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Report

The future of research on display at the SOVS

03/10/2018By Lewis Williams PhD
Higher degree research students within UNSW’s School of Optometry and Vision Science presented densely packed summaries of their projects in a fast and furious four-day schedule in mid-July. LEWIS WILLIAMS showcases the highlights.

The topics covered at this year’s School of Optometry and Vision Science (SOVS)’s annual progress review ranged from contact lenses (CLs) and relevant microbiological considerations to amblyopia, binocular vision-related issues and low vision, as well as many aspects of myopia.

Along with the presentations, the review also featured interviews with the candidates and an academic panel chaired by UNSW senior lecturer Dr Maria Markoulli. During those interviews, three representatives of the higher degree research student group supported the candidates.

While all graduate students presented, not all students were present during the program and some presented via Skype accompanied by a PowerPoint presentation of their project.

Binocular vision, amblyopia, and the brain

Mr Tiong Peng Yap opened the first session with an overview of his PhD research into cortical processing in 25 children with newly diagnosed amblyopia of refractive origin, and the effects of treating the amblyopia with spectacles (refractive treatment). The children were aged between 3–9 years, and the study included 29 normals as controls.

Yap was particularly interested in orientation-specific cortical sensitivity and used the C3 amplitude in VEP (visual-evoked potential) recordings as a measure, a measure that is appearing in ophthalmic literature with increasing frequency. He also revealed that in Asia at least, most amblyopia is either non-strabismic, bilateral refractive amblyopia, or anisometropic in origin.

Because astigmatism is characteristic of that population, Yap sought evidence of orientation-specific retinal blur and reduced cortical input from stimuli in the orientations affected. His subjects were chosen for having 2 D or more spherical ametropia, 1.5 D or more astigmatism, or both errors.

He found significant meridional anisotropy based on altered C3 amplitude but found no difference in C3 latency. Confirming what has already been published (e.g., Essock et al., 2003) Yap found that horizontal effects might need to be considered normal and indicative of an immature visual system.

The next presentation was from Ms Revathy Mani, who is studying the visual, oculomotor, and eye-hand co-ordination deficits resulting from traumatic brain injury (TBI). She is investigating the roles played by attention, working memory, and memory guidance on saccades, antisaccades, and smooth-pursuit eye movements, all with and without attentional loading (i.e., deliberate distractions).

Part of the motivation for her project is the expense and expertise required by more conventional assessments of TBI, most especially neuroimaging and CT/MRI. Furthermore, those techniques fail to detect TBI’s signature problem of diffuse axonal injuries. Her project seeks an objective, cost-effective, and sensitive biomarker to detect and monitor TBI.

Eye tracking was thought to be a contender for an objective, non-invasive, and sensitive test for TBI as deficits in saccadic and smooth-pursuit eye movements are often present in TBI. This is due to their origins in the frontal and parietal lobes, the most common areas affected by trauma. Generally, reflex and self-paced saccades tend not to be affected adversely.

Mani’s research will also study saccadic suppression and eye-hand co-ordination to assess what additional information they might provide. She has commenced investigational work using a Gazepoint GP3 Eye Tracker, and uses MathWorks MATLAB to program the device.

Clinical research manager and senior Brien Holden Vision Institute (BHVI) optometrist Mr Daniel Tilia is studying the association between binocular vision disorders and CL wearer dissatisfaction. He estimated that about one-third of CL wearers are dissatisfied at some stage and blamed discomfort for some of those problems. More importantly, he stated that about 48% of adult CL wearers have binocular vision disorders (BVDs), such as accommodative lag, low amplitude of accommodation, or lower accommodative facility.

Tilia limited his study group to myopes between 18 and 40 years of age, i.e., non-presbyopes. He is also seeking to determine the relative efficacy of the different types of CLs in use by those with a BVD, and he eventually plans to explore possible CL designs that might assist those with a BVD.

Although the discomfort-wearer dissatisfaction link is well known, the significance of BVDs in the mix remains unexplored largely. No questionnaires exist that explore such a connection.

Three questionnaires that have wide acceptance are: OSDI (ocular surface disease index), CLIQ (CL impact on quality-of-life), and RSS (ranked symptoms scale). Other instruments include: CLDEQ-8 (CL DE questionnaire) and CISS (convergence insufficiency syndrome survey).

To date, 65 subjects have been assessed and 22% exhibit a BVD. Counterintuitively, that subgroup scored both the CISS and the OSDI significantly higher than normals did, due largely to the vision subscale of the OSDI results (possibly a short tear break-up time [TBUT] issue). Importantly, the lack of significant differences in the other results (CLIQ and RSS, OSDI and CLDEQ-8) suggests that BVD-caused dissatisfaction is different from CL discomfort.

