Myopia: attempts to arrest progression
S M Saw, G Gazzard, K-G Au Eong, D T H Tan
Br J Ophthalmol 2002;86:1306–1311
Previous studies have evaluated the efficacy of several
interventions to decrease the progression of myopia.
These include devices that alter the perception of the
visual environment and pharmacological treatments.
There is no conclusive evidence thus far that alteration
of the pattern of spectacle wear, bifocals, ocular
hypotensives, or contact lenses retards the progression
of myopia. Several randomised clinical trials have
demonstrated that the rate of progression of myopia is
lower in children given atropine eye drops than those
given placebo. However, atropine is associated with
short term side effects such as photophobia and possible
long term adverse events including light induced retinal
damage and cataract formation. Other more selective
antimuscarinic agents such as pirenzipine are presently
being evaluated. Further well conducted randomised
clinical trials with large sample sizes and adequate
follow up designed to evaluate treatments to retard the
progression of myopia should be conducted, since the
identification of an effective intervention may have a
greater public health impact on the burden and
morbidity from myopia than the few treatments currently
recorded use of convex lenses for presbyopia in
the late 13th century in Florence, Italy, the
correction of myopic refractive error had to await
the development of concave lenses in the mid
Myopia may be classified as “school myopia”or
“adult onset myopia.”3School myopia develops
during the school age and stabilises around 15–17
years of age,while adult onset myopia develops in
young adults. The aetiology, pathogenesis, and
treatment of myopia have been hotly debated in
the ophthalmic community for decades.4There
are several theories on the mechanism of develop-
ment of myopia arising from disruption of the
emmetropisation process. Emmetropisation is
achieved when the optical power of the eye
matches the axial length, resulting in a focused
image of a distant object on the retina without
accommodative effort.5It has been proposed that
overacting intraocular muscles may result in
emmetropisation.6The two basic mechanisms by
which animal myopia may be induced are form
deprivation and optical defocus.Form deprivation
yopia has been known for more than 2000
years and was first described by the
ancient Greeks.1 2However, despite the
myopia can be induced by the application of
retinal effects may occur and the resultant scleral
growth modulated by
antagonists.7–9Negative spectacle lenses in chicks
Suitable therapeutic modalities such as phar-
macological interventions and optical corrective
devices that may retard the progression of myopia
in myopic individuals have been reported. The
overwhelming majority of these reports have
been cited in optometry and not ophthalmology
journals. The optical correction of myopia and
optimal strategies to prevent the progression of
myopia have been developed and prescribed
largely by optometrists.On the other hand,issues
regarding the causes and prevention of myopia
have only gained interest among ophthalmolo-
gists in the recent decade. The objective of this
review is to summarise in a comprehensive man-
ner the current evidence for the postulated
mechanisms of action, efficacy, and adverse
effects of these various treatments to arrest myo-
ALTERATION OF PATTERN OF SPECTACLE
When myopia is not corrected, lack of a clear
visual image may lead to “form deprivation
myopia.”11Conversely, correcting a child’s myopia
with negative lenses may result in compensatory
aberrant eye growth and the development of
myopia.10Animal experiments have shown that
compensatory changes in the axial length of an
eye may occur in response to error signals from
lens induced defocus.10 12In a non-randomised
clinical trial evaluating part-time distance specta-
cle wear in the United States, 43 myopes were
categorised into four treatment groups: (a) full
time spectacle wear,(b) wear for distance viewing
and then a switch to full time wear, (c) wear for
distance viewing only, and (d) non-wear. Over a
period of 3 years, there were no significant differ-
ences in refractive shifts as measured by non-
cycloplegic distance retinoscopy between the
treatment groups.13In a non-masked randomised
clinical trial of 240 myopic schoolchildren aged
9–11 years in Finland, children were randomised
to (a) minus lenses with full correction for
continuous use, (b) minus lenses with full
correction to be used for distance vision only, and
(c) bifocal lenses. There were no significant
differences in the rate of myopia progression in
the different groups after 3 years.14
Distance undercorrection may reduce accom-
modative focus.15Straub compared fully corrected
See end of article for
Dr Seang-Mei Saw,
Department of Community,
Occupational and Family
University of Singapore, 16
Medical Drive, Singapore
117597, Republic of
Accepted for publication
26 June 2002
and undercorrected myopic teenagers and concluded that full
correction does not have an effect on the progression of
myopia.16However, this trial was not randomised. In another
