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Medical Forum / General / Vision / March 2005Myopia and gene therapy
If, as most eye doctors say, myopia is due to genetics. I hope one day someone uses gene therapy to treat myopia if it's possible. Current technology to correct myopia using lasers on the cornea seems to be attacking the wrong part of the eye, since as research has shown myopia is largely due to overgrowth of the back of the eye. > If, as most eye doctors say, myopia is due to genetics. I hope one day > someone uses gene therapy to treat myopia if it's possible. > > Current technology to correct myopia using lasers on the cornea seems to be > attacking the wrong part of the eye, since as research has shown myopia is > largely due to overgrowth of the back of the eye. This seems a long way off at this point in time http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml#status So far I am being told by experts working on this problem that no specific genes have been found for any form of eye problem other than very strongly genetic problems such as Marfans Syndrome. Studies of what have been described as "Mendelian" high myopia that is "certainly inherited" have so far found that each family has different chromosomes being effected. (This is the work of Terri Young OD) But even Identical twins can have large refractive error differences. In 2004 twin study authors have suggested 'a gene called PAX6 may play a crucial part in the development of myopia' however it is known that PAX6 is not specifically involved since when mutated it creates deformed eyes. "Our genomewide scan shows significant linkage to four chromosome regions - the largest one is right in the region of the PAX6 gene. Further detailed examination of PAX6 is now needed to work out the exact role of the gene and exactly where the mutations occur." These myopia gene studies are all using the "linkage method", which is different to the design used to find ARMD genes. In current myopia studies no specific factor is being correlated to a possible gene. Even if a gene is found via such a study that gene could mean that people prefer sweet foods or really just about anything at all. More importantly, fundamentally the debate over nature versus nuture is still unresolved. Studies that are assuming a very strong relationship between genetics and myopia in the 5 or so family studies so far done are finding different chromosomes for different families. Data that supports environmental factors as much as any possible genetic factor. However if myopia has genetic tendencies and genetic engineering can reinforce the correcting tendencies its possible that some kind of therapy might be possible. The first stage still seems to find if myopia has any genetic tendencies. While studies to support the genetic argument ignore possible environmental factors and pro genetic researchers find that ommission acceptable this discussion is not likely to be resolved any time soon. Andrew >More importantly, fundamentally the debate over nature versus nuture is >still unresolved...... >The first stage still seems..... wow we were all just saying to ourselves "I wonder what andrew thinks about this" kind of taken with yourself aren't you andrew? >> If, as most eye doctors say, myopia is due to genetics. I hope one day >> someone uses gene therapy to treat myopia if it's possible. [quoted text clipped - 8 lines] > > http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml#status Thanks. Maybe in another 50 years... :D > If, as most eye doctors say, myopia is due to genetics. I hope one day > someone uses gene therapy to treat myopia if it's possible. > > Current technology to correct myopia using lasers on the cornea seems to > be attacking the wrong part of the eye, since as research has shown myopia > is largely due to overgrowth of the back of the eye. Actually, no one tissue is to blame for myopia, myopia is a mismatch between the various components that make up the refractive apparatus of the eye. Gene therapy is a long way away for any condition. It really is only feasible for conditions due to a single gene that codes the "wrong" protein. Therapy would, in theory, introduce a new gene that codes correctly into the body. Since myopia is a failure of co ordination between several different systems that control the formation, growth and rate of growth of several different tissues, and that failure is also slightly influenced by environmental factors, gene therapy may never be available. Dr Judy Dear Dr Judy We can agree I feel sure that myopia is complex. Often philosophy can arrive at truths before researchers find evidence for those truths. In a way this is basis of science; we make hypothesis based on what might be possible based on our current knowledge and then test to find if our hypothesis can be true. In a normal human eye having normal sight there