Concern for myopia progression increases with alarming rise in global prevalence

As one of the most common eye disorders across the world, myopia’s prevalence has alarmingly increased over the years, starting at younger ages than ever before.

Understanding myopic progression is important, but the condition also needs to be recognized as an epidemic, according to OSN Contact Lenses Section Editor Penny A. Asbell, MD, FACS, MBA.

“It’s something that ophthalmologists should be thinking about it,” Asbell said. “A lot of ophthalmologists may be missing the boat of thinking about how this fits into their opportunities to care for patients.”

Globally, high myopia is ranked second behind cataracts as the leading cause of visual impairment, with 10% of all myopes having 6 D of refractive error or more, according to a review published by Liu and colleagues.

Image: Asbell PA

Myopia has nearly doubled in the last 30 years in the U.S., going from a 25% prevalence rate in 12- to 54-year-olds in 1971-1972 to a 42% prevalence rate in 1999-2004.

In East Asia, nearly 50% of urban populations are myopic, while its prevalence in university student populations is approximately 90%, Smith and Walline wrote in a review in Adolescent Health, Medicine and Therapeutics.

There are many contributing factors to the growing epidemic and limited measures to control and manage it, so now there is greater scientific interest in understanding myopia’s development and progression, particularly in adolescents.

The rate of progression is fastest in young children, with an approximate rate of 0.5 D of progression per year across various ethnicities. Younger age at onset has been linked to faster progression, which leads to increased myopic severity.

“There is a myth that myopia is just corrected with spectacles, contact lenses or refractive surgery. The most worrying aspect of the myopia epidemic is the exponential increase in diseases related to the stretching of the eye with increasing axial length,” David Mackey, MBBS, MD, FRANZCO, FRACS, said.

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.

“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.”

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.

Environmental factors

Although an understanding of the prevalence of myopia is known, the condition’s associated susceptibility and risk factors are not fully understood. However, environmental susceptibility to myopia tends to be common across all ethnicities.

Prolonged near work tasks, such as reading, writing or portable device use, may increase the risk of myopia development in children.

“I think the reality of our world is that near work has increased because of the increase in the use of electronic devices. I don’t think we’re going to stop that trend just because we find that it’s increasing the prevalence of myopia, so I think we need to be more vigilant about detecting it early and considering myopia prevention strategies,” OSN Pediatrics/Strabismus Board Member Erin D. Stahl, MD, said.

Increased outdoor activity has been shown to protect against myopia development, with an increase in myopic progression during winter months compared with the summer.

The protective effect of time spent outdoors may be due to high-intensity outdoor light, the chromaticity of daylight or increased vitamin D levels.

“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. 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.

Genetic factors

Parental myopia plays a predominant role in myopia development. A child with two myopic parents has a fivefold to sixfold increased risk of myopia development compared with a child with one or no myopic parents, Gifford and Gifford reported in Optometry and Vision Science.

Myopic parents already know the ill effects of myopia and want to diminish those effects in their own children, according to Asbell: “These are the people who think, ‘What can I do for my child who is 7 years old and already a little myopic?’”

The Consortium for Refractive Error and Myopia (CREAM) and the company 23andMe have each found more than 20 gene markers associated with myopia, according to Mackey.

“This is just the start of the identification of myopia genes, and much more work and many more gene markers will be identified in the near future,” he said.

There is debate, however, on whether children’s susceptibility to myopia is solely inherited through genetics or if the influence of myopic parents in an environmental setting is more significant. Some theories suggest that children of any ethnicity with myopic parents tend to spend less time outdoors compared with children without myopic parents, according to Gifford and Gifford.

Demographic factors

Ethnicity has also been found to play a role in myopic susceptibility. Generally, the prevalence of myopia is highest in Asian populations, followed by Hispanic, African-American and Caucasian populations.

According to a study published in Eye, prevalence of myopia in Australian schoolchildren was reported to be 42.7% and 59.1% in 12- and 17-year-old school-aged children of East Asian ethnicity, respectively, compared with only 8.3% and 17.7% in European Caucasian children of the same age, respectively.

“One could presume a genetic cause, but the behaviors of Asian children differ because they study more and spend less time outside,” Mackey said.

Geographic location may play a role in the prevalence of myopia. For example, the myopic prevalence is 16.2% in children in rural areas of China vs. 38.1% and 36.7% in the metropolitan areas of Guangzhou and Hong Kong, respectively, according to Foster and colleagues.

