{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:05:17Z","timestamp":1789441517815,"version":"build-2803163510"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T00:00:00Z","timestamp":1596153600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T00:00:00Z","timestamp":1596153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glaucoma is a leading cause of irreversible vision loss predicted to affect more than 100 million people by 2040. Intraocular pressure (IOP) reduction prevents development of glaucoma and vision loss from glaucoma. Glaucoma surgeries reduce IOP by facilitating aqueous humor outflow through a vent fashioned from the wall of the eye (trabeculectomy) or a glaucoma drainage implant (GDI), but surgeries lose efficacy overtime, and the five-year failure rates for trabeculectomy and tube shunts are 25\u201345%. The majority of surgical failures occur due to fibrosis around the vent. Alternatively, surgical procedures can shunt aqueous humor too well, leading to hypotony. Electrospinning is an appealing manufacturing platform for GDIs, as it allows for incorporation of biocompatible polymers into nano- or micro-fibers that can be configured into devices of myriad combinations of dimensions and conformations. Here, small-lumen, nano-structured glaucoma shunts were manufactured with or without a degradable inner core designed to modulate aqueous humor outflow to provide immediate IOP reduction, prevent post-operative hypotony, and potentially offer significant, long-term IOP reduction. Nano-structured shunts were durable, leak-proof, and demonstrated biocompatibility and patency in rabbit eyes. Importantly, both designs prevented hypotony and significantly reduced IOP for 27\u00a0days in normotensive rabbits, demonstrating potential for clinical utility.<\/jats:p>","DOI":"10.1038\/s41598-020-69687-4","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T10:05:51Z","timestamp":1596189951000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Nano-structured glaucoma drainage implant safely and significantly reduces intraocular pressure in rabbits via post-operative outflow modulation"],"prefix":"10.1038","volume":"10","author":[{"given":"Kunal S.","family":"Parikh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Josyula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revaz","family":"Omiadze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Young","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youlim","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Ensign","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Hanes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Pitha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,31]]},"reference":[{"key":"69687_CR1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1136\/bjo.2005.081224","volume":"90","author":"HA Quigley","year":"2006","unstructured":"Quigley, H. A. & Broman, A. T. The number of people with glaucoma worldwide in 2010 and 2020. Br. J. Ophthalmol. 90, 262\u2013267. https:\/\/doi.org\/10.1136\/bjo.2005.081224 (2006).","journal-title":"Br. J. Ophthalmol."},{"key":"69687_CR2","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","volume":"121","author":"YC Tham","year":"2014","unstructured":"Tham, Y. C. et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology 121, 2081\u20132090. https:\/\/doi.org\/10.1016\/j.ophtha.2014.05.013 (2014).","journal-title":"Ophthalmology"},{"key":"69687_CR3","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1001\/archopht.120.6.701","volume":"120","author":"MA Kass","year":"2002","unstructured":"Kass, M. A. et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch. Ophthalmol. 120, 701\u2013713 (2002) (discussion 829\u2013730).","journal-title":"Arch. Ophthalmol."},{"key":"69687_CR4","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1001\/archopht.120.10.1268","volume":"120","author":"A Heijl","year":"2002","unstructured":"Heijl, A. et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch. Ophthalmol. 