refractive development: main partsvoi.opt.uh.edu/voi/emmetropization 1 2007.pdf · during early...
TRANSCRIPT
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Refractive Development: Main Parts
• Prevalence of refractive errors and changes with age.
• Factors affecting refractive development.• Mechanisms that mediate vision-
dependent emmetropization.• How does visual experience influence
refractive development in humans?
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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.
from Sorsby, 1957
theoreticalGaussian
distribution
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Ametropia (D)-10 -8 -6 -4 -2 0 2 4 6 8
Per
cent
age
of S
ampl
e
0
10
20
30Class of 2009SORSBY
92% myopic
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-8 -6 -4 -2 0 2 4 6 8 10 12
Freq
uenc
y (%
)
0
10
20
30
40
Nearsighted Farsighted
Newborns(Cook & Glasscock)
Age 4-6 yrs(Kempf et al)
Newborns frequently have large optical errors, however, these errors usually disappear.
Ideal Optical Conditions
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Changes in Refractive Error with Age
Age Norms of Refraction(Slataper, 1950)
Age (years)
0 10 20 30 40 50 60 70 80 90
Ref
ract
ive
Erro
r (D
)
0
1
2
3
4
more typical
Average data are not very predictive of changes on an individual basis before about 20
years. Thereafter, most people
experience the same trends.
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Myopia in Premature Infants
Age (weeks)
Am
etro
pia
(D)
Born before 32 weeks &/or birth weights < 1500 g; no ROP
Myopia associated with short axial lengths & steep corneas. Recovery primarily due to corneal flattening.
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Age (days)
0 200 400 600
Mea
n A
met
ropi
a (D
)
0
1
2
3
4
Edwards, 1991Wood et al., 1995Thompson (1987) from SaundersSaunders, 1995Gwiazda et al, 1993Atkinson et al., 1996
Human Infants
Emmetropization occurs very rapidly.
Most infants develop the ideal refractive error by
12-18 months.
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Emmetropization - Rate of Change in Humans
From Saunders et al. 1995
Infants with large initial refractive errors show faster changes.
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Age (days)0 20 40 60 80 100 120
Am
etro
pia
(D)
0
5
10
25
Tree Shrew (Norton & McBrien)Chick (Wallman & Adams)Rhesus Monkey (Bradley et al.)Marmoset (Graham & Judge)Chick (Li et al.)Rhesus Monkey (Smith et al.)
Emmetropization is qualitatively similar in many species.
Not corrected for potentialretinoscopy artifacts.
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Age (years)0 1 2 3 4 5
95%
con
fiden
ce li
mits
(D)
0.0
0.2
0.4
0.6
0.8
1.0
cylindersspheres
n = 360Normal Infants
Net Anisometropia
Howland & Sayles (1987) During the period of rapid emmetropization,
the degree of anisometropia typically
decreases (i.e., “isometropization”
occurs).
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Age (years)0 1 2 3 4
Num
ber o
f Pat
ient
s
0
10
20
30
40
>1.0 Dnew casesloss of aniso
Prevalence of Anisometropia(Abrahamsson et al., 1990)
n=310Normal Infants
“Isometropization”
Anisometropia is frequently
transient during early
development.
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Axial Length Development
Age (years)0 1 2 3
Axi
al L
engt
h (m
m)
14
16
18
20
22
Gordon & Donzis Larsen, malesLaren, femalesZadnik et alFledelius
Axial Length Development
Age (years)0 5 10 15 20 25 30
Axi
al L
engt
h (m
m)
14
16
18
20
22
24
Gordon & Donzis Larsen, malesLaren, femalesZadnik et alFledelius
Rapid Infantile phase (0-3 yrs) -- axial length increases about 5-6 mm.Slower Juvenile phase (3-14 yrs) -- axial length increase about 1 mm.
