Topical ophthalmic administration: Can a drug instilled onto the ocular surface exert an effect at the back of the eye?

Topical ophthalmic instillation is an appealing strategy to deliver drugs to the back of the eye to treat retinal diseases such as neovascular age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, and glaucomatous optic neuropathy. It has several advantages such as being no...

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Published inFrontiers in Drug Delivery Vol. 2
Main Author del Amo, Eva M.
Format Journal Article
LanguageEnglish
Published 08.09.2022
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Abstract Topical ophthalmic instillation is an appealing strategy to deliver drugs to the back of the eye to treat retinal diseases such as neovascular age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, and glaucomatous optic neuropathy. It has several advantages such as being non-invasive and user-friendly, e.g., allowing self-administration. However, the main obstacle has been how to achieve therapeutic drug concentrations in the retina due to the eye’s protective mechanisms, flows, and barriers. Less than 4% of the instilled drug dose enters the anterior chamber, and much less is expected to reach the posterior segment. It is crucial to understand a drug’s topical pharmacokinetics in humans and how one can extrapolate data from rabbits to humans. In this review, the available data on the retina and vitreous drug concentrations from pharmacokinetics studies conducted in human patients and rabbits have been compiled, together with the critical physiological factors to be considered for this route of administration. Improvements in the design of preclinical studies are suggested to increase their translatability to the treatment of human patients. Finally, the current status of clinical trials with topical ophthalmic formulations intended to treat the back of the eye is depicted. At present, no topical ophthalmic formulations to treat neovascular age-related macular degeneration or other retinal neurodegenerative illnesses have reached the market.
AbstractList Topical ophthalmic instillation is an appealing strategy to deliver drugs to the back of the eye to treat retinal diseases such as neovascular age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, and glaucomatous optic neuropathy. It has several advantages such as being non-invasive and user-friendly, e.g., allowing self-administration. However, the main obstacle has been how to achieve therapeutic drug concentrations in the retina due to the eye’s protective mechanisms, flows, and barriers. Less than 4% of the instilled drug dose enters the anterior chamber, and much less is expected to reach the posterior segment. It is crucial to understand a drug’s topical pharmacokinetics in humans and how one can extrapolate data from rabbits to humans. In this review, the available data on the retina and vitreous drug concentrations from pharmacokinetics studies conducted in human patients and rabbits have been compiled, together with the critical physiological factors to be considered for this route of administration. Improvements in the design of preclinical studies are suggested to increase their translatability to the treatment of human patients. Finally, the current status of clinical trials with topical ophthalmic formulations intended to treat the back of the eye is depicted. At present, no topical ophthalmic formulations to treat neovascular age-related macular degeneration or other retinal neurodegenerative illnesses have reached the market.
Author del Amo, Eva M.
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Cites_doi 10.1089/jop.2018.0138
