Suprachoroidal space drug delivery_Chinese Journal of Ocular Fundus Diseases

Authors：

Chen Mei ,  Cheng Lingyun

1. Institute of Ocular Pharmacology, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, China (Chen Mei, now working at Department of Ophthalmology, Dazhou Central Hospital of Sichuan Province);

Corresponding author：

Cheng Lingyun, Email: lingyunc@hotmail.com

Keywords：

Administration, ophthalmic; Suprachoroidal space drug administration; Review

DOI：

10.3760/cma.j.issn.1005-1015.2017.02.027

Video：

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The suprachoroidal space (SCS) is the potential space between the sclera and choroid. Drugs delivered through SCS can bypass the sclera, avoiding clearance by conjunctival and scleral blood vessels and lymphatic circulation, so that more drugs can reach the disease tissues such as choroid and retina. SCS drug delivery does not disrupt the ocular integrity, is safer than the intravitreal drug injection and more effective than trans-scleral drug delivery. In addition, SCS delivery only needs a very small volume of drug, which makes it possible to be carried out in multiple parts of the sclera, and the specific disease area can be more precisely targeted. SCS drug delivery is suitable for the treatment of choroidal and retinal diseases. However, currently SCS drug delivery is still a novel field and many aspects need to be more in-depth studied, including its safety, delivery methods, drug formulation and effectiveness.

Citation： Chen Mei, Cheng Lingyun. Suprachoroidal space drug delivery. Chinese Journal of Ocular Fundus Diseases, 2017, 33(2): 209-212. doi: 10.3760/cma.j.issn.1005-1015.2017.02.027 Copy

