Anti-VEGF Therapy for Persistent Neovascularization after Complete Panretinal Photocoagulation in Proliferative Diabetic Retinopathy

Mehanna, Carl-Joe; Fattah, Maamoun Abdul; Haddad, Sandra; Tamim, Hani; Ghazi, Nicola G.; Salti, Haytham I.

doi:10.1016/j.oret.2019.02.001

Cited by 10 publications

(7 citation statements)

References 27 publications

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“…Multiple preclinical and clinical studies have established vascular endothelial growth factor (VEGFA) as a key mediator of the pathological angiogenesis in neovascular age-related macular degeneration (nAMD), 1 diabetic retinopathy (DR) 2 and diabetic macular edema (DME), 3 or macular edema due to retinal vein occlusion (RVO). 4 Indeed, anti-VEGFA agents such as ranibizumab, bevacizumab, and aflibercept have demonstrated efficacy in controlling pathological neovascularization and macular edema in these diseases.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Aflibercept Expression in NHPs following Intravitreal Administration of ADVM-022, a Potential Gene Therapy for nAMD

Kiss

Grishanin²,

Nguyen³

et al. 2020

Molecular Therapy - Methods & Clinical Development

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Several standard-of-care therapies for the treatment of retinal disease, including aflibercept, inhibit vascular endothelial growth factor (VEGFA). The main shortcoming of these therapies is potential undertreatment due to a lack of compliance resulting from the need for repeated injections. Gene therapy may provide sustained levels of anti-VEGFA proteins in the retina following a single injection. In this nonhuman primate study, we explored whether ADVM-022, a recombinant adeno-associated virus (AAV) vector designed to express aflibercept, could induce anti-VEGFA protein levels comparable with those observed following a single-bolus intravitreal (IVT) injection of the standard-of-care aflibercept recombinant protein. The results demonstrated that intraocular levels of aflibercept measured at 56 days after a single IVT injection of ADVM-022 were equivalent to those in the aflibercept recombinant protein-injected animals measured 21–32 days post-administration. ADVM-022-injected animals exhibited signs of an initial self-limiting inflammatory response, but overall all doses were well tolerated. ADVM-022 administration did not result in systemic exposure to aflibercept at any dose evaluated. These results demonstrated that a single IVT injection of ADVM-022 resulted in safe and efficacious aflibercept levels in the therapeutic range, suggesting the potential of a gene therapy approach for long-term treatment of retinal disease with anti-VEGF therapy.

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Section: Introductionmentioning

confidence: 99%

Analysis of Aflibercept Expression in NHPs following Intravitreal Administration of ADVM-022, a Potential Gene Therapy for nAMD

Kiss

Grishanin²,

Nguyen³

et al. 2020

Molecular Therapy - Methods & Clinical Development

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“…This inflammation is believed to actively contribute to associated damage of the retinal vasculature through its ability to trigger apoptosis of RPE cells and promotion of retinal neovascularization. Of the main damage inducing molecules whose activity and expression is known to be upregulated in the diabetic eye, it is the increased secretion of vascular endothelial growth factor (VEGF) which triggers neovascularisation and onset of the proliferative stage of diabetic retinopathy [ 175 ]. Coupled with the breakdown of tight junctions between cells of the RPE, disruption to the retinal pigment epithelium allows for these newly developed and fragile blood vessels to push through and leak into the macula.…”

Section: The Therapeutic Potential Of Blocking Cx43 In Diabetic Retinopathymentioning

confidence: 99%

Connexin 43: A Target for the Treatment of Inflammation in Secondary Complications of the Kidney and Eye in Diabetes

Cliff

Williams

Chadjichristos

et al. 2022

IJMS

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Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease and blindness in the working population, more than ever is there a demand to develop clinical interventions which can both delay and prevent disease progression. Connexins are membrane bound proteins that can form pores (hemichannels) in the cell membrane. Gated by cellular stress and injury, they open under pathophysiological conditions and in doing so release ‘danger signals’ including adenosine triphosphate into the extracellular environment. Linked to sterile inflammation via activation of the nod-like receptor protein 3 inflammasome, targeting aberrant hemichannel activity and the release of these danger signals has met with favourable outcomes in multiple models of disease, including secondary complications of diabetes. In this review, we provide a comprehensive update on those studies which document a role for aberrant connexin hemichannel activity in the pathogenesis of both diabetic eye and kidney disease, ahead of evaluating the efficacy of blocking connexin-43 specific hemichannels in these target tissues on tissue health and function.

