World Glaucoma Congress 2019: Sharing the Knowledge

With a strong focus on glaucoma education, the 8th World Glaucoma Congress delivered over 21 symposia, 24 courses, grand rounds, a film festival, rapid fire presentations, and the largest surgical wetlab in the field of glaucoma. The congress also featured several symposia organised by society members of the World Glaucoma Association.

big data appears to be an important future player in targeted glaucoma treatment

PRESIDENT’S WELCOME

Dr Keith Martin, the president of the World Glaucoma Association, welcomed delegates to the World Glaucoma Congress in Melbourne and highlighted dedicated sessions on paediatric glaucoma, angle closure glaucoma, and normal tension glaucoma as well as debates on controversies in glaucoma. The congress included updates in glaucoma genetics, new therapies, and artificial intelligence. The challenges faced in delivering a glaucoma service in different global settings were also discussed, allowing participants to share and learn from each other’s experiences.

NEW FRONTIERS IN MEDICAL MANAGEMENT

This session began with a discussion on the ciliary muscle as a new target for glaucoma therapy. Potential methods include laser ’softening’ and biological approaches with gene therapy to increase elasticity of ciliary muscle attachments and improve aqueous outflow.

Rho-kinase inhibitors were discussed as another new frontier in medical glaucoma management, shown to be efficacious in ocular hypertension, primary open angle glaucoma, primary angle closure glaucoma, and secondary glaucoma subtypes (e.g. pseudoexfoliation). Rho-kinase associated signalling leads to cell contractility, cytoskeletal rearrangement, and cell motility to increase trabecular meshwork resistance to aqueous outflow. Rho-kinase inhibitors are thought to act on endothelial cells in Schlemm’s canal, the cytoskeleton of the trabecular meshwork and inhibit extracellular matrix production to reduce resistance in the conventional outflow pathway and thus lower the intraocular pressure (IOP). The IOP reduction effect is maximal at two hours and lasts approximately 24 hours. Common sideeffects include conjunctival hyperaemia (4%), conjunctivitis (1.4%), and blepharitis (0.8%).

Pharmacogenomics and optimising glaucoma management via biomarkers was another focus of discussion. Groups around the world are ‘biobanking’ genotypes, proteomics, phenotypes (clinical data) and environmental exposures to understand the pathophysiology of glaucoma and thus improve treatment targets. We now have greater understanding of human genes and more people are engaged in their health and can track and share their data. The aspirational arenas for precision-based glaucoma treatment include large datasets to discover biomarkers for outcomes; understand mechanisms of clinical risk factors (e.g. IOP, corneal thickness) and understand mechanisms of aging, oxidative stress, autophagy, and the role of environmental exposures. This will allow us to target high risk individuals who are most at risk of blindness from glaucoma. We now have technologies that can collect and process huge amounts of data – ‘big data’ appears to be an important future player in targeted glaucoma treatment.

Another new molecular target for IOP lowering is nitric oxide. Nitric oxide (NO) is already a target in cardiovascular disease, it regulates gastrointestinal function and also platelet adhesion. In the eye, NO is produced in response to raised IOP. It increases cytoskeletal relaxation and thus improves conventional outflow to subsequently reduce IOP. NO also increases cyclic guanosine monophosphate (cGMP), which may have a neuroprotective effect on retinal ganglion cells. NO synthase enzymes (which produce NO) are located throughout ocular tissue, including the trabecular meshwork. Studies have shown that eyes with primary open angle glaucoma (POAG) exhibit lower levels of NO synthase activity. This led to the development of latanoprost bunod – a dualagent medication (prostaglandin and NO) which has shown efficacy in reducing IOP. It is yet to be available in Australia.

New delivery systems were another focus of discussion during the meeting. The need for new delivery systems may be required due to ocular surface side effects, compliance, and quality of life reduction associated with chronic treatment. Even once drops are in, 80% of a drop is lost after one single blink. Areas of research in novel delivery systems include contact lenses with a thin drug polymer film encapsulated within the periphery of the contact lens. The polymer film helps modulate the release for the drug from the lens. Expected IOP reduction in early trials is 3-6mmHg. Punctal plugs containing prostaglandins are also an area of current research. Finally, biodegradable anterior chamber implants containing slow release prostaglandin are being studied regarding safety, stability, and efficacy in early human trials. These implants are hoped to reduce adverse effects and improve tolerability of anti-glaucoma agents.

DILEMMAS IN GLAUCOMA SURGERY

The first dilemma discussed during this session was on clinical scenarios in which to consider minimally invasive glaucoma surgery (MIGS). The aim of MIGS is to increase the outlook pathways in the eye. They can be divided into trabecular MIGS, suprachoroidal MIGS, and MIGSPlus (with use of anti-metabolite and formation of a bleb), based on the tissues targeted and materials used.

Trabecular MIGS create a pathway through the trabecular meshwork. They may be considered in ocular hypertension or early-mild glaucoma in medically treated patients undergoing cataract surgery for the opportunity to reduce or eliminate IOP lowering drops.

