INTRODUCTION
Myopia is defined as the dioptric condition of the eye in which incident parallel rays of light from infinity come to a focus anterior to the retina, with the accommodation of the eye at rest. The increasing prevalence of myopia, especially in this Corona virus disease-2019 (COVID-19) pandemic era is a major challenge worldwide, leading to an epidemic in certain regions.
Myopia develops and progresses in a predictable pattern, beginning with normal vision at a young age. A myopic shift and rapid growth in myopia begins around school age and lasts until late adolescence.[1] According to a meta-analysis in 2020, the prevalence of myopia among Indian school children was 8.5% in urban and 6.1% in rural populations, with the highest prevalence in urban 11- to 15-year age group children in the last decade.[2] High myopia is defined as a condition in which the spherical equivalent refractive error of an eye is − 6.00D or above when ocular accommodation is relaxed.[3] Progressive myopia can lead to potentially blinding complications. Through this article, we are shedding light on a few strategies to prevent myopia progression.
Risk factors for progression
In defining a child's refractive error status, genetics appear to play an important role. Parental myopia is a risk factor not just for having myopia, but also for developing progressive myopia in children.[4] Children with at least one myopic parent had higher rates of myopic progression than children without a myopic parent (0.63 diopters/year vs. 0.42 diopters/year, respectively), according to Saw et al.[5]
Lack of outdoor activities has been demonstrated to increase the incidence and progression of myopia.[6] Higher light intensity present outdoors is thought to increase the depth of focus and lessen image blur. Furthermore, light stimulates the release of dopamine from the retina, and dopamine can impede eye growth.[7] So high levels of ambient light can significantly delay the onset and progression of form-deprivation myopia.[8]
A few studies have identified a robust link between near work and myopia progression. Most people accommodate only a fraction of what is required to bring the target into focus. The gap between the accommodating stimulus and the observed accommodative response is used to quantify this underaccommodation, which is referred to as a lag of accommodation. The development and progression of myopia have been linked to a greater lag of accommodation in connection with near work.[9] Myopes may experience extended periods of retinal defocus as a result of poorer accommodation to near targets, which has been shown to contribute toward increased eye growth, particularly vitreous chamber elongation in animal models of myopia.[10] Children who live in an urban environment and spend little time outdoors and those who are doing excess of near work are at a greater risk of progressive myopia.
CONTROL OF MYOPIA PROGRESSION
Myopia progression can lead to significant sight-threatening complications, such as amblyopia, myopic macular degeneration (MMD), retinal detachment, and cataract.[1112]
Chief beneficiaries of myopia control are children with low myopia who would otherwise progress to high myopia, with the attendant risks of visual morbidity later in life. The beginning of myopia at a younger age appears to be linked to a faster rate of progression.[13] The strategies for control of myopia progression include lifestyle modifications, pharmacological agents, and optical interventions. Despite lower efficacy, optical interventions may appear more appealing than pharmaceutical interventions because of the less significant side effects and the fact that myopic children are likely to wear an optical appliance anyway. Contact lens-based interventions generally appear to have a more robust effect in slowing myopia progression than spectacle-based interventions.[13] Knowledge of prior progression rate helps in deciding the appropriate intervention and it also provides a benchmark against which the efficacy of future treatment can be assessed. Initial cycloplegic refraction provides a baseline objective assessment before starting any intervention.
Lifestyle modification
The mechanism by which increased time spent outdoors is linked to a lower myopia incidence has not completely been elucidated so far. Animal models suggest that light exposure can stimulate retinal dopaminergic pathways, which then interfere with eye growth signaling pathways, preventing excessive elongation of the eyeball.[14] Variations in the chromatic light composition, differences in dioptric topographies, less near work, and a decrease in the accommodative demand are the other proposed reasons for the prevention of myopia incidence and progression.[15] Spending more than 2 h a day outside was linked to a lower risk of myopia, even in children who did a lot of near work.[7] A systematic review and meta-analysis were conducted to evaluate the effects of outdoor light exposure on myopia by Ciao-Lin Ho et al.,[16] and they suggest 10 h/week of outdoor light exposure time at school for myopia prevention. According to them, 10 h/week or 120 min/day can reduce myopia incidence by 63.7%. The risk of rapid myopia progression was 54% lower in children who spent at least 11 h/week outdoors at the end of 1 year according to the study done by Pei-Chang Wu et al. They also concluded that longer periods of relatively low outdoor light intensity, as in the shade of trees, maybe sufficient for the prevention of myopia onset and progression.[17]
Pharmacological agents to control myopia progression
Atropine eye drops