small non-randomised trial by Tokoro and Kabe, 11 subjects
who wore full correction had a mean rate of progression of
−0.83 dioptre (D) per year, compared to a mean rate of −0.47
D per year in five subjects who had undercorrection
BIFOCALS AND MULTIFOCALS
The reduced accommodative response of myopic children to
near objects may be associated with retinal blur and possible
uncoordinated eye growth.18Bifocal lenses may reduce
accommodative demand during near work and thus decrease
the rate of progression of myopia. However, bifocals may not
control accommodation at all distances since there are only
two focal zones (a distance zone and a near zone) and there
may be slightly out of focus retinal images at other
Optometrists have been using bifocal lenses as a possible
treatment for myopia since the 1940s. In 1955, Warren
prescribed lenses with a +1.25 D addition in an 18 year old
myopic college student.20However,no results were reported.A
large number of clinical trials and retrospective studies that
have evaluated bifocal lenses are severely limited by small
sample size, lack of a control group, lack of randomisation in
the allocation of treatment groups or a combination of these
deficiencies.21–29Furthermore, bifocal lenses may be less
cosmetically acceptable, are difficult to adapt to, and
compliance with spectacle wear may be a problem. In
addition, children may not always use the lower segment of
the lens for reading. Recently, there have been several well
designed randomised clinical trials of bifocal lenses conducted
in children in the United States, Finland, and Denmark.30–33
The bifocal trials tested a range of vision additions (+1.00 D to
+2.00D) and the sample sizes of the trials varied from 32 to
240. In all these trials, there were no significant differences in
the myopia progression rates.
Progressive addition multifocal lenses are more cosmeti-
cally acceptable and allow children to have clear vision at all
distances without adjustment of the focal mechanism of the
eye. In young myopes, however, the progressive addition lens
must be fitted very high to facilitate the use of the segment for
reading. In a clinical trial conducted by Leung and Brown in
Hong Kong, 22 children were assigned to wear progressive
lenses with +1.50 D addition,14 to lenses with +2.00 D addi-
tion, and 32 to single vision lenses. The mean progression rate
of myopia was −3.73 D for the children assigned to +1.50 D
additions, −3.67 D for children wearing +2.00 D additions,
and −3.67 D for children wearing single vision lenses
(p<0.001). However, the assignment was not random:
subjects with even case record numbers were placed in the
progressive lenses group, while subjects with odd case record
numbers were placed in the single vision lenses group.19A Tai-
wanese randomised clinical trial by Shih and colleagues
showed a non-significant reduction of the progression of
myopia (mean myopia progression −1.19 D per year in multi-
focal group versus −1.40 D per year in single vision group) in
227 myopic children aged 6–12 years after 11⁄2 years.34The
Correction of Myopia Evaluation Trial (COMET) is a large
ongoing 3 year multicentre randomised, double masked trial
evaluating the effect of progressive addition lenses versus sin-
gle vision lenses in 469 myopic children (spherical equivalent
between −1.25 and −4.50 D) aged 6–11 years in the United
States.35 36The results from this trial may provide new evidence
for the efficacy of multifocal lenses.
Contact lenses have a long history of use as optical correction
since their introduction by Eugen Fick in 1888.37Contact
lenses may increase peripheral vision, provide cosmetic
benefits, and promote more outdoor activity. However, poten-
tial complications of contact lens use include allergic conjunc-
tivitis, corneal infiltrates, and infective keratitis, and contact
lens hygiene compliance may be a problem in less responsible
In infant primates wearing minus contact lenses, compen-
satory ocular growth may lead to functional myopia.38 39A
large number of reports on the efficacy of various types of
contact lenses (silicone acrylate contact lenses, hydrophilic
contact lenses, hydrogel lenses) were not randomised, had
small sample sizes, and high dropout rates.40–47In a ran-
domised clinical trial of the efficacy of soft contact lenses in
175 children by Horner and associates in the United States,
there was no significant difference in the rate of progression of
myopia between the contact lens (−0.36 D per year) and con-
trol group (−0.30 D per year).48
Morrison in 1956 fitted 1021 myopic children (7–9 years)
flatter than the flattest curvature with polymethyl methacr-
ylate (PMMA) hard contact lenses, thus altering the shape of
the cornea.49However, there were hypoxia related corneal
changes. New rigid gas permeable lenses with high oxygen
permeability are a suitable and safer alternative.45The poten-
tial mechanisms of action of rigid contact lenses include tran-
sient flattening of the cornea, and improved quality of the
retinal image with reduced peripheral image “blur.” Perhaps
rigid contact lenses may even retard axial elongation.
