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The Optimization of an Anti-VEGF Therapeutic Regimen for Neovascular Glaucoma.

ABSTRACT: This study investigates the safety and efficacy of conbercept injection through different routes for neovascular glaucoma (NVG) treatment, in which seventy-four patients (81 eyes) with NVG caused by ischemia retinopathy had participated. Patients were divided into three stages according to the progression of NVG and were randomly assigned to receive intracameral or intravitreal conbercept injection. After conbercept injection, patients experienced improved best-corrected visual acuity (BCVA), good intraocular pressure (IOP) control, and neovascularization of Iris (NVI) regression. In stage III, patients required trabeculectomy with mitomycin C plus pan-retinal photocoagulation (PRP) to achieve complete NVI regression. Compared to the intravitreal group, the intracameral group had significantly lower IOP in 2 days in stage III and 1 day in stages I and II after injection, complete NVI regression before PRP in stages I and II, and better NVI regression in stage III. The rates of hyphema after trabeculectomy and malfunction filtering bleb suffering needle bleb revision were lower in the intracameral group, but only the hyphema rate was significantly different. Injections through different routes are all safe. We recommend intravitreal injections for patients in stages I and II, but for stage III, intracameral injection is better, and trabeculectomy with mitomycin C should be conducted within 2 days after injection to maximally reduce the risk of perioperative hyphema. Trial Registration: ClinicalTrials.gov, identifier NCT03154892.

SUBMITTER: Bai L

PROVIDER: S-EPMC8784790 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo establish a comprehensive treatment strategy and evaluate the efficacy of combination of anti-vascular endothelial growth factor (VEGF) injection, pars plana vitrectomy (PPV), endoscopic pan-retinal photocoagulation (PRP), and endoscopic cyclophotocoagulation (ECP) surgery for neovascular glaucoma (NVG) patients.MethodsThis retrospective study included 30 patients (30 eyes) who were suffering from NVG and treated with PPV & PRP & ECP (ECP group, 16 eyes), or Ahmed glaucoma valve implantation (Ahmed group, 14 eyes). The intraocular pressure (IOP), number of postoperative anti-glaucoma medications, best-corrected visual acuity (BCVA), successful rate of surgery, and postoperative complications were recorded and statistically analyzed at the time points of preoperative, 1-day, 1-month, 3-months, 6-months, and 12-months after operation.ResultsAn obvious reduction in IOP and number of postoperative anti-glaucoma medications were observed in both the ECP group and Ahmed group after operation (P < 0.05), and the ECP group showed a significantly lower IOP compared to the Ahmed group at the 6-months (P = 0.014) and 12-months (P = 0.047) postoperative time points, while there was no significant difference of medication number between the two groups except for 1-day after surgery. The BCVA showed no marked difference between the two groups preoperatively and postoperatively (P > 0.05), while it was significantly improved in ECP group at 3-months (P = 0.001), 6-months (P = 0.004), and 12-months (P = 0.010) time points comparing with preoperative BCVA. The surgical success rates in ECP group were also slightly higher than Ahmed group. And the complications after operation showed no marked differences.ConclusionsThe comprehensive treatment of PPV, endoscopic PRP, and ECP surgery for NVG patients after anti-VEGF injection can control IOP effectively and be friendly to patients' BCVA without obvious serious complications throughout a 12-months follow-up period.

Project description:Intravitreal anti-vascular endothelial growth factor (VEGF) drugs have revolutionized the treatment of neovascular age-related macular degeneration (NVAMD). However, many patients suffer from incomplete response to anti-VEGF therapy (IRT), which is defined as (1) persistent (plasma) fluid exudation; (2) unresolved or new hemorrhage; (3) progressive lesion fibrosis; and/or (4) suboptimal vision recovery. The first three of these collectively comprise the problem of persistent disease activity (PDA) in spite of anti-VEGF therapy. Meanwhile, the problem of suboptimal vision recovery (SVR) is defined as a failure to achieve excellent functional visual acuity of 20/40 or better in spite of sufficient anti-VEGF treatment. Thus, incomplete response to anti-VEGF therapy, and specifically PDA and SVR, represent significant clinical unmet needs. In this review, we will explore PDA and SVR in NVAMD, characterizing the clinical manifestations and exploring the pathobiology of each. We will demonstrate that PDA occurs most frequently in NVAMD patients who develop high-flow CNV lesions with arteriolarization, in contrast to patients with capillary CNV who are highly responsive to anti-VEGF therapy. We will review investigations of experimental CNV and demonstrate that both types of CNV can be modeled in mice. We will present and consider a provocative hypothesis: formation of arteriolar CNV occurs via a distinct pathobiology, termed neovascular remodeling (NVR), wherein blood-derived macrophages infiltrate the incipient CNV lesion, recruit bone marrow-derived mesenchymal precursor cells (MPCs) from the circulation, and activate MPCs to become vascular smooth muscle cells (VSMCs) and myofibroblasts, driving the development of high-flow CNV with arteriolarization and perivascular fibrosis. In considering SVR, we will discuss the concept that limited or poor vision in spite of anti-VEGF may not be caused simply by photoreceptor degeneration but instead may be associated with photoreceptor synaptic dysfunction in the neurosensory retina overlying CNV, triggered by infiltrating blood-derived macrophages and mediated by Müller cell activation Finally, for each of PDA and SVR, we will discuss current approaches to disease management and treatment and consider novel avenues for potential future therapies.

