Transcript No Slide Title

Refractive Development: Main Parts
• Prevalence of refractive errors and
changes with age.
• Factors affecting refractive development.
• Operational properties of the visiondependent mechanisms that mediate
emmetropization.
• How visual signals are transformed into
biochemical signals for eye growth.
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
Newborns frequently
have large optical errors,
however, these errors
usually disappear.
Frequency (%)
40
30
Age 4-6 yrs
(Kempf et al)
20
Newborns
(Cook & Glasscock)
10
0
-8
-6
-4
-2
Nearsighted
0
2
4
6
8
Farsighted
Ideal Optical Conditions
10
12
Changes in Refractive Error with Age
Age Norms of Refraction
(Slataper, 1950)
4
Average data are
not very predictive
of changes on an
individual basis
before about 20
years. Thereafter,
most people
experience the
same trends.
Refractive Error (D)
3
2
1
0
more typical
0
10
20
30
40
50
Age (years)
60
70
80
90
Ametropia (D)
Myopia in Premature Infants
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.
Human Infants
Mean Ametropia (D)
4
3
Edwards, 1991
Wood et al., 1995
Thompson (1987) from Saunders
Saunders, 1995
Gwiazda et al, 1993
Atkinson et al., 1996
2
1
0
0
200
400
Age (days)
600
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.
95% confidence limits (D)
Net Anisometropia
Howland & Sayles (1987)
Normal Infants
n = 360
1.0
0.8
During the period of
rapid emmetropization,
the degree of
anisometropia typically
decreases (i.e.,
“isometropization”
occurs).
cylinders
spheres
0.6
0.4
0.2
0.0
0
1
2
3
Age (years)
4
5
“Isometropization”
Prevalence of Anisometropia
(Abrahamsson et al., 1990)
40
Number of Patients
Normal Infants
n=310
30
>1.0 D
new cases
loss of aniso
20
10
0
0
1
2
3
Age (years)
4
Anisometropia
is frequently
transient during
early
development.
Axial Length Development
Axial Length Development
Axial Length (mm)
22
Axial Length (mm)
24
20
22
20
Gordon & Donzis
Larsen, males
Laren, females
Zadnik et al
Fledelius
18
16
14
0
5
10
15
Age (years)
18
Gordon & Donzis
Larsen, males
Laren, females
Zadnik et al
Fledelius
16
14
0
1
2
3
Age (years)
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.
20
25
30
Corneal Development
Corneal Development
Corneal Power (D)
56
Gordon & Donzis
54
Woodrift
52
Corneal Power (D)
56
Woodrift
Zadnik et al.
52
50
48
46
44
42
0
5
10
15
20
25
Age (years)
Zadnik et al.
50
Gordon & Donzis
54
Major Optical Changes:
1) flatter cornea (6-8 D)
2) deeper AC (0.8D)
3) flatter lens (12-15 D)
48
46
44
42
0
1
Age (years)
2
3
30
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).
Lens Development
Lens Development
45
Gordon & Donzis
Zadnik et al.
Lens Power (D)
45
Gordon & Donzis
Zadnik et al.
40
Lens Power (D)
40
35
30
25
20
15
0
5
10
15
20
25
30
Age (years)
35
Major Optical Changes:
1) flatter cornea (6-8 D)
2) deeper AC (0.8D)
3) flatter lens (12-15 D)
30
25
20
0
1
Age (years)
2
3
Zadnik et al., 1993
Early School Years
Age Norms of Refraction
(Slataper, 1950)
4
1
0
-1
3
4
6
8
10
12
14
Age (yrs)
2
1
0
0
10
20
30
40
50
Age (years)
60
70
24
80
23 90
22
From about 2 to 7-8
years, the mean refractive
error is quite stable & the
degree of variability is low.