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Corneal Development
Age (years)0 1 2 3
Cor
neal
Pow
er (D
)
42
44
46
48
50
52
54
56
Gordon & DonzisWoodriftZadnik et al.
Corneal Development
Age (years)0 5 10 15 20 25 30
Cor
neal
Pow
er (D
)
42
44
46
48
50
52
54
56
Gordon & DonzisWoodriftZadnik et al.
Increase in AL counterbalanced by:
1) flatter cornea (6-8 D)2) deeper AC (0.8D)3) flatter lens (12-15 D)
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Corneal Development - Horizontal Diameter
Birth
Weale, 1982
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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).
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Lens Development
Age (years)0 1 2 3
Lens
Pow
er (D
)
20
25
30
35
40
45
Gordon & DonzisZadnik et al.
Lens Development
Age (years)0 5 10 15 20 25 30
Lens
Pow
er (D
)
15
20
25
30
35
40
45
Gordon & DonzisZadnik et al.
Increase in AL counterbalanced by:
1) flatter cornea (6-8 D)2) deeper AC (0.8D)3) flatter lens (12-15 D)
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Age Norms of Refraction(Slataper, 1950)
Age (years)
0 10 20 30 40 50 60 70 80 90
Ref
ract
ive
Erro
r (D
)
0
1
2
3
4
4 6 8 10 12 14
Am
etro
pia
(D)
-1
0
1
2
Age (yrs)
From about 2 to 7-8 years, the mean refractive error is quite stable & the
degree of variability is low.
Zadnik et al., 1993
Changes with Age
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4 6 8 10 12 14
Cor
neal
Pow
er (D
)
41
42
43
44
45
46
47
4 6 8 10 12 14
Am
etro
pia
(D)
-1
0
1
2
Age (years)
4 6 8 10 12 14
Axi
al L
engt
h (m
m)
21
22
23
24
25
Age (years)
4 6 8 10 12 14
Lens
Pow
er (D
)
18
19
20
21
22
23
24
Refractive Development: Early School YearsRefractive Error
LensAxial Length
Cornea
Zadnik et al., 1993
During early adolescence, the cornea is relatively stable. The slow increases in axial length are counterbalanced by a decrease in lens power.
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Refractive Development: Early School YearsAnterior Segment
Larsen, 1971
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Age in Years0 10 20 30 40
Myo
pia
(per
cent
)
0
5
10
15
20
25
30
35
Jackson, 1932
Tassman, 1932
Prevalence of Myopia in HumansSchool Years
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.
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Males
Females
Myopic Progression
“Youth-Onset” or “Juvenile-Onset”, or
“School” Myopia
For many individuals, myopic progression stops in late teenage
years…associated with the normal cessation of
axial growth.
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Myopic Progression (D/year)-1.6 -1.4 -1.2 -1.0 -0.8 -0.6 -0.4 -0.2 0.0 0.2 0.4
Pro
porti
on o
f Sam
ple
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
MalesFemales
Annual Rate of Myopic Progression
Rate varies considerably between individuals. Average =
-0.40 to -0.6 D/yr(before age 15 yrs)
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Age of Onset vs. Degree of Myopia
From Goss, 1998
The earlier the onset of myopia…the higher rate of progression and the final degree of myopia.
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The rate of myopic progression is highly correlated with the
rate of axial elongation.
Axial Nature of Myopia
From Goss, 1998
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Ametropia (D)-0.5 0.0 0.5 1.0 >1.5
0.0
0.2
0.4
-0.5 0.0 0.5 1.0 >1.5Pro
porti
on o
f Sam
ple
0.0
0.2
0.4
-0.5 0.0 0.5 1.0 >1.50.0
0.2
0.4 Predictability of Refractive Errors at Age 13-14 Years
From Hirsch, 1964
Children with Refractive Errors at 5-6 yearsMyopia >0.50 D
Emmetropia -0.49 to +0.99 D
Hyperopia >1.0 D
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Classification 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 yearsLate adult-onset = occurs after 40 years
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Early Adult Onset Myopia
McBrien & Adams, 1997
Examples of adult onset myopia associated with a change in occupation.
