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Microfluidic synthesis of PLGA/carbon quantum dot microspheres for vascular endothelial growth factor delivery
摘要： In this study, vascular endothelial growth factor (VEGF) loaded poly(D,L-lactide-co-glycolide) (PLGA) – carbon quantum dot microspheres were produced using micro?uidic platforms. The microcapsules were fabricated in ?ow-focusing geometry with a biphasic ?ow to generate solid/oil/water (s–o–w) droplets. To avoid any damage to protein functional and structural stability during the encapsulation process, the VEGF was PEGylated. The produced microspheres were intact and highly monodisperse in size (CV < 5%). Furthermore, microspheres in a size range of 16–36 mm were achieved by adjusting the ?ow ratio parameter. The encapsulation e?ciency, release pro?le, and bioactivity of the produced microparticles were also studied. The loading e?ciency of PEGylated VEGF in the microparticles was varied from 51–69% and more than 90% of PEGylated VEGF was released within 28 days. Furthermore, the release of VEGF was indirectly monitored by carbon quantum dots. The present monodisperse and controllable VEGF loaded microspheres with reproducible manner could be widely used in tissue engineering and therapeutic applications.
关键词： PLGA,vascular endothelial growth factor,carbon quantum dot,drug delivery,Micro?uidic synthesis
更新于2025-09-16 10:30:52
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SEVERE RECURRENT FIBROVASCULAR PROLIFERATION AFTER COMBINED INTRAVITREAL BEVACIZUMAB INJECTION AND LASER PHOTOCOAGULATION FOR AGGRESSIVE POSTERIOR RETINOPATHY OF PREMATURITY
摘要： To describe the clinical features of severe recurrent fibrovascular proliferation after combined intravitreal bevacizumab injections and laser photocoagulation for aggressive posterior retinopathy of prematurity. This retrospective, nonrandomized case series reviewed the medical and ophthalmic records in the referral hospital and our hospital. Four patients (seven eyes) with aggressive posterior retinopathy of prematurity. The patients were referred for vitrectomy with/without lensectomy for recurrent fibrovascular proliferation with a tractional retinal detachment after combined intravitreal bevacizumab injections and laser photocoagulation. Three patients were born at 22 weeks or 23 weeks’ gestational age and one patient at 29 weeks’ gestational age. Preoperatively, fluorescein angiography images showed all eyes had tractional retinal detachment from regrowth of fibrovascular proliferation 3 months to 5 months after the intravitreal bevacizumab injection and abnormal retinal vasculature; four eyes had a broad ischemic retina. Postoperatively, four eyes had retinal attachment and three eyes a total retinal detachment. Neovascular glaucoma developed in five of the seven eyes during the clinical course. Severe fibrovascular proliferation may recur due to widespread retinal ischemia with capillary dropout and abnormal vasculature after failed combined intravitreal bevacizumab and laser photocoagulation therapy as the initial treatment for aggressive posterior retinopathy of prematurity. Careful follow-up is important especially after anti–vascular endothelial growth factor treatment, with recognition that severe reactivation is possible.
关键词： intravitreal bevacizumab injection,vitrectomy,retinopathy of prematurity,fluorescein angiography,stage 5 ROP,vascular endothelial growth factor,stage 4 ROP,fibrovascular proliferation,laser photocoagulation,ROP surgery
更新于2025-09-12 10:27:22
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Rescue with intravitreal bevacizumab in aggressive posterior retinopathy of prematurity poorly responsive to laser treatment
摘要： Successful management of a case of aggressive posterior retinopathy of prematurity (APROP) poorly responsive to laser therapy with intravitreal bevacizumab (IVB) is discussed. IVB is useful as rescue therapy in such cases, if given within the correct window period post laser therapy.
关键词： Aggressive posterior retinopathy of prematurity (APROP),laser in retinopathy of prematurity (ROP),anti-vascular endothelial growth factor (anti-VEGF)
更新于2025-09-11 14:15:04
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Comparative Effects of Coenzyme Q10 or n-3 Polyunsaturated Fatty Acid Supplementation on Retinal Angiogenesis in a Rat Model of Oxygen-Induced Retinopathy
摘要： Neonatal intermittent hypoxia (IH) or apnea afflicts 70% to 90% of all preterm infants <28 weeks gestation, and is associated with severe retinopathy of prematurity (ROP). We tested the hypotheses that coenzyme Q10 (CoQ10) or omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation during neonatal IH reduces the severity of oxygen-induced retinopathy (OIR). Newborn rats were exposed to two IH paradigms: (1) 50% O2 with brief hypoxia (12% O2); or (2) 21% O2 with brief hypoxia, until postnatal day 14 (P14), during which they received daily oral CoQ10 in olive oil, n-3 PUFAs in fish oil, or olive oil only and compared to room air (RA) treated groups. Pups were examined at P14, or placed in RA until P21. Retinal angiogenesis, histopathology, and morphometry were determined. Both IH paradigms produced severe OIR, but these were worsened with 50/12% O2 IH. CoQ10 and n-3 PUFAs reduced the severity of OIR, as well as ocular growth factors in both IH paradigms, but CoQ10 was more effective in 50/12% O2 IH. Supplementation with either CoQ10 or n-3 PUFAs targeting IH-induced retinal injury is individually effective for ameliorating specific characteristics consistent with ROP. Given the complexity of ROP, further studies are needed to determine whether combined CoQ10 and n-3 PUFAs supplementation would optimize their efficacy and result in a better outcome.