Atropine is a non-specific muscarinic acetylcholine receptor antagonist. The mechanism through which atropine slows down myopia progression is unknown. Two theories have been proposed to explain the action of atropine using experimental animal models. The first theory is that atropine binds to M1/M4 receptors in the retina and slows eyeball elongation through a neurochemical cascade; the second theory is that atropine directly inhibits glycosaminoglycan synthesis by scleral fibroblasts.[18] The Atropine for the Treatment of Myopia study (ATOM1) was a double-masked, randomized placebo-controlled trial of atropine eye drops, which involved 400 children with myopia in Singapore.[19] They found that the group which used 1% atropine eye drops in one eye every night for 2 years showed dramatic reduction in myopia progression and axial elongation when compared to the control group. The ATOM2 experiment looked at lower concentrations of atropine, such as 0.5%, 0.1%, and 0.01%, because 1% atropine caused allergic reactions, glare owing to pupil dilatation, photophobia, and blurry near vision due to cycloplegia.[20] When compared to 0.1% and 0.5% atropine, 0.01% atropine had fewer side effects and had a comparable effect on myopia progression. The 0.05% atropine was shown to be most effective in preventing myopia progression and axial elongation.[21]
The myopic rebound effect was more significant in eyes that got 1.0%, 0.5%, and 0.1% atropine than in eyes that received 0.01% atropine when treatment was stopped.[20] Previous studies showed that younger age and greater severity of myopia were risk factors for progression in a subgroup of children despite getting atropine treatment.[22]
In summary, there is a strong evidence that atropine can help delay the progression of myopia. Some long-term safety issues have not yet been addressed. However, the general consensus of the clinical studies is that the treatment is safe. Lower concentrations (0.01% and 0.1%) of atropine are better tolerated and could be an excellent clinical choice.[23] However, the efficacy of the weaker doses of atropine could be a concern[24] A once- or twice-weekly application of high-concentration atropine (0.5% or 1.0%) could be an alternative therapy option.[23]
Pirenzepine is a selective muscarinic M1 acetylcholine receptor antagonist. According to a multicenter trial conducted in Hong Kong, it can also be utilized in the form of a 2% gel to prevent myopia progression.[25] However, the use of pirenzepine eye drops as a myopia reduction therapy was discontinued, and it is no longer available as a therapeutic option.[26]
Optical control of myopia progression
Myopia of −3 to −5 D does not provide a substantial risk of amblyopia since near vision is often unaffected. Low myopes should have their glasses prescribed when they are three to four years old, as this is when they begin to spend considerable time looking at things far away. If the power is greater than −3D, glasses should be prescribed even in less than 3-year-old children. The goal is to prescribe the least amount of minus power necessary for the optimal visual acuity, and over-correction should be avoided at all costs.[27] According to recent research, under-correction may accelerate instead of slowing down myopic progression in children.[28] Six monthly reviews have to be done to watch for progression of myopia, if a single vision spectacle for correction is given.[26] It is critical to stick to the recommended wearing time and have regular clinical reviews.
Bifocal or progressive addition spectacles (PALs)
The fundamental mechanism by which progressive addition lenses reduce myopic progression is by minimizing accommodative lag during near work. This reduces retinal hyperopic blur which is a stimulus for the growth of eyeball.[29] It has been proposed that PALs are a better alternative to bifocal lenses because they provide clear vision at all distances and are more cosmetically pleasing, potentially improving compliance. A near addition of +1D to +2 D was found to be effective in reducing the progression of myopia. One reason why bifocal or PAL spectacles have not been very effective in delaying myopia progression is that children prefer to observe near objects through the distance portion of the spectacle lens rather than the near addition.
Correction of Myopia Evaluation Trial (COMET) is a randomized, double-masked, controlled clinical trial that compares the progression of myopia in children wearing PALs to children wearing standard single vision lenses (SVLs). Over a 3-year follow-up period, progression of myopia was significantly less in PAL group (+2D add) than in SVL group. Children wearing PALs had a mean increase in the spherical equivalent of −1.28D and axial length of only 0.64 mm compared to −1.48D and 0.75 mm in the case of the SVL group.[30]
Multifocal soft contact lenses
Multifocal soft contact lenses usually feature circular zones of varying power within them to let the eye concentrate on both far-away and close-up objects at the same time. Recently, a novel dual-focus (DF) soft contact lens, with a central correction zone and concentric treatment zones that simultaneously create myopic retinal defocus (focal point anterior to the retina), has successfully been shown to reduce the progression of both the myopic refractive error and the abnormal axial elongation of the eye.[31] The safest approach to wearing contact lenses is using daily disposable lenses. A child has to wear soft multifocal contact lenses for most of the waking hours for 6 to 7 days a week. According to Walline et al.,[32] soft multifocal contact lens wear resulted in a 50% reduction in the progression of myopia and a 29% reduction in axial elongation during the 2-year treatment period compared to the control group.
