- •Contents
- •Foreword
- •Dedication
- •Message
- •About the Editors
- •List of Contributors
- •Acknowledgments
- •Introduction
- •Methodologic Issues
- •Review of Studies (Table 1)
- •Cohort Effects on Myopia
- •Risk Factors for Myopia
- •Near work
- •Education/Income
- •Outdoor activity
- •Race/Ethnicity
- •Nuclear cataract
- •Family aggregation/Genetics
- •Siblings
- •Parent-child
- •Other family members
- •Genetics
- •Comments
- •Acknowledgments
- •References
- •Introduction
- •Definition of Myopia in Epidemiologic Studies
- •Risk Factors for Myopia and Ocular Biometry
- •Family history of myopia
- •Near work
- •Outdoor activity
- •Stature
- •Birth parameters
- •Smoking history
- •Breastfeeding
- •Conclusion
- •References
- •Introduction
- •Aetiological Heterogeneity of Myopia
- •Clearly genetic forms of myopia
- •School or acquired myopia
- •Misunderstandings of Heritability and Twin Studies
- •But Heritability has Its Uses
- •Evidence for Genetic Associations of School Myopia
- •Evidence for the Impact of Environmental Factors on Myopia Phenotypes
- •Gene-Environment Interactions and Ethnicity
- •Gene-Environment Interactions and Parental Myopia
- •Conclusion
- •Acknowledgments
- •References
- •Introduction
- •Economic evaluations
- •Full vs partial evaluations
- •Economic evaluation of myopia
- •The Economic Cost of Myopia: A Burden-of-Disease Study
- •China
- •India
- •Europe
- •Singapore
- •Southeast Asia
- •Africa
- •South America
- •Bangladesh
- •ii. Proportion of myopes paying for correction
- •Uncorrected and undercorrected refractive error, spectacle coverage rate and reasons for spectacles nonwear
- •iii. Amount paid for myopic correction
- •Singapore
- •The burden of myopia
- •Further Directions for Economic Research
- •References
- •Introduction
- •Impact of Myopia in Adults
- •Overall Conclusion
- •Future Studies
- •References
- •Introduction
- •Definition of Pathological Myopia
- •Cataract
- •Glaucoma
- •Myopic Maculopathy
- •Myopic Retinopathy
- •Retinal Detachment
- •Optic Disc Abnormalities
- •References
- •Conclusion
- •Introduction
- •The Association Between Myopia and POAG
- •Information from epidemiological studies
- •Asian populations: Myopia and POAG
- •Myopia in other situations
- •Myopia and ocular hypertension
- •Myopia in angle closure
- •Myopia in Pigment Dispersion Syndrome (PDS)
- •Theories for a Link Between Myopia and POAG
- •Glaucoma Assessment in Myopic Eyes
- •Biometric differences
- •Axial length and CCT
- •Optic disc assessment in myopic eyes
- •Visual fields in myopic eyes
- •Imaging tests and variations with myopia
- •ONH susceptibility to damage
- •The Influence of Myopia on the Clinical Management of the Glaucoma Patient
- •Glaucoma progression and myopia
- •References
- •Posterior Staphyloma
- •Myopic Chorioretinal Atrophy
- •Lacquer Cracks
- •Myopic Choroidal Neovascularization
- •Myopic Foveoschisis
- •Myopic macular hole detachments
- •Lattice degeneration
- •Retinal tears and detachments
- •References
- •Introduction
- •Electroretinography
- •Ganzfeld electroretinography
- •Multifocal electroretinography
- •Assessment of Retinal Function
- •Outer retinal (photoreceptor) function
- •Post-receptoral (bipolar cell) and retinal transmission function
- •Inner retinal function
- •Macular function in myopic retina
- •Effect of Long-Term Atropine Usage on Retinal Function
- •Macular Function Associates with Myopia Progression
- •Factors Associated with ERG Changes in Myopia
- •Conclusion
- •References
- •Introduction
- •Genomic Convergence Using Genomic Content
- •Pathway Analysis
- •Pathway analysis in cancer genomics
- •Pathway analysis in GWAS
- •Non-parametric approaches
- •Parametric approaches
- •P-values combining approaches
- •Conclusion
- •References
- •Introduction
- •Definition of Myopia
- •The Classical Twin Model
- •What is the classical twin model?
