People who work in occupations that involve intensive near work are thought to have a higher chance of developing myopia than other people. For example, microscopists in the United Kingdom have a higher prevalence of myopia than that of the general community. The prevalence of myopia in Hong Kong is extremely high (71 %) and Hong Kong Chinese people are particularly susceptible to myopia development and progression due to environmental factors. It is possible that this environmental susceptibility may lead to Hong Kong Chinese microscopists developing even greater levels of myopia. We found that the prevalence of myopia in Hong Kong microscopists (n=47, mean age=31 years) was higher than that of United Kingdom microscopists (87 % c.f. 71 %) and similar aged people within the general Hong Kong population (87 % c.f. 71 %; −4.45 D c.f. -3.00 D). However, while in most microscopists (83 % of 36 microscopists followed for a two-year period) the amount of myopia and vitreous chamber depth increased over a two year monitoring period (−0.11 D, 0.06 mm), the increase was not clinically significant. We hypothesised that the slower myopia progression rate in Hong Kong microscopists may be the result of their older average age (Hong Kong microscopists: 31.7 years c.f. United Kingdom microscopists: 29.7 years). When a person looks into a microscope, excessive accommodation occurs even though the microscope is designed to render the magnified image at optical infinity (zero accommodation and vergence demand). This over accommodation is called instrument myopia. It is possible that this over accommodation is linked to the myopia development and progression that occurs in users of these instruments. We found that instrument myopia remained consistent with different viewing conditions and microscope settings (inexperienced microscopists, n=20, mean age: 24.1 years, mean spherical refractive error: −2.83 D). The magnitude of instrument myopia was not correlated with either the age or refractive error of the microscope user, while it was lower in those users with greater experience (inexperienced microscopists: 1.03 D c.f. experienced microscopists: 0.43 D). As the Hong Kong microscopists (n=10, mean age: 31.2 years, mean spherical refractive error: −3.39 D) who partook in this study were experienced (6.3 years spent working in this field), this may have contributed to the lower myopia progression that was observed. Studies to determine the main contribution to the phenomena of instrument myopia were also conducted. Instrument myopia was not correlated with convergence when looking into microscope (r= −0.224, p=0.342), near phoria (r=0.351, p=0.129), AC/A ratio (r= −0.135, p=0.571), the convergence induced by the excessive accommodative response (r= −0.028, p=0.906), lag of accommodation (r=0.065, p=0.785) and tonic accommodation (r=0.142, p=0.551). We suggest that the main contribution to instrument myopia during microscopy is proximal accommodation due to the awareness of the closeness, caused by the height of the microscope (i.e. the distance between the viewer and the table where the microscope is placed), during microscopy. For example, we found that the magnitude of instrument myopia increased significantly (from 0.64 D to 1.16 D) when the height of the microscope decreased from 50 cm to 35 cm. In conclusion we have added, through direct observation, to the understanding of the characteristics of instrument myopia. Guidelines for new microscopists aimed at minimising the amount of instrument myopia that is experienced have been developed. This information might help to reduce the amount of myopia progression in commencing microscopists.

