Online citations, reference lists, and bibliographies.
← Back to Search

Topical Sustained Drug Delivery To The Retina With A Drug-eluting Contact Lens.

Amy E. Ross, Lokendrakumar C. Bengani, Rehka Tulsan, D. Maidana, Borja Salvador-Culla, H. Kobashi, P. E. Kolovou, Hualei Zhai, K. Taghizadeh, Liangju Kuang, M. Mehta, D. Vavvas, D. Kohane, Joseph B. Ciolino
Published 2019 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
Intravitreal injections and implants are used to deliver drugs to the retina because therapeutic levels of these medications cannot be provided by topical administration (i.e. eye drops). In order to reach the retina, a topically applied drug encounters tear dilution, reflex blinking, and rapid fluid drainage that collectively reduce the drug's residence time on the ocular surface. Residing under the tears, the cornea is the primary gateway into the eye for many topical ophthalmic drugs. We hypothesized that a drug-eluting contact lens that rests on the cornea would therefore be well-suited for delivering drugs to the eye including the retina. We developed a contact lens based dexamethasone delivery system (Dex-DS) that achieved sustained drug delivery to the retina at therapeutic levels. Dex-DS consists of a dexamethasone-polymer film encapsulated inside a contact lens. Rabbits wearing Dex-DS achieved retinal drug concentrations that were 200 times greater than those from intensive (hourly) dexamethasone drops. Conversely, Dex-DS demonstrated lower systemic (blood serum) dexamethasone concentrations. In an efficacy study in rabbits, Dex-DS successfully inhibited retinal vascular leakage induced by intravitreal injection of vascular endothelial growth factor (VEGF). Dex-DS was found to be safe in a four-week repeated dose biocompatibility study in healthy rabbits.
This paper references
10.1001/ARCHOPHT.1968.03850040368003
Corneal thickness after topical corticosteroid therapy.
J. Baum (1968)
10.1016/0002-9394(67)91314-1
Response of rabbits to corticosteroids. I. Influence on growth, intraocular pressure and lens transparency.
D. Wood (1967)
10.1016/J.ADDR.2005.09.004
Topical and systemic drug delivery to the posterior segments.
Patrick M Hughes (2005)
10.1001/ARCHOPHT.1988.01060140852025
Visual field constriction caused by colored contact lenses.
M. Insler (1988)
10.1021/IE0507934
Modeling Ophthalmic Drug Delivery by Soaked Contact Lenses
Chi-Chung Li (2006)
10.1167/iovs.13-13187
The TFOS International Workshop on Contact Lens Discomfort: report of the contact lens interactions with the ocular surface and adnexa subcommittee.
N. Efron (2013)
10.1111/J.1600-0420.2007.00885.X
Topical and systemic absorption in delivery of dexamethasone to the anterior and posterior segments of the eye.
H. Sigurdsson (2007)
10.2165/00002018-200225010-00004
Locally Administered Ocular Corticosteroids
C. McGhee (2002)
10.2147/OPTH.S28083
Dendritic immune cell densities in the central cornea associated with soft contact lens types and lens care solution types: a pilot study
C. Sindt (2012)
Effect of dexamethasone on corneal endothelial function in Fuchs' dystrophy.
S. Wilson (1988)
10.3928/1081-597X-20000701-07
Topical tetracaine with bandage soft contact lens pain control after photorefractive keratectomy.
H. Brilakis (2000)
10.1016/0002-9394(67)91315-3
Response of rabbits to corticosteroids. II. Influence of topical therapy on lens, aqueous humor, serum and urine composition.
C. Wood (1967)
10.1136/bjo.76.11.681
Pharmacokinetics of ophthalmic corticosteroids.
C. McGhee (1992)
10.1089/JOP.1987.3.185
Steroid-induced ocular hypertension in the rabbit: a model using subconjunctival injections.
D. Hester (1987)
10.1038/eye.2013.107
Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature
K. G. Falavarjani (2013)
10.1080/02713680600719036
Safety and Pharmacokinetics of an Intravitreal Biodegradable Implant of Dexamethasone Acetate in Rabbit Eyes
S. L. Fialho (2006)
Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes.
M. Lemp (1995)
10.1016/j.preteyeres.2010.03.001
Preservatives in eyedrops: The good, the bad and the ugly
C. Baudouin (2010)
10.1016/j.survophthal.2012.08.003
Intraocular pressure monitoring post intravitreal steroids: a systematic review.
