Concern for myopia progression increases with alarming rise in global prevalence

The prevalence of myopia, one of the most common eye disorders across the world, has alarmingly increased over the years, starting at younger ages than ever before. A systematic review and meta-analysis recently published in Ophthalmology estimated that myopia and high myopia will affect nearly 5 billion people and 1 billion people, respectively, by 2050.

Studies of East Asian populations report a two-, three- or even fourfold increase in the number of teenagers and young adults developing the disorder. In Taiwan and Singapore, the prevalence of myopia is 20% to 30% among 6- to 7-year-olds, reaching as high as 84% in high school students in Taiwan. The myopia progression rate in East Asian children is high, nearly –1 D per year, and approximately 24% of the population become high myopes as adults, Pei-Chang Wu, MD, PhD, said.

In the U.S., myopia has nearly doubled in the last 30 years, going from a 25% prevalence rate in 1971 to 1972 to a 42% prevalence rate in 1999 to 2004. Europe has similar patterns and similar rates, as shown by a study published in 2015 by the European Eye Epidemiology Consortium in Ophthalmology.

“The prevalence of the condition is important to take note of,” Donald T.H. Tan, MBBS, FRCSG, FRCSE, FRCOphth, OSN APAO Edition Board Member, said. “More important is the fact that, the more myopic prevalence increases, the more the percentage of patients end up with high myopia. And it is the high myopia group that is most likely to develop ocular comorbidities or significant ocular problems in adulthood.”

Higher degrees of myopia are associated with an increased rate of glaucoma, retinal detachment, macular choroidal degeneration, myopic choroidal neovascularization and myopic retinoschisis, as well as early-onset cataract, amblyopia and strabismus. Researchers have conducted many studies to review the varying factors associated with myopia and to evaluate treatment and management options in order to control the problem and prevent its debilitating public health consequences.

Risk factors

Multiple familial studies and twin studies support a genetic component of myopia, and genome-wide association studies in adults have identified 39 loci associated with refractive error. However, the exponential increase of myopia in recent years has shifted the interest of researchers toward environmental causes and their interaction with genetic susceptibility.

The Consortium for Refractive Error and Myopia investigated gene-environment interactions in 5,200 children assessed longitudinally across ages 7 years to 15 years, involving major environmental risk factors, near work and time outdoors. One of the investigators, David Mackey, MBBS, MD, FRANZCO, FRACS, also published a systematic review and meta-analysis of studies investigating the association between time spent outdoors and myopia in children and adolescents. A significant protective association was found between increasing time spent outdoors and prevalent myopia in nearly 10,000 children and adolescents 20 years of age and younger. Each increase in hours per week of time spent outdoors was associated with a 2% reduced odds of myopia after adjustment for potential confounders.

“The analysis of what it is about time outdoors that protects against myopia is still in the early phases. There is certainly a hundredfold or more difference in illumination between indoors and outdoors,” Mackey said.

Increased light intensity leads to pupil constriction, increased depth of focus and release of dopamine, which inhibits axial elongation. In addition, more time spent outdoors goes hand in hand with less time spent on near work. Reading and other tasks requiring prolonged near vision have long been proposed as environmental risk factors for myopia that children are ubiquitously exposed to during their school years.

“Whether we can prevent myopia by increasing lighting in classrooms or enlarging windows, even to the extent of having almost a glasshouse classroom, needs to be studied,” Mackey said.

Daylight exposure

Outdoor intervention programs carried out in East Asia have shown promising results.

The ROC (recess outside classroom) study was conducted at two elementary schools in Taiwan to see if the educational policy could decrease myopia incidence. One school with 333 students turned off the classroom light and required children to go outside the classroom for outdoor activities during recess time, around 80 minutes per day. The other school with 238 students did not have any special programs during recess time.

“After 1 year, new onset myopia was found in only 8% of kids in the ROC school, while the incidence in the control school was 17.5%. ROC could decrease by over 50% the new onset of myopia,” Wu, the leader of the study, said.

Other projects of this kind followed. A study carried out at six schools in Guangzhou, China, proved that the addition of 40 minutes of outdoor activity per day resulted in a significant decrease in myopia incidence after 3 years. Parents were also encouraged to engage their children in outdoor activities after school hours, especially during weekends and holidays.

Image: Wu PC

“Outdoor activities is a simple and effective method to prevent myopia onset. The Taiwan schoolchildren vision care program of the Ministry of Education has adopted the ROC strategy and continues to promote ‘everyday outdoor 120 minutes’ in schools throughout the country. Results at 4 years are quite remarkable. In China, 40-minute outdoor time per day has become a widespread practice in schools,” Wu said.

He said that a minimum of 10 to 14 hours of outdoor activity per week is required to protect from myopia. Below this threshold, studies have failed to prove efficacy.

According to epidemiological studies, children in East Asian develop myopia at an earlier age as compared with Europe and the U.S. The rate of progression is faster in younger children, and early onset is therefore associated with higher degrees of myopia in later life.

