RESUMO
BACKGROUND: This study investigated the effects of systemic factors in response to intravitreal injections in patients with macular edema due to non-proliferative diabetic retinopathy (NPDR). METHODS: We retrospectively reviewed the medical records of patients treated with intravitreal injections for macular edema secondary to NPDR between January 2018 and January 2021. The patients were divided into three groups according to the injection response. When patients with diabetic macular edema showed 20µ or more reduction in central retinal thickness compared to baseline, they were classified as responsive group, and if not, they were classified as refractory group. The responsive group was further divided into the complete and incomplete response groups. Patients with complete disappearance of edema at seven months were classified as the complete response group, whereas those in which edema did not disappear were classified as the incomplete response group. The clinical characteristics of each group, including medical history, ophthalmic examination results, and laboratory examination results at the time of diagnosis, were analyzed. RESULTS: Of the 112 eyes (91 patients) that satisfied the inclusion criteria, 89 (77 patients) in the responsive group and 23 (14 patients) in the refractory group were included in the analysis. The responsive group was further divided into the complete (51 eyes) and incomplete (38 eyes) response groups. The refractory group had significantly higher glycated hemoglobin levels and significantly lower estimated glomerular filtration rates than the responsive group (p = 0.026 and p = 0.012, respectively). In the multivariate logistic regression analysis, both factors were found to be significant in predicting the degree of response (all p < 0.05). No factor showed a significant difference between the incomplete and complete response groups(all p > 0.05). CONCLUSIONS: In macular edema caused by NPDR, low glomerular filtration rates and high glycated hemoglobin levels may be used as predictors of poor response to intravitreal injection therapy. In addition to blood glucose control, education should be provided regarding the need for the continuous monitoring of renal function.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Retinopatia Diabética/complicações , Retinopatia Diabética/tratamento farmacológico , Injeções Intravítreas , Fatores de Crescimento Endotelial , Hemoglobinas Glicadas , Estudos Retrospectivos , Retina , EdemaRESUMO
Purpose: In a previous study, we documented that the Intravitreal injections (IVIs) of bevacizumab in rats caused a retinal inflammatory response. We now study whether the IVI of other humanized anti-VEGF: ranibizumab and aflibercept also cause an inflammatory reaction in the rat retina and if it depends on the dose administered. Finally, we study whether this reaction affects retinal ganglion cell (RGC) survival. Methods: Albino Sprague-Dawley rats received a single IVI of 5 µL of PBS or ranibizumab or aflibercept at the concentration used in clinical practice (10 µg/µL or 40 µg/µL) or at a lower concentration (0.38 µg/µL and 1.5 µg/µL) calculated to obtain within the rat eye the same concentration as in the human eye in clinical practice. Others received a single 5 µL IVI of a polyclonal goat anti-rat VEGF (0.015 µg/µL) or of vehicle (PBS). Animals were processed 7 days or 1 month later. Retinal whole mounts were immunolabeled for the detection of microglial, macroglial, RGCs, and intrinsically photosensitive RGCs (ipRGCs). Fluorescence and confocal microscopy were used to examine retinal changes, and RGCs and ipRGCs were quantified automatically or semiautomatically, respectively. Results: All the injected substances including the PBS induced detectable side effects, namely, retinal microglial cell activation and retinal astrocyte hypertrophy. However, there was a greater microglial and macroglial response when the higher concentrations of ranibizumab and aflibercept were injected than when PBS, the antibody anti-rat VEGF and the lower concentrations of ranibizumab or aflibercept were injected. The higher concentration of ranibizumab and aflibercept resulted also in significant RGC death, but did not cause appreciable ipRGC death. Conclusions: The IVI of all the substances had some retinal inflammatory effects. The IVI of humanized anti-VEGF to rats at high doses cause important side effects: severe inflammation and RGC death, but not ipRGC death.