W. Kiddee (2013)
10.1007/s11095-010-0159-x
Biodegradable Implants for Sustained Drug Release in the Eye
S. Lee (2010)
10.4239/wjd.v7.i16.333
Treatment of diabetic retinopathy: Recent advances and unresolved challenges.
M. Stewart (2016)
10.1111/j.1463-5224.2012.01041.x
Normal corneal thickness measurements in pigmented rabbits using spectral-domain anterior segment optical coherence tomography.
X. Wang (2013)
10.1016/j.exer.2015.06.002
Animal models of glucocorticoid-induced glaucoma.
D. Overby (2015)
10.2174/1872211308666140130093301
Drug delivery to the back of the eye following topical administration: an update on research and patenting activity.
S. H. S. Boddu (2014)
10.1080/08820530902802161
Contact Lenses for Drug Delivery
Joseph B. Ciolino (2009)
10.1016/J.ORET.2018.11.002
Loss to Follow-up After Intravitreal Anti-Vascular Endothelial Growth Factor Injections in Patients with Diabetic Macular Edema.
Xinxiao Gao (2019)
10.1016/S0014-4835(70)80042-2
Effect of topical application of hydrocortisone on the corneal thickness.
T. Hara (1970)
10.1001/jamaophthalmol.2018.3578
Loss to Follow-up Among Patients With Neovascular Age-Related Macular Degeneration Who Received Intravitreal Anti–Vascular Endothelial Growth Factor Injections
Anthony Obeid (2018)
10.4103/0975-7406.149810
An alternative in situ gel-formulation of levofloxacin eye drops for prolong ocular retention
Himanshu Gupta (2015)
10.1016/J.SURVOPHTHAL.2003.12.009
Determinants of eye drop size.
L. Van Santvliet (2004)
10.1167/iovs.14-14386
CD147 required for corneal endothelial lactate transport.
Shimin Li (2014)
10.1111/j.2042-7158.1986.tb04611.x
A comparison of the effect of viscosity on the precorneal residence of solutions in rabbit and man
I. Zaki (1986)
10.1080/02713683.2017.1418893
Measurement of the Retention Time of Different Ophthalmic Formulations with Ultrahigh-Resolution Optical Coherence Tomography
C. Gagliano (2018)
10.1167/iovs.08-2826
A drug-eluting contact lens.
Joseph B. Ciolino (2009)
10.1159/000050858
Effects of Contact Lenses on Corneal Endothelium – A Morphological and Functional Study
S. Chang (2001)
10.1081/E-EBPP-120013950
Polylactic-co-Glycolic Acid (PLGA)
K. Avgoustakis (2015)
10.1016/J.IJPHARM.2006.11.028
Encapsulation of dexamethasone into biodegradable polymeric nanoparticles.
Carolina Gómez-Gaete (2007)
Effects of dexamethasone, progesterone, and testosterone on IOP and GAGs in the rabbit eye.
P. Knepper (1985)
10.1016/S0161-6420(95)30926-8
Controlled evaluation of a bandage contact lens and a topical nonsteroidal anti-inflammatory drug in treating traumatic corneal abrasions.
E. Donnenfeld (1995)
10.2147/IJN.S6428
Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits
L. Zhang (2009)
10.1007/s00276-011-0889-4
White-to-white corneal diameter, pupil diameter, central corneal thickness and thinnest corneal thickness values of emmetropic subjects
J. Sanchis-Gimeno (2011)
Contact lens-induced edema in vitro. Pharmacology and metabolic considerations.
J. Huff (1991)
10.3390/ijms19092830
Ocular Drug Delivery: Role of Degradable Polymeric Nanocarriers for Ophthalmic Application
Cheng-Han Tsai (2018)
10.1016/J.EXER.2004.09.013
Corticosteroids inhibit VEGF-induced vascular leakage in a rabbit model of blood-retinal and blood-aqueous barrier breakdown.
J. Edelman (2005)
Physiologic changes of the cornea with contact lens wear.
T. Liesegang (2002)
A closed eye contact lens model of corneal inflammation. Part 1: Increased synthesis of cytochrome P450 arachidonic acid metabolites.
M. Conners (1995)
10.1016/j.ejphar.2007.12.033
Glucocorticoids shift arachidonic acid metabolism toward endocannabinoid synthesis: a non-genomic anti-inflammatory switch.
