This thesis aimes to illustrate and describe the current status of refraction and axial length in German children and adolescents. In contrast to previous studies growth curves were generated, instead of analysing myopia prevalence at separate age groups. This allows for an easier understanding and comparison of eye development.:Introduction and Motivation Aims Background Refractive development in infants and children Eye-growth and axial length Methods Study population Measurements Statistical analysis Cumulative part Refractive status in a German paediatric cohort: A cross-sectional analysis of the LIFE Child data Reference curves for refraction in a German cohort of healthy children and adolescents Longitudinal analysis of axial length growth in a German cohort of healthy children and adolescents Zusammenfassung der Arbeit Summary Conclusion Prospect References Appendix Einreichungserklärung Declaration Wissenschaftliche Beiträge zu den Publikationen Acknowledgments

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20278号 / 医博第4237号 / 新制||医||1021(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 森田 智視, 教授 佐藤 俊哉, 教授 中山 健夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The main experimental work of this thesis has been a cross-sectional study of the prevalence of refractive error and its biometric correlates in Middle Eastern adults. In addition dynamic accommodative responses and twenty-four hour axial length fluctuations were investigated in young myopic adults. The prevalence of myopia in 3000 Middle Eastern adults (age range 17-40 years) was similar to previously reported levels of myopia in the West. Myopia was associated with a higher level of education, occupations with a high nearwork demand and positive family history of myopia; all of which have been identified as risk factors for myopia development and progression Diurnal variations in axial length (AL) of similar magnitude to those previously reported in emmetropes were observed in myopes recruited in the current thesis. However, the pattern of the diurnal variation in AL was significantly different between early-onset myopes (EOMs) and late-onset myopes (LOMs). There were no significant differences between EOMs and LOMs in the dynamic accommodative response to a sinusoidally oscillating target. The accommodative phase lag was increased following 30 minute adaptation to myopic defocus using +2.00 D lens. However, intense prolonged (30 minute) nearwork was found to have no effect on accommodative gain or phase lag. A number of recommendations for further work on the prevalence of refractive error in the Middle East are suggested along with further research on diurnal AL variations and dynamic accommodative responses in EOMs and LOMs.

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Yes / Appeals have been made for eye care professionals to start prescribing anti-myopia therapies as part of their routine management of myopic children. 1–3 These calls are fuelled by two key considerations. Firstly, that interventions to slow myopia progression have shown success in randomized controlled trials (RCTs) 4–7, and secondly, appreciation that the risk of sight-threatening complications rises dose-dependently with the level of myopia. 8,9 Notwithstanding existing gaps in knowledge regarding the efficacy of current treatments (see below), these considerations argue that myopia control interventions should be widely adopted, and that they should be instigated at an early age – especially in children most at risk – in order to reduce the final level of myopia. Therefore in managing a child with myopia, an eye care professional would have to decide not only which therapy to recommend, but at what age to start treatment. In this review we discuss the future role of genetic prediction in helping clinicians treat myopia. / NIHR Senior Research Fellowship. Grant Number: SRF‐2015‐08‐005

Yes / Background A recent Genome-wide association meta-analysis (GWAS) of refractive error reported shared genetics with anthropometric traits such as height, BMI and obesity. To explore a potential relationship with refractive error and ocular structure we performed a life-course analysis including both maternal and child characteristics using data from the Avon Longitudinal Study of Parents and Children cohort. Methods Measures collected across the life-course were analysed to explore the association of height, weight, and BMI with refractive error and ocular biometric measures at age 15 years from 1613children. The outcome measures were the mean spherical equivalent (MSE) of refractive error (dioptres), axial length (AXL; mm), and radius of corneal curvature (RCC; mm). Potential confounding variables; maternal age at conception, maternal education level, parental socio-economic status, gestational age, breast-feeding, and gender were adjusted for within each multi-variable model. Results Maternal height was positively associated with teenage AXL (0.010 mm; 95% CI: 0.003, 0.017) and RCC (0.005 mm; 95% CI: 0.003, 0.007), increased maternal weight was positively associated with AXL (0.004 mm; 95% CI: 0.0001, 0.008). Birth length was associated with an increase in teenage AXL (0.067 mm; 95% CI: 0.032, 0.10) and flatter RCC (0.023 mm; 95% CI: 0.013, 0.034) and increasing birth weight was associated with flatter RCC (0.005 mm; 95% CI: 0.0003, 0.009). An increase in teenage height was associated with a lower MSE (− 0.007 D; 95% CI: − 0.013, − 0.001), an increase in AXL (0.021 mm; 95% CI: 0.015, 0.028) and flatter RCC (0.008 mm; 95% CI: 0.006, 0.010). Weight at 15 years was associated with an increase in AXL (0.005 mm; 95% CI: 0.001, 0.009). Conclusions At each life stage (pre-natal, birth, and teenage) height and weight, but not BMI, demonstrate an association with AXL and RCC measured at age 15 years. However, the negative association between refractive error and an increase in height was only present at the teenage life stage. Further research into the growth pattern of ocular structures and the development of refractive error over the life-course is required, particularly at the time of puberty.