Assuntos
Fatores de Crescimento Endotelial , Células Ganglionares da Retina , Humanos , Ratos , Animais , Injeções Intravítreas , Ranibizumab/toxicidade , Fator A de Crescimento do Endotélio Vascular , Ratos Sprague-Dawley , Cabras , NeurogliaRESUMO
This study aimed to elucidate 1-year outcomes following switching to the aflibercept (3 mg) therapy for treatment-resistant wet age-related macular degeneration (wAMD). In this prospective, open-label, non-controlled clinical trial, 18 patients with wAMD who had multiple recurrences or persistent exudation despite intravitreal injections of anti-vascular endothelial growth factor agents (except aflibercept) received a 3-mg intravitreal aflibercept injection every 4 weeks. Each patient received 3 to 8 injections. The central retinal thickness and fibrovascular pigment epithelial detachment height decreased significantly at 1 month after initiation of the aflibercept injection, and the values were 146 and 163.2 µm, respectively, at the final visit. The morphological improvement was sustained. The intraretinal and subretinal fluid was completely absorbed at the end of the follow-up. The logMAR vision increased from baseline 0.68 to 0.59 (Pâ <â .05). No ocular or systemic adverse events occurred. The intravitreal injection of 3-mg aflibercept seems to be feasible in the treatment of wAMD unresponsive to other anti-vascular endothelial growth factor agents.
Assuntos
Fatores de Crescimento Endotelial , Degeneração Macular Exsudativa , Humanos , Inibidores da Angiogênese/uso terapêutico , Fatores de Crescimento Endotelial/uso terapêutico , Injeções Intravítreas , Estudos Prospectivos , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Retina , Tomografia de Coerência Óptica , Resultado do Tratamento , Degeneração Macular Exsudativa/tratamento farmacológicoAssuntos
Anticorpos Biespecíficos , Neoplasias Pulmonares , Humanos , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/metabolismo , Fatores de Crescimento Endotelial , Receptor de Morte Celular Programada 1 , Fator A de Crescimento do Endotélio VascularAssuntos
Degeneração Macular , Degeneração Macular Exsudativa , Humanos , Fatores de Crescimento Endotelial/uso terapêutico , Ranibizumab/uso terapêutico , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Degeneração Macular/tratamento farmacológico , Esteroides/uso terapêutico , Injeções Intravítreas , Degeneração Macular Exsudativa/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is used for myopic choroidal neovascularization (mCNV). Patchy chorioretinal atrophy (pCRA) enlargement has been reported in mCNV cases associated with vision loss. Our aim was to compare the long-term effectiveness of anti-VEGF therapy alone versus anti-VEGF followed by posterior scleral reinforcement (PSR) in controlling myopic maculopathy in mCNV eyes. METHODS: We performed a retrospective review of the medical records of 95 high myopia patients (refractive error ≥ 6.00 diopters, axial length ≥ 26.0 mm) with mCNV. Patients were treated with anti-VEGF alone (group A) or anti-VEGF followed by PSR (group B). The following data were collected: refractive error, best corrected visual acuity (BCVA), ophthalmic fundus examination, ocular coherence tomography and ocular biometry at 12 and 24 months pre- and postoperatively. The primary outcomes were changes in pCRA and BCVA. RESULTS: In 26 eyes of 24 patients, the mean pCRA size significantly increased from baseline (0.88 ± 1.69 mm2) to 12 months (1.57 ± 2.32 mm2, t = 3.249, P = 0.003) and 24 months (2.17 ± 2.79 mm2, t = 3.965, P = 0.001) postoperatively. The increase in perilesional pCRA in group B (n = 12) was 98.2% and 94.2% smaller than that in group A (n = 14) at 12 and 24 months (Beta 0.57 [95% CI 0.01, 191 1.13], P = 0.048). In group B, 7 eyes (58.3%) gained more than 2 lines of BCVA compared with only 4 eyes (28.6%) in group A at 24 months. CONCLUSION: Anti-VEGF therapy followed by PSR achieved better outcomes than anti-VEGF therapy alone in controlling the development of myopic maculopathy in mCNV and may constitute a better treatment option by securing a better long-term VA outcome.
