12 months of treatment was 3.6 (2.8-4.4) letters for eyes in Group A versus 5.2 (4.4-5.9) letters for eyes in Group B (P = 0.005). The mean (95% CI) central subfield thickness (CST) change was -69 (-76 to -61) µm and -85 (-92 to -78) µm for eyes in Group A versus Group B, respectively (P = 0.002). A moderate positive correlation was observed between the number of injections received over 12 months of treatment and the change in VA (P < 0.001). Additionally, eyes that received more injections had a moderately greater CST reduction. CONCLUSIONS: This registry analysis found that overall VA and anatomic outcomes tended to be better in DME eyes treated at a greater proportion of visits in the first year of intravitreal VEGF inhibitor therapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Inhibidores de la Angiogénesis , Retinopatía Diabética , Inyecciones Intravítreas , Edema Macular , Ranibizumab , Sistema de Registros , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Humanos , Edema Macular/tratamiento farmacológico , Edema Macular/diagnóstico , Edema Macular/etiología , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/complicaciones , Inhibidores de la Angiogénesis/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Masculino , Femenino , Tomografía de Coherencia Óptica/métodos , Persona de Mediana Edad , Estudios de Seguimiento , Ranibizumab/administración & dosificación , Resultado del Tratamiento , Anciano , Bevacizumab/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factores de Tiempo , Estudios Retrospectivos , Proteínas Recombinantes de Fusión/administración & dosificaciónRESUMEN
PURPOSE: This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy and safety of anti-VEGFR tyrosine kinase inhibitors (TKIs) for GBM treatment. METHODS: A comprehensive literature review was conducted using PubMed up to August 2023. Boolean operators and MeSH term "glioma," along with specific VEGFR-related keywords, were utilized following thorough examination of existing literature. RESULTS: VEGFR correlates with glioma grade and GBM progression, presenting a viable therapeutic target. Regorafenib and axitinib show promise among studied TKIs. Other multi-targeted TKIs (MTKI) and combination therapies exhibit potential, albeit limited by blood-brain barrier penetration and toxicity. Combining treatments like radiotherapy and enhancing BBB penetration may benefit patients. Further research is warranted in patient quality of life and biomarker-guided selection. CONCLUSION: While certain therapies hold promise for GBM, future research should prioritize personalized medicine and innovative strategies for improved treatment outcomes.
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Neoplasias Encefálicas , Glioblastoma , Inhibidores de Proteínas Quinasas , Receptores de Factores de Crecimiento Endotelial Vascular , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacologíaRESUMEN
INTRODUCTION: Increasing evidence from preclinical and clinical studies suggests the role of vascular endothelial growth factor (VEGF) signaling in melanoma progression, response to therapy, and overall survival. Moreover, the discovery of the potential involvement of the VEGF pathway in resistance to immunotherapy has led to new clinical trials with VEGFR inhibitors. AREAS COVERED: We have reviewed recent literature, mainly published within the last 5 years, on VEGFR-targeted treatments for advanced melanoma, including mucosal, acral, and uveal melanoma. The VEGFR inhibitors were used as a single therapy or combined with either immunotherapy or chemotherapy, and they were employed in treatment for KIT-mutated cutaneous melanoma and for patients with brain metastases. EXPERT OPINION: Trials involving monotherapy have been unsuccessful in demonstrating meaningful efficacy. Despite some activity, the combination of VEGFR-targeting tyrosine kinase inhibitors (TKIs) with immune checkpoint inhibitors (ICI) in patients with ICI-resistant melanoma, the combination did not significantly improve outcomes compared to anti-PD-1 monotherapy in the first-line settings. On the contrary, some patients with mucosal, acral or KIT-mutant melanoma may benefit from TKI-based therapies. Further studies focused on biomarker discovery and randomized trials are necessary to better understand the role of VEGFR1-3 as a therapeutic target in melanoma.
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Melanoma , Inhibidores de Proteínas Quinasas , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Animales , Antineoplásicos/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inmunoterapia/métodos , Resistencia a AntineoplásicosRESUMEN
PURPOSE: To compare the functional and anatomical outcomes of ranibizumab, aflibercept, and dexamethasone implant monotherapy in treatment-naive eyes with diabetic macular edema (DME) in real-life conditions. METHODS: In this retrospective cohort study, data were obtained from the hospital database of treatment-naive patients diagnosed with DME with at least 12 months of follow-up. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) at baseline, third month, sixth month, ninth month, and 12th month were recorded. In addition, a subgroup analysis was performed based on having good (below 0.4 log of minimum angle of resolution [logMAR]) or poor (0.4 logMAR and above) vision. RESULTS: A total of 219 eyes of 142 patients were included in the study. The change in the mean BCVA from baseline to 12th month was from 0.62 logMAR to 0.42 logMAR (P < 0.001) in the ranibizumab group, from 0.56 logMAR to 0.39 logMAR (P < 0.001) in the aflibercept group, and from 0.46 logMAR to 0.5 logMAR (P = 0.653) in the dexamethasone group. There was no significant difference between the treatment groups at any time point (P > 0.05). The mean amount of CRT change was statistically significant at 12 months in all groups (ranibizumab: -175.4 µm, aflibercept: -153.3 µm, dexamethasone: -71.4 µm) (P < 0.05). In eyes with initially good vision, the final BCVA at 12 months was significantly better in the ranibizumab group compared to the dexamethasone group (P = 0.008). The aflibercept group had better visual acuity than the dexamethasone group, but there was no statistically significant difference (P = 0.059). There was no significant difference in final BCVA in eyes with initially poor vision. No serious ocular/systemic complications were noted. CONCLUSION: At the 12th month, a significant decrease in CRT was achieved in all treatment groups, whereas only ranibizumab and aflibercept groups had a significant BCVA increase. In eyes with initially good vision, the final BCVA at 12 months was better in the ranibizumab group compared to the dexamethasone group, whereas it was similar in all groups having initially poor vision.