1.	Patel SR, Lin AS, Edelhauser HF, et al. Suprachoroidal drug delivery to the back of the eye using hollow microneedles[J]. Pharm Res, 2011, 28(1): 166-176.
2.	Edelhauser HF, Boatright JH, Nickerson JM, et al. Drug delivery to posterior intraocular tissues: third Annual ARVO/Pfizer Ophthalmics Research Institute Conference[J]. Invest Ophthalmol Vis Sci, 2008, 49(11): 4712-4720.
3.	Ghate D, Edelhauser HF. Ocular drug delivery[J]. Expert Opin Drug Deliv, 2006, 3(2): 275-287.
4.	Kim SH, Lutz RJ, Wang NS, et al. Transport barriers in transscleral drug delivery for retinal diseases[J]. Ophthalmic Res, 2007, 39(5): 244-254.
5.	Angulo Bocco MC, Glacet-Bernard A, Zourdani A, et al. Intravitreous injection: retrospective study on 2028 injections and their side effects[J]. J Fr Ophtalmol, 2008, 31(7): 693-698.
6.	Falavarjani KG, Aghamirsalim M, Modarres M, et al. Endophthalmitis after resident-performed intravitreal bevacizumab injection[J]. Can J Ophthalmol, 2015, 50(1): 33-36.
7.	Shen L, You Y, Sun S, et al. Intraocular and systemic pharmacokinetics of triamcinolone acetonide after a single 40-mg posterior subtenon application[J]. Ophthalmology, 2010, 117(12): 2365-2371.
8.	Shen L, Mao J, Chen Y, et al. Transscleral permeation of subtenon triamcinolone in different vitreoretinal diseases[J]. Ophthalmology, 2015, 122(3): 649-651.
9.	Nan K, Sun S, Li Y, et al. Characterisation of systemic and ocular drug level of triamcinolone acetonide following a single sub-Tenon injection[J]. Br J Ophthalmol, 2010, 94(5): 654-658.
10.	Liu X, Li Y, Zhang Y, et al. Comparison of intraocular pressure elevation after anterior versus posterior subtenon triamcinolone acetonide acetate injection: a retrospective study[J]. Retina, 2012, 32(9): 1838-1843.
11.	Ozerdem U, Levi L, Cheng L, et al. Systemic toxicity of topical and periocular corticosteroid therapy in an 11-year-old male with posterior uveitis[J]. Am J Ophthalmol, 2000, 130(2): 240-241.
12.	Del Amo EM, Urtti A. Current and future ophthalmic drug delivery systems: a shift to the posterior segment[J]. Drug Discov Today, 2008, 13(3-4): 135-143.
13.	Kim YC, Park JH, Prausnitz MR. Microneedles for drug and vaccine delivery[J]. Adv Drug Deliv Rev, 2012, 64(14): 1547-1568.
14.	Olsen TW, Feng X, Wabner K, et al. Cannulation of the suprachoroidal space: a novel drug delivery methodology to the posterior segment[J]. Am J Ophthalmol, 2006, 142(5): 777-787.
15.	Olsen TW, Feng X, Wabner K, et al. Pharmacokinetics of pars plana intravitreal injections versus microcannula suprachoroidal injections of bevacizumab in a porcine model[J]. Invest Ophthalmol Vis Sci. 2011,52(7):4749-4756. DOI: 10.1167/iovs.10-6291.
16.	Peden MC, Min J, Meyers C, et al. Ab-externo AAV-mediated gene delivery to the suprachoroidal space using a 250 micron flexible microcatheter[J/OL]. PLoS One, 2011, 6(2): 17140[2011-02-11]. . DOI: 10.1371/ journal.pone.0017140.