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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
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Adult Onset Myopic Progression
Age (years)20-25 25-30 30-35 35-40 40-45
Pro
porti
on P
rogr
essi
ng (%
)
0
10
20
30
40
50
60
Progression = >0.75 D over 5 years
Population of contact lens wearers.
Bullimore, 1998
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Changes in Refractive Error with Age
Age Norms of Refraction(Slataper, 1950)
Age (years)
0 10 20 30 40 50 60 70 80 90
Ref
ract
ive
Erro
r (D
)
0
1
2
3
4
more typical
Acquired hyperopia due to:
1) presbyopia2) lens continues to flatten3) refractive index of lens
cortex increases
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Age (years)43-54 yrs 55-64 yrs 65-74 yrs >75 yrs
Freq
uenc
y (%
)
0
20
40
60
80
% myopic% hyperopic
Age and Refractive Error
Wang, 1994 (Beaver Dam Eye Study)
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Lens Development - Mass
The crystalline lens continues to grow
throughout life.
Weale, 1982
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Acquired Hyperopia
Vitreous Chamberyoung adult (22 yrs) = 16.14 mmMature adult (54 yrs) = 15.7 mm
Ooi & Grosvenor, 1995
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Changes in Refractive Error with Age
Age Norms of Refraction(Slataper, 1950)
Age (years)
0 10 20 30 40 50 60 70 80 90
Ref
ract
ive
Erro
r (D
)
0
1
2
3
4
more typical
Decrease in hyperopiadue to increase in
refractive index of core of crystalline lens.
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Prevalence of Astigmatism(young adult population)
Amount of Astigmatism (D)0.0 0.5 1.0 1.5 >2
Per
cent
age
of P
opul
atio
n
0
10
20
30
40
50
Astigmatism is the most common
ametropia. The magnitude is,
however, usually relatively small.
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Prevalence of Astigmatism: Infants
Marked levels of astigmatism are
common in young infants -- due
primarily to corneal toricity.
Atkinson et al. 1980
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Age (weeks)0 10 20 30 40 50
Pre
vale
nce
(%)
0
20
40
60
80
100
Santonastaso, 1930Howland et al., 1978Mohindra et al., 1978Atkinson et al., 1980Fulton et al., 1980Gwiazda et al., 1984Edwards, 1991Saunders, 1995
.Prevalence of Astigmatism (>1 D)in Human Infants
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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
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Axis of Astigmatism
Neonates show a high prevalence of A-t-R astigmatism.
There is a suggestion that the
direction of axis varies with ethnicity.
Dobson et al. 1984
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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
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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.
age in decades
A-t-R
oblique
W-t-R
Bennett & Rabbetts, 1989
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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
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My Eyelash
About 200 microns
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Distribution of Refractive Errors(young adult population)
from Sorsby, 1957
theoreticalGaussian
distribution
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)
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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
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Nature of Refractive Errorsemmetropes ametropes Not all emmetropic eyes
are alike.Ks = 39.0 – 47.6 D
Lens = 15.5 – 23.9 DAC = 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
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Factors that influence refractive state
• 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
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Ethnic CategorySwedish British Israeli Malay Indian Eurasian Chinese
Pre
vale
nce
of M
yopi
a (%
)
0
10
20
30
40
50
60
Prevalence of Myopia in Different Ethnic Groups
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Myopic Parents
None One Both
Per
cent
Chi
ldre
n M
yopi
c
0
5
10
15from Zadnik, 1995 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.
Familial Inheritance Patterns
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Twin A: Refractive Error (D)-4 -2 0 2 4 6 8
Twin
B: R
efra
ctiv
e E
rror
(D)
-4
-2
0
2
4
6
8
(Sorsby et al., 1962)
Identical twins have very similar refractive errors.