120, 1268\u20131279 (2002).","journal-title":"Arch. Ophthalmol."},{"key":"69687_CR5","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.ophtha.2008.09.004","volume":"116","author":"CO Okeke","year":"2009","unstructured":"Okeke, C. O. et al. Adherence with topical glaucoma medication monitored electronically the Travatan Dosing Aid study. Ophthalmology 116, 191\u2013199. https:\/\/doi.org\/10.1016\/j.ophtha.2008.09.004 (2009).","journal-title":"Ophthalmology"},{"key":"69687_CR6","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.ajo.2005.02.013","volume":"140","author":"HD Jampel","year":"2005","unstructured":"Jampel, H. D. et al. Perioperative complications of trabeculectomy in the collaborative initial glaucoma treatment study (CIGTS). Am. J. Ophthalmol. 140, 16\u201322. https:\/\/doi.org\/10.1016\/j.ajo.2005.02.013 (2005).","journal-title":"Am. J. Ophthalmol."},{"key":"69687_CR7","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ajo.2006.07.022","volume":"143","author":"SJ Gedde","year":"2007","unstructured":"Gedde, S. J. et al. Surgical complications in the Tube Versus Trabeculectomy Study during the first year of follow-up. Am. J. Ophthalmo 143, 23\u201331. https:\/\/doi.org\/10.1016\/j.ajo.2006.07.022 (2007).","journal-title":"Am. J. Ophthalmo"},{"key":"69687_CR8","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1016\/j.ophtha.2007.02.005","volume":"114","author":"PY Ramulu","year":"2007","unstructured":"Ramulu, P. Y., Corcoran, K. J., Corcoran, S. L. & Robin, A. L. Utilization of various glaucoma surgeries and procedures in Medicare beneficiaries from 1995 to 2004. Ophthalmology 114, 2265\u20132270. https:\/\/doi.org\/10.1016\/j.ophtha.2007.02.005 (2007).","journal-title":"Ophthalmology"},{"key":"69687_CR9","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1016\/j.ophtha.2015.04.015","volume":"122","author":"KS Arora","year":"2015","unstructured":"Arora, K. S., Robin, A. L., Corcoran, K. J., Corcoran, S. L. & Ramulu, P. Y. Use of various glaucoma surgeries and procedures in medicare beneficiaries from 1994 to 2012. Ophthalmology 122, 1615\u20131624. https:\/\/doi.org\/10.1016\/j.ophtha.2015.04.015 (2015).","journal-title":"Ophthalmology"},{"key":"69687_CR10","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/j.ophtha.2011.09.046","volume":"119","author":"JF Solus","year":"2012","unstructured":"Solus, J. F. et al. Comparison of limbus-based and fornix-based trabeculectomy: success, bleb-related complications, and bleb morphology. Ophthalmology 119, 703\u2013711. https:\/\/doi.org\/10.1016\/j.ophtha.2011.09.046 (2012).","journal-title":"Ophthalmology"},{"key":"69687_CR11","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1001\/jamaophthalmol.2015.57","volume":"133","author":"JA Olayanju","year":"2015","unstructured":"Olayanju, J. A., Hassan, M. B., Hodge, D. O. & Khanna, C. L. Trabeculectomy-related complications in Olmsted County, Minnesota, 1985 through 2010. JAMA Ophthalmol 133, 574\u2013580. https:\/\/doi.org\/10.1001\/jamaophthalmol.2015.57 (2015).","journal-title":"JAMA Ophthalmol"},{"key":"69687_CR12","doi-asserted-by":"publisher","first-page":"e60","DOI":"10.1097\/IJG.0000000000000008","volume":"23","author":"OJ Saeedi","year":"2014","unstructured":"Saeedi, O. J., Jefferys, J. L., Solus, J. F., Jampel, H. D. & Quigley, H. A. Risk factors for adverse consequences of low intraocular pressure after trabeculectomy. J. Glaucoma 23, e60-68. https:\/\/doi.org\/10.1097\/IJG.0000000000000008 (2014).","journal-title":"J. Glaucoma"},{"key":"69687_CR13","doi-asserted-by":"publisher","first-page":"265","DOI":"10.3109\/08820538.2010.518840","volume":"25","author":"S Patel","year":"2010","unstructured":"Patel, S. & Pasquale, L. R. Glaucoma drainage devices: a review of the past, present, and future. Semin. Ophthalmol. 