10.1016/j.jddst.2018.04.007
10.1016/j.ijpharm.2021.121361
10.1111/j.1755-3768.1987.tb08493.x
10.1016/0039-6257(93)90141-s
10.1016/j.ejps.2020.105553
10.2174/1872211308666140130093301
10.3390/pharmaceutics14010134
10.1016/j.ejps.2012.05.007
10.1007/978-3-540-69469-4_2
10.1089/jop.1997.13.41
10.1007/978-3-030-76367-1_21
10.1016/j.ejpb.2021.06.003
10.4155/cli.15.5
10.1016/j.ejpb.2022.01.005
10.1159/000266930
10.1016/j.ejps.2017.07.027
10.1016/j.exer.2015.05.003
10.3109/02713683.2015.1050738
10.1007/978-3-030-27492-4_6
10.1016/j.addr.2017.12.008
10.1007/978-3-030-76367-1_1
10.1002/prp2.545
10.1007/s13346-015-0275-6
10.1167/iovs.16-19952
10.1016/j.survophthal.2021.12.003
10.1016/B978-0-12-374203-2.00169-X
10.1016/j.ejps.2018.07.034
10.1002/jps.2600760802
10.1016/0378-5173(87)90092-5
10.1021/acs.molpharmaceut.8b00038
10.1177/000331979404500603
10.1097/IAE.0b013e3181b094e6
10.1021/js9802594
10.1016/j.jconrel.2004.10.004
10.1586/eop.10.55
10.1016/j.ejpb.2015.01.003
10.1124/dmd.30.4.421
10.1089/jop.1995.11.489
10.1167/tvst.10.14.23
10.1016/0014-4835(78)90086-6
10.1038/s41573-021-00284-4
10.1016/j.preteyeres.2016.12.001
10.1002/jps.2600620712
10.1007/978-3-642-69222-2_2
10.3109/02713688809031801
10.1016/s0002-9394(14)78371-0
10.1111/bcp.13794
10.1021/acs.molpharmaceut.9b01024
10.1016/s0002-9394(14)70490-8
10.1016/j.ejps.2018.03.034
10.1016/j.ophtha.2014.05.013
10.1124/jpet.118.248427
10.1097/APO.0000000000000291
10.1016/j.ijpharm.2021.120332
10.1021/acs.molpharmaceut.0c01154
10.1021/acs.jmedchem.7b01731
10.1016/j.addr.2018.03.013
10.1016/0002-9394(86)90771-3
10.1016/j.ijpharm.2022.121515
10.1016/S2214-109X(13)70145-1
10.1136/bmjophth-2019-000398
10.1016/0014-4835(73)90185-1
10.1016/j.exer.2015.10.009
10.1007/s11095-010-0132-8
10.1016/0169-409X(95)00010-5
10.1152/ajpheart.00643.2003
10.1016/s0161-6420(00)00654-0
10.1016/s0002-9394(14)73646-3
10.1016/0378-5173(90)90215-p
10.1016/j.xphs.2020.09.051
10.1167/iovs.05-0945
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References B64
Heikkinen (B37) 2018; 123
Prausnitz (B67) 1998; 87
Slack (B84) 2022; 21
Wong (B91) 2014; 2
Mishima (B58) 1966; 5
Urtti (B87) 1990; 61
Rimpelä (B71) 2018; 15
Acheampong (B1) 1995; 11
del Amo (B26) 2022; 2022
Huupponen (B44) 2009; 65
del Amo (B25) 2022; 613
Sebag (B79) 1994; 45
Ahmed (B7) 1987; 38
Hopkins (B39)
Schoenwald (B77) 1997; 13
Adams (B4) 2018; 61
Tham (B86) 2014; 121
Varner (B89) 2015; 5
Alm (B10) 1973; 15
Holló (B38) 2006; 47
Sigurdsson (B83) 2005; 102
Balla (B16) 2022; 172
Loch (B54) 2012; 47
Yu (B92) 2004; 286
Naageshwaran (B59) 2022; 615
B78
Boddu (B18) 2014; 8
Acheampong (B2) 2002; 30
Lederer (B53) 1986; 101
Hayreh (B35) 2006
Petternel (B66) 2004; 45
Rimpelä (B70) 2018; 126
Rush (B73) 2016; 57
Barany (B17) 1949; 32
Hopkins (B40)
Kent (B48) 2001; 108
Sherman (B81) 1978; 27
Hammid (B34) 2021; 18
Kompella (B51) 2019; 35
Neervannan (B61) 2021
Ramsay (B68) 2018; 119
Chiou (B22) 1989; 21
Ambati (B11) 2000; 41
Fayyaz (B32) 2021; 166
del Amo (B27) 2017; 57
Joussen (B47) 2019; 85
Shikamura (B82) 2016; 41
Nilsson (B62) 2012
Huang (B42) 1989; 30
Shalaby (B80) 2022; 67
Chrai (B23) 1973; 62
Lau (B52) 2018; 126
O’Rourke (B63) 2021
Anand-Apte (B12) 2010
Hämäläinen (B33) 1997; 38
Maurice (B57) 1984
Ahmed (B8) 1985; 26
Kidron (B49) 2010; 27
Johannsdottir (B46) 2018; 45
Mandell (B56) 1993; 115
Naageshwaran (B60) 2021; 110
Askew (B14) 2018; 366
del Amo (B29) 2015; 95
B94
B95
Chastain (B21) 2016; 145
Alghamdi (B9) 2020
del Amo (B28) 2015; 137
Brubaker (B20) 1982; 80
Horita (B41) 2019; 7
Sahlin (B74) 1996; 122
Klar (B50) 2015; 56
Schauersberger (B76) 2002; 43
B15
Chua (B24) 2010; 5
Heier (B36) 2009; 29
