key: cord-0901897-oy1127py authors: Karthikeyan, Siddharth K; Ashwini, D L; Priyanka, M; Nayak, Anush; Biswas, Sayantan title: Physical activity, time spent outdoors, and near work in relation to myopia prevalence, incidence, and progression: An overview of systematic reviews and meta-analyses date: 2022-02-25 journal: Indian J Ophthalmol DOI: 10.4103/ijo.ijo_1564_21 sha: c376152df891e02536a3bd9a4ee5c5dba3af353b doc_id: 901897 cord_uid: oy1127py Myopia has reached epidemic levels in recent years. Stopping the development and progression of myopia is critical, as high myopia is a major cause of blindness worldwide. This overview aims at finding the association of time spent outdoors (TSO), near work (NW), and physical activity (PA) with the incidence, prevalence, and progression of myopia in children. Literature search was conducted in PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, ProQuest, and Web of Science databases. Systematic reviews (SR) and meta-analyses (MA) on the TSO, NW, and PA in relation to myopia were reviewed. Methodological nature of qualified studies were evaluated utilizing the Risk of Bias in Systematic Review tool. We identified four SRs out of which three had MA, which included 62 unique studies, involving >1,00,000 children. This overview found a protective trend toward TSO with a pooled odds ratio (OR) of 0.982 (95% confidence interval (CI) 0.979–0.985, I(2) = 93.5%, P < 0.001) per extra hour of TSO every week. A pooled OR 1.14 (95% CI 1.08–1.20) suggested NW to be related to risk of myopia. However, studies associating myopia with NW activities are not necessarily a causality as the effect of myopia might force children to indoor confinement with more NW and less TSO. PA presented no effect on myopia. Though the strength of evidence is less because of high heterogeneity and lack of clinical trials with clear definition, increased TSO and reduced NW are protective against myopia development among nonmyopes. STATA version 12.0 software (STATA Corporation, College Station, TX, USA) was used to perform statistical analysis. Pooled odds ratio (OR) and Mantel-Haenszel random-effects model with 95% CI was used to analyze dichotomous outcome data and data for MA, respectively. I 2 test was used to assess statistical heterogeneity; high heterogeneity was considered if I 2 ≥50%. MA and heterogeneity calculation were done only to estimate prevalence of myopia in association with TSO. The MA was done after removing the duplicates to avoid repetition of data. There were six overlaps, and finally, it was 14 primary study data used for MA after removing duplicates. As the number of included data were minimum, duplicates were removed manually. Standardized effect estimated values of included papers have been incorporated in the MA of current study. We identified 6768 articles from the various databases. After removing the duplicates and screening of the articles for eligibility, we identified four SRs out of which three had MA included for review. The included SRs had 62 unique studies. [ Table 1 and Appendix-Tables A4-A6]; details mentioned in Fig. 1 . Among two prospective cohort studies, one with 9109 children, extreme levels of PA had borderline association with incident myopia (≥ -1.0 DS), (OR: 0.88, 95% CI: 0.76-1.01, P = 0.062). Similarly, myopia had a higher risk (HR: 1.17, 95% CI: 1.10-1.24) related to sedentary time (accelerometer). [11] Another questionnaire-based study with 151 medical students (mean age 23.1 years) showed that nonmyopic students had more PA than their myopic counterparts (60 vs 51 min/day, P = 0.049). The increase prevalence of myopia (≥ -0.50 DS) was from 37 to 42.7% within 2 years of study span [ Table 1 and Appendix- Table A6 ]. [24] Among six cross-sectional studies (8242 children), comparison between children with PA (>3 h/week) vs sedentary lifestyle revealed that self-reported PA was associated with lower prevalence of myopia (≥ -0.50 DS) (OR: 0.46, 95% CI: 0.23-0.90, P = 0.027). [25] Results with PA measured using wrist-worn accelerometers and myopia (≥ -0.75 DS); the mean difference in the PA levels between the emmetropic and myopic participants was not significant (P = 0.14). [26] Questionnaire-based studies demonstrated myopic children spent less time playing sports than emmetropes ([1.87 vs 4.04 hours/day, P < 0.0001], [27] [0.72 vs 0.85 h/day, P = 0.007], [28] and [7.4 vs 9.7 h/week]). [29] Protective effect (questionnaire-based) on myopia was found with daily PA and sports (OR: 0.89, 95% CI: 0.86-0.93) [27] and weekly PA (OR: 0.94, 95% CI: 0.89-0.98, P = 0.0045). [29] Questionnaire-based PA assessment demonstrated myopic refraction which is least (+0.56 DS, 95% CI: 0.38-0.75, P = 0.04) in participants with high levels of outdoor activity and low levels of NW. [30] The association of outdoor sports was high with reduced myopia prevalence (OR: 0.90, 95% CI: 0.84-0.96, P = 0.004) and indoor PA failed to show any such association. [28] However, participants with low levels of outdoor activity and high levels of NW demonstrated myopic refraction more (+0.27 DS, 95% CI: 0.02-0.52, P = 0.06). [30] One case-control study (131 adult men) investigating childhood effect of PA and myopia (≥ -0.25 DS) concluded that myopic adults recollected being less interested in PA during their childhood compared to the nonmyopic adults (25% vs 5.7%, P < 0.03) [ Table 1 and Appendix- Table A6 ]. [31] Time spent outdoors and myopia Three clinical trials [32] [33] [34] (2865 children) demonstrated protective effect on incident myopia (risk ratio (RR): 0.536, 95% CI: 0.338-0.850, I 2 = 87.7%, P heterogeneity < 0.001) with increasing TSO during school recess. On excluding He et al. [32] study for sensitivity analysis, two clinical trials showed lower risk (RR: 0.435, 95% CI: 0.344-0.550, I 