Education Committee Highlights WGC-2019 – part 6

The Education Committee carefully selects presentations from the WGC-2019 for your benefit. This month Ronnie George introduces the sessions: Controversies in angle closure treatment, International Society of Glaucoma Surgery – Glaucoma Surgical Nightmares and New Potions from the Hogwarts Cauldron for Treating Glaucoma.

Controversies in angle closure treatment

This session is in a debate format which takes up the questions of laser peripheral iridotomy for all in PACS, the role of laser peripheral iridotomy for all in PACS, iridoplasty in PACG and clear lens extraction are based on cases introduced by Dr Yaxing Wang, Dr Tin Aung and Dr Rahat respectively and then debated by the other speakers.

Controversies in iridotomy

Dr Yaxing Wang presents a lady with recurrent headaches with primary angle closure in the right eye and PACG in the left eye who underwent YAG laser peripheral iridotomy in both eyes. Following the the procedure her symptoms improved. She reviews the ophthalmology technology assessment on laser peripheral iridotomy in primary angle closure which is a meta analysis of studies on iridotomy. She reviews the short term and long term angle response, the reported risks of IOP elevation in different disease stages while bringing out the lack of information on outcomes in angle closure due to different mechanisms.

Dr Norlina Ramli argues against Iridotomy in PACS. She focusses on the huge disease burden in the population and highlights that LPI only addresses the pupillary block mechanism. She reviews 6 studies that used gonioscopy, ASOCT and UBM to assess outcome of LPI that showed other causative mechanisms. She argues against LPI for PACS by quoting from the ZAP study which reports a low risk of progression in a randomised control trial designed to study the impact of LPI on progression of PACS.

Prof Tin Aung introduces the second case to discuss the role of iridoplasty. He discusses the limitations of LPI alone in controlling IOP control and reducing the need for future surgery. He discusses the rationale and describes the procedure of iridoplasty. The case for discussion is a 59-year-old lady with good vision, elevated IOP, closed angles opening on compression with 1-2 clock hours of PAS. The discs show significant damage and the visual fields severe glaucomatous damage.

Dr Poeman Chan argues in favour a doing an iridoplasty. He reviews the evidence provided by Narayanswamy et al in their randomised control trial that reported no benefit with iridoplasty and advances reasons why the he challenges these conclusions. The importance of appropriate patient selection and the benefit of iridoplasty in different published studies are used to make his case. He also reviews other options such as clear lens extraction and long term medications n this situation with respect to the risk of macular wipeout and raises pertinent questions about the reluctance of many patients to undergo surgery for a clear lens. medications

Dr Suman Thapa speaks about the different mechanisms of angle closure glaucoma and how LPI addresses only pupillary block. He also outlines the long term reduction in therapeutic effect of an LPI. He reviews articles on long term angle outcomes following iridoplasty and the need for medications with time. The results of an RCT on iridoplasty are discussed and Dr Thapa concludes with what his approach would be.

Clear lens extraction for PACS

Dr Rahat Husain presents a 67-year-old female Chinese race with PACS with no PAS, disc or field changes and highlights that this is common in Asia. He mentions other clinical information that he would consider asking for in these patients. He reviews both the published risk of progression of PACS, the low risk of acute closure in these eyes as well as the fact that PACG is a more blinding disease. The risks of clear lens extraction are reviewed. He speaks of other factors that he would take into account that would impact his decision making and that in different clinical settings financial and access to care would also play a role.

Prof Clement Tham argues for clear lens extraction. He describes how lens characteristics have always be discussed as being important in angle closure and that clear lens extraction should be consider an option. He shares a case, a 46 year old lady with high hyperopia, occasional migraine, narrow angles and a healthy optic nerve. He outlined the possible outcomes in this lady and why clear lens extraction would be a valid therapeutic option which would also have refractive benefits.

Dr Marcelo Hatanaka spoke against the motion. He introduces a case of a 54-year-old lady who had undergone LPI in the past and healthy discs and fields with early lens changes. He goes on to describe the outcomes of cataract surgery in her eyes. He reviews the risk of progression in PACS reported from different studies as well as the EAGLE study while emphasising that PACS, PAC and PACG are different stages of the disease and ends with an old surgical dictum.

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International Society of Glaucoma Surgery – Glaucoma Surgical Nightmares

This session by the International Society of Glaucoma Surgery has four talks, three of which are available online. The lectures deal with difficult situations related to glaucoma surgery.

Michael Coote spoke about the rescue of a failing filter. He advocated a stepwise approach to dealing with a hypotonous eye describing how to tackle a choroidal drainage, the techniques of a Palmberg suture to strap the bleb with his modification of using a large absorbable suture to induce inflammation and produce adequate compression. A stepwise approach to managing hypotony is advocated reserving a flap revision as the last step in case of persistent hypotony. The problem with high IOP related to bleb failure was divided into scarring at the level of the flap, the areas around it and related to absorption of aqueous into the tissues. The options of and indications for needling, a limited bleb revision and a bleb revision are nicely described. He also emphasised that bleb revision is an option for encapsulated belbs following glaucoma drainage device insertion and discussed the impact of IOP on permeability of the bleb wall.

