June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
A conjunctival implant of Lenalidomide minimises immunological and inflammatory responses to local therapy in an experimental model of glaucoma filtration surgery
Author Affiliations & Notes
  • Ashkan Khalili
    NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital & UCL Institute of Ophthalmology, London, United Kingdom
  • Hanieh Khalili
    NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital & UCL Institute of Ophthalmology, London, United Kingdom
    UCL School of Pharmacy, London, United Kingdom
  • Garima Sharma
    NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital & UCL Institute of Ophthalmology, London, United Kingdom
    UCL School of Pharmacy, London, United Kingdom
  • Steve Brocchini
    NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital & UCL Institute of Ophthalmology, London, United Kingdom
    UCL School of Pharmacy, London, United Kingdom
  • Peng Tee Khaw
    NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital & UCL Institute of Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships Ashkan Khalili, None; Hanieh Khalili, None; Garima Sharma, None; Steve Brocchini, WO09/063222 (P); Peng Khaw, WO09/063222 (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2665. doi:
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      Ashkan Khalili, Hanieh Khalili, Garima Sharma, Steve Brocchini, Peng Tee Khaw; A conjunctival implant of Lenalidomide minimises immunological and inflammatory responses to local therapy in an experimental model of glaucoma filtration surgery . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2665.

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

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Abstract

Purpose: Glaucoma filtration surgery (GFS) is one of the most effective treatments to reduce the intraocular pressure<br /> (IOP) when medical treatment or minimally invasive techniques fail in glaucoma patients. GFS often fails because of scarring. Various conjunctival implants have been developed to minimise the scarring but may cause a foreign body reaction and capsule formation resulting in reduced efficacy and sub-optimal pharmacokinetics. Immunomodulating agents such as lenalidomide have both anti-angiogenic and anti-fibrotic effects. Our aim was to investigate the foreign body response and capsule formation to a conjunctival lenalidomide implant following GFS in a rabbit model of wound healing.

Methods: Lenalidomide (Shijiazhuang SanxinChemPharma) was fabricated into an implant (diameter =3 mm, thickness approximately 1mm) at two dosages: 7.7 mg (n=1) and 3.5 mg (n=1). Gamma irridation was used to sterlise the implants. The implant was inserted sub-conjunctivally before the closure of conjuctiva at the end of GFS. At the end of the study (day 30), histological examination of the implant was conducted using hematoxylin and eosin (H&E) staining.

Results: Lenalidomide implants, at both low and high dosages, had disappeared completely as determined by clinical examination at day 18 and day 22 respectively. The histological examination showed no evidence of capsule formation or foreign body response with minimum cell infiltration and collagen deposition, although a small tattoo-like spot was observed clinically where the implant was placed. The histology examination showed no significant immune response, suggesting a non-immunogenic impurity in the formulation that resulted in a ‘tattoo’ effect.

Conclusions: The lenalidomide conjunctival implant showed no capsule formation or foreign body response with minimal scarring after experimental GFS. An agent or agents with multiple activities may minimise local immunogenic and inflammatory responses to local therapy.

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