Retinal detachment is a clinical emergency which, if left untreated, can lead to severe vision loss and even blindness. To repair the detached retina, the vitreous will have to be removed and replaced by an internal tamponade agent. Despite the clinical importance of treating it, innovation in this field has remained stagnant, with silicone oil, an invention approved by the FDA back in 1996 being its latest success story. Silicone oil is potentially toxic to the eye if left in-situ for too long. Other solutions previously developed, like expansile & inert gases, confer limitations like a requirement for prolonged face-down position post-operatively. Most importantly, patients with retinas that have undergone tamponade with expansile gases cannot travel via flight until the gas is completely resorbed after 4 weeks. This prevents the expansion of the gas under conditions of reduced atmospheric pressure. For such an important clinical condition, these solutions definitely leave much to be desired.
The origins of this project started when Associate Professor Lingam, a senior vitreo-retinal consultant at the National University Hospital, realised that the procedure needed great improvements in order to confer the quality of life that patients truly desired. Through his many years of experience, he inspired us to seek a solution for this unmet clinical need.
Our clinician and materials engineering collaboration had its origin more than 20 years ago. Dr. Loh Xian Jun and I were junior high school mates and we knew each other through a research competition held in 1998. As our paths diverged, I completed my MD/PhD in the University of Cambridge followed by my ophthalmology residency training in Singapore to become a clinician-scientist in vitreo-retinal surgery. Meanwhile, Dr. Loh Xian Jun, had developed his expertise in polymer engineering. He developed a new class of urethane-based thermogelling polymers and was seeking clinical applications for it. In 2014, it was serendipity which led us to integrate our insights from our individual professions to develop a novel retinal tamponade material.
The initial concept of the experiment was simple: to test the tamponade effect of thermogels in the eye and its potential to be used as a vitreous substitute. With an initial proof of concept grant from A*STAR’s Biomedical Engineering Programme, we assembled a multi-disciplinary team including vision scientists (such as Dr Liu Zeng Ping from the National University of Singapore, and others from the Institute of Molecular and Cell Biology A*STAR, and the Singapore Eye Research Institute) and biomaterial scientists (Dr Liow Sing Shy, from the Institute of Material Research and Engineering, A*STAR). With the team’s efforts, the results generated were surprising. The thermogel mimicked the jelly-like consistency of human vitreous humour as it gelated upon injection into the eye. It also had a similar refractive index to vitreous, offering good immediate post-operative vision. Most importantly, it was biodegradable, which meant that there was no need for subsequent removal.
In this paper published in Nature Biomedical Engineering, as its next step towards clinical utility, we tested the thermogel for its long-term biocompatibility and tamponade function in rabbit vitrectomy models. Its surgical efficacy in non-human primate retinal detachment models was tested too. What came as the greatest surprise was that while it degraded, the thermogel was replaced by a vitreous-like body similar to endogenous vitreous in consistency and composition. This challenged the age-old belief that vitreous humour has no regenerative ability.
Given its suitability as a vitreous substitute, other important ocular applications for the thermogel are being explored. It can potentially be used as a sustained drug delivery platform for anti-vascular endothelial growth factor (anti-VEGF) administration in the treatment of age-related macular degeneration and diabetic macular oedema. It can also be used as a scaffold for the protection of retinal pigment epithelium grafts during transplant surgery.
To fuel our efforts to bring this thermogel to clinical usage, we will be forming a company with a business collaborator. We believe this new biomaterial has great potential in revolutionising vitreoretinal surgery, making the post-operation experience a hassle-free one.
a) Schematic diagram illustrating the process of retinal detachment repair with the thermogel.
b) Polymerization procedure of the thermogel.
c) Comparison of consistency and clarity of regenerated (left) and native (right) vitreous body.
1. Dissection of the EPC-filled eye, 3 months post-operation: https://static-content.springer.com/esm/art%3A10.1038%2Fs41551-019-0382-7/MediaObjects/41551_2019_382_MOESM5_ESM.mp4
2. Dissection of the native vitreous: https://static-content.springer.com/esm/art%3A10.1038%2Fs41551-019-0382-7/MediaObjects/41551_2019_382_MOESM6_ESM.mp4
3. Dissection of the operated control (BSS-filled eye), 3 months post-operation: https://static-content.springer.com/esm/art%3A10.1038%2Fs41551-019-0382-7/MediaObjects/41551_2019_382_MOESM7_ESM.mp4