Myopia Medications and Genetics – MYOPIA * Prevention

Biological processes are all ultimately how chemical processes react with their surroundings. The more detail that is known about a process, the greater our ability to modify it. Myopia is a complex interplay of many factors that result in an eyeball being too long for the focal plane of light entering the eye. Why this happens will ultimately be understood as the interplay of many molecular processes and the study of the very basic parts of this process will eventually allow us to greatly modify, if not control, myopia.

These references are mostly, but not exclusively, related to the lower levels of juvenile myopia. More references can be found by searching for your own articles using the PubMed (National Library of Medicine) database. Just enter some terms such as "myopia gene". There were 629 such articles listed on 04 October 2011.

MyopiaPrevention.org comment: Subtitled Myopia Control with Atropine 0.01% Eyedrops. From the conclusions: "Over 5 years, atropine 0.01% eyedrops were more effective in slowing myopia progression with less visual side effects compared with higher doses of atropine."

Read the commentary by Jeffrey Cooper: Practice Update. Eye Care. Expert Comment. August 25, 2015. "This study completes a series of clinical trials demonstrating the efficacy of atropine in slowing the progression of myopia and makes a strong case for clinical use of atropine in young patients."

MyopiaPrevention.org comment: The data is now five years old, but it shows that atropine use increased over the years while the concentration of the drop used decreased. In 2007, approximately 50% of children diagnosed with myopia were prescribed atropine, 40% of those getting .1% atropine. Among 9-10 year olds with myopia, 60% were prescribed atropine. Over the seven year period, atropine use increased 34%.

MyopiaPrevention.org comment: This ATOM2 followup of the ATOM1 study sought to determine if concentrations weaker than the previously studied 1% would have a similar effect. A dose as low as .01% was shown to slow myopia clinically at the same rate as 1% with "negligible effect on accommodation and pupil size, and no effect on near visual acuity." There were no reports of allergic conjunctivitis or dermatitis. This is a significant finding that could change how myopia is treated.

MyopiaPrevention.org comment: The abstract talks about the gene mutation identified in a specific population: "Bedouin Israeli consanguineous kindred." In other words, a very small, specific population. Such studies allow researchers to more easily determine the actions of a specific gene. Further research is then needed to determine if this action is somehow impaired in myopic individuals who do not have the specific mutation.

MyopiaPrevention.org comment: A retrospective study of controlled clinical trials. Atropine slowed myopic progression by .773D/yr compared to placebo. Effects of .5% and 1% were similar.

MyopiaPrevention.org comment: While atropine (a muscarinic antagonist) has been shown to reduce myopic progression, the specific receptor that mediates the effect has not been identified. This study indicates that "muscarinic antagonists prevent myopia progression through an M4-receptor mediated mechanism, most likely located in the retina."

This is important in that, if proven true, it would permit the development of a more targeted drug for myopia control than the more broad acting atropine.

MyopiaPrevention.org comment: This study of 22 subjects aged 13 to 25 found that myopes had slightly lower levels of Vitamin D in their blood compared to non-myopes when adjusted for age and diet, but the results were questioned because the study did not find that outdoor time was related to myopia.

MyopiaPrevention.org comment: A comprehensive review of the drugs used to study myopia progression involving various receptor targets within the eye. Various models for myopia progression are discussed. "...new bioengineering approaches for drug delivery" are called for.

MyopiaPrevention.org comment: Not yet read. The abstract states that "The findings that have resulted from this study have not only provided greater insight into the role of genes and other factors involved in myopia but have also gone some way to uncovering the aetiology of other refractive errors."

MyopiaPrevention.org comment: This is a study that looked at varying the dosage of atropine based on the season, with the idea of increasing the dose when the sun exposure is the least. It was found to be effective and tolerable to the students.

MyopiaPrevention.org comment: Insulin-like growth factor-1 (IGF-1) "may play a role in control of eye growth" and this study found a "genetic association between IGF-1 and high-grade myopia."