Huang (B43) 2021; 10
Pelkonen (B65) 2017; 109
Watsky (B90) 1988; 7
Acheampong (B3) 1995; 23
Araie (B13) 1982; 26
Urtti (B88) 1993; 37
Khanna (B93) 2019; 4
Fayyaz (B31); 155
Boettger (B19) 2015; 56
Fayyaz (B30); 17
Agarwal (B5) 2016; 6
Järvinen (B45) 1995; 16
Löscher (B55) 2022; 14
Rodrigues (B72) 2018
Ahmed (B6) 1987; 76
Remington (B69) 2021
Samanta (B75) 2020; 9
Sripetch (B85) 2021; 597
References_xml – volume: 35
  start-page: 457
  year: 2019
  ident: B51
  article-title: ISOPT clinical hot topic panel discussion on ocular drug delivery
  publication-title: J. Ocular Pharmacol. Ther.
  doi: 10.1089/jop.2018.0138
– volume: 45
  start-page: 449
  year: 2018
  ident: B46
  article-title: Topical drug delivery to the posterior segment of the eye: Dexamethasone concentrations in various eye tissues after topical administration for up to 15 days to rabbits
  publication-title: J. Drug Deliv. Sci. Technol.
  doi: 10.1016/j.jddst.2018.04.007
– volume: 56
  start-page: 2294
  year: 2015
  ident: B19
  article-title: Topically administered regorafenib eye drops inhibit grade IV lesions in the non-human primate laser CNV model
  publication-title: Investig. Ophthalmol. Vis. Sci.
– volume: 5
  start-page: 264
  year: 1966
  ident: B58
  article-title: Determination of tear volume and tear flow
  publication-title: Investig. Ophthalmol.
– start-page: 288
  volume-title: Clinical anatomy and physiology of the visual system
  year: 2021
  ident: B69
  article-title: Clinical anatomy and physiology of the visual system
– start-page: 67
  volume-title: Ophthalmic drugs: Diagnostic and therapeutic uses
  ident: B40
  article-title: Ophthalmic dosage forms
– volume: 45
  start-page: 4930
  year: 2004
  ident: B66
  article-title: Fosfomycin in human vitreous: –in–vitro investigation of the protein binding of fosfomycin in human vitreous –fosfomycin levels in the vitreous cavity after intravenous administration
  publication-title: Investig. Ophthalmol. Vis. Sci.
– volume: 23
  start-page: 708
  year: 1995
  ident: B3
  article-title: Comparative ocular pharmacokinetics of brimonidine after a single dose application to the eyes of albino and pigmented rabbits
  publication-title: Drug Metab. Dispos.
– volume: 613
  start-page: 121361
  year: 2022
  ident: B25
  article-title: Ocular metabolism and distribution of drugs in the rabbit eye: Quantitative assessment after intracameral and intravitreal administrations
  publication-title: Int. J. Pharm.
  doi: 10.1016/j.ijpharm.2021.121361
– volume: 65
  start-page: 63
  year: 2009
  ident: B44
  article-title: The pharmacokinetics of ocularly applied timolol in rabbits
  publication-title: Acta Ophthalmol.
  doi: 10.1111/j.1755-3768.1987.tb08493.x
– volume: 37
  start-page: 435
  year: 1993
  ident: B88
  article-title: Minimizing systemic absorption of topically administered ophthalmic drugs
  publication-title: Surv. Ophthalmol.
  doi: 10.1016/0039-6257(93)90141-s
– ident: B64
– volume: 155
  start-page: 105553
  ident: B31
  article-title: Topical ocular pharmacokinetics and bioavailability for a cocktail of atenolol, timolol and betaxolol in rabbits
  publication-title: Eur. J. Pharm. Sci.
  doi: 10.1016/j.ejps.2020.105553
– volume: 8
  start-page: 27
  year: 2014
  ident: B18
  article-title: Drug delivery to the back of the eye following topical administration: An update on research and patenting activity
  publication-title: Recent Pat. Drug Deliv. Formul.
  doi: 10.2174/1872211308666140130093301
– volume: 30
  start-page: 684
  year: 1989
  ident: B42
  article-title: Paracellular permeability of corneal and conjunctival epithelia
  publication-title: Investig. Ophthalmol. Vis. Sci.