Lens Power (D)
25
Axial Length (mm)
Refractive Error (D)
Corneal Power (D)
Changes with Age
Ametropia (D)
2
Refractive Development: Early School Years
47
Ametropia (D)
Corneal Power (D)
Refractive Error
2
1
0
-1
Zadnik et al., 1993
Cornea
46
45
44
43
42
41
4
6
8
10
12
14
4
8
10
12
14
24
Axial Length
Lens
23
Lens Power (D)
Axial Length (mm)
25
6
24
23
22
22
21
20
19
18
21
4
6
8
10
Age (years)
12
14
4
6
8
10
12
14
Age (years)
During early adolescence, the cornea is relatively stable. The slow decrease in
lens power is counterbalanced by an increase in axial length.
Refractive Development: Early School Years
Anterior Chamber Depth
Wong et al., 2010
Refractive Development: Early School Years
Lens Thickness
Wong et al., 2010
Refractive Development: Early School Years
Anterior Segment
Larsen, 1971
Prevalence of Myopia in Humans
School Years
Myopia (percent)
35
Jackson, 1932
30
Tassman, 1932
25
20
15
10
5
0
0
10
20
30
Age in Years
40
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.
Myopic Progression
Males
“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.
Females
Annual Rate of Myopic Progression
Proportion of Sample
0.35
0.30
Males
Females
0.25
Rate varies
considerably between
individuals. Average =
-0.40 to -0.6 D/yr
(before age 15 yrs)
0.20
0.15
0.10
0.05
0.00
-1.6
-1.4
-1.2
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
Myopic Progression (D/year)
0.2
0.4
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.
Axial Nature of Myopia
The rate of myopic
progression is highly
correlated with the
rate of axial
elongation.
From Goss, 1998
0.4
Predictability of Refractive
Errors at Age 13-14 Years
Proportion of Sample
0.2
0.0
-0.5
0.0
0.5
1.0
>1.5
0.4
0.2
Refractive Error Distributions
for Children at 5-6 years who
develop:
Myopia >0.50 D
Emmetropia -0.49 to +0.99 D
0.0
-0.5
0.0
0.5
1.0
>1.5
Hyperopia >1.0 D
0.4
0.2
0.0
-0.5
0.0
0.5
1.0
Ametropia (D)
>1.5
From Hirsch, 1964
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
Early Adult Onset Myopia
Adult Onset
Adult Progression
McBrien & Adams, 1997
Examples of adult onset myopia associated with
a change in occupation.
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
Adult Onset Myopia
Vitale et al 2009
Percent Myopic
50
44.0
42.9
44.8
30% of myopes
become myopic
after 17 yrs
38.1
40
33.9
30
27.7
24.0
24.2
24.5
24.8
20
1971 to 1972
10
1999 to 2004
0
12
18
25
to 17 to 24 to 34
yrs
yrs
yrs
35
to 44
yrs
Age Group
45
to 54
yrs
Changes in Refractive Error with Age
Acquired hyperopia due
to:
1) presbyopia
2) lens continues to flatten
3) refractive index of lens
cortex increases
Age Norms of Refraction
(Slataper, 1950)
4
Refractive Error (D)
3
2
1
0
more typical
0
10
20
30
40
50
Age (years)
60
70
80
90
Lens Development - Mass
The crystalline lens
continues to grow
throughout life.
Weale, 1982
Acquired Hyperopia
Vitreous Chamber
Young adult (22 yrs) = 16.14 mm
Mature adult (54 yrs) = 15.7 mm
Ooi & Grosvenor, 1995
Changes in Refractive Error with Age
Age Norms of Refraction
(Slataper, 1950)
4
Decrease in hyperopia
due to increase in
refractive index of core of
crystalline lens.
Refractive Error (D)
3
2
1
0
more typical
0
10
20
30
40
50
Age (years)
60
70
80
90
Prevalence of Astigmatism
(young adult population)
Percentage of Population
50
Astigmatism is
the most common
ametropia. The
magnitude is,
however, usually
relatively small.
40
30
20
10
0
0.0
0.5
1.0
1.5
>2
Amount of Astigmatism (D)
Astigmatism Axis vs Spherical Ametropia
Young Adult Population
Mandel et al., 2010
Prevalence of Astigmatism: Infants
Marked levels of
astigmatism are
common in young
infants -- due
primarily to corneal
toricity.
