Myopia

Goldschmidt, in his 1968 review on the aetiology of myopia, quoted Waardenburg (1932)1 on the topic of genetics.
In this quote, Waardenburg noted the vast amount of literature that had been produced on the subject of the hereditary disposition of refractive errors but that conclusions still cannot be drawn due to the lack of conclusive evidence.

PARENTAL HISTORY
To investigate the genetic basis for the prevalence of myopia it is necessary to obtain the refractive status of the parents of the children in question.
Most studies researching this particular field of myopia epidemiology have used questionnaires sent to the parents. The Orinda Longitudinal Study2 involved a survey given to parents on enrolment of their child, followed by annual correspondence to document the child's medical and ocular history, to assess their visual activity profile and to determine the parents' myopic status.
Pacella et al3 collated refraction data from parents, either by gathering their spectacle or contact lens prescriptions, by contacting their eye care practitioner for the information, by using non-cycloplegic distance retinoscopy to determine refractive status, or by asking the individual or a close family member a series of questions regarding their visual history.
Both methods appeared to provide adequate information. Pacella et al, however, did not specify the criteria for a parent to be regarded as myopic. This automatically created some uncertainty in the comparison between the two studies, although results were very similar.
Zadnik4 stated that a parent was classified as myopic if they reported that they wore glasses primarily for distance viewing, or if they wore glasses that were equally important for distance and near viewing with the spectacles having been prescribed before the age of 16 years old.
Zadnik agreed with Pacella et al that there is a positive correlation between parental myopia and myopia in their children. Zadnik, on examining 716 children between six years and 14.9 years, found that the odds ratio for having two myopic parents compared with having no myopic parents was 5.21, which is a similar figure to that of Pacella et al at 5.09.
The latter group stated that individuals with two myopic parents were 6.42 times as likely to become myopic as those with one or no myopic parents. Their results also indicated that there is no significant difference in the prevalence of myopia among children with one or no myopic parents.
Zadnik obtained an odds ratio of 1.32 for having one myopic parent compared to no myopic parents which, although slightly higher, confirms an increased risk of myopia in children with two myopic parents. These figures indicate a stronger correlation than would be expected by chance.
Pacella et al took their study further. Not only did they look for a positive correlation between having myopic parents and their children subsequently being myopic, they also looked at the age at which the second generation became myopic, thus specifically looking at juvenile-onset myopia.
Included in data gathering was an examination of the child's early year refractions, in order to compare early refractive error to later myopic development (but still within a juvenile-onset boundary of 15 years). They found that two myopic parents and a lower manifest refraction at one year of age are associated with the development of myopia at school age, thereby providing evidence for a genetic component in the aetiology of myopia.
Goss and Jackson,5 like Zadnik and Pacella et al, reported a significant association between parental history of myopia and myopia development in the offspring, stating that the risk of becoming myopic is greater if both parents are myopic than if one parent is myopic.
They also issued a questionnaire, but they questioned the accuracy of the information received by this method on parental refractive status. They cited Teikari et al6 who, on comparing questionnaire findings with actual refractive prescriptions, found a 5.5 per cent false negative rate and a 1.8 per cent false positive rate.
In their conclusion, Goss and Jackson suggested that the variation in refractive error might not always be associated with inheritance, despite the association found. They proposed that common familial tendencies, such as increased reading, could cause myopia in, for example, mother and child, if the child follows by example. However, their proposition was made on the basis of observation of their patients, rather than experimental analysis.
Table 1 shows comparable results from a number of studies.
MODE OF INHERITANCE
None of the studies mentioned so far, looked in detail into the mode of inheritance. Wold classified the pattern of inheritance as being of three types: dominant inheritance, recessive inheritance and sex-linked inheritance.8
The nucleus of each human cell contains a genetic code in the form of 24-paired chromosomes. Genes present along the chromosomes account for the physical individuality of a human. A gene generally consists of two alleles and it is the type of allele that determines the expression of the gene.
In his study, Wold examined a number of kindred in which at least two generations of confirmed myopia or of myopia in different but related families of the same generation were found. Following the inheritance pattern within each case led him to the conclusion that hereditary myopia can be of the three mentioned types. A dominant allele is that which is physically expressed in a heterozygous (two different alleles) or a homozygous (two alleles the same) individual. It must be possessed by at least one of the two parents.
A recessive allele is that which is masked by its paired allele in a heterozygous individual and is only expressed in a homozygous individual. For a child to have a recessive condition, both parents must contribute to the same gene.
A sex-linked recessive character is one that is carried from one sex through the second generation of the opposite sex to appear in the third generation of the original sex.8 The expression of the gene is more common in males than females; however, only the females can pass the trait on to the children.
Wold reported a dominant inheritance as being the most prevalent, followed by recessive inheritance and finally the sex-linked form being the least common.
Goss et al10 reviewed a variety of studies on the mode of inheritance of myopia and found a number of theories. Some proposed an autosomal dominant mode of inheritance, some an autosomal recessive mode and others an X-linked mode of inheritance. Pacella et al, however, obtained results that were inconclusive as to the mode of inheritance. They found equal numbers of affected males and females in the pedigree families that were analysed, therefore providing no evidence of an X-linked trait. Their data did not support an autosomal dominant or an autosomal recessive mode of inheritance either. If myopia was autosomal dominant, one would expect 50 per cent of offspring to be affected and an autosomal recessive trait would expect 25 per cent of offspring to be affected. However, in their study, 63 per cent were affected.
Sveinsson,11 who investigated the refractive error of Icelanders by obtaining refractive information from his patients over a period of 50 years, found that less than half of the young people, whom he had treated for myopia, had myopic parents. The reason for this apparent unclear mode of inheritance could be that a person's susceptibility to myopia may be determined by more than one gene.
This possibility was not investigated by Pacella et al or Wold but it was investigated by Ashton9, cited by Pacella et al. He suggested that myopia is not inherited via a single gene but that it is polygenic and may be influenced by more than one gene. This seems possible due to the heterogeneity of myopia. There are so many forms of myopia that it seems improbable that each one has the same mode of inheritance or that myopia follows a 'monomeric mode of inheritance'.12 Young et al13 discovered significant genetic linkage on chromosome 18p for high myopia and his data supported an autosomal dominant inheritance.
Further genetic evidence was presented by Zadnik et al.14 They found that even before the onset of myopia, children with myopic parents have longer eyes than children with non-myopic parents.