Lo Peng-iok. / Includes questionnaire in Chinese. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 51-58). / List of tables --- p.V / List of figures --- p.VIII / List of abbreviations --- p.IX / Acknowledgments --- p.X / Abstract --- p.XI / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Literature review --- p.3 / Chapter 2.1 --- The history of myopia --- p.3 / Chapter 2.2 --- The epidemiological study of myopia --- p.4 / Chapter 2.3 --- The relationship between myopia and optical components --- p.7 / Chapter 2.4 --- The classification of myopia --- p.9 / Chapter 2.5 --- Myopia and blindness --- p.11 / Chapter Chapter 3 --- Material and methods --- p.13 / Chapter 3.1 --- Material --- p.13 / Chapter 3.2 --- Methods --- p.14 / Chapter 3.2.1 --- Questionnaire --- p.14 / Chapter 3.2.2 --- Eye examination --- p.15 / Chapter I). --- Autorefraction --- p.15 / Chapter II). --- Keratometry --- p.16 / Chapter III). --- Opthalmoscopy --- p.16 / Chapter IV). --- A-scan Biometry --- p.16 / Chapter V). --- Tonometry --- p.17 / Chapter 3.2.3 --- Data analysis --- p.17 / Chapter Chapter 4 --- Results --- p.19 / Chapter 4.1 --- The distribution of refraction --- p.19 / Chapter 4.1.1 --- The distribution of refraction among 2150 eyes of 1075 students --- p.19 / Chapter 4.1.2 --- The distribution of refraction (right eye) by sex and age --- p.20 / Chapter 4.1.3 --- The distribution of refraction (right eye) by faculty --- p.21 / Chapter 4.1.4 --- The astigmatism among 1075 freshmen --- p.22 / Chapter 4.1.5 --- The anisometropia and isometropia among 1075 freshmen --- p.22 / Chapter 4.2 --- Relationship between the ocular refraction and its optical components --- p.23 / Chapter 4.2.1 --- The results of keratometry and A-scan ultrasound measurements --- p.24 / Chapter 4.2.2 --- The distribution of the ocular components --- p.24 / Chapter 4.2.3 --- The association between the refraction and optical components --- p.25 / Chapter 4.2.4 --- The association between various optical components --- p.27 / Chapter 4.2.5 --- The association between the myopia and optical components --- p.28 / Chapter 4.3 --- "Relationship between refraction and corrected visual acuity, fundus changes and intraocular pressure" --- p.30 / Chapter 4.3.1 --- The association between refraction and corrected visual acuity --- p.30 / Chapter 4.3.2 --- The association between refraction and fundus changes --- p.31 / Chapter 4.3.3 --- The association between refraction and intraocular pressure --- p.32 / Chapter 4.4 --- Relationship between myopia and environmental factors --- p.32 / Chapter 4.4.1 --- Present myopia in relation to age at onset of myopia --- p.33 / Chapter 4.4.2 --- The Influence of nearwork on myopia in freshmen --- p.34 / Chapter 4.4.3 --- The Influence of sports on myopia in freshmen --- p.35 / Chapter 4.4.4 --- The influence of achievement on myopia --- p.36 / Chapter 4.4.5 --- "The influence of time spent in front of TV set and computer, sleeping habit on myopia" --- p.36 / Chapter 4.5 --- The relationship between myopia and family background --- p.37 / Chapter 4.5.1 --- The relation between myopia and parents' refractive status --- p.37 / Chapter 4.5.2 --- The relation between myopia and parents' education level --- p.38 / Chapter 4.5.3 --- The relation between myopia and family income --- p.38 / Chapter Chapter 5 --- Discussion --- p.40 / Chapter 5.1 --- The high prevalence and high degree of myopia in Hong Kong Chinese students --- p.40 / Chapter 5.2 --- The relationship between refraction and its optical components in Hong Kong Chinese students --- p.43 / Chapter 5.3 --- The relationship between myopia and age at onset of myopia in Hong Kong Chinese students --- p.46 / Chapter 5.4 --- The relationship between myopia and environmental factors in Hong Kong Chinese students --- p.48 / References --- p.51 / Tables --- p.59 / Figures --- p.93 / Chapter Appendix I --- Questionnaire --- p.106 / Chapter Appendix II --- An English translation of the questionnaire --- p.110

