Refractive Development: Main Parts

1. Refractive Development: Main Parts • Prevalence of refractive errors and changes with age. • Factors affecting refractive development. • Operational properties of the vision-dependent mechanisms that mediate emmetropization. • How visual signals are transformed into biochemical signals for eye growth.

2. Distribution of Refractive Errors (young adult population) • Major differences from random distribution: • - more emmetropes than predicted • - fewer moderate errors (e.g., -2.0 D) • more high errors (e.g., -6.0 D) • i.e., the function is leptokurtotic. theoretical Gaussian distribution from Sorsby, 1957

3. Newborns frequently have large optical errors, however, these errors usually disappear. Age 4-6 yrs (Kempf et al) Newborns (Cook & Glasscock) Ideal Optical Conditions

4. Changes in Refractive Error with Age Average data are not very predictive of changes on an individual basis before about 20 years. Thereafter, most people experience the same trends. more typical

5. Myopia in Premature Infants Ametropia (D) Born before 32 weeks &/or birth weights < 1500 g; no ROP Age (weeks) Myopia associated with short axial lengths & steep corneas. Recovery primarily due to corneal flattening.

6. Emmetropization is the process that guides ocular growth toward the optimal optical state. It occurs very rapidly; most infants develop the ideal refractive error by 12-18 months.

7. During the period of rapid emmetropization, the degree of anisometropia typically decreases (i.e., “isometropization” occurs).

8. “Isometropization” Anisometropia is frequently transient during early development.

9. Rapid Infantile phase (0-3 yrs) -- axial length increases about 5-6 mm. Slower Juvenile phase (3-14 yrs) -- axial length increases about 1 mm.

10. Major Optical Changes: 1) flatter cornea (6-8 D) 2) deeper AC (0.8D) 3) flatter lens (12-15 D)

11. Anterior Chamber Depth Birth AC depth increases from about 2.4 mm at birth to about 3.5 mm at 3 years (about 0.8 D).

12. Major Optical Changes: 1) flatter cornea (6-8 D) 2) deeper AC (0.8D) 3) flatter lens (12-15 D)

13. Zadnik et al., 1993 Changes with Age Early School Years Age (yrs) From about 2 to 7-8 years, the mean refractive error is quite stable & the degree of variability is low.

14. Refractive Development: Early School Years Refractive Error Cornea Zadnik et al., 1993 Axial Length Lens During early adolescence, the cornea is relatively stable. The slow decrease in lens power is counterbalanced by an increase in axial length.

15. Refractive Development: Early School Years Anterior Chamber Depth Wong et al., 2010

16. Refractive Development: Early School Years Lens Thickness Wong et al., 2010

17. Refractive Development: Early School Years Anterior Segment Larsen, 1971

18. The decrease in mean refractive error between about 8 and 20 years is due primarily to the onset of “school” myopia in a small proportion of the population.

19. Myopic Progression “Youth-Onset” or “Juvenile-Onset”, or “School” Myopia Males For many individuals, myopic progression stops in late teenage years…associated with the normal cessation of axial growth. Females

20. Annual Rate of Myopic Progression Rate varies considerably between individuals. Average = -0.40 to -0.6 D/yr (before age 15 yrs)

21. Age of Onset vs. Degree of Myopia From Goss, 1998 The earlier the onset of myopia…the higher the rate of progression and the final degree of myopia.

22. Axial Nature of Myopia The rate of myopic progression is highly correlated with the rate of axial elongation. From Goss, 1998

23. Predictability of Refractive Errors at Age 13-14 Years Refractive Error Distributions for Children at 5-6 years who develop: Myopia >0.50 D Emmetropia -0.49 to +0.99 D Hyperopia >1.0 D From Hirsch, 1964

24. Classifications of Myopia Grosvenor, 1987 Congenital = present at birth & persists through infancy. Youth-onset = occurs between 6 years and early teens. Early adult-onset = occurs between 20 & 40 years Late adult-onset = occurs after 40 years

25. Early Adult Onset Myopia Adult Onset Adult Progression McBrien & Adams, 1997 Examples of adult onset myopia associated with a change in occupation.