Atkinson et al. 1980
Prevalence (%)
Prevalence of Astigmatism (>1 D)
in Human Infants
Santonastaso, 1930
100
Howland et al., 1978
Mohindra et al., 1978
80
Atkinson et al., 1980
Fulton et al., 1980
Gwiazda et al., 1984
Edwards, 1991
Saunders, 1995
60
40
20
0
0
10
20
30
Age (weeks)
40
50
.
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
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
Change in Axis of Astigmatism
W-t-R
A-t-R
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.
oblique
age in decades
Bennett & Rabbetts, 1989
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
My Eyelash
About 200 microns
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
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
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
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
Prevalence of Myopia in Different Ethnic Groups
Prevalence of Myopia (%)
60
50
40
30
20
10
0
Swedish
British
Israeli
Malay
Indian
Ethnic Category
Eurasian Chinese
Percent Children Myopic
Familial Inheritance Patterns
15
from 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.
10
5
0
None
One
Both
Myopic Parents
Intrapair Correlations for Refractive Error
Monozygotic vs Dizygotic Twins (Dirani et al., 2006)
Monozygotic Twins
r = 0.36
Twin 2 Ametropia (D)
r = 0.82
Dizygotic Twins
Twin 1 Ametropia (D)
Twin 1 Ametropia (D)
Dr. Y. Chino
Monozygotic Twins
Twin B: Refractive Error (D)
8
6
(Sorsby et al., 1962)
4
2
Evil twin?
Good twin?
0
Identical twins have very
similar refractive errors.
-2
-4
-4
-2
0
2
4
6
Twin A: Refractive Error (D)
8
Concordance of Optical Components
(from Sorsby et al., 1962)
uniovular twins
Procentage of Sample
100
other pairs
80
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
60
40
20
0
1
2
3
4
5
6
Number of Individual Components
Myopia and Genetics
(peer-reviewed publications per year)
Published Papers
80
60
40
20
0
1970
1980
1990
2000
2010
Genetic Loci for Myopia
1990-2003
Locus
Location
Study
Myopia Severity
MYP1
Xq28
Schwartz et al, 1990
-6.75 to -11.25 D
MYP2
18p11.31
Young et al, 1998
-6.00 to -21 D
MYP3
12q21-q23
Young et al, 1998
-6.25 to -15 D
MYP4
7q36
Naiglin et al, 2002
Avg = -13.05 D
MYP5
17q21-q22
Paluru et al, 2003
-5.50 to -50 D
Genetic Loci for Myopia
2005 to 2009
Locus
Location
Study
Myopia Severity
MYP6
22q12
Stambolian et al, 2004
-1.00 D or lower
MYP7
11p13
Hammond et al, 2004
-12.12 to +7.25 D
MYP8
3q26
Hammond et al, 2004
-12.12 to +7.25 D
MYP9
4q12
Hammond et al, 2004
-12.12 to +7.25 D
MYP10
8p23
Hammond et al, 2004
-12.12 to +7.25 D
MYP11
4q22-q27
Zhang et al, 2005
-5 to -20 D
MYP12
2q37.1
Paluru et al, 2005
-7.25 to -27 D
MYP13
Xq23-q25
Zhang et al, 2006
-6.00 to -20 D
MYP14
1p36
Wojcechowski et al, 2006
Avg = -3.46 D
MYP15
10q21.1
Nallasamy et al, 2007
Avg = -7.04
MYP16
5p15.33-p15.2
Lam et al,2008
-7.13 to -16.68 D
MYP?
1q41
Klein et al, 2007
Range of Errors
MYP?
7p21
Klein et al, 2007
Range of Errors
MYP?
22q11.23-12.3
Klein et al, 2007
Range of Errors
MYP?
7p15
Ciner et al, 2008
Avg = -2.87 D
MYP?
3q26
Andrew et al, 2008
-20 to +8.75 D
MYP?