Taarek Shaarawy spoke on rescue surgeries with MIGS. He started by reminding us that the perception that glaucoma surgeries have high complication rates is true. He demonstrates how to repair a leaking bleb post non penetrating surgery. The management of iris incarceration following aggressive goniopuncture procedure after an NPDS is presented. The correct technique of performing a goniopuncture is described. The problem of tube exposure following AGD is dealt with, suggesting the use of tutoplast to cover the exposed tube. Careful apposition of the conjunctiva and the use a conjunctival graft to prevent undue stretch is advocated. A novel approach of placing the tube in a tunnel covered with the scleral flap is shown which reduced exposure rates substantially by keeping a flatter profile. The importance of avoiding a blood vessel while injecting the Xen implant was highlighted as was the risk of creating an inadvertent cyclodialysis cleft during the procedure. Bleb revision with the Preserflo device is also demonstrated.

Leon Yu spoke about Problems with Plumbing dealing with glaucoma drainage devices. The challenges in deciding between an immediate IOP reduction obtained with an AGV versus better long term control with the Baerveldt implant are discussed. The various techniques of reducing risk of hypotony, including blocking the tube, ligatures with Sherwood slits with the nonvalved device are demonstrated while emphasising that none of the techniques are foolproof and hypotony can occur with any of them. Various tips of how to manage hypotony in this situation are demonstrated. The use of a healon GV to reform the anterior chamber is helpful but can be unpredictable. This may need to be combined with tube occlusion using prolene or supramid. The risk of corneal endothelial loss in GDD’s is very significant with a 5.5% annual decrease in cell counts for tubes placed in the anterior chamber. Dr Yu strongly advocates placing the tube in the sulcus in pseudophkic eyes and demonstrates both an ab externo and an ab interno approach. He also introduced potential solutions in the future for tube related hypotony offered by the Paul glaucoma implant and titratable IOP control with the Eyewatch device.

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New Potions from the Hogwarts Cauldron for Treating Glaucoma

This was a very absorbing session on cutting edge research focussing on potential novel therapeutic approaches for glaucoma.

Keith Martin: Gene therapy for glaucoma

Keith Martin presents the rationale for gene therapy along with other non IOP lowering treatments since not all our glaucoma patients are stable with IOP control alone and about 13.5% of people progress to blindness. He briefly reviews the evolution of gene therapy. Adenovirus vectors have been used to deliver brain derived neurotrophic facto (BDNF) into the retina with short term rescue of 40% of retinal ganglion cells. This effect did not last because of down regulation occurring very soon within a week itself. A new approach using a a non conventional design including both TrkN and BNDF which replaces the TrkB receptor in the target and releases BDNF. He presented evidence about how mBDNF and TrkB proteins were expressed in correct cellular locations and this increased RGC TrkB and mBDNF expression lasted or at least 6 months. There were no adverse effects even on high doses on ERG, IOP, gliosis or survival of other retinal cells and an AAV-TrkB-BDNF provided RGC axon preservation even in a raised IOP model in elderly rats. He showed comparisons with the BDNF alone model in in optic nerve crush models and in acute and chronic elevated IOP model. The impact of the new construct on axonal transport is explored. Some of the design concerns in a soon to be initiated clinical trial are shared as well as speculation as to where gene therapy would fit in the therapeutic regimen.

Yvonne Yu: Rescuing Susceptible Retinal Ganglion Cells

In order to address this Yvonne YU addresses fundamental questions about cell type specificity, and in a step wise manner addresses the issues of which ganglion cells are lost first and whether the different ganglion cells have differing susceptibility to IOP elevation. She breaks down how the circuit is disassembled by focussing on whether there is there loss of synapses because presynaptic bipolar cells die, are both sides of excitatory synapses dismantled at the same time and if synapse loss across different types of bipolar cells is uniform . The evidence regarding plasticity and capacity of adult ganglion cells for rewiring is presented. The experimental evidence on timing of synapse loss in relation to dendritic pruning following RGC loss is presented.

Toshihiro Inoue: Targeting the Meshwork-A 21st Century Renaissance

Prof Inoue explains how one success story of targeting the trabecular meshwork for IOP reduction has been achieved with the ROCK inhibitors which are now commonly used for glaucoma treatment. He demonstrated how ROCK inhibitors work by showing time dependent depolymerisation of actin fibres and change of cell shape resulting in wider spaces in the TM and less outflow resistance. He discusses the effect of TGF beta on decreasing outflow facility and caused actin contraction thus being potentially involved in IOP regulation. TGF-β activates Rho-ROCK signalling in TM cells, which is suppressed by ROCK inhibitor. The cross-talk between IL-6 and TGF-β pathway in TM cells and its interaction can in part explain the effect of ROCK inhibitors . He explores the interaction of IL 6 and TGFB receptors 1 and 2 and the interaction between the TGF beta and IL 6 pathways.

Jonathan Crowston: Vitamin B3 (Niacin) in glaucoma-to good to be true?

Jonathan Crowston introduces the reasons why Vit B3 may serve as a glaucoma therapeutic option because of its impact on the bioenergetic deficiency associated with ageing. Older age is associated with greater risk of developing POAG and Prof Crowston lists the associations with Mitochondrial dysfunction and reduced NAD+ reduced with age as possible contributory factors. The high energy requirements of neuronal tissue could explain this decline with age. Since RGC’s are very long and partly myelinated there may be different energy requirements in different portions with corresponding susceptibility. He presents evidence from clinical POAG and LHON cohorts that demonstrate an association with mitochondrial dysfunction seen as complex I abnormality especially with age. The reasons for NAD + decrease with age are discussed. He presents data from animal experiments that have demonstrated that Niacin modulated mitochondrial dysfunction prevented glaucoma in an inherited mice model for glaucoma even at low doses.

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