25, 265\u2013270. https:\/\/doi.org\/10.3109\/08820538.2010.518840 (2010).","journal-title":"Semin. Ophthalmol."},{"key":"69687_CR14","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1097\/01.ijg.0000131759.48295.5c","volume":"13","author":"RR Breckenridge","year":"2004","unstructured":"Breckenridge, R. R., Bartholomew, L. R., Crosson, C. E. & Kent, A. R. Outflow resistance of the Baerveldt glaucoma drainage implant and modifications for early postoperative intraocular pressure control. J. Glaucoma 13, 396\u2013399 (2004).","journal-title":"J. Glaucoma"},{"key":"69687_CR15","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1097\/IJG.0b013e31802b3944","volume":"16","author":"DD Gilbert","year":"2007","unstructured":"Gilbert, D. D. & Bond, B. Intraluminal pressure response in Baerveldt tube shunts: a comparison of modification techniques. J. Glaucoma 16, 62\u201367. https:\/\/doi.org\/10.1097\/IJG.0b013e31802b3944 (2007).","journal-title":"J. Glaucoma"},{"key":"69687_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5005\/jp-journals-10008-1128","volume":"7","author":"E Jones","year":"2013","unstructured":"Jones, E., Alaghband, P., Cheng, J., Beltran-Agullo, L. & Sheng Lim, K. Preimplantation flow testing of ahmed glaucoma valve and the early postoperative clinical outcome. J. Curr. Glaucoma. Pract. 7, 1\u20135. https:\/\/doi.org\/10.5005\/jp-journals-10008-1128 (2013).","journal-title":"J. Curr. Glaucoma. Pract."},{"key":"69687_CR17","doi-asserted-by":"publisher","first-page":"4789","DOI":"10.1167\/iovs.15-16625","volume":"56","author":"A Sheybani","year":"2015","unstructured":"Sheybani, A., Reitsamer, H. & Ahmed, I. I. Fluid dynamics of a novel micro-fistula implant for the surgical treatment of glaucoma. Investig. Ophthalmol. Vis. Sci. 56, 4789\u20134795. https:\/\/doi.org\/10.1167\/iovs.15-16625 (2015).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"69687_CR18","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1016\/j.jcrs.2015.01.019","volume":"41","author":"A Sheybani","year":"2015","unstructured":"Sheybani, A., Lenzhofer, M., Hohensinn, M., Reitsamer, H. & Ahmed, I. I. Phacoemulsification combined with a new ab interno gel stent to treat open-angle glaucoma: pilot study. J. Cataract. Refract. Surg. 41, 1905\u20131909. https:\/\/doi.org\/10.1016\/j.jcrs.2015.01.019 (2015).","journal-title":"J. Cataract. Refract. Surg."},{"key":"69687_CR19","unstructured":"Sheybani, A. American Society of Cataract & Refractive Surgery (San Diego, CA, 2015)."},{"key":"69687_CR20","doi-asserted-by":"publisher","first-page":"e58","DOI":"10.1097\/IJG.0000000000000368","volume":"25","author":"JF Batlle","year":"2016","unstructured":"Batlle, J. F. et al. Three-year follow-up of a novel aqueous humor microshunt. J. Glaucoma 25, e58-65. https:\/\/doi.org\/10.1097\/IJG.0000000000000368 (2016).","journal-title":"J. Glaucoma"},{"key":"69687_CR21","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1002\/jbm.b.33525","volume":"105","author":"L Pinchuk","year":"2015","unstructured":"Pinchuk, L. et al. The development of a micro-shunt made from poly(styrene-block-isobutylene-block-styrene) to treat glaucoma. J Biomed Mater Res B Appl Biomater 105, 211\u2013221. https:\/\/doi.org\/10.1002\/jbm.b.33525 (2015).","journal-title":"J Biomed Mater Res B Appl Biomater"},{"key":"69687_CR22","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s40123-018-0131-0","volume":"7","author":"P Agrawal","year":"2018","unstructured":"Agrawal, P. & Bradshaw, S. E. Systematic literature review of clinical and economic outcomes of micro-invasive glaucoma surgery (MIGS) in primary open-angle glaucoma. Ophthalmol. Ther. 7, 49\u201373. https:\/\/doi.org\/10.1007\/s40123-018-0131-0 (2018).","journal-title":"Ophthalmol. Ther."