关键词： n-3 polyunsaturated fatty acids,oxygen-induced retinopathy,insulin-like growth factor-I,coenzyme Q10,vascular endothelial growth factor,neonatal intermittent hypoxia
更新于2025-09-10 09:29:36
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Aflibercept Treatment for Neovascular Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy Refractory to Anti-vascular Endothelial Growth Factor
摘要： Purpose: To report the results of switching treatment to vascular endothelial growth factor (VEGF) Trap-Eye (aflibercept) in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) refractory to anti-VEGF (ranibizumab and bevacizumab). Methods: This is a retrospective study involving 32 eyes from 29 patients; 18 were cases of neovascular AMD and 14 were cases of PCV. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) of spectral-domain optical coherence tomography were evaluated. Results: BCVA and CMT improved from 0.58 to 0.55 (p = 0.005) and from 404 to 321 μm (p < 0.001), respectively, after switching to aflibercept. The 14 eyes that received 6 or more aflibercept injections remained stable at 0.81 to 0.81 and 321 to 327 μm (p = 1.0, 0.29), respectively, after 3 aflibercept injections. The 10 eyes that received 3 or more bevacizumab injections after 3 or more aflibercept injections worsened, from 0.44 to 0.47 and from 332 to 346 μm (p = 0.06, 0.05), respectively. The results showed similar improvement of BCVA and CMT in neovascular AMD and PCV. Conclusions: Aflibercept seems to be effective for improvement and maintenance of BCVA and CMT for neovascular AMD and PCV refractory to anti-VEGF. Switching from aflibercept back to bevacizumab treatment may not be a proper strategy.
关键词： Aflibercept,Polypoidal choroidal vasculopathy,Bevacizumab,Macular degeneration,Anti-vascular endothelial growth factor
更新于2025-09-10 09:29:36
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LONG-TERM VISUAL OUTCOMES AND CLINICAL FEATURES AFTER ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION–RELATED ENDOPHTHALMITIS
摘要： Purpose: To determine long-term visual outcomes in patients who developed endophthalmitis after intravitreal anti–vascular endothelial growth factor injections and to correlate visual outcomes with clinical features. Methods: This is a retrospective, multicenter, consecutive case series of patients diagnosed with anti–vascular endothelial growth factor injection–related endophthalmitis who were treated at Mid Atlantic Retina, the Retina Service of Wills Eye Hospital, Philadelphia, PA, and the University of Southern California Roski Eye Institute, Los Angeles, CA. Patients were included if they had at least 1 year of follow-up. Primary outcome was to evaluate long-term visual outcomes up to 5 years of follow-up. The secondary outcome was to determine clinical features (e.g., culture results) that may predict long-term visual acuity outcomes. Results: A total of 56 cases of endophthalmitis from 168,247 anti–vascular endothelial growth factor injections were identi?ed (0.033%, 1/3,004 injections), from which 51 eyes met inclusion criteria. Mean follow-up period was 3.3 years (median 4 years; range 1–5 years). A total of 24 patients (47%) reached a maximum ?nal follow-up of 5 years. Mean Snellen visual acuity at the causative injection visit was 20/102 and decreased to counting ?ngers at diagnosis (P , 0.001). At 6-month follow-up, mean visual acuity improved to 20/644 (P , 0.001) and remained stable up to 5 years (20/480, P = 0.003) follow-up compared with diagnosis. At the ?nal follow-up, 20 eyes had visual acuity that returned to within one line of baseline visual acuity (visual recovery group), whereas 31 patients’ visual acuity was at least one line worse than initial visual acuity (visual deterioration group). The cultures for the visual recovery group were more likely to grow coagulase-negative Staphylococcus, whereas the visual deterioration group primarily grew Streptococcus species, Staphylococcus aureus, and Enterococcus faecalis (P = 0.002, comparing organisms isolated in the visual recovery and deterioration group). Conclusion: Visual outcomes after anti–vascular endothelial growth factor injection– related endophthalmitis seem to reach peak improvement by 6 months and remain stable up to a median of 4-year follow-up. Patients who develop culture-negative endophthalmitis or endophthalmitis secondary to coagulase-negative Staphylococcus are more likely to regain baseline visual acuity compared with cases secondary to Streptococcus species.
