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HomemistoryA Long View on Short-Sightedness: Ramifications of Higher Myopia Rates and New Treatments

A Long View on Short-Sightedness: Ramifications of Higher Myopia Rates and New Treatments

Many articles focusing on the epidemic of myopia in East Asia have been published recently and there is speculation about the potential for this increase to be seen world-wide. Indeed, with over 80 per cent of young adults affected in East Asian cities and predictions of 50 per cent of the global population affected by 2050,1 it is possible that the incidence of myopia will exceed rates of other chronic conditions, such as obesity and diabetes. But how robust are these predictions, what are the concerns, and what measures should be taken to try to stem the tide?

GENETIC AND ENVIRONMENTAL FACTORS

Great progress has been made in understanding the genetics of myopia, particularly from the meta-analyses of genome-wide association studies (GWAS) from the international Consortium for Refractive Error And Myopia (CREAM).2 However, only part of the heritability has been explained to date.3

the permanent vision loss from pathological myopia, associated with maculopathy, retinal detachment and glaucoma warrants greater effort in prevention

Environmental factors contributing to myopia have been proposed for centuries, with near work and studying long suspected. Wearing glasses is still often associated with being studious, intellectual, and not outdoorsy or athletic. Indeed, during the Pol Pot regime in Cambodia, those wearing glasses were assumed to be intellectuals and specifically targeted for punishment. More recently, a greater number of years of education and lack of time spent outdoors in daylight have been associated with myopia. Increased screen time has also come under scrutiny. Of course, these risk factors are intertwined. Years of education is easier to tease out than other measures, such as time spent outdoors or using electronic devices. It is not a simple case of nature versus not enough time spent out in nature. Further work in genetics and environmental analyses and, importantly, analysis of geneenvironment interactions will be crucial for determining individuals’ risk profiles.

EVIDENCE FOR THE EPIDEMIC

Comparing myopia rates will always be challenging when there are both age and cohort effects involved. Additionally, confounding factors, such as the changing threshold for cataract surgery over the last 50 years and that people with myopia are more likely to develop cataracts, also pose a challenge.

adults with skin cancer had half the rate of myopia compared to those without skin cancer

Furthermore, the modern accurate autorefractors we use today were not available in the early 1990s when many population studies began, and studies using vertometry or subjective refraction do not have the smooth normal distribution curves (with skew and leptokurtosis) we are familiar with today. In fact, some studies implicating a rise in myopia only impute refractive error from the level of uncorrected acuity in earlier studies. Despite this imputation, other causes of vision loss in young adults are rare and the dramatic increases in myopia rates in East Asia would appear real, as outlined in the article by Dolgin.

The case for an Australian epidemic is not as strong. We presented our preliminary analysis at the Association for Research and Vision and Ophthalmology (ARVO) meeting in Honolulu in 2018. As a historical comparison, in Australians born before World War ll who were examined in the 1990s as part of the Blue Mountains Eye Study and the Melbourne Visual Impairment Project, myopia rates of 21 per cent and 23 per cent, respectively, were reported. Compared to contemporaneous studies in the northern hemisphere, the Australian studies had some of the lowest rates for myopia across most ages studied. By comparison, recent studies in Western Australia – the Busselton Healthy Aging Study and the Generation 1 Raine Eye Health Study – reported rates of 36 per cent and 30 per cent, respectively. These data were based on cut offs of < – 0.5D. Using different cut offs gives different rates and different levels of apparent increase. The younger generation 2 of the Raine Eye Health Study had rates of myopia of 23 per cent at age 20 years in 2010–2012 and the cohort is being re-examined at age 28. Preliminary data suggest only a few young adults have progressive myopia. Although there is an increase in myopia in Australia, we are not on track for an 80 per cent myopia rate and probably not a 50 per cent myopia rate. It is disappointing that the recently completed National Eye Health Survey only conducted autorefraction if participants had reduced visual acuity. Hopefully autorefraction will be conducted routinely in any follow-up study.

WHY WORRY?

Decreasing stigma associated with wearing glasses and the tremendous precision with which we can treat refractive errors with spectacles, contact lenses, or refractive surgery has delayed the need for research into preventing myopia. Why try to prevent myopia when we can so readily treat it? However, the permanent vision loss from pathological myopia, associated with maculopathy, retinal detachment, and glaucoma warrants greater effort in prevention. These all have detrimental effects on productivity and quality of life. Moreover, the financial costs for individuals and healthcare systems are substantial – the global cost of myopia in 2011 was estimated at US$65 billion.5

In China, mass population measures such as limiting children’s screen time and increasing time spent outdoors are already in place

TREATMENTS: THEIR EVIDENCE BASE AND SAFETY

Of all refractive measures to prevent myopia progression, orthokeratology has the best results according to multiple systematic reviews and metaanalyses.6 The drop out of patients is high and the risk of infectious keratitis, although low, is a real concern as is the cost. Thus, only a small number of children with myopia are under this treatment.

The use of off-label low-dose (0.01 per cent) atropine drops to slow the progression of myopia has increased dramatically in recent years. This is based on the outcome of the Singapore ATOM 2 study, which found that although the placebo arm of the trial (0.01 per cent atropine) had the least effect during active treatment, it had the least rebound after treatment was stopped. The control arm, then used for justifying the long-term effect, was the control data from the earlier ATOM 1 study. Although randomised studies are underway to compare 0.01 per cent atropine with placebo in Asia, Europe, and Australia (ACTRN12617000598381), we do not yet have these results, which should define the long term benefit and safety of the treatment.