2 = 0%, P heterogeneity = 0.829) without any heterogeneity when pooled [ Table 1 and Appendix- Table A6 ]. [35] Three cohort studies [11, 36, 37] (4064 children) reported significantly reduced risk of incident myopia associated with high TSO levels (RR: 0.574, 95% CI: 0.395-0.834, I 2 = 70.9%, P heterogeneity = 0.032). For sensitivity analysis, only the removal of younger cohort by French et al. [36, 37] study showed higher risk (RR: 0.693, 95% CI: 0.548-0.877, I 2 = 0%, P heterogeneity = 0.933) with no heterogeneity [ Table 1 and Appendix- Table A6 ]. [35] Thirteen cross-sectional studies [28, 29, [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] (23,112 children) investigated the effect of TSO on incident myopia and found an OR of 0.964, 95% CI: 0.945-0.982, I 2 = 93.2%, P heterogeneity < 0.001). Although the overall OR did not change substantially on exclusion of any study (OR: 0.960-0.984), exclusion of Guo et al. [47] reduced the heterogeneity from 93.2 to 39.8% [ Table 1 and Appendix- Table A6 ]. [35] Seven studies [11, 32, 33, 37, [49] [50] [51] (8437 children) studied the doseresponse relationship of TSO with myopia. The dose-response curve between incident myopia risk and TSO was linear, with an inverse relationship (R 2 = 0.586). The linear equation relating TSO and myopia (y = -0.189 ln(x) + 0.9136), showed TSO of 1 h/day (7 h/week) reduces incident myopia by 45% compared to controls, while 76 min/day (8.9 h/week) showed 50% [ Table 1 and Appendix- Table A6 ]. [35] Dividing the TSO into tertiles shows the lowest tertile (≤13.5-16 h/week) had significantly (P < 0.01) higher OR for incident myopia than the highest tertile (>22.5-23 h/week). Three clinical trials [32] [33] [34] (2865 children) estimated the risk of myopia progression or shift concerning the TSO and had a weighted mean difference of -0.30 D, 95% CI: -0.18 to -0.41D, I 2 = 58.6%, and P heterogeneity = 0.089 [ Table 1 and& Appendix- Table A6 ]. [35] Six studies [51] [52] [53] [54] [55] [56] (3956 children) evaluated dose-response between myopia progression and TSO and failed to find any relationship (R 2 = 0.00064). [35] Only one study showed protective treatment effect on myopia progression (mean difference between test and control eye -0.14 D, 95% CI: -0.22 to -0.06). [52] Other studies had no statistically significant effect (range -0.12 D to 0.013 D) [ Table 1 and Appendix- Table A6 ]. On analyzing the data available for TSO and myopia prevalence, we calculated the pooled OR to be 0.982 (95% CI: 0.979-0.985, I 2 = 93.5%, P heterogeneity < 0.001) per additional hour of TSO/week [ Fig. 2 ]. Near work and myopia Among 15 cross-sectional studies examining the prevalence of myopia and the effect of NW, 10 studies [27, 29, 38, 40, 47, [57] [58] [59] [60] (9076 children) reported increased prevalence myopia with increased NW among 6-18 years old children. Myopic children had more NW compared to the nonmyopic (2.7 ± 0.7 vs 2.3 ± 1 h/ day, P = 0.0027). [59] Additionally, reading two or more books/ week were associated with higher odd (OR: 1.43 of SE ≤ -0.50D and OR: 3.05 of SE ≤ -3D) of developing myopia than those reading less than two books/week. [58] Moreover, continuous reading (>30 min) and close reading distance (<30 cm) increased the risk of myopia by 1.5 times (95% CI: 1.05-2.10) and 2.5 times (95% CI: 1.7-4.0), respectively. [40] The multivariate risk of myopia in children in terms of 1 diopter-h of NW/ week is estimated to be 1.02. [29, 57] Myopic children were also found to watch more television (12.78 ± 9.28 vs 8.91 ± 5.95 h/ week, P = 0.02) compared to the nonmyopes. [38] Longer hour of reading (>5 h per day) was associated with the higher prevalence of myopia (43.1% vs 28.6%, P < 0.001). [57] Others reported an increase in odds of having myopia for every additional hour spent reading, writing, studying, or computer work by 16-38% [ Table 1 and Appendix- Table A6 ]. [27, 47] The other five studies [30, 39, [61] [62] [63] (7297 children) failed to show any association between NW and myopia even after factors adjusted for age, sex, and parental education. There was weak or no correlation between myopia and NW such as watching television, computer, reading, and writing. [61] Myopic and nonmyopic children spent similar time on NW activities like personal reading (23.8 ± 24.7 vs 20.7 ± 21.2 diopter-h/week, P = 0.12), computer use and playing video games (18.9 ± 24.9 vs. 21.8 ± 24.7 diopter-h/week, P = 0.11), homework (35.3 ± 25.9 vs. 34 ± 24.4 diopter-h/week, P = 0.62), and watching television (6.8 ± 5.3 versus 6.2 ± 5.2 diopter-h/ week, P = 0.22). [39] Furthermore, prevalence of myopia among children spending various levels of NW (0-2, 1.6-3.1, and >2.6-3.0 h/day) were also similar (P > 0.05) among different age groups (6 and 12-year olds). [30] Similarly, other levels of NW (<2.79, 2.79-3.85, and 3.86-8 h/day) reported similar refraction in children (6-12 and 13-17-year olds). [62] However, the prevalence of myopia was lower in Sydney (3.3%) than in Singapore (29.1%) [ Table 1 , Appendix- Table A6 ]. [63] The pooled OR from cross-sectional studies resulted in 1.14 (95% CI: 1.08-1.20) indicating the association of NW with myopia risk. However, the studies MA explained the influence of small-study effect and potential publication bias in the studies with the asymmetrical distribution of the studies in their funnel plot (P = 0.003). Subgroup analysis reported myopia's likelihood with children performing more NW (OR: 1.85, 95% CI: 1.31-2.62, I 2 = 85%) with an additional 2% increased risk of myopia for 1 diopter-hour of NW/week. [20] Six cohort studies [11, 37, [49] [50] [51] 64] estimated the association between incidence of myopia and NW. The increase in prevalence of myopia in association with NW was reported in only two studies (3432 