20q11.23-13.2
Ciner et al, 2009
Avg = -4.39 D
MYP?
9q34.11
Li et al, 2009
<-5.00 D
MYP?
15q14
Solouki et al, 2009
Range of Errors
MYP?
15q25
Hysi et al, 2009
Range of Errors
Myopia has historically been
associated with nearwork.
Nearsighted (percent)
35
University Students
30
Tscherning, 1882
25
(Duke-Elder, 1970)
20
Clerks
Cultured people (actors & musicians)
15
Tailors
10
Skilled workmen (butchers)
5
Farmers and Seamen
0
1
2
3
Heavy Near Work
4
5
6
Little Near Work
Occupation
Nearsighted (percent)
The prevalence of myopia
is synchronized with
the onset of formal schooling.
(Jackson, 1932; Tassman, 1932)
School Years
35
30
25
20
15
10
5
0
0
10
20
30
Age in Years
40
Significant Associations in Myopia
Myopia & Education
Proportion of Myopes (%)
Myopia & Intelligence
25
30
25
20
20
15
15
10
10
5
5
0
0
<80
81-96
97-103 104-111 112-127
IQ Score
>127
<8
9
10
11
Years of Education
>12
An Epidemic of Myopia
Average Degree of Myopia (D)
Taiwanese School Children
Prevalence Rate (%)
100
2000
80
60
1995
40
1986
20
Lin et al., 2004
0
6
8
10
12
14
Age (years)
16
18
20
4
1986
2000
3
2
1
0
12 Years 15 Years 18 Years
Age
The prevalence and average degree of myopia is
increasing rapidly over time.
An Epidemic of Myopia
National Health and Nutrition Examination Survey data from 1971-1972 vs 1999-2004
Prevalence of Myopia (%)
Females
Males
1999-04
1971-72
Vitale et al., 2009
Age (yrs)
Age (yrs)
The prevalence of myopia is increasing too fast to reflect genetic changes;
something in the environment is affecting the pattern of refractive errors.
Outdoor activities have a strong
protective effect against myopia.
Mitchell et al., 2006
2.5
2.0
1.0
Low
Moderate
High
0.5
0.0
High
Moderate
Low
near-work
Multivariable-Adjusted Odds for Myopia
oo
r
1.5
ou
td
Odds ratio
3.0
Restricted environments promote myopia.
Monkeys in Restricted Environment
(from Young, 1963)
-0.2
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.
Refractive Error (D)
-0.4
-0.6
-0.8
-1.0
Mean (n=12)
-1.2
Mean (n=18)
-1.4
0
10
20
30
40
Time in Restricted Environment (weeks)
50
Emmetropization Requires Vision
Dark-reared Monkeys
Normal Monkeys
Ametropia (D)
10
8
6
4
2
0
0
50
100
150
200
Age (days)
0
200
400
Human days
Age (days)
Guyton et al., 1987
600
800
Chronic Image Degradation Causes Myopia
Monocularly Form-Deprived Monkeys
Vitreous Chamber Growth
deprived eye
Vitreous Chamber (mm)
normal eye
14
12
10
deprived eye
fellow eye
8
0
Wiesel & Raviola, 1977
10
20
Age (months)
The potential for a clear retinal image is essential for
normal refractive development.
30
Old World
FDM occurs in a wide variety of animals.
Marsupialia
New World
Primates
Human
Aves
Tree
Shrews
Terrestrial
vertebrates
Placental
mammals
Carnivora
Vertebrata
Rodentia
Lagomorpha
Form-Deprivation Myopia
Form-deprivation Myopia
Monkeys
Humans
Percentage of Cases
70
60
70
Raviola and Wiesel, 1990
von Noorden and Crawford, 1978
Smith et al., 1987
"deprived humans"
60
50
Normal humans
50
Rabin et al. (1981)
Normal Monkeys
40
40
Deprived Monkey Eyes
30
30
20
20
10
10
0
0
-15
-10
-5
0
Ametropia (D)
5
10
-15
-10
-5
0
5
Ametropia (D)
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.