MyopiaPrevention.org comment: The study shows the type of work needed to identify a genetic component to myopia progression. A single gene was studied and was found to be associated with both hyperopia and myopia. No attempt is made to identify how the gene might create its influence.

MyopiaPrevention.org comment: Just like the title says. This is different than has been found in other populations.

MyopiaPrevention.org comment: In simplified terms, glucose levels in the body are regulated by insulin (lowers glucose) and glucagon (raises glucose). Chick eyes were studied for the effect of these two hormones and their ability to control ocular elongation and choroidal thickness, both responsible for emetropization and myopic development. The relationship is complicated. "the simplest view of how glucagon and insulin might control emmetropization would be that insulin stimulates the eye to elongate and the choroid to thin, thus acting like a negative lens, whereas glucagon does the reverse, slowing the elongation and causing the choroid to thicken, thus acting like a positive lens. We conclude the situation is considerably more complex." It appears that this more simplistic action is maintained if the eye is compensating for defocus during which time the eye is less responsive to the drug that would be expected to slow the process in either direction.

MyopiaPrevention.org comment: Pirenzepine was shown to slow myopia to .58 diopters over two years vs. .99 diopters for the placebo group, thus cutting the progression approximately in half. An editorial in the same edition (How should we try to affect myopic progression?) by Sherwin J. Isenberg notes that although atropine and pirenzepine have the best results "in properly conducted clinical trials" for myopia control, the former is an "off-label" use and the later is not available in the United States.

MyopiaPrevention.org comment: "The experiments reported here demonstrate that both unselective blocking of potassium channels and selective inhibition of the sodium-potassium-chloride symporter can produce dramatic interference with refractive compensation to optically induced blur." "The action of bumetanide appears to combine a defocus-sensitve inhibition of refractive compensation under conditions that would normally lead to myopia"

MyopiaPrevention.org comment: This adenosine antagonist (in tablet form) was tested in a study of 68 children of average age 11 for three years. The first year half the students received the tablets, the second year all students were given the choice of once a day or twice a day tablets and the third year all medication was stopped. The authors conclude that 7-mx is efficient in retarding myopia, but I don't see that from their results and study design.

MyopiaPrevention.org comment: Paired box gene 6 (PAX6) showed no association with myopia. COL2A1 (a collagen gene) was indicated as possibly associated with myopia.

MyopiaPrevention.org comment: In the chick eye, the perception of blur does not drive emmetropization but rather the energy at high spatial frequencies in an image, leading them to conclude that amacrine cells within the retina may be sufficient to drive emmetropization.

MyopiaPrevention.org comment: The title says it all.

MyopiaPrevention.org comment: Melatonin is a hormone that "transmits daily and seasonal timing information to a variety of tissues in essentially all vertebrate species." Application of systemic melatonin altered the growth of various ocular tissues where receptors have been identified. Further study is called for to elicit more specific data.

MyopiaPrevention.org comment: A pdf of the slides presented at a lecture for ARVO's (Association for Research in Vision and Ophthalmology) symposium. A discussion of the biochemical signals controlling growth that are operating within the retina.

MyopiaPrevention.org comment: Abstract in Polish translated into English on Pubmed.com. The abstract is perhaps most interesting for the listing of potential chemicals for myopia prevention.

MyopiaPrevention.org comment: Glucagon, a chemical messenger in the body, was investigated to see whether it is involved with signaling the eye to change its growth in response to plus lenses. It was shown to thicken the choroid and may contribute to myopia prevention by reducing sclera growth.

MyopiaPrevention.org comment: "That the combination of apomorphine and atropine were not additive suggests that combining dopaminergic and muscarinic agents is not a useful strategy for improving the efficacy of these antimyopia drug treatments."

