Myopia Control: Are We Ready for an Evidence Based Approach?

Considerable evidence suggests that spending more time outdoors, exposed to sunlight offers protection against myopia, even after adjusting for factors such as near work, parental myopia, and ethnicity [13‐15, 33, 68‐70]. Several investigations identified education and time spent outdoors as significant risk factors in the development of myopia [13, 40]. While the exact underlying mechanisms have not been confirmed, studies report a higher prevalence of myopia with decreased outdoor time and increased intensity, as well as duration of education [6]. In the attempt to explain the protective aspects of outdoor time, several theories have been proposed [70‐72], including higher light intensity and the spectral composition of sunlight as possible influential factors [8, 30, 69, 71, 73‐78].

A relevant amount of evidence indicates that interventions focused on increasing time spent outdoors by 40 to 120 min per day appear to have a positive impact on reducing the onset of myopia and slowing its progression [14, 15, 32‐34, 79‐82]. Among others, Cao et al. estimated the positive effect of outdoor time with an improved pooled risk ratio of 0.76 (95% confidence interval [CI], 0.67–0.87) for new myopia cases. Also, the effect on myopia progression reached a pooled mean difference of 0.15 (95% CI 0.06–0.23) D benefit on refractive error [68]. In the present literature search five articles [34, 80, 83‐85] reporting results from RCTs involving increased outdoor time or activity as an intervention were identified (Supplementary Table 2). One of these studies indicates that it is more the aspect of being outdoors, rather than the activity level that contributes to the protective effect of outdoor times [84]. A large cluster-randomized study from China estimated that 40 min of additional outdoor time per day decreased adjusted incidence by 16% (incidence risk ratio [IRR], 0.84; 95% CI 0.72–0.99; p = 0.035), compared to the control group maintaining their habitual outdoor time [83]. In Taiwan, an educational policy mandating a minimum of 80 min of daily outdoor time led to a notable reduction of myopia incidence, dropping from 17% to 8%, and a decrease in the myopic progression from 0.38 to 0.25 D, particularly evident in children who had not yet developed myopia [80, 86].

Although spending time outdoors seems generally safe, it is nonetheless important to consider the potential risks linked to outdoor activities, which necessitates appropriate application of sun protection for both the eyes and skin [19]. Increased outdoor time is accessible to all individuals but may be constrained by social factors such as academic expectations, weather conditions, and seasonal variations [87]. A shift towards more outdoor activity could even increase student productivity and performance: a recent Chinese study showed that school children, aged 8 to 10 years, who spent an additional 2 h outdoors, reached statistically higher academic performance compared to those who followed the regular curriculum without extracurricular physical activity outdoors [85]. However, successful implementation of such a public health intervention still requires more public and governmental awareness, as well as strategies to overcome existing hurdles to achieve more time outdoors each day [6].

The use of electronic devices in education and daily life has led to increased screen time and indoor activities associated with myopia in children, especially since the COVID-19 pandemic [88, 89]. In the Generation R study, Enthoven et al. found a connection between myopia and increased computer usage among 9-year-old children: near work activities, including reading and computer usage, was estimated to have an odds ratio of 1.072 (95% CI 1.047–1.098) for myopia [36]. School-based photo examinations in 2020 suggested a noticeable increase in myopia progression, surpassing the highest recorded levels between 2015 and 2019 in younger children aged 6–8 years [90]. Similarly, Wong et al. suggested that more time spent on digital screens is associated with a higher risk of myopia [91]. Hence behavioral approaches to reduce prolonged near work are gaining more attention [19, 20, 92]. Interventions restricting screen time in schools have been implemented in mainland China to mitigate myopia [19]. Tools like the Clouclip® are promoted in China to notify children and parents about detrimental viewing habits [93, 94]. To this point, it is still challenging to measure the effect of reduced screen time or prolonged near work as a myopia control intervention. However, there are no safety issues regarding a reduction in near work time. Also, there are no costs involved unless special measurement tools are employed.