10
Recovery from Form-Deprivation Myopia
10
0
Monkey LIS
0
-2
0
0
-2
-2
-4
ays)
2
-4
0
600
4
0
-4
400
End of Treatment
6
-2
Vitreous Chamber (mm)
(treated eye – control eye)
Anisometropia (D)
-4
8
Ametropia (D)
Normal Monkeys
Treatment Period
Recovery Period
End of Treatment
-2
0
200
400
Age (days)
600
Deprived Eye
Non-Treated Eye
100
200
300
200
300
11
treatment period
10
9
8
0
100
Age (days)
Emmetropization is guided by optical defocus.
Optically imposed refractive errors produce predictable refractiveerror changes.
Positive Treatment
Lens
Imposed Myopia: To
compensate, the eye must
become more hyperopic.
Negative Treatment
Lens
Imposed Hyperopia: To
compensate, the eye must
become more myopic.
Lens Compensation in Monkeys
RE vs. Age for Binocularly Lens-Reared Monkeys
+9.0 D
10
8
Ametropia (D)
+6.0 D
+3.0 D
0.0 D
6
-6.0 D
-3.0 D
4
2
0
Expected
Ametropia
-2
-4
-6
0
100
0
100
0
100
0
Age (days)
100
0
100
0
100
Vitreous Chamber Length (mm)
Negative lenses cause the eye to grow faster;
positive lenses reduce growth.
Negative Lenses
Positive Lenses
11
10
9
0
50
100
Age (days)
150
.
Emmetropization: Effective Operating Range
Chick (Wallman & Wildsoet, 1995)
Chick (Irving et al., 1995)
25
Ametropia (D)
Tree Shrew (Siegwart & Norton, 1993)
20
Monkey (Smith et al.)
15
Marmoset (Whatham & Judge, 2001)
10
Moderate powered
treatment lenses
produce predictable
changes in refractive
error in many species.
5
0
-5
-10
-15
-20
-10
0
10
Lens Power (D)
20
30
.
Effective Operating Range for Emmetropization
Monkeys vs Humans
Change in Refractive Error (D)
Monkeys
Humans
B. Effective Emmetropization Range
4
0
-4
r ² = 0.76
-8
-12
-8
-4
0
4
8
12
Effective Refractive Error (D)
Large refractive errors produce unpredictable growth –
possibly these eyes have faulty emmetropization
mechanisms.
Optically Imposed Anisometropia
RE = -3.0 D lens
LE = Plano lens
RE = +3.0 D lens
LE = Plano lens
6
6
4
Ametropia (D)
RE = Positive lenses
LE = Negative lenses
4
4
2
2
2
0
0
0
-2
-2
0
50
100
150
0
50
100
Age (days)
150
0
50
100
Positive Lens
Negative Lens
Plano Lens
Regulation of refractive development is largely
independent in the two eyes.
150
Optically Imposed Anisometropia
Interocular Differences in Refractive Error
Monkeys
2
Treated eye = -3.0 D lens
Fellow eye = Plano lens
1
Anisometropia (D)
Humans
Philips, 2005
Monovision correction
0
-1
-2
-3
-4
0
50
100
150
Age (days)
Humans and monkeys respond in a similar manner to
imposed defocus.
Can defocus/spectacles predictably alter
refractive development in children?
Adolescent Children
Increase in Myopia (D/yr)
0.8 0.8
Goss,
1984
Goss,
1984
5 5
4 4
Ametropia (D)
Ametropia (D)
Increase in Myopia (D/yr)
1.0 1.0
Control
Control
Treated
Treated
Untreated
Untreated
Infants
0.6 0.6
3 3
0.4 0.4
2 2
0.2 0.2
1 1
0.0 0.0
Atkinson et al., 1996
0 0
0 0
300300
600600
Atkinson et al., 1996
Overminused
Optimal
Overminused
Optimal
Rx Rx
Rx Rx
900
900
1200
1200
Age
(days)
Age
(days)
Why is there little evidence that spectacles alter human refractive
development? Faulty Emmetropization; Humans vs. Monkeys; Age;
Compliance (temporal Integration); Spatial Integration of Visual Signals
Can spectacles predictably alter
refractive development in children?
