Spotlight on myopia at Brien Holden tribute event

The day-long series of presentations and workshops on myopia organised by the Brien Holden Vision Institute (BHVI) Acady on 31 July was held as a tribute to the BHVI’s founder, Professor Brien Holden, and the first anniversary of his passing.More than 200 delegates attended, in addition to BHVI staff and exhibitor representatives. Pleasingly, the program featured the doyenne of myopia research, Professor Kathryn Rose, Head of Discipline (Orthoptics) at Sydney’s University of Technology (UTS).Other presenters included Professor Kovin Naidoo, chief executive officer of the BHVI; Associate Professor Padmaja Sankaridurg, Program Leader, BHVI; Mr Daniel Tilia, Senior Research Optometrist, BHVI; Dr Pauline Kang, ROK Group, School of Optometry and Vision Science (SOVS), UNSW; Ms Kate Gifford, current Optometry Australia National President, research student, and orthokeratologist; Ms Jessie Huang and Ms Jaclyn Chiang, optometrists from the Centre for Eye Health; and Dr Monica Jong, Executive Manager of Science and Business, BHVI.Many presenters were well known to one another but their interactions are more likely to occur at overseas events than Australian ones. It is hoped that the 31 July Sydney meeting represents the start of a reversal of that situation.Ms Yvette Waddell, chief operating officer of the BHVI, opened the program with an overview of the institute’s history, activities, and funding. Myopia is now a focus of BHVI activities and its role in myopia research was underlined by its hosting of the World Health Organization’s (WHO) Global Scientific Meeting on Myopia in Sydney in early 2015.Ms Waddell summarised the probl of vision impairment (VI) by estimating that about 10% of the world’s population suffers significant VI, and by 2020 it is estimated that there will be 2.5 billion myopes, with that number expected to keep rising.A WORD FROM THE CEOProf Naidoo began his address by revealing that myopia is now the second biggest cause of blindness worldwide. He added that the number of world blind from all causes increased by 600 million over the 20-year period from 1990 to 2010. Ranked in detrimental order, the most common causes are cataract, refractive error (including myopia), glaucoma, age-related macular degeneration, diabetic retinopathy, trachoma, and ‘other’.{{image2-a:r-w:400}}Although not the biggest cause of blindness, myopia is the biggest cause of VI, accounting for about 27% of cases worldwide in 2010 – 3% of which are high myopes. However, figures for individual countries are often much higher (eg, US 42%, China 47%, Hong Kong 62%, Singapore 53%, and South Africa 10%, with some sub-groups as low as 3–5%).At the 2015 WHO-BHVI Global Scientific Meeting on Myopia, myopia was newly defined as ≥-0.50 D and high myopia as ≥-5.00 D. Such a decision was required to standardise the definitions in light of the number of differing definitions that appear in the literature to this day.A 2010 estimate of the number of myopes worldwide was about two billion, and that figure is estimated to swell to the overwhelming figure of five billion or 50% of the world’s population by 2050. The estimates for 2050 suggest that 40% will be myopes, a further 9.8% will be high myopes, and the raining 50.2% will be a combination of metropes (mostly) and a minority of hyperopes.As the myopes age, especially the high myopes, they are expected to become a serious public health issue and a burden to society. As a result, myopic maculopathy is expected to account for an increasing proportion of blindness and VI. It is already the second major cause of blindness in the Asia-Pacific. High myopia is associated with other ocular probls as well; for example, the glaucoma risk is some 14.4X higher, retinal pathology 7.8X higher, and cataract 3.3X higher.Prof Naidoo finished with an overview of Our Children’s Vision 2020, a project by a consortium of non-government organisations to screen 50 million children for VI by the year 2020. Consortium mbers include the BHVI, Essilor’s Vision for Life, International Agency for the Prevention of Blindness, International Council of Ophthalmology, World Council of Optometry, Optometry Giving Sight, and Revo sunglasses. The project is funded partially to the tune of US$10 million (AU$13.2 m) by Bono, lead singer of the band U2 and Revo’s brand ambassador and sunglass model.MYOPIA CONTROL WITHOUT OPTICAL DEVICESProf Rose, along with some high-profile colleagues from the Australian National University, Westmead Hospital, and University of Newcastle, published a sinal paper (Rose et al., 2008) titled Outdoor Activity Reduces the Prevalence of Myopia in Children in the journal Ophthalmology. That paper resulted from the Sydney Myopia Study (2003–05) in which 1,765 six-year-old and 2,367 12-year-old school children were studied.Before coming to the titular conclusion, appropriate adjustments were made for near work, parental myopia, and student ethnicity. Subsequent studies by others have supported that conclusion and have led to several schools-based trials incorporating forced outdoor school-day activities in myopia-prone countries, especially in southeast Asia.Before the 1970s, myopia could not be related to the use of ‘computers’ in all their guises. More importantly, high myopia, now defined universally as ≥-5.00 D, once had a 1:12 myope prevalence whereas now it is more likely to be 1:4 to 1:5 myopes. Given that the prevalence of myopia has been reported to be as high as 96.5% (South Korea), the probl of high myopia and all its ramifications becomes clearer.

