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1.
BMC Ophthalmol ; 24(1): 166, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38616277

ABSTRACT

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.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Humans , Macular Edema/drug therapy , Macular Edema/etiology , Diabetic Retinopathy/complications , Diabetic Retinopathy/drug therapy , Intravitreal Injections , Endothelial Growth Factors , Glycated Hemoglobin , Retrospective Studies , Retina , Edema
2.
Invest Ophthalmol Vis Sci ; 65(4): 10, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38573620

ABSTRACT

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.


Subject(s)
Endothelial Growth Factors , Retinal Ganglion Cells , Humans , Rats , Animals , Intravitreal Injections , Ranibizumab/toxicity , Vascular Endothelial Growth Factor A , Rats, Sprague-Dawley , Goats , Neuroglia
3.
Medicine (Baltimore) ; 103(16): e37839, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38640269

ABSTRACT

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 (P < .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.


Subject(s)
Endothelial Growth Factors , Wet Macular Degeneration , Humans , Angiogenesis Inhibitors/therapeutic use , Endothelial Growth Factors/therapeutic use , Intravitreal Injections , Prospective Studies , Ranibizumab/therapeutic use , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Retina , Tomography, Optical Coherence , Treatment Outcome , Wet Macular Degeneration/drug therapy
4.
Clín. investig. arterioscler. (Ed. impr.) ; 36(2): 60-70, mar.-abr. 2024. tab, graf
Article in English | IBECS | ID: ibc-231494

ABSTRACT

Background Combined oral contraceptives (COCs), use in individuals are associated with increased risk of thrombotic events. This highlights the significance of assessing the impact of COC on promoting coagulation and endothelial activation in high-fat diet (HFD)-fed Sprague Dawley rats. Methods Twenty (20) five-weeks-old female Sprague Dawley rats weighing between 150 and 200g were subjected to both LFD and HFD-feeding for 8-weeks to determine its influence on basic metabolic status, hemostatic profile, hemodynamic parameters (blood pressure and heart rate), as well as selected biomarkers of coagulation (tissue factor and D-dimer) and endothelial activation (Von Willebrand factor and nitric oxide). Thereafter HFD-fed animals were treated with receive high dose combined oral contraceptive (HCOC) and low dose combine oral contraceptive (LCOC) for 6 weeks. Results Our results showed that beyond weight gain, HFD-feeding was associated with hyperglycemia, increased mean arterial pressure, and reduced nitric oxide levels when compared with LFD group (p<0.05). Interestingly, treatment with high dose of COC for 6-weeks did not significantly alter atherothrombotic markers (p>0.05). However, this study is not without limitation as regulation of these markers remains to be confirmed within the cardiac tissues or endothelial cells of these animals. Conclusion HFD-feeding orchestrate the concomitant release of pro-coagulants and endothelial activation markers in rats leading to haemostatic imbalance and endothelial dysfunction. Short-term treatment with COC shows no detrimental effects in these HFD-fed rats. Although in terms of clinical relevance, our findings depict the notion that the risk of CVD in association with COC may depend on the dosage and duration of use among other factors especially in certain conditions. ... (AU)


Antecedentes El uso de anticonceptivos orales combinados (AOC) en individuos se asocia con un mayor riesgo de eventos trombóticos. Esto resalta la importancia de evaluar el impacto de los AOC en la promoción de la coagulación y la activación endotelial en ratas Sprague Dawley alimentadas con una dieta alta en grasas (HFD). Métodos Veinte (20) ratas Sprague Dawley hembra de 5semanas de edad con un peso entre 150-200g fueron tratadas mediante una alimentación con dieta baja en grasas (LFD) y alta en grasas (HFD) durante 8 semanas para determinar su influencia en el estado metabólico básico, perfil hemostático, parámetros hemodinámicos (presión arterial y frecuencia cardíaca), así como biomarcadores seleccionados de coagulación (factor tisular y D-dímero) y activación endotelial (factor de von Willebrand y óxido nítrico). Posteriormente, los animales alimentados con HFD fueron tratados con dosis alta de anticonceptivo oral combinado (AOC-AL) y dosis baja de anticonceptivo oral combinado (AOC-BL) durante 6 semanas. Resultados Nuestros resultados mostraron que, además del aumento de peso, la alimentación con HFD se asoció con hiperglucemia, aumento de la presión arterial media y niveles reducidos de óxido nítrico en comparación con el grupo LFD (p<0,05). Curiosamente, el tratamiento con dosis alta de AOC durante 6 semanas no alteró significativamente los marcadores aterotrombóticos (p>0,05). Sin embargo, este estudio no está exento de limitaciones, ya que la regulación de estos marcadores aún debe confirmarse en los tejidos cardíacos o las células endoteliales de estos animales. Conclusión La alimentación con HFD orquesta la liberación concomitante de procoagulantes y marcadores de activación endotelial en ratas, lo que conduce a un desequilibrio hemostático y disfunción endotelial. El tratamiento a corto plazo con AOC no muestra efectos perjudiciales en estas ratas alimentadas con HFD. ... (AU)