- •Historical perspective
- •Statistical approaches
- •Twins, Myopia and Heritability Studies
- •Heritability studies for myopia using twins
- •Limitations of using twins in heritability studies
- •Twins and Myopia — Other Studies
- •The Importance of Twin Registries
- •Concluding Comments
- •Acknowledgments
- •References
- •Introduction
- •Candidate Gene Selection Strategies for Myopia
- •Genes Associated With Myopia-Related Phenotypes
- •The HGF/cMET ligand-receptor axis
- •The collagen family of genes
- •Concluding Remarks
- •Acknowledgments
- •References
- •Introduction
- •Phenotypes for Myopia Genetic Studies
- •Study Design
- •Genotyping and Quality Controls
- •Population Structure
- •Association Tests
- •Correlated Phenotypes
- •Imputation and Meta-Analysis
- •Visualization Tools
- •Drawing Conclusions
- •Acknowledgments
- •References
- •Introduction
- •The Search for Error Signals
- •The blur hypothesis
- •Bidirectional lens-compensation
- •Recovery from ametropia vs. compensation for lenses
- •The complication of the emmetropization end-point
- •Optical aberrations as error signals
- •Other possible visual error signals
- •How Important is Having a Fovea?
- •Mechanisms of Emmetropization
- •Scleral similarities and differences between humans and chickens
- •Retinal signals
- •Glucagon-insulin
- •Retinoic acid
- •Dopamine
- •Acetylcholine
- •Choroidal signals
- •The Role of the Choroid in the Control of Ocular Growth
- •Diurnal rhythms and control of ocular growth
- •Conclusions
- •References
- •Introduction
- •Gross Scleral Anatomy
- •Structural organization of the sclera
- •Cellular content of the sclera
- •Mechanical properties of the sclera
- •Structural Changes to the Sclera in Myopia
- •Development of structural and ultrastructural scleral changes in myopia
- •Scleral pathology and staphyloma
- •Biochemical Changes in the Sclera of Myopic Eyes
- •Structural biochemistry of the sclera in myopia
- •Degradative processes in the sclera of myopic eyes
- •Cellular changes in the sclera in myopia
- •Biomechanical Changes in the Sclera of Myopic Eyes
- •Regulators of scleral myofibroblast differentiation
- •Myofibroblast-extracellular matrix interactions
- •Cellular and matrix contributions to altered scleral biomechanics and myopia
- •Scleral Changes in Myopia are Reversible
- •Eye growth regulation during recovery from induced myopia
- •Summary and Conclusions
- •Acknowledgments
- •References
- •Introduction
- •Spatial Visual Performance and Optical Features of the Eye
- •Axial eye growth and development of refractive state
- •Lens thickness and vitreous chamber depth
- •Corneal radius of curvature
- •Schematic eye data
- •Techniques Currently Available for Myopia Studies in the Mouse, Both for Its Induction and Measurement
- •Devices to induce refractive errors
- •Techniques to measure the induced refractive errors and changes in eye growth
- •Refractive state
- •Corneal radius of curvature
- •Axial length measurements and ocular biometry
- •Measurements of the optical aberrations of the mouse eye
- •Behavioral measurement of grating acuity and contrast sensitivity in the mouse
- •Recent Studies on Myopia in the Mouse Model: Some Examples
- •Magnitudes of experimentally induced refractive errors in wild-type mice
- •Refractive development in mutant mice
- •Pharmacological studies to inhibit axial eye growth in mice
- •Image processing and regulation of retinal genes and proteins
- •Summary
- •Acknowledgments
- •References
- •Introduction
- •A Brief Introduction to Comparative Genomics
- •Comparative Expression
- •Genes in Retina and Sclera in Animal Models of Myopia
- •ZENK (EGR-1)
- •Scleral Gene Expression in a Mouse Model of Myopia
- •RNA, Target cDNA and Microarray Chip Preparation
- •Microarray Data Analysis
- •Scleral Gene Expression in the Myopic Mouse
- •Summary
- •References
- •Introduction
- •Possible Mechanisms of Pharmacological Treatment
- •Efficacy Studies
- •Other Issues Related to Drugs
- •Potential Side Effects
- •The Future of Drug Treatment in Myopia
- •Conclusions
- •References
- •Introduction
- •Accommodation
- •Close work
- •Physical characteristics of the retinal image
- •Visual deprivation
- •Compensatory changes in refraction
- •Intensity and periodicity of light exposure
- •Spatial frequency
- •Light periodicity
- •Image clarity
- •Outdoor activity and retinal image blur
- •Light vergence and photon catch
- •Chromaticity
- •Therapeutic implications
- •References
- •Index
154 C. D. Luu and A. W. L. Chia
a significant correlation between first-order kernel mfERG responses and refractive error. The findings showed that the amplitude of the mfERG decreased as the degree of myopia increased. The mfERG P1 amplitude is negatively correlated with the axial length. The mfERG P1 implicit time increased with an increase in axial length and severity of myopia.
Effect of Long-Term Atropine Usage on Retinal Function
To date, only atropine eye drops have been shown to have a consistent effect on the retardation of myopia progression.28,29 There are, however, at least two potential chronic side effects associated with the long-term use of atropine. Firstly, accumulation of atropine over a period of time might be toxic to the neural retina. Secondly, constant pupillary dilatation will increase the amount of light entering the eye and could theoretically cause photic damage to the retina.
