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Report

Southern Regional Congress continues to surprise

06/08/2018By Lewis Williams PhD
Tips for managing AMD before it starts, advances in ocular imaging, and a new technique for learning feature in part two of LEWIS WILLIAMS’ SRC report.

A highlight of this year’s Southern Regional Congress (SRC) was the H Barry Collin Medal Lecture by world-renowned microbiologist and eye and CL researcher, Professor Mark Willcox. The medal was first awarded eponymously to Professor Collin in 1977 and, subsequently, has been awarded to a list of recipients that reads like a who’s who of Australian optometric and ocular/vision research luminaries.

The academic contributions of Willcox, who is based at the UNSW’s School of Optometry and Vision Science (SOVS), can be summarised as: 390 publications, 14 patents, 13 book chapters, and presentations that are too numerous to count. He has been a full professor within SOVS since 2004 and since 2014 he has been an Associate Dean at the UNSW’s Faculty of Science.

Collin medal lecture

Willcox gave an engaging lecture on the development of antimicrobial CLs – from laboratory to clinical trials – and opened with the factors predisposing eyes to corneal infection. Unfortunately, CL wear is the most significant contributor, followed by ocular surgery, previous episodes of microbial keratitis, ocular trauma, and episodes of HSV keratitis. Dry eye is further back in the list of minor contributors.

CL-related MK rates range from a low of 1/10,000 for RGP CLs worn on a daily wear basis, to 1/500 when SCLs are worn day and night (1/5,000 if worn during the day only). Surprisingly, the advent of SiHy SCLs altered the figures minimally and in the case of extended wear (EW), SiHy figures are slightly higher (19.5/10,000 versus 25.4/10,000) although the incidents involving permanent vision decreases are less severe with SiHy CLs – 4/10,000 versus 2.8/10,000.

For reasons that have yet to be discovered, the incidence of corneal infiltrative events (CIEs) with SiHy CLs is as high or higher in EW than from hydrogel CLs, especially in a 30-day wear context (in a 6-night context they are similar). Generally, SiHy CLs increase the risk of CIEs by a factor of 2.18x, and changing CL care products (LCPs) has little effect on that figure.

Adding to the motivation to reduce adverse events by whatever means is the increasing role CLs are playing in anti-myopia programs involving a younger demographic, as well as the increasing number of wearers in the so-called BRICS cluster (Brazil, Russia, India, China, and South Africa).

Research by Willcox and colleagues over a number of years led them to conclude that CIEs were caused by bacterial colonisation of CLs that usually do not lead to an infection. However, the micro-organisms involved are becoming increasingly resistant to the antimicrobials being used to treat the infection they cause and as such Willcox referred to the near future as the post-antibacterial era, not just in an ocular context.

"An important factor in monitoring the state of the macula is an assessment of the concentrations of the yellow macula pigments, zeaxanthin and lutein."

Whereas MK is an ulceration of the cornea, CIEs such as CLARE, CLPU, IK, asymptomatic IK, and asymptomatic corneal infiltrates are due to colonisation of the CLs and not the cornea or eyelids, or contained infiltrates from Gram negative micro-organisms, or causes unknown with or without overlying corneal staining.

The most promising candidate for a suitable antimicrobial CL treatment, melimine, was identified via a process of elimination. Melimine is a cationic (positive charged) peptide, formed from the best parts of protamine and melittin. It reacts with negatively-charged molecules in the cytoplasmic membranes of both Gram-positive and Gram-negative bacteria, resulting in fatal water imbibition.

Impressively, bacteria do not become resistant to melamine or a derivative, Mel-4, and the novel product is also autoclave and ethylene oxide-resistant (methods of sterilisation), and has a broad spectrum of antimicrobial activity. Mel-4 is synthesised with 17 amino acids, principally lysine and arginine, and Mel-4-coated CLs have demonstrated an ability to reduce the incidence of MK, possibly by preventing biofilm formation.

Following animal studies, Mel-4-coated CLs have been trialled successfully in 17 human subjects with a few exhibiting some corneal staining that was not attributable to Mel-4 itself. Serendipitously, Mel-4 also enhances CL surface wettability.

Furthermore, Mel-4-coated CLs showed decreased colonisation, a significant decrease in Gram-positive bacteria, and an approximately 50% decrease in CIEs, CLAREs, and IKs. Usually, all adverse effects occur towards the end of the EW period (13 days and later), whereas with Mel-4-coated CLs, that period is extended out to 22 days or later.

