The myopia epidemic – can we stop it?
It is now clear that genetics and environment both play a role in the development of myopia.
The prevalence of myopia has rapidly increased over the last 30 years, with the World Health Organization (WHO) estimating a worldwide incidence of 23%, projected to increase to 50% by 2050.
Asian populations, especially Japanese, Koreans and Chinese, have a much higher incidence, especially of high myopia. The increased incidence (myopia in 50% of young adults in the USA and Europe and 90-95% in many East Asian countries) naturally begs the question as to what is driving this epidemic and if there is something that can be done to stop this.
The risk of myopia is three times higher when both parents are myopic than when none are. In the last two decades, more than 20 genetic loci and variants have been identified. Visual feedback regulates eye growth and refractive development. Specific retinal neurons and signalling mechanisms (e.g. changes in normal diurnal dopamine levels that are released by retinal amacrine cells) that regulate refractive development may cause myopia. Indeed, it is likely that genetic and environmental factors may interact towards development of myopia.
Studies have shown the protective effect of outdoor activities in reducing myopic onset and progression in schoolchildren. Increased dopamine release under high light conditions has been thought to reduce axial elongation. Retinal dopamine is regulated by retinal illuminance, spatial frequency of image, temporal contrast etc. A Chinese study by He et al in six-year-olds showed reduced myopic incidence over the next three years by the addition of 40 minutes of outdoor activity at school.
Though longer-term studies are needed, this and other similar studies may indicate a need for lifestyle modifications and change in public policies at school. The Sydney Myopia Study found that participation in indoor sports was not protective and the total time spent outdoors was more important.
However, what about the harmful effects of increased UV exposure? Ken Nischal MD, Chief, Paediatric Ophthalmology and Strabismus, Children’s Hospital of Pittsburgh, USA, says: “There is always a balance needed. There is evidence that increased daylight exposure has a protective effect and studies suggest a minimum of two hours a day, however, as outlined by a WSPOS Consensus Statement (http://wspos.org/sunlight-exposure-and-childrens-eyes), children’s eyes are at higher risk of UV damage and appropriate protection such as UVA/B blocking glasses and brimmed caps are important during sunlight exposure. Remember also that daylight exposure is not always linked to dangerous UV exposure. Climate and geography also play a role.”
Ian Flitcroft MD, Consultant Ophthalmologist, Children’s University Hospital, Dublin, Ireland, however states: “Evidence to date has shown that outdoor activity has an influence, but this seems to relate mostly to younger children and has a small to moderate impact on myopia onset. There is now good evidence that it does not influence myopic progression in older children. As authors of studies in China have noted, results have not been as strong as they had hoped. It is therefore a viable but limited intervention for myopia prevention, provided it does not lead to increased UV skin damage. One thing is now certainly clear, claims that time outdoors is the answer are grossly overstated.”
A 13-year-old girl doing her homework outdoors with the use of spectacles, in a park in Paris, France. Courtesy of the film ‘LOSING SIGHT – Inside the Myopia Epidemic’ by Jane Weiner, a co-production of ARTLINE FILMS & JP Weiner Productions, Inc. Camera: Boris Carreté. Copyrighted photos published with permission
Near work has also been implicated in myopia development. Retinal defocus and retinal image contrast degradation are thought to trigger eye growth as a compensatory mechanism. Studies have shown that early-onset myopes and progressive myopes have significantly greater axial elongation than emmetropes following prolonged near task work. There have also been studies with no significant difference in magnitude of eye elongation in myopic and emmetropic subjects. Contraction of ciliary muscle during accommodation results in forward and inward pulling of choroid, thus decreasing circumference of the sclera, and elongating axial eye length.
In individuals with high genetic risk, those with university level education had higher risk of myopia, while those with only primary schooling had a much lower risk. The combined effect of these two factors was far higher than their sum, showing synergy. Twin studies by Dirani et al conclude that degree of educational attainment is strongly associated with genes and these same factors may also be responsible for refractive error development.
So, are the worldwide increasing levels of education and increased near work time responsible? Is staring at smartphones and laptops contributing? Do those born to be myopic naturally gravitate to academic studies and near-work occupations, or does engaging in these activities, particularly during development, cause myopia?
Though there is no final conclusion on this, the World Society of Paediatric Ophthalmology and Strabismus (WSPOS) statement does suggest that intensity of near work, i.e. sustained reading at closer distance (less than 30cm) with fewer breaks, may be more important than total hours spent. The 20-20-20 rule (focusing 20 feet away for 20 seconds every 20 minutes of near work) may therefore be important not just for decreasing dry eyes but also myopia.
So what can we do about the growing incidence of myopia in young people? Children on pirenzepine gel, cyclopentolate eye drops and atropine eye drops have been shown to have less myopic progression, however side effects such as blurred near vision, photophobia and concerns about long-term safety have discouraged this approach. These agents act not by eliminating accommodation but by anti-muscarinic receptor binding that causes a local retinal biochemical change which slows eye growth.