Assuntos
Neovascularização de Coroide , Degeneração Macular , Miopia Degenerativa , Doenças Retinianas , Humanos , Inibidores da Angiogênese/uso terapêutico , Fatores de Crescimento Endotelial/uso terapêutico , Miopia Degenerativa/complicações , Miopia Degenerativa/diagnóstico , Acuidade Visual , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/etiologia , Doenças Retinianas/diagnóstico , Degeneração Macular/tratamento farmacológico , Esclera , Estudos Retrospectivos , Tomografia de Coerência Óptica , Angiofluoresceinografia , Injeções IntravítreasRESUMO
PURPOSE: To evaluate the tear level of VEGF and the quantity of tear film in type 2 diabetic patients. METHODS: Thirty patients with diabetic retinopathy (DR group) and 30 patients with no DR (NDR group), and 30 healthy subjects with age and gender matching were enrolled in this prospective comparative study. The tear samples were collected using the Schirmer strips, and the amount of moisture absorbed by the strips was used to determine the quantitative level of the tear film. The concentration of VEGF in the tear samples was measured using the enzyme-linked immunosorbent assay method. The variables were compared with an independent t-test and covariance analysis. RESULTS: Mean tear level of VEGF was significantly higher in DR group (235.42 pg/ml) compared to NDR (75.11 pg/ml) and control (58.77 pg/ml) groups (P ≤ 0.001). There was no significant difference in the mean of VEGF between NDR and control patients (P = 1.00). Mean quantitative tear film levels were 7.15%, 9.72%, and 15.11% in DR, NDR, and healthy subjects, respectively (P < 0.05). The pairwise analysis showed significant differences in the level of VEGF between DR and both NDR (P = 0.001) and normal (P = 0.017) groups. However, there was no significant difference observed between NDR and normal eyes (P = 0.743). CONCLUSION: The VEGF level in tear was higher in diabetic patients with DR, independent of tear volume. The tear VEGF measurement can be used as a valuable predictor to prevent DR in diabetic patients.
Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Retinopatia Diabética/metabolismo , Fatores de Crescimento Endotelial/metabolismo , Diabetes Mellitus Tipo 2/complicações , Fator A de Crescimento do Endotélio Vascular/metabolismo , Estudos ProspectivosRESUMO
Diabetic retinopathy (DR) is a blinding disease caused by diabetes, characterized by neovascularization of the retina. The aim of this study was to investigate the roles of epidermal growth factor-like structural domain 7 (EGFL7) on human retinal vascular endothelial cells (HRECS) and retinas from rats with DR. An in vitro model of DR was established through culturing HRECS in high glucose. The in vivo model of DR was established by injecting SD rats with streptozotocin (STZ) to induce diabetes. The differences in the expressed levels of EGFL7, PI3K, AKT, P-AKT and VEGFA in high-glucose cultured cells and retinal tissues of diabetic rats were detected in compared to those in the control group. Stable EGFL7 knockdown cell lines were generated by transfecting HRECS with lentiviral vectors and the effects of EGFL7 knockdown on angiogenesis, cell migration and proliferation were investigated. The results showed that EGFL7, PI3K, P-AKT and VEGFA was increased in cells and tissues under high glucose conditions. Knockdown of EGFL7 downregulated the proliferation, migration and angiogenesis capacity of HRECS, and blocked the PI3K/AKT/VEGFA signaling pathway. Furthermore, overexpression of PI3K reversed the effects of EGFL7 inhibition. These findings provide new ideas for the treatment of neovascularisation in DR.