},{"key":"69687_CR23","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/eye.2017.162","volume":"32","author":"SZ Tan","year":"2017","unstructured":"Tan, S. Z., Walkden, A. & Au, L. One-year result of XEN45 implant for glaucoma: efficacy, safety, and postoperative management. Eye 32, 324. https:\/\/doi.org\/10.1038\/eye.2017.162 (2017).","journal-title":"Eye"},{"key":"69687_CR24","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.biotechadv.2010.01.004","volume":"28","author":"N Bhardwaj","year":"2010","unstructured":"Bhardwaj, N. & Kundu, S. C. Electrospinning: a fascinating fiber fabrication technique. Biotechnol. Adv. 28, 325\u2013347. https:\/\/doi.org\/10.1016\/j.biotechadv.2010.01.004 (2010).","journal-title":"Biotechnol. Adv."},{"key":"69687_CR25","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1002\/adma.200400719","volume":"16","author":"D Li","year":"2004","unstructured":"Li, D. & Xia, Y. Electrospinning of Nanofibers: Reinventing the Wheel?. Adv. Mater. 16, 1151\u20131170. https:\/\/doi.org\/10.1002\/adma.200400719 (2004).","journal-title":"Adv. Mater."},{"key":"69687_CR26","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1089\/ten.TEA.2012.0772","volume":"20","author":"KR Kam","year":"2014","unstructured":"Kam, K. R. et al. The effect of nanotopography on modulating protein adsorption and the fibrotic response. Tissue Eng. Part A 20, 130\u2013138. https:\/\/doi.org\/10.1089\/ten.TEA.2012.0772 (2014).","journal-title":"Tissue Eng. Part A"},{"key":"69687_CR27","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1007\/s10439-015-1309-4","volume":"43","author":"RS Harake","year":"2015","unstructured":"Harake, R. S., Ding, Y., Brown, J. D. & Pan, T. Design, fabrication, and in vitro testing of an anti-biofouling glaucoma micro-shunt. Ann. Biomed. Eng. 43, 2394\u20132405. https:\/\/doi.org\/10.1007\/s10439-015-1309-4 (2015).","journal-title":"Ann. Biomed. Eng."},{"key":"69687_CR28","doi-asserted-by":"publisher","first-page":"5603","DOI":"10.1016\/j.polymer.2008.09.014","volume":"49","author":"S Agarwal","year":"2008","unstructured":"Agarwal, S., Wendorff, J. H. & Greiner, A. Use of electrospinning technique for biomedical applications. Polymer 49, 5603\u20135621. https:\/\/doi.org\/10.1016\/j.polymer.2008.09.014 (2008).","journal-title":"Polymer"},{"key":"69687_CR29","doi-asserted-by":"publisher","first-page":"4713","DOI":"10.1016\/j.polymer.2008.08.022","volume":"49","author":"S-C Wong","year":"2008","unstructured":"Wong, S.-C., Baji, A. & Leng, S. Effect of fiber diameter on tensile properties of electrospun poly(\u025b-caprolactone). Polymer 49, 4713\u20134722. https:\/\/doi.org\/10.1016\/j.polymer.2008.08.022 (2008).","journal-title":"Polymer"},{"key":"69687_CR30","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1097\/ICU.0b013e32834ff1e7","volume":"23","author":"H Saheb","year":"2012","unstructured":"Saheb, H. & Ahmed, I. I. Micro-invasive glaucoma surgery: current perspectives and future directions. Curr. Opin. Ophthalmol. 23, 96\u2013104. https:\/\/doi.org\/10.1097\/ICU.0b013e32834ff1e7 (2012).","journal-title":"Curr. Opin. Ophthalmol."},{"key":"69687_CR31","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1586\/17434440.3.4.509","volume":"3","author":"RS Ayyala","year":"2006","unstructured":"Ayyala, R. S., Duarte, J. L. & Sahiner, N. Glaucoma drainage devices: state of the art. Expert Rev. Med. Devices 3, 509\u2013521. https:\/\/doi.org\/10.1586\/17434440.3.4.509 (2006).","journal-title":"Expert Rev. Med. Devices"},{"key":"69687_CR32","doi-asserted-by":"publisher","first-page":"5420","DOI":"10.1021\/acs.nanolett.5b01815","volume":"15","author":"J Joseph","year":"2015","unstructured":"Joseph, J., Nair, S. V. & Menon, D. Integrating substrateless electrospinning with textile technology for creating biodegradable three-dimensional structures. Nano Lett. 15, 5420\u20135426. https:\/\/doi.org\/10.1021\/acs.nanolett.5b01815 (2015).","journal-title":"Nano Lett."