are a great many different factors controlling many different component parts. Dispite that complexity normal sight is statistically more likely than refractive error. (We both said recently that emmetropisation creates a peak in the continuum from plus to minus) Therefore, although genetic factors effecting the component parts do exist, there is also a mechanism that allows for that variation in normal sight and corrects for it. Therefore, since all eyes already have great genetic variation but normal sighted eyes are more likely due to an active process the impact of genetic variation seems of lesser importance than the impact of factors that interfere with that emmetropisation. If we throw our hands up in horror at the genetic complexity we might decide nothing can be done its all too hard. However other researchers are noticing for example: Astigmatism might be related to posture and habitual movement Esophoric myopes might benefit from plus. Myopia might be related to anxiety Myopia versus none myopia might be predictable via a psychological questionnaire with 75% success (Francis Young 1976) Larger eye differences might be related to preferential stimulation of the contralateral hemisphere via the patching effect of small refractive errors Similarly if we totally ignore all the obove research and assume environmental factors are not relevant in myopic families or when comparing an identical twin who has a special bond with his/her twin and who cannot be told apart by teachers versus a behaviourally and physically different twin we might say genetics is the most important factor. But truth has a way of becoming known. Dispite the complexity of our bodies and their underlying genetic nature, various refractive errors seem related to different external phenomenon of one kind or another rather than something that is only determined from within us without our control. Andrew does writing this stuff make you feel good about yourself. noone necessarity agrees with a lot of the BS, such as: >Astigmatism might be related to posture and habitual movement >Esophoric myopes might benefit from plus. >Myopia might be related to anxiety >Myopia versus none myopia might be predictable via a psychological questionnaire with 75% success >Larger eye differences might be related to preferential stimulation of the contralateral hemisphere via the patching effect of small refractive errors Retinula said >does writing this stuff make you feel good about yourself. noone necessarity agrees with a lot of the BS, such as: [quoted text clipped - 7 lines] questionnaire with 75% success >Larger eye differences might be related to preferential stimulation of the contralateral hemisphere via the patching effect of small refractive errors This is a similar line to the one adopted by Otis. One where an opinion is unsupported by any research or commonsense observations, and where no amount of reason or research will alter the already decided viewpoint. Francis Youngs work on personality and refractive error is interesting. In order to decide if its bullshit or not first it has to be read. The research undertaken by Heidi Roth et al potentially changes the way we look at refractive error. In order to decide if its bullshit or not first it has to be read. Do we need more people like Otis? I guess you are saying you and Otis are alike. I concur. === > Retinula said > [quoted text clipped - 22 lines] > > Do we need more people like Otis? RM said >I guess you are saying you and Otis are alike. I concur. Perhaps if you guessed less and instead applied some kind of reasoning you might be better informed. Dr Judy said >>Since myopia is a failure of co ordination between several different systems that control the formation, growth and rate of growth of several different tissues, and that failure is also slightly influenced by environmental factors Dr Judy I found what you said to be surprising and a bit confusing. Just to clarify here, if the failure is "only slightly influenced by environmental factors" are you saying: Its "only slightly influenced by environment" and majorly influenced by: 1.genetic factors only or 2. Some other factor that is not environment or genetics or 3. Genetic factors and some other factor that is not environment In the case of an identical twin having more than 6 diopters of difference to their identical twin is that: 1 "only slightly influenced by environmental factors" or 2. Some other factor that is not environment or genetics or 3. "only slightly influenced by environmental factors" and some other factor that is not environment and/or genetics If its some other factor that is not genetic or environment can you be specific please? Andrew > Dr Judy said > [quoted text clipped - 15 lines] > 2. Some other factor that is not environment or genetics or > 3. Genetic factors and some other factor that is not environment Studies of