Younger age may also contribute to high myopia. According to a review published in Adolescent Health, Medicine and Therapeutics, myopia typically develops at approximately 8 years of age and progresses through 15 to 16 years of age with an average progression rate of approximately 0.5 D per year. Conversely, those who develop myopia later in life do not face as severe a progression rate as adolescents.

Socioeconomically, years of education increase the risk of myopia while also increasing a person’s likely income; thus, people with myopia tend to have higher incomes, according to Mackey.

Treatments with negligible effect on progression

“Undercorrection of myopia, gas permeable contact lenses, and bifocal or multifocal spectacles have all been proven to be ineffective for myopia control,” Smith and Walline wrote in Adolescent Health, Medicine and Therapeutics.

Contact lenses are an option for children, especially reverse geometry lenses that have shown some efficacy in myopia control, but the risk-benefit ratio needs to be carefully considered given the risk of infection, according to Asbell, as discussed in Eye & Contact Lens.

And whereas undercorrection of myopia is commonly thought to reduce accommodative effort and lag, it either increases progression or has no effect, according to Smith and Walline.

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

Pharmacologic prevention

“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. Treatment was then ceased for 1 year, and children in any group with myopia progression of more than 0.5 D during the washout period were restarted on atropine 0.01% for an additional 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. After atropine was stopped for 1 year, there was a rapid increase in myopia in those who received higher concentrations of atropine, with 68% of children in the 0.5% group, 59% of children in the 0.1% group and 24% of children in the 0.01% group requiring re-treatment with 0.01% atropine.

Younger children and those with greater myopic progression were more likely to require re-treatment, the study said.

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. The benefit really was to go down to a concentration that is low enough to have minimal side effects.”

Additionally, a U.S.-based study, published in the Journal of Ocular Pharmacology and Therapeutics, evaluated atropine 0.01% in an ethnically diverse population of 60 children over a broad range of myopia. The drug significantly reduced the rate of myopic progression over 1 year with minimal side effects. The study suggested that atropine 0.01% was most effective in children with low initial myopia but may not control rapid progression in some patients.

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 strategies

Contact lenses are currently used for the refractive correction of myopia but show minimal to no effect on myopia control. Ideally, axial lengthening must be slowed in order to help control myopia.

Orthokeratology uses custom-designed rigid lenses (reverse geometry contact lenses) worn overnight to temporarily modify the curvature of the cornea. These lenses, such as CRT (Paragon), are FDA approved in the U.S. for correcting myopia but have shown to slow myopia progression in children in some clinical trials in Asia, according to Asbell.

“Orthokeratology probably has the most data on its use for correcting myopia. That’s what it was developed for as an alternative to LASIK or other ways of correcting myopia, and it unexpectedly turned out that it seemed to slow myopia progression,” Asbell said.

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.

If orthokeratology can be deemed a safe and effective management option, Asbell said patients would benefit from the ease of use.

“The benefits are that it seems to be helpful to slow progression,” Asbell said. “The advantages from the patient point of view is they’re not doing anything during the day, and they’re not worried about comfort so much because they’re putting the contact lenses on right before they go to bed when their eyes are closed and removing in the morning.”

The biggest limitation with orthokeratology, like other lenses, is the risk of infection.

“Initially there were lots of reports, primarily in China, but it turns out that many of those lenses were not properly fit and had poor follow-up. They might not have told them about contact lens hygiene, they used tap water — all sorts of things that are not appropriate for contact lens care,” Asbell said. “So the risk for infection is real, but it’s probably similar to other overnight contact lens use.”

According to a review published in Optometry and Vision Science, the ideal myopia-controlling contact lens should:

• induce peripheral myopia without compromising vision;
• reduce lag of accommodation;
• reduce near esophoria;
• provide controlled release of antimuscarinic agents;
• provide a beneficial shift in positive spherical aberration to improve near point depth of focus without compromising image quality; and
• measure ocular biometrics and analyze surroundings to provide real-time advice and training in avoiding visual situations or environments that increase the risk of myopia progression.

“The optical strategies right now, we’re looking at contact lenses, and strangely enough it’s not the focus of myopia, correcting your refractive error. It’s the focus on the periphery that seems to be important for a stimulus to prevent or slow progression,” Asbell said.

Public health consequences

Because the onset of visual complications occurs earlier in life, myopia’s impact on quality of life is also seen much earlier.

“Quality of life is affected because some of these people feel like they’re legally blind, which they are if they don’t have their glasses or contact lenses immediately at hand to use,” Asbell said.

“You may be limited in the activities that you are able to participate in. Depending on how severe your refractive error is in general, it can have an impact on the different roles you play in life,” Susan Vitale, PhD, MHS, a research epidemiologist at the National Eye Institute, said.