However, the permanence of these mechanisms of action is
In the 3 year Houston study of rigid gas permeable contact
lenses, 100 myopic children aged 8–13 years were fitted with
Paraperm oxygen plus contact lenses and were compared with
20 spectacle wearers. The average progression of myopia was
significantly different: 0.48D per year for rigid contact lens
wearers compared with −1.53 D per year for spectacle
wearers.50However, the allocation of treatment was not
randomised. It was also observed that approximately half of
the effect of rigid gas permeable contact lenses was due to
transient corneal flattening. In a non-randomised study of 45
rigid contact lens wearers and 45 spectacle wearers in Singa-
pore 10 year old children, the mean increase in myopia over a
3 year period of spectacle wearers was −2.3 D in contrast with
−1.3 D for contact lens wearers (p<0.05).51No major adverse
events were noted. However, in a more recent and larger ran-
domised clinical trial of rigid contact lenses with 383
Singapore children aged 6–12 years over 2 years, there was no
significant differences in the rate of progression of myopia or
axial length in the two groups (Katz J et al,submitted for pub-
The technique known as orthokeratology has been practised
for decades: the cornea is flattened by fitting progressively
flatter rigid contact lenses until the corneal shape is
sufficiently altered to achieve myopia reduction.52The tempo-
rary alteration of corneal shape and hence correction of myo-
pia allows for periods of clear unaided vision during the day
without the use of lenses,but requires constant use of retainer
lens,usually worn overnight,with the potential complications
of infective keratitis relating to closed eye contact lens wear.
However, corneal flattening does not treat the intrinsic cause
of myopia and may be a remedy rather than a cure.In the Ber-
keley Orthokeratology Study, 80 subjects were randomised to
orthokeratology or a control group wearing contact lenses fit-
ted in the standard clinical manner. There was a significantly
larger reduction in myopia for the patients randomised to
orthokeratology, but the reduction did not persist after
orthokeratology.52Thus, orthokeratology has little clinical
value for the retardation of myopia progression.
ATROPINE AND PIRENZIPINE EYE DROPS
Atropine is an alkaloid from the deadly nightshade Atropa bel-
ladonna and has several proposed mechanisms of action.
Firstly, atropine may block accommodation and reduce the
putative effects of excessive accommodation on the progres-
sion of myopia.11Secondly, atropine is a non-selective
muscarinic antagonist and it has been observed that in
animals treated with atropine, form deprivation myopia may
be suppressed with retardation of axial length elongation.53–55
Atropine also affects dopamine neurotransmitter release from
cellular stores and thus may influence retinal signals that
control the growth of the eye.56Thirdly, atropine may reach
sufficient levels in the bloodstream to have systemic effects.
Atropine suppresses growth hormone secretion from the
pituitary gland which could disturb normal eye growth.57 58
The first reports of atropine treatment for myopia were by
Wells in the 19th century.3In 1979, Bedrossian evaluated the
effect of 1% atropine ointment instilled once at night in one
eye for 1 year with the fellow eye as the control in a
non-randomised trial. After 1 year, treatment was switched to
the fellow eye, and the control eyes showed significant
increases in the rate of myopia.59However, the fellow eye may
not be suitable as a control as there may be systemic residual
effects of atropine on the fellow eye.Several other studies have
evaluated topical atropine therapy but unfortunately had suf-
conclusions.15 16 60–67A range of concentrations (0.1% to 1%) of
atropine eye drops were tested in three randomised clinical
trials of schoolchildren in Taiwan and the rate of progression
of myopia in the atropine group was significantly lower com-
pared with the control group.34 68 69Higher doses of atropine
(1% atropine) may, however, be associated with an increased
incidence and severity of local effects (examples include
mydriasis, photophobia, blurred vision, allergic dermatitis)
and systemic effects34 68 69; lower doses of atropine (0.5%,
0.25%,0.1%) were better tolerated.68The long term side effects
of atropine eye drops in children are relatively unknown and
there may be a risk of long term ultraviolet light related reti-
nal damage and cataract formation as a result of chronic
Pirenzipine is a relatively selective M1 subtype muscarinic
receptor antagonist and M1 receptors are found in the ciliary
processes.70–74In both avian and mammalian models, piren-
zipine has been shown to block form deprivation myopia and
axial elongation.75–77The tolerability of pirenzipine gel formu-
lation was tested in a double masked placebo controlled ran-
domised clinical trial of children aged 9–12 years in the United
States.78The subjects received pirenzipine 0.5% for the first
week, 1.0% for the second week, and 2.0% for an additional 2
weeks. Another study of 49 adult male volunteers found that
pirenzepine ophthalmic gel at 0.5%, 1.0%, and 2.0% was well
tolerated, produced minimal mydriasis, and the only adverse
event noted was a transient unilateral loss of visual acuity in
one patient which recovered by the next visit.79Although ran-
domised clinical trials are currently in progress, efficacy data
are not yet available.