Atropine is a non-specific muscarinic acetylcholine receptor antagonist. The specific mechanism through which it decreases the progression of myopia is not completely understood. Currently, a non-accommodative mechanism is considered most plausible. Accordingly, alternative atropine targets have been suggested, e.g., eye growth regulatory pathways originating in the retina and transmitted to the sclera [95, 96].

While higher concentrations of atropine have demonstrated higher effectiveness, the increased side effects, e.g., cycloplegia with near vision disturbances and photophobia as well as more pronounced rebound effect, limit its use [45, 97‐102]. Low-dose atropine for myopia control has been extensively investigated around the world, but mostly in Asia and Chinese children [45, 103‐106]. In the Low-Concentration Atropine for Myopia Progression (LAMP) study, involving children aged 4–12 years, those treated with 0.01%, 0.02%, and 0.05% atropine showed reductions in spherical equivalent progression by 27%, 43%, and 67%, and axial length growth by 12%, 29%, and 51%, respectively [105]. In contrast, the 3-year results of the Childhood Atropine for Myopia Progression (CHAMP) study indicate a larger effect on myopia progression in the group receiving a lower low-dose atropine of 0.01% (with a significantly increased responder proportion, odds ratio [OR], 4.54; 95% CI 1.15–17.97; p = 0.03) compared to 0.02% low-dose atropine (OR, 1.77; 95% CI 0.50–6.26; p = 0.37) (Supplementary Table 3) [107]. Moreover, poor response to atropine can occur in more than 10% of patients, which seems to be associated with younger age, higher baseline myopia, and myopic parents [99]. In the recent network meta-analysis (NMA) conducted by Ha et al., eight different concentrations of atropine were compared, five of which demonstrated a higher mean difference (MD) relative to the control treatment: 1% (MD, 0.81; 95% CI 0.58–1.04), 0.5% (MD, 0.70; 95% CI 0.40–1.00), 0.1% (MD, 0.50; 95% CI 0.14–0.87), 0.05% (MD, 0.62; 95% CI 0.17–1.07), and 0.01% (MD, 0.39; 95% CI 0.21–0.57). However, head-to-head comparisons revealed no statistical difference among atropine concentrations, except for 0.01% vs. 1% (MD, − 0.42; 95% CI − 0.71 to − 0.13) [48]. Similarly, in another recently published systematic review the estimated mean difference (MD) for myopia progression for atropine was found to be 0.29 D (95% CI 0.22–0.36; p = 0.03) [58]. In the present review, the most recent 16 out of initial 41 articles on RCTs were analyzed (Supplementary Table 3): a noticeable difference between these studies can be observed in terms of sample size [107‐109], study length and design [110‐114], the age of the children studied [106, 109], location of trial [115‐117], and the different atropine doses, which varied between 0.0025% and 1%, as well as the application frequency of drops [110, 114, 118, 119], and lastly their aims [109, 111, 112, 120]. Almost half of the selected studies were conducted in East Asia, in predominately Chinese ethnic children [109, 110, 114, 115, 118‐120]. Four studies were conducted in Europe [107, 111, 112, 116], two in India [113, 117], one in Iran [108], one in the USA [121], and one in Australia [106]. Upon comparing these studies, it may be inferred that varying ethnic groups exhibit dose-dependent differences in the pharmacokinetics and the effect of atropine. While reduced myopia progression was observable in several studies with low-dose atropine [108, 110, 112, 113, 115, 117‐119], in two studies, one conducted in the USA and one in Ireland, 0.01% low dose atropine was not or only minimally effective [116, 121] (Supplementary Table 3). Another possible explanation could be the differences in atropine eye drop composition, e.g., content of preservatives and pH, in the various studies as recently pointed out by Iribarren et al. [122]. It was noticed that studies conducted in Western Caucasian populations [107, 116, 121], showing low to no effect on myopia progression, used the same patented formulation with low pH and containing benzalkonium chloride, while previous studies in Asia had used compounded drops. Similarly, there are differences regarding safety and adverse events (AE). While in Chinese Asians even higher low-dose atropine doses, such as 0.1%, still entail relatively acceptable AE, the same doses seem to be problematic in non-Chinese ethnic children. Therefore, in Asian regions, there is ongoing debate about the appropriate dose, frequency, and tapering of atropine to mitigate rebound effects. Whereas in Europe and North America the debate addresses the effectiveness and safety of atropine.