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“…Such cases would see the use of individualised treatment regimens using selective anti-VEGF in combination with PRP or vitrectomy. 57 The use of intravitreal anti-VEGF also leads to an infrequent complication termed “crunch syndrome”, which is characterised by the sudden loss of vision within 1–6 weeks of anti-VEGF injection due to new or progressing TRD, especially bevacizumab. 68 Further, anti-VEGF is associated with the problem of microdosing: research findings reveal that giving half the dose is suitable to prevent bleeding during PPV.…”

Section: Limitations Of Anti-vegf Agents In Pdrmentioning

confidence: 99%

“…However, the therapy was not considered successful due to the occurrence of certain events (NV in three eyes), traction development in five eyes, dense VH in six eyes. 57 In certain rare scenarios, protein aggregation has been observed after IVB injection in the American Academy of Ophthalmology survey. This might be attributable to the other ingredients present in the injection besides the active ingredients.…”

Section: Limitations Of Anti-vegf Agents In Pdrmentioning

confidence: 99%

“…54 There are other various pivotal global studies that established the effectiveness of anti-VEGF therapy. [56][57][58] Preoperative anti-VEGF injections have also been shown to decrease surgical time required, as well as being associated with reduced intraoperative bleeding. An IVB also helps in overcoming the complications of VH by minimising the need for PPV and decreasing vitreous clear-up time.…”

Section: Advantages Of Using Anti-vegf Therapy In Pdrmentioning

confidence: 99%

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A Paradigm Shift in the Management Approaches of Proliferative Diabetic Retinopathy: Role of Anti-VEGF Therapy

Raman

Ramasamy²,

Shah³

2022

OPTH

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Diabetic retinopathy (DR) is considered one of the leading causes of vision loss globally. It principally causes upregulation of pro-angiogenic, proinflammatory, and vascular permeability factors such as vascular endothelial growth factor (VEGF), leading to neovascularisation. The advanced stage of DR or proliferative diabetic retinopathy (PDR) is of more concern, as it leads to vitreous haemorrhage and traction retinal detachment. Various risk factors associated with PDR include hyperglycemia, hypertension, neuropathy, dyslipidemia, anaemia, nephropathy, and retinal complications of drugs used for diabetes. Current management approaches for PDR have been stratified and involve pan-retinal photocoagulation, vitrectomy, and anti-VEGF agents. Given the emerging role of anti-VEGF agents as a favourable adjunct or alternative therapy, they have a critical role in the management of PDR. The review emphasises current management approaches for PDR focusing on anti-VEGF therapy. The review also highlights the risk/benefit evaluation of the various approaches employed for PDR management in various clinical scenarios.

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Anti-VEGF Therapy for Persistent Neovascularization after Complete Panretinal Photocoagulation in Proliferative Diabetic Retinopathy

Cited by 10 publications

References 27 publications

Analysis of Aflibercept Expression in NHPs following Intravitreal Administration of ADVM-022, a Potential Gene Therapy for nAMD

Analysis of Aflibercept Expression in NHPs following Intravitreal Administration of ADVM-022, a Potential Gene Therapy for nAMD

Connexin 43: A Target for the Treatment of Inflammation in Secondary Complications of the Kidney and Eye in Diabetes

A Paradigm Shift in the Management Approaches of Proliferative Diabetic Retinopathy: Role of Anti-VEGF Therapy

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