Intravitreal Injection of Therapeutic Agents

Peyman, Gholam A.; Lad, Eleonora M.; Moshfeghi, Darius M.

doi:10.1097/iae.0b013e3181a94f01

Cited by 221 publications

(142 citation statements)

References 444 publications

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“…[25][26][27][28]66 The advantages of intraocular injection are that high concentrations of drug can be achieved near the target tissue while minimizing systemic adverse effects. 66 However, repeated intraocular injection significantly increases the risk of ocular complications, including discomfort or pain, subconjunctival or vitreal hemorrhage, acute and sterile intraocular inflammation, uveitis, and endophthalmitis. 66,67 Reviews of clinical trials and patient charts to determine the safety of AMD intravitreal therapies have found that incidence rates for endophthalmitis range from 0 to 0.16%.…”

Section: Discussionmentioning

confidence: 99%

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Lambert

Carlson

Ende

et al. 2015

Trans. Vis. Sci. Tech.

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Purpose: We examined the efficacy of an extended-release drug delivery system, nanosponge (NS) encapsulated compounds, administered intravitreally to lower intraocular pressure (IOP) in mice.Methods: Bilateral ocular hypertension was induced in mice by injecting microbeads into the anterior chamber. Hypertensive mice received NS loaded with ocular hypotensive drugs via intravitreal injection and IOP was monitored. Retinal deposition and retinal ganglion cell (RGC) uptake of Neuro-DiO were examined following intravitreal injection of Neuro-DiO-NS using confocal microscopy.Results: Brimonidine-loaded NS lowered IOP 12% to 30% for up to 6 days (P , 0.02), whereas travoprost-NS lowered IOP 19% to 29% for up to 4 days (P , 0.02) compared to saline injection. Three bimatoprost NS were tested: a 400-nm NS and two 700-nm NS with amorphous (A-NS) or amorphous/crystalline (AC-NS) crosslinkers. A single injection of 400 nm NS lowered IOP 24% to 33% for up to 17 days compared to saline, while A-NS and AC-NS lowered IOP 22% to 32% and 18% to 26%, respectively, for up to 32 days (P , 0.046). Over time retinal deposition of Neuro-DiO increased from 19% to 71%; Neuro-DiO released from NS was internalized by RGCs.Conclusions: A single injection of NS can effectively deliver ocular hypotensive drugs in a linear and continuous manner for up to 32 days. Also, NS may be effective at targeting RGCs, the neurons that degenerate in glaucoma.Translational Relevance: Patient compliance is a major issue in glaucoma. The use of NS to deliver a controlled, sustained release of therapeutics could drastically reduce the number of patients that progress to vision loss in this disease.

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Section: Discussionmentioning

confidence: 99%

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Lambert

Carlson

Ende

et al. 2015

Trans. Vis. Sci. Tech.

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“…Due to the chronic nature of the disease and short intravitreal half-life of bevacizumab (5), frequent intravitreal injections are indicated to maintain therapeutic concentrations at the retina/choroid. Such frequent administrations are inconvenient and cause potential ocular complications such as endophthalmitis, retinal detachment, retinal hemorrhage and, more importantly, patient noncompliance (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Novel Pentablock Copolymer-Based Nanoparticulate Systems for Sustained Protein Delivery

et al. 2014

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Abstract. The design, synthesis, and application of novel biodegradable and biocompatible pentablock (PB) copolymers, i.e., polyglycolic acid-polycaprolactone-polyethylene glycol-polycaprolactonepolyglycolic acid (PGA-PCL-PEG-PCL-PGA) and polylactic acid-polycaprolactone-polyethylene glycolpolycaprolactone-polylactic acid (PLA-PCL-PEG-PCL-PLA) for sustained protein delivery, are reported. The PB copolymers can be engineered to generate sustained delivery of protein therapeutics to the posterior segment of the eye. PB copolymers with different block arrangements and molecular weights were synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance ( 1 H-NMR), gel permeation chromatography (GPC), and X-ray diffraction (XRD) spectroscopy. Immunoglobulin G (IgG) was selected as a model protein due to its structural similarity to bevacizumab. The influence of polymer molecular weight, composition, and isomerism on formulation parameters such as entrapment efficiency, drug loading, and in vitro release profile was delineated. Crystallinity and molecular weight of copolymers exhibited a substantial effect on formulation parameters. A secondary structure of released IgG was confirmed by circular dichroism (CD) spectroscopy. In vitro cytotoxicity, cell viability, and biocompatibility studies performed on human retinal pigment epithelial cells (ARPE-19) and/or macrophage cell line (RAW 264.7) demonstrated PB copolymers to be excellent biomaterials. Novel PB polymers may be the answer to the unmet need of a sustained release protein formulation.

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“…Intravitreal injections are widely used nowadays as an inoffice procedure to deliver anti-infectious, anti-inflammatory, anticancer, anti-VEGF medications, as well as gas into the eye (1). One of the most common side effects due to this treatment is discomfort or pain at the site of injection.…”

Section: Introductionmentioning

confidence: 99%

Shortening Ocular Pain Duration following Intravitreal Injections

Rifkin

Schaal

2012

European Journal of Ophthalmology

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Purpose. To determine ocular pain duration after routine in-office intravitreal injection and to determine whether topical eyedrops are beneficial in increasing patient comfort. Methods. Forty injection-naïve patients receiving routine intravitreal injections of bevacizumab for age-related macular degeneration were randomized into 3 groups: group 1 (control, no drops), group 2 (generic artificial tears), and group 3 (ketorolac tromethamine 0.4% eyedrops). Those who received topical medications were given a Visual Analog Pain score survey and asked to record their pain on a scale from 0 (no distress) to 10 (unbearable distress) daily until a score of 0 was achieved, at which point they were instructed to discontinue use of their given drops. Self-reported pain scores were assessed. Results. Pain after routine intravitreal injection lasts on average between 3 and 7 days. Patients receiving topical ketorolac eyedrops reported the fewest average number of pain days (2.25±1.22) vs patients receiving artificial tears (3.54±1.13) or those who received no postprocedure eyedrops (5.13±1.25); p<0.05. At most, patients receiving ketorolac eyedrops reported 3 days of recordable pain. Those who received artificial tears reported at most 5 days of recordable pain, and patients who did not receive any postprocedure eyedrops reported at most 7 days of recordable pain. Conclusions. Pain after intravitreal injection is generally mild, may be reduced by postinjection topical ketorolac eyedrops, and lasts less than 1 week.

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Intravitreal Injection of Therapeutic Agents

Abstract: The IVI technique is a valuable tool that can be tailored to the disease process of interest based on the pharmacological agent selected. This review provides the reader with a comprehensive summary of the IVI technique and its multitude of uses.

Cited by 221 publications

References 444 publications

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Novel Pentablock Copolymer-Based Nanoparticulate Systems for Sustained Protein Delivery

Shortening Ocular Pain Duration following Intravitreal Injections

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