TWIN STUDIES
Further evidence indicating the importance of the genetic factor, is the high concordance of refraction between monozygotic twins (identical) when compared with dizygotic (non-identical) twins.
Minkovitz et al15 compared refractive parameters in monozygotic and dizygotic twins. Their method of determining zygosity was somewhat vaguer than that of Lin and Chen.16 Minkovitz et al determined zygosity by similarity and by questions adapted from the Finnish Twin Registry Questionnaire. Lin and Chen, however, used red-cell antigen systems, birth membranes, and similarity index. Only the abstract was accessible for the former study and it did not specify the cut-off criterion that they used for concordance, thus making comparison between the two studies not entirely valid.
Both did, however, report a significant genetic basis for the overall refractive error. Lin and Chen specified a cut-off criterion for concordance as a difference of no more that 0.50D in ocular refraction. They found that intra-pair differences of ocular refraction in monozygotic twins increased with age and also with progression of myopia.
Minkovitz et al did not investigate in as much detail, but they did report that mean intra-pair differences in refractive error were less for monozygotic twins than for dizygotic twins, thus indicating a genetic link. Other such studies have also acknowledged the genetic link that can be deduced from similarities of monozygotic twins. However, it is necessary to take into account the common occurrence that twins are most often not brought up in isolation from each other. Therefore, identical twins most often engage together in their hobbies, possibly more so than non-identical twins, so any environmental influences would be the same in each twin in an identical pair resulting in less intra-pair differences than in dizygotic twins.

ETHNICITY
The wide variability in the prevalence of myopia in different ethnic groups points towards the biological theory in the epidemiology of myopia.
Angle and Wissmann17 found such evidence was apparent and correlated it together from a number of sources.18-20 Figures from these sources show the stark difference in myopia prevalence between people of different races. In Asia the prevalence is as high as 70-90 per cent, in Europe and America it is 30-40 per cent and in Africa it is 10-20 per cent.
It is well known that the Chinese and Japanese racial groups are more prone to myopia than others. The Kodansha Encyclopaedia of Japan, quoted by Yap et al,21 states that it is believed that the Japanese are descendants of people from Northern Asia and that there have been centuries of recorded contact between Japan and China. As a result there are many similarities between the two races shown by the similar high prevalence of myopia among the Japanese and Chinese.22

Asian peoples
In 1949, Crawford and Hammon (cited by Yap et al21) compared the refractive states of schoolchildren of various races living in Hawaii and found the highest prevalence in the Chinese, followed by the Japanese and Korean students, with the lowest prevalence among the indigenous Hawaiians or part-Hawaiians.
Their study was one of excellent value in terms of incidence of myopia among children of many racial and ethnic groups living in an indigenous environment, including data on more than 50,000 subjects, the method of analysis (screening of a non-visually selected sample), and a common school environment.
A study by Zhang et al,23 aimed at comparing the prevalence of myopia in Chinese children in different locations but of similar genetic inheritance, reported a prevalence of 12.3 per cent in Singapore, which is comparable to the 12.0 per cent prevalence found by Lin et al in Taiwan.16
Comparing these figures to the less than 5 per cent prevalence from the Orinda Longitudinal Study in California and the 6 per cent prevalence in Canada, it is possible to see the pattern emerging.
Chandran24 also investigated this clear racial difference in refractive status, comparing the refractive errors of the Malay, the Chinese and the Indian populations in west Malaysia. He reported that the Malaysian population as a whole has an excess of myopia in comparison with Sorsby's Caucasian series.25
Comparing the three ethnic groups within west Malaysia, Chandran found the highest prevalence of myopia among the Chinese race, followed by the Malayan, then the Indian, once again agreeing with the general trend proposed by Zhang et al and Lin et al. The Malay race is more likened to the Chinese race than the Indian race so it follows that the prevalence of myopia among the Malay population is next in line after the Chinese.

Jewish people
Jews as an ethnic group have been studied by a number of researchers. Tenner,26 working in the US, found a higher prevalence of myopia among this group, while in the UK Stephenson27 also found a higher prevalence among Jews than non-Jews. Kantor28 also found Jewish people to have a higher prevalence of myopia. However, despite the early agreement between authors that Jewish people have a higher prevalence of myopia than non-Jews, later studies have reported insignificant differences.29
Shapiro et al30 conducted a well-controlled study investigating the effect of sex, ethnic origin and environment on myopia and found no significant differences among the Jewish population in Israel. In order to investigate the possibility of ethnic differences, comparisons were made between subjects born in countries where the subjects did not normally interbreed with Jewish people from other countries or with the surrounding population.
Studies reviewed by Adams et al,22 many of which were later in the century, did not seem to provide strong evidence supporting the belief that myopia prevalence is unusually high among Jewish people. A point to consider, however, is that most of the articles studied do not specify what 'non-Jew' means. If not Jewish, then what race are they? This would have been an important difference between studies that would definitely influence results.

Afro-Caribbean people
Katz et al31 compared the prevalence of myopia among adult black and white Americans. They used subjects aged 40 and over in east Baltimore and defined myopia as being -0.50D spherical equivalent. The results of the Baltimore Eye Survey reported a 48.1 per cent myopia prevalence among white persons age 14-54 years compared with 42.2 per cent among black persons in the same age group. Angle and Wissman17 concluded that blacks, whether in Africa or in the US have been observed to have a low prevalence of myopia. These percentages appear to be quite high, possibly due to the testing methods or because of the broad range of subjects within the experiment.

The Inuit
The Inuit have traditionally been regarded as a race in which myopia is considered rare on account of explorers emphasising their excellent distance vision for hunting.32 Bind33 found no cases of myopia in the eastern Canadian Arctic among the 250 Inuit examined.
Skeller34 investigated the prevalence of myopia in the isolated district of Angmagssalik in east Greenland and found no myopia greater than -1.25D. He also reported myopia of more than -0.75D in only 13 eyes out of 1,123 spherical eyes examined.
In contrast to these results, Alsbirk35 investigated west Greenland Inuit and concluded that myopia is fairly frequent in all adult age categories. He made reference to Skeller's study stressing that it was an isolated community under study, a community under the influence of natural selection resulting in low myopia prevalence due to its eradication. He hinted at a change in environmental influences as the reason for his findings of an increase in myopia prevalence, a very likely suggestion that is discussed further in the next article of this series. Before the advent of compulsory schooling and the introduction of an Inuit language, which was taught in schools, myopia prevalence was consistently found to be low.
Fledelius36 suggested that differences between races might occur not only because of direct genetic inheritance, but also by a particular race having a genetic susceptibility to a particular environmental factor or factors that cause myopia.

conclusion
It can be seen that many researchers have set about trying to prove the existence of the biological theory of myopia prevalence and progression. However, it seems there are a great number of variables that need to be controlled in order to examine the influence of genetics alone, variables such as time. Experimental processes, therefore, need to be extremely accurate in order to get conclusive results.