Evil twin? Good twin?
Dr. Y. ChinoMonozygotic Twins
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Concordance of Optical Components
Number of Individual Components1 2 3 4 5 6
Pro
cent
age
of S
ampl
e
0
20
40
60
80
100 other pairsuniovular twins
(from Sorsby et al., 1962)
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 DAC depth = 0.1 mm
lens thickness = 0.1 mmtotal power = 0.9 D
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Candidate Genes• X-linked recessive form (associated with cone dysfunction)
– MYP1 (1990)
• AD severe high-grade myopia– MYP2 (18p11.31) (1998)– MYP3 (12q23.1-q24) (1998)– MYP5 (17q21-q23) (2003)– MYP4 (chromosome 7 at q36) (2002)– MYP6 (chromosome 22 at q12) (2004)
• Common myopia– Chromosome 11 at p13 in the PAX6 gene region (2004)
• Myopia is a disorder characterized by genetic heterogeneity.
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Occupation
1 2 3 4 5 6
Nea
rsig
hted
(per
cent
)
0
5
10
15
20
25
30
35
Heavy Near Work Little Near Work
University Students
Farmers and Seamen
TailorsSkilled workmen (butchers)
ClerksCultured people (actors & musicians)
Tscherning, 1882(Duke-Elder, 1970)
Myopia has historically been associated with nearwork.
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Age in Years0 10 20 30 40
Nea
rsig
hted
(per
cent
)
0
5
10
15
20
25
30
35
The prevalence of myopia is synchronized with the onset of formal schooling.
School Years (Jackson, 1932; Tassman, 1932)
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Significant Associations in MyopiaMyopia & Intelligence
IQ Score<80 81-96 97-103 104-111 112-127 >127
Pro
porti
on o
f Myo
pes
(%)
0
5
10
15
20
25
30
Myopia & Education
Years of Education<8 9 10 11 >12
0
5
10
15
20
25
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Age (years)6 8 10 12 14 16 18 20
Pre
vale
nce
Rat
e (%
)
0
20
40
60
80
100
1995
1986
Taiwanese School Children
Prevalence of Myopia
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Restricted environments promote myopia.
Monkeys in Restricted Environment
Time in Restricted Environment (weeks)0 10 20 30 40 50
Ref
ract
ive
Erro
r (D
)
-1.4
-1.2
-1.0
-0.8
-0.6
-0.4
-0.2(from Young, 1963)
Mean (n=12)
Mean (n=18)
Adolescent Monkeys: 4-6 years of age Monkeys reared in restricted visual
environments develop myopia. Avoids many
of the confounding variables in human
studies -- in particular self selection.
Attributed to excessive accommodation.
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Form Deprivation MyopiaMonocularly lid-sutured
Monkey
Sherman et al., 1977
Monocularly lid-sutured Tree Shrews
Interocular Differences in Refractive Error Monocularly Form-deprived Monkeys
0 10 20 30 40 50
Ani
som
etro
pia
(D)
(dep
rived
eye
- co
ntro
l eye
)
-16
-12
-8
-4
0
4
Dep
rived
eye
m
ore
myo
pic
n=53normal eye
Ani
som
etro
pia
(D)
(dep
rived
eye
–co
ntro
l eye
)
Individual Subjects
FDM is a consistent, robust, phenomenon. The 2 eyes are
largely independent.
Wiesel & Raviola, 1977
deprived eye
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Lagomorpha
Carnivora
Rodentia
New World
Old World
Tree Shrews
Marsupialia
Vertebrata
Aves
Terrestrial vertebrates
Placental mammals
Human
FDM occurs in a wide variety of animals.