families consistently show that about 85% of refractive error variation can be attributed to heritable features and the remainder to environmental factors. Genetic factors interact with environmental factors, so I guess if you are trying to think of something that is neither genetic nor environmental it would be the interation. My personal opinion is that refractive error is due to multiple genetic factors interacting with multiple environmental factors. > In the case of an identical twin having more than 6 diopters of difference > to their identical twin is that: [quoted text clipped - 6 lines] > If its some other factor that is not genetic or environment can you be > specific please? It is not possible to state what influenced a particular individual; it is possible to say what influences a population. Dr Judy > Andrew Dr Judy said >>Studies of families consistently show that about 85% of refractive error variation can be attributed to heritable features and the remainder to environmental factors. This is not true. Studies of families instead **ignore** environmental factors **assume** its genetic and then 'look for genetic relationships'. The none genetic component is then assumed to be environment. Unless parallel tests are done on the families that assume environment is responsible and then look for that environmental relationship then these tests are meaningless and foolishly biased. Similarly studies of black people and intelligence ignore environment, and look for genetic relationships. Not surprisingly such studies conclude black people are genetically inferior. Are they inferior? Are yellow people more able than whites? Studies where two groups of (black and white people in the same test room) were given identical tests found: Black peopled scored worse when told 'this test is to test your ability' Black people scored better when told 'this is just to gather some information' Andrew > Dr Judy said > [quoted text clipped - 11 lines] > for that environmental relationship then these tests are meaningless and > foolishly biased. Here is a typical study that finds both genetic and environmental influences, and does not ignore enviromental influences. Two myopic parents makes a child 6x more likely to be myopic than having only one or no myopic parents. Child with less hyperopia at 6 months of age are 4x more likely to be myopic later in life. Do you think that all two parent myope families share a common environmental influence? Does some common environment happen in the first 6 months of life to all the low hyperopes but not to all the higher hyperopes? Role of genetic factors in the etiology of juvenile-onset myopia based on a longitudinal study of refractive error. Pacella R, McLellan J, Grice K, Del Bono EA, Wiggs JL, Gwiazda JE. Myopia Research Center, New England College of Optometry, Boston, Massachusetts 02115, USA. In an attempt to determine the role of genetic factors in the development of myopia, we examined the relationship of infantile refractive error and parental history to juvenile-onset myopia and analyzed 43 pedigrees affected by juvenile-onset myopia. Refraction data collected at regular intervals from a sample of juvenile subjects participating in a 24-year longitudinal study of refractive error were used. Results showed that children with two myopic parents were 6.42 times as likely to become myopic as children with one or no myopic parents. Furthermore, children who had refractions in the lower half of the distribution at 6 to 12 months of age were 4.33 times as likely to develop myopia as children who had refractions in the upper half of the distribution at 6 to 12 months of age. The pedigree analysis indicated that 63% of individuals considered at risk for developing juvenile-onset myopia actually became myopic, with an equal number of affected males and females. These results suggest that juvenile-onset myopia of moderate amounts may be inherited as a complex trait involving both genetic and environmental factors. And here are the COMET folks, looking for psychological factors: The relationship between self-esteem of myopic children and ocular and demographic characteristics. Dias L, Manny RE, Hyman L, Fern K; Correction of Myopia Evaluation Trial Group. Dept of Preventive Medicine, Stony Brook University Health Sciences Center, Stony Brook, New York 11794-8036, USA. ldias@notes.cc.sunysb.edu PURPOSE: To evaluate self-esteem and its relationship with various ocular and demographic characteristics in 469 myopic children participating in the Correction of Myopia Evaluation Trial (COMET), an ongoing, randomized, multicenter clinical trial designed to evaluate the effects of progressive addition lenses vs. single vision lenses on the progression of juvenile-onset myopia. METHODS: Baseline data collection included demographic information, refractive error measurements, parent-reported myopia