Royal Prince Alfred Hospital (RPAH) is one of Australia’s premier tertiary referral hospitals, the principal teaching hospital of the University of Sydney, and the flagship hospital of the Sydney Local Health District. In this article, five leading ophthalmologists explore the exciting developments happening at RPAH and its affiliated institutions. They also offer an insight into new and emerging technologies on the radar of the ophthalmologists working there.
Establishment of Sydney Biomedical Accelerator
Professor Peter McCluskey
In the lead up to the 2019 NSW State Election, the NSW Government committed AU$750 million to the redevelopment of RPAH to deliver a new hospital building and refurbishment of existing spaces. This is the most significant investment in the hospital’s 140-year history. The redevelopment of RPAH will also complement the NSW Government’s creation of Tech Central, one of the largest innovation communities in the Southern Hemisphere. Located within the Tech Central precinct will be the Sydney Biomedical Accelerator (SBA).
Figure 1. Zeiss patented Quattro Pump’s synchronised fluid-exchange system.
The SBA is a co-funded partnership project between NSW Health, Sydney Local Health District, and the University of Sydney. It will be a state-of-the-art biomedical research complex spanning the University campus and the District’s RPAH campus, and will offer a unique global concentration of biomedical research talent. A first-in-kind complex in the Australian context, the SBA will be purpose built to genuinely integrate fundamental research at the molecular and cellular level with clinical and patient-centred research and health outcomes.
Dr Teresa Anderson, Chief Executive of Sydney Local Health District has said, “The SBA’s researchers and industry collaborators will work together on solving critical health challenges and providing options for patients who may have limited choices. Investing in the state-of-the-art facilities, so closely located between a leading hospital and university, will dramatically shorten the time between scientific discovery and health outcomes for patients and our community.”
Sydney University has a long and proud history of excellence in vision basic science. In 2020, following a competitive process, the Faculty of Medicine and Health at Sydney University appointed the Save Sight Institute (SSI) as one of its seven flagship research centres. This is formal recognition of the importance of ophthalmology and vision science.
To further advance vision science research and take advantage of the new opportunities the SBA brings, a team from the Faculty of Medicine and Health, the SSI and RPAH have recruited Professor Jonathan Crowston, a high-profile, internationally recognised, vision science researcher, to lead Vision Science and Ophthalmology on the Camperdown Health Precinct and the SBA research complex.
Professor Crowston’s research interests centre on glaucoma, optic neuropathy, ageing and neuroprotection. Although he will hold a clinical appointment in ophthalmology at RPAH, his role will be focused on leading basic vision science research. Professor Crowston’s appointment underscores the commitment of the University of Sydney to the SSI and RPAH to ophthalmology. It is also a massive boost to vision science and ophthalmology in Australia.
In the meantime, research at RPAH continues with new technologies and approaches to surgeries and treatments enhancing patient outcomes, as we see here.
Zeiss Quatera 700: A New Technology for Phacoemulsification
Dr Jay Yohendran
For many years, cataract surgery using phacoemulsification has been recognised as one of the safest and most successful operations worldwide. Nevertheless, ophthalmologists and our industry partners are constantly working to develop further advances in cataract surgery technologies.
Figure 2. Dimensions of the Preserflo MicroShunt.
In September 2021, a new phacoemulsification system was introduced to the European market – the Quatera 700 from Zeiss. While not yet commercially available in Australia, in March 2022 I had the opportunity to use the new device in a wet lab setting, and by the time of publication, I will have been one of three ophthalmologists in Australia to have used it on patients. Zeiss has given early access to one surgeon in each of New South Wales, Victoria and Queensland.
Based on my reading and limited initial experience, I am confident that the Quatera will provide better anterior chamber stability when compared to currently available phacoemulsification machines. This should translate to safer surgery and better patient outcomes.
A decade ago, I was impressed by the then new laser-assisted cataract surgery technology. My initial experience was in a wet lab environment, and then on a limited number of my own patients. I was hopeful that this technology would translate to safer surgery and better patient outcomes. Unfortunately, like many of my colleagues who were enthusiastic early adopters of the laser, when taking into account our clinical experience, and the results of the most recent research, this hoped improvement in safety and patient outcomes with the laser has not been borne out. Certainly, at a public hospital like Royal Prince Alfred Hospital, I cannot justify the purchase of a femtosecond laser to assist in cataract surgery. I am hopeful that my experience with the Zeiss Quatera will be different to the femtosecond laser.