A clinical trial is proposed to determine if wearer dissatisfaction, as measured by OSDI, can be reduced by the use of different CL designs. Depending on the results of that trial, a third trial to design improved CLs might be conducted. Tilia believes that around 75% of those with a BVD might benefit from a near plus add.

KEYNOTE SPEAKERS

Tiong Yap

Revathy Mani

Thomas Eze

Daniel Tilia

Ornella Mekountchou

Divya Kandi

Rehabilitation services

Nigerian-trained optometrist Dr Thomas Eze is studying factors affecting when and how vision-impaired patients access low vision services. His MSc research explores the preferred timing of referral to different types of low vision or rehabilitation services from a patient perspective. Eze intends to apply that information to the development of a set of collaborative guidelines for clinicians in the hope of improving access to, and timing of, rehabilitation services.

To help achieve this, he recruited clients from Vision Australia, Guide Dogs, VisAbility Australia, and the UNSW low vision clinic. Eventually, a total of 31 suitable clients were assessed in-depth. Of those, 21 were female.

The study group had a median age of 70 but the age range was 14–81 years. Participants who thought their access to suitable services was late, harboured regrets and attributed their problem to be largely a lack of awareness. Their strong preference was to receive suitable information about relevant services verbally, directly (not a brochure) from their practitioner at the time of diagnosis. That finding applied across all types of services.

Referrals were: 48.4% self, 22.6% by optometrist, 19.4% by ophthalmologist, 3.2% by GP, 3.2% by friend, and 3.2% via other paths. Eze concluded that referral at the time of diagnosis was best but as a general guide, the sooner, the better.

Optometric CPD

Saudi Arabian optometrist Ms Sally Alkhawajah has started a research project examining the effectiveness of continuing education (CE/CPD) of optometrists in Australia and Saudi Arabia – two countries with significantly different ideas of what CE/CPD is about, apparently. She aims to identify factors that influence practitioners’ attitudes to, and beliefs about, CE/CPD.

A good case can be made for using CPD rather than CE, judging by the responses from some Saudi practitioners who suggested that the latter is seen as “not stopping education after their basic degree”. Such a response is unlike here, largely because CPD has been part of a voluntary process pushed by practitioner associations and societies for several decades, and a compulsory process for almost a decade.

According to Alkhawajah, the effectiveness of CPD has been studied poorly or little to date, with optometry at the centre of even fewer reports, suggesting that the effectiveness for all professions has become more an article of faith than an evidence-based pursuit. She has already recorded data from 32 Saudi practitioners in eight focus group sessions (4–15 participants in each) and subjected the transcribed information to analysis. That pursuit is ongoing and the information gathered will be analysed from social, cultural, political, organisational, and economic perspectives.

Karen Lahav-Yacouel and Maria Markoulli
Karen Lahav-Yacouel and Maria Markoulli

Presbyopia CLS

Sydney optometrist Ms Karen Lahav-Yacoeul delivered a presentation on phase-step optic CLs as a possible solution for presbyopes who would rather wear CLs than spectacles. Phase-step optics CLs have shallow (about 2.3 micron) square profile grooves on their reverse side to alter the path length light has to travel on its way to the retina.

Theoretically, such CLs, which are designed to provide an extended depth of focus (EDOF), can be made in a plus form with protrusions from the reverse side, or a minus form that has grooves on the reverse side. For obvious corneal epithelial trauma reasons, the plus form is untenable.

A difficulty is the precision required to form the grooves accurately, namely position and depth. Confounding those issues are the effects of tear and eye debris and deposits filling, either partially or fully, the grooves, leading to ‘alterations’ to the surface profile, changes in optical properties including regularity, etc.

However, by judicious alteration of the CL’s optical path lengths involved, the designers are seeking to enhance constructive interference to maximise light efficiency and contrast at near. Distance vision is claimed to be good.

Initial design work was performed with the Zemax OpticStudio design suite employing the Arizona Model Eye ocular parameters. The initial design uses 16 grooves and visual test distances were 6 m, 70 cm, 50 cm, and 40 cm. The BHVI Model Eye System II is being used to assess the CL’s imaging further at a wavelength of 550 nm, using the tried and tested USAF 1951 optical test target.

Future testing is scheduled to explore how polychromatic light affects results and what phase-plate SCLs and other EDOF CLs might offer presbyopes. All initial testing is done using rigid CLs to eliminate the complications of CL flexure, as well as early manufacturing issues. The trial CLs and their grooves were assessed using a 20 micron tool profiler.

Lahav-Yacoeul is also investigating patient parameters such as pupil size, corneal aberrations, and visual function. Because of the special nature of phase-step CLs, an optical laboratory in the US undertook the fabrication. Initially, a 2 D add (under 550 nm monochromatic light) was chosen, but results showed that the add was nearer to 4 D and bifocality was lost in white (polychromatic) light. Some reasons for that include CL decentration, the breadth of the wavelengths used for the target, as well as retinal neural and psychophysical factors. Research continues along three paths – theoretical, in vitro, and in vivo.