Project description:BackgroundNeovascular glaucoma (NVG) is a potentially blinding secondary glaucoma. It is caused by the formation of abnormal new blood vessels which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) agents are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGFs for the control of intraocular pressure (IOP) in NVG.ObjectivesTo compare the IOP lowering effects of intraocular anti-VEGF agents to no anti-VEGF treatment, as an adjunct to existing modalities for the treatment of NVG.Search methodsWe searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov/) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 January 2013.Selection criteriaWe included randomized controlled trials (RCTs) and quasi-RCTs of people treated with anti-VEGF agents for NVG.Data collection and analysisTwo authors independently assessed the search results for trials to be included in the review. Discrepancies were resolved by discussion with a third author. Since no trial met our inclusion criteria, no assessment of risk of bias or meta-analysis was undertaken.Main resultsNo RCTs were found that met the inclusion criteria for this review. Two RCTs of anti-VEGF agents for treating NVG were not included in the review due to the heterogeneity and uncontrolled assignment of adjunct treatments received by the study participants.Authors' conclusionsCurrently available evidence is insufficient to evaluate the effectiveness of anti-VEGF treatments, such as intravitreal ranibizumab or bevacizumab, as an adjunct to conventional treatment in lowering IOP in NVG. Well designed RCTs are needed to address this issue, particularly trials that evaluate long-term (at least six months) benefits and risks since the effects of anti-VEGF agents may be short-term only. An RCT comparing anti-VEGF agents with no anti-VEGF agents taking into account the need for co-interventions, such as panretinal photocoagulation (PRP), glaucoma shunt procedures, cyclodestructive procedures, cataract surgery, and deep vitrectomy, could be of use to investigate the additional beneficial effect of anti-VEGF agents in treating NVG. Since decisions for when and which co-interventions should be used are based on clinical criteria, they would not be appropriate for randomization. However, the design of a study on this topic should aim to balance groups by stratification of co-intervention at time of randomization or by enrolling a sufficient number of participants to conduct subgroup analysis by co-interventions (ideally 15 participants per treatment group for each subgroup). Alternatively, the inclusion criteria for a trial could limit participants to those who receive the same co-intervention.

Project description:PurposeTo probabilistically forecast needed anti-vascular endothelial growth factor (anti-VEGF) treatment frequency using volumetric spectral domain-optical coherence tomography (SD-OCT) biomarkers in neovascular age-related macular degeneration from real-world settings.MethodsSD-OCT volume scans were segmented with a custom deep-learning-based analysis pipeline. Retinal thickness and reflectivity values were extracted for the central and the four inner Early Treatment Diabetic Retinopathy Study (ETDRS) subfields for six retinal layers (inner retina, outer nuclear layer, inner segments [IS], outer segments [OS], retinal pigment epithelium-drusen complex [RPEDC] and the choroid). Machine-learning models were probed to predict the anti-VEGF treatment frequency within the next 12 months. Probabilistic forecasting was performed using natural gradient boosting (NGBoost), which outputs a full probability distribution. The mean absolute error (MAE) between the predicted versus actual anti-VEGF treatment frequency was the primary outcome measure.ResultsIn a total of 138 visits of 99 eyes with neovascular AMD (96 patients) from two clinical centers, the prediction of future anti-VEGF treatment frequency was observed with an accuracy (MAE [95% confidence interval]) of 2.60 injections/year [2.25-2.96] (R2 = 0.390) using random forest regression and 2.66 injections/year [2.31-3.01] (R2 = 0.094) using NGBoost, respectively. Prediction intervals were well calibrated and reflected the true uncertainty of NGBoost-based predictions. Standard deviation of RPEDC-thickness in the central ETDRS-subfield constituted an important predictor across models.ConclusionsThe proposed, fully automated pipeline enables probabilistic forecasting of future anti-VEGF treatment frequency in real-world settings.Translational relevancePrediction of a probability distribution allows the physician to inspect the underlying uncertainty. Predictive uncertainty estimates are essential to highlight cases where human-inspection and/or reversion to a fallback alternative is warranted.

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The Optimization of an Anti-VEGF Therapeutic Regimen for Neovascular Glaucoma.

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