17.	Seiler GS, Salmon JH, Mantuo R, et al. Effect and distribution of contrast medium after injection into the anterior suprachoroidal space in ex vivo eyes[J]. Invest Ophthalmol Vis Sci, 2011, 52(8): 5730-5736. DOI: 10.1167/iovs.11-7525.
18.	Abarca EM, Salmon JH, Gilger BC. Effect of choroidal perfusion on ocular tissue distribution after intravitreal or suprachoroidal injection in an arterially perfused ex vivo pig eye model[J]. J Ocul Pharmacol Ther, 2013, 29(8): 715-722. DOI: 10.1089/jop.2013.0063.
19.	Tetz M, Rizzo S, Augustin AJ. Safety of submacular suprachoroidal drug administration via a microcatheter: retrospective analysis of European treatment results[J]. Ophthalmologica, 2012, 227(4): 183-189. DOI: 10.1159/000336045.
20.	Rizzo S, Ebert FG, Bartolo ED, et al. Suprachoroidal drug infusion for the treatment of severe subfoveal hard exudates[J]. Retina, 2012, 32(4): 776-84. DOI: 10.1097/IAE.0b013e3182278b0e.
21.	Patel SR, Lin ASP, Edelhauser HF, et al. Suprachoroidal drug delivery to the back of the eye using hollow microneedles[J]. Pharm Res, 2011, 28(1): 166-76. DOI: 10.1007/s11095-010-0271-y.
22.	Sanchez I, Martin R, Ussa F, et al. The parameters of the porcine eyeball[J]. Graefe's Arch Clin Exp Ophthalmol, 2011, 249(4): 475-482. DOI: 10.1007/s00417-011-1617-9.
23.	Meek KM, Fullwood NJ. Corneal and scleral collagens--a microscopist's perspective[J]. Micron, 2001, 32(3): 261-272.
24.	Patel SR, Berezovsky DE, McCarey BE, et al. Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye[J]. Invest Ophthalmol Vis Sci, 2012, 53(8): 4433-4441. DOI: 10.1167/iovs.12-9872.
25.	Kim YC, Edelhauser HF, Prausnitz MR. Particle-stabilized emulsion droplets for gravity- mediated targeting in the posterior segment of the eye[J]. Adv Healthc Mater, 2014, 3(8): 1272-1282. DOI: 10.1002/adhm.201300696.
26.	Gilger BC, Abarca EM, Salmon JH, et al. Treatment of acute posterior uveitis in a porcine model by injection of triamcinolone acetonide into the suprachoroidal space using microneedles[J]. Invest Ophthalmol Vis Sci, 2013, 54(4): 2483-2492. DOI: 10.1167/iovs.13-11747.
27.	Tyagi P, Kadam RS, Kompella UB. Comparison of suprachoroidal drug delivery with subconjunctival and intravitreal routes using noninvasive fluorophotometry[J/OL].PLoS One, 2012,7(10): 48188[2012-10-31]. . DOI: 10.1371/journal.pone.0048188.
28.	Chen M, Li X, Liu J, et al. Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model[J]. J Control Release, 2015, 203: 109-117. DOI: 10.1016/j.jconrel.2015.02.021.
29.	Gu B, Liu J, Li X, et al. Real-time monitoring of suprachoroidal space (SCS) following scs injection using ultra-high resolution optical coherence tomography in Guinea pig eyes[J]. Invest Ophthalmol Vis Sci, 2015, 56(6): 3623-3634. DOI: 10.1167/iovs.15-16597.
30.	Touchard E, Berdugo M, Bigey P, et al. Suprachoroidal electrotransfer: a nonviral gene delivery method to transfect the choroid and the retina without detaching the retina[J]. Mol Ther, 2012, 20(8): 1559-1570. DOI: 10.1038/mt.2011.304.
