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?

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

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

-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

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.

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.

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.

Emmetropization - Rate of Change in Humans

From Saunders et al. 1995

Infants with large initial refractive errors show faster changes.

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.

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).

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.

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.

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)

Corneal Development - Horizontal Diameter

Birth

Weale, 1982

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

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)

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

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.

Refractive Development: Early School YearsAnterior Segment

Larsen, 1971

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.

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.

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)

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.

The rate of myopic progression is highly correlated with the

rate of axial elongation.

Axial Nature of Myopia

From Goss, 1998

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

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

Early Adult Onset Myopia

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 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

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

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)

Lens Development - Mass

The crystalline lens continues to grow

throughout life.

Weale, 1982

Acquired Hyperopia

Vitreous Chamberyoung adult (22 yrs) = 16.14 mmMature adult (54 yrs) = 15.7 mm

Ooi & Grosvenor, 1995

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.

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.

Prevalence of Astigmatism: Infants

Marked levels of astigmatism are

common in young infants -- due

primarily to corneal toricity.

Atkinson et al. 1980

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

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

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

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

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

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)

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)

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 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

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

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

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

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

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

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.

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.

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)

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

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

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.

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

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

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.

Vision Through Diffusers

As good as it gets

Weakest diffuser

Intermediate diffuser

Strongest diffuser

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.

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.

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.

Optically Imposed Refractive Errors

To compensate, the monkey eye mustbecome morehyperopic.

To compensate, the monkey eye mustbecome moremyopic.

Common Experimental Subjects

Rhesus Monkey

Chick

Wildsoet

Tree ShrewNorton

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

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.

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.

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.

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.

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

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?

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

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

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

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.

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

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

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

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.

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

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

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

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

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?

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

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).

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

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

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

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

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)

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

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

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

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.