No / Orthokeratology (ortho-k) is the process of deliberately reshaping the anterior cornea by utilising specialty contact lenses to temporarily and reversibly reduce refractive error after lens removal. Modern ortho-k utilises reverse geometry lens designs, made with highly oxygen permeable rigid materials, worn overnight to reshape the anterior cornea and provide temporary correction of refractive error. More recently, ortho-k has been extensively used to slow the progression of myopia in children. This report reviews the practice of ortho-k, including its history, mechanisms of refractive and ocular changes, current use in the correction of myopia, astigmatism, hyperopia, and presbyopia, and standard of care. Suitable candidates for ortho-k are described, along with the fitting process, factors impacting success, and the potential options for using newer lens designs. Ocular changes associated with ortho-k, such as alterations in corneal thickness, development of microcysts, pigmented arcs, and fibrillary lines are reviewed. The safety of ortho-k is extensively reviewed, along with an overview of non-compliant behaviours and appropriate disinfection regimens. Finally, the role of ortho-k in myopia management for children is discussed in terms of efficacy, safety, and potential mechanisms of myopia control, including the impact of factors such as initial fitting age, baseline refractive error, the role of peripheral defocus, higher order aberrations, pupil size, and treatment zone size. / The CLEAR initiative was facilitated by the BCLA, with financial support by way of Educational Grants for collaboration, publication and dissemination provided by Alcon and CooperVision.

Yes / Background: Soft contact lenses have been developed and licensed for reducing myopia progression. These lenses have different designs, such as extended depth of focus (EDOF) and dual focus (DF). In this prospective, doublemasked, cross-over study, different lens designs were investigated to see whether these had impact on accommodative microfluctuations and eye movements during reading. Methods: Participants were fitted with three lenses in a randomised order; a single vision (SV) design (Omafilcon A2; Proclear), a DF design (Omafilcon A2; MiSight), and an EDOF lens design (Etafilcon A; NaturalVue),. Accommodative microfluctuations were measured at 25 cm for at least 60s in each lens, using a Shin-Nippon SRW-5000 autorefractor adapted to continuously record accommodation at 22Hz. Eye movement data was collected with the Thomson Clinical Eye Tracker incorporating a Tobii Eye bar. Eye movements include fixations per row, fixations per minute, mean regressions per row, total number of regressions, and total rightward saccades. Accommodation data was analysed using power spectrum analysis. Differences between the lenses were compared using a related sample two-way Friedman test. Results: Twenty-three participants (18–29 years) were recruited to take part. The average mean spherical error was − 2.65D ± 1.42DS, with an average age of 23.4 ± 3.5 years. No significant difference for accommodative microfluctuations was found. Significant differences were found for fixations per row (P = 0.03), fixations per minute (P = 0.008), mean regressions per row (P = 0.002), and total number of regressions (P = 0.002), but not total rightward saccades (P = 0.10). Post-hoc analysis indicated the EDOF lens results were significantly different from the other lenses, with more regressive eye movements observed. Conclusions: Regressive saccades appear to increase when wearing EDOF lens designs, which may impact visual comfort. Further studies in children, over a longer period of adaptation are necessary to assess the potential impact of this finding on daily reading activities in children. / This project was supported by the British Contact Lens Association Summer Studentship Award (recipient Muskaan Hussain).

The main experimental work of this thesis has been a cross-sectional study of the prevalence of refractive error and its biometric correlates in Middle Eastern adults. In addition dynamic accommodative responses and twenty-four hour axial length fluctuations were investigated in young myopic adults. The prevalence of myopia in 3000 Middle Eastern adults (age range 17-40 years) was similar to previously reported levels of myopia in the West. Myopia was associated with a higher level of education, occupations with a high nearwork demand and positive family history of myopia; all of which have been identified as risk factors for myopia development and progression Diurnal variations in axial length (AL) of similar magnitude to those previously reported in emmetropes were observed in myopes recruited in the current thesis. However, the pattern of the diurnal variation in AL was significantly different between early-onset myopes (EOMs) and late-onset myopes (LOMs). There were no significant differences between EOMs and LOMs in the dynamic accommodative response to a sinusoidally oscillating target. The accommodative phase lag was increased following 30 minute adaptation to myopic defocus using +2.00 D lens. However, intense prolonged (30 minute) nearwork was found to have no effect on accommodative gain or phase lag. A number of recommendations for further work on the prevalence of refractive error in the Middle East are suggested along with further research on diurnal AL variations and dynamic accommodative responses in EOMs and LOMs.