RANZCO maintains high momentum at 49th Annual Scientific Congress

For the 49th time, ophthalmologists from Australia and New Zealand gathered to share and discuss the latest innovations, techniques, and advances in eye healthcare – this time at Perth’s Convention and Exhibition Centre.Despite its status as one of the world’s most rote capital cities, the attendance figures (1,013 all up), donstrated that the level of interest shown by delegates and the supporting industry matched previous congresses. The usual format of three and a half days of lectures and workshops, supported by various social events was continued.Up to seven concurrent sessions were run and the proximity of most theatres to one another meant it was possible to change location without missing presentations. The program itself was also aided by several industry-sponsored events including breakfasts on all four mornings.Fred hollows lectureSydney ophthalmologist Dr Geoffrey Cohn OAM presented the 2017 Hollows Lecture, titled ‘Teaching and Learning in a Resource-Poor World’. Having visited countries like Myanmar, Cambodia, and the Indian state of Andhra Pradesh as both a surgeon and educator, the South African-born Cohn is very familiar with the poorly resourced world.To both open his lecture and confirm that progress is possible, Cohn revealed that Myanmar has had great success in reducing its trachoma prevalence from a high of 43% to its current rate of just 3%. Taking the lead from the late Professor Fred Hollows, with whom Cohn had worked, he related that “Hollows was always there in the thick of it”.In the India theatre of operations, he reported the use of mid-level ophthalmic technicians in clinical, operating theatre, and community settings as a way of unloading time-consuming procedures. In doing so, more time was left to teach local medical staff.Referring to the probl of POAG in South Africa (Bophuthatswana), he observed that 90% of the affected patients presented with small pathologies. Expanding on the the of small pathologies, he nominated headache as the third biggest probl in Bophuthatswana based on his experience.{{image3-a:r-w:300}}On the other hand, Myanmar has 12.5% of its population afflicted with primary angle-closure glaucoma (PACG), resulting in people turning up at eye camps totally blind. He and his team introduced vitreo-retinal equipment and procedures to Myanmar. Over its first three years of operation, the Myanmar project went from zero to 200,000 patients per year.Reflecting on his earlier involvent in teaching in PNG, Cohn traced the methods from using cucumbers as an initial surgical model to wet labs using contporary equipment. He claimed that having the right people and the right skills (including people skills) was more important than fancy equipment and the availability of disposables.However, despite the best-laid plans, he admitted that, overall, there was more being said than done in impoverished parts of the world. Cohn said his ultimate aim was to, “do ourselves out of a job”, as local competence, once developed, would mean that visitations from outsiders would no longer be necessary.Council lectureCERA managing director Professor Jonathan Crowston delivered the 2017 Council Lecture. Titled ‘Current Challenges – Future Opportunities in Glaucoma’, Crowston stated that one of the main challenges in glaucoma was that the retinal ganglion cells (RGCs) were under pressure.He described glaucoma as characterised by distinctive, progressive, structural changes of the optic nerve head (ONH), such as neuroretinal rim loss, accompanied by a selective loss of RGCs and their axons (although it is now known that RGCs survive longer into the disease than thought initially, albeit in an altered or even dysfunctional state).Such structural changes are accompanied by predictable but variable functional changes that are still not well understood, and ultimately, blindness is a possibility. Crowston gave the main risk factors as age, a genetic predisposition, and elevated IOP, noting in passing that elevated IOP rains the only modifiable risk factor at this time. The prevalence of POAG, a condition that might exhibit normal IOP (NTG) or be preceded by ocular hypertension (OHT), is greater than the latter as both advance with age.RGCs do not exist in isolation, rather they have attendant astrocytes whose activity increases early in the disease, at least in an animal model. Microglia (CNS support tissue) and oligodendrocytes that suffer loss following axon degeneration, at least in an animal model, are also present. Furthermore, pressure on astrocytes can result in the production of damaging by-products.As a result of genome-wide association studies (GWAS), some 542 genes have already been identified as being involved with various glaucomas. The optineurin gene has been linked to POAG (NTG and adult-onset forms) as well as other neurodegenerative diseases. Even though it is sometimes viewed as a one-dimensional clinical parameter, IOP is not a static entity and is only so in short time frames.Despite how the visual effects of glaucoma are often depicted in patient information materials, the vision impairment in all but advanced cases is not usually that of large scotomata or significant ‘missing bits’. Rather, it is more likely to be some blurring with visual-field deficits made up for by the retina of the fellow eye, which is probably still functional unless the patient is particularly unlucky. Only monocular field-testing is likely to reveal the true extent of any deficit.Much research is now targeting optic nerve protection (N II neuroprotection), but to date the only probable way is IOP lowering. Ciliary neurotrophic factor (CNTF)/neurotrophic factor (NTF) implants are the subject of research currently.Glaucoma surgery, until the advent of MIGS devices, had been anti-fibrosis in nature.Crowston listed pseudoexfoliation syndrome, pigment dispersion syndrome, and OAG as current challenges presenting the ophthalmic research community with unmet needs and opportunities. However, he warned that the clumping together of those diseases was “unhelpful”, especially as each of th may in turn be representative of several diseases.A pressing probl was the ageing of the Australian population, which unceasingly adds to the number of glaucoma patients.Quoting figures he attributed to Australian commentator and dographer, Bernard Salt, Crowston said the rise in those over 65 years of age had increased from 0.7% in 1950 to 3.7% in 2016, with it projected to be 7.9% by 2050. He also reiterated the often-used figure that about half of glaucoma sufferers are unaware of their disease, in some cases despite being seen by an eyecare professional ‘recently’.