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Purpose Patients with neovascular age-related macular degeneration (nARMD) will not deteriorate on visual acuity and retinal thickness when treated with bevacizumab injection frequencies of 6 or 8 weeks compared to 4 weeks. This study aimed to investigate this non-inferiority in quality of life (QoL). We hypothesized that less frequent bevacizumab injections are not inferior regarding patients reported QoL. Methods Patients were randomized to bevacizumab every 4 ( n  = 64), 6 ( n  = 63), and 8 weeks ( n  = 64). Patients were at least 65 years old, have a best-corrected visual acuity of 20/200 to 20/20, no previous ARMD treatment and active leakage. Vision-related QoL questionnaire NEI VFQ-39 was used to assess QoL at baseline and after 1 year. General QoL questionnaire SF-36 was included for secondary analysis. Multilevel analyses were performed, correcting for age, gender and baseline. Results The 6 (3.68; 95% CI − 0.63 to 8.00) and 8 (2.15; 95% CI − 2.26 to 6.56) weeks bevacizumab regimens resulted in non-inferior QoL differences compared to 4 weeks on the NEI VFQ-39. Also on the SF-36 the differences were well within the non-inferiority limits. Conclusion Non-inferiority of the 6 and 8 weeks frequencies was demonstrated compared to 4 weeks on vision-related and general QoL in patients with nARMD. These results are in line with previously published results of lower frequency injections regarding visual acuity and central retinal thickness. Lower injection frequency may reduce burden, side effects, and treatment costs. In consideration of these results, 8 weeks frequency injections of intravitreal bevacizumab could be considered in patients with nARMD.

Aims. To confirm the therapeutic efficacy of conbercept for the treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) by using optical coherence tomography angiography (OCTA) and to find out the differences in therapeutic efficacy between ischemic and nonischemic retinal vein occlusion (iRVO or non-iRVO) after conbercept treatment. Methods. In this prospective, randomized, and comparative study, 60 unilateral eyes suffered from RVO combined with macular edema were included and fellow eye as controls. After an initial intravitreal injection of conbercept (IVIC), a pro re nata (PRN) strategy was adopted, and the follow-up time was 6 months. The foveal avascular zone (FAZ), vascular density of superficial capillary plexus (SCP), and vascular density of deep retinal capillary plexus (DCP), nonperfused areas (NPAs) were evaluated with OCTA on baseline and after treatment. Results. The mean intravitreal injection number was 2.9±0.89 times during six months in iRVO patients and 2.1±0.86 times in non-iRVO patients, with statistically significant difference (p<0.05). On baseline, central macular thickness (CMT) and FAZ were significantly thickened and enlarged compared to those of healthy fellow eyes; the vascular density of SCP and DCP were significantly decreased, and the differences were statistically significant (p<0.05). Compared to baseline, after treatment, the best-corrected visual acuity (BCVA) was improved in either iRVO or non-iRVO (−0.601±0.387, −0.241±0.341 logMAR, p<0.05). In iRVO, the improvement was more substantial than that of the non-iRVO group. FAZ in the non-iRVO group had significantly decreased compared to that in iRVO group (−0.044±0.040 versus 0.014±0.043 mm2, p<0.05). CMT, the vascular density of SCP, and DCP had no significant difference. Conclusions. The changes of microvascular structure can be quantitatively evaluated by using OCTA for the patients with RVO. Conbercept had a significant effect on treatment of RVO with macular edema. A more profound effect was achieved in the iRVO group on visual improvement and FAZ reduction in the non-iRVO group after conbercept treatment.

To determine whether patients prefer topical anesthesia or subconjunctival anesthesia for intravitreal injection. Consecutive patients receiving bilateral simultaneous injections of anti-vascular endothelial growth factor agents were asked to participate in this within-patient, prospective, single-blinded, randomized, factorial study. Fifty-seven patients completed the study. Both eyes were treated with topical anesthesia. One eye was also injected with subconjunctival lidocaine. Anesthesia for the next treatment visit was based on patient preference at the conclusion of the study visit and at a 4-hour and 24-hour follow-up telephone call. Patients were allowed to change their anesthesia preference during the next three visits. The final endpoint for the study was anesthesia preference for ongoing intravitreal injections. Fifty patients (88%) preferred subconjunctival anesthesia and seven patients (12%) preferred topical anesthesia for ongoing treatments. (P = .0003) CONCLUSION: Given the choice, most patients prefer subconjunctival anesthesia to topical anesthesia for intravitreal injections.

BackgroundThe preservation of globe integrity has always been a major concern during the treatment of retinoblastoma for fear of extraocular or metastatic spread. Intravitreal chemotherapy has been attempted as a desperate salvage therapy only for eyes with refractory retinoblastoma. Published data on the safety and efficacy of this route are, however, limited.MethodsA modified technique of intravitreal injection in eyes with retinoblastoma is described. All children with retinoblastoma who received one or more intravitreal injections using this technique were retrospectively reviewed concerning ocular complications of the injection procedure as well as clinical or histopathological evidence of tumour spread.Results30 eyes of 30 children with retinoblastoma received a total of 135 intravitreal injections, with a median follw-up duration of 13.5 months. No extraocular spread was seen on clinical follow-up in any patients and there was no tumour contamination of the retrieved entry sites histopathologically analysed among the five enucleated eyes. No significant ocular side effects were observed except transient localised vitreous haemorrhage (3/135).ConclusionThis technique is potentially safe and effective at a low cost and may play a promising role, especially in the treatment of recurrent and/or resistant vitreous disease in retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy. However, this treatment should not replace the primary standard of care of retinoblastoma and should not be considered in group E eyes. Its application should be approved by an ophthalmological-oncological team and it should be performed by an experienced eye surgeon in a tertiary referral centre after careful selection of a tumour-free injection site.