– volume: 14
  year: 2022
  ident: B55
  article-title: Topical drug delivery to the posterior segment of the eye
  publication-title: Pharmaceutics
  doi: 10.3390/pharmaceutics14010134
– volume: 47
  start-page: 131
  year: 2012
  ident: B54
  article-title: Determination of permeability coefficients of ophthalmic drugs through different layers of porcine, rabbit and bovine eyes
  publication-title: Eur. J. Pharm. Sci.
  doi: 10.1016/j.ejps.2012.05.007
– volume: 26
  start-page: 248
  year: 1982
  ident: B13
  article-title: Beta-adrenergic blockers: Ocular penetration and binding to the uveal pigment
  publication-title: Jpn. J. Ophthalmol.
– start-page: 25
  volume-title: Ocular blood flow
  year: 2012
  ident: B62
  article-title: Determination of ocular blood flows with the microsphere method
  doi: 10.1007/978-3-540-69469-4_2
– volume: 13
  start-page: 41
  year: 1997
  ident: B77
  article-title: Penetration into the anterior chamber via the conjunctival/scleral pathway
  publication-title: J. Ocul. Pharmacol. Ther.
  doi: 10.1089/jop.1997.13.41
– volume-title: Controlled release society focus group – ocular webinar, feb 2021
  year: 2021
  ident: B63
  article-title: The development and commercialization of sustained-release ocular drug delivery delivery technologies
  doi: 10.1007/978-3-030-76367-1_21
– volume: 166
  start-page: 155
  year: 2021
  ident: B32
  article-title: Ocular pharmacokinetics of atenolol, timolol and betaxolol cocktail: Tissue exposures in the rabbit eye
  publication-title: Eur. J. Pharm. Biopharm.
  doi: 10.1016/j.ejpb.2021.06.003
– volume: 5
  start-page: 457
  year: 2015
  ident: B89
  article-title: Ophthalmic pharmaceutical clinical trials: Design considerations
  publication-title: Clin. Investig. (Lond).
  doi: 10.4155/cli.15.5
– volume: 56
  start-page: 246
  year: 2015
  ident: B50
  article-title: Effects of the multi-kinase inhibitor regorafenib on ocular neovascularization
  publication-title: Investig. Ophthalmol. Vis. Sci.
– volume: 172
  start-page: 53
  year: 2022
  ident: B16
  article-title: Understanding dexamethasone kinetics in the rabbit tear fluid: Drug release and clearance from solution, suspension and hydrogel formulations
  publication-title: Eur. J. Pharm. Biopharm.
  doi: 10.1016/j.ejpb.2022.01.005
– start-page: 257
  volume-title: Ophthalmic drugs:diagnostic and therapeutic uses
  ident: B39
  article-title: Indications and contraindications for ophthalmic drugs
– volume: 21
  start-page: 406
  year: 1989
  ident: B22
  article-title: Microvascular access to the uveal tract in the rabbit eye for ocular pharmacologic studies.
  publication-title: Ophthalmic Res.
  doi: 10.1159/000266930
– volume: 109
  start-page: 162
  year: 2017
  ident: B65
  article-title: Melanin binding study of clinical drugs with cassette dosing and rapid equilibrium dialysis inserts
  publication-title: Eur. J. Pharm. Sci.
  doi: 10.1016/j.ejps.2017.07.027
– volume: 137
  start-page: 111
  year: 2015
  ident: B28
  article-title: Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data
  publication-title: Exp. Eye Res.