children). [37, 64] The myopic group had 3 diopter-hours/week of NW more than the nonmyopic group, which increased by 1.7 diopter-hours/week, compared to the previous year when the eyes were nonmyopic. [64] Also, younger children (6-year-old) who became myopic significantly performed more NW than those who did not become myopic (19.4 vs 17.6 h/week, P = 0.02). [37] Although not significant, similar results with higher risk of developing myopia (HR: 1.22, 95% CI: 0.96-1.55, P = 0.098) were obtained for children spending >3 h/day in reading in comparison with less than 3 h/day. [11] Distinctively, multivariate RR of 0.99 (95% CI: 0.97-1.01) per diopter-hour/week of NW was reported. [49] Similarly, a 5-year follow-up on children revealed that newly myopic and nonmyopic children spent similar time (39.49 ± 20.79 vs 39.22 ± 19.67 diopter-h/week, P = 0.90) on NW activity. [50] After adjusting for the recess period outside the classroom, NW like painting, reading, computer use, writing, playing piano, or watching television does not affect the risk of developing myopic in school children. [51] The pooled OR from the cohort studies gave a RR of 1.00 (95% CI: 0.99-1.01, I 2 = 43%) for every diopter-hour of increasing NW [ Table 1 , Appendix- Table A6 ]. [20] Among six longitudinal studies [52, 53, 56, [65] [66] [67] evaluating the relationship between myopia progression and NW activity among children, two studies (355 children) reported a higher risk of myopia progression associated with NW. [66, 67] However, the other four (1547 children) did not support this conclusion showing any relationship between the two. [52, 53, 56, 65] In group where myopia progression was faster (-2.9 ± 0.6D), it was reported to have a significantly closer reading distance (22 ± 3.8 vs 24.1 ± 4.3 cm) and more NW activity (3.5 ± 0.9 vs 2.9 ± 0.8 h/day) in comparison with the group with slower myopia progression (-0.5 ± 0.3 D). [66] A higher proportion of children (48.8%) with 6 h/day of reading and NW had myopia progression compared to a lower proportion of children (18.9%) in the control group. [67] Interestingly, there is a reported significant difference in myopia progression (0.52 ± 0.19 D vs 0.38 ± 0.15 D, P < 0.01) among the intervention group performing less near and middle vision work (<30 h/week) and more outdoor activity (>14-15 h/week) compared to the control group (>30 h/week and <14-15 h/week). Although the time spent in NW were found to be similar among the two groups, the intervention group had significantly higher outdoor activity (13.7 ± 2.4 vs 6.2 ± 1.6 h/week, P < 0.01). [52] Linear regression analysis of cycloplegic refraction changes over 2 years in children also yielded no statistically significant association with NW activities. [53] Likewise, it was reported that there is no association between myopia progression per year and hours of NW activity. Others said a 2% increase (nonsignificant, P = 0.07) in risk of myopia progression among children performing each additional hour of NW. [65] Due to varying definition of myopia progression and different outcomes, the MA could not combine their results [ Table 1 , Appendix- Table A6 ]. On analyzing myopes and nonmyopes for the time spent on NW activities, it was found that myopic children spend 0.66 h/week more on reading (95% CI: 0.16-1.17) concerning nonmyopes. NW such as watching television, playing computer games, and studying were not associated with myopia. [20] Age Analyzing the effect of age on the risk of myopia and TSO in cohort studies, it was found that younger age groups (6-year-olds) have more protective effect against myopia (RR: 0.380, 95% CI: 0.259-0.558) than older kids (11-12-years) . In case of cross-sectional studies, there was no significant difference between the groups of myopia prevalence (<20%, 20-80%, >80%) or between age groups (<6, 6-18, >18-years) on the protective effect of TSO [ Table 1 , Appendix: Table A6 ]. [35] Gender Studies after adjusting for age, initial refraction, and NW show a significant association between increasing TSO with reduced myopic progression with no reduced final spherical equivalent in females but in males. [9] Geographical location represented in studies In all the four review papers, [2, 9, 20, 35] wide geographical locations have been selected [ Table 1 ]. The various definitions of myopia have been described in the literature and included in Table 1 , which ranged spherical equivalent less than from -0.25 to -1.00 DS. [2, 9, 20, 35] The current systematic overview aimed to summarize all relevant evidence concerning TSO, NW, and PA related to myopia development and progression [ Table 2a and 2b]. At younger ages, myopia progression is rapid. [20] Therefore, the current review included articles that studied population aged ≤20 years. The studies found a general relation of lower risk of myopia and PA without any associated effect or trend of the study population, ethnicity, or age connecting the two. Most children of 7-15 years were the participants with exception in few studies where students aged 11-20, [28] adults with mean age of 23.1 years, [24] and even 33-37 years men [31] were included. The physiological pathway behind how PA protects against myopia is not confirmed. Theories have hypothesized that increased blood flow causing choroidal layer expansion might reduce axial length. On the other hand, animal studies proved reduction of eye growth with increased thickness and blood flow. [68, 69] Physical activity measurement method Most of the studies measured PA using questionnaire and interviews, thus paving recall bias risking both over or underestimation of myopia. Only Jacobsen et al. [24] did retesting of questionnaires to increase the validity. Although accelerometers are more objective than questionnaires but not suitable