Orthokeratology (Ortho K)
Ortho K lenses consist of reverse geometry contact lenses that are worn overnight by children and removed when they wake up. It involves precise fitting of rigid contact lenses during nighttime. To restore clear vision, the central area of the cornea is flattened and this approach allows for spectacle-free vision throughout the day, while the mid-peripheral area is steepened to control myopia progression.[33] The current explanation for how Ortho K lenses might delay myopia progression is based on a shift in the position and shape of the image shell relative to the peripheral retina. Several investigations have documented this shift in peripheral refraction from predominantly hyperopic to predominantly myopic peripheral retinal defocus.[13] Contact lens application in youngsters can be challenging; this is greater in younger children. In addition, during the nocturnal usage of any contact lens, there is an inherently increased risk of corneal infection. The use of orthokeratology in high myopes is complicated by the natural rebound to its original corneal contour over the day, as there is a myopic shift toward the end of the day, which leads to decreasing vision over time.[34] Orthokeratology lenses are only worn at night and hence at home, parents will be able to monitor every element of use. The inhibitory effect of Ortho K lenses on axial elongation for 2 years has been reported to be from 32% to 63%, as compared with single-vision spectacles and contact lenses.[35]
Newer myopia control options
The status of the peripheral retina's refractive state can have an impact on eye growth.[36] Peripheral hyperopic retinal defocus was first suggested as a risk factor for myopia in the 1970's.[37] Based on the experiments in animals, it has been hypothesized that peripheral retinal hyperopic defocus in the human eye can cause accelerated eye growth. Therefore, optical lenses that either eliminate peripheral hyperopic defocus or produce myopic peripheral defocus slow the progression of myopia in children[38] [Figure 1].
;)
Figure 1: Peripheral retinal hyperopic defocus causing progression of myopia
Defocus incorporated soft contact (DISC) lens achieve peripheral retinal myopic defocus by incorporating concentric rings that provide addition of +2.5 D, in a manner that alternates with normal distance correction. Over a 1-year period, significant reductions in myopia progression and axial elongation were noted in the DISC group according to a randomized control trial performed in Hong Kong.[39]
Defocus incorporated multiple segments (DIMS) spectacle lenses were designed later to avoid the inconvenience and risk of contact lens use in youngsters. The lenses have a central optical zone that corrects myopia, as well as several segments of myopic defocus that stretch from the central zone to the lens's mid-periphery. The DIMS technology is based on the idea of creating simultaneous defocus during both distance and near viewing; one plane on the retina due to the lens' single vision zone (s) and one plane creating myopic defocus due to the + 3.50D defocus lenslets. DIMS had no effect on near phoria or accommodation lag[40] [Figure 2].
Figure 2: Defocus incorporated multiple segments lens designs (open access journal-Lam CSY, et al. Br J Ophthalmol: 104:363-368. doi: 10'1136/bjophthalmol-2018-313739)
Highly Aspherical Lenslet Target (H.A.L.T.) technology also aims at peripheral retinal defocus, thereby reducing myopic progression. Rather than concentrating light on two different surfaces, these aspherical lenses deviate rays of light in a nonlinear fashion, creating a three-dimensional quantity of light in front of the retina, called as the volume of myopic defocus.[41] These lenses consist of aspherical front surface with 11 concentric rings formed by lenslets of diameter 1.1 mm. The area without lenslets provides distance correction [Figure 3].
Figure 3: HALT lens technology (open access journal- Jinhua Bao et al. Br J Ophthalmol doi: 10.1136/bjophthalmol-2020-318367)
COMBINED THERAPY
Practitioners may think about combining the effects of more than one technique in cases of excessive myopia or exceptionally high rate of progression. Partially correcting vision using Ortho K lenses overnight and low-powered eyewear during the day is a viable solution. When considering other methods, care must be taken to ensure that the two strategies complement each other or at the very least do not work in opposition to one another. For example, the favorable effect of contact lenses for peripheral retinal defocus, which rely on active accommodation to deliver myopic retinal defocus during near tasks, may not be boosted by concurrent use of atropine 1%, which paralyzes accommodation.
UNDER TRIAL
Myopia X, a digital treatment to delay the progression of myopia, is a multicenter randomized control trial to see if it is safe and effective.[42] Artificial intelligence (AI) and other digital technological solutions have emerged as a viable adjunct for myopia management. Machine learning (ML), deep learning (DL), genomics, and natural language processing (NLP) are the four major AI disciplines in myopia. The majority of current AI research in myopia is focused on illness classification and prediction. By aggregating a wider range of criteria, such as genetics and environmental factors, AI will play an increasingly important role in large data analysis which may enable the development of a deep learning system. This could help us in developing a precise treatment that is both predictive and customized.[43] A study is now recruiting participants to test the efficacy of DIMS lenses and Apollo progressive addition spectacles (PALs) in preventing myopia progression in children aged 6 to 12 years.[44] The Personalized Addition Lenses Clinical Trial is a recent trial which compares the progressive addition lenses (PALs) with customized additional power, against standard +2.00D PALs and Single vision lenses.[45]
CONCLUSION
Prevention of myopia progression is very important to prevent its potentially blinding complications. Pharmacological and optical interventions along with lifestyle modification have made many contributions toward preventing the progression of myopia to some extent according to various studies. Interventions at the genetic level to tackle the problem of myopia and its progression have not been studied much. Future studies should aim at preventing the onset of myopia itself as the burden of the disease is increasing worldwide.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgements
I express my deepest gratitude to my teachers Dr. K. Mahadevan, Dr. Remya. R, Dr. Rekha. R.S Department of Ophthalmology, Sree Gokulam Medical College, Trivandrum for their valuable support and guidance.
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