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Myopia

The research into an eye model to screen myopia interventions pursued by Ms Ornella Mekountchou, an optometrist and academic from Cameroon, is motivated by the predicted prevalence of myopia by the year 2050. Current projections suggest more than 50% will have an Rx of –0.50 D or greater and about 10% will be classified as high myopes (–5 D or greater).

The measurement of the eye’s axial length (AL) and choroidal thickness (ChT) has been central to previous and current studies, especially in response to optical defocus. However, most observations to date have been in relation to the central retina, a situation Mekountchou is keen to change by introducing studies on the peripheral retina as well.

Because clinical studies are long-term, complex and expensive and negative outcomes always remain a possibility, the development of an eye model of interventions, current and novel, has obvious attractions. Her aim is to develop an eye model based on AL and ChT data following short-term exposure to optical defocus.

The project’s rationale is to provide a means of screening and selecting optical interventions based on their ability to deliver an appropriate response before a long-term clinical trial is undertaken. The concept that the efficacy of optical interventions cannot be predicted from the result of short-term clinical trials of the effects of optical defocus on AL and ChT, is also to be tested.

So far, Mekountchou has assessed the repeatability of central and peripheral AL and ChT in healthy eyes using the Haag-Streit Lenstar LS900 (for AL with internal and external fixation controls out to 30°) and the Topcon DRI OCT Triton (for ChT out to 20° only, as 30° is not possible with that instrument).

Assessments are made an hour before defocus is applied, at the end of a 1-hour defocus session, and after an hour of no defocus to track recovery. Short-term effects were found and generally, changes in AL are the opposite to those of ChT, i.e., if the AL lengthens, the ChT thins. An example given was that if the AL shortens by 5–30 microns, the ChT thickens by 2–20 microns.

The next phase is planned to evaluate the effects of short-term exposure to central and peripheral optical defocus on AL and ChT. The final stage will involve the development and validation of the eye model developed to screen such optical interventions.

Indian optometrist Ms Divya Kandi is another myopia researcher from SOVS, UNSW investigating myopia progression. In her opening words, she reported that myopia as a ‘condition’ has been documented since 350 BCE at least. Currently, apart from the usual potential pathological considerations, myopes can also have issues with quality-of-life (QofL) and feelings of inferiority because of the obviousness of their spectacles if CLs are either unsuitable or rejected as a vision correction option.

According to Kandi, despite the rising prevalence of myopia, relatively little is known about its onset, development, and progression. Furthermore, little is also known about the relationship, if any, between peripheral refractive error in different meridians, and optic disc parameters and the RNFL thickness in those meridians.

Her study seeks to predict myopia progression using peripheral refraction, optic disc features, and RNFL thickness. It is already known that disc factors such as ovality and torsion cannot, alone, predict myopia progression but other factors such as tilt angle, RNFL thickness, location of tessellations, thickness asymmetries, and the Bruch’s to Bruch’s gap, determined with the aid of OCT, might contribute to predictions.

Subjects at least 18 years of age are used in her studies and the BHVI Eye Mapper is used to determine peripheral refraction meridionally. The mapper’s optics can be rotated up to 90°, meaning all meridians are within its reach. Eccentricities out to 20° are assessed in her studies. It has already been shown that in cases of lesser myopic progression, less optic disc torsion is more likely to be observed.

Vietnamese ophthalmologist Dr Huy Tran delivered a presentation on his research into the safety and efficacy of low-dose atropine and caffeine eye drops in slowing the progression of myopia in children.

Atropine in relatively high doses is known to be the most effective anti-myopia treatment available, but the known and obvious side-effects, and the unknown long-term safety profile of the pharmaceutical have deterred its widespread adoption. Atropine is a muscarinic-receptor antagonist (i.e., an antimuscarinic agent) whereas caffeine (principally its methyl xanthine component) is an adenosine-receptor antagonist (i.e., an antiadenosine agent).

Tran’s study uses the drugs either separately or in combination. A meta-analysis of the literature suggests that up to 0.03% atropine is well tolerated and up to 2% caffeine is tolerable. In his 2-week pilot study, 58 subjects aged 6–12 years were treated with 0.01%, 0.02%, or 0.03% atropine eye drops. From a baseline amplitude of accommodation of around 19.5 D, the 0.01% reduced the amplitude by <5 D, whereas the 0.03% drops gave a reduction of nearly 10 D.

The pupil dilations ranged from almost 1 mm (0.01%) to almost 2.2 mm (0.03%). Interestingly, photophobia was reported by almost 5%, 10.5%, and 23.5% of subjects (0.01, 0.02, 0.03% atropine respectively). As a result of his pilot study, Tran settled on 0.02% atropine, 2% caffeine, or both for his subsequent studies.

