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Myopia control--intervention strategies.

Promising outcomes in the field of myopia research show potential for intervention strategies to control myopia. This article discusses current developments in myopia control allowing practitioners to give informed advice to patients in practice

Course code: C-36384 | Deadline: June 6, 2014

Learning objectives

To be able to explain to patients about the clinical implications of myopia (Group 1.2.4)

To be able to advise on myopia control strategies based upon relevant history (Group 2.2.5)

To be able to understand the relationship between myopia and ocular disease (Group 6.1.1)

Learning objectives

To be able to understand the appropriate prescribing decisions relating to myopia correction (Group 7.1.3)

Introduction

Myopia is often accepted as a seemingly benign disorder, an inconvenience, for which spectacles and contact lenses remedy the blurred vision. Although the economic burden of myopia over an individual's lifetime is substantial, myopia is also associated with a number of pathological sight-threatening ocular conditions such as retinal detachment, glaucoma and macular disease. A meta-analysis published in 2012 highlighted the often complacent attitude towards 'physiological' or lower levels of myopia. (1) The analysis presented a particularly persuasive argument for myopia control by demonstrating that the risk of developing glaucoma and cataract associated with myopia is comparable to the risk of stroke from smoking greater than 20 cigarettes per day. Crucially, the risk of retinal detachment and myopic maculopathy associated with myopia is also greater than 'any identified population risk factor for cardiovascular disease'. The prevalence of myopia varies worldwide (see Figure 1) with near epidemic levels occurring by late adolescence in some East Asian countries. In the UK, myopia prevalence is approximately three times greater in 12 to 13-year-olds compared to six to seven-year-old children, highlighting the need for early intervention strategies to inhibit myopia progression. Furthermore, myopia prevalence is reported to be approximately double in South Asian children compared to white European children. (2) The underlying cause for myopia is unclear; differentiating between environmental and genetic factors is challenging since complex multi-way interactions between genes and specific environmental influences are believed to exist. (3)

As the prevalence of myopia increases, the risk of myopia related pathologies will also rise, thus there is a need to try and reduce myopia progression and ultimately to stop the development of myopia. Currently, while many possible interventions for myopia inhibition have been proposed, the data from research studies only supports some of these solutions.

Myopia control strategies

Myopia control strategies can be broadly divided into optical, pharmaceutical, and those which introduce a lifestyle change. (9) Vision training, biofeedback theories and behavioural techniques have also been purported as methods of myopia control; however, these have not been detailed in this article due to lack of evidence-based research.

There are several theories of myopia development underpinning the supposition that optical intervention strategies could arrest myopia progression. Myopia occurs when there is an imbalance between the three main refracting components of the eye: axial length, corneal power and lens power. Object rays converge at a point anterior to the fovea creating the blurred image experienced by myopes. In some animals, myopia can be induced by rearing neonates in the absence of all visual stimuli (form deprivation myopia) or, more commonly, through the use of negative powered lenses (lens induced myopia). The negative lens power shifts the focal point posterior to the retina, and in turn this prompts axial elongation and transient choroidal thinning leading to myopic refractive error. (10) The exact mechanism driving such eye growth is unknown, however, a widely accepted theory is that since there is no image anterior to or focused upon the fovea, the eye assumes the image must lie somewhere behind the retina and thus by axial elongation the retina 'searches' for the image (see Figure 2, page 48).

Research based upon animal models has led to the hypothesis that under-correction of myopia by single vision or multifocal lenses may help control eye growth in humans. A key point is that the eye does not know when to stop growing; if it did then we would have a perfect homeostatic system and refractive error would be self-limiting. (10) Some researchers have suggested that although a homeostatic mechanism may be in operation, in ametropic individuals growth may be regulated to a specific dioptric value (other than zero) predetermined by genetics or otherwise.

Another closely related theory is that of relative peripheral hyperopia. In the 1970s a series of studies set out to identify factors which contributed to pilots becoming myopic. It was reported that emmetropic pilots who had previously had a peripheral refractive error which was hyperopic relative to the central refractive error were more likely to develop myopia, although the interpretation of these studies has recently been challenged, relative peripheral hyperopia remains a popular theory of myopia development. (11-13) Further evidence supporting a dominant role of the peripheral retina in modulation of refractive error is from animal studies where despite a complete absence of foveal visual stimuli (but normal peripheral stimuli) the emmetropisation process is unaffected. (14)

Further work on humans has implicated ocular motor imbalances, namely, near esophoria and high accommodative lags in the development of myopia. The various theories have culminated in numerous investigations of standard and new optical appliances for the purposes of reducing myopia progression.

