Extraocular, periocular, and intraocular routes for sustained drug delivery for glaucoma

Kompella, Uday B.; Hartman, Rachel R.; Patil, Madhoosudan A.

doi:10.1016/j.preteyeres.2020.100901

Cited by 63 publications

(86 citation statements)

References 207 publications

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“…In the current study, the importance of the administration route and the nature of the device in the observed effect has also been demonstrated. The intracameral route is used for the administration of antibiotics and recently several intracameral implants are undertaking clinical trials or are already commercialized [46]. In the case of implants and from a clinical point of view, one of the side effects of the intracameral implantation is related to the iridocorneal angle.…”

Section: Discussionmentioning

confidence: 99%

“…In the case of implants and from a clinical point of view, one of the side effects of the intracameral implantation is related to the iridocorneal angle. In fact, the use of therapeutic devices such as the case of Durysta, an implant made from PLGA and bimatoprost (Allergan, Irvine, CA, USA), is restricted in patients with small angle or any issue that could promote the deposit of the device in the inferior angle [46]. Taking into account this mentioned side effect, we used the microspheres to promote an obstruction of the trabecular meshwork which in turn promotes an increase of IOP.…”

Section: Discussionmentioning

confidence: 99%

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Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration

et al. 2021

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Progressive degeneration of neuroretinal tissue with maintained elevated intraocular pressure (IOP) to simulate chronic glaucoma was produced by intracameral injections of poly (lactic-co-glycolic) acid (PLGA) microspheres (Ms) in rat eyes. The right eye of 39 rats received different sizes of PLGA-Ms (2 µL suspension; 10% w/v): 14 with 38–20 µm Ms (Ms38/20 model) and 25 with 20–10 µm particles (Ms20/10 model). This novel glaucoma animal model was compared to the episcleral vein sclerosis (EPI) model (25 eyes). Injections were performed at baseline, two, four and six weeks. Clinical signs, IOP, retina and optic nerve thicknesses (using in vivo optical coherence tomography; OCT), and histological studies were performed. An IOP increment was observed in all three groups, however, the values obtained from the PLGA-Ms injection resulted lower with a better preservation of the ocular surface. In fact, the injection of Ms20/10 created a gentler, more progressive, and more sustained increase in IOP. This IOP alteration was correlated with a significant decrease in most OCT parameters and in histological ganglion-cell count for the three conditions throughout the eight-week follow-up. In all cases, progressive degeneration of the retina, retinal ganglion cells and optic nerve, simulating chronic glaucoma, was detected by OCT and corroborated by histological study. Results showed an alternative glaucoma model to the well-known episcleral vein model, which was simpler to perform, more reproducible and easier to monitor in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration

et al. 2021

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“…In March 2020, the US Food and Drug Administration (FDA) approved the bimatoprost implant Durysta™ by Allergan plc to lower IOP in human open‐angle glaucoma (OAG) and ocular hypertension patients. Other implants for sustained intraocular drug release are in preclinical and clinical trials 32,33 …”

Section: Glaucoma—definition and Current Therapiesmentioning

confidence: 99%

Looking into the future: Gene and cell therapies for glaucoma

Komàromy

Koehl

Park

2021

Veterinary Ophthalmology

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Glaucoma is a complex group of optic neuropathies that affects both humans and animals. Intraocular pressure (IOP) elevation is a major risk factor that results in the loss of retinal ganglion cells (RGCs) and their axons. Currently, lowering IOP by medical and surgical methods is the only approved treatment for primary glaucoma, but there is no cure, and vision loss often progresses despite therapy. Recent technologic advances provide us with a better understanding of disease mechanisms and risk factors; this will permit earlier diagnosis of glaucoma and initiation of therapy sooner and more effectively. Gene and cell therapies are well suited to target these mechanisms specifically with the potential to achieve a lasting therapeutic effect. Much progress has been made in laboratory settings to develop these novel therapies for the eye. Gene and cell therapies have already been translated into clinical application for some inherited retinal dystrophies and age‐related macular degeneration (AMD). Except for the intravitreal application of ciliary neurotrophic factor (CNTF) by encapsulated cell technology for RGC neuroprotection, there has been no other clinical translation of gene and cell therapies for glaucoma so far. Possible application of gene and cell therapies consists of long‐term IOP control via increased aqueous humor drainage, including inhibition of fibrosis following filtration surgery, RGC neuroprotection and neuroregeneration, modification of ocular biomechanics for improved IOP tolerance, and inhibition of inflammation and neovascularization to prevent the development of some forms of secondary glaucoma.

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“…Moreover, eyedrops medications are characterised by a pulsatile drug-delivery, with a concentration peak followed by a tough until the next drop instillation [18]. Consequently, drug effect may not be constant over time, and IOP may change during the day [18].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, eyedrops have low bioavailability because only 1-7% of the drug is absorbed by the eye [18]. In particular, the lacrimal drainage consequent to blinking removes about 80% of the instilled drop [19].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Efficacy of Contact Lens Drug-Delivery Systems in Glaucoma Management. A Systematic Review

et al. 2021

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Adherence is crucial in medical glaucoma therapy, although half of the patients skip eyedrops. In recent years alternative drug-delivery systems have been developed. One of the most promising seems the contact lens (CL). This systematic review aims to present the in vivo efficacy of different CL drug-delivery systems. A total of 126 studies were identified following a literature search adhering to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. After full-text evaluation, 19 studies about CL drug-delivery systems were included. To date, the following drug-delivery systems have been investigated in vivo: drug-soaked CL, CL with physical barriers (vitamin E), molecularly imprinted CL, CL with implants, and nanoparticle-loaded CL. Nanoparticle-loaded CL and CL with implants seem the most promising drug-delivery systems, although initial burst drug release and patient acceptance may limit their widespread use in current practice. Clinical trials are warranted to understand the role of CL as a drug-delivery system in improving glaucomatous patient care.

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Extraocular, periocular, and intraocular routes for sustained drug delivery for glaucoma

Cited by 63 publications

References 207 publications

Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration

Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration

Looking into the future: Gene and cell therapies for glaucoma

In Vivo Efficacy of Contact Lens Drug-Delivery Systems in Glaucoma Management. A Systematic Review

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