One of the most feared cataract surgery complications is a posterior capsular tear, usually caused by an unstable anterior chamber, and the posterior capsule moving anteriorly during phacoemulsification. This can lead to the patient requiring an anterior vitrectomy, and the intraocular lens (IOL) not being able to be placed in the capsular bag. In such cases, the chance of post-operative macular oedema, retinal detachment and endophthalmitis are higher than average. The incidence rate of posterior capsular tears ranges from about one in 300 for experienced surgeons, to one in 50 for early trainees. I am confident that the rate of posterior capsular tears will be less with the Zeiss Quatera.
The Zeiss Quatera features a new patented pump called the Quattro Pump. Differing from traditional venturi and peristaltic pumps, the Quattro Pump directly controls both infusion and aspiration via four syringe-like chambers that provide synchronous exchange of infusion and aspiration (Figure 1). Sensors directly measure actual irrigation and aspiration flow and automatically compensate for incisional leakage to maintain the pre-set target intraocular pressure (IOP) independent of vacuum limit or IOP level.
The Quattro Pump is designed to keep the anterior chamber stable throughout surgery, and at least in my experience in the wet lab, it achieves this goal. Assuming this translates to the operating theatre, the rate of posterior capsular tears will reduce. Although my personal rate of posterior capsular tears is very low, I feel that trialling this system, and working with Zeiss to optimise the Quatera experience, will be of benefit to the local ophthalmic community.
There are two other benefits of the Zeiss Quatera 700 worth briefly mentioning:
- Automated ultrasound power on demand. The ultrasound power is automatically deactivated when the nuclear material of the lens is not at the tip of the ultrasound probe. This allows the surgeon to not waste ultrasound energy within the eye, and remove the cataract with less energy.
- Digitally integrated surgical workflow.
The Quatera is capable of digital integration with the IOL Master and Callisto Eye. This allows data taken in the clinic to be displayed on the Quatera screen in the operating theatre, which helps with surgical flow, minimises human input errors, and helps with post-operative audits.
PreserFlo MicroShunt: A New Glaucoma Surgery Implant
Assoc/Prof Mitchell Lawlor
The surgical options available for treating glaucoma have significantly increased over the last ten years under the broad banner of ‘minimally invasive glaucoma surgery’ (MIGS). To date, the MIGS label has covered both devices that bypass the trabecular meshwork, as well as devices that form filtration blebs. The former have an exceptionally high safety profile with modest efficacy, whereas the latter have many of the potential risks that come with bleb surgery, but with a potentially greater reduction in IOP. This has led to the latter devices now being referred under the heading of ‘minimally invasive bleb surgery’ (MIBS).
Figure 3. Eye anatomy with the Preserflo MicroShunt implanted.
The newest of the MIBS devices is the PreserFlo MicroShunt; it has the capacity to produce a significant pressure decrease, and therefore may be suitable for a large range of glaucoma patients, including those with advanced glaucoma. Prepandemic, the first of these microshunts implanted in Australia were performed at RPAH. The dimensions of Preserflo have been carefully selected to regulate flow and prevent hypotony. At 8.5mm in length with an internal lumen of 70μm in diameter (Figure 2), the device provides sufficient resistance to aqueous outflow to prevent IOP falling below 6.5mmHg. The procedure is significantly less invasive than trabeculectomy (Figure 3). It is not necessary to perform a scleral flap, sclerostomy, or iridectomy; all of which are essential steps for trabeculectomy.1
RPAH recognises the value of public patients having access to new technologies and has a streamlined process for achieving this. We were able to organise this technology for several patients, most of whom were at high risk of hypotony from traditional glaucoma surgery. A further possible use for the Preserflo MicroShunt is to assist in safer outcomes for doctors who do not perform a lot of trabeculectomy surgeries. The Royal Australian and New Zealand College of Ophthalmologists (RANZCO) recently changed its requirements, such that trainees no longer need to learn to perform independent trabeculectomy surgery as part of their training. For surgeons who infrequently perform filtration surgery, the Preserflo may prove to be a safer option with lower rates of hypotony. Having the technology available in the public sector allows trainees to become familiar with it, and they may potentially incorporate it into their practice.
