Breakthrough treatment reduces post-surgical scarring for glaucoma patients

(Press-News.org) Scientists at the Singapore Eye Research Institute (SERI) and Nanyang Technological University (NTU) have developed an innovative way to combat post-surgical scarring for glaucoma patients.

A clinical trial has shown that the use of a new drug delivery method has resulted in 40 per cent fewer injections needed by glaucoma patients to prevent scarring after surgery. This also means fewer hospital visits for these patients in future.

Glaucoma, a disease characterised by a build-up of pressure in the eye, is a major cause of blindness worldwide. It affects about 3 per cent of the population in Singapore and an estimated 30 per cent of sufferers require surgery to adequately control the disease.

However, success rates for glaucoma surgery in Asian patients are considerably lower than those reported in Caucasian patients because Asians have a higher risk of scarring after such surgery. Up to one in three operated patients requires a minor surgical procedure in the first six months in order to maintain the ideal low post-operative eye pressure.

"The post-operative scarring response is the major obstacle for successful glaucoma surgery. We've seen in our clinics that Asian patients scar earlier and more aggressively than their Caucasian counterparts, and a significant number require at least one post-operative intervention to treat this scarring response," said Associate Professor Tina Wong, Senior Consultant with SNEC's Glaucoma Service, and Head of the Ocular Therapeutics and Drug Delivery Research Group at SERI. She is also the senior author of this study.

The breakthrough treatment method is made possible by Professor Subbu Venkatraman, Acting Chair of NTU's School of Materials Science and Engineering, who invented a way to make the drug, which prevents post-surgical scarring, last longer at the site of the injection. This considerably increases the interval before the drug has to be administered again.

Using a gel known as hyaluronic acid, Prof Venkatraman discovered a way to contain the drug, 5-Fluorouracil (5-FU) inside the gel. "Leveraging NTU's expertise in controlled-release technology, we have found a way to deliver the drug 5-Fluorouracil gradually into the patient. This allows the drug to be time-released over several days, compared to the current effect of the drug which remains at the injected site for only a few hours. The benefit for patients who have undergone glaucoma surgery is clear – fewer injections of the drug are needed. This results in less post-surgical scarring and fewer visits to the hospital."

The aim of glaucoma surgery is to create a new pathway for the aqueous fluid to flow out, thereby lowering eye pressure. During glaucoma surgery, a flap is created using the patient's own tissue to regulate the outflow of aqueous fluid. A small blister, known as a conjunctival bleb, marks the new surgically created filtration site.

The flap that allows fluid to flow out can be blocked if scar tissue forms, preventing the fluid from draining effectively and causing the eye pressure to rise again. This is a particularly common problem in Asian patients. To restore outflow through the surgical flap, the obstructing scar tissue needs to be removed by injecting 5-FU which prevents further scarring. This procedure is called bleb needling.*

The clinical trial involved 49 patients, who were randomised to receive an injection of either the current 5-FU solution or the new combined formulation following bleb needling. All subjects were followed up for three months. The trial was conducted at the Singapore National Eye Centre.

The team found that the subjects who were randomised to receive the new treatment had an improved post-operative outcome. "With this novel treatment, we observed a dramatically lower rate for repeat needling, with only 12 per cent requiring further intervention, whereas 50 per cent of subjects receiving the standard 5-FU solution treatment required further needling," said Dr Arun Kumar Narayanaswamy, Senior Clinical Research Fellow, SERI, and first author of this study.

"In addition, because these patients require fewer interventions, their risk of ocular infection and side effects are significantly reduced," he added.

Assoc Prof Wong, also an adjunct professor at NTU's School of Materials Science and Engineering, and Prof Venkatraman together with his team of scientists, are improving the new treatment method further using nano-encapsulation. The team aims to achieve a precise release of the correct amount of drug at a steady daily dose over a course of several weeks instead of just a few days as shown by the study.

"Because the acute and most active stage of wound healing occurs in the first twelve weeks after surgery, we ideally need a sustained time release of the anti-scarring drug that can be administered as a single injection and provide the right amount of drug to continually suppress the scarring response for that crucial time frame. That way, we won't have to keep injecting patients with top-ups, often on a fortnightly or even weekly basis which is not only inconvenient for the patient but greatly increases the risk of complications with each additional injection," said Assoc Prof Wong.

In the future, this novel treatment could also be applied at the time of the glaucoma surgery to further improve surgical outcomes, as well as reduce the possible need for or frequency of bleb needling interventions after surgery.

The study, published in the journal Ophthalmology early this year, has been shortlisted for a Best Clinical Research Oral Presentation Award at the second SingHealth Duke-NUS Scientific Congress, which will take place on 3 and 4 August at Raffles City Convention Centre.