  doi: 10.1016/j.exer.2015.05.003
– volume: 41
  start-page: 653
  year: 2016
  ident: B82
  article-title: Hydrogel ring for topical drug delivery to the ocular posterior segment
  publication-title: Curr. Eye Res.
  doi: 10.3109/02713683.2015.1050738
– start-page: 17
  volume-title: Extemporaneous ophthalmic preparations
  year: 2020
  ident: B9
  article-title: Topical ophthalmic drug forms
  doi: 10.1007/978-3-030-27492-4_6
– volume: 126
  start-page: 23
  year: 2018
  ident: B70
  article-title: Implications of melanin binding in ocular drug delivery
  publication-title: Adv. Drug Deliv. Rev.
  doi: 10.1016/j.addr.2017.12.008
– volume: 43
  start-page: 1853
  year: 2002
  ident: B76
  article-title: -vitro investigation of the protein binding of different antibiotics in the human vitreous
  publication-title: Investig. Ophthalmol. Vis. Sci.
– start-page: 3
  volume-title: Ophthalmic product development: From bench to bedside
  year: 2021
  ident: B61
  article-title: Introduction and history of ophthalmic product development
  doi: 10.1007/978-3-030-76367-1_1
– volume: 7
  start-page: e00545
  year: 2019
  ident: B41
  article-title: Species differences in ocular pharmacokinetics and pharmacological activities of regorafenib and pazopanib eye-drops among rats, rabbits and monkeys
  publication-title: Pharmacol. Res. Perspect.
  doi: 10.1002/prp2.545
– volume: 6
  start-page: 634
  year: 2016
  ident: B5
  article-title: In vitro and ex vivo corneal penetration and absorption models
  publication-title: Drug Deliv. Transl. Res.
  doi: 10.1007/s13346-015-0275-6
– volume: 57
  start-page: 5864
  year: 2016
  ident: B73
  article-title: Administration of menadione, vitamin K3, ameliorates off-target effects on corneal epithelial wound healing due to receptor tyrosine kinase inhibition
  publication-title: Investig. Ophthalmol. Vis. Sci.
  doi: 10.1167/iovs.16-19952
– volume: 67
  start-page: 1062
  year: 2022
  ident: B80
  article-title: A review of potential novel glaucoma therapeutic options independent of intraocular pressure
  publication-title: Surv. Ophthalmol.
  doi: 10.1016/j.survophthal.2021.12.003
– start-page: 9
  volume-title: Encyclopedia of the eye
  year: 2010
  ident: B12
  article-title: Developmental anatomy of the retinal and choroidal vasculature
  doi: 10.1016/B978-0-12-374203-2.00169-X
– volume: 123
  start-page: 106
  year: 2018
  ident: B37
  article-title: Esterase activity in porcine and albino rabbit ocular tissues
  publication-title: Eur. J. Pharm. Sci.
  doi: 10.1016/j.ejps.2018.07.034
– volume: 76
  start-page: 583
  year: 1987
  ident: B6
  article-title: Physicochemical determinants of drug diffusion across the conjunctiva, sclera, and cornea
  publication-title: J. Pharm. Sci.
  doi: 10.1002/jps.2600760802
– volume: 38
  start-page: 9
  year: 1987
  ident: B7
  article-title: Disposition of timolol and inulin in the rabbit eye following corneal versus non-corneal absorption
  publication-title: Int. J. Pharm. X.
  doi: 10.1016/0378-5173(87)90092-5
– volume: 15
  start-page: 2174
  year: 2018
  ident: B71
  article-title: Binding of small molecule drugs to porcine vitreous humor
  publication-title: Mol. Pharm.
  doi: 10.1021/acs.molpharmaceut.8b00038
– volume: 45
  start-page: 429
  year: 1994
  ident: B79
  article-title: Effects of pentoxifylline on choroidal blood flow in nonproliferative diabetic retinopathy
  publication-title: Angiology
  doi: 10.1177/000331979404500603
– start-page: 1130
  volume-title: Eye
  year: 2006
  ident: B35
  article-title: Orbital vascular anatomy
– volume: 2022
  start-page: 59
  year: 2022
  ident: B26
  article-title: Pharmacokinetic models: Indispensable tools for ophthalmic drug development
  publication-title: ONdrugDelivery
– volume: 26
  start-page: 584
  year: 1985
  ident: B8
  article-title: Importance of the noncorneal absorption route in topical ophthalmic drug delivery
  publication-title: Investig. Ophthalmol. Vis. Sci.