The therapeutic benefits of many cell types involve paracrine mechanisms. Inspired by the paracrine functions of exosomes and the sustained degradation properties of microcapsules, here we report the therapeutic benefits of exosome-loaded degradable poly(lactic-co-glycolic acid) microcapsules with micrometric pores for the treatment of vitreoretinal diseases. On intravitreal injection in a mouse model of retinal ischaemia-reperfusion injury, microcapsules encapsulating mouse mesenchymal-stem-cell-derived exosomes settled in the inferior vitreous cavity, released exosomes for over one month as they underwent degradation and led to the restoration of retinal thickness to nearly that of the healthy retina. In mice and non-human primates with primed mycobacterial uveitis, intravitreally injected microcapsules loaded with exosomes from monkey regulatory T cells resulted in a substantial reduction in the levels of inflammatory cells. The exosome-encapsulating microcapsules, which can be lyophilised, may offer alternative treatment options for vitreoretinal diseases. Degradable polymeric porous microcapsules loaded with exosomes from mesenchymal stem cells or regulatory T cells led to the restoration of retinal thickness in mice with retinal ischaemia-reperfusion injury and to reductions in inflammatory cells in monkeys with mycobacterial uveitis.

Pathological angiogenesis is the hallmark of many vision-threatening diseases. Anti-VEGF is a primary treatment with substantial beneficial effects. However, such agents require frequent intravitreal injections. Our previous work established a method for effectively modifying exosomes (EXOs) for loading therapeutic peptides. Here, we used this system to load the anti-angiogenic peptide KV11, aiming to establish an EXO-based therapy strategy to suppress neovascularization in the retina. Using an anchoring peptide, CP05, we linked KV11 to endothelial cell (EC) derived EXOs, yielding EXO . We tested the delivery efficiency of EXO via two commonly used ocular injection methods: retro-orbital injection and intravitreal injection. Deploying an oxygen-induced retinopathy (OIR) model and a VEGF injection model, we tested the effects of EXO on neovascular formation, EC proliferation, and vascular permeability. experiments were used to test the mechanism and to analyze the effects of EXO on EC proliferation, migration, and sprouting. : By using the EXO loading system, KV11 was more efficiently delivered to the blood vessels of the mouse retina via retro-orbital injection. In both OIR model and VEGF injection model, EXO was more effective than KV11 alone in inhibiting neovascularization and vessel leakage. The therapeutic effect of retro-orbital injection of EXO was comparable to the intravitreal injection of VEGF-trap. Mechanistically, KV11 alone inhibited VEGF-downstream signaling, while EXO showed a stronger effect. We used EXOs as a carrier for intraocular delivery of KV11. We showed that KV11 itself has an anti-angiogenic effect through retro-orbital injection, but that this effect was greatly enhanced when delivered with EXOs. Thus, this system has the potential to treat proliferative retinopathy via retro-orbital injection which is a less invasive manner compared with intravitreal injection.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory agents. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. Changes in the correct visual acuity and reduction in geographic atrophy progression were evaluated. Several new drugs have shown promising results, including those targeting the complement cascade and neuroprotective agents. The potential action of the two groups of drugs is to block complement cascade upregulation of immunomodulating agents, and to prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. Our analysis indicates that finding treatments for dry AMD will require continued collaboration among researchers to identify additional molecular targets and to fully interrogate the utility of pluripotent stem cells for personalized therapy.

To determine the characteristics of diabetic macular edema (DME) patients refractory to intravitreal bevacizumab (IVB) treatments and an additional dexamethasone implant. We classified 119 DME patients according to whether or not they are responsive to 3 consecutive monthly anti-VEGF treatments and/or an additional dexamethasone implant. We compared their concentrations of IL (interleukin)-1β, IL-8, IL-10, IL-17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) in the aqueous humor as well as their optical coherence tomography (OCT) findings, and baseline characteristics. We used logistic regression analyses to identify preoperative factors related to refractoriness to treatments. Of 119 treatment-naïve DME patients, 50 (42.02%) patients showed responsiveness [central subfield thickness (CST) < 300μm] after 3 IVBs, and 59 (49.58%) patients showed responsiveness after an additional dexamethasone implant, but 10 (8.40%) patients showed CST 300 ≥ μm even after both treatments. Refractory DME patients showed significantly higher number of hyperreflective foci (HF) in the OCT and higher average level of aqueous IL-1β at baseline (p<0.001 and p = 0.042, respectively). In the logistic regression analysis, higher number of HF in the OCT was associated with the refractoriness to both treatments (odds ratio [OR]: 7.03, p = 0.007). Higher number of HF in the OCT at the initial visit was associated with poor responses to IVBs and an additional dexamethasone implant.