MyopiaPrevention.org comment: A study of genes within a region previously identified as associated with high myopia. No significant gene was found. Includes a good summary of the incidence of eye problems associated with increased myopia in the section "Ocular Morbidity" including such facts as the lifetime risk of retinal detachment is 9.3% for those with myopia over 5.00 D. A necessary read for anyone thinking that identifying the genetic component of myopia should be easy.

MyopiaPrevention.org comment: Pirenzepine appeared to be safe to use in children but the study did not attempt to determine if it was effective in myopia prevention.

MyopiaPrevention.org comment: 331 children aged 6-12 studied over two years showed that myopia progressed 1.20 diopters in the control (placebo drops) group and .25 diopters in the group given 1% atropine drops daily. Results for axial elongation (another measure of myopia progression) were similar.

MyopiaPrevention.org comment: A summary of many of the issues in myopia research.

MyopiaPrevention.org comment: The concern is that long term atropine use might cause either toxic problems or lead to increased light damage to the eye due to atropine dilating pupils. This study did multifocal electroretinograms (mfERG) to determine if such damage was detectable for those who had used atropine for two years. The results showed slight changes of unknown significance in the atropine group. The author states "The clinical implications of these findings need to be further explored."

MyopiaPrevention.org comment: A review of the molecular techniques being used to study myopia.

MyopiaPrevention.org comment: Pirenzepine (a selective muscarinic antagonist) studied in 353 Asian children ages 6-12. 2% drops twice a day (progressed -.47 D), once a day (progressed -.70 D) and placebo(progressed -.84 D), thus showing a 43% drop in myopic progression for 2% pirenzepine drops given twice a day. Side effects included follicles and papillae (bumps on the inner lids) that were stated to be usually symptom free with overall "minimal anti-muscarinic safety issues."

MyopiaPrevention.org comment: An extensive review of the pharmacology of myopia presented at the 9th International Myopia Conference. You must be able to read .ppt files. From Dr. Wildsoet's web site.

MyopiaPrevention.org comment: Three groups (total 188 students age 6-13): Atropine + multifocal glasses, multifocal glasses, and single vision glasses. Followed for 18 months. Progression was least for atropine+multifocals (.40 D), and more for multifocals (1.19 D) and single vision lenses (1.40 D). Although the two glasses group did differ from each other, it was not felt the difference was strong enough to say multifocals were better at prevention than single vision glasses.

MyopiaPrevention.org comment: Amacrine cells within the retina "respond differentially" depending on whether the eye is myopic or hyperopic and thus may be important in emmetropization.

MyopiaPrevention.org comment: 168 children, age 6-13 were treated with either of .5%, .25% or .1% atropine drops nightly for up to two years. Myopic progression rates were .04, .45 and .47 Diopters/year respectively compared to a control of 1.06 Diopters/year. The .5% was the most effective.

MyopiaPrevention.org comment: A study of 214 students in Olmsted County, Minnesota (USA) received atropine for various lengths of time, from 18 weeks to 11.5 years. Photophobia and blurred vision were frequently reported, but the author did not classify those as "serious side effects". The atropine group had very little myopic change (.05 units/year) vs the "no-drug" group (.36 units/year). The article has a fairly extensive discussion of atropine in various myopia control studies and background data on myopia in general. Forty five pages.

The same article appears as Kennedy RH, Dyer JA, Kennedy MA, Parulkar S, Kurland LT, Herman DC, McIntire D, Jacobs D, Luepker RV.(2000) Reducing the progression of myopia with atropine: a long term cohort study of Olmsted County students. (ABSTRACT) Binocul Vis Strabismus Q. 2000;15(3 Suppl):281-304.

MyopiaPrevention.org comment: Injected atropine in chick eyes dramatically slowed myopic progression but did not reduce accommodation. Atropine eye drops would not stop myopic progression by affecting accommodation, further proof that accommodation or reading does not by itself cause myopia.

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Myopia Medications and Genetics - MYOPIA * Prevention