– volume: 29
  start-page: 1310
  year: 2009
  ident: B36
  article-title: Vitreous nonsteroidal antiinflammatory drug concentrations and prostaglandin E2 levels in vitrectomy patients treated with ketorolac 0.4%, bromfenac 0.09%, and nepafenac 0.1%.
  publication-title: Retina
  doi: 10.1097/IAE.0b013e3181b094e6
– volume: 87
  start-page: 1479
  year: 1998
  ident: B67
  article-title: Permeability of cornea, sclera, and conjunctiva: A literature analysis for drug delivery to the eye.
  publication-title: J. Pharm. Sci.
  doi: 10.1021/js9802594
– volume: 102
  start-page: 255
  year: 2005
  ident: B83
  article-title: Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration
  publication-title: J. Control. Release
  doi: 10.1016/j.jconrel.2004.10.004
– volume: 5
  start-page: 627
  year: 2010
  ident: B24
  article-title: Neuroprotective agents in glaucoma therapy: Recent developments and future directions
  publication-title: Expert Rev. Ophthalmol.
  doi: 10.1586/eop.10.55
– volume: 95
  start-page: 215
  year: 2015
  ident: B29
  article-title: Intravitreal clearance and volume of distribution of compounds in rabbits: In silico prediction and pharmacokinetic simulations for drug development
  publication-title: Eur. J. Pharm. Biopharm.
  doi: 10.1016/j.ejpb.2015.01.003
– volume: 30
  start-page: 421
  year: 2002
  ident: B2
  article-title: Distribution of brimonidine into anterior and posterior tissues of monkey, rabbit, and rat eyes
  publication-title: Drug Metab. Dispos.
  doi: 10.1124/dmd.30.4.421
– volume: 11
  start-page: 489
  year: 1995
  ident: B1
  article-title: Comparison of concentration-time profiles of levobunolol and timolol in anterior and posterior ocular tissues of albino rabbits
  publication-title: J. Ocul. Pharmacol. Ther.
  doi: 10.1089/jop.1995.11.489
– volume: 10
  start-page: 23
  year: 2021
  ident: B43
  article-title: A novel eye drop formulation for potential treatment of neovascular age-related macular degeneration
  publication-title: Transl. Vis. Sci. Technol.
  doi: 10.1167/tvst.10.14.23
– volume: 38
  start-page: 627
  year: 1997
  ident: B33
  article-title: Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera
  publication-title: Investig. Ophthalmol. Vis. Sci.
– volume: 27
  start-page: 159
  year: 1978
  ident: B81
  article-title: The fate of anterior chamber flurescein in the monkey eye. 1. The anterior chamber outflow pathways.
  publication-title: Exp. Eye Res.
  doi: 10.1016/0014-4835(78)90086-6
– volume: 21
  start-page: 60
  year: 2022
  ident: B84
  article-title: Emerging therapeutic opportunities for integrin inhibitors
  publication-title: Nat. Rev. Drug Discov.
  doi: 10.1038/s41573-021-00284-4
– start-page: 245
  volume-title: Pharm. Res.
  year: 2018
  ident: B72
  article-title: Topical drug delivery to the posterior segment of the eye: Addressing the challenge of preclinical to clinical translation
– volume: 57
  start-page: 134
  year: 2017
  ident: B27
  article-title: Pharmacokinetic aspects of retinal drug delivery
  publication-title: Prog. Retin. Eye Res.
  doi: 10.1016/j.preteyeres.2016.12.001
– ident: B94
– volume: 62
  start-page: 1112
  year: 1973
  ident: B23
  article-title: Lacrimal and instilled fluid dynamics in rabbit eyes
  publication-title: J. Pharm. Sci.