PRESENTERS
Yvette Waddell	Kovin Naidoo	Kathryn Rose	Padmaja Sankaridurg	Daniel Tilia

In some countries, high myopia has already reached the level of a public health issue because of the VI attributable to it. The myopic retinopathy/maculopathy and the myopic degeneration that ensues is just one aspect of the probl. The fact that it now occurs, on average, almost 10 years earlier is another. It is already significant in urban-based, older Asians.When the younger high myopes age, the probl will become more serious. Not only does myopia afflict younger people but their rates of progression have also increased, leaving younger high myopes with retinal changes being detected at younger ages than previous experience would have suggested. The prevalence, the rate of progression, and the issue surrounding high myopia are building towards a perfect storm if myopia is left unchecked.While education intensity and duration, and time spent outdoors have been shown to be causal, other factors such as near work and, to some extent, ethnicity have been supported less consistently in many recent studies. The role schooling plays in the aetiology of myopia can be summarised in the following finding: if the prevalence of myopia in a group is >70%, it will be found that more school hours will have been accrued.Myopia is less of a probl in Finland, and that has been attributed to their schooling not starting until children are seven years old. Many other countries start at five or six years of age, and many of those have regimented pre-school systs involving even younger children.Referring to the Sydney Myopia Study, Prof Rose noted that children exposed to large amounts of near work combined with lots of outdoor time were no worse off than those who spent similar amounts of time outdoors but engaged in much less near work. Sport (indoor or outdoor) is not an anti-myopigenic factor per se; rather, it is the time spent outdoors. Conversely, little outdoor activity combined with large amounts of indoor near work has been shown to be myopigenic. The actual underlying mechanisms are not well understood and this research area is a work in progress.Intriguingly, a 1993 paper (Pärssinen and Lyyra, 1993 – children were recruited from 1983–84 into a three-year study) on myopia and myopia progression in school children found that in boys, 57% of their final Rx’s spherical equivalent (SEQ) could be explained by their initial SEQ, age first Rx worn, time spent on sport and ‘outdoor activities’, and on reading and close work.For girls, 49% of their final SEQ could be explained similarly with the exception of sport and ‘outdoor activities’ and with the addition of reading distance (whether reading distance was the egg or the chicken was not discerned). Uniquely, the study group were revisited 20 years after the initial investigation (Pärssinen et al., 2014). Almost half the cases of school-days myopia progressed into adulthood. Higher levels of myopia were related mainly to a parental history of myopia and less time spent on sports and outdoor activities in childhood.{{quote-A:R-W:450-I:8-Q:"Ortho-K is not applicable in a control sense to adult-onset myopia, only in a ‘correction’ sense"-WHO:Dr Pauline Kang, ROK Group, School of Optometry and Vision Science (SOVS)}}Despite discussing the ‘outdoor’ issue at some length, oddly, the Rose et al., 2008 paper was not cited in Pärssinen et al., 2014, although a related 2008 paper by the same team was. The data suggests that not only is time outdoors important but when it occurs in life is also important because it is exposure earlier in life that has a protective effect later on. That probably translates to before six or seven years of age.Handled appropriately, education need not be myopigenic. Prof Rose’s UTS department collaborated with the Zhongshan Ophthalmic Centre at Sun Yat-sen University, Guangzhou, China in a three-year investigation of an intervention study that introduced a 40-minute outdoor component to the school day. Initial data showed an almost 10% reduction (38.2% to 28.8%) in the prevalence of myopia. Equally, the average SEQ had also decreased, suggesting a decrease in the magnitude of the myopia developed during the study.Studies in Taiwan are investigating 80- and 120-minute outdoor times on each school day, and time outdoors is now being incorporated into official policy. Another policy introduced there prohibits the use of digital devices by children under two years of age.The theories on the underlying mechanisms are many and varied but the stimulation of retinal dopamine – which inhibits the growth of axial elongation – by the greater amounts of incident light offered by outdoor exposure is regarded as a