for all kinds of exercises. Moreover, the results might be influenced by the type of exercise, the intensity and duration. Besides, the placement of accelerometer in wrist vs waist is also important and it is recommended to place it at core of body as back or waist for better results. Questionnaire approach was subjective in all the studies that relied on answers from the child or parents and even recollected from their childhood. Jacobsen et al. [24] used a closed-ended questionnaire (yes/no) to reduce the bias and error. This helped to reduce the misinterpretation, recall bias, and interview bias. The repeated test results of the questionnaires had high correlations coefficient (0.97) in a subgroup of participants. Some studies used a comprehensive questionnaire to determine time spent indoors and outdoors accurately. [28, 30, 70] Both outdoor leisure time and outdoor sports showed a protective effect over indoor sports, thus, suggesting the associated element to be TSO rather than sports. Also, the wording "Sports" might have led to misinterpretation by the participants who categorized only exercise and games as sports and not cycling, walking and falsely categorized them in leisure time. Many studies failed to distinguish between TSO and PA, also to quantify different degrees of PA. Some studies lack record on PA whether performed indoor or outdoor. [24, 25] The visual measurement methods and cycloplegia usage varied across the studies with some using cycloplegia, whereas others were not using it. However, cycloplegic refraction is important while studying young subjects considering their ability for accommodation. [71] Use of a retinoscope or an autorefractometer to assess the refractive status [72, 73] using different kinds of visual acuity charts (Snellen, logMAR, etc.) affects the outcome. [74] Another important factor is the variation in the myopia definition as some studies defined myopia as -1.0 DS, which underestimates myopia, as most studies use -0.50 DS definition of myopia. Hence, prevalence of myopia across studies should be carefully compared. In the prospective cohort studies, there were many missing data (14%) and dropouts (8.3%). [2] In studies with large number of children, the number of children tested in each visit varied. This may somewhat limit the representation of general population. In cross-sectional studies, study participants were from respective local areas and mostly from schools representing the general population. Some studies were small; [26] rest were large with sample size ranging from 366 to 4088, [25, [27] [28] [29] [30] which might overestimate the intervention effects. Perhaps it might not be the lesser PA resulting in myopia. The inability to distinguish between exposure and outcome is a limitation of cross-sectional study. A child's refraction and need for spectacle might have denied sports engagement in myopic children. Among risk factors, other than PA, studies also assessed potential risk factors like amount of NW (computer usage, writing, watching television, and reading), refractive status of the parents, and cognitive skills with factors confounding like higher likelihood of reading among myopes, urban lifestyle, and better cognitive test results were taken care of. [24, 25, 27] However, including participants of different age has complicated our understanding as age, and high level of education are confounders of myopia. It was demonstrated that the TSO is the most important protective factor. Since, mostly PA is likely to occur outdoors, there is a possibility of confounding. In the only case-control study included to study PA and myopia, the sample size was low (n = 65), with more men than women. Different tables in the study presented discrepancies throughout the study, suggesting that several subjects left the questionnaire unfinished. However, it is the only study in the presence of exposures (e.g., PA) that considered possible confounders while comparing the risk of myopia. [31] Time spent outdoors The Sydney Myopia Study by Rose et al. [30, 75] was the earliest study to propose the protective effect of outdoor activity on developing myopia against PA and time spent on indoor activity. [30, 75] This protective effect of TSO on myopia have been confirmed recently in two large randomized controlled trials (RCT). [32, 51] Additionally, three studies supported TSO over PA's effect on myopia. [11, 28, 75] The studies on degree of myopia and axial length and PA were not conflicting; instead, PA was more active outdoors than indoors. However, PA could be an important and independent element with different theoretical pathogenic pathways. Most of the questionnaire-based studies reported that PA has a protective association on development and progression of myopia and vice versa. [25, [27] [28] [29] [30] Studies evaluating PA using accelerometers found that myopia in correlation with other factors might be linked to PA. [11, 26] The protective effect of TSO on myopia may be due to several mechanisms working individually or in conjunction, starting from release of retinal dopamine due to sunlight, ultraviolet radiation, increased depth of focus, decreased image blur, low accommodative demand, and also the resultant reduced NW (substitution effect). [30, 38, [76] [77] [78] [79] [80] Studies demonstrated TSO to have a protective effect on the onset of myopia but not on myopia progression. Similarly, the dose-response curve indicates that, although exposure to outdoors may decrease the chances of developing myopia, it was not protective in myopia progression in prediagnosed myopes. [9, 35] Dose-response analysis results in a linear curve indicating a linear relationship between TSO and the risk of myopia onset. However, it should be noted that the studies included for this