},{"key":"69687_CR33","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1021\/bm060680j","volume":"7","author":"QP Pham","year":"2006","unstructured":"Pham, Q. P., Sharma, U. & Mikos, A. G. Electrospun poly(\u03b5-caprolactone) microfiber and multilayer nanofiber\/microfiber scaffolds: characterization of scaffolds and measurement of cellular infiltration. Biomacromol 7, 2796\u20132805. https:\/\/doi.org\/10.1021\/bm060680j (2006).","journal-title":"Biomacromol"},{"key":"69687_CR34","doi-asserted-by":"publisher","first-page":"158","DOI":"10.3390\/fib2020158","volume":"2","author":"J Yao","year":"2014","unstructured":"Yao, J., Bastiaansen, C. & Peijs, T. High strength and high modulus electrospun nanofibers. Fibers 2, 158 (2014).","journal-title":"Fibers"},{"key":"69687_CR35","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1001\/archopht.118.8.1081","volume":"118","author":"RS Ayyala","year":"2000","unstructured":"Ayyala, R. S., Michelini-Norris, B., Flores, A., Haller, E. & Margo, C. E. Comparison of different biomaterials for glaucoma drainage devices: part 2. Arch. Ophthalmol. 118, 1081\u20131084 (2000).","journal-title":"Arch. Ophthalmol."},{"key":"69687_CR36","doi-asserted-by":"publisher","first-page":"397","DOI":"10.3109\/08820538.2014.959199","volume":"29","author":"M Giovingo","year":"2014","unstructured":"Giovingo, M. Complications of glaucoma drainage device surgery: a review. Semin. Ophthalmol. 29, 397\u2013402. https:\/\/doi.org\/10.3109\/08820538.2014.959199 (2014).","journal-title":"Semin. Ophthalmol."},{"key":"69687_CR37","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/978-1-4614-9434-8_2","volume-title":"Focal Controlled Drug Delivery","author":"W Khan","year":"2014","unstructured":"Khan, W., Muntimadugu, E., Jaffe, M. & Domb, A. J. In Focal Controlled Drug Delivery (eds AbrahamDomb, J. & Khan, W.) 33\u201359 (Springer US, New York, 2014)."},{"key":"69687_CR38","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1002\/9783527690916.ch12","volume-title":"Biomedical Applications of Polymeric Materials and Composites","author":"R Francis","year":"2016","unstructured":"Francis, R., Joy, N. & Sivadas, A. In Biomedical Applications of Polymeric Materials and Composites (eds Francis, R. & Kumar, D. S.) 361\u2013382 (Springer, New York, 2016)."},{"key":"69687_CR39","doi-asserted-by":"publisher","first-page":"189","DOI":"10.2147\/OPTH.S80490","volume":"10","author":"GM Richter","year":"2016","unstructured":"Richter, G. M. & Coleman, A. L. Minimally invasive glaucoma surgery: current status and future prospects. Clin. Ophthalmol. 10, 189\u2013206. https:\/\/doi.org\/10.2147\/OPTH.S80490 (2016).","journal-title":"Clin. Ophthalmol."},{"key":"69687_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.progpolymsci.2017.03.002","volume":"70","author":"CT Lim","year":"2017","unstructured":"Lim, C. T. Nanofiber technology: current status and emerging developments. Prog. Polym. Sci. 70, 1\u201317. https:\/\/doi.org\/10.1016\/j.progpolymsci.2017.03.002 (2017).","journal-title":"Prog. Polym. Sci."},{"key":"69687_CR41","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ajo.2017.07.023","volume":"183","author":"DS Grover","year":"2017","unstructured":"Grover, D. S. et al. Performance and safety of a new ab interno gelatin stent in refractory glaucoma at 12 months. Am. J. Ophthalmol. 183, 25\u201336. https:\/\/doi.org\/10.1016\/j.ajo.2017.07.023 (2017).","journal-title":"Am. J. Ophthalmol."