As to long-term effects, a recently published analysis, on 18% and 40% of study participants of the Atropine for the Treatment of Myopia (ATOM) 1 and ATOM2 studies after 20 and 10 years, respectively, who received short-term use of atropine in childhood, found no long-term side effects. There was not an increased rate of cataract or other ocular complications in the atropine-treated eyes 10 and 20 years later, respectively. Also, no differences in spherical equivalent refraction (SER) and axial length (AL) between atropine-treated and untreated fellow/placebo eyes were observed [123]. However, this may have been caused by a rebound effect since most of the study participants discontinued atropine treatment abruptly without tapering. Other publications on long-term effects of atropine indicate that the use of topical atropine eye drops does not lead to ocular hypertension and observed treatment effects are not correlated with the total cumulative dosage of atropine administered [124]. The effect of atropine (0.05% and 0.1%) has shown to last up to 4.5 years, with smaller rebound in long-term use [48, 125]. Despite its extensive use in numerous clinical trials (Supplementary Table 3), no systemic adverse effects have been reported [19]. However, both the effect and safety of atropine remain controversial, which likely has led to differing opinions on its use [66, 121, 126]. In regions where atropine is relatively widely used to control myopia progression in children, studies are being conducted to investigate its use for preventing myopia onset in premyopic children and have shown positive results [109, 120].

Besides the differences in the formulation of atropine eye drops, there are important differences in the availability and accessibility, as well as their actual costs. According to various sources, estimated costs range between 120 and 1000 USD per year [127‐130]. Since the US Food and Drug Administration (FDA) and most regulatory authorities, with some few exceptions, have not granted regulatory approval for the use of any pharmacological agents for myopia control, in most countries, atropine is used off-label. Manufacturing atropine in low doses in bulk quantities would likely make it cost-effective [131].

Introduced in the 1990s as an attempt to slow myopia, progressive addition lens (PALs) and bifocal spectacles have been the subject of multiple studies, mostly conducted before 2000 [64, 132, 133]. Brennan and Cheng carefully analyzed the literature and concluded that results are indeed still very contradictory [134]. Some studies found minimal effects with bifocal spectacles [64]; whereas others suggested a substantial reduction in myopia progression among children using bifocals, with certain executive bifocal spectacles showing a decrease in myopia progression by 39% [133]. However, the effect may be more pronounced in children with higher myopia (< − 3.0 D), accommodative lag, or near esophoria [132, 135]. For PALs, a meta-analysis reported modest reductions in myopia progression (0.25 D, 95% CI 0.13–0.38; nine trials) and AL (− 0.12 mm, 95% CI − 0.18 to − 0.05; six trials) [136]. The sole article found on an RCT investigating PALs for myopia control was authored by Hasebe et al. in 2014 (Supplementary Table 4). They conducted a masked, crossover RCT including 303 children aged 6 to 12 years with myopia of − 1.0 to − 4.5 D. A total of 169 children completed follow-up at 24 months. Only the stronger + 1.5 D positively aspherized PALs showed some retardation of myopia progression [137]. PALs and bifocal spectacles may be more readily available compared to other optical interventions; also, associated costs are moderate to high (in the range of 300–900 USD) [138]. However, since these spectacles can cause some visual distortion and influence the appearance of the wearer, they are generally unpopular [6].

