&lt;p&gt;Therapeutic Potential of the Ranibizumab Port Delivery System in the Treatment of AMD: Evidence to Date&lt;/p&gt;

Chen, Eric R.; Kaiser, Peter K.

doi:10.2147/opth.s194234

Cited by 32 publications

(32 citation statements)

References 27 publications

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“…Despite recent advances in the treatment of CNV for wet AMD with anti-vascular endothelial growth factor A (VEGF) agents [ 23 ], anti-VEGF treatments remain ineffective for some patients and a significant proportion of these patients still develop severe visual loss and progress to legal blindness over time [ 24 ]. Recent evidences point to the possibility of an association between anti-VEGF therapy and progression of geographic atrophy [ 25 ]. There is currently no satisfactory treatment for the dry form of AMD, although clinical trials have investigated an increasing number of therapeutic options [ 26 ] (Table 1 ).…”

Section: Amd Pathophysiologymentioning

confidence: 99%

The complement system in age-related macular degeneration

Armento

Ueffing

Clark

2021

Cell. Mol. Life Sci.

140

128

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Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.

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Section: Amd Pathophysiologymentioning

confidence: 99%

The complement system in age-related macular degeneration

Armento

Ueffing

Clark

2021

Cell. Mol. Life Sci.

140

128

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“…The success of traditional anti-VEGF therapies raised the question of whether a longer-acting ranibizumab could be delivered via an implantable reservoir. Thus, the Port Delivery System (PDS) was developed, allowing for the continuous release of ranibizumab into the vitreous via passive diffusion [ 38 ]. PDS is intended to reduce the frequency of intravitreal injections and potentially allow patients with nAMD to go several months before needing a refill of the implant.…”

Section: Emerging Neovascular Amd Therapiesmentioning

confidence: 99%

New and Innovative Treatments for Neovascular Age-Related Macular Degeneration (nAMD)

Patel

Sheth²

2021

JCM

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Age-related macular degeneration (AMD) is one of the most common causes of vision loss. Advanced forms of AMD are seen in primarily two types—neovascular AMD (nAMD) with the presence of choroid neovascularization and non-neovascular AMD (nnAMD) with geographic atrophy. Neovascular AMD is characterized by choroidal neovascularization (CNV), which leads to a cascade of complications, including exudation, leakage, and ultimately fibrosis with photoreceptor loss. Inhibition of VEGF represents the current standard of care. However, there is a tremendous gap between the outcomes in randomized clinical trials and real-world settings. New agents for nAMD might offer the potential to improve treatment outcomes and reduce treatment of frequent intravitreal injections. We summarize all the newer molecules, their pivotal clinical trial results, and their unique mechanisms of action; these include longer-acting agents, combination strategies, sustained release, and genetic therapies.

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“…Another clinical trial studied the efficacy of a refillable ranibizumab port delivery system in patients with a neovascular form of AMD (Lucentis, Genentech), which consists of a sustained release reservoir (the study has now passed phase 1). 64 , 65 This system is aimed to reduce the number of required repeated IVIs. The study also showed that the mean number of system refills was 4.8/patient/12 months.…”

Section: Discussionmentioning

confidence: 99%

Novel Needle for Intravitreal Drug Delivery: Comparative Study of Needle Tip Aspirates, Injection Stream and Penetration Forces

Lytvynchuk¹,

Petrovski²,

Dam³

et al. 2021

OPTH

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Purpose To study the efficacy of a novel needle for intravitreal injection (IVI) in comparison to the conventional needle under experimental conditions. Methods The newly designed 30-gauge (G) needle (NDN) (EP 18158 542.3, patent pending) with occluded outer orifice and a side port for drug delivery was compared to the conventional standard hypodermic 30 G needle for IVI (SHN). An animal study to obtain needle tip aspirates was performed on 10 albino rat eyes. During IVIs, cellular content, which was cut by the needle tip, was aspirated. Cellular material was studied in regard to cell types and their quantity. The injection stream was studied using trypan blue dye in vitro and pig cadaver eyes. The penetration force was tested on polyurethane Testing Foil Strips PU 04 (Melab, Leonberg, Germany) by applying a velocity of 100 mm/min. The results were analyzed using descriptive statistics, correlation matrices and t -test methods with p <0.05 as statistically significant. Results Cytological analysis of the needle aspirates showed the presence of cellular content in each case. The amount of conjunctival, ciliary body epithelial cells and granulated basophilic protein sediments (sign of cellular damage) in the case of the NDN tips was significantly lower compared to the SHN. The average penetration force of the NDN was 0.791 N, and in the case of the SHN was 0.566 N. The injection stream study revealed a difference in the initial injection phase between the two needle types, although the diffuse filling of the vitreous area which surrounded the needle tip appeared to be similar. Discussion The NDN demonstrated superior performance with regard to a significantly reduced number of cells being captured by the needle tip. Delivery of the injected fluid into the vitreous cavity was comparable. In order to investigate superior properties of the NDN needle design, further studies with improved prototypes would be necessary.

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<p>Therapeutic Potential of the Ranibizumab Port Delivery System in the Treatment of AMD: Evidence to Date</p>

Cited by 32 publications

References 27 publications

The complement system in age-related macular degeneration

The complement system in age-related macular degeneration

New and Innovative Treatments for Neovascular Age-Related Macular Degeneration (nAMD)

Novel Needle for Intravitreal Drug Delivery: Comparative Study of Needle Tip Aspirates, Injection Stream and Penetration Forces

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