Research Projects
Evaluation of Vitamin D3 as an Antifibrotic Agent in Experimental Glaucoma Filtration Surgery


Programme(s) to which this project applies:

☑ MPhil/PhD ☒ MRes[Med] ☒ URIS
About the Project

Aim

To evaluate the antifibrotic effect of vitamin D3 on subconjunctival fibrosis in a long term in a rabbit model of glaucoma filtration surgery (GFS) in vivo.

 

Background

Glaucoma is a group of optic nerve disease characterized by specific changes of the optic discs with corresponding visual field and optic nerve fibre defects. It is the second leading cause of irreversible blindness worldwide, according to the World Health Organization (www.who.int/blindness/causes/priority/en/index7.html). The risk is estimated to be 2 - 3% for individuals over 40 years of age which rises to 10% for those above 80. The global glaucoma population is estimated to be around 64.3 million in 2013 (aged 40-80 years), which is expected to increase to 76.0 million in 2020, and 111.8 million by 2040.      

Progression of glaucoma to blindness is mainly due to an intraocular pressure (IOP) level which is too high for that patient, although the specific “safe” IOP level varies for each individual patient and also for the same patient, at different stage of their disease. Nevertheless, reduction of IOP remains the only proven method of preventing disease progression and worsening visual impairment. First line treatment for glaucoma is often medications (usually in the form of eye drops), or less frequently, laser therapy. The aim of either treatment modality being the same, that is, to reduce the intraocular pressure to a level which is compatible with disease stability. 

Not infrequently, especially over time, many glaucoma patients require surgery when they either failed to respond adequately to medical or laser treatment, or are intolerant to the medications. Glaucoma filtration surgery (GFS, or trabeculectomy) and its related variants such as tube-shunts (Ahmed Glaucoma Valve, Baerveldt Glaucoma Implant) and various subconjunctival implants (EX-PRESS device, XEN Gel Stent) are the most common type of glaucoma surgery performed today. Their common mechanism of action is the creation of an alternative aqueous outflow (drainage) pathway with lower resistance (than the patient's current outflow pathways) in the subconjunctival space, thus allowing for the lowering of intraocular pressure (IOP) and preventing glaucoma progression. Compared to other glaucoma surgeries, the subconjunctival drainage procedures, as a group, are the most effective in terms of achievable magnitude of intraocular pressure reduction. However, postoperative success with these procedures is often limited by subsequent progressive subconjunctival scarring, which can lead to increasing aqueous outflow resistance and a recurrence of intraocular pressure elevation (surgical failure). A key factor affecting postoperative scarring is the healing response of the subconjunctival tissue (specifically, the Tenon's fibroblasts) to injury from surgery. An excessive healing response is undesirable as it will lead to extensive subconjunctival fibrosis and scarring, but current uses of cytotoxic agents like mitomycin-C (MMC) to suppress fibrosis following subconjunctival drainage procedures are constrained by their toxicity on corneal epithelial and conjunctival cells which can result in epitheliopathy and conjunctival wound dehiscence or blebitis, respectively.

 

Rationale

Our previous in vitro experiment on human Tenon’s fibroblasts (HTF) had shown the inhibiting effect of vitamin D3 on cellular proliferation and migration, but without any discernible cellular toxicity. If the in vitro effect can be translated to an in vivo animal model, this will pave the way for possible clinical studies in patients. The main aim of this follow-up project is to compare the antifibrotic effect of vitamin D3 with that of mitomycin C (MMC), which is the most frequently used antifibrotic agent following filtration surgery currently, in a standardized rabbit glaucoma filtration surgery (GFS) model.

About the Supervisor

Dr JCH Chan, Department of Ophthalmology

Dr Jonathan Cheuk Hung Chan has been a clinical assistant professor of the Department of Ophthalmology at the University of Hong Kong since December 2015. 

Dr Chan studied medicine at the University of New South Wales, Australia, graduating with the degree of Bachelor of Medicine, Bachelor of Surgery (Hons.), and Bachelor of Medical Science. After returning to Hong Kong, he worked as a medical officer in ophthalmology at United Christian Hospital, where he completed his ophthalmology specialist training. He was promoted to associate consultant in ophthalmology at Queen Mary Hospital, in 2008, before eventually taking up his current position at the University of Hong Kong in 2015.

Dr Chan obtained his Fellowships with the Hong Kong Academy of Medicine (Ophthalmology) in 2004, the College of Ophthalmologists of Hong Kong in 2005, and the Royal College of Surgeons, Edinburgh (Ophthalmology) in 2007. 

Dr Chan’s main area of research interest include glaucoma surgery and therapeutics, cataract surgery, and eye disease (especially diabetic retinopathy) screening. He has authored over 60 publications in peer reviewed journals, mostly in the fields of glaucoma, diabetic retinopathy, and epidemiology of eye diseases. He is also involved with the development of diabetic retinopathy screening in Hong Kong and is the current head of training and arbitration for the diabetic retinopathy screening program of the Hospital Authority of Hong Kong.

Biography
jonochan@hku.hk

Next Step?

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

  1. your CV,
  2. a brief description of your research interest and experience, and
  3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website.

General admission enquiries should be directed to rpgmed@hku.hk.