31.	Einmahl S, Savoldelli M, D'Hermies F, et al. Evaluation of a novel biomaterial in the suprachoroidal space of the rabbit eye[J]. Invest Ophthalmol Vis Sci, 2002, 43(5): 1533-1539.
32.	Gilger BC, Wilkie DA, Clode AB, et al. Long-term outcome after implantation of a suprachoroidal cyclosporine drug delivery device in horses with recurrent uveitis[J]. Vet Ophthalmol, 2010, 13(5): 294-300. DOI: 10.1111/j.1463-5224.2010.00807.x.
33.	Kadam RS, Williams J, Tyagi P, et al. Suprachoroidal delivery in a rabbit ex vivo eye model: influence of drug properties, regional differences in delivery, and comparison with intravitreal and intracameral routes[J]. Mol Vis, 2013,19:1198-1210.
34.	Wang M, Liu W, Lu Q, et al. Pharmacokinetic comparison of ketorolac after intracameral, intravitreal, and suprachoroidal administration in rabbits[J]. Retina, 2012, 32(10): 2158-2164. DOI: 10.1097/IAE.0b013e3182576d1d.
35.	Waterbury LD, Flach AJ. Efficacy of low concentrations of ketorolac tromethamine in animal models of ocular inflammation[J]. J Ocul Pharmacol Ther, 2004, 20(4): 345-352.
36.	Tyagi P, Barros M, Stansbury JW, et al. Light-activated, in situ forming gel for sustained suprachoroidal delivery of bevacizumab[J]. Mol Pharm, 2013, 10(8): 2858-2867. DOI: 10.1021/mp300716t.
37.	Heller J. Ocular delivery using poly(ortho esters)[J]. Adv Drug Deliv Rev, 2005, 57(14): 2053-2062.
38.	Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration[J]. N Engl J Med, 2006, 355(14): 1419-1431.
39.	Emerson MV, Lauer AK, Flaxel CJ, et al. Intravitreal bevacizumab (Avastin) treatment of neovascular age-related macular degeneration[J]. Retina, 2007, 27(4): 439-444.
40.	Deak GG, Bolz M, Kriechbaum K, et al. Effect of retinal photocoagulation on intraretinal lipid exudates in diabetic macular edema documented by optical coherence tomography[J]. Ophthalmology, 2010, 117(4): 773-779. DOI: 10.1016/ j.ophtha.2009.09.027.
41.	Guyot-Argenton C, El Maftouhi A. Failure of photocoagulation therapy for diabetic macular edema[J]. J Fr Ophtalmol, 2004, 27(6 Pt 1): 597-603.
42.	Ciardella AP, Klancnik J, Schiff W, et al. Intravitreal triamcinolone for the treatment of refractory diabetic macular oedema with hard exudates: an optical coherence tomography study[J]. Br J Ophthalmol, 2004, 88(9): 1131-1136.
43.	Avci R, Kaderli B. Intravitreal triamcinolone injection for chronic diabetic macular oedema with severe hard exudates[J]. Graefe's Arch Clin Exp Ophthalmol, 2006, 244(1): 28-35.
44.	Dahr SS, Cusick M, Rodriguez-Coleman H, et al. Intravitreal anti-vascular endothelial growth factor therapy with pegaptanib for advanced von Hippel-Lindau disease of the retina[J]. Retina, 2007, 27(2): 150-158.
45.	Hou J, Tao Y, Jiang YR, et al. In vivo and in vitro study of suprachoroidal fibrin glue[J]. Jpn J Ophthalmol, 2009, 53(6): 640-647. DOI: 10.1007/s10384-009-0725-0.