Assuntos
Proteínas de Ligação ao Cálcio , Retinopatia Diabética , Família de Proteínas EGF , Animais , Humanos , Ratos , Proteínas de Ligação ao Cálcio/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Família de Proteínas EGF/metabolismo , Família de Proteínas EGF/farmacologia , Células Endoteliais/metabolismo , Fatores de Crescimento Endotelial , Glucose/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neovascularização Patológica/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: EGFL6, a growth factor produced by adipocytes, is upregulated in and implicated in the tumorigenesis of multiple tumor types. Given the strong link between obesity and endometrial cancer, we sought to determine the impact of EGFL6 on endometrial cancer. METHODS: EGFL6 expression in endometrial cancer and correlation with patient outcomes was evaluated in the human protein atlas and TCGA. EGFL6 treatment, expression upregulation, and shRNA knockdown were used to evaluate the impact of EGFL6 on the proliferation and migration of 3 endometrial cancer cell lines in vitro. Similarly, the impact of EGFL6 expression and knockdown on tumor growth was evaluated. Western blotting was used to evaluate the impact of EGFL6 on MAPK phosphorylation. RESULTS: EGFL6 is upregulated in endometrial cancer, primarily in cony-number high tumors. High tumor endometrial cancer expression of EGFL6 predicts poor patient prognosis. We find that EGFL6 acts to activate the MAPK pathway increasing cellular proliferation and migration. In xenograft models, EGFL6 overexpression increases endometrial cancer tumor growth while EGFL6 knockdown decreases endometrial cancer tumor growth. CONCLUSIONS: EGFL6 is a marker of poor prognosis endometrial cancers, driving cancer cell proliferation and growth. As such EGFL6 represents a potential therapeutic target in endometrial cancer.
Assuntos
Movimento Celular , Proliferação de Células , Neoplasias do Endométrio , Feminino , Humanos , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Animais , Linhagem Celular Tumoral , Camundongos , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Camundongos Nus , Sistema de Sinalização das MAP Quinases , Fatores de Crescimento Endotelial/genética , Fatores de Crescimento Endotelial/metabolismo , Regulação para Cima , Moléculas de Adesão CelularRESUMO
PURPOSE: To introduce the treatment of diabetic macular edema (DME) with subthreshold micropulse diode laser (SMPL), to summarize the biological impact, therapeutic effects, and safety of this treatment, and to discuss the response to DME when SMPL is combined with anti-vascular endothelial growth factor (anti-VEGF) or steroid. METHODS: The literature search was performed on the PubMed database, with a selection of English-language articles published from 2000 to 2023 with the following combinations of search terms: diabetes macular (o) edema, micropulse laser or subthreshold micropulse laser, anti-vascular endothelial growth factor, and steroid. RESULTS: SMPL is a popular, invisible retinal laser phototherapy that is inexpensive, safe, and effective in the treatment of DME. It can selectively target the retinal pigment epithelium, reduce the expression of pro-inflammatory factors, promote the absorption of macular edema, and exert a similar and lasting clinical effect to traditional lasers. No significant difference was found in the therapeutic effects of SMPL between different wavelengths. However, HbA1c level and pretreatment central macular thickness (CMT) may affect the therapeutic outcomes of SMPL. CONCLUSION: SMPL has a slow onset and produces lasting clinical effects similar to conventional photocoagulation. It has been reported that SMPL combined with the intravitreal anti-VEGF injection can significantly reduce the number of injections without influencing the therapeutic effect, which is essential for clinical applications and research. Although 577 nm SMPL is widely used clinically, there are no standardized protocols for SMPL. Additionally, some important problems regarding the treatment of SMPL require further discussion and exploration.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/cirurgia , Edema Macular/diagnóstico , Edema Macular/etiologia , Edema Macular/cirurgia , Lasers Semicondutores/uso terapêutico , Fatores de Crescimento Endotelial , Fotocoagulação a Laser/métodos , Esteroides , Resultado do Tratamento , Tomografia de Coerência ÓpticaRESUMO