  doi: 10.1002/jps.2600620712
– start-page: 19
  volume-title: Pharmacology of the eye
  year: 1984
  ident: B57
  article-title: Ocular pharmacokinetics
  doi: 10.1007/978-3-642-69222-2_2
– volume: 7
  start-page: 483
  year: 1988
  ident: B90
  article-title: Comparison of conjunctival and corneal surface areas in rabbit and human
  publication-title: Curr. Eye Res.
  doi: 10.3109/02713688809031801
– volume: 32
  start-page: 177
  year: 1949
  ident: B17
  article-title: The rate of flow of aqueous humor*
  publication-title: Am. J. Ophthalmol.
  doi: 10.1016/s0002-9394(14)78371-0
– volume: 85
  start-page: 347
  year: 2019
  ident: B47
  article-title: The developing regorafenib eye drops for neovascular age-related macular degeneration (DREAM) study: An open-label phase II trial
  publication-title: Br. J. Clin. Pharmacol.
  doi: 10.1111/bcp.13794
– volume: 17
  start-page: 588
  ident: B30
  article-title: Ocular intracameral pharmacokinetics for a cocktail of timolol, betaxolol, and atenolol in rabbits
  publication-title: Mol. Pharm.
  doi: 10.1021/acs.molpharmaceut.9b01024
– volume: 122
  start-page: 701
  year: 1996
  ident: B74
  article-title: Evaluation of the lacrimal drainage function by the drop test
  publication-title: Am. J. Ophthalmol.
  doi: 10.1016/s0002-9394(14)70490-8
– volume: 119
  start-page: 83
  year: 2018
  ident: B68
  article-title: Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye
  publication-title: Eur. J. Pharm. Sci.
  doi: 10.1016/j.ejps.2018.03.034
– volume: 121
  start-page: 2081
  year: 2014
  ident: B86
  article-title: Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis
  publication-title: Ophthalmology
  doi: 10.1016/j.ophtha.2014.05.013
– volume: 366
  start-page: 244
  year: 2018
  ident: B14
  article-title: Ocular distribution and pharmacodynamics of SF0166, a topically administered αvβ3 integrin antagonist, for the treatment of retinal diseases.
  publication-title: J. Pharmacol. Exp. Ther.
  doi: 10.1124/jpet.118.248427
– volume: 9
  start-page: 250
  year: 2020
  ident: B75
  article-title: Emerging therapies in neovascular age-related macular degeneration in 2020
  publication-title: Asia Pac J. Ophthalmol. (Phila)
  doi: 10.1097/APO.0000000000000291
– volume: 597
  start-page: 120332
  year: 2021
  ident: B85
  article-title: Topical drug delivery to the posterior segment of the eye: Thermodynamic considerations
  publication-title: Int. J. Pharm.
  doi: 10.1016/j.ijpharm.2021.120332
– volume: 18
  start-page: 1305
  year: 2021
  ident: B34
  article-title: Carboxylesterase activities and protein expression in rabbit and pig ocular tissues
  publication-title: Mol. Pharm.
  doi: 10.1021/acs.molpharmaceut.0c01154
– volume: 61
  start-page: 1622
  year: 2018
  ident: B4
  article-title: The discovery of N-(1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6- ((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide (acrizanib), a VEGFR-2 inhibitor specifically designed for topical ocular delivery, as a therapy for neovascular age-related macular degeneration
  publication-title: J. Med. Chem.
  doi: 10.1021/acs.jmedchem.7b01731
– ident: B95
– volume: 126
  start-page: 145
  year: 2018
  ident: B52
  article-title: Controlled release technology for anti-angiogenesis treatment of posterior eye diseases: Current status and challenges
  publication-title: Adv. Drug Deliv. Rev.
  doi: 10.1016/j.addr.2018.03.013
– volume: 101
  start-page: 691
  year: 1986
  ident: B53
  article-title: Drop size of commercial glaucoma medications
  publication-title: Am. J. Ophthalmol.
  doi: 10.1016/0002-9394(86)90771-3
– volume: 615
  start-page: 121515
  year: 2022
  ident: B59
  article-title: Topical pharmacokinetics of dexamethasone suspensions in the rabbit eye: Bioavailability comparison
  publication-title: Int. J. Pharm.
  doi: 10.1016/j.ijpharm.2022.121515
– volume: 2
  start-page: e106
  year: 2014
  ident: B91
  article-title: Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis
  publication-title: Lancet. Glob. Health
  doi: 10.1016/S2214-109X(13)70145-1
– volume: 41
  start-page: 1181
  year: 2000
  ident: B11
  article-title: Diffusion of high molecular weight compounds through sclera
  publication-title: Investig. Ophthalmol. Vis. Sci.