1. Patel SR, Lin AS, Edelhauser HF, et al. Suprachoroidal drug delivery to the back of the eye using hollow microneedles[J]. Pharm Res, 2011, 28(1): 166-176.
2. Edelhauser HF, Boatright JH, Nickerson JM, et al. Drug delivery to posterior intraocular tissues: third Annual ARVO/Pfizer Ophthalmics Research Institute Conference[J]. Invest Ophthalmol Vis Sci, 2008, 49(11): 4712-4720.
3. Ghate D, Edelhauser HF. Ocular drug delivery[J]. Expert Opin Drug Deliv, 2006, 3(2): 275-287.
4. Kim SH, Lutz RJ, Wang NS, et al. Transport barriers in transscleral drug delivery for retinal diseases[J]. Ophthalmic Res, 2007, 39(5): 244-254.
5. Angulo Bocco MC, Glacet-Bernard A, Zourdani A, et al. Intravitreous injection: retrospective study on 2028 injections and their side effects[J]. J Fr Ophtalmol, 2008, 31(7): 693-698.
6. Falavarjani KG, Aghamirsalim M, Modarres M, et al. Endophthalmitis after resident-performed intravitreal bevacizumab injection[J]. Can J Ophthalmol, 2015, 50(1): 33-36.
7. Shen L, You Y, Sun S, et al. Intraocular and systemic pharmacokinetics of triamcinolone acetonide after a single 40-mg posterior subtenon application[J]. Ophthalmology, 2010, 117(12): 2365-2371.
8. Shen L, Mao J, Chen Y, et al. Transscleral permeation of subtenon triamcinolone in different vitreoretinal diseases[J]. Ophthalmology, 2015, 122(3): 649-651.
9. Nan K, Sun S, Li Y, et al. Characterisation of systemic and ocular drug level of triamcinolone acetonide following a single sub-Tenon injection[J]. Br J Ophthalmol, 2010, 94(5): 654-658.
10. Liu X, Li Y, Zhang Y, et al. Comparison of intraocular pressure elevation after anterior versus posterior subtenon triamcinolone acetonide acetate injection: a retrospective study[J]. Retina, 2012, 32(9): 1838-1843.
11. Ozerdem U, Levi L, Cheng L, et al. Systemic toxicity of topical and periocular corticosteroid therapy in an 11-year-old male with posterior uveitis[J]. Am J Ophthalmol, 2000, 130(2): 240-241.
12. Del Amo EM, Urtti A. Current and future ophthalmic drug delivery systems: a shift to the posterior segment[J]. Drug Discov Today, 2008, 13(3-4): 135-143.
13. Kim YC, Park JH, Prausnitz MR. Microneedles for drug and vaccine delivery[J]. Adv Drug Deliv Rev, 2012, 64(14): 1547-1568.
14. Olsen TW, Feng X, Wabner K, et al. Cannulation of the suprachoroidal space: a novel drug delivery methodology to the posterior segment[J]. Am J Ophthalmol, 2006, 142(5): 777-787.
15. Olsen TW, Feng X, Wabner K, et al. Pharmacokinetics of pars plana intravitreal injections versus microcannula suprachoroidal injections of bevacizumab in a porcine model[J]. Invest Ophthalmol Vis Sci. 2011,52(7):4749-4756. DOI: 10.1167/iovs.10-6291.
16. Peden MC, Min J, Meyers C, et al. Ab-externo AAV-mediated gene delivery to the suprachoroidal space using a 250 micron flexible microcatheter[J/OL]. PLoS One, 2011, 6(2): 17140[2011-02-11]. . DOI: 10.1371/ journal.pone.0017140.
17. Seiler GS, Salmon JH, Mantuo R, et al. Effect and distribution of contrast medium after injection into the anterior suprachoroidal space in ex vivo eyes[J]. Invest Ophthalmol Vis Sci, 2011, 52(8): 5730-5736. DOI: 10.1167/iovs.11-7525.
18. Abarca EM, Salmon JH, Gilger BC. Effect of choroidal perfusion on ocular tissue distribution after intravitreal or suprachoroidal injection in an arterially perfused ex vivo pig eye model[J]. J Ocul Pharmacol Ther, 2013, 29(8): 715-722. DOI: 10.1089/jop.2013.0063.
19. Tetz M, Rizzo S, Augustin AJ. Safety of submacular suprachoroidal drug administration via a microcatheter: retrospective analysis of European treatment results[J]. Ophthalmologica, 2012, 227(4): 183-189. DOI: 10.1159/000336045.
20. Rizzo S, Ebert FG, Bartolo ED, et al. Suprachoroidal drug infusion for the treatment of severe subfoveal hard exudates[J]. Retina, 2012, 32(4): 776-84. DOI: 10.1097/IAE.0b013e3182278b0e.
21. Patel SR, Lin ASP, Edelhauser HF, et al. Suprachoroidal drug delivery to the back of the eye using hollow microneedles[J]. Pharm Res, 2011, 28(1): 166-76. DOI: 10.1007/s11095-010-0271-y.
22. Sanchez I, Martin R, Ussa F, et al. The parameters of the porcine eyeball[J]. Graefe's Arch Clin Exp Ophthalmol, 2011, 249(4): 475-482. DOI: 10.1007/s00417-011-1617-9.
23. Meek KM, Fullwood NJ. Corneal and scleral collagens--a microscopist's perspective[J]. Micron, 2001, 32(3): 261-272.
24. Patel SR, Berezovsky DE, McCarey BE, et al. Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye[J]. Invest Ophthalmol Vis Sci, 2012, 53(8): 4433-4441. DOI: 10.1167/iovs.12-9872.