Renato Malcher-Lopes (2008)
10.1016/j.optom.2014.12.001
Tear exchange and contact lenses: a review.
A. Muntz (2015)
10.3109/02713688809031801
Comparison of conjunctival and corneal surface areas in rabbit and human.
M. Watsky (1988)
10.1001/ARCHOPHT.1989.01070020445052
Collagen shield enhancement of topical dexamethasone penetration.
D. Hwang (1989)
10.1007/BF01739643
Effect of corticosteroids on healing of the corneal endothelium in cats
A. Solomon (2005)
10.1167/iovs.11-8178
Topical dexamethasone-cyclodextrin microparticle eye drops for diabetic macular edema.
M. Tanito (2011)
10.1016/S0378-5173(03)00124-8
In vitro uptake and release studies of ocular pharmaceutical agents by silicon-containing and p-HEMA hydrogel contact lens materials.
C. Karlgard (2003)
10.1517/17425247.2013.821462
Contact lenses as a platform for ocular drug delivery
Lokendrakumar C. Bengani (2013)
10.1021/bm300520u
Localized Delivery of Dexamethasone from Electrospun Fibers Reduces the Foreign Body Response
Nathaniel Vacanti (2012)
10.1016/j.preteyeres.2009.12.002
The multifunctional choroid
D. Nickla (2010)
10.1136/bjo.63.9.646
Ocular changes in rabbits with corticosteroid-induced ocular hypertension.
U. Ticho (1979)
10.1097/ICL.0b013e31827d4f25
Uptake and Release Phenomena in Contact Lens Care by Silicone Hydrogel Lenses
L. Jones (2013)
10.1016/j.clae.2016.02.008
Changes in corneal Langerhans cell density during the first few hours of contact lens wear.
Yahya A. Alzahrani (2016)
10.1097/00006324-198701000-00006
Visual field loss with colored hydrogel lenses.
Josephson Je (1987)
Critical oxygen levels to avoid corneal edema for daily and extended wear contact lenses.
B. Holden (1984)
THE SIDE EFFECTS OF CORTICOSTEROIDS.
B. Becker (1964)
10.1111/j.1755-3768.2010.02016.x
A rabbit model of age‐dependant ocular hypertensive response to topical corticosteroids
Y. Qin (2012)
10.1001/ARCHOPHT.1974.01010010425011
Ocular penetration of prednisolone and the hydrophilic contact lens.
D. S. Hull (1974)
10.1097/ICL.0b013e3181b26c49
Uptake and Release of Dexamethasone Phosphate From Silicone Hydrogel and Group I, II, and IV Hydrogel Contact Lenses
A. Boone (2009)
10.1016/j.lfs.2013.12.020
Polymeric delivery systems for dexamethasone.
Justyna Urbańska (2014)
10.1076/ceyr.23.1.1.5422
Corneal epithelial VEGF and cytochrome P450 4B1 expression in a rabbit model of closed eye contact lens wear
V. Mastyugin (2001)
Drug delivery for posterior segment eye disease.
D. Geroski (2000)
10.1111/j.1444-0938.2010.00553.x
Drug delivery to the posterior segment of the eye through hydrogel contact lenses
C. Schultz (2011)
10.1038/sj.eye.6701895
Corticosteroid-induced glaucoma: a review of the literature
J. Kersey (2006)
An experimental model of preretinal neovascularization in the rabbit.
A. Antoszyk (1991)
10.1016/S0002-9394(99)00129-4
High concentration of dexamethasone in aqueous and vitreous after subconjunctival injection.
O. Weijtens (1999)
10.1016/j.ophtha.2016.06.038
Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys.
Joseph B. Ciolino (2016)
10.1111/aos.12560
Topical dexamethasone–cyclodextrin microparticle eye drops for uveitic macular oedema
S. Krag (2014)
10.1016/j.lfs.2018.09.050
Thermo‐sensitive gel in glaucoma therapy for enhanced bioavailability: In vitro characterization, in vivo pharmacokinetics and pharmacodynamics study
Youmei Zeng (2018)
10.1001/ARCHOPHT.1996.01100140208016
Corticosteroid therapy of eye disease. Fifty years later.
M. Raizman (1996)
10.1691/PH.2008.7322
Topical drug delivery to the posterior segment of the eye: anatomical and physiological considerations.