PURPOSE OF REVIEW: The increasing prevalence of diabetic macular edema (DME) necessitates an updated review of treatment modalities. While the shift from laser to anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed patient outcomes, benefits of these agents are not fully realized in real-world implementation relative to the setting of controlled clinical trials. This review outlines the evolution of intravitreal anti-VEGF treatment extension protocols for DME that reflect efforts to address treatment adherence challenges while optimizing visual outcomes. RECENT FINDINGS: Recent studies highlight the efficacy of extended-interval dosing with anti-VEGF agents in managing DME. Trials such as RISE/RIDE, VISTA/VIVID, and LUCIDATE have established the foundation of these regimens by demonstrating sustained visual gains with continuous treatment. However, newer trials including PROTOCOL T, KESTREL/KITE, YOSEMITE/RHINE, and PHOTON have furthered this concept, revealing that less frequent dosing of various anti-VEGF agents can maintain similar visual acuity and anatomical outcomes to traditional monthly injections. SUMMARY: The reviewed findings suggest a paradigm shift in DME treatment toward less frequent anti-VEGF injections. This has significant implications for clinical practice, potentially leading to greater adherence to treatment regimens and sustained visual function in patients, while minimizing treatment burden and healthcare costs. Further investigation into the long-term effects of extended dosing intervals is required.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Fatores de Crescimento Endotelial/uso terapêutico , Inibidores da Angiogênese/efeitos adversos , Fator A de Crescimento do Endotélio Vascular , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Retratamento , Injeções Intravítreas , Ranibizumab/uso terapêutico , Diabetes Mellitus/tratamento farmacológicoRESUMO
PURPOSE: To analyze the clinical features of refractory cystoid macular edema related to retinal vein occlusion associated with the response to three consecutive loading doses of anti-vascular endothelial growth factor. METHODS: A retrospective chart review was performed on retinal vein occlusion patients treated by three anti-vascular endothelial growth factor injections. They were divided into a group according to resolution of macular edema in optical coherence tomography (Group 1) and with persistent macular edema (Group 2). We analyzed qualitative and quantitative morphologic features of optical coherence tomography. RESULTS: We enrolled a total of 120 eyes from 120 patients (Group 1: n = 54, Group 2: n = 66). The baseline choroidal thickness differed significantly between groups 1 and 2 (290.70 ± 19.58 µm and 311.06 ± 17.87 µm P < 0.001). The presence of Hyperreflective foci (16.70% vs. 36.40% P < 0.001), Disorganization of the retinal inner layers (14.80% vs. 87.90%) and external limiting membrane disruption (16.60% vs. 39.3% P < 0.001) differed significantly. Logistic regression analysis showed that the initial central macular thickness (B = 0.012; P = 0.006), baseline choroidal thickness (B = 0.232; P = 0.016) and presence of hyperreflective foci (B = 1.050; P = 0.019), disorganization of the retinal inner layers (B = 1.132; P = 0.001) and external limiting membrane disruption (B = 1.575; P = 0.012) significantly affected the anti-vascular endothelial growth factor treatment response. CONCLUSION: A thicker sub-fovea choroid and the presence of hyperreflective foci, disruption of the external limiting membrane and disorganization of the retinal inner layers associated with a poorer response to three loading anti-vascular endothelial growth factor injections in macular edema associated retinal vein occlusion.
Assuntos
Bevacizumab , Edema Macular , Oclusão da Veia Retiniana , Humanos , Fatores de Crescimento Endotelial , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Retina , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/imunologia , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Bevacizumab/uso terapêuticoRESUMO
Chemically defined oocyte maturation media supplemented with FGF2, LIF, and IGF-1 (FLI medium) enabled significantly improved oocyte quality in multiple farm animals, yet the molecular mechanisms behind such benefits were poorly defined. Here, we first demonstrated that FLI medium enhanced mouse oocyte quality assessed by blastocyst formation after in vitro fertilization and implantation and fetal development after embryo transfer. We then analyzed the glucose concentrations in the spent media; reactive oxygen species concentrations; mitochondrial membrane potential; spindle morphology in oocytes; and the abundance of transcripts of endothelial growth factor-like factors, cumulus expansion factors, and glucose metabolism-related genes in cumulus cells. We found that FLI medium enabled increased glucose metabolism through glycolysis, pentose phosphate pathway, and hexosamine biosynthetic pathway, as well as more active endothelial growth factor-like factor expressions in cumulus cells, resulting in improved cumulus cell expansion, decreased spindle abnormality, and overall improvement in oocyte quality. In addition, the activities of MAPK1/3, PI3K/AKT, JAK/STAT3, and mTOR signaling pathways in cumulus cells were assessed by the phosphorylation of MAPK1/3, AKT, STAT3, and mTOR downstream target RPS6KB1. We demonstrated that FLI medium promoted activations of all these signaling pathways at multiple different time points during in vitro maturation.