plausible biological pathway.The smaller ocular dioptric changes outdoor (not so near to very far) has been thought to be a possible explanation for the reduced magnitude of changes in myopia when outdoor activity is ‘encouraged’ (or forced), but observation has shown that school children still do a lot of near work outdoors.Although no longer available for research, the D2-dopamine antagonist, spiperone, was earmarked for trials as an anti-myopia agent, and early primate studies showed that spiperone reduced the protective effects dopamine had on axial elongation (French et al., 2013).In summarising her presentation, Prof Rose suggested that 10–15 hours per week outdoors was desirable and a ‘prevent and delay’ strategy should be pursued. She felt that a school-based program had the best prospects for success. While acknowledging that 0.01% atropine had a lower rebound effect, she harboured concerns about atropine at any concentration because of that rebound effect and other known side-effects.In a workshop later in the program, SOVS’ Dr Isabelle Jalbert revealed some of the high costs of atropine due to availability and compounding issues. Later still, BHVI’s Dr Jong noted that only optometrists with therapeutic endorsent are eligible to use atropine – diagnostic certification alone is not enough.Prof Rose’s pursuit of myopia control without optical devices or pharmaceuticals is ongoing.MYOPIA CONTROL WITH OPTICAL DEVICESA tag-team effort between Assoc Prof Sankaridurg and Mr Tilia delivered information on the use of spectacles and contact lenses (CLs) to control myopia and limit its progression.Assoc Prof Sankaridurg estimated that about 20% of Australians were myopic in 2000, and that number is expected to be greater by 2020. In a 2011 survey of ethnic differences in myopia, children of Asian origin were more likely to have higher myopia than Caucasians (1.44 D versus 0.95 D) and that difference was sustained three years later (1.89 D versus 1.31 D).Furthermore, younger myopes tend to progress more rapidly, resulting in even higher levels of myopia in early adulthood. Parental history of myopia is also an issue, with the worst-case scenario being to have both parents myopic. Those factors combined translates to younger myopes being more likely to have both parents myopic.Moving to the topic of deliberate optical defocus (the central retina is supplied with a clear image while the peripheral retina is supplied with an altered focus simultaneously and deliberately) as pioneered by Professor Earl Smith in primates, it has been shown that while peripheral visual signals can dominate central refractive development, in the simultaneous defocus situation, it is the most myopic focus that drives the final outcome.To that end, spectacles delivering a full correction centrally and plus power peripherally have been trialled. The peripheral plus portion of the Rx dominates the development of refractive error, and trials to reduce myopia or slow its progression have been undertaken.{{quote-A:L-W:450-I:9-Q:"Clinicians need to drive the changes required to arrest the steady increase in the prevalence of myopia"-WHO:Ms Kate Gifford, current Optometry Australia National President, research student, and orthokeratologist}}Results show that as little as about 18% of the lens area needs to be devoted to myopia control optics. To be acceptable, a final figure of a 20% reduction in myopia was selected as a minimum. The resulting appliance must also be safe to wear, provide good VA, be affordable, and easy to use.Previous attpts at spectacle-based myopia control met with mixed results. Under-correcting myopia actually made the error worse; PPL spectacles produced a small improvent (about 0.25 D) that, while statistically significant, was deed irrelevant clinically; executive bifocals (add: +1.50 and 1.5 PD base-in OU) showed some benefit; peripheral defocus was not very successful; and lenses combining peripheral defocus and PPL characteristics were slightly better than, but not superior to, simpler approaches.Assoc Prof Sankaridurg summarised by saying no under-correction, only executive bifocal showed a small benefit, with limiting factors to a spectacle approach including: eye movent behind the unmoving spectacle lens altered the retinal area being treated, compliance was an issue, a need existed to reduce image ‘swim’ due to eye movents, and there was a further need to reduce the aberrations in the periphery while still providing good central vision.Switching to the CL option, Mr Tilia confirmed that single-vision CLs were of no value to myopia control and bifocal CLs were probably of most use to correct myopes with an esophoria. Peripheral defocus CLs (periphery