analysis had an increase in TSO ranging from 1 to 9.8 h/week [36, 37, 49] and does not determine the effect of TSO more than this upper limit used. Hence, we need to determine the effect of TSO beyond 9.8 h/week on myopia. Likewise, the threshold TSO to prevent the onset of myopia is unknown. [50, 62] Cross-sectional studies had high heterogeneity, but sensitivity analysis reduced the heterogeneity. Participants in the control group playing together with the children from intervention group might have potential contamination. Also, removing studies using noncycloplegic refraction reduced heterogeneity as the results were an overestimated myopia prevalence due to classifying children with emmetropia inappropriately and low hyperopia as myopia. [47, 71, 81, 82] However, cross-sectional studies have a fundamental limitation of inability to distinguish between exposure and outcome and nonexclusion of reverse causality. TSO is more effective on younger children (6 years) than older children (11-12 years) because ocular growth patterns are more sensitive and mature more in younger children. [35] Analysis of the studies shows that TSO has a greater protective effect on nonmyopic eyes in preventing the onset than on already myopic eyes in progression. However, only one study which demonstrated a significant protective effect of TSO and myopia progression was designed to instruct the children to perform less NW and more outdoor activities, thus signifying the effect as combination of both. Summarizing, these findings suggest that the effect of increased TSO is limited to prevent myopia onset and progression among nonmyopic children. Similar to any questionnaire-based data, the reported TSO have source of bias, inaccurate reporting, and recall bias. Thus, questionnaires require validation against TSO's objective measures as light meters, Actigraph, GPS-based systems, and biomarkers such as vitamin D and conjunctival ultraviolet autofluorescence. [2, 35] Despite the high heterogeneity among the studies due to differences in study design, ethnicity, and age of the participants, there is an established protective effect of TSO in most studies. Conversion of TSO from per day to per week in hours may be erroneous as only a few studies provide the actual difference between weekdays and weekends. [11, 28, 38, 42] The strength of evidence (rating) for clinical recommendation regarding decreased NW based on the available evidences are category II, level B. [20] This indicates that there is adequate literature to support the recommendation on reducing the risk of children developing myopia with decreased time spent reading though there is a lack qualities for solid support. The quality of evidence it lacks is that most were observational studies with only one RCT. [20] SRs and MA have estimated 2% increased risk of myopia among children involved per additional diopter-hour of NW per week. They appropriately used 6-18 years age group children among whom the development and progression of myopia are the highest. [20] The primary studies of the included review studied myopia development and progression of population from various ethnicity. These studies found eastern countries to have more myopic population compared with western countries. [2, 9, 20, 35] However, we should also remember that academic pressure, peer pressure, and educational system are different among the eastern (Asian) and western countries. Eastern parents pay more attention to academic, NW, and TSO, whereas in the western side, parents pay more attention to PA and TSO. This might result in high prevalence of myopia in Asia and less in western countries. Moreover, after school tutorials popular in Asian countries might increase the NW and associated with a high prevalence of myopia. [83] Calculating with a factual example, if a child spends four hours a day for NW (at 33 cm) after school hours, he or she is likely to have myopia by 120%. On one hand, the MA indicated an 80% higher risk of myopia in children performing NW. On the other hand, the behavioral pattern indicated myopic children reading more than nonmyopic children with similar levels of computer, watching television, and other NW. This might be possibly explaining that reading alone is providing the effect of NW on myopia. [20] It should be borne in mind that although activities such as NW and reading show an association with myopia, they are not necessarily causal in nature. A reverse causality or the effect of myopia might actually force children to do more NW and less outdoor activity. This might be a confounder in the studies associating NW with myopia. The number of prospective studies and RCT on myopia incidence and progression are minimal. In addition to this, other factors which might be giving such inconsistent conclusions are different study designs: ethnicity studied, myopia and NW definition, inaccuracy, and bias in self-or parent-reported questionnaire, to name a few. Importantly, the effect of lighting on myopia, text size used to read, break in reading, and cumulative effect over time were not considered, affecting the results. [20] Further prospective evidence in preventing myopia is a mandate to elucidate the balance and relationship of NW with outdoor activities. To our knowledge, this is the first overview of SR and MA on the effect of TSO, PA, and NW on the prevalence, incidence, and progression of myopia. We were able to identify and synthesize the evidence available so far, estimated the overlap of index publications in the included reviews. However, there are certain limitations to this overview. First of all, the high heterogeneity among the primary studies in the overview restricted our MA only to TSO and myopia. Likewise, the topic of NW activity and PA concerning myopia is relatively