References
1 Waardenburg PJ. Das menschliche Auge und seine Erbanlagen. Bibliographie Genetica, 1932; 7: 481-521 (cited by Goldschmidt12).
2 Zadnik K. Myopia development in childhood. Opt Vis Sci, 1997; 74: 603-608.
3 Pacella R, McLelan J, Grice K, Del Boro EA, Wiggs JL, Gwiazda JE. Role of genetic factors in the etiology of juvenile-onset myopia based on the longitudinal study of refractive error. Opt Vis Sci, 1999; 76: 381-386.
4 Zadnik K. The Glenn A. Fry Award Lecture (1995): Myopia development in childhood. Opt Vis Sci, 1997; 74: 603-608.
5 Goss DA, Jackson TW. Clinical findings before the onset of myopia in youth: 4. Parental history of myopia. Opt Vis Sci, 1996; 73: 279-282.
6 Teikari JM, Kaprio J, Markku K, O'Donnell J. Heritability of defects of far vision in young adults Ð a twin study. Scandinavian Journal of the Society of Medicine, 1992; 20: 73-78.
7 Gwiazda J, Thorn F, Bauer J, Held R. Emmetropisation and the progression of manifest reaction in children followed from infancy to puberty. Clinical Visual Science 1993b; 8: 337-344.
8 Wold KC. Hereditary myopia. Archives of Ophthalmology, 1949; 42: 225-237.
9 Ashton GC. Segregation analysis of ocular refraction and myopia. Human Medicine, 1985; 35: 232-239.
10 Goss DA, Hampton MJ, Wickham MG. Selected review on genetic factors in myopia. Journal of American Optometry Association, 1988; 59: 875-884.
11 Sviensson K. The refraction of Icelanders. Acta Ophthalmologica 1982; 60: 779-787.
12 Goldschmidt E. On the aietiology of myopia. Acta Ophthalmologica, 1968; Suppl 98.
13 Young TL, Ronan SM, Bunio A, Wildenberg S, Ottung W, Attwood LD, Wilken D, King R. Genetic mapping of two myopia loci to chromosomes 18p and 12q. Investigative Ophthalmology and Visual Science, 1998; 38: 5280.
14 Zadnik K. Myopia development in childhood. Opt Vis Sci, 1997; 74: 603-608.
15 Minkovitz JB, Essary LR, Walker RS, Chansue E, Cabrera GM, Koch DD, Pepose JS. Comparative corneal topography and refractive parameters in monozygotic and dizygotic twins. Investigative Opt Vis Sci, ARVO Abstracts, 1993; 34 (Suppl): 1218.
16 Lin LLK, Chen CJ. A twin study on myopia in Chinese school children. Acta Ophthalmologica, 1988; (Suppl) 185: 51-53.
17 Angle J, Wissman DA. The epidemiology of myopia. American Journal of Epidemiology, 1980; 111: 220-228.
18 Callan P. Examination of coloured school children's eyes. American Journal of Medical Science, 1875; 69: 331-339.
19 Rasmussen OD. Incidence of myopia in China. BJO, 1936; 20: 350-360.
20 Kantor D. Racial aspects of myopia in compositors. BJO, 1932; 16: 49-50.
21 Yap M, Wu M, Wang SH, Lee FL, Liu ZM. Environmental factors and refractive error in Chinese school children. Clinical and Experimental Optometry, 1994; 77: 8-13.
22 Adams AJ, Baldwin WR, Bierderman I, Curtin BJ, Ebenholtz SM, Goss DA, Hutchison GB, Seddon JM, Wallman J. Analysis of the prevalence literature. Chapter 2: Myopia, Prevalence and Progression. National Academy Press, Washington DC, 1989.
23 Zhang M, Saw S, Hong R, Fu Z, Hui Y, Yap MKH, Chew S. Refractive errors in Singapore and Xiamen, China Ð a comparative study in school-aged children aged 6 to 7 years. Opt Vis Sci, 2000; 77: 302-308.
24 Chandran S. Comparative study of refractive errors in West Malaysia. BJO, 1972; 56: 492.
25 Sorsby A, Benjamin B, Daevy JB, Sheridan M, Tanner JM. Emmetropia and its aberrations. Spec Rep Ser Med Res Coun (Lond), 1957; 293: 17. (cited by Chandran24).
26 Tenner A. Refraction in school children; 4,800 refractions tabulated according to age, sex and nationality. New York Medical Journal, 1915; 102: 611-614 (cited by Baldwin 1967).
27 Stephenson W. Proceedings from the Royal Society of Medicine (Section on Disease of Children) 1919, p215.
28 Kantor D. Racial aspects of myopia in compositors. BJO, 1932; 16: 49-50.
29 Adams AJ, Baldwin WR, Bierderman I, Curtin BJ, Ebenholtz SM, Goss DA, Hutchinson GB, Seddon JM, Wallman J. Myopia: Prevalence and progression. National Academy Press, Washington DC, 1989.
30 Shapiro A, Stollman E, Merin S. Do sex, ethnic origin or environment affect myopia? Acta Ophthalmologica, 1982; 60: 803-808.
31 Katz J, Tielsch JM, Sommer A. Prevalence and risk factors for refractive errors in an adult inner city population. Investigative Optometry and Visual Science, 1997; 38: 334-341.
32 Johnson GJ. Myopia in Arctic regions. Acta Ophthalmologica 1988; Suppl 185:13-18.
33 Bind E. Carrying optometrical service to the Eskimos of the eastern Arctic. American Journal of Optometry and Archives of the Academy of Optometry, 1950; 2: 24-31.
34 Skeller I. Anthropological and ophthalmological studies on the Angmagssalik Eskimos. Meddelelser om Gronland, 1954; 107: 1-211.
35 Alsbirk PM. Refraction in adult west Greenland Eskimos. A population study of spherical refractive errors, including oculometric and familial correlations. Acta Ophthalmologica, 1979; 57: 84-95.
36 Fledelius HC. Myopia prevalence in Scandinavia. A survey with emphasis on factors of relevance for epidemiological refraction studies in general. Acta Ophthalmologica (Copenh) 1988; Suppl 185: 44-50.

Rabiyyah Giga is a pre-reg optometrist with Dollond & AitchisonGoldschmidt, in his 1968 review on the aetiology of myopia, quoted Waardenburg (1932)1 on the topic of genetics.
In this quote, Waardenburg noted the vast amount of literature that had been produced on the subject of the hereditary disposition of refractive errors but that conclusions still cannot be drawn due to the lack of conclusive evidence.