Primates
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Form-deprivation Myopia
Ametropia (D)-15 -10 -5 0 5 10
0
10
20
30
40
50
60
70"deprived humans"Normal humans
Rabin et al. (1981)
Ametropia (D)-15 -10 -5 0 5 10
Per
cent
age
of C
ases
0
10
20
30
40
50
60
70
Normal MonkeysDeprived Monkey Eyes
Raviola and Wiesel, 1990von Noorden and Crawford, 1978Smith et al., 1987
Monkeys Humans
FDM occurs in a wide variety of animals -- including humans--which suggests that the mechanisms responsible for FDM are
probably fundamental to ocular development. The potential for a clear retinal image is essential for normal emmetropization.
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Vision Through Diffusers
As good as it gets
Weakest diffuser
Intermediate diffuser
Strongest diffuser
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Monocular Form Deprivation
0 50 100 150
Am
etro
pia
(D)
-8
-4
0
4
Age (days)0 50 100 150
-8
-4
0
4
0 50 100 150
-8
-4
0
4Monkey PE
Monkey CH Monkey JStreatment period
Weakest DiffuserWeakest Diffuser Intermediate DiffuserIntermediate Diffuser Strongest DiffuserStrongest Diffuser
The greater the degree of image degradation -- the greater the axial myopia.
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Recovery from Form-Deprivation Myopia
-4
-2
0
-4
-2
0
Normal MonkeysTreatment PeriodRecovery PeriodEnd of Treatment
-4
-2
0
Age (days)0 200 400 600
-4
-2
0
-9
-6
-3
0
-9
-6
-3
0
Ani
som
etro
pia
(D)
(Tre
ated
Eye
- C
ontro
l Eye
)
-9
-6
-3
0
Age (days)0 200 400 600
-9
-6
-3
0
Recovery from myopia only occurs early in life when the cornea and
lens are normally decreasing in power.
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0 100 200 300
Am
etro
pia
(D)
-2
0
2
4
6
8
10Monkey LIS Deprived Eye
End of TreatmentNon-Treated Eye
Age (days)0 100 200 300
Vitr
eous
Cha
mbe
r (m
m)
8
9
10
11treatment period
0 100 200 300 400 500
Age (days)
-0.01
0.00
0.01
0.02
mm
/day Vitreous Chamber Depth Growth Rate
Deprived Eye
Non-Deprived Eye Normal Controls
Recovery from Form-Deprivation MyopiaRecovery is primarily associated with a dramatic decrease in VC growth rate in the deprived eye.
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Optically Imposed Refractive Errors
To compensate, the monkey eye mustbecome morehyperopic.
To compensate, the monkey eye mustbecome moremyopic.
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Common Experimental Subjects
Rhesus Monkey
Chick
Wildsoet
Tree ShrewNorton
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Lens Compensation in MonkeysRE vs. Age for Binocularly Lens-Reared Monkeys
+9.0 D
Age (days)0 100 0 100 0 100 0 100 0 100 0 100
Am
etro
pia
(D)
-6
-4
-2
0
2
4
6
8
10
+6.0 D +3.0 D 0.0 D -3.0 D -6.0 D
ExpectedAmetropia
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Age (days)0 50 100 150
Vitr
eous
Cha
mbe
r Len
gth
(mm
)
9
10
11Positive LensesNegative Lenses
Negative lenses cause the eye to grow faster;positive lenses reduce growth.
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Lens Power (D)-10 -5 0 5 10 15
Am
etro
pia
(D)
-10
-5
0
5
10Chick (Wallman & Wildsoet, 1995)Chick (Irving et al., 1995)Tree Shrew (Siegwart & Norton, 1993)
Monkey (Smith et al.)
Marmoset (Whatham & Judge, 2001)
Emmetropization: Effective Operating Range
Moderate powered treatment lenses
produce predictable changes in refractive
error in many species.
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Optically Imposed Anisometropia
Age (days)0 50 100 150
0
2
4
6
0 50 100 150
Am
etro
pia
(D)
-2
0
2
4
Plano Lens
0 50 100 150
-2
0
2
4
6
Positive LensNegative Lens
RE = -3.0 D lensLE = Plano lens
RE = +3.0 D lensLE = Plano lens
RE = Positive lensesLE = Negative lenses
Anisometropic lenses can cause one eye to grow faster or slower than the fellow eye.