history, child-reported visual symptoms, and self-esteem in several areas (scholastic/athletic competence, physical appearance, social acceptance, behavioral conduct, and global self-worth) as measured by the Self-Perception Profile for Children. Univariate and multiple regression analyses were used to identify factors associated with self-esteem. RESULTS: The Self-Perception Profile for Children is a reliable measure of self-esteem in COMET children as indicated by the high internal consistency reliabilities (0.74 to 0.81) obtained for the various domains. COMET children's mean self-esteem scores ranged from 2.72 +/- 0.69 for athletic competence to 3.36 +/- 0.56 for global self-worth and were similar to normative samples. Multiple regression analyses showed that less symptomatic children had higher self-esteem in all areas (p < 0.05), except athletic competence, after adjusting for other ocular and demographic characteristics. Self-esteem also varied significantly by age, gender, and ethnicity (p < 0.05). CONCLUSIONS: Baseline self-esteem is associated with visual symptoms, age, gender, and ethnicity, but not with magnitude of refractive error. Follow-up reports will assess whether there are changes in self-esteem associated with myopia progression and lens assignment. Dr Judy Dr Judy said: >>Here is a typical study that finds both genetic and environmental influences, and does not ignore enviromental influences. Two myopic parents makes a child 6x more likely to be myopic than having only one or no myopic parents. Child with less hyperopia at 6 months of age are 4x more likely to be myopic later in life. Do you think that all two parent myope families share a common environmental influence? Does some common environment happen in the first 6 months of life to all the low hyperopes but not to all the higher hyperopes? Role of genetic factors in the etiology of juvenile-onset myopia based on a longitudinal study of refractive error. Pacella R, McLellan J, Grice K, Del Bono EA, Wiggs JL, Gwiazda JE. Myopia Research Center, New England College of Optometry, Boston, Massachusetts 02115, USA. In an attempt to determine the role of genetic factors in the development of myopia, we examined the relationship of infantile refractive error and parental history to juvenile-onset myopia and analyzed 43 pedigrees affected by juvenile-onset myopia. Refraction data collected at regular intervals from a sample of juvenile subjects participating in a 24-year longitudinal study of refractive error were used. Results showed that children with two myopic parents were 6.42 times as likely to become myopic as children with one or no myopic parents. Furthermore, children who had refractions in the lower half of the distribution at 6 to 12 months of age were 4.33 times as likely to develop myopia as children who had refractions in the upper half of the distribution at 6 to 12 months of age. The pedigree analysis indicated that 63% of individuals considered at risk for developing juvenile-onset myopia actually became myopic, with an equal number of affected males and females. These results suggest that juvenile-onset myopia of moderate amounts may be inherited as a complex trait involving both genetic and environmental factors. And here are the COMET folks, looking for psychological factors: The relationship between self-esteem of myopic children and ocular and demographic characteristics. Dias L, Manny RE, Hyman L, Fern K; Correction of Myopia Evaluation Trial Group. Dept of Preventive Medicine, Stony Brook University Health Sciences Center, Stony Brook, New York 11794-8036, USA. ldias@notes.cc.sunysb.edu PURPOSE: To evaluate self-esteem and its relationship with various ocular and demographic characteristics in 469 myopic children participating in the Correction of Myopia Evaluation Trial (COMET), an ongoing, randomized, multicenter clinical trial designed to evaluate the effects of progressive addition lenses vs. single vision lenses on the progression of juvenile-onset myopia. METHODS: Baseline data collection included demographic information, refractive error measurements, parent-reported myopia history, child-reported visual symptoms, and self-esteem in several areas (scholastic/athletic competence, physical appearance, social acceptance, behavioral conduct, and global self-worth) as measured by the Self-Perception Profile for Children. Univariate and multiple regression analyses were used to identify factors associated with self-esteem. RESULTS: The Self-Perception Profile for Children is a reliable measure of self-esteem in COMET children as indicated by the high internal consistency reliabilities (0.74 to 0.81) obtained for the various domains. COMET children's mean self-esteem scores ranged from 2.72 +/- 0.69 for athletic competence to 3.36 +/- 0.56 for global self-worth and were similar to normative samples. Multiple regression analyses