new. There is a lack of MA on those topics, which further reduced our ability to analyze further data. Including the limited number SR/MA on PA has a high risk of bias. Other limitations are the difference in study designs: ethnicity studied, small sample size, subjectivity and effect of recall bias in questionnaires, lack of adjustment for confounding factors, and lack of information on participants who were lost of follow-up, which we have discussed before in the relevant sections. However, despite the limitations, we can find an association between the TSO, NW, and myopia. Future studies will need objective measurement with wrist-worn accelerometers to get more accurate estimation of the PA. An enhanced version of the existing questionnaire is needed to eliminate recall bias about PA. The questionnaires need to be accurate in differentiating and quantifying the time spent on various indoor and outdoor settings. Additionally, participants' fitness tests (physical status) should be used as a further confirmation (indirect measure). RCT with longitudinal follow-up of refractive error/axial length progression on children with varying degrees of PA would give the highest level of evidence. Such studies concentrating on childhood would be more practical considering the crucial period for ocular development. [1] However, this would be a huge and difficult task to perform considering recruitment, ethical considerations, and compliance. As mentioned, a clear distinction between PA and outdoor activity is a mandate without overlap in future studies. From the overview, we can conclude that there is evidence suggesting that an increase in the TSO and decrease in NW has a protective effect in reducing myopia among nonmyopes. Although several activities like NW show an association with myopia, they are not necessarily causal. PA is not an independent factor affecting myopia. However, none of the factors had any effect on reducing the progression of myopia in existing myopes. Nevertheless, a distinct difference between the outdoor activity and PA is needed to study their individual effect on myopia accurately. RCT looking at incidence of myopia and myopic progression as primary endpoints is required to study further the dose-duration response of TSO, PA, and NW. The COVID-19 pandemic has increased the risk of myopia onset and progression with increased NW and digital screen time and reduced the TSO drastically, thus multiplying the risk several times with the continuation of home confinement, especially for children at large. Recommendations for digital screen time are needed to reduce further myopia development and progression. [21] Methodologically, rigorous clinical research is critical to draw a clearer picture and achieve the required consensus. We recommend more RCT with large sample sizes and long-term follow-up to investigate the physical relationship between myopia and its risk factors. Physical activity in relation to development and progression of myopia-A systematic review Prevalence of myopia in taiwanese schoolchildren Prevalence of myopia and its association with body stature and educational level in 19-year-old male conscripts in Seoul How genetic is school myopia? The increasing prevalence of myopia: Implications for Australia Increased prevalence of myopia in the United States between Accelerometer use in physical activity: Best practices and research recommendations The association between time spent outdoors and myopia in children and adolescents: A systematic review and meta-analysis Interventions to control myopia progression in children: Protocol for an overview of systematic reviews and meta-analyses Time outdoors and physical activity as predictors of incident myopia in childhood: A prospective cohort study Darkness and near work Myopia and ambient lighting at night A randomized trial of the effect of single-vision vs. bifocal lenses on myopia progression in children with esophoria Progressive-addition lenses versus single-vision lenses for slowing progression of myopia in children with high accommodative lag and near esophoria Monovision slows juvenile myopia progression unilaterally Myopia and natural lighting extremes: Risk factors in Finnish army conscripts Muszyńska-Lachota I. Role of light emitted by incandescent or fluorescent lamps in the development of myopia and astigmatism A randomized clinical trial of progressive addition lenses versus single vision lenses on the progression of myopia in children The association between near work activities and myopia in children-A systematic review and meta-analysis Screen time for children and adolescents during the COVID-19 pandemic Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement ROBIS: a new tool to assess risk of bias in systematic reviews was developed Does the level of physical activity in university students influence development and progression of myopia?--A 2-year prospective cohort study Risk factors for childhood myopia: Findings from the NICER study Light exposure and physical activity in myopic and emmetropic children Prevalence and risk indicators of myopia among schoolchildren in Amman Outdoor activity and myopia in Singapore teenage children Parental myopia, near work, school achievement, and children's refractive error Outdoor activity reduces the prevalence of myopia in children use of eyes, and living habits among men aged 33-37 years Effect of time spent outdoors at school on the development of myopia among children in China: A randomized clinical trial Effect of outdoor activity on myopia onset and progression in school-aged children in northeast China: The Sujiatun eye care study Risk factors of myopic shift among primary school children in Beijing, China: A prospective study Time spent in outdoor activities in relation to myopia