Overall, there is an estimated economic burden of $2 billion annually in the United States, according to Liu and colleagues.

“First, you have the risks associated with high myopia, and second, they’re definitely going to have to spend costs on either glasses, contact lenses or maybe when they’re older on refractive surgery. In other words, there are costs that go on in a lifetime. It’s not just a cost when they are managing the myopia progression,” Asbell said.

“Although myopia is a really common condition and is relatively easily treated using corrective lenses or in some cases refractive surgery, it is a very prevalent condition. If you just look at it from an economic standpoint, it is a tremendous cost just to provide lenses to so many people in the country,” Vitale said.

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.”

Future

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.

“I think that [researchers] are learning more and more all of the time about the different mechanisms of myopia, but they still don’t completely understand what the cause is. They particularly don’t understand the cause of this increased prevalence seen over the last 10 to 20 years in a lot of different countries,” Vitale said.

Mackey said that it is vital to understand the precise epidemiology of myopia in order to discern management options to prevent progression.

“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.

“As a pediatric ophthalmologist, I think it’s important that instead of just putting our myopes in glasses, to be more conscious about myopia progression. This monitoring could include serial axial length measurements and watching out for kids who have a faster progression in their myopia and who are heading toward higher myopia. Another part is to ask about family history and how myopic the parents are,” Stahl said.

“We don’t totally have the answer. What we do have is an increasing amount of evidence from several different sources, several different methodologies, that may be able to impact myopia progression. I think that’s a big take-home message, that it’s not just inevitable,” Asbell said. – by Kristie L. Kahl

• References:
• Asbell P. Eye Contact Lens. 2016;doi:10.1097/ICL.0000000000000224.
• Chia A, et al. Ophthalmology. 2015;doi:10.1016.j.ophtha.2015.07.004.
• Clark TY, et al. J Ocul Pharmacol Ther. 2015;doi:10.1089/jop.2015.0043.
• Foster PJ, et al. Eye (Lond). 2014;doi:10.1038/eye.2013.280.
• Gifford P, et al. Optom Vis Sci. 2015;doi:10.1097/OPX.0000000000000762.
• Smith MJ, et al. Adolesc Health Med Ther. 2015;doi:10.2147/AHMT.S55834.
• Liu YM, et al. Eye Contact Lens. 2016;doi:10.1097/ICL.0000000000000219.

• For more information:
• Penny A. Asbell, MD, FACS, MBA, can be reached at Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1183, New York, NY 10029; email: penny.asbell@mssm.edu.
• David Mackey, MBBS, MD, FRANZCO, FRACS, 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.
• Erin D. Stahl, MD, can be reached at Children’s Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108; email: edstahl@cmh.edu.
• Donald T.H. Tan, MBBS, FRCSG, FRCSE, FRCOphth, can be reached at Singapore National Eye Center, 11 Third Hospital Avenue, Singapore 198751; email: donald.tan.t.h@snec.com.sg.
• Susan Vitale, PhD, MHS, can be reached at National Eye Institute, National Institutes of Health, 10 Center Drive, Room 10D45, Mail Stop 1863, Bethesda, MD 20892; email: sev@nei.nih.gov.

Disclosures: Stahl reports she is an advisor to TreeHouse Health. Asbell, Mackey, Tan and Vitale report no relevant financial disclosures.

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

Low dose is effective

Yes, it is time to consider atropine as therapy to reduce the progression of myopia. The key for me is that a low dose of atropine (0.01%) administered as a drop once daily has been shown to be effective in reducing the progression of myopia by 0.5 D per year in some children.

I have always been reluctant to prescribe atropine drops because of the side effects of reduced vision and photophobia. Frankly, most parents are unwilling to accept treatment because of this. In the ATOM clinical trial, Tan found that the 0.01% concentration group had minimal pupil dilation, minimal loss of accommodation and no near vision loss. In this day and age of 2-year-olds playing with small handheld electronic devices and progressive myopia increasing at epidemic proportions, a readily available low concentration of atropine drop would be welcomed by many for therapy. Many of us now tell our patients’ families that outdoor activities are of benefit in reducing the progression of myopia, but this really is not enough and not so easy to accomplish in the winter months in northern latitudes. I would love to see a large multicenter, well-designed longitudinal cohort study for additional evidence of the efficacy of low-dose atropine therapy for the treatment of myopia.

Rudolph S. Wagner, MD, is an OSN Pediatrics/Strabismus Board Member. Disclosure: Wagner 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 Pediatrics/Strabismus Board Member. Disclosure: Wilson reports no relevant financial disclosures.