Subject(s)
Animals , Female , Rats , Contraceptives, Oral, Combined/adverse effects , Blood Coagulation/drug effects , Blood Coagulation Factors , Dietary Fats/adverse effects , Diet, High-Fat/adverse effects , Endothelial Growth Factors , Obesity , Cardiovascular Diseases
5.
BMC Ophthalmol ; 24(1): 118, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38481176

ABSTRACT

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.


Subject(s)
Choroidal Neovascularization , Macular Degeneration , Myopia, Degenerative , Retinal Diseases , Humans , Angiogenesis Inhibitors/therapeutic use , Endothelial Growth Factors/therapeutic use , Myopia, Degenerative/complications , Myopia, Degenerative/diagnosis , Visual Acuity , Choroidal Neovascularization/diagnosis , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/etiology , Retinal Diseases/diagnosis , Macular Degeneration/drug therapy , Sclera , Retrospective Studies , Tomography, Optical Coherence , Fluorescein Angiography , Intravitreal Injections
6.
Int Ophthalmol ; 44(1): 143, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38498296

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Humans , Diabetic Retinopathy/metabolism , Endothelial Growth Factors/metabolism , Diabetes Mellitus, Type 2/complications , Vascular Endothelial Growth Factor A/metabolism , Prospective Studies
9.
Curr Opin Ophthalmol ; 35(3): 197-204, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38345051

ABSTRACT

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.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Humans , Macular Edema/drug therapy , Diabetic Retinopathy/drug therapy , Endothelial Growth Factors/therapeutic use , Angiogenesis Inhibitors/adverse effects , Vascular Endothelial Growth Factor A , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Retreatment , Intravitreal Injections , Ranibizumab/therapeutic use , Diabetes Mellitus/drug therapy
10.
Life Sci ; 340: 122483, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38307238

ABSTRACT

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.


Subject(s)
Calcium-Binding Proteins , Diabetic Retinopathy , EGF Family of Proteins , Animals , Humans , Rats , Calcium-Binding Proteins/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Diabetic Retinopathy/metabolism , EGF Family of Proteins/metabolism , EGF Family of Proteins/pharmacology , Endothelial Cells/metabolism , Endothelial Growth Factors , Glucose/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Neovascularization, Pathologic/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats, Sprague-Dawley , Transcription Factors/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
11.
Int Ophthalmol ; 44(1): 3, 2024 Feb 03.
Article in English | MEDLINE | ID: mdl-38315299

ABSTRACT

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.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Humans , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/surgery , Macular Edema/diagnosis , Macular Edema/etiology , Macular Edema/surgery , Lasers, Semiconductor/therapeutic use , Endothelial Growth Factors , Laser Coagulation/methods , Steroids , Treatment Outcome , Tomography, Optical Coherence
12.
Diabetes Obes Metab ; 26(4): 1510-1518, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38240052

ABSTRACT

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.


Subject(s)
Diabetic Retinopathy , Macular Edema , Sodium-Glucose Transporter 2 Inhibitors , Symporters , Humans , Macular Edema/drug therapy , Macular Edema/epidemiology , Macular Edema/chemically induced , Ranibizumab/adverse effects , Bevacizumab/adverse effects , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/adverse effects , Endothelial Growth Factors/therapeutic use , Vascular Endothelial Growth Factor A/therapeutic use , Cohort Studies , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Japan/epidemiology , Diabetic Retinopathy/complications , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/epidemiology , Symporters/therapeutic use , Glucose/therapeutic use , Sodium , Intravitreal Injections
13.
BMC Ophthalmol ; 24(1): 30, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38254100

ABSTRACT

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.