showed that less symptomatic children had higher self-esteem in all areas (p < 0.05), except athletic competence, after adjusting for other ocular and demographic characteristics. Self-esteem also varied significantly by age, gender, and ethnicity (p < 0.05). CONCLUSIONS: Baseline self-esteem is associated with visual symptoms, age, gender, and ethnicity, but not with magnitude of refractive error. Follow-up reports will assess whether there are changes in >>self-esteem associated with myopia progression and lens assignment. Dr Judy These results are definately very interesting. Thanks for finding them. Study one. ---------- OK lets assume that eyeball parameters are hugely variable at birth. Babies have distance vision of around 14"? up to age 8 months. I am not sure if thats due to accommodative factors or that most human eyes 'arrive' in that condition. But its not so important really. In an equal environment, babies who 'arrive' with more hypermetropia could be reasoned to develop less myopia given any mypopia aetilogy scenario. If myopia is related to anxiety of a particular kind related to feeling secure/loved so that there is a feeling of insecurity and apprehension, then having two myopic insecure apprehensive parents is going to be bad news for a baby regardless of its condition upon arrival. Study two --------- This one is **very** interesting to me in its conclusions. "CONCLUSIONS: Baseline self-esteem is associated with visual symptoms, age, gender, and ethnicity, but not with magnitude of refractive error. Follow-up reports will assess whether there are changes in self-esteem associated with myopia progression and lens assignment" Ok. Comet study is a myopia study. The study has found that myopes have some issue with self esteem but its not related to myopic refraction. Roberto Kaplan says "My findings show a very strong relationship between with the rule astigmatism, self esteem and its next door neighbours sensuality and sexuality" With the rule is the most common astigmatism. Suggesting that commonly myopes have some issue with self esteem but its not related to myopic refraction. Roberto Kaplan also told me privately that "because you (andrew) have 90 degree astigmatism then the correlations for 180 are your relative strength" Retinula on this list has said several times about me 'you rather like yourself dont you'. Is that observation just coincidence? Kaplan found the 'visual style' of WTR was associated with a 'survival way of seeing things (survival perception) of 'inflexibility, impatience and intolerance'. Arguably i am bending over backwards here to provide a reasoned argument in the face of overwhelming hostility:-) My strength is that i ***am*** patient tolerant and flexible:-) If COMET is capable of finding relationships via statistical methods then **if** they are prepared to look for relationships for the subsets (the atoms) in the total population of myopia (the bucket of atoms) then if they are prepared to publish the results I believe what Kaplan found empirically will be shown to be correct. Sounds to me like bit by bit we are moving in the right direction! But of course we see only what we can believe Andrew > Dr Judy said: > [quoted text clipped - 11 lines] > higher hyperopes? > These results are definately very interesting. Thanks for finding them. > If myopia is related to anxiety of a particular kind related to feeling > secure/loved so that there is a feeling of insecurity and apprehension, > then having two myopic insecure apprehensive parents is going to be bad > news for a baby regardless of its condition upon arrival. You assume all myopes are anxious and therefore all their children are raised in an anxious environment. --- please provide valid evidence that all myopes are anxious. > "CONCLUSIONS: Baseline self-esteem is associated with > visual symptoms, age, gender, and ethnicity, but not with magnitude of [quoted text clipped - 4 lines] > Ok. Comet study is a myopia study. The study has found that myopes have > some issue with self esteem but its not related to myopic refraction. Exactly, the issues with self esteem are related to "visual symptoms" (you'll have to get the whole study and find out how that was defined) not to myopia. Also the study found: "children's mean self-esteem scores ranged from 2.72 +/- 0.69 for athletic competence to 3.36 +/- 0.56 for global self-worth and were similar to normative samples." In other words, the COMET population, which consisted entirely of myopes, was just like the general population in terms of self esteem --- the myopes do not have self esteem problems. Dr Judy > You assume all myopes are anxious and therefore all their children are > raised in an anxious environment. --- please provide valid evidence that all > myopes are anxious. That is completely unreasonable! You want me to provide valid evidence that 100% of myopes are