made more myopic) held more promise because they moved with the eye, offering better control of which retinal area is being ‘treated’.Results of up to a 39% reduction were recorded over a 3–3.5 year period using the patened Eye Mapper, a special wavefront-sensing instrument developed in-house at the BHVI. The Eye Mapper takes nine meridional peripheral measurents (Zernike co-efficients, the lower ones of which include sphere and cylinder) of peripheral defocus in less than a second, including one on the fixation axis and four on either side, each at 5 ° intervals. Single-vision spectacles were worn by a control group to make valid comparisons.Dual-focus CLs (CooperVision’s MiSight) worn monocularly and based on the original work of Anstice and Phillips (2011) of New Zealand, showed a 36% reduction in the SEQ Rx and a 49% reduction in axial length (AL). The study had to be conducted as a cross-over design so as not to induce anisometropia ultimately.Another CL design using alternating concentric zones of plano and +2.50 D well into the periphery resulted in a 25% reduction in SEQ and a 31% reduction in AL. Ortho-K, which was the subject of later lectures by Ms Gifford and Dr Kang, was stated to give a ≥50% reduction in AL.Using the BHVI-developed extended depth-of-focus CLs that produce poorer quality images behind the retina to discourage myopic growth, reductions of up to 35% by the first six months were realised but their efficacy tapered off after that initial period.Assoc Prof Sankaridurg summarised the state of play with device-based myopia control as: spectacles: 10–20%, CLs (all types): 30% or more reduction, adequate outdoor exposure: 11–34%. She left comment on atropine out of her discussion as it featured frequently during the day’s program but mentioned another pharmaceutical, 7-methylxanthine (an adenosine antagonist), that in a 2008 Danish children study showed good efficacy when used but growth continued after cessation of the trial (12 months).In a slightly larger Dutch study, a 66% reduction of myopic progression and a 44% deduction in AL was claimed. However, as the product is not available commercially, interest ses to have waned. The apparent disconnect between Rx and AL changes is yet to be explained.MYOPIA AND ORTHO-KIn her overview of Ortho-K, Dr Kang revealed that in some studies, high myopes have donstrated greater responses to Ortho-K than lesser myopes. Despite promising results, Ortho-K is not 100% effective, was not applicable in a control sense to adult-onset myopia, only in a ‘correction’ sense, and it may be shown eventually that a combination of anti-myopia treatments produce the best results.In SOVS trials, results of up to 41% reductions in myopia have been achieved. Encouraged by the research results, Dr Kang now heads amyopia clinic at SOVS that is investigating the use of 0.01% atropine (requires compounding from a higher concentration commercial version as there is no commercial source of 0.01% atropine anywhere), multifocal and PPL CLs (MiSight and Proclear/Biofinity MF SCLs), and of course, Ortho-K.Overlapping the Ortho-K topic was a presentation by Ms Kate Gifford, a Brisbane-based Ortho-K practitioner and myopia researcher. Quoting Flitcroft, 2012 – “there is no such thing as ‘physiological’ myopia” – she launched into an overview of myopia and its impacts.Where relevant, case studies were used to illustrate particular points. Quoting Dr Noel Brennan’s 2012 paper, a reduction in the rate of myopia of 33% could produce a 73% reduction in high myopia, while a reduction of 50% in myopia could see a 90% reduction in high myopia based on recent figures.Ms Gifford did note that the rate of myopia progression decreases with age (>12) such that by 18 years of age, the rate of progress is usually 0.25 D or less per annum. Tracking cases through the various stages of life and estimating risks with either spectacles or Ortho-K CLs (for myopia reduction) for two similar children – one wearing spectacles until 18 then SCLs for 40 years, the other, 25 years of Ortho-K and then no CLs at all for 33 years – she predicted that end-stage myopia at 58 years of age would be much less (-7.50 versus -4.75) for a risk of microbial keratitis (MK) of one in 95 (-7.50) or one in 51 (-4.75).However, the purpose of her exercise was to highlight the greater risks that the high myope was then exposed to as a direct result of their Rx being -7.50 D. Table 1 summarises her analysis for the two 58-year-olds.Ms Gifford’s data was based on the work of several authors, and Table 2 outlines the increased risks of cataract, retinal detachment, and myopic maculopathy from the Flitcroft paper and others. The probls of high myopia are obvious.