Subject(s)
Bevacizumab , Macular Edema , Retinal Vein Occlusion , Humans , Endothelial Growth Factors , Macular Edema/diagnosis , Macular Edema/drug therapy , Macular Edema/etiology , Retina , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/drug therapy , Retrospective Studies , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/immunology , Vascular Endothelial Growth Factor A/therapeutic use , Bevacizumab/therapeutic use
14.
Biol Reprod ; 110(4): 672-683, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38263524

ABSTRACT

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.


Subject(s)
Fibroblast Growth Factor 2 , In Vitro Oocyte Maturation Techniques , Animals , Mice , Female , In Vitro Oocyte Maturation Techniques/veterinary , Fibroblast Growth Factor 2/metabolism , Insulin-Like Growth Factor I/metabolism , Endothelial Growth Factors/analysis , Endothelial Growth Factors/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Oocytes/metabolism , TOR Serine-Threonine Kinases/metabolism , Dietary Supplements , Glucose/pharmacology , Glucose/metabolism , Cumulus Cells/metabolism
16.
Acta Ophthalmol ; 102(1): e31-e41, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37042340

ABSTRACT

PURPOSE: Retinal non-perfusion (RNP) is fundamental to disease onset and progression in diabetic retinopathy (DR). Whether anti-vascular endothelial growth factor (anti-VEGF) therapy can modify RNP progression is unclear. This investigation quantified the impact of anti-VEGF therapy on RNP progression compared with laser or sham at 12 months. METHODS: A systematic review and meta-analysis of randomised controlled trials (RCTs) were performed; Ovid MEDLINE, EMBASE and CENTRAL were searched from inception to 4th March 2022. The change in any continuous measure of RNP at 12 months and 24 months was the primary and secondary outcomes, respectively. Outcomes were reported utilising standardised mean differences (SMD). The Cochrane Risk of Bias Tool version-2 and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines informed risk of bias and certainty of evidence assessments. RESULTS: Six RCTs (1296 eyes) and three RCTs (1131 eyes) were included at 12 and 24 months, respectively. Meta-analysis demonstrated that RNP progression may be slowed with anti-VEGF therapy compared with laser/sham at 12 months (SMD: -0.17; 95% confidence interval [CI]: -0.29, -0.06; p = 0.003; I2 = 0; GRADE rating: LOW) and 24-months (SMD: -0.21; 95% CI: -0.37, -0.05; p = 0.009; I2 = 28%; GRADE rating: LOW). The certainty of evidence was downgraded due to indirectness and due to imprecision. CONCLUSION: Anti-VEGF treatment may slightly impact the pathophysiologic process of progressive RNP in DR. The dosing regimen and the absence of diabetic macular edema may impact this potential effect. Future trials are needed to increase the precision of the effect and inform the association between RNP progression and clinically important events. PROSPERO REGISTRATION: CRD42022314418.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/complications , Ranibizumab , Bevacizumab , Endothelial Growth Factors , Vascular Endothelial Growth Factor A , Retina
17.
Retina ; 44(1): 136-143, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37748439

ABSTRACT

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.


Subject(s)
Choroid Diseases , Choroid Neoplasms , Nevus , Polyps , Humans , Middle Aged , Aged , Retrospective Studies , Endothelial Growth Factors , Choroid Diseases/drug therapy , Choroid/pathology , Choroid Neoplasms/pathology , Tomography, Optical Coherence/methods , Fluorescein Angiography/methods , Polyps/drug therapy , Intravitreal Injections
18.
Retina ; 44(4): 652-658, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38064668

ABSTRACT

PURPOSE: To investigate the 5-year treatment outcomes of retinopathy of prematurity in infants <500 g birth weight and compare laser and anti-vascular endothelial growth factor therapies. METHODS: A multicenter retrospective study comprised 24 eyes of 13 patients treated for Type 1 retinopathy of prematurity, followed for 5 years. Initial treatment was laser and anti-vascular endothelial growth factor in 13 and 11 eyes, respectively. Data collected included sex, birth characteristics, retinopathy of prematurity characteristics at the time of treatment, best-corrected visual acuity (BCVA), spherical equivalent, and astigmatism at 5 years posttreatment. RESULTS: Median BCVA was 0.15 logarithm of the minimum angle of resolution (interquartile range, 0.0-0.5). Snellen BCVA was ≥20/40 in 73% and ≥20/20 in 27% of eyes. Median spherical equivalent was -2.37 (interquartile range, -6.1 to -0.1); 75% had myopia (≤-0.5 D), and 25% had high myopia (≤-6.0 D). Median astigmatism was 1.25 (interquartile range, 0.9-3.0); 46% had ≥1.5 D. Anti-vascular endothelial growth factor-treated eyes showed less myopia ( P < 0.009), with no BCVA or astigmatism difference ( P = 0.997, P = 0.271) compared with laser-treated eyes. CONCLUSION: One-quarter of the eyes exhibited good visual acuity (Snellen BCVA of ≥20/20) 5 years after retinopathy of prematurity treatment. Refractive errors were common. Anti-vascular endothelial growth factor therapy may be superior to laser therapy in myopic refractive error.


