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.

Audrey Chia, Qing-Shu Lu, Donald Tan. (2015) Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2. (ABSTRACT) Ophthalmology Published Online August 11, 2015. Accessed 8/30/2015; doi: org/10.1016/j.ophtha.2015.07.004

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."

Y-T Fang, Y-J Chou, C Pu, P-J Lin, T-L Liu, N Huang and P Chou. (2013) Prescription of atropine eye drops among children diagnosed with myopia in Taiwan from 2000 to 2007: a nationwide study. (ABSTRACT) Eye 4 January 2013 doi:10.1038/eye.2012.279

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%.

Audrey Chia, Wei-Han Chua, Yin-Bun Cheung, Wan-Ling Wong, Anushia Lingham, Allan Fong, Donald Tan. (2011) Atropine for the Treatment of Childhood Myopia: Safety and Efficacy of 0.5%, 0.1%, and 0.01% Doses (Atropine for the Treatment of Myopia 2). (FULL TEXT) Ophthalmology published online 03 October 2011 doi:10.1016/j.ophtha.2011.07.031

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.

Shikma Mordechai, Libe Gradstein, Annika Pasanen, Rivka Ofir, Khalil El Amour, Jaime Levy, Nadav Belfair, Tova Lifshitz, Sara Joshua, Ginat Narkis, Khalil Elbedour, Johanna Myllyharju, Ohad S. Birk. (2011) High Myopia Caused by a Mutation in LEPREL1, Encoding Prolyl 3-Hydroxylase 2 . (ABSTRACT) The American Journal of Human Genetics Article in press - Published online Sept 2011. doi:10.1016/j.ajhg.2011.08.003

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.

Song YY, Wang H, Wang BS, Qi H, Rong ZX, Chen HZ.(2011) Atropine in ameliorating the progression of myopia in children with mild to moderate myopia: a meta-analysis of controlled clinical trials. (ABSTRACT) J Ocul Pharmacol Ther. Aug;27(4):361-8. Epub 2011 Jun 7. doi:10.1089/jop.2011.0017

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.

Neville A McBrien, Baskar Arumugam, Alex Gentle, Anna Chow, Srujana Sahebjada.(2011) The M4 muscarinic antagonist MT-3 inhibits myopia in chick: evidence for site of action. (FULL TEXT)Ophthalmic & Physiological Optics Volume 31, Issue 5, pages 529–539, September 2011 doi: 10.1111/j.1475-1313.2011.00841.x

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.

Mutti, Donald O.; Marks, Amanda R. (2011) Blood Levels of Vitamin D in Teens and Young Adults with Myopia. (FULL TEXT) Optometry & Vision Science March 2011 - Volume 88 - Issue 3 - pp 377-382 doi: 10.1097/OPX.0b013e31820b0385

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.

Prema Ganesan and Christine F Wildsoet. (2010) Pharmaceutical intervention for myopia control. (FULL TEXT) Expert Review of Ophthalmology Vol. 5, No. 6, Pages 759-787 , DOI 10.1586/eop.10.67

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.

Paul N. Baird, Maria Schäche, Mohamed Dirani (2010)The GEnes in Myopia (GEM) study in understanding the aetiology of refractive errors. (ABSTRACT and Article Outline) Progress in Retinal and Eye Research available online 1 June 2010

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."

Paul Lu and Jackie Chen. (2010) Retarding Progression of Myopia with Seasonal Modification of Topical Atropine. (FULL TEXT) Journal of Ophthalmic & Vision Research. April; 5(2):75–81

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.

Ravikanth Metlapally, Chang-Seok Ki, Yi-Ju Li, Khanh-Nhat Tran-Viet, Diana Abbott, Francois Malecaze, Patrick Calvas, David A Mackey, Thomas Rosenberg, Sandrine Paget, Jeremy A Guggenheim, and Terri L Young. (2010) Genetic association of insulin-like growth factor-1 polymorphisms with high-grade myopia in an international family cohort. (ABSTRACT) Investigative Ophthalmology and Visual Science published online ahead of print April 30, 2010

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."

Veerappan S, Pertile KK, Islam AF, Schäche M, Chen CY, Mitchell P, Dirani M, Baird PN. (2010) Role of the hepatocyte growth factor gene in refractive error. (ABSTRACT) Ophthalmology. 2010 Feb;117(2):239-45.e1-2. Epub 2009 Dec 14.

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.

M. Schache, C.Y. Chen, M. Dirani, and P.N. Baird.(2009) The hepatocyte growth factor receptor (MET) gene is not associated with refractive error and ocular biometrics in a Caucasian population. (FULL TEXT) Mol Vis. 2009; 15: 2599–2605.

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

Xiaoying Zhu, Josh Wallman.(2009) Opposite Effects of Glucagon and Insulin on Compensation for Spectacle Lenses in Chicks. (FULL TEXT) Investigative Ophthalmology and Visual Science 2009;50:24-36

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.

Siatkowski RM, Cotter SA, Crockett RS, Miller JM, Novack GD, Zadnik K; U.S. Pirenzepine Study Group. (2008) Two-year multicenter, randomized, double-masked, placebo-controlled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia. (ABSTRACT) J AAPOS. 2008 Aug;12(4):332-9. Epub 2008 Mar 24.

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.