关键词： bevacizumab,anti-vascular endothelial growth factor,diabetic macular edema,intravitreal injection,endophthalmitis,a?ibercept,long-term,ranibizumab,neovascular age-related macular degeneration,retinal vein occlusion
更新于2025-09-10 09:29:36
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Optical Coherence Tomography and the Development of Antiangiogenic Therapies in Neovascular Age-Related Macular Degeneration
摘要： To explain the pivotal role optical coherence tomography (OCT) imaging had in the development of antiangiogenic therapies for the treatment of neovascular age-related macular degeneration (nvAMD). A historical literature review was combined with personal perspectives from the introduction of OCT imaging and the early clinical use of vascular endothelial growth factor (VEGF) inhibitors. At the time that OCT emerged, the gold standard for imaging of nvAMD was fluorescein angiography (FA), a time-consuming, dye-based, invasive technique that provided en face images of the retina and was used to characterize leakage, perfusion status, and the types of macular neovascularization (MNV). In comparison, OCT imaging was a fast, safe, noninvasive technique that complemented FA imaging by providing cross-sectional images of the macula. OCT was able to visualize and quantify the macular fluid that was associated with the presence of excess VEGF, which was identified by intraretinal fluid, subretinal fluid, and fluid under the retinal pigment epithelium (RPE). Clinicians quickly appreciated the benefits of OCT imaging for following macular fluid after anti-VEGF therapy. By observing the qualitative and quantitative changes in macular fluid depicted by OCT imaging, clinicians were empowered to compare anti-VEGF drugs and move from fixed-dosing regimens to patient-specific dosing strategies requiring fewer injections. Optical coherence tomography imaging was adopted as a VEGF-meter, a method to detect excess VEGF, and evolved to become the gold standard imaging strategy for diagnosing nvAMD, assessing treatment responses to anti-VEGF drugs, deciding when to re-treat, and evaluating disease progression.
关键词： neovascularization,anti-vascular endothelial growth factor,exudation,optical coherence tomography,antiangiogenesis
更新于2025-09-10 09:29:36
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The outcomes of aflibercept therapy in patients with age-related macular degeneration resistant to bevacizumab or ranibizumab
摘要： Purpose: This study was designed to assess the functional and anatomic outcomes of intravitreal a?ibercept injection in patients with wet age-related macular degeneration (AMD) refractory to intravitreal bevacizumab or ranibizumab therapy. Methods: This retrospective study included 43 eyes of 43 patients resistant to treatment with at least 6 injections of bevacizumab or ranibizumab. Persistent intraretinal and subretinal ?uid (IRF and SRF) on optical coherence tomography (OCT), no improvement in best corrected visual acuity (BCVA), and a central macular thickness (CMT) increase of more than 100 mm due to SRF and/or IRF compared to baseline for at least 6 monthly intravitreal bevacizumab or ranibizumab injections were de?ned as resistant to bevacizumab/ranibizumab therapy. BCVA, intraocular pressure (IOP), CMT, maximum retinal thickness (MRT), and maximum pigment epithelial detachment (PED) height (MPEDH) were evaluated before and after a?ibercept injections. Result: After initiating a?ibercept treatment, the mean ?nal BCVA logarithm of the minimum angle of resolution or recognition (logMAR) improved to 0.84 ± 0.59 which was statistically signi?cant compared to baseline (1.14 ± 0.51), (P < 0.001). After a?ibercept injection, statistically signi?cant reduction was noted in mean CMT (402.6 ± 196.7 mm vs 264.2 ± 52.85 mm, P < 0.05), MRT (435.3 ± 195.2 mm vs 282.2 ± 31.8 mm, P < 0.05), and MPEDH (154.2 ± 86.0 mm vs 68.3 ± 70.6 mm, P < 0.05). There was no correlation between the total number of previous injections and the increase of BCVA (r ? (cid:2)0.10, P ? 0.265). The decrease of mean IOP was statistically signi?cant under a?ibercept treatment (P < 0.001). Conclusions: The present study showed the ef?cacy of a?ibercept treatment in eyes with persistent retinal or SRF under bevacizumab or ranibizumab therapy. A signi?cant anatomical and functional improvement was noted.
关键词： A?ibercept,Age related macular degeneration,Bevacizumab,Ranibizumab,Anti-vascular endothelial growth factor
更新于2025-09-04 15:30:14