Purpose: To study ???on??? and ???off-axis??? wavefront aberration of eyes of children and to determine the relationship with refractive error development. Methods: On and off-axis ocular aberrations of cyclopleged eyes of children (mostly 12 year olds) were measured and compared to data obtained from a group of mostly 6 year old children. Only data from the right eyes were analysed (pupil diameter=5 mm) and categorised into refractive error groups based on ???M???. Differences in ???on??? and ???off-axis??? aberrations between refractive and ethnic groups were analysed using univariate and multivariate analyses of variance with adjustment for multiple comparisons. Off-axis refraction was analysed using skiagrams and mean relative spherical equivalent. Results: Data from 1,636 12 year old children (mean age 12.6 ?? 0.4 years) was analysed. Lower order aberrations were the largest and higher order aberrations contributed to only 25% of the wavefront. There were no differences in the amount of total higher orders between refractive groups. Of the individual higher orders, spherical aberration was greater in hyperopic eyes (0.07 ?? 0.06 ??m) in comparison to emmetropic and myopic eyes (0.05 ?? 0.04 ??m and 0.05 ?? 0.04 ??m) (p<0.001). Myopic eyes had more positive values of Z(3,-1) (p<0.05). Similar results were obtained for the 1,364 6 year old children (mean age 6.7 ??? 0.4 years). Despite East Asian children being more myopic than other ethnic groups (p<0.01), there were no differences in higher orders except for low hyperopic East Asian eyes presenting with higher levels of positive spherical aberrations (p<0.001). When compared to the fovea, off-axis myopic eyes had hyperopia (0.55 to 1.66 D) and emmetropes and hyperopes had myopia (0.10 to -2.00 D). Astigmatism and defocus were the dominant off-axis aberrations. The magnitude of higher order aberrations (mostly 3rd orders) increased with eccentricity but was similar across refractive error groups. Conclusions: Myopic eyes do not have abnormal or excessive levels of on and off-axis higher order aberrations but had patterns of off-axis refraction that may be associated with progression. Considerable inter-subject variability in higher order aberrations was seen for all refractive groups. However, their magnitude was small and suggests that any impact on the optical quality of the eye is negligible.

Purpose: To study ???on??? and ???off-axis??? wavefront aberration of eyes of children and to determine the relationship with refractive error development. Methods: On and off-axis ocular aberrations of cyclopleged eyes of children (mostly 12 year olds) were measured and compared to data obtained from a group of mostly 6 year old children. Only data from the right eyes were analysed (pupil diameter=5 mm) and categorised into refractive error groups based on ???M???. Differences in ???on??? and ???off-axis??? aberrations between refractive and ethnic groups were analysed using univariate and multivariate analyses of variance with adjustment for multiple comparisons. Off-axis refraction was analysed using skiagrams and mean relative spherical equivalent. Results: Data from 1,636 12 year old children (mean age 12.6 ?? 0.4 years) was analysed. Lower order aberrations were the largest and higher order aberrations contributed to only 25% of the wavefront. There were no differences in the amount of total higher orders between refractive groups. Of the individual higher orders, spherical aberration was greater in hyperopic eyes (0.07 ?? 0.06 ??m) in comparison to emmetropic and myopic eyes (0.05 ?? 0.04 ??m and 0.05 ?? 0.04 ??m) (p<0.001). Myopic eyes had more positive values of Z(3,-1) (p<0.05). Similar results were obtained for the 1,364 6 year old children (mean age 6.7 ??? 0.4 years). Despite East Asian children being more myopic than other ethnic groups (p<0.01), there were no differences in higher orders except for low hyperopic East Asian eyes presenting with higher levels of positive spherical aberrations (p<0.001). When compared to the fovea, off-axis myopic eyes had hyperopia (0.55 to 1.66 D) and emmetropes and hyperopes had myopia (0.10 to -2.00 D). Astigmatism and defocus were the dominant off-axis aberrations. The magnitude of higher order aberrations (mostly 3rd orders) increased with eccentricity but was similar across refractive error groups. Conclusions: Myopic eyes do not have abnormal or excessive levels of on and off-axis higher order aberrations but had patterns of off-axis refraction that may be associated with progression. Considerable inter-subject variability in higher order aberrations was seen for all refractive groups. However, their magnitude was small and suggests that any impact on the optical quality of the eye is negligible.