{{image4-a:r-w:300}}Crowston promoted the GONE project (Glaucomatous Optic Neuropathy Evaluation), spearheaded by CERA Drs Kong, O’Neill, Gurria, Coote, and Crowston himself, claiming that ophthalmologists and optometrists could enhance their glaucoma detection skills by using the training materials and photographs on the project’s website.He also confirmed the known compliance probl with glaucoma patients – 50% cease all drop usage by six months, while only 37% are still compliant at the 12-month mark. Just 10% have no gaps in their medication refill history.As a result, slow-release, polymer-hosted intraocular drugs are under investigation. Preventative therapies are also being investigated and vitamin B3, a restorer of mitochondrial reserves, is one possibility.Electrophysiology was named the tool of choice to monitor RGC activity. Using that technology, it has been shown that physical exercise can enhance RGC recovery after injury from IOP elevation, as well as lowering IOP itself.According to Crowston, while still sometime away, RGC regeneration and RGC replacent using st cell technology are other possible future treatments. Optic nerve regeneration using a zinc chelator known to encourage axon regrowth all the way back to the superior colliculus, has also been considered. Returning to the subject of MIGS, he stated that an anti-fibrosis therapy was still needed.Looking to the future, he believes that by 2030, glaucoma will be diagnosed with the assistance of RGC-health and retinal metabolic stress monitoring, hyperspectral imaging, reflectance patterns, and spectral and spatial information derived from each pixel of ocular images. He expects that glaucoma surgery will be done relatively early and the process will be titratable, with predictability and success rates similar to the current cataract surgery model.Crowston also predicted a future for neuroprotection and saw roles for collaborative care, artificial intelligence (AI), and possibly cell regeneration.Dame IDA Mann lecture{{image5-a:r-w:300}}University of Auckland cell biologist Professor Trevor Sherwin’s lecture was titled ‘The Prise and the Promise of Regenerative Medicine’. By way of the promise, Sherwin offered the salamander as an example of regeneration. However, he revealed that the animal’s regeneration was not st cell based, rather its regeneration deployed real bone, real muscle, real nerves, etc.Sherwin traced successful tissue transplantation and other manipulations of nature from blood transfusions (1874), bone marrow (1957), mammal cloning (1997), and skin transplants (1994), to st cells (iPSCs – 2006). He then explained cell potency, a cell’s ability to differentiate into multiple types.Totipotent cells can become any cell type; pluripotency refers to the ability to differentiate into any of the three germ layers, endo, meso, or ectoderm; multipotency can differentiate into discrete cell types; oligopotency can differentiate into only a few cell types; and finally, unipotent cells, which can differentiate into only one cell type.Adult st cells (SCs) have limited ability to proliferate (oligopotency), making direct transplant problatic, including the possibility of tumorigenicity, while there have also been difficulties getting requests past ethics committees.Corneal regeneration is probably limited to autologous SCs, induced pluripotent st cells (iPSCs), and cell reprogramming. Of those, expanded SC transplants have been performed successfully.The important properties of SCs in an ocular sense are: sphere-forming ability, the ability to produce SC markers (used to isolate and identify SCs), the ability to maintain homeostasis including in the long-term, sometimes after periods of inactivity, and the ability to undergo asymmetric division. SCs have been used to repopulate the human corneal limbus successfully, but efforts so far have not done the same for the sclera, as it is more of a 3D task.While much pre-clinical research has been done on iPSCs, the one AMD trial in humans was aborted due to the cancer caused, probably due to the general make-up of the SCs used in the trial. Experiments with bryoid bodies (3D aggregates of pluripotent SCs) formed by iPSCs have been induced to form neural crest cells (the cornea is an bryological derivative of the neural crest) in the hope of inducing a transition to keratocytes eventually.{{image6-a:r-w:400}}Generally, markers are used to identify the SCs present and thus the stage reached, while autologous SCs are preferred because they avoid any immunological probls.Cell reprogramming endeavours target keratoconus currently, trying to offset that condition’s losses of extracellular matrices, kerotocytes, and stromal integrity. What is envisaged is in vivo tissue engineering. A 2016 patent of a ‘pachymatrix’ consisting of dexamethasone and TGFb3 is intended to produce collagen type II, in the hope that later type I collagen will replace the type II.As far as physical properties are concerned, the properties of ex vivo corneas have been improved considerably in the lab, and the processes used have been turned on and off as required, successfully.One technique under investigation for myopia is to use existing methods, such as a CL in an Ortho-K-like context or intrastromal rings, to reshape the cornea prior to treating it with thickening or stiffening technologies that will retain its new, more desirable shape and properties. So far, the corneas of sheep have been reshaped and stiffened successfully.However, a Lancet Commission report on SCs and regenerative medicine released in October 2017 showed poor quality science, unclear funding models, and poor, little, or no regulation of clinics purporting to perform SC transplants/implants.Additionally, the ‘patients’ were described as desperate people, press exposure was prature and unwarranted, and as a result, the expectations of the field were ‘overblown’ to such an extent that the report felt that ‘regenerative medicine’s social licence to operate was threatened’.Already, the FDA has shut down at least one US-based SC centre purporting to be able to treat AMD. The clinic had no track record in the field and committed the gravest of errors by treating both eyes in the same session, leading to bilateral serious vision impairment or blindness in at least three cases. Essentially, they were in contravention of the central tenet of medicine – first, do no harm.

RANZCO's Flagship Event Gallery

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More reading: Special Report Part 2: RANZCO 2017: Myopia, collaborative care, and beyond