Recent developments of the technology have seen modifications to the coating method, to which polyethylene glycol (PEG) has been added in the interest of reduced protein deposition and denaturation, as well as microbial adhesion. However, it has been shown that some SiHy materials, e.g., lotrafilcon B, cannot be coated with the current process.

Co-operation with the CSIRO and the LV Prasad Eye Institute (Hyderabad, India) is ongoing and a large-scale (n=176 subjects), Phase III clinical trial involving 14-day EW periods totalling three months, was completed in December. Subjects were monitored for one month after experimental CL wear ceased to ensure that there were no trailing effects of the clinical trial. The incidence of CIEs, CLARE, and IK were all lower with the experimental lens treatment.

More recent work has resulted in the development of an acrylic acid plasma coating for some SiHy CLs. A timeline for when the treated CLs could become available commercially wasn’t offered, but if they were to pass all regulatory hurdles, Mel-4 and its variants would represent a significant improvement in CL-wearer safety.

KEYNOTE SPEAKERS

Mark Willcox

Femke Hannes

Brian Fernandez

Craig Woods

James Armitage

Pete Haydon

Preventative management for AMD

Medical scientist and nutritionist, Dr Femke Hannes, gave a wide-ranging presentation on AMD and its management that was sponsored by France Medical. Long established as the leading cause of vision impairment in the 60–70 year age bracket, AMD is usually a result of factors such as lifestyle, age, and genetics.

With the exception of lifestyle, most are unavoidable factors making the prevention and management of the disease difficult. Lifestyle factors include smoking (all forms), sun exposure, nutrition/diet, hypertension/cardiovascular disease, and obesity. Other, non-modifiable factors include family eye history, lighter coloured eyes – as they block less light, regardless of pupil size – ethnicity, and gender.

Unfortunately, once late-stage disease is reached, the effects are irreversible and maintenance of that advanced state’s impaired vision is the best that can be achieved with current medications and other interventions.

An important factor in monitoring the state of the macula is an assessment of the concentrations of the yellow macula pigments, zeaxanthin and lutein. Macula lipid oxidation and its by-products peroxidation and oxidation of polyunsaturated fatty acids (which are believed to have inflammatory and degenerative effects, including the production of lipofuscin that appears in the RPE), metabolic debris, and neovascularisation are central to the progression of AMD.

Given the societal burden of AMD, early detection is an ongoing pursuit in the hope that early interventions will reduce vision loss and the magnitude of the burden on immediate associates specifically, and society generally.

More recently, the actinic effects of blue light (400–490 nm, excitation peak wavelength of interest is around 440 nm) have become a focus of a whole ‘blue blocking’ industry. Blue blocking efforts include specialised spectacle and contact lenses, modifications to the spectral emissions of LEDs, OLEDs, and other sources, and nighttime software modifications to digital device displays that decrease their effects on the viewer’s circadian rhythm.

While it is accepted that blue light can have deleterious effects on the macula and is therefore an AMD risk factor, there is little comparison between indoor exposure and outdoor exposure (orders of magnitude higher). The ‘blue’ wavelengths of light provide some 19% of the photonic energy of the visible spectrum and, according to Hannes, up to 30% of direct sunlight.

However, the light incident on the retina is dependent on more than that incident on the eye’s anterior surface, because the interposed ocular components each have characteristic absorption, reflection, and optical diffusion properties.

Should the retina’s antioxidant properties be compromised for whatever reason, blue light can be expected to be a bigger contributor to AMD subsequently because of the risk it poses to the photoreceptors.

The advent of digital devices has increased our exposure to blue light and now, those 30 years old or older, spend at least five hours per day on devices, while Millennials spend more than nine hours per day on them. Interestingly, relevant experts have made few comments about the use of superior OLED screen technology wherein each pixel is a light emitter and only the pixels required to form a colour picture are active at any one time, rather than the ‘white’ LED backlight system of LCD displays. Theoretically at least, OLEDs and their derivative displays should pose less of a problem.

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Complicating the issue of light incident on the retina is the fact that the young and the very young (0–8 years) lack age-related yellowing of their crystalline lenses, meaning that the blue light incident on their retinae is at a maximum. Therefore, very young screen users are arguably at the greatest risk.