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Can optical defocus predictably alter refractive development in children?
-Optically Imposed Anisometropia-
Interocular Differences in Ref Error
Philips, 2005Subjects: n = 1311-year-old myopic children
Treatment: Monovision CLs-Dominant eye corrected for distance.-Fellow eye uncorrected or corrected to maintain <2.0 D aniso.
Results:Distance corrected eye progressed 0.36 D more than the fellow eye.
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Can defocus/spectacles predictably alter refractive development in children?
Incr
ease
in M
yopi
a (D
/yr)
0.0
0.2
0.4
0.6
0.8
1.0
Optimal Rx
OverminusedRx
Goss, 1984
Adolescent Children
Age (days)0 300 600 900 1200
Am
etro
pia
(D)
0
1
2
3
4
5ControlTreatedUntreated
Atkinson et al., 1996
Infants
Why is there little evidence that spectacles alter human refractive development? Faulty Emmetropization; Humans vs. Monkeys; Age;
Compliance
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Age (days)0 300 600 900 1200
Mea
n A
met
ropi
a (D
)
-2
0
2
4
Edwards, 1991
Wood et al., 1995
Thompson (1987) from Saunders
Saunders, 1995
Atkinson et al., 1996
Gwiazda et al., 1993
controls
treated hyperopes
untreatead hyperopes
Additions from Atkinson et al., 1996
- Faulty Emmetropization- Humans vs. Monkeys- Age- Compliance
Can spectacles predictably alter refractive development in children?
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Age (monkey years)0 1 2 3 4 5
Age (human years)0 4 8 12 16 20
Axi
al L
engt
h (m
m)
12
14
16
18
20
22
24
Normal MonkeysGordon & Donzis Larsen, malesLaren, femalesZadnik et alFledeliusTreated Monkeys
Age Effects: Are vision dependent mechanisms only active early in life?
Onset ofJuvenileMyopia
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Age (years)2 4 6 8
Vitr
eous
Cha
mbe
r (m
m)
(trea
ted
eye
- fel
low
eye
)
0.0
0.5
1.0
1.5
Age (Human Years)8 16 24 32
Individual Subjects1 2 3 4 5 6 7 8
Ani
som
etro
pia
(D)
(fello
w e
ye -
treat
ed e
ye)
0
1
2
3
4
5
6Vitreous Chamber Depth Anisometropia
(End of Treatment)
Late Onset Form Deprivation
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Temporal Integration Properties of Emmetropization
Daily Exposure History
Hours of the Light Cycle0 2 4 6 8 10 12
Form DeprivationUnrestricted Vision
Continuous FD
1 hr
2 hr
4 hr
n=6
n=7
n=7
n=4
Treatment period:onset: 24 ± 3 days
duration: 120 ± 17 days
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Temporal Integration Properties: Similarities Between Species
Hours of Unrestricted Vision
0 2 4 6 8 10 12V
itreo
us C
ham
ber (
mm
)(tr
eate
d ey
e - f
ello
w e
ye)
0.0
0.2
0.4
0.6
0.8
n = 6
n = 7
n = 4n = 7
n = 14
Hours of Unrestricted Vision
0 2 4 6 8 10 12
Ani
som
etro
pia
(D)
(trea
ted
eye
- fel
low
eye
)
0
1
2
3
4
5
6
7
n = 6
n = 7
n = 4n = 7
n = 14
4 months of age
Refractive Error Vitreous Chamber
Brief daily periods of unrestricted vision counterbalance long daily periods of form deprivation.