26. Early Adult Onset Myopia Change in refractive error for myopic subjects following onset of microscopy career. 48% of myopes showed myopic changes >0.37 D (i.e., myopic progression). Median age = 29.7 years McBrien & Adams, 1997

27. Adult Onset Myopia Vitale et al 2009 30% of myopesbecome myopic after 17 yrs 44.8 44.0 42.9 38.1 33.9 27.7 24.5 24.8 24.2 24.0

28. Changes in Refractive Error with Age Acquired hyperopia due to: 1) presbyopia 2) lens continues to flatten 3) refractive index of lens cortex increases more typical

29. Lens Development- Mass The crystalline lens continues to grow throughout life. Weale, 1982

30. Acquired Hyperopia Vitreous Chamber Young adult (22 yrs) = 16.14 mm Mature adult (54 yrs) = 15.7 mm Ooi & Grosvenor, 1995

31. Changes in Refractive Error with Age Decrease in hyperopia due to increase in refractive index of core of crystalline lens. more typical

32. Astigmatism is the most common ametropia. The magnitude is, however, usually relatively small.

33. Astigmatism Axis vs Spherical AmetropiaYoung Adult Population Mandel et al., 2010

34. Prevalence of Astigmatism: Infants Marked levels of astigmatism are common in young infants -- due primarily to corneal toricity. Atkinson et al. 1980

35. Prevalence of Astigmatism (>1 D) in Human Infants

36. Longitudinal Changes in Astigmatism Almost every infant shows a decrease in astigmatism during early infancy. Early astigmatism may not be very predictive of astigmatism later in life. Atkinson et al. 1980

37. Axis of Astigmatism Right eye astigmatism at 9 months of age (n = 143, Cambridge, UK). W-t-R astigmatism predominates. from Ehrlich et al., 1997

38. Change in Axis of Astigmatism With age the prevalence of W-t-R decreases & there is a concomitant increase in A-t-R. Most of the changes occur after about 35 years of age and occur at a rate of about 0.25 D every 10 years. A-t-R W-t-R oblique age in decades Bennett & Rabbetts, 1989

39. Change in Corneal Power & Astigmatism After age 35 years, the cornea gets progressively steeper. The reduction in the radius of curvature is greater for the horizontal meridian. Bennett & Rabbetts, 1989

40. My Eyelash About 200 microns

41. Distribution of Refractive Errors (young adult population) Major differences from random distribution: - more emmetropes than predicted - fewer moderate errors (e.g., -2.0 D) - more high refractive errors (e.g., -6.0 D) theoretical Gaussian distribution from Sorsby, 1957

42. Frequency Distributions for Individual Ocular Components Since the distribution of refractive errors is leptokurtic, there can not be free association between individual components. Highest correlation is typically found between refractive error and axial length. from Sorsby, 1978

43. Nature of Refractive Errors emmetropes ametropes Not all emmetropic eyes are alike. Ks = 39.0 – 47.6 D Lens = 15.5 – 23.9 D AC = 2.5 – 4.2 mm AL = 22.3 – 26.0 mm Ametropic eyes between -4 D and +6 D frequently have individual ocular components that fall within the range for emmetropic populations. With larger ametropias, one component, typically axial length, falls outside the range for emmetropia. from Sorsby, 1978

44. Genetic Factors ethnic differences in the prevalence of refractive errors familial inheritance patterns monozygotic twins candidate genes Environmental Factors humans: epidemiological studies of prevalence of myopia lab animals: restricted environments lab animals: altered retinal imagery Factors that influence refractive state

45. Prevalence of Myopia in Different Ethnic Groups

46. Familial Inheritance Patterns If both parents are myopic, the child is 4-5 times more likely to be myopic than if neither of the child’s parents are myopic.

47. Monozygotic Twins Dizygotic Twins r = 0.82 r = 0.36 Twin 2 Ametropia (D) Twin 1 Ametropia (D) Twin 1 Ametropia (D) Intrapair Correlations for Refractive Error Monozygotic vs Dizygotic Twins (Dirani et al., 2006)

48. Dr. Y. Chino Monozygotic Twins Evil twin? Good twin? Identical twins have very similar refractive errors.

49. Not only do twins have identical refractive errors, their eyes have very similar dimensions. Concordance limits: Axial length = 0.5 mm corneal & lens power = 0.5 D AC depth = 0.1 mm lens thickness = 0.1 mm total power = 0.9 D

50. Myopia and Genetics (peer-reviewed publications per year)