to precludeany reliable
TROPICAMIDE EYE DROPS
Tropicamide is a short acting cycloplegic agent that relaxes
ciliary muscle tone and blocks accommodation. In a study of
61 children aged 6–16 years given 0.4% tropicamide eye drops,
the average degree of myopia was reduced from −0.85 D to
−0.62 D.80There was, however, no control group. A matched
pair design of 25 twins in the United States given a combina-
tion of 1% tropicamide eye drops with bifocals against single
vision spectacles, showed no significant differences in myopia
progression after 31⁄2 years of follow up.81Tropicamide has a
shorter half life than atropine and its associated side effects
are correspondingly more transient. Studies of several
thousand applications of tropicamide showed no adverse
experiences.66 82However, the shorter duration of action
requires more frequent administration for continual blockade
of accommodation, and therefore is less convenient.
It has been hypothesised that the increase in eye size in myo-
pia may be due to passive stretching of the sclera because of
increased intraocular pressure from an increase in vitreous
chamber volume.83It has been postulated that excessive
accommodation or convergence may increase intraocular
pressures, producing an increased force in the sclera, causing
axial elongation. However, previous studies have found that
patients who accommodated at near had slightly lower or
similar intraocular pressures.84–87Perhaps during accommoda-
tion, traction is exerted on the scleral spur resulting in the
opening of the trabecular network and increased aqueous
outflow. In addition, there is little conclusive evidence that
myopic children have higher intraocular pressures than their
Ocular hypotensives that have been assessed for their effect
on myopia progression include labetalol and timolol (β adren-
ergic blockers).89Previous studies have found that timolol
maleate may affect sympathetic innervation to the ciliary
muscles and shift the resting position of accommodation.90 91
When labetalol eye drops (0.5% or 0.25%) were given twice
daily to 50 Japanese subjects, aged 6–14 years old for 2–4
months, a 0.25 D improvement in 68% of the eyes was
observed.80The results of these studies are difficult to interpret
because there was no control group. Several other studies also
did not include a control group or were not randomised.92 93A
randomised clinical trial of timolol 0.25% against spectacles in
150 Danish children showed no significant difference in the
progression of myopia in the two groups (−0.59 D per year in
the timolol group versus −0.57 D per year in the single vision
group) after 2 years.33Other ocular hypotensives that have
been evaluated in non-randomised clinical trials include
adrenergic agents such as adrenaline (epinephrine) and para-
sympathomimetic agents such as pilocarpine.3 94In general,
there is a lack of evidence supporting the hypothesis that
decreasing intraocular pressure may retard myopia progres-
sion and there may be risks of significant side effects such as
bronchospasm in susceptible individuals.95 96
BIOFEEDBACK VISUAL TRAINING
As early as the 1940s, Bates proposed that overaction of
accommodation.97Bates’s system of eye exercises are adminis-
tered by repeated testing with the same Snellen chart daily.
Visual training may change the way the autonomic nervous
system regulates the accommodative process.98This occurs
through a learning process possibly mediated by the
sympathetic nervous system. However, the efficacy of this
treatment has not been proved in randomised clinical trials.
Trachtman postulated that the ciliary muscle action responsi-
ble for refractive error change is susceptible to biofeedback
training.99Several other non-randomised studies have evalu-
ated “biofeedback visual training”and behavioural techniques
to improve visual acuity and reduce myopia.100–105If there were
any improvement in visual acuity, it was not clear whether it
was attributable to biofeedback visual training or, in fact, to a
learning effect after several repeated measures of visual
acuity.101There is currently no conclusive evidence that
biofeedback visual training is effective in retarding myopia.