Yes / Importance: Myopia is a leading cause of untreatable visual impairment and is increasing in prevalence worldwide. Interventions for slowing childhood myopia progression have shown success in randomized clinical trials; hence, there is a need to identify which children would benefit most from treatment intervention. Objectives: To examine whether genetic information alone can identify children at risk of myopia development and whether including a child’s genetic predisposition to educational attainment is associated with improved genetic prediction of the risk of myopia. Design, Setting, and Participants: Meta-analysis of 3 genome-wide association studies (GWAS) including a total of 711 984 individuals. These were a published GWAS for educational attainment and 2 GWAS for refractive error in the UK Biobank, which is a multisite cohort study that recruited participants between January 2006 and October 2010. A polygenic risk score was applied in a population-based validation sample examined between September 1998 and September 2000 (Avon Longitudinal Study of Parents and Children [ALSPAC] mothers). Data analysis was performed from February 2018 to May 2019. Main Outcomes and Measures: The primary outcome was the area under the receiver operating characteristic curve (AUROC) in analyses for predicting myopia, using noncycloplegic autorefraction measurements for myopia severity levels of less than or equal to −0.75 diopter (D) (any), less than or equal to -3.00 D (moderate), or less than or equal to −5.00 D (high). The predictor variable was a polygenic risk score (PRS) derived from genome-wide association study data for refractive error (n = 95 619), age of onset of spectacle wear (n = 287 448), and educational attainment (n = 328 917). Results: A total of 383 067 adults aged 40 to 69 years from the UK Biobank were included in the new GWAS analyses. The PRS was evaluated in 1516 adults aged 24 to 51 years from the ALSPAC mothers cohort. The PRS had an AUROC of 0.67 (95% CI, 0.65-0.70) for myopia, 0.75 (95% CI, 0.70-0.79) for moderate myopia, and 0.73 (95% CI, 0.66-0.80) for high myopia. Inclusion in the PRS of information associated with genetic predisposition to educational attainment marginally improved the AUROC for myopia (AUROC, 0.674 vs 0.668; P = .02), but not those for moderate and high myopia. Individuals with a PRS in the top 10% were at 6.1-fold higher risk (95% CI, 3.4–10.9) of high myopia. Conclusions and Relevance: A personalized medicine approach may be feasible for detecting very young children at risk of myopia. However, accuracy must improve further to merit uptake in clinical practice; currently, cycloplegic autorefraction remains a better indicator of myopia risk (AUROC, 0.87). / PhD studentship grant from the College of Optometrists (Drs Guggenheim and Williams; supporting Mr Mojarrad) entitled Genetic prediction of individuals at-risk for myopia development) and National Institute for Health Research (NIHR) Senior Research Fellowship award SRF-2015-08-005 (Dr Williams). The UK Medical Research Council and Wellcome grant 102215/2/13/2 and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children (ALSPAC). A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was conducted using the UK Biobank Resource (application 17351). The UK Biobank was established by the Wellcome Trust, the UK Medical Research Council, the Department for Health (London, England), the Scottish government (Edinburgh, Scotland), and the Northwest Regional Development Agency (Warrington, England). It also received funding from the Welsh Assembly Government (Cardiff, Wales), the British Heart Foundation, and Diabetes UK.