PARENTAL HISTORY
To investigate the genetic basis for the prevalence of myopia it is necessary to obtain the refractive status of the parents of the children in question.
Most studies researching this particular field of myopia epidemiology have used questionnaires sent to the parents. The Orinda Longitudinal Study2 involved a survey given to parents on enrolment of their child, followed by annual correspondence to document the child's medical and ocular history, to assess their visual activity profile and to determine the parents' myopic status.
Pacella et al3 collated refraction data from parents, either by gathering their spectacle or contact lens prescriptions, by contacting their eye care practitioner for the information, by using non-cycloplegic distance retinoscopy to determine refractive status, or by asking the individual or a close family member a series of questions regarding their visual history.
Both methods appeared to provide adequate information. Pacella et al, however, did not specify the criteria for a parent to be regarded as myopic. This automatically created some uncertainty in the comparison between the two studies, although results were very similar.
Zadnik4 stated that a parent was classified as myopic if they reported that they wore glasses primarily for distance viewing, or if they wore glasses that were equally important for distance and near viewing with the spectacles having been prescribed before the age of 16 years old.
Zadnik agreed with Pacella et al that there is a positive correlation between parental myopia and myopia in their children. Zadnik, on examining 716 children between six years and 14.9 years, found that the odds ratio for having two myopic parents compared with having no myopic parents was 5.21, which is a similar figure to that of Pacella et al at 5.09.
The latter group stated that individuals with two myopic parents were 6.42 times as likely to become myopic as those with one or no myopic parents. Their results also indicated that there is no significant difference in the prevalence of myopia among children with one or no myopic parents.
Zadnik obtained an odds ratio of 1.32 for having one myopic parent compared to no myopic parents which, although slightly higher, confirms an increased risk of myopia in children with two myopic parents. These figures indicate a stronger correlation than would be expected by chance.
Pacella et al took their study further. Not only did they look for a positive correlation between having myopic parents and their children subsequently being myopic, they also looked at the age at which the second generation became myopic, thus specifically looking at juvenile-onset myopia.
Included in data gathering was an examination of the child's early year refractions, in order to compare early refractive error to later myopic development (but still within a juvenile-onset boundary of 15 years). They found that two myopic parents and a lower manifest refraction at one year of age are associated with the development of myopia at school age, thereby providing evidence for a genetic component in the aetiology of myopia.
Goss and Jackson,5 like Zadnik and Pacella et al, reported a significant association between parental history of myopia and myopia development in the offspring, stating that the risk of becoming myopic is greater if both parents are myopic than if one parent is myopic.
They also issued a questionnaire, but they questioned the accuracy of the information received by this method on parental refractive status. They cited Teikari et al6 who, on comparing questionnaire findings with actual refractive prescriptions, found a 5.5 per cent false negative rate and a 1.8 per cent false positive rate.
In their conclusion, Goss and Jackson suggested that the variation in refractive error might not always be associated with inheritance, despite the association found. They proposed that common familial tendencies, such as increased reading, could cause myopia in, for example, mother and child, if the child follows by example. However, their proposition was made on the basis of observation of their patients, rather than experimental analysis.
Table 1 shows comparable results from a number of studies.
MODE OF INHERITANCE
None of the studies mentioned so far, looked in detail into the mode of inheritance. Wold classified the pattern of inheritance as being of three types: dominant inheritance, recessive inheritance and sex-linked inheritance.8
The nucleus of each human cell contains a genetic code in the form of 24-paired chromosomes. Genes present along the chromosomes account for the physical individuality of a human. A gene generally consists of two alleles and it is the type of allele that determines the expression of the gene.
In his study, Wold examined a number of kindred in which at least two generations of confirmed myopia or of myopia in different but related families of the same generation were found. Following the inheritance pattern within each case led him to the conclusion that hereditary myopia can be of the three mentioned types. A dominant allele is that which is physically expressed in a heterozygous (two different alleles) or a homozygous (two alleles the same) individual. It must be possessed by at least one of the two parents.
A recessive allele is that which is masked by its paired allele in a heterozygous individual and is only expressed in a homozygous individual. For a child to have a recessive condition, both parents must contribute to the same gene.
A sex-linked recessive character is one that is carried from one sex through the second generation of the opposite sex to appear in the third generation of the original sex.8 The expression of the gene is more common in males than females; however, only the females can pass the trait on to the children.
Wold reported a dominant inheritance as being the most prevalent, followed by recessive inheritance and finally the sex-linked form being the least common.
Goss et al10 reviewed a variety of studies on the mode of inheritance of myopia and found a number of theories. Some proposed an autosomal dominant mode of inheritance, some an autosomal recessive mode and others an X-linked mode of inheritance. Pacella et al, however, obtained results that were inconclusive as to the mode of inheritance. They found equal numbers of affected males and females in the pedigree families that were analysed, therefore providing no evidence of an X-linked trait. Their data did not support an autosomal dominant or an autosomal recessive mode of inheritance either. If myopia was autosomal dominant, one would expect 50 per cent of offspring to be affected and an autosomal recessive trait would expect 25 per cent of offspring to be affected. However, in their study, 63 per cent were affected.
Sveinsson,11 who investigated the refractive error of Icelanders by obtaining refractive information from his patients over a period of 50 years, found that less than half of the young people, whom he had treated for myopia, had myopic parents. The reason for this apparent unclear mode of inheritance could be that a person's susceptibility to myopia may be determined by more than one gene.
This possibility was not investigated by Pacella et al or Wold but it was investigated by Ashton9, cited by Pacella et al. He suggested that myopia is not inherited via a single gene but that it is polygenic and may be influenced by more than one gene. This seems possible due to the heterogeneity of myopia. There are so many forms of myopia that it seems improbable that each one has the same mode of inheritance or that myopia follows a 'monomeric mode of inheritance'.12 Young et al13 discovered significant genetic linkage on chromosome 18p for high myopia and his data supported an autosomal dominant inheritance.
Further genetic evidence was presented by Zadnik et al.14 They found that even before the onset of myopia, children with myopic parents have longer eyes than children with non-myopic parents.

TWIN STUDIES
Further evidence indicating the importance of the genetic factor, is the high concordance of refraction between monozygotic twins (identical) when compared with dizygotic (non-identical) twins.
Minkovitz et al15 compared refractive parameters in monozygotic and dizygotic twins. Their method of determining zygosity was somewhat vaguer than that of Lin and Chen.16 Minkovitz et al determined zygosity by similarity and by questions adapted from the Finnish Twin Registry Questionnaire. Lin and Chen, however, used red-cell antigen systems, birth membranes, and similarity index. Only the abstract was accessible for the former study and it did not specify the cut-off criterion that they used for concordance, thus making comparison between the two studies not entirely valid.
Both did, however, report a significant genetic basis for the overall refractive error. Lin and Chen specified a cut-off criterion for concordance as a difference of no more that 0.50D in ocular refraction. They found that intra-pair differences of ocular refraction in monozygotic twins increased with age and also with progression of myopia.
Minkovitz et al did not investigate in as much detail, but they did report that mean intra-pair differences in refractive error were less for monozygotic twins than for dizygotic twins, thus indicating a genetic link. Other such studies have also acknowledged the genetic link that can be deduced from similarities of monozygotic twins. However, it is necessary to take into account the common occurrence that twins are most often not brought up in isolation from each other. Therefore, identical twins most often engage together in their hobbies, possibly more so than non-identical twins, so any environmental influences would be the same in each twin in an identical pair resulting in less intra-pair differences than in dizygotic twins.