Assuntos
Fator 2 de Crescimento de Fibroblastos , Técnicas de Maturação in Vitro de Oócitos , Animais , Camundongos , Feminino , Técnicas de Maturação in Vitro de Oócitos/veterinária , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fatores de Crescimento Endotelial/análise , Fatores de Crescimento Endotelial/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Oócitos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Suplementos Nutricionais , Glucose/farmacologia , Glucose/metabolismo , Células do Cúmulo/metabolismoRESUMO
AIM: We assessed the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti-vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database. MATERIALS AND METHODS: This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti-VEGF agents after initiating SGLT2is or other antidiabetic drugs. RESULTS: Among 2412 matched patients with DMO, the incidence rates of anti-VEGF agent injections were 230.1 per 1000 person-year in SGLT2i users and 228.4 times per 1000 person-year in non-users, respectively, and the risk ratio for events was unchanged in both groups. Sub-analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti-VEGF agent use [p = .027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.91]. SGLT2is reduced the risk for the first (p = .023, HR: 0.45, 95% CI: 0.22-0.91) and second (p = .021, HR: 0.39, 95% CI: 0.17-0.89) anti-VEGF agent injections. CONCLUSIONS: There was no difference in the risk ratio for the addition of anti-VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti-VEGF agent administration in patients with DMO requiring anti-VEGF therapy. Therefore, SGLT2i therapy may be a novel, non-invasive, low-cost adjunctive therapy for DMO requiring anti-VEGF therapy.
Assuntos
Retinopatia Diabética , Edema Macular , Inibidores do Transportador 2 de Sódio-Glicose , Simportadores , Humanos , Edema Macular/tratamento farmacológico , Edema Macular/epidemiologia , Edema Macular/induzido quimicamente , Ranibizumab/efeitos adversos , Bevacizumab/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/efeitos adversos , Fatores de Crescimento Endotelial/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Estudos de Coortes , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Japão/epidemiologia , Retinopatia Diabética/complicações , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/epidemiologia , Simportadores/uso terapêutico , Glucose/uso terapêutico , Sódio , Injeções IntravítreasRESUMO
OBJECTIVE: To report on anti-vascular endothelial growth factor (anti-VEGF) discontinuation in neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive nAMD patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Demographics, treatment start and end dates, number of injections, treatment length, reason for discontinuation, and baseline and final data (i.e., age, best-corrected visual acuity, and central subfield thickness) were recorded. Statistical analyses using STATA 17.0 assessed differences between baseline and final values and between treatment-discontinuation subgroups. RESULTS: A total of 619 eyes of 502 treatment-naive patients (9015 injections) were included (age, 81.6 ± 8.4 years; 64.0% female). Discontinuation rate was 58.3% (361 of 619), with 310 patients discontinuing because of the lack of visual benefit (nâ¯=â¯152), severe comorbidity or death (nâ¯=â¯82), transferred (nâ¯=â¯33), stable off active treatment (nâ¯=â¯19), lack of benefit plus stable off treatment (nâ¯=â¯14), patient decision (nâ¯=â¯6), and ocular comorbidity (nâ¯=â¯4). Among the 309 remaining patients, 51 (16.5%) were lost to follow-up. Discontinuation occurred within the first year in 49.3% (nâ¯=â¯178). Visual acuity was at least maintained in all groups and improved in the following groups: severe comorbidity or death (p < 0.0001), lost to follow-up (pâ¯=â¯0.0003), transferred (pâ¯=â¯0.0004), and stable off treatment (pâ¯=â¯0.0053). The lack of visual benefit group had no improvement in vision regardless of treatment length. Compared with other subgroups, those stable off treatment group was younger (pâ¯=â¯0.0055), had better baseline vision (pâ¯=â¯0.0018), received more injections (pâ¯=â¯0.0437) over a longer time (pâ¯=â¯0.0034), and achieved better final vision (p < 0.0001). CONCLUSION: While there was a high discontinuation rate over 7.5 years, most were attributable to disease or treatment factors and nonmodifiable patient factors. Discontinuation frequently occurred within the first year.