A pilot study analogous to the atropine study is underway using caffeine as the anti-myopia agent. Colouring that decision is the doubt surrounding the efficacy of 0.01% atropine on AL, even though it does have a significant effect on spherical equivalent results.

KEYNOTE SPEAKERS

Huy Tran

Dinesh Subedi

Shyam Tummanapalli

Muhammad Yasir

Mahjabeen Khan

Parthasarathi Kalaiselvan

Microbiology

Several graduate students are working with recent Collin Medal winner Professor Mark Willcox to investigate antibiotic resistance, antibacterial CL coatings, and microbial keratitis.

Indian microbiologist Mr Dinesh Subedi is studying the antimicrobial resistance of Pseudomonas aeruginosa; a bacterium that is now resistant to multiple drugs and whose resistance is increasing. Initially, clinical isolates of P. aeruginosa from cystic fibrosis cases from Australian and India are being used and disinfectant resistance is determined by MICs (minimum inhibitory concentrations) and MBCs (minimum bactericidal concentrations).

The bacteria’s whole genome sequence (genome-wide sequencing [GWS]) was determined using Illumina and Oxford nanopore sequencing technology. It’s believed that clinical isolates have a wider genome than the same species in the ‘wild’. Further, it is believed that ocular clinical isolates are more pathogenic (larger accessory genomes) than those from other sources.

P. aeruginosa can have up to 147 virulence genes, some sourced apparently from water sources. Subedi has already determined that Indian isolates are notably more resistant than their Australian counterparts, as well as being resistant to a wider range of antimicrobials. Of specific interest is the resistance of P. aeruginosa to betalactams, aminoglycosides, and fluoroquinolones.

Pakistani microbiologist Mr Muhammad Yasir is part of the Willcox-led team investigating the mechanism(s) of action of the in-house developed melimine and its derivative Mel-4 when used as surface-bound or free antimicrobials. He has shown that neither free P. aeruginosa nor S. aureus develop resistance to either melimine or Mel-4 over 30 days of serial exposure. However, while bound melimine could penetrate the membrane of P. aeruginosa it could not enter S. aureus.

Indian optometrist Mr Parthasarathi Kalaiselvan is studying the role antimicrobial CLs might have in reducing the incidence of infiltrative events (IEs), such as infiltrative keratitis [IK] and CL-related acute red eye (CLARE) in EW CLs. His project also involves Mel-4 as a CL coating.

Kalaiselvan uses disposable hydrogel CLs currently, because the technology to coat SiHy CLs is not yet available. So far, a study of 135 wearers has confirmed the general clinical acceptability of CLs coated with Mel-4 and a reduced incidence of IEs by around 50%. However, due to the low incidence of IEs generally (and even lower rates in Mel-4-coated CLs), the data did not reach statistical significance.

Continuing the P. aeruginosa theme because of its significance to microbial keratitis (it’s the most likely causative agent) among other reasons, fellow Pakastani microbiologist Ms Mahjabeen Khan is comparing the drug resistance of P. aeruginosa isolated from CLs and non-CL sources.

Given its propensity to form a protective biofilm in and on CL paraphernalia, its resistance to disinfectants present in CL care products is well known. Because of that, CL case care instructions have a clear focus on frequent biofilm disruption and regular case disposal.

Her study aims to identify the resistance genes of P. aerugosa. Again, MIC and MBC are being used to assess resistance, along with molecular techniques including multi-locus sequence typing and nucleotide sequencing. The efficacy of current multi-purpose solutions (MPSs) as disinfectants will also be determined.

Khan has already determined that pre-exposure to CL MPSs results in an increase in resistance and non-CL isolates are more susceptible to fluoroquinolones at least. Without prior MPS exposure, CL isolates are actually less resistant to antimicrobials. MPS exposure reverses that situation.

Corneal nerves

Indian optometrist Mr Shyam Tummanapalli is researching the relationship between the structural and electrophysiological measures of peripheral corneal nerves in Type 1 diabetes. Diabetes is, in essence, a progressive peripheral nerve neuropathy and the corneal nerves eventually show characteristic inferior whorl-like formations. Initially, the small peripheral corneal nerves are affected, but peripheral nerve damage can be reversed if detected early enough.

Tummanapalli’s study is monitoring changes in corneal nerves and their release of neurotransmitters in vivo into the tear film. Corneal confocal microscopy is used to image the nerves, however whether these changes affect nerve function is not yet known. His study subjects include diabetics and those suffering from diabetes-induced chronic kidney disease. Normal subjects are to be used as controls in clinical studies.

The award for best presentation was made after a detailed analysis of the results from a panel of experienced academic reviewers. The 2018 award went to Ms Karen Lahav-Yacouel, who is also a previous recipient of the award.

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