Luu et al.30 recorded the mfERG responses in children (n = 48) receiving atropine eye drops once daily for two years, and in those receiving placebo eye drops (n = 57) for a similar duration. Their results showed that there was no significant difference in the mfERG response amplitudes and implicit times between the atropine treated and placebo control groups, suggesting that atropine use for two years has no significant effect on retinal function.
Macular Function Associates with Myopia Progression
Studies have examined the relationship between macular function changes and the rate of myopia progression. Chen et al.14 studied the multifocal oscillatory potential (mfOP) changes in emmetropes, stable myopes, and progressing myopes. They found that progressing myopes had significantly shorter mfOP implicit times compared to emmetropes and stable myopes. There were, however, no statistically significant differences in OP amplitudes between the groups.
Luu et al.31 examined the mfERG responses of 81 children (aged 9–10 years) with myopia (mean spherical equivalent refraction ranging from −1.00 D to −5.88 D), and they showed that the initial mfERG P1 amplitude within the central 5 degrees was significantly associated with the subsequent two-year myopia progression rate, but not with the initial degree of
155 Retinal Function
myopia. The mfERG P1 amplitude of the central ring was significantly reduced in a high progression group, defined as a progression rate of at
least 1 D per two years, compared to a medium progression group (progression rate of >0.25 D and <1 D per two years) or a low/no progression
group (progression rate of ≤0.25 D per two years). Responses from rings 2–5 (central 5 to 35 degrees retina) were similar for all the progression groups. No significant differences in mfERG response implicit times were found in any of the progression groups at any of the locations tested.
Factors Associated with ERG Changes in Myopia
Although the reduction in ERG response in adults with myopia has been well recognized, the actual mechanisms of ERG reduction in myopia are unclear.
It has been suggested that the reduction in ERG amplitudes seen in adults with myopia may be owing to a reduced image size and decreased retinal illumination, known as the optical factor, as a result of axial elongation of the eye.32 By examining the stimulus intensity response function, Kawabata and Adachi-Usami23 claimed that decreased retinal illuminance did not explain the reduced ERG response because the responses of the high-myopic eye had much lower saturated amplitudes than for the emmetropic eye.
It has been suggested that the ERG amplitudes are reduced in persons with myopia because of a higher resistance between the source of the current (the retina) and the place where the current is measured (the cornea). It is believed that increased distance between the electrical source and the recording corneal electrode, also referred to as the electrical factor, due to a larger eyeball, caused an increase in the ocular resistance to electric current.9,33
Decreased retinal photoreceptor density, morphological changes in the photoreceptor outer segment, and photoreceptor dysfunction have been postulated as the causes for ERG reduction in myopia.24,34 Altered neural processing could result, in part, from retinal stretching in the enlarged myopic eye, which may produce both increased retinal cell spacing and post-receptoral retinal dysfunction, and lead to a decrease in retinal sampling.34 Another mechanical attribute of the eye in axial myopia might be an increase in the subretinal space and subsequent reduction in photoreceptor response.34
156 C. D. Luu and A. W. L. Chia
Luu et al.25 examined the relationship between ERG amplitude and myopia in adults and children with various degrees of myopia. While their results confirm that there is a significant correlation between the refractive error and ERG amplitude in adults with myopia, they also discovered that such a relationship is absent in children with myopia. In light of the results obtained from this study, the optical and electrical factors are unlikely to be the cause of the ERG reduction because of the absence of any relationship between ERG amplitudes and the severity of myopia in children. Similarly, with photoreceptor morphological and functional changes in myopic eyes, a good correlation between ERG amplitude reduction and severity of myopia would be expected irrespective of the subject’s age. These data provide strong evidence that the reduction of ERG response seen in adults with myopia is not directly due to the severity of myopia. The lack of correlation between ERG amplitude and the degree of myopia in children suggest that other mechanisms must be responsible for the reduction in ERG. It is postulated that the reduction in ERG response seen in the adult group may be owing to retinal function modifications that are associated with long-standing myopia.
Conclusion
There are demonstrable changes in retinal function in subjects with myopia. In studies involving Ganzfield electroretinography, there is a progressive reduction in both a-wave (photoreceptor) and b-wave (bipolar cell) responses in adult subjects with increasing myopia, and reduction in b-/a-wave amplitude ratio in those with very high myopia. Similar reduction in P1 responses of the mfERG were seen in the macular regions. The exact nature of ERG reduction in myopia remains unknown. Gradual changes do occur in myopic fundi over time with the development of posterior staphyloma, peripalliary atrophy, and myopic macular degeneration, and there may be clinically significant visual loss in some individuals.
Future directions include a better understanding on what, when, and where functional changes occur within the myopic retina over time. Of interest is also whether these changes precede or even induce anatomical changes and whether they can be used to identify individuals at greatest risk of developing high myopia. Electroretinography can also be used to
157 Retinal Function
monitor the safety and efficacy of new drug therapies for myopia as they become available in the future.
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Section 3
Genetics of Myopia
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