Optical interventions

Single vision under-correction

Under-correction of myopia reduces the accommodative demand for near work and the accommodative lag associated with development of myopia. Evidence from animal studies supports under-correction as a means of arresting myopia progression, however, on humans the results are equivocal. Ong et aP5 compared myopia progression rates in children who wore spectacles full-time with uncorrected myopes over a minimum period of three years, but failed to show any significant difference between the two groups. Conversely, other studies have reported that under-correction of myopia in children (by approximately 0.50-0.75D) can exacerbate myopia progression. (16-17) Data from monocular under-correction of myopia has yielded promising results with under corrected eyes showing an average of 0.36D/year less progression in myopia compared to the fellow fully corrected eye. (18)

At present, there is no consensus on the effectiveness of under-correction as a myopia control therapy and further investigation is required. Authors of the Full Correction and Under-correction of Myopia Evaluation Trial (FUMET) (19) identified a number of confounding variables which may have affected the outcomes of earlier studies; they hope to address these using a more rigorous experimental protocol.

Bifocal and progressive addition lenses

Prescribing multifocal spectacles reduces the near accommodative demand, and unlike under-correction, clear vision for distance objects is retained. Varying degrees of success have been reported for both bifocal and progressive addition lenses; in some cases success has been limited to subjects with large near esophoria, (20) large accommodative lags, (21-22) or rapid myopia progression rates. (23)

A recent report highlighted the likelihood of inducing an exophoric shift with bifocals in myopic children and, therefore, compared the effects of prismatic bifocal lenses with single vision and bifocal lenses. (24) Following a three-year trial, mean myopia progression rates were significantly slower in the groups wearing prismatic bifocals and bifocals (mean changes -0.34D/year and -0.42D/year respectively) compared to the single vision lens wearers (mean change -0.69D/year). Contrary to reports that near-phoria status dictate treatment success, there were no significant differences in progression rates between the two types of bifocal lenses.

Furthermore, although a significant difference in myopia progression rates between the bifocal and single vision lenses was reported for a three-year period, statistically significant changes only occurred in the first two years of the trial. Following publication of the preliminary trial outcomes at one year, (25) a Cochrane review highlighted some protocol shortcomings relating to the randomisation of children to the bifocal, prismatic bifocal and single vision groups. (26)

The results are similar to reports of multifocal lenses reducing myopia progression by approximately 0.25D/year, (27) although despite myopia progression in Asian children being significantly slower through use of multifocal lenses versus single vision lenses, in Caucasian children there was no significant difference.

Contact lenses

It has long been deliberated whether prescribing conventional contact lenses in place of spectacles will accelerate a child's myopia progression; most studies making this comparison have not found significant differences. (28-30) However, changing from spectacles to contact lenses does alter the peripheral refractive status, changing the relative defocus to myopic defocus with contact lenses. (31) If relative peripheral refraction is implicated in myopia development, such a change in peripheral refraction may reduce myopia progression.

Multifocal contact lenses

Soft multifocal contact lenses with a distance-centre design may slow the average growth of the myopic eye. A novel dual-focus (DF) soft contact lens, with a central correction zone and concentric treatment zones that simultaneously create myopic retinal defocus, has been shown to reduce the progression of both the myopic refractive error and the corresponding axial elongation of the eye. (32) The study design was a crossover paired eye control trial whereby one eye had a dual-focus lens with +2.00D peripheral myopic blur arranged concentrically in two treatment zones, and the other had a single vision lens. Both lenses were worn for a period of 10 months and then switched over for an equivalent period. The treatment, that is the imposition of dual focus, was significant, with a 0.25D reduction in myopia matched by correlated changes in axial length. This is an impressive result for a relatively short trial period and for a group of mixed ethnicity. The mean change in the DF lens wear eye (0.44D) was less than in the eye wearing the conventional lens (0.69D).