- Faulty Emmetropization
- Humans vs. Monkeys
- Age
- Compliance
treated hyperopes
Mean Ametropia (D)
4
untreatead hyperopes
2
Edwards, 1991
controls
Wood et al., 1995
Thompson (1987) from Saunders
0
Saunders, 1995
Atkinson et al., 1996
Additions from Atkinson et al., 1996
-2
0
300
600
Age (days)
900
1200
Gwiazda et al., 1993
Age Effects: Are vision dependent
mechanisms only active early in life?
Axial Length (mm)
24
22
20
18
Normal Monkeys
Gordon & Donzis
Larsen, males
Laren, females
Zadnik et al
Fledelius
Treated Monkeys
16
Onset of
Juvenile
Myopia
14
12
0
4
8
12
16
20
4
5
Age (human years)
0
1
2
3
Age (monkey years)
Late Onset Form Deprivation
Anisometropia
Vitreous Chamber Depth
1.0
0.5
(fellow eye - treated eye)
Anisometropia (D)
(treated eye - fellow eye)
1.5
Vitreous Chamber (mm)
(End of Treatment)
6
5
4
3
2
1
0.0
0
2
4
6
8
16
2
3
4
5
6
7
Individual Subjects
Age (years)
8
1
24
Age (Human Years)
32
8
Temporal Integration Properties of
Emmetropization
Form Deprivation
Unrestricted Vision
Daily Exposure History
Continuous FD
n=6
1 hr
n=7
2 hr
n=7
4 hr
n=4
0
2
4
6
8
Hours of the Light Cycle
Treatment period:
onset:
24  3 days
duration: 120  17 days
10
12
Temporal Integration Properties:
Similarities Between Species
Refractive Error
Vitreous Chamber
4 months of age
n=6
5
4
3
n=7
2
n=7
1
n = 14
n=4
0
0
2
4
6
8
10
Hours of Unrestricted Vision
12
0.8
(treated eye - fellow eye)
(treated eye - fellow eye)
Anisometropia (D)
6
Vitreous Chamber (mm)
7
n=6
0.6
0.4
n=7
0.2
n=7
n = 14
n=4
0.0
0
2
4
6
8
10
Hours of Unrestricted Vision
Brief daily periods of unrestricted vision
counterbalance long daily periods of form deprivation.
12
Effects of Brief Periods of Unrestricted Vision on
Compensation for Binocular Negative Lenses
-3 D Lenses
Unrestricted Vision
Daily Exposure History
n=6
n=6
0
2
4
6
8
Hours of the Light Cycle
Treatment period:
onset:
24  3 days
duration: 115  8 days
10
12
Lens Compensation for Continuous -3D Lenses
Normal Monkeys
Continuous -3 D Lenses
8
4
+2.45 D
6
Ametropia (D)
Ametropia (D)
End of Treatment
Averages
4
2
0
2
0
-0.68 D
-2
0
30
60
90
Age (days)
120
150
-2
Effects of 1 hour of vision through plano
lenses on compensation for –3 D lenses.
Normal Monkeys
1-hr Plano Lenses
Continuous -3 D Lenses
End of Treatment
Averages
6
4
Ametropia (D)
Ametropia (D)
4
2
0
+2.45 D
2
0
-0.68 D
-2
-2
0
30
60
90
Age (days)
120
150
+2.63 D
Implications for Nearwork
-3 D continuous
Normals
1 hr plano lens
Ametropia (D)
4
2
Diopter Hours
Relative to Controls
“0” D-hrs
+33 D-hrs
per day
-3 D Lenses
Unrestricted Vision
0
2
4
6
8
10
12
Hours of the Light Cycle
0
-2
+36 D-hrs / day
•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.