25. Kim YC, Edelhauser HF, Prausnitz MR. Particle-stabilized emulsion droplets for gravity- mediated targeting in the posterior segment of the eye[J]. Adv Healthc Mater, 2014, 3(8): 1272-1282. DOI: 10.1002/adhm.201300696.
26. Gilger BC, Abarca EM, Salmon JH, et al. Treatment of acute posterior uveitis in a porcine model by injection of triamcinolone acetonide into the suprachoroidal space using microneedles[J]. Invest Ophthalmol Vis Sci, 2013, 54(4): 2483-2492. DOI: 10.1167/iovs.13-11747.
27. Tyagi P, Kadam RS, Kompella UB. Comparison of suprachoroidal drug delivery with subconjunctival and intravitreal routes using noninvasive fluorophotometry[J/OL].PLoS One, 2012,7(10): 48188[2012-10-31]. . DOI: 10.1371/journal.pone.0048188.
28. Chen M, Li X, Liu J, et al. Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model[J]. J Control Release, 2015, 203: 109-117. DOI: 10.1016/j.jconrel.2015.02.021.
29. Gu B, Liu J, Li X, et al. Real-time monitoring of suprachoroidal space (SCS) following scs injection using ultra-high resolution optical coherence tomography in Guinea pig eyes[J]. Invest Ophthalmol Vis Sci, 2015, 56(6): 3623-3634. DOI: 10.1167/iovs.15-16597.
30. Touchard E, Berdugo M, Bigey P, et al. Suprachoroidal electrotransfer: a nonviral gene delivery method to transfect the choroid and the retina without detaching the retina[J]. Mol Ther, 2012, 20(8): 1559-1570. DOI: 10.1038/mt.2011.304.
31. Einmahl S, Savoldelli M, D'Hermies F, et al. Evaluation of a novel biomaterial in the suprachoroidal space of the rabbit eye[J]. Invest Ophthalmol Vis Sci, 2002, 43(5): 1533-1539.
32. Gilger BC, Wilkie DA, Clode AB, et al. Long-term outcome after implantation of a suprachoroidal cyclosporine drug delivery device in horses with recurrent uveitis[J]. Vet Ophthalmol, 2010, 13(5): 294-300. DOI: 10.1111/j.1463-5224.2010.00807.x.
33. Kadam RS, Williams J, Tyagi P, et al. Suprachoroidal delivery in a rabbit ex vivo eye model: influence of drug properties, regional differences in delivery, and comparison with intravitreal and intracameral routes[J]. Mol Vis, 2013,19:1198-1210.
34. Wang M, Liu W, Lu Q, et al. Pharmacokinetic comparison of ketorolac after intracameral, intravitreal, and suprachoroidal administration in rabbits[J]. Retina, 2012, 32(10): 2158-2164. DOI: 10.1097/IAE.0b013e3182576d1d.
35. Waterbury LD, Flach AJ. Efficacy of low concentrations of ketorolac tromethamine in animal models of ocular inflammation[J]. J Ocul Pharmacol Ther, 2004, 20(4): 345-352.
36. Tyagi P, Barros M, Stansbury JW, et al. Light-activated, in situ forming gel for sustained suprachoroidal delivery of bevacizumab[J]. Mol Pharm, 2013, 10(8): 2858-2867. DOI: 10.1021/mp300716t.
37. Heller J. Ocular delivery using poly(ortho esters)[J]. Adv Drug Deliv Rev, 2005, 57(14): 2053-2062.
38. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration[J]. N Engl J Med, 2006, 355(14): 1419-1431.
39. Emerson MV, Lauer AK, Flaxel CJ, et al. Intravitreal bevacizumab (Avastin) treatment of neovascular age-related macular degeneration[J]. Retina, 2007, 27(4): 439-444.
40. Deak GG, Bolz M, Kriechbaum K, et al. Effect of retinal photocoagulation on intraretinal lipid exudates in diabetic macular edema documented by optical coherence tomography[J]. Ophthalmology, 2010, 117(4): 773-779. DOI: 10.1016/ j.ophtha.2009.09.027.
41. Guyot-Argenton C, El Maftouhi A. Failure of photocoagulation therapy for diabetic macular edema[J]. J Fr Ophtalmol, 2004, 27(6 Pt 1): 597-603.
42. Ciardella AP, Klancnik J, Schiff W, et al. Intravitreal triamcinolone for the treatment of refractory diabetic macular oedema with hard exudates: an optical coherence tomography study[J]. Br J Ophthalmol, 2004, 88(9): 1131-1136.
43. Avci R, Kaderli B. Intravitreal triamcinolone injection for chronic diabetic macular oedema with severe hard exudates[J]. Graefe's Arch Clin Exp Ophthalmol, 2006, 244(1): 28-35.
44. Dahr SS, Cusick M, Rodriguez-Coleman H, et al. Intravitreal anti-vascular endothelial growth factor therapy with pegaptanib for advanced von Hippel-Lindau disease of the retina[J]. Retina, 2007, 27(2): 150-158.
45. Hou J, Tao Y, Jiang YR, et al. In vivo and in vitro study of suprachoroidal fibrin glue[J]. Jpn J Ophthalmol, 2009, 53(6): 640-647. DOI: 10.1007/s10384-009-0725-0.

Chinese Journal of Ocular Fundus Diseases

Suprachoroidal space drug delivery

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