prevention and control: A meta-analysis and systematic review Patterns of myopigenic activities with age, gender and ethnicity in Sydney school children Risk factors for incident myopia in Australian schoolchildren: The Sydney adolescent vascular and eye study Children's refractions and visual activities in the school year and summer Associations between near work, outdoor activity, and myopia among adolescent students in rural China: The Xichang Pediatric Refractive Error Study Role of near work in myopia: Findings in a sample of Australian school children Relative contribution of risk factors for early-onset myopia in young Asian children Disordered sleep and myopia risk among Chinese Children Ethnic variations in myopia and ocular biometry among adults in a rural community in China: The Yunnan minority eye studies Prevalence of myopia in schoolchildren in Ejina: The Gobi desert children eye study Risk factors for and progression of myopia in young Taiwanese men Analysis of myopia prevalence and influencing factors among primary school students in the urban area of Lanzhou city Outdoor activity and myopia among primary students in rural and urban regions of Beijing Family history, near work, outdoor activity, and myopia in Singapore Chinese preschool children A cohort study of incident myopia in Singaporean children Parental history of myopia, sports and outdoor activities, and future myopia Outdoor activity during class recess reduces myopia onset and progression in school children Influence of near-work and outdoor activities on myopia progression in school children Factors related to the progression of myopia in Singaporean children Time outdoors and myopia progression over 2 years in Chinese children: The Anyang childhood eye study Influence of indoor and outdoor activities on progression of myopia during puberty Time outdoors, visual activity, and myopia progression in juvenile-onset myopes Risk factors for refractive errors in primary school children (6-12 years old) in Nakhon Pathom Province Nearwork in early-onset myopia Near-work activity and myopia in rural and urban schoolchildren in China Prevalence of myopia in a sample of Greek students Effects of outdoor activities on myopia among rural school children in Taiwan Near work, outdoor activity, and their association with refractive error Myopia, lifestyle, and schooling in students of Chinese ethnicity in Singapore and Sydney Visual activity before and after the onset of juvenile myopia Visual activity and its association with myopia stabilisation Myopia and myopic progression among schoolchildren: A three-year follow-up study The effect of reading and near-work on the development of myopia in emmetropic boys: A prospective, controlled, three-year follow-up study Temporal relationship of choroidal blood flow and thickness changes during recovery from form deprivation myopia in chicks Transient increases in choroidal thickness are consistently associated with brief daily visual stimuli that inhibit ocular growth in chicks The evidence for environmental factors Cycloplegic refraction is the gold standard for epidemiological studies A comparison of manifest refractions, cycloplegic refractions and retinoscopy on the RMA-3000 autorefractometer in children aged 3 to 15 years Accuracy of noncycloplegic refraction in primary school children in southern Thailand Prospective evaluation of visual acuity assessment: A comparison of Snellen versus ETDRS charts in clinical practice (an aos thesis) Near-work and outdoor activities and the prevalence of myopia in Australian school students aged 12-13 years: The Sydney myopia study Time outdoors and the prevention of myopia Dopaminergic agents affect the ability of brief periods of normal vision to prevent form-deprivation myopia Outdoor activity and myopia Vitamin D receptor (VDR) and group-specific component (GC, Vitamin D-binding protein) polymorphisms in myopia Light, literacy and the absence of ultraviolet radiation in the development of myopia Myopic shift and outdoor activity among primary school children: One-year follow-up study in Beijing Effect of cycloplegia on the refractive status of children: The Shandong children eye study Myopia and international educational performance OR ((short-sighted[Title/ Abstract]) OR short-sighted[Text Word])) OR ((short-sightedness[Title/Abstract]) OR short-sightedness[Text Word])) OR ((shortsight[Title/Abstract]) OR shortsight[Text Word])) OR ((short sighted[Title/Abstract]) OR short sighted[Text Word])) OR ((short sightedness[Title/Abstract]) OR short sightedness[Text Word])) OR ((near-sight[Title/Abstract]) OR near-sight Title/Abstract]) OR exercise[Text Word]) OR exercise[MeSH Terms])) OR (((physical activity[Title/Abstract]) OR physical activity OR motor activity[MeSH Terms])) OR (((exercises[Title/Abstract]) OR exercises[Text Word]) OR exercises[MeSH Terms])) OR (((motor activities[Title/ Abstract]) OR motor activities[Text Word]) OR motor activities[MeSH Terms])) OR ((outdoor*[Title/Abstract]) OR outdoor*[Text Word])) OR ((outside[Title/Abstract]) OR outside Time spent outdoor[Title/Abstract]) OR Time spent outdoor OR ((studying[Title/ Abstract]) OR studying[Text Word])) OR (((reading[Title/Abstract]) OR reading[Text Word]) OR reading[MeSH Terms])) OR ((reading distance[Title/Abstract]) OR reading distance[Text Word])) OR ((working distance[Title/ Abstract]) OR working distance OR exercise OR (((physical activity[Title/Abstract]) OR physical activity[Text Word]) OR physical activity OR physical activities[Text Word]) OR physical activities[MeSH Terms])) OR (((motor activity[Title/Abstract]) OR motor activity OR sport*[Text Word])) OR ((hobb*[Title/Abstract]) OR hobb*[Text Word])) OR ((Environment[Title/Abstract]) OR Environment[Text Word])) OR ((Time spent outdoor[Title/Abstract]) OR