ETHNICITY
The wide variability in the prevalence of myopia in different ethnic groups points towards the biological theory in the epidemiology of myopia.
Angle and Wissmann17 found such evidence was apparent and correlated it together from a number of sources.18-20 Figures from these sources show the stark difference in myopia prevalence between people of different races. In Asia the prevalence is as high as 70-90 per cent, in Europe and America it is 30-40 per cent and in Africa it is 10-20 per cent.
It is well known that the Chinese and Japanese racial groups are more prone to myopia than others. The Kodansha Encyclopaedia of Japan, quoted by Yap et al,21 states that it is believed that the Japanese are descendants of people from Northern Asia and that there have been centuries of recorded contact between Japan and China. As a result there are many similarities between the two races shown by the similar high prevalence of myopia among the Japanese and Chinese.22

Asian peoples
In 1949, Crawford and Hammon (cited by Yap et al21) compared the refractive states of schoolchildren of various races living in Hawaii and found the highest prevalence in the Chinese, followed by the Japanese and Korean students, with the lowest prevalence among the indigenous Hawaiians or part-Hawaiians.
Their study was one of excellent value in terms of incidence of myopia among children of many racial and ethnic groups living in an indigenous environment, including data on more than 50,000 subjects, the method of analysis (screening of a non-visually selected sample), and a common school environment.
A study by Zhang et al,23 aimed at comparing the prevalence of myopia in Chinese children in different locations but of similar genetic inheritance, reported a prevalence of 12.3 per cent in Singapore, which is comparable to the 12.0 per cent prevalence found by Lin et al in Taiwan.16
Comparing these figures to the less than 5 per cent prevalence from the Orinda Longitudinal Study in California and the 6 per cent prevalence in Canada, it is possible to see the pattern emerging.
Chandran24 also investigated this clear racial difference in refractive status, comparing the refractive errors of the Malay, the Chinese and the Indian populations in west Malaysia. He reported that the Malaysian population as a whole has an excess of myopia in comparison with Sorsby's Caucasian series.25
Comparing the three ethnic groups within west Malaysia, Chandran found the highest prevalence of myopia among the Chinese race, followed by the Malayan, then the Indian, once again agreeing with the general trend proposed by Zhang et al and Lin et al. The Malay race is more likened to the Chinese race than the Indian race so it follows that the prevalence of myopia among the Malay population is next in line after the Chinese.

Jewish people
Jews as an ethnic group have been studied by a number of researchers. Tenner,26 working in the US, found a higher prevalence of myopia among this group, while in the UK Stephenson27 also found a higher prevalence among Jews than non-Jews. Kantor28 also found Jewish people to have a higher prevalence of myopia. However, despite the early agreement between authors that Jewish people have a higher prevalence of myopia than non-Jews, later studies have reported insignificant differences.29
Shapiro et al30 conducted a well-controlled study investigating the effect of sex, ethnic origin and environment on myopia and found no significant differences among the Jewish population in Israel. In order to investigate the possibility of ethnic differences, comparisons were made between subjects born in countries where the subjects did not normally interbreed with Jewish people from other countries or with the surrounding population.
Studies reviewed by Adams et al,22 many of which were later in the century, did not seem to provide strong evidence supporting the belief that myopia prevalence is unusually high among Jewish people. A point to consider, however, is that most of the articles studied do not specify what 'non-Jew' means. If not Jewish, then what race are they? This would have been an important difference between studies that would definitely influence results.

Afro-Caribbean people
Katz et al31 compared the prevalence of myopia among adult black and white Americans. They used subjects aged 40 and over in east Baltimore and defined myopia as being -0.50D spherical equivalent. The results of the Baltimore Eye Survey reported a 48.1 per cent myopia prevalence among white persons age 14-54 years compared with 42.2 per cent among black persons in the same age group. Angle and Wissman17 concluded that blacks, whether in Africa or in the US have been observed to have a low prevalence of myopia. These percentages appear to be quite high, possibly due to the testing methods or because of the broad range of subjects within the experiment.

The Inuit
The Inuit have traditionally been regarded as a race in which myopia is considered rare on account of explorers emphasising their excellent distance vision for hunting.32 Bind33 found no cases of myopia in the eastern Canadian Arctic among the 250 Inuit examined.
Skeller34 investigated the prevalence of myopia in the isolated district of Angmagssalik in east Greenland and found no myopia greater than -1.25D. He also reported myopia of more than -0.75D in only 13 eyes out of 1,123 spherical eyes examined.
In contrast to these results, Alsbirk35 investigated west Greenland Inuit and concluded that myopia is fairly frequent in all adult age categories. He made reference to Skeller's study stressing that it was an isolated community under study, a community under the influence of natural selection resulting in low myopia prevalence due to its eradication. He hinted at a change in environmental influences as the reason for his findings of an increase in myopia prevalence, a very likely suggestion that is discussed further in the next article of this series. Before the advent of compulsory schooling and the introduction of an Inuit language, which was taught in schools, myopia prevalence was consistently found to be low.
Fledelius36 suggested that differences between races might occur not only because of direct genetic inheritance, but also by a particular race having a genetic susceptibility to a particular environmental factor or factors that cause myopia.

conclusion
It can be seen that many researchers have set about trying to prove the existence of the biological theory of myopia prevalence and progression. However, it seems there are a great number of variables that need to be controlled in order to examine the influence of genetics alone, variables such as time. Experimental processes, therefore, need to be extremely accurate in order to get conclusive results.