Studies have shown that glaucoma patients on IOP lowering drops have higher inflammatory and fibrotic activity than normal controls

Suprachoroidal MIGS create a direct pathway into the suprachoroidal space. They may be used in mild-moderate glaucoma with similar clinical indications to those outlined above.

MIGS Plus require use of an antimetabolite and management of a bleb. Nevertheless, they may have the potential to control IOP without the need for trabeculectomy in mild-moderate cases.

The next discussion focused on the decision between undertaking a trabeculectomy versus glaucoma drainage device. Recent three-year data from the primary tube vs trabeculectomy study in open angle glaucoma showed that mean IOP was lower in the trabeculectomy group than the tube group at all assessed time points. Preoperative IOP was the only baseline factor that appeared to influence surgical failure.

Managing a bleb after trabeculectomy has proven a challenge, even with the implementation of anti-metabolites such as mitomycin-C. Studies have shown that glaucoma patients on IOP-lowering drops have higher inflammatory and fibrotic activity than normal controls. As such, targeting pro-inflammatory cytokines which drive inflammation and scarring preoperatively may improve surgical outcomes. Interestingly, some centres around the world use pre-operative oral steroids or nonsteroidal anti-inflammatory drugs (NSAIDs) to minimise post-operative fibrosis.

Post-operative management of scarring includes surgical procedures such as bleb needling. Currently, studies are being performed on agents such as hyaluronic acid which may have an anti-fibrotic effect and act as a spacer to inflamed tissue post-needling. It is critical to understand the role of all cellular players in wound healing after filtration surgery. Nevertheless, early recognition of persistent inflammation or impending bleb failure and immediate intervention is vital to successful blebs after trabeculectomy.

INNOVATIONS IN SURGICAL MANAGEMENT

Dr Nathan Kerr chaired the symposium on innovations in the surgical management of glaucoma. This symposium provided an overview of the current and potential future roles of surgery in glaucoma management. Dr Ike Ahmed introduced the new paradigm of interventional glaucoma, intervening proactively to prevent blindness, reduce treatment related quality of life issues, and improve overall quality of life using safer and less invasive surgical techniques. The importance of intraocular pressure reduction was highlighted, with data from the Ocular Hypertension Treatment Study (OHTS) and the United Kingdom Glaucoma Treatment Study (UKGTS) showing that for each mmHg IOP is reduced, the risk of progression decreases by 10–19%. Data showing continued progression despite medical therapy was presented as was data from the Advanced Glaucoma Intervention Study showing that patients who consistently achieved an IOP below 18mmHg at all visits over six years experienced virtually no deterioration in visual field score on average. Other challenges with medical therapy include adherence, side effects, and drop instillation. Surgical intervention produces lower IOPs, reduces progression risk, reduces IOP fluctuation and peak IOP, improves ocular perfusion, addresses adherence, and may reduce local side effects from topical glaucoma medications. Dr Ahmed argued that the shift to safer glaucoma surgery has allowed for the shifting of targets and that bleb-based surgery provides the most consistent way to get an IOP < 13mmHg without medications.

Dr Stalmans presented surgical options available for achieving low IOP, including the Preserflo MicroShunt, which is designed for implantation into the subconjunctival space. Manufactured from a biocompatible material used in cardiac stents, the MicroShunt elicits minimal foreign body reaction, inflammation, scarring, and capsule formation. Placed superiorly, either nasal or temporal of superior rectus, the MicroShunt drains aqueous to the subconjunctival/subtenons space creating a posterior bleb. Surgical videos were shown and pearls shared for optimum placement and avoidance of complications.

During a symposium on innovations in the surgical management of glaucoma, Dr Kerr highlighted the importance of bleb management techniques to improve clinical outcomes in bleb-based surgery. Like any surgery, bleb-based surgery triggers a wound healing response characterised by bleeding, inflammation, proliferation, and remodelling. Simple measures taken pre-operatively, intraoperatively, and post-operatively can enhance IOP lowering and bleb survival. A common cause of pre-operative inflammation is chronic treatment with topical glaucoma medications, especially those containing benzalkonium chloride preservatives. Withholding glaucoma medications and using oral carbonic anhydrase inhibitors to control IOP, or changing to preservative free glaucoma drops, as well pre-operative use of topical steroids has been shown to reduce conjunctival inflammation and enhance bleb survival following surgery. Intraoperatively, topical vasoconstrictors, careful conjunctival handling, haemostasis, and minimally traumatic surgery can avoid the release of blood cells and minimise the trigger for the inflammatory phase. Where safe, anti-coagulants or antiplatelet medications can be withheld prior to surgery to reduce the risk of intraoperative bleeding. The application of antimetabolites, such as 5-fluorouracil or mitomycin C, has revolutionised blebbased surgery, particularly in patients at high risk of surgical failure. These potent anti-scarring agents have been shown in randomised trials to increase bleb survival. Post-operatively, topical steroids and non-steroidal anti-inflammatories may modulate inflammation, limit immune activation, and reduce vascular permeability. Novels agents like tranilast or FT011, currently undergoing clinical trials at the Centre for Eye Research Australia, may further enhance surgical success.