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Effects of Brief Periods of Unrestricted Vision on Compensation for Binocular Negative Lenses
Daily Exposure History
Hours of the Light Cycle0 2 4 6 8 10 12
-3 D LensesUnrestricted Vision
n=6
n=6
Treatment period:onset: 24 ± 3 daysduration: 115 ± 8 days
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Lens Compensation for Continuous -3D Lenses
Am
etro
pia
(D)
-2
0
2
4+2.45 D
-0.68 D
Age (days)0 30 60 90 120 150
Am
etro
pia
(D)
-2
0
2
4
6
8 Normal MonkeysContinuous -3 D Lenses
End of Treatment Averages
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Effects of 1 hour of vision through plano lenses on compensation for –3 D lenses.
Age (days)0 30 60 90 120 150
Am
etro
pia
(D)
-2
0
2
4
6
Normal Monkeys1-hr Plano LensesContinuous -3 D Lenses
Amet
ropi
a (D
)
-2
0
2
4
+2.45 D
-0.68 D
+2.63 D
End of Treatment Averages
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Implications for Nearwork
Hours of the Light Cycle0 2 4 6 8 10 12
-3 D LensesUnrestricted Vision
Am
etro
pia
(D)
-2
0
2
4
-3 D continuous Normals1 hr plano lens
Diopter HoursRelative to Controls
+36 D-hrs / day
+33 D-hrsper day
“0” D-hrs
•Visual signals that increase axial growth and those that normally reduce axial growth are not weighed equally.
•To stimulate axial growth, a myopiagenic visual stimulus must be present almost constantly.
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Central vs. Peripheral Vision
From Rodieck, 1998
Because resolution acuity is most acute at the fovea and decreases rapidly with eccentricity, central vision was
thought to dominate refractive development.
Eccentricity (deg)0 5 10 15 20 25 30
Sne
llen
Frac
tion
0.0
0.2
0.4
0.6
0.8
1.0
Data from Wertheim
Cone Density vs. Eccentricity Visual Acuity vs. Eccentricity
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Why look in the periphery?
However,• high acuity is not essential for emmetropization (e.g., tree shrew = 2 cy/deg).
• detection acuity remains high in the periphery and is strongly influenced by defocus.
• peripheral retinal diseases and laser treatment regimens are frequently associated with refractive errors.
Ametropia (D)
Per
cent
age
of E
yes
0-20 -10 +10
Nathan et al., 1985
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Is an intact fovea essential for normalemmetropization?
Foveal Ablations (n=5)• The fovea and most of the peri-
fovea were ablated in one eye using either an argon (50 msec, 400 µ spot size, 300-500 mW) or a frequency-doubled YAG laser (150 mW; 150 msec).
Age: 19.0 ± 1.6 days
Treated Eye
Photoreceptor Layer
Fellow Eye
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Is an intact fovea essential for normal emmetropization?
Age (days)0 100 200 300
Am
etro
pia
(D)
0
2
4
6
0 100 200 300
Am
etro
pia
(D)
0
2
4
6Control MonkeysTreated EyeFellow Eye
Mky ZAK
0 100 200 300
0
2
4
6 Mky YOY
Mky COR
Age (days)0 100 200 300
0
2
4
6 Mky KAR
Laser Laser
Laser Laser
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Foveal Ablations (n=8)• The fovea and most of the peri-
fovea were ablated in one eye using a argon laser (500 mW; 400 µ spot size; 50 msec). Form deprivation was optically induced in thetreated eye
ora serrata
LesionIs an intact fovea essential for Form
Deprivation Myopia?
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Interocular Differences in Refractive Error
Age (days)0 50 100 150
Ani
som
etro
pia
(D)
(trea
ted
eye
- fel
low
eye
)
-6
-4
-2
0
2
4
Control MonkeysTreated Monkeys
-10
-8
-6
-4
-2
0
2
End of Treatment
Contro
lsLa
ser +
MD
MD Only
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0 100 200 300 400 500
Am
etro
pia
(D)
-2
0
2
4
6
8
Control MonkeysRight EyeLeft Eye
Age (days)0 100 200 300 400 500
Vitr
eous
Cha
mbe
r (m
m)
8
9
10
11
Mky LEI
Is an intact fovea essential for
recovery?