T. Loftsson (2008)
10.1007/s11095-018-2519-x
Topical Drug Delivery to the Posterior Segment of the Eye: Addressing the Challenge of Preclinical to Clinical Translation
G. Rodrigues (2018)
10.1080/09273948.2016.1184284
Common and Rare Ocular Side-effects of the Dexamethasone Implant
Janelle M Fassbender Adeniran (2017)
10.1167/iovs.10-6935
A prototype antifungal contact lens.
Joseph B. Ciolino (2011)
10.1248/CPB.52.1290
A pharmacokinetic model for ocular drug delivery.
K. Tojo (2004)
The effects of ophthalmic solutions on the transmission of light through hydrogel lenses.
G. Bergen (1990)
10.1016/j.biomaterials.2013.09.032
In vivo performance of a drug-eluting contact lens to treat glaucoma for a month.
Joseph B. Ciolino (2014)
10.1016/S0161-6420(02)01176-4
Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate.
O. Weijtens (2002)
10.1097/IJG.0b013e31814b990d
Barriers to Glaucoma Drug Delivery
D. Ghate (2008)
10.1097/01.ICL.0000107181.42704.D8
Therapeutic Use of a Lotrafilcon A Silicone Hydrogel Soft Contact Lens as a Bandage After LASEK Surgery
J. Szaflik (2004)
10.1016/j.jconrel.2008.01.004
Evaluation of in vivo-in vitro release of dexamethasone from PLGA microspheres.
B. S. Zolnik (2008)
10.1111/aos.12744
Topical dexamethasone–cyclodextrin nanoparticle eye drops for non‐infectious Uveitic macular oedema and vitritis – a pilot study
S. Shulman (2015)
10.1001/ARCHOPHT.1970.00990030005003
Corneal swelling caused by contact lens wear.
R. Mandell (1970)
10.1016/S0896-1549(02)00066-4
The evolution in therapeutic contact lenses.
C. Shah (2003)



This paper is referenced by
10.1002/adfm.201908476
Material, Immunological, and Practical Perspectives on Eye Drop Formulation
Naomi H. Bennett (2020)
10.1080/17425247.2020.1787983
Commercialization challenges for drug eluting contact lenses
Olivia Lanier (2020)
10.1016/j.ijpharm.2020.119688
Sustained delivery of epalrestat to the retina using PEGylated solid lipid nanoparticles laden contact lens.
Yanni Zhu (2020)
10.1155/2020/8476025
A Facile Route to Fabricate CS/GO Composite Film for the Application of Therapeutic Contact Lenses
Chen Pin (2020)
10.1016/j.actbio.2020.08.013
Steroid-eluting contact lenses for corneal and intraocular inflammation.
Lokendrakumar C. Bengani (2020)
10.1016/j.jddst.2020.101949
Ketotifen loaded solid lipid nanoparticles laden contact lens to manage allergic conjunctivitis
T. Zhang (2020)
10.2174/0929867326666190726121711
Pharmacological Advances in the Treatment of Age-related Macular Degeneration.
M. Gil-Martínez (2020)
10.1080/09205063.2020.1712175
Therapeutic contact lenses for ophthalmic drug delivery: major challenges
Xiu-ju Zhang (2020)
10.1016/j.ejpb.2020.09.010
Design of circular-ring film embedded contact lens for improved compatibility and sustained ocular drug delivery.
Yidan Wei (2020)
10.1016/j.jsps.2020.01.008
Bioresorbable hydrogels prepared by photo-initiated crosslinking of diacrylated PTMC-PEG-PTMC triblock copolymers as potential carrier of antitumor drugs
Yuandou Wang (2020)
10.1039/d0tb01508c
Reversible antibiotic loading and pH-responsive release from polymer brushes on contact lenses for therapy and prevention of corneal infections.
Yishun Guo (2020)
10.1016/j.actbio.2020.08.025
Evaluation of commercial soft contact lenses for ocular drug delivery: a review.
Xin Fan (2020)
10.1039/c9bm01582e
Cytosine-functionalized bioinspired hydrogels for ocular delivery of antioxidant transferulic acid.
Angela Varela-García (2020)
10.3390/app10155151
Contact Lenses as Drug Delivery System for Glaucoma: A Review
A. Peral (2020)
Semantic Scholar Logo Some data provided by SemanticScholar