References
1 Waardenburg PJ. Das menschliche Auge und seine Erbanlagen. Bibliographie Genetica, 1932; 7: 481-521 (cited by Goldschmidt12).
2 Zadnik K. Myopia development in childhood. Opt Vis Sci, 1997; 74: 603-608.
3 Pacella R, McLelan J, Grice K, Del Boro EA, Wiggs JL, Gwiazda JE. Role of genetic factors in the etiology of juvenile-onset myopia based on the longitudinal study of refractive error. Opt Vis Sci, 1999; 76: 381-386.
4 Zadnik K. The Glenn A. Fry Award Lecture (1995): Myopia development in childhood. Opt Vis Sci, 1997; 74: 603-608.
5 Goss DA, Jackson TW. Clinical findings before the onset of myopia in youth: 4. Parental history of myopia. Opt Vis Sci, 1996; 73: 279-282.
6 Teikari JM, Kaprio J, Markku K, O'Donnell J. Heritability of defects of far vision in young adults Ð a twin study. Scandinavian Journal of the Society of Medicine, 1992; 20: 73-78.
7 Gwiazda J, Thorn F, Bauer J, Held R. Emmetropisation and the progression of manifest reaction in children followed from infancy to puberty. Clinical Visual Science 1993b; 8: 337-344.
8 Wold KC. Hereditary myopia. Archives of Ophthalmology, 1949; 42: 225-237.
9 Ashton GC. Segregation analysis of ocular refraction and myopia. Human Medicine, 1985; 35: 232-239.
10 Goss DA, Hampton MJ, Wickham MG. Selected review on genetic factors in myopia. Journal of American Optometry Association, 1988; 59: 875-884.
11 Sviensson K. The refraction of Icelanders. Acta Ophthalmologica 1982; 60: 779-787.
12 Goldschmidt E. On the aietiology of myopia. Acta Ophthalmologica, 1968; Suppl 98.
13 Young TL, Ronan SM, Bunio A, Wildenberg S, Ottung W, Attwood LD, Wilken D, King R. Genetic mapping of two myopia loci to chromosomes 18p and 12q. Investigative Ophthalmology and Visual Science, 1998; 38: 5280.
14 Zadnik K. Myopia development in childhood. Opt Vis Sci, 1997; 74: 603-608.
15 Minkovitz JB, Essary LR, Walker RS, Chansue E, Cabrera GM, Koch DD, Pepose JS. Comparative corneal topography and refractive parameters in monozygotic and dizygotic twins. Investigative Opt Vis Sci, ARVO Abstracts, 1993; 34 (Suppl): 1218.
16 Lin LLK, Chen CJ. A twin study on myopia in Chinese school children. Acta Ophthalmologica, 1988; (Suppl) 185: 51-53.
17 Angle J, Wissman DA. The epidemiology of myopia. American Journal of Epidemiology, 1980; 111: 220-228.
18 Callan P. Examination of coloured school children's eyes. American Journal of Medical Science, 1875; 69: 331-339.
19 Rasmussen OD. Incidence of myopia in China. BJO, 1936; 20: 350-360.
20 Kantor D. Racial aspects of myopia in compositors. BJO, 1932; 16: 49-50.
21 Yap M, Wu M, Wang SH, Lee FL, Liu ZM. Environmental factors and refractive error in Chinese school children. Clinical and Experimental Optometry, 1994; 77: 8-13.
22 Adams AJ, Baldwin WR, Bierderman I, Curtin BJ, Ebenholtz SM, Goss DA, Hutchison GB, Seddon JM, Wallman J. Analysis of the prevalence literature. Chapter 2: Myopia, Prevalence and Progression. National Academy Press, Washington DC, 1989.
23 Zhang M, Saw S, Hong R, Fu Z, Hui Y, Yap MKH, Chew S. Refractive errors in Singapore and Xiamen, China Ð a comparative study in school-aged children aged 6 to 7 years. Opt Vis Sci, 2000; 77: 302-308.
24 Chandran S. Comparative study of refractive errors in West Malaysia. BJO, 1972; 56: 492.
25 Sorsby A, Benjamin B, Daevy JB, Sheridan M, Tanner JM. Emmetropia and its aberrations. Spec Rep Ser Med Res Coun (Lond), 1957; 293: 17. (cited by Chandran24).
26 Tenner A. Refraction in school children; 4,800 refractions tabulated according to age, sex and nationality. New York Medical Journal, 1915; 102: 611-614 (cited by Baldwin 1967).
27 Stephenson W. Proceedings from the Royal Society of Medicine (Section on Disease of Children) 1919, p215.
28 Kantor D. Racial aspects of myopia in compositors. BJO, 1932; 16: 49-50.
29 Adams AJ, Baldwin WR, Bierderman I, Curtin BJ, Ebenholtz SM, Goss DA, Hutchinson GB, Seddon JM, Wallman J. Myopia: Prevalence and progression. National Academy Press, Washington DC, 1989.
30 Shapiro A, Stollman E, Merin S. Do sex, ethnic origin or environment affect myopia? Acta Ophthalmologica, 1982; 60: 803-808.
31 Katz J, Tielsch JM, Sommer A. Prevalence and risk factors for refractive errors in an adult inner city population. Investigative Optometry and Visual Science, 1997; 38: 334-341.
32 Johnson GJ. Myopia in Arctic regions. Acta Ophthalmologica 1988; Suppl 185:13-18.
33 Bind E. Carrying optometrical service to the Eskimos of the eastern Arctic. American Journal of Optometry and Archives of the Academy of Optometry, 1950; 2: 24-31.
34 Skeller I. Anthropological and ophthalmological studies on the Angmagssalik Eskimos. Meddelelser om Gronland, 1954; 107: 1-211.
35 Alsbirk PM. Refraction in adult west Greenland Eskimos. A population study of spherical refractive errors, including oculometric and familial correlations. Acta Ophthalmologica, 1979; 57: 84-95.
36 Fledelius HC. Myopia prevalence in Scandinavia. A survey with emphasis on factors of relevance for epidemiological refraction studies in general. Acta Ophthalmologica (Copenh) 1988; Suppl 185: 44-50.

Rabiyyah Giga is a pre-reg optometrist with Dollond & AitchisonGoldschmidt, in his 1968 review on the aetiology of myopia, quoted Waardenburg (1932)1 on the topic of genetics.
In this quote, Waardenburg noted the vast amount of literature that had been produced on the subject of the hereditary disposition of refractive errors but that conclusions still cannot be drawn due to the lack of conclusive evidence.