},{"key":"69687_CR42","doi-asserted-by":"publisher","first-page":"e691","DOI":"10.1097\/IJG.0000000000000352","volume":"25","author":"A Sheybani","year":"2015","unstructured":"Sheybani, A., Dick, B. & Ahmed, I. I. Early clinical results of a novel ab interno gel stent for the surgical treatment of open-angle glaucoma. J. Glaucoma 25, e691-696. https:\/\/doi.org\/10.1097\/IJG.0000000000000352 (2015).","journal-title":"J. Glaucoma"},{"key":"69687_CR43","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1007\/s00348-003-0753-3","volume":"36","author":"KV Sharp","year":"2004","unstructured":"Sharp, K. V. & Adrian, R. J. Transition from laminar to turbulent flow in liquid filled microtubes. Exp. Fluids 36, 741\u2013747. https:\/\/doi.org\/10.1007\/s00348-003-0753-3 (2004).","journal-title":"Exp. Fluids"},{"key":"69687_CR44","first-page":"45","volume":"37","author":"M Echavez","year":"2012","unstructured":"Echavez, M., Agulto, M. & Imelda Veloso, M. Intravitreal bevacizumab as adjunctive therapy for bleb survival in trabeculectomy in rabbit eyes. Philipp. J. Ophthalmol. 37, 45\u201351 (2012).","journal-title":"Philipp. J. Ophthalmol."},{"key":"69687_CR45","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1001\/archopht.124.12.1742","volume":"124","author":"AC Acosta","year":"2006","unstructured":"Acosta, A. C. et al. A newly designed glaucoma drainage implant made of poly(styrene-b-isobutylene-b-styrene): Biocompatibility and function in normal rabbit eyes. Arch. Ophthalmol. 124, 1742\u20131749. https:\/\/doi.org\/10.1001\/archopht.124.12.1742 (2006).","journal-title":"Arch. Ophthalmol."},{"key":"69687_CR46","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/s40123-018-0135-9","volume":"7","author":"P Bloom","year":"2018","unstructured":"Bloom, P. & Au, L. \u201cMinimally invasive glaucoma surgery (MIGS) is a poor substitute for trabeculectomy\u201d-the great debate. Ophthalmol. Ther. 7, 203\u2013210. https:\/\/doi.org\/10.1007\/s40123-018-0135-9 (2018).","journal-title":"Ophthalmol. Ther."},{"key":"69687_CR47","doi-asserted-by":"publisher","first-page":"77","DOI":"10.4161\/19420862.2014.985544","volume":"7","author":"A Lavoisier","year":"2015","unstructured":"Lavoisier, A. & Schlaeppi, J. M. Early developability screen of therapeutic antibody candidates using Taylor dispersion analysis and UV area imaging detection. MAbs 7, 77\u201383. https:\/\/doi.org\/10.4161\/19420862.2014.985544 (2015).","journal-title":"MAbs"},{"key":"69687_CR48","doi-asserted-by":"publisher","first-page":"2987","DOI":"10.1021\/acs.molpharmaceut.6b00343","volume":"13","author":"J Fu","year":"2016","unstructured":"Fu, J. et al. Subconjunctival delivery of dorzolamide-loaded poly(ether-anhydride) microparticles produces sustained lowering of intraocular pressure in rabbits. Mol. Pharm. 13, 2987\u20132995. https:\/\/doi.org\/10.1021\/acs.molpharmaceut.6b00343 (2016).","journal-title":"Mol. Pharm."},{"key":"69687_CR49","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1167\/tvst.7.2.13","volume":"7","author":"I Pitha","year":"2018","unstructured":"Pitha, I. et al. Sustained dorzolamide release prevents axonal and retinal ganglion cell loss in a rat model of IOP-glaucoma. Transl. Vis. Sci. Technol. 7, 13. https:\/\/doi.org\/10.1167\/tvst.7.2.13 (2018).","journal-title":"Transl. Vis. Sci. Technol."},{"key":"69687_CR50","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.ophtha.2005.06.037","volume":"113","author":"AP Wells","year":"2006","unstructured":"Wells, A. P., Ashraff, N. N., Hall, R. C. & Purdie, G. Comparison of two clinical Bleb grading systems. Ophthalmology 113, 77\u201383. https:\/\/doi.org\/10.1016\/j.ophtha.2005.06.037 (2006).","journal-title":"Ophthalmology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69687-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69687-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69687-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T15:13:24Z","timestamp":1670339604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69687-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,31]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["69687"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-69687-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,31]]},"assertion":[{"value":"14 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12911"}}