Assuntos
Degeneração Macular , Degeneração Macular Exsudativa , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Ranibizumab/uso terapêutico , Inibidores da Angiogênese , Fatores de Crescimento Endotelial/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Estudos Retrospectivos , Resultado do Tratamento , Degeneração Macular/tratamento farmacológico , Injeções Intravítreas , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológicoRESUMO
PURPOSE: Although pivotal trials have demonstrated efficacy of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration, there is a paucity of clinical data about the long-term (>5 years) treatment. METHODS: Retrospective analysis of all patients with neovascular age-related macular degeneration who were actively treated, had received >40 anti-vascular endothelial growth factor injections, and were followed for ≥5 years. Snellen-corrected visual acuity, initial drug choice, and times elapsed between treatments were collected. Rates of endophthalmitis and outcomes of submacular hemorrhage were also evaluated. RESULTS: A total of 88 patients (162 eyes) met the inclusion criteria: the average patient age was 86.3 years with an average follow-up period of 7.6 years. The average total number of injections per eye was 69 (18.0 SD); a total of 11,208 injections were given throughout the study period, and 6 cases (0.05%) of endophthalmitis were observed. Overall, there was a clinical and statistical difference in average Snellen-corrected visual acuity at Injections #2,#3, #4, #5, #6, #10, and #20, as compared with baseline ( P = 0.03, P < 0.01, P = 0.02, P < 0.01, P = 0.01, P = 0.01, P < 0.01, respectively). Patients in the Snellen-corrected visual acuity subgroup 20/20 to 20/40 maintained vision until injection #30. Seven eyes experienced a visually significant submacular hemorrhage. CONCLUSION: This neovascular age-related macular degeneration cohort received on average eight anti-vascular endothelial growth factor injections per year for approximately 8 years; eyes with good (≥20/40) initial baseline vision maintained their visual acuity, whereas those with worse Snellen-corrected visual acuity (≤20/50) had a robust initial improvement that diminished with time. Most patients were maintained on the same initial drug of choice and the rate of endophthalmitis was low.
Assuntos
Endoftalmite , Degeneração Macular , Degeneração Macular Exsudativa , Humanos , Pré-Escolar , Idoso de 80 Anos ou mais , Criança , Inibidores da Angiogênese/uso terapêutico , Ranibizumab/uso terapêutico , Bevacizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento Endotelial , Estudos Retrospectivos , Injeções Intravítreas , Hemorragia Retiniana/tratamento farmacológico , Degeneração Macular/tratamento farmacológico , Endoftalmite/tratamento farmacológico , Endoftalmite/epidemiologia , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico , Resultado do TratamentoRESUMO
PURPOSE: To investigate eyes with polypoidal lesions associated with choroidal nevi, their multimodal imaging characteristics, and long clinical follow-up. METHODS: Multicenter, retrospective case series study of patients with polypoidal lesions overlying choroidal nevi. Demographic and clinical information were recorded. Multimodal imaging including color fundus photography, optical coherence tomography, optical coherence tomography angiography, fundus fluorescein angiography, indocyanine angiography, and A- and B-scan ultrasonography were analyzed for nevus and polypoidal lesion characteristics. RESULTS: Fourteen eyes (14 patients; mean age: 70.3 ± 6.7 years) with polypoidal lesions overlying choroidal nevi were included. The mean follow-up duration was 50.0 ± 27.9 months (range 12-108). All nevi were pigmented on color fundus photography, flat on ultrasonography with a mean basal diameter of 3.8 ± 0.4 mm. In all but one eye, optical coherence tomography showed a shallow irregular pigment epithelium detachment overlying the nevus. A total of 11/14 eyes (78.6%) had exudative activity, 9 eyes received intravitreal anti-vascular endothelial growth factor injections, and one eye required intravitreal anti-vascular endothelial growth factor combined with photodynamic therapy. Mean visual acuity was 20/32 at baseline and 20/50 at final visit. CONCLUSION: We present the largest known cohort of eyes with polypoidal lesions associated with choroidal nevi with up to 9 years follow-up. The exudative degree of the polypoidal lesion in this condition is variable and treatment decisions should be taken on an individual basis. We hypothesize that choroidal ischemia because of altered choroidal vasculature rather than Haller layer hyperpermeability plays a role in the formation of polypoidal lesions overlying nevi.