An important part of introducing new technology is to track the safety and efficacy outcomes from new devices are in line with expectations. We have been using the Fight Glaucoma Blindness! Registry to track these outcomes. This Registry is a collaborative project of glaucoma specialists from Australia and New Zealand who have an interest in assessing real-world outcomes of glaucoma treatments. The Registry helps determine whether new treatments work, in which patients each device is most beneficial, and ultimately, whether each device is cost-effective. The Registry will also allow a comparison of real-world data between the standard of care, trabeculectomy, and the Preserflo MicroShunt. All RPAH patients are being tracked in the Registry to monitor safety and efficacy outcomes.
Artificial Intelligence and Diabetic Retinopathy Screening
Dr Peter Heydon
The implementation of artificial intelligence (AI) systems to assist ophthalmologists continues to be a flourishing area of clinical research. AI refers to software or machines that aim to mimic human cognitive functions, such as learning and problem solving. Diabetic retinopathy (DR) screening using human grading is currently time consuming, expensive, and labour intensive, and therefore represents an obvious target for AI augmentation. Different AI approaches range from those aiming to reduce the screening burden by excluding cases of no retinopathy or minimal retinopathy, to more advanced approaches that subclassify retinopathy grades and guide treatment decisions.
Figure 4. American Academy of Ophthalmology Oxford Grading System.
The SWEDDLA (South Western Eye and Diabetes Deep Learning Algorithm) Study, led by chief investigator Dr Shweta Kaushik (Campbelltown Hospital), and supported by myself as associate investigator, and a number of South Western Sydney ophthalmologists and endocrinologists, aims to assess and validate an open source, deep learning algorithm to screen for diabetic retinopathy. Forty-five-degree colour fundus photos and optical coherence tomography (OCT) images are evaluated, meaning that diabetic macular oedema can be more specifically analysed. The addition of OCT to traditional colour photographs represents an evolution in AI screening.
The incidence of diabetes is increasing across the world and in south-western Sydney, the Liverpool Eye and Diabetes Study (LEADS) revealed that among the diabetic population residing in Liverpool, 52.3% had any degree of DR, and 31.5% had vision threatening DR.2 Incorporating AI photograph-based screening provides an exciting opportunity to develop a point-of-care program within endocrinology, general practice and optometry practices for the area.
Several challenges arise from AI diabetic retinopathy screening. They have so far demonstrated excellent sensitivity and specificity but quality control and continued oversight by humans is required. The issues of ‘black box’ decision making by AI programs, data protection and privacy concerns, and the cost of implementation, particularly in the developing world, require further deliberation.
Recruitment for the SWEDDLA study has commenced in 2022.
Ikervis: A New Treatment for Severe Dry Eye Disease
Dr Athena Roufas
Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability, with potential damage to the ocular surface.3 It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Dry eyes are one of the commonest ocular complaints and can be quite debilitating when symptoms are severe. There is a myriad of treatment options available for dry eye, but in October 2021 a game changing treatment hit our Australian shores in the form of Ikervis (ciclosporin 0.1%) eye drops. Ikervis is the first cyclosporin eye drop to be listed on Australia’s Pharmaceutical Benefits Scheme (PBS) and is used to treat severe keratitis in adults with dry eye disease. I was fortunate enough to use Ikervis while working in the United Kingdom and found it to be a very beneficial adjunct treatment for severe dry eyes. So, I was incredibly pleased when Ikervis became available in Australia late last year.
Figure 5. Electrostatic attraction to the surface of the cornea means that once-daily Ikervis dosing is possible.
Milder forms of dry eye can be managed with artificial tears or thicker ointments for symptomatic relief, however more severe forms of dry eye disease are driven by a vicious cycle of inflammatory processes that require something more than artificial tears to dampen the disease. Without treating the cause, this vicious cycle can lead to severe damage of the corneal epithelium. Corticosteroids can help treat the cause by reducing ocular surface inflammation, but they have a poor side effect profile (especially with chronic use), and risk raising the IOP or inducing cataract formation. Another way to dampen ocular surface inflammation is to use a steroid-sparing agent such as a ciclosporin-containing eyedrop. This has been a challenge in Australia, up until recently, due to the absence of an approved, PBS listed product. This situation changed dramatically when Ikervis was added to the Australian PBS for the treatment of chronic severe dry eye with keratitis in adult patients. Ikervis is supplied in single-dose containers, can be stored at room temperature and has a three-year shelf-life. Dosage is one single drop into each affected eye, once daily at bedtime. Ophthalmologists and optometrists wishing to prescribe Ikervis for their patients will require phone or online authority via Health Professional Online Services (HPOS). To be eligible for Ikervis under the PBS, the patient must fulfill the following three criteria:
- A corneal fluorescein staining (CFS) grading of four at treatment initiation using the Oxford Grading System (Figure 4) or equivalent,
- An ocular surface disease index (OSDI) score ≥ 23, and
- The condition must not be adequately controlled by monotherapy with a preservative-free artificial tear substitute.