LASERS IN GLAUCOMA

This session provided a review and update of the use of lasers in glaucoma. Mr Gus Gazzard from Moorfields Eye Hospital and University College London presented the results of the LiGHT trial, a landmark multicentre randomised controlled trial of selective laser trabeculoplasty (SLT) versus eye drops for first line treatment of ocular hypertension and glaucoma. In this study, over 700 newly diagnosed patients who had received no previous treatment for glaucoma were randomised to either SLT or glaucoma eye drops and were asked to complete quality of life questionnaires and have their intraocular pressure and eye drop use monitored regularly for three years. At 36 months, 74% of patients in the selective laser trabeculoplasty group required no drops to maintain their IOP. Compared to medical therapy, eyes treated with SLT were more likely to be at target IOP and less likely to require treatment escalation or glaucoma surgery.

biodegradable anterior chamber implants containing slow-release prostaglandin are being studied regarding safety, stability and efficacy

From an ophthalmic cost perspective, SLT as first line treatment was more cost effective than eye drops. Based on these results, SLT should be offered as first line treatment for open angle glaucoma and ocular hypertension.

Prof Mingguang He from the Centre for Eye Research Australia presented the results of the ZAP Trial, a randomised controlled trial investigating laser peripheral iridotomy for the prevention of angle closure glaucoma. This study was conducted at the Zhongshan Ophthalmic Centre, a tertiary specialised hospital in Ghangzhou, China. Bilateral primary angle closure suspects aged 50–70 years received laser peripheral iridotomy in one randomly selected eye, with the other remaining untreated. While the incidence of angle closure disease was low, laser peripheral iridotomy had a significant prophylactic effect in the prevention of angle closure.

GRAND ROUNDS

The Grand Rounds session at WGC brought together challenging cases from around the world, providing an opportunity for discussion and debate. This year saw discussion on management issues in the development of bilateral cystoid macular oedema following SLT in both eyes of a patient as well as vitreous occlusion of a tube in a glaucoma drainage implant after complicated cataract surgery. Other challenging cases included secondary angle closure in microspherophakia and acquired aniridia.

WORKSHOPS

Highly educational workshops provided delegates with an opportunity to enhance their skills with optical coherence tomography (OCT) imaging, optic disc assessment, and visual field analysis. OCT imaging is playing an ever increasing role in glaucoma management. Participants learnt to recognise artefacts in OCT imaging and judge the quality of images. This was followed by interpretation of images through a multitude of clinical cases and supported by evidence from larger studies.

Optic disc assessment was taught by top graders from the European Optic Disc Assessment Trial (EODAT) who showed participants the basics of assessing optic discs using stereoscopic displays, helping them get to know which features are the most important for a diagnosis of glaucoma.

Visual fields play an important role in the management of glaucoma. There are, however, many pearls and pitfalls in their interpretation. In a highly interactive course, participants learnt how to correctly interpret Humphrey visual fields.

FILM FESTIVAL

The film festival saw many interesting and educational videos including a novel technique for easy and precise tube insertion, management of tube migration and persistent hypotony, how to fix a short tube, how to insert the iStent Inject, and innovations in trabeculectomy amongst others.

CONCLUSIONS

The World Glaucoma Congress was a great success and an unforgettable event. Bringing together people from all around the world, it has made a positive impact on glaucoma globally.

Dr Alp Atik is a Glaucoma Fellow at the Royal Victorian Eye and Ear Hospital. He graduated from the University of Newcastle with a Bachelor of Medicine (with Distinction) and Bachelor of Medical Science (Class 1 Honours). He undertook his residency at Royal Prince Alfred Hospital in Sydney, before moving to the United States to complete a Master of Public Health at Harvard University. During this time, he also undertook a Master of Medicine (Ophthalmic Science) and conducted research at Massachusetts Eye and Ear Infirmary as an Australian Government Endeavour Scholar. Dr Atik’s interests include diagnosing and managing glaucoma, retinal disease and cataract. He also has a keen interest in ophthalmic education and research. 

Dr Nathan Kerr, is a fellowship-trained glaucoma subspecialist in Melbourne, Australia. A recipient of the Bayer Scholarship, he completed a prestigious fellowship at Moorfields Eye Hospital in London where he trained in Minimally Invasive Glaucoma Surgery (MIGS) under world-renowned surgeon Mr Keith Barton. Dr Kerr was amongst the first surgeons in Australia to be accredited in the use of several novel MIGS procedures. He serves as a Glaucoma Section Editor for Clinical and Experimental Ophthalmology and is the Glaucoma Surgical Trial Lead at the Centre for Eye Research Australia. Dr Kerr is a Consultant Ophthalmologist at the Royal Victorian Eye and Ear Hospital and consults privately at Eye Surgery Associates in East Melbourne, Doncaster, and Vermont South. doctorkerr.com.au