“For the children in East Asia, myopia progression is around –1 D per year in primary school and junior high school, –0.5 D in senior high school and stable after puberty,” Wu said.

The recently released Myopia Consensus Statement of the World Society of Paediatric Ophthalmology and Strabismus (WSPOS) recommends increasing daylight exposure and reducing intense periods of near work as part of the strategy to retard the progression of myopia. However, outdoor activity by itself could not effectively prevent myopia progression after myopia onset, Wu said. Medical intervention should be added.

Pharmacological method

Varying concentrations of atropine eye drops have been further studied in recent years as treatments that may slow myopia progression.

“With atropine the problem really is twofold, whether there are systemic side effects with atropine as a cardiac drug and whether there are any topical side effects,” Tan said.

The Atropine for the Treatment of Myopia (ATOM2) clinical trial, published in Ophthalmology, compared the safety and efficacy of different concentrations of atropine eye drops to control myopia progression over 5 years.

In the double-masked study, 400 children were randomized 2:2:1 to receive 0.5%, 0.1% or 0.01% of atropine once daily in both eyes for 2 years. Children who received higher concentrations of atropine initially demonstrated a greater effect in slowing myopia progression; however, there was no significant difference between dosage groups at 2 years. The 76% of children who did not require re-treatment in the 0.01% group after year 3 continued with a persistent response in reduced progression; had the lowest overall myopia progression and change in axial elongation; and had minimal pupil dilation, minimal loss of accommodation and no near visual loss compared with the higher concentrations of atropine at the end of the 5-year follow-up.

Tan said he believes the 0.01% concentration has minimal side effects while still reducing the rate of myopia progression by 50% to 60%.

“The average pupil dilation is about 1 mm, which we don’t think is that clinically significant,” Tan said. “Very few children, if any, will get glare. And there is minimal effect on accommodation, so children with this lower dose have actually no problem in reading and studying.”

In the WSPOS consensus statement, atropine 0.01% is No. 1 in the list of “What does work” in retarding progression of myopia. It “appears to offer an appropriate risk-benefit ratio, with no clinically significant visual side effects balanced against a reasonable and clinically significant 50% reduction in myopia progression,” according to the document.

Tan said more studies are needed to make management options more customizable because “one size doesn’t fit all.” He recommended reviewing atropine with adjunctive treatments.

“For example, you could use atropine eye drops and some of these optical aids like contact lenses or bifocals/spectacles, as well as environmental and behavioral modifications — get parents to make sure the child has outdoor activities. This needs to be done, but it’s many more years of work,” he said.

Optical strategy

Orthokeratology aims at reshaping the front surface of the cornea by wearing reverse geometry contact lenses overnight. Studies demonstrated that besides the immediate refractive effect during the day, orthokeratology may reduce myopia progression in children. The WSPOS consensus document noted that orthokeratology results in an approximately 40% reduction in the progression of myopia, although sustained myopia control is still unproven and no washout data are available. Some concern, however, is expressed about the “more than one hundred cases of severe microbial keratitis related to orthokeratology” reported since 2001.

A study, published in Eye & Contact Lens, reviewed 170 publications to evaluate the ocular safety of orthokeratology treatment to correct and delay myopia. Potential complications significantly associated with orthokeratology included microbial keratitis, corneal staining and lens binding; however, the study authors found it to be a generally safe treatment option. Long-term success of the treatment, they say, “depends on a combination of multiple factors including proper fitting of the lenses, rigorous compliance to lens use and care regimen, adherence to routine follow-ups, and timely and appropriate treatments to complications.”

“The lens hygiene is very important,” Wu said.

Although Wu uses atropine as first-line treatment, there are cases in which he offers orthokeratology as an option.

“Most commonly, I would use the lowest effective dose of atropine eye drop at bedtime every day initially. Most kids do not feel photophobia with 0.01% atropine, and the pupil does not dilate in the morning. In some circumstances, however, I would use orthokeratology to control myopia progression because some parents feel more comfortable with a non-pharmacological option,” he said.

The future

In Singapore, there are more than 700 optical outlets for 5 million people, with the optical business accumulating more than $350 million in business. The country spends $115 million on eyeglasses alone per year, Tan said.

“There is also the inherent cost of treating the complications of myopia — retinal detachment, macular degeneration — that probably is estimated to be about $2 million to $2.5 million,” he said. “So it is a significant financial burden on the population and I would expect that these figures would be replicated in other East Asian countries, but also in the West where myopia prevalence is high.”

Over the past decade, there has been an abundance of large-scale population-based prevalence studies however, there is a need for well-designed longitudinal cohort studies to help understand the mechanisms and factors driving the fast increased prevalence seen over the last 10 to 20 years in large areas of the world.

It is vital to understand the precise epidemiology of myopia in order to discern management options to prevent progression, control the problem and prevent its debilitating public health consequences.