PARENTAL HISTORY
To investigate the genetic basis for the prevalence of myopia it is necessary to obtain the refractive status of the parents of the children in question.
Most studies researching this particular field of myopia epidemiology have used questionnaires sent to the parents. The Orinda Longitudinal Study2 involved a survey given to parents on enrolment of their child, followed by annual correspondence to document the child's medical and ocular history, to assess their visual activity profile and to determine the parents' myopic status.
Pacella et al3 collated refraction data from parents, either by gathering their spectacle or contact lens prescriptions, by contacting their eye care practitioner for the information, by using non-cycloplegic distance retinoscopy to determine refractive status, or by asking the individual or a close family member a series of questions regarding their visual history.
Both methods appeared to provide adequate information. Pacella et al, however, did not specify the criteria for a parent to be regarded as myopic. This automatically created some uncertainty in the comparison between the two studies, although results were very similar.
Zadnik4 stated that a parent was classified as myopic if they reported that they wore glasses primarily for distance viewing, or if they wore glasses that were equally important for distance and near viewing with the spectacles having been prescribed before the age of 16 years old.
Zadnik agreed with Pacella et al that there is a positive correlation between parental myopia and myopia in their children. Zadnik, on examining 716 children between six years and 14.9 years, found that the odds ratio for having two myopic parents compared with having no myopic parents was 5.21, which is a similar figure to that of Pacella et al at 5.09.
The latter group stated that individuals with two myopic parents were 6.42 times as likely to become myopic as those with one or no myopic parents. Their results also indicated that there is no significant difference in the prevalence of myopia among children with one or no myopic parents.
Zadnik obtained an odds ratio of 1.32 for having one myopic parent compared to no myopic parents which, although slightly higher, confirms an increased risk of myopia in children with two myopic parents. These figures indicate a stronger correlation than would be expected by chance.
Pacella et al took their study further. Not only did they look for a positive correlation between having myopic parents and their children subsequently being myopic, they also looked at the age at which the second generation became myopic, thus specifically looking at juvenile-onset myopia.
Included in data gathering was an examination of the child's early year refractions, in order to compare early refractive error to later myopic development (but still within a juvenile-onset boundary of 15 years). They found that two myopic parents and a lower manifest refraction at one year of age are associated with the development of myopia at school age, thereby providing evidence for a genetic component in the aetiology of myopia.
Goss and Jackson,5 like Zadnik and Pacella et al, reported a significant association between parental history of myopia and myopia development in the offspring, stating that the risk of becoming myopic is greater if both parents are myopic than if one parent is myopic.
They also issued a questionnaire, but they questioned the accuracy of the information received by this method on parental refractive status. They cited Teikari et al6 who, on comparing questionnaire findings with actual refractive prescriptions, found a 5.5 per cent false negative rate and a 1.8 per cent false positive rate.
In their conclusion, Goss and Jackson suggested that the variation in refractive error might not always be associated with inheritance, despite the association found. They proposed that common familial tendencies, such as increased reading, could cause myopia in, for example, mother and child, if the child follows by example. However, their proposition was made on the basis of observation of their patients, rather than experimental analysis.
Table 1 shows comparable results from a number of studies.
MODE OF INHERITANCE
None of the studies mentioned so far, looked in detail into the mode of inheritance. Wold classified the pattern of inheritance as being of three types: dominant inheritance, recessive inheritance and sex-linked inheritance.8
The nucleus of each human cell contains a genetic code in the form of 24-paired chromosomes. Genes present along the chromosomes account for the physical individuality of a human. A gene generally consists of two alleles and it is the type of allele that determines the expression of the gene.
In his study, Wold examined a number of kindred in which at least two generations of confirmed myopia or of myopia in different but related families of the same generation were found. Following the inheritance pattern within each case led him to the conclusion that hereditary myopia can be of the three mentioned types. A dominant allele is that which is physically expressed in a heterozygous (two different alleles) or a homozygous (two alleles the same) individual. It must be possessed by at least one of the two parents.
A recessive allele is that which is masked by its paired allele in a heterozygous individual and is only expressed in a homozygous individual. For a child to have a recessive condition, both parents must contribute to the same gene.
A sex-linked recessive character is one that is carried from one sex through the second generation of the opposite sex to appear in the third generation of the original sex.8 The expression of the gene is more common in males than females; however, only the females can pass the trait on to the children.
Wold reported a dominant inheritance as being the most prevalent, followed by recessive inheritance and finally the sex-linked form being the least common.
Goss et al10 reviewed a variety of studies on the mode of inheritance of myopia and found a number of theories. Some proposed an autosomal dominant mode of inheritance, some an autosomal recessive mode and others an X-linked mode of inheritance. Pacella et al, however, obtained results that were inconclusive as to the mode of inheritance. They found equal numbers of affected males and females in the pedigree families that were analysed, therefore providing no evidence of an X-linked trait. Their data did not support an autosomal dominant or an autosomal recessive mode of inheritance either. If myopia was autosomal dominant, one would expect 50 per cent of offspring to be affected and an autosomal recessive trait would expect 25 per cent of offspring to be affected. However, in their study, 63 per cent were affected.
Sveinsson,11 who investigated the refractive error of Icelanders by obtaining refractive information from his patients over a period of 50 years, found that less than half of the young people, whom he had treated for myopia, had myopic parents. The reason for this apparent unclear mode of inheritance could be that a person's susceptibility to myopia may be determined by more than one gene.
This possibility was not investigated by Pacella et al or Wold but it was investigated by Ashton9, cited by Pacella et al. He suggested that myopia is not inherited via a single gene but that it is polygenic and may be influenced by more than one gene. This seems possible due to the heterogeneity of myopia. There are so many forms of myopia that it seems improbable that each one has the same mode of inheritance or that myopia follows a 'monomeric mode of inheritance'.12 Young et al13 discovered significant genetic linkage on chromosome 18p for high myopia and his data supported an autosomal dominant inheritance.
Further genetic evidence was presented by Zadnik et al.14 They found that even before the onset of myopia, children with myopic parents have longer eyes than children with non-myopic parents.

TWIN STUDIES
Further evidence indicating the importance of the genetic factor, is the high concordance of refraction between monozygotic twins (identical) when compared with dizygotic (non-identical) twins.
Minkovitz et al15 compared refractive parameters in monozygotic and dizygotic twins. Their method of determining zygosity was somewhat vaguer than that of Lin and Chen.16 Minkovitz et al determined zygosity by similarity and by questions adapted from the Finnish Twin Registry Questionnaire. Lin and Chen, however, used red-cell antigen systems, birth membranes, and similarity index. Only the abstract was accessible for the former study and it did not specify the cut-off criterion that they used for concordance, thus making comparison between the two studies not entirely valid.
Both did, however, report a significant genetic basis for the overall refractive error. Lin and Chen specified a cut-off criterion for concordance as a difference of no more that 0.50D in ocular refraction. They found that intra-pair differences of ocular refraction in monozygotic twins increased with age and also with progression of myopia.
Minkovitz et al did not investigate in as much detail, but they did report that mean intra-pair differences in refractive error were less for monozygotic twins than for dizygotic twins, thus indicating a genetic link. Other such studies have also acknowledged the genetic link that can be deduced from similarities of monozygotic twins. However, it is necessary to take into account the common occurrence that twins are most often not brought up in isolation from each other. Therefore, identical twins most often engage together in their hobbies, possibly more so than non-identical twins, so any environmental influences would be the same in each twin in an identical pair resulting in less intra-pair differences than in dizygotic twins.