Two types of pre-DIMS spectacle lenses failed to demonstrate a significant effect on myopia progression [139‐141], before Lam et al. introduced the DIMS lenses [142, 143]. The DIMS lens design includes a central optical zone for correcting refractive error and multiple segments with constant myopic defocus (+ 3.50 D) around the central zone. This enables clear central vision providing myopic defocus simultaneously [19, 144]. Lam et al. conducted a clinical trial in Hong Kong: after 2 years children using DIMS lenses exhibited 52% less myopia progression and 62% less axial elongation compared to those wearing single vision spectacle lenses (Supplementary Table 4) [144]. After 3 years significantly lower SER and AL were observed: Specifically, the adjusted mean differences were − 0.18 ± 0.42 D for SER (p = 0.012) and 0.08 ± 0.15 mm for AL (p = 0.001), comparing DIMS to the historical control group, and − 0.30 ± 0.42 D for SER (p < 0.001) and 0.12 ± 0.16 mm for AL (p < 0.001), comparing the control-to-DIMS to the historical control group [144]. Notably, approximately 20% of DIMS lens wearers showed no myopia progression during the study. In the framework of the present literature search, two further reports were identified, but not included as they reported results from the same study population [145, 146]. Liu et al. reported data from a large RCT involving patients aged 6 to 16 years, 3639 with DIMS and 6838 with single vision lens (SVL). Significantly slower progression at both 1-year (2240 pairs) and 2-year follow-up (725 pairs) with DIMS was observed. In the 1-year subset, 40% and 19% showed myopia progression of maximum 0.25 D for the DIMS and the SVL groups, respectively (χ², p < 0.001). DIMS spectacles appear to be safe. The main reported complaint in the mentioned studies was occasional blurred vision in the mid-periphery [143].

Another new lens design incorporates (highly) aspherical lenslets. Bao et al. first presented these lenses in a study in which children aged 8–13 were randomly assigned to three different treatment options: single vision lenses (SVL), lenses with highly aspherical lenslets (HAL), and mildly aspherical lenslets (SAL). Spectacles with aspherical lenslets were more effective in slowing axial growth compared to SVL. Moreover, their study indicated that the efficacy of myopia treatment increased with higher levels of lenslet asphericity [147]. The myopia control efficacy measured as SER was 67% (with a difference of 0.53 D) for HAL and 41% (with a difference of 0.33 D) for SAL in comparison to SVL. For AL, HAL showed a 64% reduction (with a difference of 0.23 mm), while SAL exhibited a 31% reduction (with a difference of 0.11 mm) (p < 0.01) [147]. Li et al. reported the 3-year results of the Bao et al. study, showing a continued effect of reduced myopic progression with HAL compared to a new control group (Supplementary Table 4) [148]. Another RCT conducted in Vietnam was double-masked, crossover and involved 119 children randomly assigned to either HAL or SVL for 6 months before switching spectacle types. The observed mean change after 12 months was − 0.05 ± 0.37 D with HAL vs. − 0.33 ± 0.27 D with SV for SER and 0.05 ± 0.12 mm with HAL vs. 0.17 ± 0.13 mm with SV in AL [149]. No relevant side effects were mentioned. Overall, the discomfort of wearing any of the novel lenses appears to be comparable to SVL.

DOT lenses were designed on the basis of the hypothesis that reduced contrast signaling in the retina may slow myopia progression [150]. Although our current comprehension of the optical signals influencing refractive development in humans remains incomplete and the literature presents mixed findings, it seems the accommodated eye experiences reduced vergence-related blur during indoor activities, potentially resulting in higher-contrast signaling [8]. Currently, there is one three-armed RCT ongoing, the Control of Myopia Using Peripheral Diffusion Lenses Efficacy and Safety Study (CYPRESS) (Supplementary Table 4). Two types of diffusion optics technology, test 1 and test 2 lenses are assessed. The 12-month results published in 2022 showed a mean difference in SER progression for DOT test 1 vs. SVL of − 0.40 D (p < 0.0001), and − 0.32 D for DOT test 2 (p < 0.0001). The difference in AL progression for DOT test 1 vs. control was 0.15 mm (p < 0.0001) and DOT test 2 vs. control was 0.10 mm (p = 0.0018) [150]. No additional publications reporting results from RCTs on DOT were found.