Despite this, a large number of paediatric ophthalmologists and optometrists in Australia are prescribing 0.01 per cent atropine, which is prepared by compounding pharmacies. The Australian Therapeutic Goods Administration (TGA) has accepted that this is a low (almost homeopathic) dose of an already licenced drug. Nonetheless some children do experience blurring or light sensitivity. Systemic effects are uncommon. If one compares the current treatment of amblyopia with weekend drops of 1 per cent atropine for a year, which would be around 100 drops of 1 per cent, this is a similar dose to 14 years of daily bilateral myopia drops (700 drops per annum) of 0.01 per cent. So although overall toxicity may not be a problem, the other long-term adverse effects on the eye, and knowing when to stop treatment and observe, is unknown. The European Medicines Agency has taken a different approach and is assessing low-dose 0.01 per cent atropine as a new agent and requiring indicationspecific clinical trials.

It is well established that myopia rates are inversely proportional to time spent outdoors. However, managing the prescription of time spent outdoors is a major conundrum. Australia has one of the highest rates of skin cancer in the world, although it was eclipsed by New Zealand for melanoma rates, probably because many new Australian immigrants have higher levels of protective skin pigmentation than earlier Northern European immigrants. We have spent two generations emphasising sun smart protection (slip, slap, slop, seek, and slide) yet our skin cancer rates remain high. We don’t know if wearing sunglasses negates the effect of time outdoors or whether the anti-myopia benefit can be obtained from early morning and late afternoon outdoor time when the risk of UV skin and eye damage is lowest. The Busselton Healthy Aging Study in Western Australia showed the trade off – adults with skin cancer had half the rate of myopia compared to those without skin cancer.

In children of Asian ancestry at higher risk of myopia, who have less cancer-prone skin, a personalised medicine approach of recommending increased time outdoors may be safe. In China, mass population measures such as limiting children’s screen time and increasing time spent outdoors are already in place. Of note four years ago, when we questioned a group of 75 Chinese medical students spending two months studying in Perth, Western Australia, we found that not one of them spent an average of one hour outside per day (or seven hours per week) while studying in China. Even convicts in solitary confinement at Fremantle Prison were given one hour outside per day! This year about 20 per cent of the current Chinese student cohort self-reported spending an hour or more outside per day. When asked about their activity during their two months period while studying in Perth, Western Australia, most were spending more than an hour outside per day.

FUTURE DIRECTIONS

Increasing the number of participants and the depth of genetic analysis of myopia and associated biometry will expand our understanding of the molecular mechanisms of myopia. Big data and mobile device technology will improve our epidemiological studies. With much data on off-label myopia treatments not being captured by clinical trials, our group is setting up an Australian Registry of Childhood Myopia Treatment (ARCMT). This is in line with other Australian eye disease registries, such as the Australian Corneal Graft Registry and Australian and New Zealand Registry of Advanced Glaucoma (both based at Flinders University) and The Fight Retinal Blindness! and Fight Corneal Blindness! registries (both at the Save Sight Institute in Sydney). From the ARCMT we hope to monitor the use of atropine, outdoor time, and orthokeratology, and the combination of these used by eye care practitioners throughout Australia.

The evidence base for treatments that prevent myopia are weak but orthokeratology, low-dose atropine eye drops, and increasing time spent outdoors all seem promising. However, if we are to be treating 50 per cent of all children to prevent myopia, then the risk/benefit profile of these treatments needs to be greatly improved. In addition the cost/ benefit ratio of potentially decades of treatment must be calculated. With genetics studies identifying new and known molecular pathways for myopia, trials of other therapeutic interventions are likely in the future. Ideally a combination of treatments will let us reverse or prevent the myopia epidemic worldwide.

Professor David Mackey is the chair of Ophthalmology at the University of Western Australia and Managing Director of the Lions Eye Institute in Perth. He is a former councillor of the Royal Australian and New Zealand College of Ophthalmologists and current RANZCO representative on the Council of the Asia Pacific Academy of Ophthalmology. He is past president of the International Society for Genetic Eye Disease and Retinoblastoma. Prof Mackey is a renowned international researcher in the genetics of eye disease and has published over 340 peerreviewed papers since 1989. He is the world’s most published author in glaucoma genetics and is a lead investigator in the International Glaucoma Genetics Consortium (IGGC) and the Consortium for Refractive Error and Myopia (CREAM). In 1993 Professor Mackey initiated the Glaucoma Inheritance Study in Tasmania (GIST) , thereby creating one of the largest glaucoma biobanks in the world, with over 5,000 DNA samples and clinical material from familial and sporadic cases of glaucoma. 

References 

  1. Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, Wong TY, Naduvilath TJ, Resnikoff S. Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050. Ophthalmology. 2016;123:1036-42. 
  2. Tedja MS Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. Nat Genet. 2018 Jun;50(6):834-848. 
  3. Sanfilippo PG, Hewitt AW, Hammond CJ, Mackey DA. The Heritability of Ocular Traits. Surv Ophthalmol. 2010;55:561-83. 
  4. Dolgin E. The myopia boom. Nature 2015;519(7543):276-278. 
  5. Lim CSS, Frick KD. The economics of myopia. In: Beuerman RW, Saw SM, Tan DHH, Wong TY, editors. Myopia: animal models to clinical trials. Singapore: World Scientific; 2011.
  6. Mackey DA. Myopia -The future progression of myopia: Seeing where we are going, Ophthalmic Genetics 2016;37:4, 361-365