“What are the molecular pathways involved in myopia development and progression that explain how education and outdoor activity influence myopia? Genetics research will help find these pathways. Then we need the basic science research to elucidate the mechanism and hopefully result in some new treatments,” Mackey said. – by Michela Cimberle and Kristie L. Kahl

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Wolffsohn JS, et al. Cont Lens Anterior Eye. 2016;doi:10.1016/j.clae.2016.02.005.

World Society of Paediatric Ophthalmology & Strabismus Myopia Consensus Statement. http://wspos.org/wp-content/uploads/2016/04/WSPOS_Consensus-Statement_Myopia.pdf.

Wu PC, et al. Ophthalmology. 2013;doi:10.1016/j.ophtha.2012.11.009.

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For more information:

David Mackey, MBBS, MD, FRANZCO, FRACS, is professor of ophthalmology at the Lions Eye Institute, University of Western Australia, Perth, Australia. He can be reached at the Centre for Ophthalmology and Visual Science, The University of Western Australia, 2 Verdun St., Perth, WA 6009, Australia; email: david.mackey@uwa.edu.au.

Donald T.H. Tan, MBBS, FRCSG, FRCSE, FRCOphth, is senior advisor of the Singapore National Eye Centre and chairman of the Singapore Eye Research Institute. He can be reached at Singapore National Eye Center, 11 Third Hospital Avenue, Singapore 198751; email: donald.tan.t.h@snec.com.sg.

Pei-Chang Wu, MD, PhD, is director of the Department of Ophthalmology at Kaohsiung Chang Gung Memorial Hospital and professor at Chang Gung University College of Medicine, Kaohsiung, Taiwan. He can be reached at email: wpc@adm.cgmh.org.tw.

Disclosures: Mackey, Tan and Wu report no relevant financial disclosures.

 

 

Is it time to consider atropine as first-line therapy to reduce progression of myopia?

Low dose is effective

Atropine blocks muscarinic receptors non-selectively. Muscarinic receptors are found in human ciliary muscle, retina and sclera. Although the exact mechanism of atropine in myopia control is not known, it is believed that atropine acts directly or indirectly on the retina or sclera, inhibiting thinning or stretching of the sclera, and thereby eye growth. The ATOM1 study on 400 Singaporean children suggested that 1% atropine slowed myopic progression by 77% and reduced axial length elongation. The ATOM2 study demonstrated a dose-related response with 0.5%, 0.1% and 0.01% atropine slowing myopia progression by an estimated 75%, 70% and 60% with spherical equivalent changes of 0.3 D, 0.38 D and 0.48 D, respectively, over 2 years. However, when atropine was stopped, there was an inverse increase in myopia, with rebound being greater in the children previously on higher doses. This resulted in myopia progression being signicantly lower in children previously assigned to the 0.01% group at 36 months and 5 years. It was estimated that, overall, atropine 0.01% slowed myopia progression by at least 50%.

The efficacy of lower-dose atropine is corroborated by Taiwanese cohort studies. Atropine 0.01% caused minimal pupil dilation (0.8 mm), minimal loss of accommodation (2 D to 3 D) and no near visual loss compared with higher doses. Children on atropine 0.01% did not need progressive additional lenses, unlike those on higher doses. These results encouraged us to use atropine as first-line therapy in children with progressive myopia. However, it should be taken into account that there are children who are poor responders to atropine. In ATOM1, 12.1% of children (younger, with higher myopia and greater tendency of myopic progression) had myopia progression of more than 0.5 D after 1 year of treatment with atropine 1%. In addition, low dose atropine 0.01% is not commercially available in most countries. There are still a lot of unknown factors to be worked out, including the exact mechanism of atropine in myopia progression retardation and the optimal duration of treatment.

Seo Wei Leo, MD, is a senior consultant ophthalmologist, Mount Elizabeth Medical Centre, Singapore. Disclosure: Leo reports no relevant financial disclosures.

More work is needed

More work is needed before atropine can be considered a first-line therapy to reduce progression of myopia. The ATOM1 study documented an average of only –0.29 D progression of myopia over 2 years in the 1% atropine group. However, visual function suffered, and side effects made the treatment unpopular. ATOM2 showed, surprisingly, that very dilute atropine (0.01%) can still slow myopia progression, although not as markedly as the 1% solution (average progression of –0.49 D). This very dilute solution has not been adequately tested across a diverse patient population, and it is not commercially available in the U.S. While compounding pharmacies can mix it, a short shelf life may make it difficult to stock and costly to dispense. In addition, the optimal duration of use has not been worked out, and rebound myopic progression after discontinuation may reduce the long-term benefit. Atropine use has not been linked, thus far, with a reduction in the most serious side effects of high myopia (myopic maculopathy and retinal detachment). Optimal treatment strategies will require not only a more complete understanding of atropine’s effects on axial eye growth, but also the consequences of and remedies for relative peripheral hyperopia, accommodation errors and the indoor visual environment of children with myopia.

 

M. Edward Wilson, MD, is an OSN U.S. Edition Pediatrics/Strabismus Board Member. Disclosure: Wilson reports no relevant financial disclosures.