The CARE lenses were recently patented as myopia control lenses. Developed by researchers at Wenzhou Medical University, these lenses generate blur signals on the retina by induction of high-order aberrations. These lenses comprise a central optical area providing full correction and a control area featuring numerous microcylinders arranged in concentric circles. A recently published article by Liu et al. reported the 1-year results of an RCT conducted with the CARE lenses (Supplementary Table 4) [151]: in comparison to SVL spectacles, study participants wearing CARE spectacles presented significantly reduced rate of axial elongation (with 0.27 ± 0.02 mm and 0.35 ± 0.02 mm for the CARE and SVL groups, respectively; F = 6.692, p = 0.011). However, the model-adjusted 1-year changes in SER − 0.56 ± 0.06 D for the CARE and − 0.71 ± 0.07 D for the SVL group were not statistically significant.

The SMC lens involves a central vertical aperture, known as the central vertical canal, designed to correct distance refractive error. The outer region of the lens features a power profile with a comparatively higher positive power than the central aperture, resulting in peripheral defocus. In an RCT conducted in Israel, Yuval et al. found SMC lenses to slow down AL elongation, but not SER progression after 1 year compared to SVL by 0.11 mm (35%, p < 0.05) and 0.16 D (25%, p = 0.122), respectively (Supplementary Table 4) [152].

Additional studies in diverse populations including clinical trials and real-world settings are necessary to confirm and validate the effectiveness of these newer optical interventions. Overall, these spectacles are gaining more and more popularity [66], because they seem safe, they do not create visual distortion, and above all their appearance is similar to SVL spectacles. Compared to SVL spectacles, however, these myopia control spectacles are significantly more expensive and not accessible to everyone. A pair of DIMS or HAL spectacles involves costs in a range of 500 to 1000 USD [153‐157]. DOT test 1 spectacles, CARE, and SMC are in the process of approval in various countries [158, 159].

There is an increasing use of different bifocal and multifocal soft contact lenses (SCL) and approved myopia control lenses for managing myopia in children [160]. Several studies investigating the effects of different SCL exist and effects of slowing myopia progression by 30–45% and AL by 31–51% over 24 months with bifocal SCL have been reported [49, 161‐163]. In children with faster myopia progression, effectiveness may improve with increased wear time, and with lens designs possessing higher hyperopic power in the mid-periphery (up to 6 D) [164, 165]. In a recent meta-analysis Lanca et al. [58] estimated the myopia progression mean differences (MD) for SCL at 0.39 D (95% CI 0.21, 0.56; p < 0.001); however, different types of myopia-controlling bifocal and multifocal SCL were included in this investigation. Besides the study reported by Lam et al., in which defocus incorporated soft contact (DISC) lenses reduced myopia progression by 60% [166], four more recently published RCTs about different SCL to reduce myopia progression were included in this review (Supplementary Table 5) [167‐170]: The first reported results from a double-masked RCT conducted in multiple centers in China and North America involved approximately 200 children, randomly assigned to four arms: two prototype myopia control SCL with non-coaxial ring-focus designs, one for enhancing efficacy (EE) and one for enhancing vision (EV), compared to dual-focus and SV SCL. The EE SCL showed the most significant effect on axial elongation reduction (compared to the dual-focus: − 0.049 mm [− 0.093, − 0.004]) [167]. The second study also compared two myopia control SCL with SV, and both myopia control SCL showed similar effectiveness in delaying myopia progression [168]. The third and fourth studies, one from Spain and a smaller one from Malaysia, reported similar effects of again other myopia control SCL [169, 170]. In summary, a heterogenous group of different myopia control SCL exists. As all contact lenses do, myopia control with SCL carries a potential risk of infective keratitis and contact lens intolerance, especially in children and if proper hygiene is lacking. Hence the indication to employ contact lenses should be made with caution by clinicians. Besides local adverse reactions and the possibility of infection, there is currently also nearly no data on the effects of discontinuation and potential rebound effects of SCL used in myopia control. Despite potentially irreversible complication of these contact lenses, their use is increasing, possibly because of demand and pressure from patients and their parents who may prioritize the greater convenience of contact lenses and being free of spectacles [171, 172]. The expenses are considerably high, with annual costs for some daily disposable soft multifocal contact lenses starting at around 1500 USD [173].