When all these issue are accounted for, the case for consumption of lutein-rich foods is obvious, because lutein and zeaxanthin are nature’s own blue-light filters. Seddon (1994) has already demonstrated that lutein and zeaxanthin reduce the risk of AMD (a high intake reduced the risk by 57%).

The three main dietary factors are lutein, meso-zeaxanthin, and dietary-zeaxanthin – the latter two differing only by the location of their double bonds within their otherwise identical molecules. Dietary zeaxanthin and lutein can be found in green leafy plants, such as kale, spinach, broccoli, etc., and the recommended daily intakes are 10 mg of lutein and 2 mg of zeaxanthin, preferably in natural (plant) form rather than as a pill/capsule/tablet.

Using a supplement based on AREDS I formulation recommendations, AMD risk reduction can be as high as 10% in normals and 26% in those who are lutein and zeaxanthin-deficient. It is also assumed to reduce the rate of progression in established disease, and those figures are unlikely to be changed much by AREDS II recommendations as the new guidelines changed little.

Identifying those at risk can be difficult but there are now ways of measuring the macular pigment optical density (MPOD), including the MPS II (macular pigment screener) by Elektron Technology, represented in Australia by France Medical. The MPS II uses heterochromatic flicker photometry (HFP) as its measuring basis. Underlining the need for AMD prevention and risk reduction is the expectation that its prevalence will triple over the next 15 years.

Currently, a cure is not available (and may never be), and the treatment is very expensive and not particularly effective. About a third improve, a third stay the same, and a third get worse, leaving only lifestyle issues such as blue-light blocking, controlling sun exposure, and diet – especially an increased intake of appropriate antioxidants. As an added incentive, there is some suggestion that lutein and zeaxanthin also help prevent or slow the development of cataracts.

Devices such as the MPS II can not only screen for MPOD but can also track changes induced by lifestyle/diet changes recommended by the managing professional. However, Hannes noted that young people have been very reluctant to change their ways, even after such recommendations were made.


Modern learning

A team of academic optometrists from Deakin University’s School of Medicine gave a two-hour demonstration of Team-Based Learning (TBL), using the 2017 DEWS II report as the session’s vehicle. All delegates were pre-registered and came prepared for the session, which was delivered by Professor Craig Woods, Associate Professor James Armitage, and Dr Alissa Maillet.

Deakin-sourced tablet computers loaded with the appropriate software (from TBL specialists, InteDashboard) were supplied to delegates, who were then divided into small groups.

TBL is the evolution of a concept developed by Dr Larry Michaelson at the University of Oklahoma in 1979, which aims to provide a safe and challenging learning environment. It requires pre-session preparation for it to be effective and gives ‘students’ information on why the correct answer is appropriate and why the alternatives are incorrect or less appropriate.

Students don’t progress through the TBL process until each stage is completed correctly/satisfactorily and all team members have reached an understanding of the stage at hand. Because answers are often not black and white situations, especially in clinical studies, TBL takes a single best answer (SBA) approach to a successful outcome rather than a right or wrong dichotomy.

To assess an individual’s level of preparedness before a TBL session, a 10-minute iRAT (individual Readiness Assurance Test) is carried out once they are logged into the session. The team equivalent of iRAT (tRAT) is the session outcome and, to discourage cross-pollination, the answers are randomised between teams so that a simple transcription of an existing answer set from another team is pointless. Typically, and deliberately, the questions posed or the requests made, are not straightforward and, likewise, the answers and distractors provided are more than a match for the questions/requests.

TBL is not an MCQ series as we know it. It became obvious quite early that TBL engendered enthusiasm from the participants and the level of ‘buy-in’ to the TBL process was high in all cases. Typically, each application exercise (AppEx) is five questions in 30 minutes, and a class-wide interactive discussion usually follows a completed session.

While relevant literature can be provided, more commonly online references are suggested or the students are left to research the information either requested or needed to support their responses. One downside to TBL is the significant and time-consuming preparation typically required before each session.

In a brief conversation with senior Deakin academic and optometrist, Professor Alex Gentle, Insight learned that the university had created around 30 TBL modules over past 3–5 years. The ‘library’ is expanded regularly as the need for new modules arises, while existing TBLs are reused as needed.

Other universities are also adopting TBL methodology, but it would seem that Deakin was among the first to do so and TBL is no longer a novelty for its students or staff. From the demonstration given and the enthusiasm shown by the self-selecting SRC 2018 delegates, it is reasonable to assume that more TBL sessions will be employed in the future.

