Preventive treatment of childhood myopia

Klaus Trier, MD, ophthalmologist
Tingskiftevej 6
DK-2900 Hellerup
Denmark

Mail: ktrier@dadlnet.dk

 

The length of the human eye increases from 17 mm at birth to normally 24 mm at age 14. In myopic children, however, the eye elongates too quickly, and the eye can reach a length of over 30 mm. At the age of 16-20, the connective tissue of the eye matures, which causes the myopia to gradually stabilize. The final degree depends on the age of myopia onset. If the myopia starts before the age of 10, it will most likely progress to 6 diopters (D) or more.

 

Myopia is associated with an increased risk of sight-threatening eye disorders such as retinal detachment, degeneration of the retina, and glaucoma. Because of these complications, myopia is among the leading causes of blindness. For example, half of the approx. 600 cases of retinal detachment that occur every year in Denmark would be avoided if myopia progression could be limited to 3 D.

For a focused image to form on the retina, the length of the eye must match the refraction of light in the cornea and lens with an accuracy of less than 0.1 mm. Since the growth of the eye cannot be genetically programmed so accurately, the eye has a feedback mechanism which adapts the elongation rate. This mechanism works by regulating the mechanical strength of the outer wall of the eye, the sclera (the white of the eye). The ability of the sclera to resist deformation is determined by the content of collagen, a protein which makes up 80% of the dry weight of the sclera.

 

At birth, the eye is too short relative to the refraction of light in the cornea and lens, and the eye is therefore far-sighted. This is detected by the retina, which activates a collagen-degrading enzyme in the sclera. The enzyme softens the sclera, and the pressure inside the eye then pushes the eye into a more elongated shape. When the eye gradually has achieved the correct length, the collagen content in the sclera is upregulated and the elongation rate diminishes.

 

In myopic children, the content of collagen in the sclera is reduced. As a result, the eye elongates too quickly. The elongation rate may reach up to 1 mm/year against normally 0.1-0.2 mm/year.

 

Myopia typically increases by 0.5-1.0 D/year between the ages of 7 and 12 years and 0.25-0.5 D/year between the ages of 13 and 16 years. This corresponds to an excess elongation of the eye of 0.22 mm/year at the age of 7-12 years, 0.15 mm/year at the age of 13-14 years, and 0.10 mm/year at the age of 15-16 years. If this excess elongation is avoided, the myopia will not progress.

 

7-methylxanthine

 

7-methylxanthine (7-MX) is formed naturally in the body by breakdown of caffeine contained in coffee, cocoa, chocolate etc. 7-MX increases the content of collagen in the sclera and has repeatedly been shown to counteract the development of myopia in animals. Unlike caffeine, 7-MX has very little ability to penetrate the blood/brain barrier and is therefore devoid of stimulatory effects.

 

In 2003, the Danish Medicines Agency approved a trial in which the effect of 7-MX (one tablet of 400 mg daily) on myopia in children aged 8-13 was assessed. The trial showed a statistically significant effect and led to pharmacy-produced 7-MX tablets becoming available in Denmark from 2009 with reimbursement from the public health insurance.

 

Since 7-MX is excreted quite quickly, it is necessary to take the tablet three times a day to ensure full effect.

 

An analysis of data from 711 children collected in the period 2000-2021 has shown that the effect of 7-MX is proportional to the dosage. The results were published in 2022 by the highly respected journal "British Journal of Ophthalmology".

 

The analysis was repeated in July 2023 with data from 757 children aged 7-15 years who had up to 10 D myopia at baseline and who were followed with annual measurements for up to 9 years. Model calculations based on the entire material showed that a child who takes an average of one tablet 2.5 times a day will have 1.07 D less myopia and 0.35 mm shorter eyes after 6 years than an untreated child.

 

However, the effect is significantly greater if the treatment is started while the myopia is still moderate.

 

Thus, the same analysis based on data from 313 children aged 7-10 years, whose myopia did not exceed 4 D at the start showed that a child who takes one tablet 2.5 times a day will have 1.71 D less myopia and 0.65 mm shorter eyes after 6 years than an untreated child. This corresponds to reduction of myopia progression of 49%, 55%, and 63% for children aged 7, 9, and 11 years at start, respectively.

 

There is no indication that the efficacy of 7-MX diminishes with time.

 

No side effects of the treatment have been reported among around 1200 children treated since 2009. In addition, long-term studies of laboratory animals given a  30-50 times higher dose than used for myopic children have demonstrated that 7-MX is safe.

 

The 7-MX tablets are produced by Glostrup Apotek and available on prescription at all pharmacies in Denmark. 100 tablets of 400 mg cost approx. DKK 650. The ophthalmologist can apply for 85% reimbursement from the public health insurance. With three tablets a day, the cost after deduction of the public health insurance reimbursement is approx. DKK 1,400 per year. For members of the "Danmark" health insurance additional reimbursement is possible.