Orthokeratology (OK) lenses are rigid gas-permeable contact lenses worn during sleep to alter corneal topography [6, 174]. Typically modern OK lenses are designed to incorporate four zones: a central optic zone for flattening the central cornea and refractive correction, the reverse zone with a steeper curvature, the alignment zone (usually aspherical or tangent) for lens centration, and the peripheral zone [6, 175]. Myopia control with OK is primarily based on the hypothesis of inducing myopic defocus on the peripheral retina, but further research is necessary to understand the precise mechanism responsible for OK effectiveness [176‐178]. Several clinical studies have demonstrated the effectiveness of various OK lens designs in inhibiting myopic progression [175, 179]. Meta-analyses have shown a 30–60% reduction in myopia progression rate with OK lenses compared to controls using SV spectacles over 1–2 years of treatment [180‐187]. In a meta-analysis by Sun et al., the pooled results revealed a mean AL reduction of 0.27 mm (95% CI 0.22, 0.32) after 2 years, corresponding to a 45% reduction in myopic progression [188]. A similar result was recently reported by Lanca et al., who estimated the AL elongation MD for OK to be − 0.24 mm (95% CI − 0.33, − 0.15) [189]. However, the effect of OK appears to decrease gradually over time, and a distinct rebound effect has been noted upon sudden cessation of the treatment. Discontinuation of OK before the age of 14 years may lead to acceleration of AL elongation [190]. Additionally, there is a potential non-response rate of 7–12% [183, 190, 191]. The effect of OK, as well as the effect of previously described myopia control SCL, seems to be stronger in individuals with large pupils, while a reduced effect of OK lenses was reported in the presence of astigmatism [192, 193]. Three articles on RCTs were further identified and included in this review (Supplementary Table 5) [194‐196]. Corneal staining is the most common complication in OK treatment, and the frequency and severity of staining are associated with overnight lens wear [197‐199]. Safety concerns with OK lenses are considerable because of the risk of sight-threatening microbial keratitis with potentially irreversible corneal scarring [182]. OK lenses pose a risk of infective keratitis similar to overnight SCL wear, with an estimated incidence of 13.9 per 10,000. Specialists’ support is required, and OK lenses should only be indicated in selected cases, such as older children and in higher degrees of myopia [200, 201]. Costs of OK lenses reach up to 3000 USD initially and thereafter they are in the range of those for multifocal SCL. Despite the safety and rebound issues, OK lenses are popular because they offer improved unaided vision during the day and the ability to control myopia progression [197].