Experiments in chicks indicate that recovery from FDM is vision-dependent. If
you correct the myopic errors with minus lenses,
the eyes don’t recover (Wildsoet & Schmid, 2000).
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Can the periphery mediate emmetropizing responses?
0 100 200 300 400 500
Am
etro
pia
(D)
-4
-2
0
2
4
6
8
Control MonkeysRight EyeLeft Eye
Age (days)0 100 200 300 400 500
Vitr
eous
Cha
mbe
r (m
m)
8
9
10
11
12
Mky MIT
Laser
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Can the periphery mediate emmetropizing responses?
0 50 100 150 200 250 300 350
Am
etro
pia
(D)
0
2
4
6
Control MonkeysRight EyeLeft Eye
Age (days)0 50 100 150 200 250 300 350
Vitr
eous
Cha
mbe
r (m
m)
8
9
10
11
12Mky LAU
Laser
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Clear Vision
Form Deprived
Form Deprived
Subjects (n = 12)4 mm = 24 deg 8 mm = 37 deg
14 mmvertex
entrancepupil
Can peripheral form deprivation &/or
defocus alter refractive development?
Controls (n = 24)21 normals3 plano lens controls
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Peripheral Form Deprivation: End of TreatmentA
met
ropi
a (D
)
-6
-4
-2
0
2
4
6
Normals4 mm8 mm
Normals = +2.39 ± 0.92 DTreated = +0.01 ± 2.27 D
Refractive Error
Ametropia (D)-6 -4 -2 0 2 4
Vitr
eous
Cha
mbe
r (m
m)
9
10
11
Vitreous Chamber
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Can peripheral hyperopic defocus produce central axial myopia?
Unrestricted
MultifocalZone
Always Defocused
Field of View (n=8)unrestricted = 6.8 deg
mixed focus = 30.5 deg
-3.0 D spectacle lenses(6 mm apertures)
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Age (days)0 50 100 150
Am
etro
pia
(D)
-4
-2
0
2
4
6
controls
-3 D full field
-3 D periphery
Am
etro
pia
(D)
-4
-2
0
2
4
6
Average Sph EquivalentControls = +2.49 ± 0.99 D
-3 D full field = -0.68 ± 1.82 D-3 D periphery = +0.37 ± 2.31 D
Peripheral Hyperopic Defocus-3 D lenses with 6 mm apertures
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Is an intact fovea essential for lens compensation?
Foveal Ablations (n=6)• The fovea and most of the peri-
fovea were ablated in one eye using a argon laser (500 mW; 400 µ spot size; 50 msec).
Treated Eye
Fellow Eye
Photoreceptor Layer
-3.0 D lenses
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Controls
-3 D full field
-3 D periphery
-3 D + laser
Am
etro
pia
(D)
-10
-8
-4
-2
0
2
4
6
Age (days)0 50 100 150
Am
etro
pia
(D)
-10
-8
-4
-2
0
2
4
6
Peripheral Hyperopic Defocus-3 D lenses & monocular foveal ablation
Controls = +2.49 ± 0.99 D-3 D full field = -0.68 ± 1.82 D
-3 D periphery = +0.37 ± 2.31 D-3 D + laser = -1.13 ± 3.24 D
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Impact of peripheral visionIn monkeys...• Peripheral form deprivation and peripheral hyperopic
defocus can produce axial myopia at the fovea, even in the presence of unrestricted central vision.
• Photoablation of the fovea does not: – interfere with normal emmetropization. – prevent recovery from induced refractive errors.– prevent form-deprivation myopia.– compensation to imposed hyperopic defocus
Peripheral vision can have a substantial influence on foveal refractive development in primates.