Sheila G. Crewther, Melanie J. Murphy, David P. Crewther.(2008) Potassium Channel and NKCC Cotransporter Involvement in Ocular Refractive Control Mechanisms. (FULL TEXT) Accessed July 11, 2010 Open Access: Creative Commons Attribution License

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"

Klaus Trier, Søren Munk Ribel-Madsen, Dongmei Cui, and Søren Brøgger Christensen (2008) Systemic 7-methylxanthine in retarding axial eye growth and myopia progression: a 36-month pilot study. (FULL TEXT) J Ocul Biol Dis Infor. 2008 December; 1(2-4): 85–93.

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.

Mutti DO, et al. (2007) Candidate gene and locus analysis of myopia. (FULL TEXT) Mol Vis. 13:1012-9.

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

Hess RF, Schmid KL, Dumoulin SO, Field, D.J., & Brinkworth, D.R. (2006). What image properties regulate eye growth? (FULL TEXT) Curr Biol. 16: 687-691

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.

Qu J, Zhou X, Xie R, Zhang L, Hu D, Li H, Lu F. (2006). The presence of m1 to m5 receptors in human sclera: evidence of the sclera as a potential site of action for muscarinic receptor antagonists. (ABSTRACT) Curr Eye Res. 2006 Jul-Aug;31(7-8):587-97.

MyopiaPrevention.org comment: The title says it all.

Rada JA, Wiechmann AF (2006). Melatonin receptors in chick ocular tissues: implications for a role of melatonin in ocular growth regulation. (FULL TEXT) Invest Ophthalmol Vis Sci. 47: 25-33.

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.

Wildsoet, Christine.(2006) The Role of the Retinal Pigment Epithelium (RPE) as a Signal Relay in the Control of Eye Growth. (pdf SLIDES) ARVO Development in Biochemistry and Cell Biology Symposium. Wildsoet 2006

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.

Czepita D. (2005) [Fundamentals of modern treatment of myopia] (ABSTRACT) Ann Acad Med Stetin. 2005;51(2):5-9.

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.

Kirstan A. Vessey, Kathy A. Lencses, David A. Rushforth, Victor J. Hruby, and William K. Stell. (2005). Glucagon receptor agonists and antagonists affect the growth of the chick eye: a role for glucagonergic regulation of emmetropization? (FULL TEXT) Invest Ophthalmol Vis Sci. 46: 3922-3931.

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.

Schmid KL, Wildsoet CF. (2004) Inhibitory effects of apomorphine and atropine and their combination on myopia in chicks. (FULL TEXT) Optom Vis Sci. 2004 Feb;81(2):137-47

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."

Young TL (2004). Dissecting the genetics of human high myopia: a molecular biologic approach. (FULL TEXT) Trans Am Ophthalmol Soc. 102:423-45.

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.

Bartlett JD, Niemann K, Houde B, Allred T, Edmondson MJ, Crockett RS (2003). A tolerability study of pirenzepine ophthalmic gel in myopic children. (ABSTRACT) J Ocul Pharmacol Ther. 19: 271-9

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.

Chua WH, Balakrishnan V, Tan D, Chan YH. (2003) Efficacy results from the Atropine in the Treatment Of Myopia (ATOM) study. (ABSTRACT) Invest Ophthalmol Vis Sci 2003;44; ARVO E-Abstract 3119.

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.

Feldkamper M, F (2003). Interactions of genes and environment in myopia. (ABSTRACT) Dev Ophthalmol. 37:34-49

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

Luu CD, Lau AMI, Koh AHC, Chua WH, Balakrishnan V, Tan D (2003). Effect of long-term atropine usage on retinal function. (ARVO abstracts), #4790 (ABSTRACT) Invest Ophthalmol Vis Sci

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."

Schaeffel F, Simon P, Feldkaemper M, Ohngemach S, Williams RW (2003). Molecular biology of myopia. (ABSTRACT) Clin Exp Optom. 2003 Sep;86(5):295-307.

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

Tan DT, Lam D, Chua WH, Crockett RS (2003). Pirenzepine ophthalmic gel (PIR): Safety and efficacy for pediatric myopia in a one-year study in Asia. (ABSTRACT) Invest Ophthalmol Vis Sci (ARVO abstracts), #801.

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."

Christine Wildsoet. (2002) Pharmacological Aspects of Myopia Accessed July 05, 2010 (Power Point Presentation)

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.

Shih YF, Hsiao CK, Chen CJ, Chang CW, Hung PT, Lin LL. (2001). An intervention trial on efficacy of atropine and multi-focal glasses in controlling myopic progression. (ABSTRACT) Acta Ophthalmol Scand. 2001 Jun;79(3):233-6.

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.

Fischer AJ, McGuire JJ, Schaeffel F, Stell WK (1999). Light- and defocus-dependent expression of the transcription factor ZENK in the chick retina. (ABSTRACT) Nature Neuroscience 2: 706-712

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.

Yung-Feng Shih, Chien-Hsiung Chen, Ai-Chuan Chou, Tzyy-Chang Ho, Luke L.-K. Lin, Por-Tying Hung. (1999) Effects of Different Concentrations of Atropine on Controlling Myopia in Myopic Children. (ABSTRACT) Journal of Ocular Pharmacology and Therapeutics Volume: 15 Issue 1: January 30, 2009 doi

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.

R H Kennedy.(1995) Progression of myopia. (FULL TEXT) Trans Am Ophthalmol Soc. 1995; 93: 755–800.

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.

Neville A. McBrien, Hadi 0. Moghaddam, and Anne P. Reeder.(1993) Atropine Reduces Experimental Myopia and Eye Enlargement Via a Nonaccommodative Mechanism. (FULL TEXT) Investigative Ophthalmology & Visual Science January 1993, Vol. 34, No.1; 205-215

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.