Recently repeated low-level or low-intensity red-light (RLRL) has been introduced for myopia control. Red-light encompasses visible light ranging from 600 to 700 nm in wavelength and seems to influence mitochondrial function, with potential for improving hypoxia and inhibiting inflammation, e.g., by reducing pro-inflammatory cytokines [202]. RLRL has been employed in other clinical sectors to treat a variety of diseases, including among others dermatologic and orthopedic disorders [203]. Since retinal photoreceptor cells contain many mitochondria, the idea arose to apply RLRL to the eye and thereby specifically to control myopia. However, the mechanism behind RLRL in controlling myopia remains unclear [202, 204]. Currently, limited evidence is available, as only a few clinical studies have been conducted. So far three groups from China have published results on RCTs in which red-light for myopia control was investigated (Supplementary Table 6): Jiang et al. and Xiong et al. tested a red-light (wavelength of 650 nm) desktop light device and showed effective AL elongation reduction at 12- and 24-month follow-up visits for the group undergoing red-light treatment. The overall axial elongation was the smallest in the continuous RLRL treatment group (0.16 ± 0.37 mm), and highest in the SV spectacles group (0.64 ± 0.29 mm; p < 0.001) after 24 months [205, 206]. Similarly, Tian et al. also found a significant effect on the median 6-month changes in AL of the red-light and control groups: − 0.06 mm (IQR − 0.15, 0) and 0.14 mm (IQR 0.07, 0.22; p < 0.001) [207]. A third, smaller study by Chen et al. showed an effect on AL with RLRL treatment [208]. All three aforementioned RCTs did not report any structural changes by means of optical coherence tomography (OCT) or significant severe adverse events during and after the red-light treatment [205, 206, 208]. Nevertheless, caution is advised regarding the safety of RLRL, because the reported RCTs did not involve any independent safety monitoring. Well-designed and larger RCTs with longer follow-up periods are necessary [209]. One case reported by Liu et al. raised some further uncertainty: a 12-year-old girl experienced bilateral vision loss over 2 weeks following 5 months of repeated exposure to RLRL treatment for moderate myopia in both eyes. In addition to the vision loss, her fundus showed darkened foveae and OCT revealed disruptions in the foveal ellipsoid and interdigitation zone. After 3 months without RLRL therapy, there was partial recovery of bilateral outer retinal damage, and visual acuity improved [210]. The case was discussed and a genetic evaluation was recommended, as the possibility was expressed that the girl may have preclinical Stargardt disease [211]. The recommended genetic clarification of the case has not been carried out to date. Ostrin et al. expressed further concerns after studying two red-light therapy devices regarding their thermal and photochemical effects. Both devices approached or surpassed the maximum permissible exposure [212]. Despite the still limited data available, particularly on the safety of this intervention, RLRL treatment for myopia control is already commercially available in China, and is becoming available in Australia, New Zealand, Japan, and Europe. Information on the yearly treatment cost is vague, but the costs will most likely be around 1000 USD for one year [213, 214]. Meanwhile, over a dozen trial registrations have been identified for ongoing investigations on efficacy and safety of RLRL treatment [215‐230].

Sunlight comprises a notable portion of short-wavelength visible and non-visible light, including blue and ultraviolet light [75]. Since in animal studies exposure to blue and violet light was found to inhibit myopic shift and axial elongation [231‐233], Torri et al. suggested that VL, with a wavelength of 360–400 nm, mostly absent in indoor environments, may play a role in inhibiting myopia development and progression [234]. In the attempt to prove this theory, a retrospective analysis was conducted comparing children wearing spectacles and contact lenses blocking VL with children using VL-transmitting contact lenses or spectacles. Significant differences in the AL of the two groups (p > 0.05) in favor of the VL-transmitting lenses were found [234]. Similarly, they also found that in highly myopic adults with two different types of phakic intraocular lenses, non-VL-transmitting and VL-transmitting, the non-VL-transmitting lens group had significantly higher myopia [235]. To date, there is one publication, from the same research group, reporting results from an RCT conducted in Japan: children randomly received VL-transmitting or conventional spectacles (Supplementary Table 6). Per protocol analysis revealed the AL variation after 24 months was 0.758 mm (95% CI 0.711–0.810) in the placebo group and 0.728 mm (95% CI 0.682–0.775) in the VL group. The VL group exhibited a slight average reduction in AL and a small non-significant change in SER. A statistically significant difference in mean AL change in the VL group (difference, − 0.206 mm; 95% CI − 0.351, 0.060; p = 0.006) was found in a small subgroup of 11 children, who were first-time spectacle wearers [236]. In summary, although VL could be promising, the evidence regarding its effect is currently very limited. Further studies are underway, including some in which VL-emitting spectacles are being tested [237, 238].