1308 Saw, Gazzard, Au Eong, et al
TRADITIONAL CHINESE INTERVENTIONAL
Facial “Qi Qong” eye exercises were created in the 1950s in
China. It was postulated that massaging the various acupunc-
ture pressure points around the eye improves venous blood
circulation, relaxes the muscles, and reduces eye strain. These
eye exercises are part of the school routine in many parts of
China, and teachers guide the children in the performance of
these eye exercises as often as twice a day for 10 minutes. The
evidence from two non-randomised studies conducted in Sin-
gapore and Taiwan were inconclusive.106 107In another non-
randomised clinical trial of 242 adolescent eyes in 295 people
in Beijing, small pieces of adhesive pressure plaster grains of
Semen impatiens were evaluated. Significant treatment effects
CLINICAL IMPLICATIONS AND FUTURE STUDIES
Despite the extensive efforts that have been made to identify
interventions that may decrease the progression of myopia,
many previous studies were often limited by methodological
flaws. Large scale high quality masked randomised clinical
trials are necessary to test the efficacy of any treatment. We
would like to propose two high quality masked randomised
clinical trials to evaluate atropine eye drops and bifocals or
multifocals. In the first proposed atropine trial (the control
group is prescribed placebo eye drops),it is important to mask
the subjects and alleviate potential side effects of atropine by
the prescription of photochromatic lenses to block ultraviolet
light. If atropine eye drops are administered in both eyes and
there is reduced accommodative ability, multifocal lenses
should also be prescribed. The second proposed trial is the
evaluation of multifocal lenses in a double masked ran-
domised trial where both multifocal and ordinary prescription
lenses appear exactly the same. The patient should be advised
not to visit other optometrists or ophthalmologists to find out
the type of lenses the children have been prescribed. In addi-
tion, an independent and separate team could be employed to
perform the refractions. It is not possible at present, however,
to conduct masked trials to evaluate the effect of contact
lenses to retard the progression of myopia, because it is not
possible to mask the control group.
An evidence based review has shown that there are
currently few (n = 10) high quality, completed, well
conducted, masked randomised clinical trials that have evalu-
ated the efficacy of interventions to retard the progression of
myopia.109At present, there are four published randomised
clinical trials that have evaluated atropine eye drops, but only
three trials (two in Taiwan and one in the United States) were
masked.34 69 81 109Five randomised clinical trials that evaluated
the role of bifocals have been published thus far, but only two
trials conducted by Fulk et al in the United States were
masked.30 31 109There are no masked trials to evaluate the effi-
cacy of contact lenses.
To date, atropine eye drops appear the most promising.
Their use significantly decreased the progression of myopia in
Taiwanese children in several studies.34 68 69However, these
studies need to be replicated in other populations with
similarly high baseline myopia progression rates and possible
serious long term side effects evaluated in careful studies with
longer follow up. The results of trials evaluating pirenzipine
are keenly awaited, and it remains to be seen whether the
potential use of pirenzipine to retard myopia progression with
minimal side effects will be realised. The results of the clinical
trial by Fulk et al,31on bifocal lenses are encouraging, but
larger double masked randomised clinical trials are needed to
confirm its efficacy. Other interventions such as tropicamide
eye drops, ocular hypotensives, or traditional Chinese treat-
ments need further evaluation in well conducted randomised
trials. The identification of an effective therapeutic interven-
tion to retard myopia progression has the potential for greater
public health impact on the burden and morbidity from myo-
pia than the few treatments for its complications currently at
SM Saw, Department of Community, Occupational and Family Medicine,
National University of Singapore, 16 Medical Drive, Singapore 117597,
Republic of Singapore
SM Saw, K-G Au Eong, The Eye Institute, National Healthcare Group,
Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433,
Republic of Singapore
SM Saw, G Gazzard, K-G Au Eong, D T H Tan, Singapore Eye
Research Institute, 5th Level, SNEC, 11 Third Hospital Avenue, Singapore
168751, Republic of Singapore
SM Saw, G Gazzard, D T H Tan, Singapore National Eye Centre, 11
Third Hospital Avenue, Singapore 168751, Republic of Singapore
G Gazzard, The Institute of Ophthalmology, 11–43 Bath Street, London
EC1V 9EL, UK
D T H Tan, Department of Ophthalmology, Faculty of Medicine,
National University of Singapore, 10 Kent Ridge Crescent, Singapore
119260, Republic of Singapore
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