Myopia is a refractive condition and develops because either the optical power of the eye is abnormally great or the eye is abnormally long, the optical consequences being that the focal length of the eye is too short for the physical length of the eye. The increase in axial length has been shown to match closely the dioptric error of the eye, in that a lmm increase in axial length usually generates 2 to 3D of myopia. The most common form of myopia is early-onset myopia (EO M) which occurs between 6 to 14 years of age. The second most common form of myopia is late-onset myopia (LOM) which emerges in late teens or early twenties, at a time when the eye should have ceased growing. The prevalence of LOM is increasing and research has indicated a link with excessive and sustained nearwork. The aim of this thesis was to examine the ocular biometric correlates associated with LOM and EOM development and progression. Biometric data was recorded on SO subjects, aged 16 to 26 years. The group was divided into 26 emmetropic subjects and 24 myopic subjects. Keratometry, corneal topography, ultrasonography, lens shape, central and peripheral refractive error, ocular blood flow and assessment of accommodation were measured on three occasions during an ISmonth to 2-year longitudinal study. Retinal contours were derived using a specially derived computer program. The thesis shows that myopia progression is related to an increase in vitreous chamber depth, a finding which supports previous work. The myopes exhibited hyperopic relative peripheral refractive error (PRE) and the emmetropes exhibited myopic relative PRE. Myopes demonstrated a prolate retinal shape and the retina became more prolate with myopia progression. The results show that a longitudinal, rather than equatorial, increase in the posterior segment is the principal structural correlate of myopia. Retinal shape, relative PRE and the ratio of axial length to corneal curvature have been indicated, in this thesis, as predictive factors for myopia onset and development. Data from this thesis demonstrates that myopia progression in the LOM group is the result of an increase in anterior segment power, owing to an increase in lens thickness, in conjunction with posterior segment elongation. Myopia progression in the EOM group is the product of a long posterior segment, which over-compensates for a weak anterior segment power. The weak anterior segment power in the EOM group is related to a combination of crystalline lens thinning and surface flattening. The results presented in this thesis confirm that posterior segment elongation is the main structural correlate in both EOM and LOM progression. The techniques and computer programs employed in the thesis are reproducible and robust providing a valuable framework for further myopia research and assessment of predictive factors.

Thesis (Ph. D.)--University of New South Wales, 2004. / Also available online.

No description available.

Ocular drug delivery remains a challenge due to the anatomical and physiological barriers of the eye. Topical drops have poor penetration and side effects, and injections are highly invasive; an alternative approach is transscleral delivery. Sustained drug release systems utilizing this delivery pathway are non-invasive yet provide extended treatment periods with single doses. Specifically, such systems would be beneficial for treating pediatric populations for diseases such as retinoblastoma and myopia. A chemo-preventative treatment for retinoblastoma, a childhood ocular cancer, has been proposed utilizing CdK inhibitors such as roscovitine and R547. Myopia, a more common, chronic condition in children, can be treated with atropine, though the dosing must be tightly controlled. Three novel delivery systems have been developed in this work to deliver these drugs, generating potential treatment platforms for these conditions. Contact lenses have been investigated previously to deliver various therapeutics, as they act as a slow, equilibrating reservoir, and the prolonged corneal residence time improves bioavailability. Silicone lenses, with their ability for continuous wear, have been explored looking at various material compositions and drug loading levels and techniques to confirm the feasibility of this system for these conditions (Chapter 2). This work has been extended to include covalent tethers for roscovitine, ensuring that it is able to survive a more commercially-relevant synthesis and providing additional ways to tailor the drug release profiles (Chapter 3). Alternatively, amphiphiles, which can self-assemble in the presence of excess water, have been explored for their drug delivery potential. Novel materials consisting of oleoylethanolamide and linoleoylethanolamide were developed to exhibit cubic phase transitions at physiologically relevant conditions, and their subsequent drug release characteristics were explored (Chapter 4). Silicone-based materials have broad usages as biomaterials, and a novel approach of incorporating PEG into the material without the use of metal catalysts were explored (Chapter 5). These exhibited a significant reduction in protein fouling, and material compositions were further iterated on, and their subsequent drug delivery capabilities were examined (Chapter 6). Overall, these three approaches have been able to successfully delivery roscovitine, R547 and atropine in non-invasive manners that have the potential to be an appropriate treatment for the childhood conditions they are intended to treat. / Dissertation / Doctor of Philosophy (PhD) / Sustained ocular drug delivery is critical to minimize side effects, maximize compliance and improve the clinical outcomes experienced by the patient. This is particularly true in pediatric applications, such as retinoblastoma and myopia. The objective of this thesis is to create drug delivery systems that could be used to treat these childhood conditions, with a focus on non-invasive delivery technologies. In this project, contact lenses are explored as drug delivery vehicles for two drugs which can be used to treat retinoblastoma and myopia. Multiple materials and drug loading are explored to create a sustained drug delivery system that meets the needs of these conditions. This is then expanded into examining systems that fit within current commercial manufacturing practices, creating a delivery system that meets the demands of the disease and industry. Alternative delivery systems that could be utilized as inserts are also explored. A lipid based system, whose materials are native to the body, are explored as a unique system capable of delivering drugs in a controlled fashion under specific hydration and temperature conditions. Alternatively, a silicone-based system is explored, whose unique chemistry eliminates many of the prohibitive biological side effects seen with these materials, allowing for a sustained drug delivery system for these ocular conditions.