 

The length of the eye and the degree of myopia should be measured once a year and the treatment should be continued until around the age of 18.

 

Until further information is available, 7-MX should not be prescribed in case of diabetes, epilepsy or other serious chronic conditions. Children with very early myopia onset usually have little progression until the age of 6-7 years. Start of treatment can therefore be postponed until the child has reached this age.

 

Since nothing can be done to reduce myopia that has already developed, it is important to start treatment as early as possible. Unfortunately, myopia is often only detected when it has already reached 1-2 D. It is therefore a good idea to carry out an examination around the age of 7, especially if one or both parents are myopic.

 

7-MX combined with myopia-inhibiting glasses or contact lenses

 

In recent years, different designs of myopia-inhibiting spectacle lenses and contact lenses have appeared on the market in Denmark. In addition to a minus correction in the center, these optical devices also have fields with plus correction in the periphery, and controlled studies with a duration of up to three years have shown that they reduce the elongation rate of the eye. It is believed that the effect is due to a thickening of the choroid (the layer between the retina and the sclera).

 

However, the efficacy of optical devices diminishes with time, and especially in young children optical devices alone cannot in all cases prevent progression to high myopia over time. The greatest accumulated effect that has been demonstrated with an optical device is an accumulated reduction of eye elongation of 0.44 mm over a period of 7 years, corresponding to a reduction of myopia progression of about 1 D. For comparison, the expected myopia progression for a child aged 7-9 years is around 5 D.

 

For a discussion of the efficacy of optical devices, see:

 

Brennan NA, Toubouti YM, Cheng X, Bullimore MA. Efficacy in myopia control. Prog Retin Eye Res. 2021 Jul;83:100923. doi: 10.1016/j.preteyeres.2020.100923. Epub 2020 Nov 27. PMID: 33253901. https://pubmed.ncbi.nlm.nih.gov/33253901/

 

The use of myopia-inhibiting spectacle lenses or contact lenses can perfectly be combined with 7-MX.

 

Preliminary results indicate that the combined treatment completely prevents myopia progression in children already from the age 8 years.

 

References

 

Trier K, Olsen EB, Kobayashi T, Ribel-Madsen SM. Biochemical and ultrastructural changes in rabbit sclera after treatment with 7-methylxanthine, theobromine, acetazolamide, or l-ornithine. Br J Ophthalmol 1999;83:1370-1375.

https://www.ncbi.nlm.nih.gov/pubmed/10574816

 

Trier K, Munk Ribel-Madsen S, Cui D, Brøgger Christensen S. Systemic 7-methylxanthine in retarding axial eye growth and myopia progression: a 36-month pilot study. J Ocul Biol Dis Infor. 2008;1:85-93.

https://pubmed.ncbi.nlm.nih.gov/20072638/

 

Cui D, Trier K, Zeng J, Wu K, Yu M, Hu J, Chen X, Ge J. Effects of 7-methylxanthine on the sclera in form deprivation myopia in guinea pigs. Acta Ophthalmol 2011;89:328-34.

https://www.ncbi.nlm.nih.gov/pubmed/19860777

 

Nie H, Huo L, Yang X, Zeng J, Trier K, Cui D. Effects of 7-methylxanthine on form-deprivation myopia in pigmented rabbits. Int J Ophthalmol 2012;5:133-37.

https://www.ncbi.nlm.nih.gov/pubmed/22762036

 

Cui D, Trier K, Ribel-Madsen SM. Effect of day length on eye growth, myopia progression, and change of corneal power in myopic children. Ophthalmology 2013;120:1074-9.

http://www.ncbi.nlm.nih.gov/pubmed/23380471

 

Hung L-F, Arumugam B, Ostrin L, Patel N, Trier K, Jong M, Smith EL III. The adenosine receptor antagonist, 7-methylxanthine, alters emmetropizing responses in infant macaques. Invest Ophthalmol Vis Sci. 2018;59:472-486.

http://iovs.arvojournals.org/article.aspx?articleid=2670518

 

Wildsoet CF, Chia A, Cho P, Guggenheim JA, Polling JR, Read S, Sankaridurg P, Saw SM, Trier K, Walline JJ, Wu PC, Wolffsohn JS. IMI - Interventions for controlling myopia onset and progression report. Invest Ophthalmol Vis Sci 2019;60:M132-M160.

https://iovs.arvojournals.org/article.aspx?articleid=2727315

 

Trier K, Cui D, Ribel-Madsen S, Guggenheim J. Oral administration of caffeine metabolite 7-methylxanthine is associated with slowed myopia progression in Danish children. Br J Ophthalmol 2022;

https://bjo.bmj.com/content/early/2022/07/18/bjo-2021-320920?rss=1

 

https://pubmed.ncbi.nlm.nih.gov/37332548/