ETHNICITY
The wide variability in the prevalence of myopia in different ethnic groups points towards the biological theory in the epidemiology of myopia.
Angle and Wissmann17 found such evidence was apparent and correlated it together from a number of sources.18-20 Figures from these sources show the stark difference in myopia prevalence between people of different races. In Asia the prevalence is as high as 70-90 per cent, in Europe and America it is 30-40 per cent and in Africa it is 10-20 per cent.
It is well known that the Chinese and Japanese racial groups are more prone to myopia than others. The Kodansha Encyclopaedia of Japan, quoted by Yap et al,21 states that it is believed that the Japanese are descendants of people from Northern Asia and that there have been centuries of recorded contact between Japan and China. As a result there are many similarities between the two races shown by the similar high prevalence of myopia among the Japanese and Chinese.22

Asian peoples
In 1949, Crawford and Hammon (cited by Yap et al21) compared the refractive states of schoolchildren of various races living in Hawaii and found the highest prevalence in the Chinese, followed by the Japanese and Korean students, with the lowest prevalence among the indigenous Hawaiians or part-Hawaiians.
Their study was one of excellent value in terms of incidence of myopia among children of many racial and ethnic groups living in an indigenous environment, including data on more than 50,000 subjects, the method of analysis (screening of a non-visually selected sample), and a common school environment.
A study by Zhang et al,23 aimed at comparing the prevalence of myopia in Chinese children in different locations but of similar genetic inheritance, reported a prevalence of 12.3 per cent in Singapore, which is comparable to the 12.0 per cent prevalence found by Lin et al in Taiwan.16
Comparing these figures to the less than 5 per cent prevalence from the Orinda Longitudinal Study in California and the 6 per cent prevalence in Canada, it is possible to see the pattern emerging.
Chandran24 also investigated this clear racial difference in refractive status, comparing the refractive errors of the Malay, the Chinese and the Indian populations in west Malaysia. He reported that the Malaysian population as a whole has an excess of myopia in comparison with Sorsby's Caucasian series.25
Comparing the three ethnic groups within west Malaysia, Chandran found the highest prevalence of myopia among the Chinese race, followed by the Malayan, then the Indian, once again agreeing with the general trend proposed by Zhang et al and Lin et al. The Malay race is more likened to the Chinese race than the Indian race so it follows that the prevalence of myopia among the Malay population is next in line after the Chinese.

Jewish people
Jews as an ethnic group have been studied by a number of researchers. Tenner,26 working in the US, found a higher prevalence of myopia among this group, while in the UK Stephenson27 also found a higher prevalence among Jews than non-Jews. Kantor28 also found Jewish people to have a higher prevalence of myopia. However, despite the early agreement between authors that Jewish people have a higher prevalence of myopia than non-Jews, later studies have reported insignificant differences.29
Shapiro et al30 conducted a well-controlled study investigating the effect of sex, ethnic origin and environment on myopia and found no significant differences among the Jewish population in Israel. In order to investigate the possibility of ethnic differences, comparisons were made between subjects born in countries where the subjects did not normally interbreed with Jewish people from other countries or with the surrounding population.
Studies reviewed by Adams et al,22 many of which were later in the century, did not seem to provide strong evidence supporting the belief that myopia prevalence is unusually high among Jewish people. A point to consider, however, is that most of the articles studied do not specify what 'non-Jew' means. If not Jewish, then what race are they? This would have been an important difference between studies that would definitely influence results.

Afro-Caribbean people
Katz et al31 compared the prevalence of myopia among adult black and white Americans. They used subjects aged 40 and over in east Baltimore and defined myopia as being -0.50D spherical equivalent. The results of the Baltimore Eye Survey reported a 48.1 per cent myopia prevalence among white persons age 14-54 years compared with 42.2 per cent among black persons in the same age group. Angle and Wissman17 concluded that blacks, whether in Africa or in the US have been observed to have a low prevalence of myopia. These percentages appear to be quite high, possibly due to the testing methods or because of the broad range of subjects within the experiment.

The Inuit
The Inuit have traditionally been regarded as a race in which myopia is considered rare on account of explorers emphasising their excellent distance vision for hunting.32 Bind33 found no cases of myopia in the eastern Canadian Arctic among the 250 Inuit examined.
Skeller34 investigated the prevalence of myopia in the isolated district of Angmagssalik in east Greenland and found no myopia greater than -1.25D. He also reported myopia of more than -0.75D in only 13 eyes out of 1,123 spherical eyes examined.
In contrast to these results, Alsbirk35 investigated west Greenland Inuit and concluded that myopia is fairly frequent in all adult age categories. He made reference to Skeller's study stressing that it was an isolated community under study, a community under the influence of natural selection resulting in low myopia prevalence due to its eradication. He hinted at a change in environmental influences as the reason for his findings of an increase in myopia prevalence, a very likely suggestion that is discussed further in the next article of this series. Before the advent of compulsory schooling and the introduction of an Inuit language, which was taught in schools, myopia prevalence was consistently found to be low.
Fledelius36 suggested that differences between races might occur not only because of direct genetic inheritance, but also by a particular race having a genetic susceptibility to a particular environmental factor or factors that cause myopia.

conclusion
It can be seen that many researchers have set about trying to prove the existence of the biological theory of myopia prevalence and progression. However, it seems there are a great number of variables that need to be controlled in order to examine the influence of genetics alone, variables such as time. Experimental processes, therefore, need to be extremely accurate in order to get conclusive results.

References
1 Waardenburg PJ. Das menschliche Auge und seine Erbanlagen. Bibliographie Genetica, 1932; 7: 481-521 (cited by Goldschmidt12).
2 Zadnik K. Myopia development in childhood. Opt Vis Sci, 1997; 74: 603-608.
3 Pacella R, McLelan J, Grice K, Del Boro EA, Wiggs JL, Gwiazda JE. Role of genetic factors in the etiology of juvenile-onset myopia based on the longitudinal study of refractive error. Opt Vis Sci, 1999; 76: 381-386.
4 Zadnik K. The Glenn A. Fry Award Lecture (1995): Myopia development in childhood. Opt Vis Sci, 1997; 74: 603-608.
5 Goss DA, Jackson TW. Clinical findings before the onset of myopia in youth: 4. Parental history of myopia. Opt Vis Sci, 1996; 73: 279-282.
6 Teikari JM, Kaprio J, Markku K, O'Donnell J. Heritability of defects of far vision in young adults Ð a twin study. Scandinavian Journal of the Society of Medicine, 1992; 20: 73-78.
7 Gwiazda J, Thorn F, Bauer J, Held R. Emmetropisation and the progression of manifest reaction in children followed from infancy to puberty. Clinical Visual Science 1993b; 8: 337-344.
8 Wold KC. Hereditary myopia. Archives of Ophthalmology, 1949; 42: 225-237.
9 Ashton GC. Segregation analysis of ocular refraction and myopia. Human Medicine, 1985; 35: 232-239.
10 Goss DA, Hampton MJ, Wickham MG. Selected review on genetic factors in myopia. Journal of American Optometry Association, 1988; 59: 875-884.
11 Sviensson K. The refraction of Icelanders. Acta Ophthalmologica 1982; 60: 779-787.
12 Goldschmidt E. On the aietiology of myopia. Acta Ophthalmologica, 19