Time spent outdoor[Text Word])) OR ((Near activity[Title/ Abstract]) OR Near activity[Text Word])) OR ((near work[Title/Abstract]) OR near work[Text Word])) OR ((studying[Title/Abstract]) OR studying[Text Word])) OR (((reading[Title/Abstract]) OR reading[Text Word]) OR reading[MeSH Terms])) OR ((reading distance[Title/Abstract]) OR reading distance[Text Word])) OR ((working distance[Title/Abstract]) OR working distance[Text Word])) OR ((Outdoor activity[Title/Abstract]) OR Outdoor activity[Text Word])) OR ((Indoor activity[Title/Abstract]) OR Indoor activity[Text Word])) OR ((sunlight exposure[Title/Abstract]) OR sunlight exposure[Text Word])) OR ((Darkness[Title/Abstract]) OR Darkness[Text Word])) OR ((Dark[Title/Abstract]) OR Dark Risk factors for childhood myopia: findings from the NICER study Time outdoors and physical activity as predictors of incident myopia in childhood: a prospective cohort study Does the level of physical activity in university students influence development and progression of myopia?-a 2-year prospective cohort study Light exposure and physical activity in myopic and emmetropic children use of eyes, and living habits among men aged 33-37 years Outdoor activity and myopia in Singapore teenage children Parental myopia, near work, school achievement, and children's refractive error Prevalence and risk indicators of myopia among schoolchildren in Amman The increasing prevalence of myopia: implications for Australia Effect of time spent outdoors at school on the development of myopia among children in China: a randomized clinical trial Effect of outdoor activity on myopia onset and progression in school-aged children in northeast China: the Sujiatun Eye Care Study Outdoor activity during class recess reduces myopia onset and progression in school children Influence of near-work and outdoor activities on myopia progression in school children Patterns of myopigenic activities with age, gender and ethnicity in Sydney schoolchildren A cohort study of incident myopia in Singaporean children Relative contribution of risk factors for early-onset myopia in young Asian children Disordered sleep and myopia risk among Chinese children Risk factors for and progression of myopia in young Taiwanese men Ethnic variations in myopia and ocular biometry among adults in a rural community in China: the yunnan minority eye studies Prevalence of myopia in schoolchildren in Ejina: the Gobi Desert children eye study Analysis of myopia prevalence and influencing factors among primary school students in the urban area of Lanzhou city Outdoor activity and myopia among primary students in rural and urban regions of Beijing Family history, near work, outdoor activity, and myopia in Singapore Chinese preschool children Children's refractions and visual activities in the school year and summer Associations between near work, outdoor activity, and myopia among adolescent students in rural China: the Xichang Pediatric Refractive Error Study Role of near work in myopia: findings in a sample of Australian school children Ozgur G Influence of indoor and outdoor activities on progression of myopia during puberty Time outdoors and myopia progression over 2 years in chinese children: the Anyang childhood eye study Prevalence of myopia and its risk factors in urban school children in Delhi: the North India Myopia Study (NIM Study) Risk factors for myopia in a discordant monozygotic twin study Analysis of poor vision conditions and risk factors of myopia in primary school He'xi district of Sanya Investigation of junior school student myopia in high-altitude Tibetan areas in Qinghai Province Near work, outdoor activity, and their association with refractive error Myopization factors affecting urban elementary school students in Taiwan Myopia prevalence and influencing factor analysis of primary and middle school students in our country The association between time spent outdoors and myopia using a novel biomarker of outdoor light exposure Yang YH Effects of outdoor activities on myopia among rural school children in Taiwan Population density and refractive error among Chinese children An epidemiological survey of refractive error and associated factors among middle school students in Deqing County of Zhejiang Province Outdoor activity reduces the prevalence of myopia in children Myopia, lifestyle, and schooling in students of Chinese ethnicity in Singapore and Sydney Near-work activity, night-lights, and myopia in the Singapore-China study Near-work activity and myopia in rural and urban schoolchildren in China Cross-sectional study of near-work and myopia in kindergarten children in Singapore Risk factors of myopic shift among primary school children in Beijing, China: a prospective study Visual activity and its association with myopia stabilisation The progression of myopia from itsonset at age 8-12 to adulthood and the influence of heredity and external factors on myopic progression. A 23-year follow-up study Myopic shift and outdoor activity among primary school children: one-year follow-up study in Beijing Myopia and myopic progression among schoolchildren: a three-year follow-up study Parental history of myopia, sports and outdoor activities, and future myopia Nearwork in Early-Onset Myopia Risk Factors for Incident Myopia in Australian Schoolchildren: The Sydney Adolescent Vascular and Eye Study Prevalence of myopia in a sample of Greek students The effect of reading and near-work on the development of myopia in emmetropic boys: a prospective, controlled, three-year follow-up study Risk factors for refractive errors in primary school children (6-12 years old) in Nakhon Pathom province Outdoor Activity during Class Recess Reduces Myopia Onset and Progression in School Children Contd... Topic not directly relevant Appendix