Subject(s)
Astigmatism , Myopia , Refractive Errors , Retinopathy of Prematurity , Infant, Newborn , Infant , Humans , Astigmatism/therapy , Retinopathy of Prematurity/surgery , Retrospective Studies , Endothelial Growth Factors , Treatment Outcome , Laser Coagulation
19.
Int Wound J ; 21(4): e14517, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38087907

ABSTRACT

Trabeculectomy is the main surgical treatment for glaucoma, but scar formation during wound healing may lead to surgical failure. In this study, we evaluated the efficacy of anti-vascular endothelial growth factor (anti-VEGF) and mitomycin C (MMC) on wound healing after glaucoma surgery. We have been looking for Pubmed, Embase and other databases. The last time we looked at an electronic database was August 2023. A case control study was conducted to compare the use of anti-VEGF and mitomycin C for the treatment of glaucoma. We used the Cochrane standard methodology for collecting and analysing the data. Based on the criteria of inclusion, we have determined 369 related papers and selected seven eligible trials for data analysis. Three hundred and twenty-six cases were treated with trabeculectomy, of which 166 were injected with anti-VEGF and 160 were given MMC for trabeculectomy. In six trials, anti-VEGF and MMC were not found to have any statistical significance on postoperative wound leakage after surgery (OR, 1.55; 95% CI, 0.71, 3.35 p = 0.27). The three trials showed that anti-VEGF and MMC did not differ in terms of reducing postoperative wound hypotony after surgery (OR, 0.78; 95% CI, 0.20, 3.11 p = 0.73). Five trials demonstrated that anti-VEGF and MMC were not associated with a lower incidence of shallow anterior chamber (OR, 1.17; 95% CI, 0.5, 2.76 p = 0.71). There is no significant difference in the effect of anti-VEGF and MMC on wound healing after glaucoma surgery. A multicentre randomized controlled trial with a larger sample size is needed to confirm this study.


Subject(s)
Glaucoma , Trabeculectomy , Humans , Trabeculectomy/methods , Mitomycin/therapeutic use , Mitomycin/pharmacology , Endothelial Growth Factors , Case-Control Studies , Glaucoma/drug therapy , Glaucoma/surgery , Wound Healing , Treatment Outcome
20.
Surv Ophthalmol ; 69(2): 173-178, 2024.
Article in English | MEDLINE | ID: mdl-37806565

ABSTRACT

Anti-vascular endothelial growth factor (anti-VEGF) injections have revolutionized the field of ophthalmology, and their use in a variety of retinal diseases is growing. One target disease is peripheral exudative hemorrhagic chorioretinopathy, a disease that is uncommon and poorly understood. Despite this, there are numerous studies and case reports outlining the potential role of intravitreal injection of anti-VEGF medicines to treat it. As such, an evidence-based understanding of its risk-benefit profile is vital. We performed a comprehensive search in the PubMed, Google Scholar, and Cochrane databases for published studies and case reports relating to the use of anti-VEGF injections in peripheral exudative hemorrhagic chorioretinopathy. Anti-VEGF was first used in 2010 to aid in the management of peripheral exudative hemorrhagic chorioretinopathy. Since then, it has been increasingly used to manage this disease. Other potential management strategies, including laser photocoagulation, cryotherapy, photodynamic therapy, and vitrectomy are explored and compared with anti-VEGF where possible. Anti-VEGF appears to be an effective therapy in managing peripheral exudative hemorrhagic chorioretinopathy, especially when there is an exudative threat to the macula.


Subject(s)
Choroid Diseases , Macula Lutea , Retinal Diseases , Humans , Endothelial Growth Factors , Vascular Endothelial Growth Factor A , Intravitreal Injections , Retinal Diseases/drug therapy , Choroid Diseases/drug therapy , Angiogenesis Inhibitors/therapeutic use , Retrospective Studies
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