Continuing on, Ms Gifford raised the issue of what practitioners can do now, presenting comparisons of the various methods already discussed. She offered three pillars of myopia control: environment, CLs, and binocular vision. Her take on the environment amounted to 90 minutes per day outdoors.CLs also included the possible adjunct use of spectacles or the possible use of atropine or some, as yet unidentified, pharmaceutical. The binocular vision category related to those cases with either an accommodative lag or who are esophoric. For those, she summarised results with PPL spectacles and bifocal spectacles (12–55% reductions).She noted that Ortho-K reduced both accommodative lag and near esophoria, and conventional multifocal CLs could reduce accommodative lag and were capable of offering some myopia control because they caused positive spherical aberration in the periphery (plus peripheral defocus). She advised against using high bifocal adds as they are not well tolerated by children. She also noted that sometimes spectacles are still needed if corrective prisms are required in severe binocular vision cases.Detection of the so-called pre-myope was also stressed (by Ms Gifford and in a later panel discussion) as the role of optometrists because less than normal hyperopic refractions (eg, an Rx of +0.50 to +1 D in a 6–7-year-old when an Rx more like +1.50 is expected, is considered a reasonably reliable indicator that the child will become, or is already becoming, myopic) at up to four years before myopia sets in are usually a reliable predictor of what lies ahead.Ms Gifford’s parting advice was to start early, and she believed clinicians needed to drive the changes required to arrest the steady increase in the prevalence of myopia and the disturbing rise in the number of high myopes and their attendant probls.By any measure, the day was a resounding success and the late Prof Holden would have been very impressed with the attendance and enthusiasm shown by all involved. Given the importance of the topic and the looming public health issues it brings with it, it would se appropriate for a day-long meeting of a similar format to be held regularly, perhaps every two years; the long-term nature of most human studies would probably work against an annual event.Co-operation between myopia research institutes and their staff and understudies should be encouraged at all levels. The appearance of Prof Rose on the program was a pleasant surprise and this author for one, hopes it is a fresh beginning within the confines of Australian myopia research. All relevant disciplines have much to offer a general effort to turn the tide of myopia progression.

REFERENCES

Anstice NS, Phillips JR, 2011. Effect of dual-focus soft contact lens wear on axial myopia progression in children. Ophthalmology 118(6): 1152 – 1161.

Brennan N, 2012. Predicted reduction in high myopia for various degrees of myopia control. BCLA meeting, 2012.

Flitcroft DI, 2012. The complex interactions of retinal, optical and environmental factors in myopia aetiology. Prog in Ret and Eye Res. 31: 622 – 660.

French et al., 2013. Time outdoors and the prevention of myopia. Exp Eye Res. 114: 58 – 68.

Pärssinen O, Lyyra AL, 1993. Myopia and myopic progression among schoolchildren: a three-year follow-up study. Invest Ophthalmol Vis Sci. 34(9): 2794 – 2802.

Pärssinen O et al., 2014. The progression of myopia from its onset at age 8–12 to adulthood and the influence of heredity and external factors on myopic progression. A 23-year follow-up study. Acta Ophthalmol. 92(8): 730 – 739.

Rose K et al., 2008. Outdoor activity reduces the prevalence of Myopia in children. Ophthalmology 115(8): 1279 – 1285.