June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
An Implantable Device for Reducing Post-Trabeculectomy Fibrosis in Glaucoma Patients
Author Affiliations & Notes
  • Alan Hibbitts
    Dept of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
    Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland
  • Mark Lemoine
    Dept of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
    Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland
  • Zulal Demir
    Dept of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Deirdre Brennan
    Dept of Anatomy, University College Dublin, Dublin, Ireland
  • Colm J O'Brien
    Institute of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland
    Dept of Anatomy, University College Dublin, Dublin, Ireland
  • Fergal O'Brien
    Dept of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
    Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland
  • Footnotes
    Commercial Relationships   Alan Hibbitts, None; Mark Lemoine, None; Zulal Demir, None; Deirdre Brennan, None; Colm O'Brien, None; Fergal O'Brien, None
  • Footnotes
    Support  Science Foundation Ireland: Technology Innovation and Development Award 17/TIDA/5098. Enterprise Ireland: Commercial Case Feasibility Fund CF20190764Y
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1418. doi:
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      Alan Hibbitts, Mark Lemoine, Zulal Demir, Deirdre Brennan, Colm J O'Brien, Fergal O'Brien; An Implantable Device for Reducing Post-Trabeculectomy Fibrosis in Glaucoma Patients. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1418.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Glaucoma is the second-leading cause of blindness with patient numbers to reach 80 million by 2020. There is no cure for glaucoma and progression can often lead to intervention via trabeculectomy. Unfortunately, 30%–50% of these procedures fail due to the formation of post-operative fibrotic fistulas. The formation of these fistulas is known to follow a two-stage process with inflammation and angiogenesis over the first 1-7 days followed collagen deposition over a 4-week period. Therefore, to target these events, we describe a modified hyaluronic acid (HyA) hydrogel capable of controlled anti-inflammatory/fibrotic drug release profiles.

Methods : Modified hydrogels were assessed for changes in swelling ratio, degradation and ease of insertion into cadaveric rabbit eyes. Following drug loading, devices were monitored for drug release kinetics over 28 days in PBS. Finally, anti-inflammatory/anti-fibrotic effect of the implanted drug-device combination was assessed using primary human conjunctiva cell culture and a chick embryo model of angiogenesis.

Results : On analysis, it was found that HyA hydrogels were capable of rapid swelling (<30 min) and were stable in physiological conditions up to a minimum of 4 weeks but demonstrated dose dependent enzymatic degradation. Secondary modification allowed for an immediate anti-fibrotic effect through a 50% drop in collagen deposition in vitro at 24hrs. Drug-loaded gels demonstrated a range of release profiles depending on the loading strategy used. Using the optimal loading strategy, prednisolone release was found to exhibit a bi-phasic release with an initial burst release over 72 hours and a more gradual release for up to 28 days. Furthermore, release drug was found to effectively inhibit angiogenesis up to 5 days in the chick embryo model (figure 1).

Conclusions : This work demonstrates a highly controllable modified hydrogel matrix capable of contact inhibition and anti-fibrotic drug release. It is now expected to be assessed in in vivo glaucoma models.

This is a 2020 ARVO Annual Meeting abstract.

 

Figure 1. A) Optimal drug loading strategy allowed for a biphasic release of Prednisolone over 28 days. Drug efficacy was evident in chick embyro model B) drug free device C) "low" drug loaded gave localised inhibition of angiogenesis as highlighted by the dashed line and D) "high" dose gave near total inhibition of angiogenesis (devices obscured by blue circles due to future IP potential).

Figure 1. A) Optimal drug loading strategy allowed for a biphasic release of Prednisolone over 28 days. Drug efficacy was evident in chick embyro model B) drug free device C) "low" drug loaded gave localised inhibition of angiogenesis as highlighted by the dashed line and D) "high" dose gave near total inhibition of angiogenesis (devices obscured by blue circles due to future IP potential).

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