The fact that the children fitted with DF contact lenses showed normal accommodative responses suggests that it is the sustained myopic de-focus in the central and peripheral retina during both distance and near viewing that is responsible for the reduction in progression of axial myopia and not changes in accommodative lag. Others have found similar results; a novel contact lens designed to reduce relative peripheral hyperopia with a progressive increase in add showed less progression in the novel contact lens group than in controls. (33) Another research team has found similar results with a centre distance multifocal contact lens with the effect accruing over a two-year period. (34)

Orthokeratology

Corneal reshaping in orthokeratology traditionally eliminates the central myopic refractive error. It is becoming well-established that orthokeratology slows myopia progression by 50% on average in children. (35-37) The theory is that changes to the position and shape of the image shell relative to the peripheral retina results from steepening of the peripheral cornea in orthokeratology. This change in peripheral refraction from predominantly hyperopic to predominantly myopic peripheral retinal defocus has been reported in several studies. (38-39) One five-year study using orthokeratology has shown an average reduction in the rate of progression of myopia of 30% by inducing a flat-centre, steeper periphery hyperopia-reducing corneal shape. (35)

Pharmaceutical interventions

Atropine

Atropine is a non-selective muscarinic antagonist better known to optometrists for its cycloplegic properties, however numerous studies have advocated the use of atropine in myopia control. The Atropine in the Treatment of Myopia (ATOM) study in Singapore was a large scale intervention trial in which children were treated monocularly with either 1% atropine or with a placebo, and after 24 months a statistically significant difference in the progression of myopia between the treatment and placebo group was found (placebo group progression was on average greater by -0.46D/year). (40) After stopping the treatment the ATOM subjects were followed up for a further 12 months (41) and mean progression of myopia in the treatment group was reported as 1.14D (over the 12 months), and 0.38D in the placebo group that is cessation of treatment accelerated the rate of myopia progression, commonly referred to as a treatment 'rebound effect. More recently, Phase 2 of the ATOM study has reported on the efficacy of lower dose of atropine, 0.5%, 0.1%, and 0.01 %, on myopia progression. At the end of the 24-month treatment period myopia progression rates were -0.30D, -0.38D, and -0.49D for the 0.5%, 0.1%, and 0.01% groups, respectively. There was a statistically significant difference in myopia progression between the 0.5% and 0.01% groups; however, the minimal side effects from using a lower dose make 0.01% atropine a favourable option. The authors reported allergic conjunctivitis as the most common adverse effect in the 0.5% and 0.1% groups, but no cases of allergic conjunctivitis were reported in the 0.01% group. (42) A recent meta-analysis has indicated that atropine is more effective at controlling myopia progression in Asian children than Caucasian children. (43)

Several reasons prevent widespread adoption of atropine as a method of myopia control: risk of ocular and systemic side effects; possible rebound effect; and a poor understanding of the mechanisms by which myopia progression is being controlled.

Pirenzepine

Pirenzepine is also an antimuscarinic drug which has been used in the treatment of myopia progression. It is associated with fewer adverse effects than atropine, (44) but studies have shown it to be significantly less effective at controlling myopia than atropine. (45)

7-methylxanthine

7-methylxanthine (7-mx) is an adenosine antagonist, a metabolite of caffeine, which is currently being used in oral tablet form in Denmark for the inhibition of myopia progression. Animal studies suggest that 7-mx may prevent axial elongation through increasing the collagen fibril diameters, thereby thickening the posterior sclera. (46-47) A clinical trial (48) in which children were given either 400mg 7-mx tablets or a placebo for the first 12 months followed by 12 months of 7-mx treatment found that myopia progression was greater in the children initially treated with the placebo (-0.84D) compared to those who received 7-mx for the whole 24 months (-0.63D). Although myopia progression and axial elongation slowed down in the treatment periods, both the progression of myopia and axial elongation resumed at an invariable speed following cessation of the treatment.

Lifestyle factors

A systematic review and meta-analysis found the odds of myopia reduced by 2% for every hour spent outdoors per day. (49) A number of other large scale studies have also reported on the benefits of time spent outdoors in relation to myopia control. (50-52)

Perhaps the most convincing data supporting time outdoors is from a study comparing myopia prevalence in children of Chinese ethnicity living in Singapore with those living in Australia. The presumption was that the two groups would have a similar genetic makeup, allowing for a comparison of their different lifestyles. The children living in Singapore spent approximately 3.05 hours per week outdoors, but children living in Australia spent 13.75 hours per week outdoors. Myopia prevalence was significantly higher in the Singaporean residents (29.1% vs. 3.3%). Perhaps surprisingly, the children in Australia were found to do more near work than children in Singapore. The authors did note that Singaporean children are subject to greater amounts of preschool near work than their Australian counterparts and this may influence myopia development and/or progression. (53)