anxious and yet the very study that you produced to support your argument shows myopes have self esteem issues but you quoted the part that supported your opinion and did not quote the part that supported the conclusions of the study! That is called Bias!!!! The comet study clearly shows that myopes have self esteem issues. Self esteem and anxiety are closely related. You said of that study > Also the study found: > [quoted text clipped - 5 lines] > was just like the general population in terms of self esteem --- the myopes > do not have self esteem problems. But if you had quoted the **very next lines** you would allow a reader to see what the study was really saying. "Multiple regression analyses showed that less symptomatic children had higher self-esteem in all areas (p < 0.05" And concludes "Baseline self-esteem is associated with visual symptoms, age, gender, and ethnicity, but not with magnitude of refractive error." Meanwhile in the interests of science i have already received a reply from the research team of COMET who have told me that "Given your interest, you might also wish to read another article I have authored evaluating self-esteem over a three-year period in COMET children. It will be published in the upcoming issue of Optometry and Vision Science, a special issue devoted entirely to myopia." Andrew Dr Judy Apologies. After having had another look at that study I am not entirely sure what they are concluding and have asked them to clarify what they mean by symptomatic Andrew I have now heard back from the study authors clarifying the word symptomatic "Children were asked to rate how often they experienced the following six symptoms when reading or studying: (1) eyes feel tired, (2) eyes hurt, (3) headaches, (4) feel sleepy, (5) double vision, and (6) words wiggle/jump on the page." >I have now heard back from the study authors clarifying the word > symptomatic [quoted text clipped - 3 lines] > (1) eyes feel tired, (2) eyes hurt, (3) headaches, (4) feel sleepy, (5) > double vision, and (6) words wiggle/jump on the page." As I suspected, these symptoms are not indicative of myopia. Could be due to anything from allergies, missing breakfast, learning disabilities, illness, boredom, depression, binocular vision problems and yes, even stress at home. Children who are not performing well at school, for any reason, may well not enjoy reading or studying and have those symptoms and poor school performance may well be related to lower self esteem. Dr Judy >> "Children were asked to rate how often they >> experienced the following six symptoms when reading or studying: >> (1) eyes feel tired, (2) eyes hurt, (3) headaches, (4) feel sleepy, (5) >> double vision, and (6) words wiggle/jump on the page." > > As I suspected, these symptoms are not indicative of myopia. All those symptoms are classic for hyperopia and rare in myopia. Why would someone use those questions in myopia studies? -MT Mike Tyner said >All those symptoms are classic for hyperopia and rare in myopia. Why would someone use those questions in myopia studies? "Although previous studies attempted to investigate the association of these factors with self-esteem,10, 11 they were limited by small sample sizes and differing definitions and measures of self-esteem. Apart from these studies, however, little is known about myopic children’s self-esteem and other ocular factors that might be related to it. For instance, children often report visual symptoms (i.e., subjective complaints) such as seeing double or words swimming together when reading.12 Because physical symptoms such as headaches and stomachaches have been found to be associated with self-esteem in young people,13 similar associations may also be found with visual symptoms and may be a fruitful area of investigation." 12 Wright JD Jr, Boger WP III. Visual complaints from healthy children. Surv Ophthalmol 1999;44:113–21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10541150 Dr Judy said >It is not possible to state what influenced a particular individual; >it is possible to say what influences a population. This is not true. With skill it is possible to get a pretty good idea of what influences an individual. With skill it is possible to get some idea of what influences a population. Finding what influences individuals can then be tested against populations to further define the population. For example some individuals are men, some women, some children etc. Studying the population only, reduces these differences to meaningless statistics. Studying a bucket of atoms gives some results but only by studying an atom can you find out the precise nature of the bucket of atoms. If you make the assumption that the trend is global/genetic, then you never look at individual differences and cannot imagine that such a thing can be possible. Andrew
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