Atropine is traditionally used in many East Asian countries. The landmark Atropine in the Treatment of Myopia (ATOM) studies found a beneficial effect for 1% atropine. Low-dose atropine 0.01% showed great promise for myopia control by over 50% with much lesser side effects. Various mechanisms have been proposed: increased dopamine release by atropine binding to muscarinic receptors of amacrine cells; reduction of γ-aminobutyric acid (GABA) levels; atropine binding to muscarinic receptors on scleral fibroblasts and interfering with scleral remodelling etc. Surprisingly, its action may not be via an accommodative mechanism.
David Granet MD, Director, Ratner Children’s Eye Centre, Shiley Eye Institute, University of California, San Diego, USA, says: “I already offer low-dose atropine to paediatric patients of Asian origin with advancing myopia. We have extensive discussions about risks, benefits and alternatives with parents. However, I am not sure it will work in eyes with differing iris pigment, genetics and epigenetic phenomenon. There is data suggestive that it will.”
Dr Nischal notes: “With any new treatment, most important is for centres in different parts of the world to replicate results. Therefore, it is very important that doctors who start to recommend atropine 0.01% document accurately refraction, axial length and fundoscopy. The Singapore group lead by Audrey Chia have developed booklets for follow-up.
“Treatment may be for several years and parents should be counselled about this. If no response, one has to be prepared to increase to perhaps 0.1% atropine. The only way to confirm if ATOM results will be universally applicable is by following the above recommendations. Indicators are that there is a subset of children who are non-responders and whether this subset is higher in non-Asian children is at present unknown.”
HUGELY IMPORTANT TRIALS
However, Dr Flitcroft cautions that while ATOM1 and ATOM2 are hugely important trials, significant questions remain. The ATOM2 study relied only on historical controls. It was conducted in a Singaporean population between six-12 years of age, which both racially and in terms of pattern of myopic progression is very different to Europe. There are also questions regarding the effect on axial length from the study data, although a recent network meta-analysis indicates that low-dose atropine had significant effect on axial length.
“Unresolved questions include when to start treatment, who benefits most (fast versus slow progressors, younger versus older patients, and possible results in less pigmented Caucasian eyes). Large-scale uncontrolled use of low-dose atropine at this stage carries the risk of muddying the waters enormously. Local compounding pharmacy dilutions also create issues of variable drug dosages, stability and increased risk of infections,” said Dr Flitcroft.
Well-organised, placebo-controlled trials in European populations would be needed in order to determine whether the ATOM trial data can be translated to Caucasian eyes. Dr Flitcroft’s group conducted the SHIELD pilot study, which looked at the impact of 0.01% atropine on pupil size, accommodation and quality of life, to assess likely acceptability in Caucasians. Concerns that low-dose atropine may have more side effects and reduced tolerability in lightly pigmented eyes were set to rest in terms of pupil size, accommodation and daily activity impact.
“The SHIELD study was a prelude to what will be Europe’s first placebo-controlled trial on efficacy and acceptability of low-dose atropine in a European population. We (Dr Flitcroft and Prof James Loughman) have just received funding for this Dublin-based clinical trial and will begin recruitment in early 2017. It will also examine the mechanism of action of atropine with a detailed analysis of biometric changes during myopia progression with and without treatment,” said Dr Flitcroft.
Orthokeratology lenses are another approach. Patients wear overnight rigid gas permeable contact lenses flatter than the cornea to cause shape change. However, corneal shape is largely regained within three days of stoppage and most parameters reach baseline within one-eight weeks. Reported problems include glare and night vision driving issues, artificially low intraocular pressure recordings, and reduced contrast sensitivity.
Dr Granet comments: “Done well, orthokeratology has supporting data with regards to rate of myopic progression. However, the risk of bacterial keratitis in a population prone to poor compliance with hygiene makes me concerned about wholesale use of this modality.”
To conclude, we are still far away from clearly elucidating all contributing factors to the alarming myopia epidemic.
However, with increasing understanding, we find ourselves going full circle back to age-old treatment modalities such as atropine, bright light exposure and avoidance of near work. Guidelines and the science behind many of these proposed treatment techniques are becoming clearer.
Three major approaches are emerging: 1) Promoting exposure to bright light and outdoor activity; 2) Optical corrections to generate growth inhibitory signals in retina, and 3) Applying atropine eye drops at low doses.
Revolutionary techniques such as genetic engineering may yet be the ones that will make their mark, however, as of now, battle lines are drawn and the future seems more optimistic.
Ken Nischal: firstname.lastname@example.org
Ian Flitcroft: email@example.com
David Granet: firstname.lastname@example.org