The mechanisms underlying the apparent benefits of being outdoors on myopia progression are unclear; animal studies have identified intensity and wavelength of light to play key roles in the development of myopia; both of these factors clearly differ between the indoor and outdoor environments. (54) One suggestion is that bright light may stimulate the release of the neurotransmitter dopamine which may, in turn, restrain eye growth. The role of vitamin D, commonly referred to as the 'sunshine vitamin' since the body produces it after exposure to UV light, has also been implicated by reports that blood levels of vitamin D is reduced in young adult myopes compared to non-myopes. (55) The role of the aforementioned peripheral retina must also be considered. Peripheral retinal defocus is believed to be greater indoors compared to outdoors due to fixation upon near tasks and enclosed spaces. However, an interesting suggestion is that under bright outdoor lighting conditions pupillary constriction may limit the amount of defocus on the peripheral retina. (54)

Despite uncertainties regarding the underlying action of time outdoors on myopia, it is still advocated as a practical solution to the increasing levels of myopia. The Singaporean Health Promotion Board have taken note of such research and launched the Keep Myopia at Bay. Go Outdoors and Play campaign in an effort to control myopia development and progression. (56) While time outdoors is a simple and inexpensive method of myopia control, prolonged exposure to sunlight can also lead to adverse consequences such as skin cancer, and so even time outdoors should be prescribed with caution.

Conclusion

Several questions remain before an optimum treatment strategy for myopia inhibition can be prescribed: When should intervention take place? Who is most likely to respond to treatment? How does the treatment work? How should success be monitored? What are the long-term effects? Is there a risk of a rebound effect? Who will fund the treatment? Research and clinical trials are ongoing and aim to address many of these questions. Additionally, until legislative measures and best guidance is issued, particularly for the pharmaceutical interventions, optometrists are somewhat restricted in prescribing myopia control therapies. For example, the University of Auckland and University of California, Berkeley are already offering patients a service for myopia control in the form of myopia control clinics. Universities in the UK are also establishing myopia control clinics (for example Aston and Glasgow Caledonian). Such endeavours will undoubtedly increase our understanding and ability to prescribe effective solutions for myopia control.

Reflective learning

Having completed this CET exam, consider whether you feel more confident in your clinical skills--how will you change the way you practice? How will you use this information to improve your work for patient benefit?

Exam questions

Under the new enhanced CET rules of the GOC, MCQs for this exam appear online at www.optometry.co.uk/cet/exams. Please complete online by midnight on June 6, 2014. You will be unable to submit exams after this date. Answers will be published on www.optometry.co.uk/cet/exam-archive and CET points will be uploaded to the GOC every two weeks. You will then need to log into your CET portfolio by clicking on 'MyGOC' on the GOC website (www.optical.org) to confirm your points.

Acknowledgement

The authors would like to thank Professor Bernard Gilmartin for his advice in writing this article.

References

Visit www.optometry.co.uk/ clinical, click on the article title and then on 'references' to download.

Manbir Nagra PhD, MCOptom, FHEA

Nicola Logan PhD, MCOptom, FHEA, PGCertHE

Dr Manbir Nagra is a post-doctoral researcher at Aston University in the field of myopia development.

Dr Nicola Logan is a lecturer in optometry at Aston University and convener of the Myopia Consortium UK.

Table 1 A review of myopia control data from 2011 (26)

Method                          Cochrane review conclusion (2011)

Spectacles

Under-correction versus full    * Limited evidence favouring
correction                      full-correction compared with
                                under-correction

Progressive addition lenses     * Clinically insignificant benefit of
versus single vision            using PALs
                                * Dioptric refractive error changes
                                are not supported by changes in axial
                                length and corneal curvature

Bifocals versus single vision   * Limited and inconsistent evidence

Contact lenses

Bifocal versus single vision    * Although a study has shown soft
                                bifocal contact lenses to help reduce
                                myopia progression, the study was
                                described in the Cochrane review as
                                being at 'high risk of bias'

Rigid gas permeable lenses      * Conflicting evidence. Success may be
                                related to subject ethnicity and/or
                                the technique to which it was being
                                compared

Pharmaceutical

Anti-muscarinic drugs           * Consistent data, inhibition of
                                myopia shown when compared to placebos
                                * Atropine found to be more effective
                                than pirenzepine and cyclopentolate
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Title Annotation:CONTINUING EDUCATION & TRAINING: 1 CET POINT
Author:Nagra, Manbir; Logan, Nicola
Publication:Optometry Today
Article Type:Disease/Disorder overview
Date:May 9, 2014
Words:3280
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