### This research was supported in part by an Individual Research Grant awarded to Assoc Prof Wong by the Singapore Ministry of Health's National Medical Research Council.

NOTES TO EDITORS:

*About bleb needling: During a bleb needling procedure, the surgeon uses a fine needle to cut and break down the scar tissue to restore drainage. A chemotherapy drug, 5-Fluorouracil (5-FU) is injected into the surrounding tissues to halt further scarring. However, the drug only acts on cells and surrounding tissues at the time of injection, which means patients often have to go back for repeat injections to provide adequate anti-scarring action against the tissues around the drainage site and improve on the long-term success of the surgery.

In addition to the possible need for repeat injections, there is also the risk that the 5-FU solution may be transferred to other parts of the eye following its injection. Repeat injections can lead to an increased risk of sight-threatening complications. The invasive procedure can also increase the patients' risk of eye infections.

About SingHealth Duke-NUS Scientific Congress 2012 The SingHealth Duke-NUS Scientific Congress 2012 is a highly anticipated event that brings together various institutions from SingHealth, Duke-NUS, and from around the region, sharing the latest medical developments and scientific advances across the medical disciplines. Pushing the frontiers of healthcare and biomedical sciences, the collaboration between SingHealth and Duke-NUS Graduate Medical School Singapore aims to boost the exchange of ideas and research findings among healthcare professionals in our pursuit of defining tomorrow's Medicine.

The 2012 Congress will be held on 3 and 4 August at the Raffles City Convention Centre and its theme is "Defining Tomorrow's Medicine". These three words are an inspiration and challenge for all healthcare practitioners and biomedical researchers, young and old. In Defining, we seek to set the standards and benchmarks for local and international clinical practice, sharpened through the rigours of academic medicine. Tomorrow's reminds us that medicine is never static but constantly evolving, with shifting global conditions and complex social trends bringing about new disease conditions and healthcare concerns. Finally, Medicine reminds us that patients, and patient-oriented services, must remain at the centre of all our activities, and that we are ultimately judged by the impact we effect on patients, at the individual or national level.

About Singapore Eye Research Institute (SERI) SERI is the national research institute for ophthalmic and vision research in Singapore. Serving as the research institute of the Singapore National Eye Centre, and affiliated to the Yong Loo Lin School of Medicine, National University of Singapore, as well the Duke-NUS Graduate Medical School SIngapore, SERI undertakes vision research in collaboration with local clinical ophthalmic centres and biomedical research institutions, as well as major eye centers and research institutes throughout the world. For further information, kindly visit: www.seri.com.sg.

About Nanyang Technological University (NTU) A research-intensive public university, Nanyang Technological University (NTU) has 33,500 undergraduate and postgraduate students in the colleges of Engineering, Business, Science, and Humanities, Arts, & Social Sciences. In 2013, NTU will enrol the first batch of students at its new medical school, the Lee Kong Chian School of Medicine, which is set up jointly with Imperial College London.

NTU is also home to four world-class autonomous institutes – the National Institute of Education, S Rajaratnam School of International Studies, Earth Observatory of Singapore, and Singapore Centre on Environmental Life Sciences Engineering – and various leading research centres such as the Nanyang Environment & Water Research Institute (NEWRI), Energy Research Institute @ NTU (ERI@N) and Institute on Asian Consumer Insight (ACI).

A fast-growing university with an international outlook, NTU is putting its global stamp on Five Peaks of Excellence: Sustainable Earth, Future Healthcare, New Media, New Silk Road, and Innovation Asia.

Besides the main Yunnan Garden campus, NTU also has a satellite campus in Singapore's science and tech hub, one-north and is setting up a third campus in Novena, Singapore's medical district. For more information, visit www.ntu.edu.sg

About the School of Materials Science and Engineering, NTU The School of Materials Science and Engineering (MSE) stands as one of the world's largest materials engineering institutions, comprising more than 1000 undergraduates and 230 research students. While continuing to equip students with the latest scientific and technological skills sets much needed by the industry, the School has evolved into a hub of excellence in its niche areas of research.

As part of NTU's College of Engineering, MSE is now recognised worldwide as a premier research institution with top universities, multinational corporations and R&D institutions as its research collaborators and funding partners. Inter-disciplinary research is emphasized, involving academics and researchers from world-class research institutions and universities. With an excellent history of successfully commercializing research concepts, MSE has received international recognition and attracted multi-million dollar funding, both locally and overseas.

Apart from nurturing students with a passion for research and innovation, the School aims to provide an integrated science-driven and application-oriented engineering education in advanced materials for cutting-edge technologies. Further information can be found on the website, www.mse.ntu.sg