Ikervis’ formulation is worth a mention as it is an emulsion containing ciclosporin 1mg/ml (0.1%) as the active ingredient together with cetalkonium chloride (CKC), a cationic surfactant. This cationic oil-inwater emulsion of ciclosporin improves the residence time of ciclosporin on the ocular surface as the positively charged nano-sized droplets of the emulsion electrostatically adhere to the negatively charged mucins on the ocular surface (Figure 5). This improves ocular retention and absorption, and the lipids in the formulation also assist in stabilising the tear film, all of which allows Ikervis its single daily dose.
Ikervis is safe and well tolerated, even with long-term treatment. The SANSIKA4 and SICCANOVE5 studies showed that treatment with Ikervis was associated with significant improvements in corneal fluorescein staining from baseline values and versus control. The SANSIKA study also found that ocular surface inflammation was significantly lower in the patients receiving Ikervis compared to the patients receiving the control.
Although Ikervis is generally well tolerated, there are a couple of things that should be discussed with the patient before initiating treatment. The active ingredient, ciclosporin, may cause eye pain or irritation upon installation, although this is usually mild-to-moderate in intensity. The second point is that it may take some time before a patient’s ocular surface disease starts to improve. While Ikervis’ effects are not immediate, it works over the longer term to reduce ocular surface inflammation and damage from dry eye disease.
Professor Peter McCluskey is Professor of Clinical Ophthalmology and Eye Health at Faculty of Medicine and Health, The University of Sydney and is the Director of the Save Sight Institute at Sydney Eye Hospital. He is an internationally recognised inflammatory eye disease specialist. He consults publicly at RRAH and Sydney Eye Hospital. He consults privately at St Vincent’s Private Hospital.
Dr Jay Yohendran is the Head of the RPAH Ophthalmology Department. He specialises in refractive cataract surgery and consults privately at Northern Sydney Cataract on Sydney’s Lower North Shore.
Assoc/Prof Mitchell Lawlor is an ophthalmologist with dual fellowship qualifications from Moorfields Eye Hospital (London) in glaucoma and neuroophthalmology. He consults publicly at RPAH and Sydney Eye Hospital. His private rooms are located at Bondi Junction, Miranda and Macquarie Street.
Dr Peter Heydon is an ophthalmologist with fellowship qualifications in medical retina and uveitis from Moorfields Eye Hospital (London). He consults publicly at RPAH and Liverpool Hospital. His private rooms are located at the RPA Medical Centre, Brookvale and Liverpool.
Dr Athena Roufas is an ophthalmologist with fellowship qualifications in cornea and anterior segment trauma from King’s College Hospital (London) and glaucoma from Westmead Hospital (Sydney). She consults publicly at RPAH. Her private rooms are located at the RPA Medical Centre, Chatswood and Mosman.
References
- Baker ND, Barnebey HS, Moster MR, et al. Ab-externo MicroShunt versus Trabeculectomy in Primary Open-Angle Glaucoma: 1-year Results from a 2-year Randomized, Multicenter Study. Ophthalmology (2021).
- Liew, G., et al. Profile of a population-based diabetic macular oedema study: the Liverpool Eye and Diabetes Study (Sydney). BMJ Open 9, e021884 (2019).
- DEWS. Diagnostic methodology of the International Dry Eye WorkShop. Ocul Surf, 5, 108-52 (2008).
- A Leonardi et al. Efficacy and safety of 0.1% ciclosporine A cationic emulsion in the treatment of severe dry eye disease: a multicentre randomized trial. Eur J Ophthalmol. 26(4):287-96 (2016)
- C Baudouin et al. A randomized study of the efficacy and safety of 0.1% cyclosporine A cationic emulsion in treatment of moderate to severe dry eye. Eur J Ophthalmol. 30;27(5):520-530 (2017).