Ocular imaging

US-based, Costa Rica-trained, medical retina ophthalmologist, Dr Brian Fernandez, gave a presentation on ocular imaging sponsored by Heidelberg Engineering, a major supplier of complex imaging instruments. Fernandez has held the position of medical imaging specialist with Heidelberg since 2009.

Heidelberg’s products target retinal specialists, neuro-ophthalmologists, and glaucoma specialists but increasingly, their instruments are also finding roles in optometry practices. In addition to their obvious imaging functions, the Heidelberg confocal scanning laser ophthalmoscopes (cSLOs – their HRT – Heidelberg Retinal Tomograph series) can also be used in cases of MS, Parkinson’s disease, Alzheimer’s disease, and stroke.

The company’s latest device in their Spectralis OCT series is the Spectralis Spirit, which now offers eye tracking (TruTrack Active Eye Tracking) that uses a second laser beam to track and offset the deleterious effects of blinking, eye movements, changes in fixation, etc. The company claims that their instruments are capable of delivering images through small pupils and useable images through many cataracts.

The HRT cSLO device images the centrocaecal area of the fundus with special reference to the optic disc. It uses false-colour for on-screen images derived from data from the three separate wavelengths it uses. The wavelengths are IR (815–820 nm) for penetration as deep as the choroid, green (514–518 nm) to image intraretinal features (e.g., RNFL), and blue (480–488 nm) to image the superficial retina.

The integral image processor constructs a multi-coloured image from data from all three wavelengths that is meaningful to the practitioner.

It is particularly good at showing the extent of changes due to optic neuritis, according to Fernandez.

Other features include noise reductions and an auto-rescan function that automatically repositions the instrument at subsequent visits to facilitate tracking of fundal changes chronologically. Those changes can be as small as 1 micron with a claimed coefficient of variation of 0.46%. However, Fernandez admitted that differentiating normal from glaucomatous eyes was not easy due to an overlap of the measures involved.

In MS, RNFL thinning can amount to 2.9 microns over a 2–3 year period and 6.1 microns over a 3–4.5 year period. Using OCT (Spectralis series), a correlation can be created between the disease (brain atrophy) and retinal structures, particularly the RNFL. The latter can be compared with the neurodisability using the EDSS (expanded disability status scale). That is possible because the non-myelinated RNFs mean that only axons are being assessed versus the assessable disability.

In Alzheimer’s disease, macular and RNFL changes occur and can be tracked. Some of those changes relate to the amount of amyloid ß-protein deposited in the retina. Compared with MRI, cSLO offers 100x the resolution, is non-invasive, affordable, and comfortable.

Heidelberg’s Anatomic Positioning System detects the centre of the optic nerve head and the position of the fovea, and uses that data to centre scans as well as normalise axon configurations. It can ‘realign’ rotated disc-fovea axes that are up to 18° ‘off axis’.

Using NSite Analytics software with a Spectralis, disc rim widths, temporal papillo-macular wedges, axon losses, oedema, thinning, asymmetries, etc., can be quantified and tracked. With claimed high specificities and sensitivities, Bruch’s membrane opening (BMO), minimum rim width, and rim analysis (especially of the temporal sectors) can also be accomplished, while asymmetry of anatomical features is often high – even in the presence of small changes. However, OCT might be better able to gauge disease progress than cSLO leading to more appropriate tailoring of medication.

Posterior-pole asymmetry analysis is useful in both glaucoma (in which asymmetry is common) and ganglion cell-loss analysis, with the latter often affecting one quadrant preferentially, leading to a so-called snail-shell pattern. Further advances usually involve another quadrant in the same hemisphere before involving both hemispheres eventually. The changes in optic neuritis are more marked and follow a different pattern than those in glaucoma – Fernandez’s advice was that if it’s not horizontal, think of something other than glaucoma. MS cases tend not to follow an obvious pattern.

As with other instrument makers, as more data, normal and pathological, becomes available and is added to population databases, better analysis of each case is provided and the usefulness of their integrated data analysis software improves.

World congress

CEO of Optometry Victoria, Mr Pete Haydon, announced that an application had been made to host the World Council of Optometry’s 2021 World Congress in Melbourne. The 2017 congress was held in Hyderabad, India, and the next world congress will be held in Orlando, Florida in October 2019.

Next year, SRC will be combined with the ODMAFAIR to create the new O=MEGA19 show, which is scheduled for July 19–21.

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