– volume: 80
  start-page: 391
  year: 1982
  ident: B20
  article-title: The flow of aqueous humor in the human eye
  publication-title: Trans. Am. Ophthalmol. Soc.
– volume: 4
  year: 2019
  ident: B93
  article-title: Current and upcoming anti-VEGF therapies and dosing strategies for the treatment of neovascular AMD: a comparative review
  publication-title: BMJ Open Ophthalmol.
  doi: 10.1136/bmjophth-2019-000398
– volume: 15
  start-page: 15
  year: 1973
  ident: B10
  article-title: Ocular and optic nerve blood flow at normal and increased intraocular pressures in monkeys (Macaca irus): A study with radioactively labelled microspheres including flow determinations in brain and some other tissues
  publication-title: Exp. Eye Res.
  doi: 10.1016/0014-4835(73)90185-1
– volume: 145
  start-page: 58
  year: 2016
  ident: B21
  article-title: Distribution of topical ocular nepafenac and its active metabolite amfenac to the posterior segment of the eye
  publication-title: Exp. Eye Res.
  doi: 10.1016/j.exer.2015.10.009
– volume: 27
  start-page: 1398
  year: 2010
  ident: B49
  article-title: Prediction of the corneal permeability of drug-like compounds
  publication-title: Pharm. Res.
  doi: 10.1007/s11095-010-0132-8
– volume: 16
  start-page: 3
  year: 1995
  ident: B45
  article-title: Ocular absorption following topical delivery
  publication-title: Adv. Drug Deliv. Rev.
  doi: 10.1016/0169-409X(95)00010-5
– volume: 286
  start-page: H419
  year: 2004
  ident: B92
  article-title: Low oxygen consumption in the inner retina of the visual streak of the rabbit
  publication-title: Am. J. Physiol. Heart Circ. Physiol.
  doi: 10.1152/ajpheart.00643.2003
– ident: B15
– volume: 108
  start-page: 784
  year: 2001
  ident: B48
  article-title: Vitreous concentration of topically applied brimonidine tartrate 0.2%
  publication-title: Ophthalmology
  doi: 10.1016/s0161-6420(00)00654-0
– ident: B78
– volume: 115
  start-page: 770
  year: 1993
  ident: B56
  article-title: Effects of inflammation and surgery on amikacin levels in the vitreous cavity
  publication-title: Am. J. Ophthalmol.
  doi: 10.1016/s0002-9394(14)73646-3
– volume: 61
  start-page: 241
  year: 1990
  ident: B87
  article-title: Controlled drug delivery devices for experimental ocular studies with timolol 2. Ocular and systemic absorption in rabbits
  publication-title: Int. J. Pharm. X.
  doi: 10.1016/0378-5173(90)90215-p
– volume: 110
  start-page: 529
  year: 2021
  ident: B60
  article-title: Comprehensive ocular and systemic pharmacokinetics of brinzolamide in rabbits after intracameral, topical, and intravenous administration
  publication-title: J. Pharm. Sci.
  doi: 10.1016/j.xphs.2020.09.051
– volume: 47
  start-page: 235
  year: 2006
  ident: B38
  article-title: Concentrations of betaxolol in ocular tissues of patients with glaucoma and normal monkeys after 1 month of topical ocular administration
  publication-title: Investig. Ophthalmol. Vis. Sci.
  doi: 10.1167/iovs.05-0945
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Snippet Topical ophthalmic instillation is an appealing strategy to deliver drugs to the back of the eye to treat retinal diseases such as neovascular age-related...
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Title Topical ophthalmic administration: Can a drug instilled onto the ocular surface exert an effect at the back of the eye?
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