Assuntos
Doenças da Coroide , Neoplasias da Coroide , Nevo , Pólipos , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Fatores de Crescimento Endotelial , Doenças da Coroide/tratamento farmacológico , Corioide/patologia , Neoplasias da Coroide/patologia , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Pólipos/tratamento farmacológico , Injeções IntravítreasRESUMO
PURPOSE: Although efficacious, intravitreal anti-vascular endothelial growth factor therapy regimens for neovascular age-related macular degeneration can prove difficult for patients to adhere to because of high cost and burden of transportation. METHODS: Analysis of electronic health record data from the San Francisco Veterans Administration Medical Center eye clinic (January 1, 2010 to December 31, 2019) was performed, extracting demographic data, anti-vascular endothelial growth factor injection history, and enrollment in the SFVA travel benefit program. Two-tailed P -values were calculated for Poisson regression examining average number of injections per year as the outcome and distance traveled as the primary predictor. Travel benefit was evaluated as a modifying effect on the distance-injection relationship. RESULTS: Three hundred and eighteen patients who received intravitreal injection for treatment of neovascular age-related macular degeneration were included in the analysis. Median (interquartile range) distance to clinic was 31.5 miles (7.4-69.4 miles). Driving distance in miles was inversely associated with average number of injections per year. Among all 318 patients, for every additional 100 miles a patient lived from our clinic, the patient received on average 2.5 fewer injections per year ( distance = -0.0025, P < 0.001), but this was not the case for patients with travel benefits ( distance = -0.0011, P = 0.362). CONCLUSION: The greater the distance from a patient's eye clinic, the lower the average number of injections per year. However, travel benefits mitigated this relationship, highlighting opportunities for improving patient's adherence through assistance programs.
Assuntos
Inibidores da Angiogênese , Degeneração Macular , Humanos , Fatores de Crescimento Endotelial , Degeneração Macular/tratamento farmacológico , Injeções Intravítreas , Viagem , Estudos RetrospectivosRESUMO
PURPOSE: Honokiol is a lignan isolated from Magnolia officinalis and exhibits anti-angiogenic properties. This study was conducted to investigate the role of honokiol in choroidal neovascularization. METHODS: C57BL/6 mice were treated with honokiol at 10-20 mg/kg by daily intraperitoneal injection from day 1 to 6 after laser photocoagulation. ARPE-19 cells were cultured under hypoxic conditions with or without the presence of honokiol. After laser photocoagulation and honokiol treatment, hematoxylin and eosin staining, immunofluorescence and fundus fluorescein angiography were used to analyze the effect of honokiol on choroidal neovascularization formation. Quantitative real-time PCR, western blot, enzyme-linked immunosorbent assay, immunofluorescence, luciferase assay, and chromatin immunoprecipitation were performed to explore the mechanism of honokiol in the pathological process of choroidal neovascularization. Finally, the role of honokiol on the human choroidal vascular endothelial cells was detected by using 5-ethynyl-20-deoxyuridine assay, Transwell and Tube formation assays. RESULTS: The results of hematoxylin and eosin staining and immunofluorescence suggested that honokiol reduced the thickness, length, and area of choroidal neovascularization lesions in laser-induced choroidal neovascularization mouse model. Fundus fluorescein angiography showed that choroidal neovascularization leakage was reduced in honokiol group and the concentration of 20 mg/kg showed better effects. Mechanism studies have shown that honokiol exerted inhibitory effects on choroidal neovascularization by inactivating hypoxia-inducible factor-1α/vascular endothelial growth factor axis through the nuclear transcription factor-kappa B signaling pathway. The same results were obtained in ARPE-19 cells under hypoxic conditions. Furthermore, the conditional medium of retinal pigmented epithelial cells promoted the proliferation, migration, and tube formation of human choroidal vascular endothelial cells, while honokiol reversed these. CONCLUSION: We demonstrated that honokiol attenuated choroidal neovascularization formation by inactivating the hypoxia-inducible factor-1α/vascular endothelial growth factor axis through nuclear transcription factor-kappa B signaling pathway.