For linkage region on chromosome 5, further fine mapping was performed on a total of three pedigrees. Linkage analysis revealed a maximum two point LOD score of 4.81 at marker D5S2505. Haplotype analysis narrowed the linkage region to 5p15.33-p15.2. Resequencing of five candidate genes, IRX2, IRX1, POLS, CCT5 and CTNND2 within the linkage region did not reveal any myopia mutation. They were therefore excluded as the myopia causative gene. Genotyping of 41 SNPs within this region in a Chinese cohort of 94 high myopia cases and 94 control subjects showed that the allele and genotypes distributions of rs370010 was significantly different between cases and controls (genotype P= 0.01176, allele P=0.00271 and trend P=0.00375). This SNP is located within a hypothetical gene LOC442129. After multiple testing corrections, none of the SNP remained significantly associated with high myopia. This is a novel myopia locus. Further work to identify the myopia gene in this region would involve candidate gene resequencing, family linkage analysis and gene-based SNPs association analysis. / High myopia is defined as refractive error below or equal to -6 dioptres (D). The prevalence of high myopia varies among different populations. The most common pathological structural abnormality in high myopia is the excessive lengthening of the posterior segment of the ocular globe. Apart from causing impaired vision, it may lead to severe ocular complications. The precise mechanistic role of genes and environmental factors in the development of high myopia is still uncertain. Studies of twins and families suggested that heredity is a major contributing factor. While no myopia gene has yet to be identified, 14 putative loci have been found on many chromosomes. In this study, we have utilized different approaches to map the myopia locus in the Chinese population. / In our family-based genome-wide scan program, the whole genome of Chinese high myopia pedigrees was screened by using microsatellite markers. Two point LOD scores > 1 were observed on chromosomes 12 and 5. Regions were further analyzed by fine mapping. For linkage region on chromosome 12, a maximum two point LOD score of 2.71 was obtained at marker D12S88 and suggested linkage region was narrowed at 12q21.31-q22 by haplotype analysis. Lumican located in this region was screened and no segregation of polymorphism was observed within the pedigree. The suggested locus in this study overlapped with the MYP3 but with a smaller interval than the one reported. Lumican was excluded to be the myopia gene in this locus. / In the candidate-gene program, the paired box gene 6 (PAX6) on 11p13, was first studied. Two dinucleotide repeats (AC)m and (AG)n in the promoter region were found to be highly polymorphic. Association was observed between these two repeats with high myopia in which patients had high repeat number in both (AC) m and (AG)n (p-value=0.0001317 and p-value=0.001). Our results indicated that the Chinese population does not show association between high myopia and polymorphisms in PAX6 coding region but the AC and AG dinucleotide repeats in the promoter region was significantly associated with high myopia. / Lam, Ching Yan. / "August 2007." / Source: Dissertation Abstracts International, Volume: 69-07, Section: B, page: 4103. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.