Assessing the rebound phenomenon in different myopia control treatments: A systematic review

270 | Ophthalmic Physiol Opt. 2024;44:270–279.wileyonlinelibrary.com/journal/opo INTRODUCTION In the next decade, myopia is expected to present a significant threat to ocular health worldwide.1 This concern arises from its increasing prevalence,2,3 as well as its close association with ocular conditions, such as cataracts, glaucoma, myopic maculopathy and retinal detachment.4,5 Therefore, myopia represents a significant challenge for the scientific and medical community, and it is crucial to address this problem effectively to prevent possible adverse consequences on visual health.6 The onset and progression of myopia have been associated with several environmental factors, such as tasks requiring nearvision, decreased time spent outdoors and REVIEW ARTICLE Assessing the rebound phenomenon in different myopia control treatments: A systematic review Miguel ÁngelSánchez- Tena1,2 | AntonioBallesteros- Sánchez3,4 | ClaraMartinez- Perez2 | CristinaAlvarez- Peregrina1 | ConcepciónDe- Hita- Cantalejo3 | María CarmenSánchez- González3 | José- MaríaSánchez- González3 Received: 29 September 2023 | Accepted: 29 December 2023 | Published online: 9 January 2024 DOI: 10.1111/opo.13277 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists. 1Optometry and Vision Department, Faculty of Optics and Optometry, Complutense University of Madrid, Madrid, Spain 2ISEC LISBOA (Instituto Superior de Educação e Ciências), Lisbon, Portugal 3Department of Physics of Condensed Matter, Optics Area, University of Seville, Seville, Spain 4Department of Ophthalmology, Clínica Novovisión, Murcia, Spain Correspondence Antonio Ballesteros- Sánchez, Department of Physics of Condensed Matter, Optics Area, University of Seville, Seville 41004, Spain. Email: [email protected] Abstract Purpose: To review the rebound effect after cessation of different myopia control treatments. Methods: A systematic review that included fulllength randomised controlled studies (RCTs), as well as posthoc analyses of RCTs reporting new findings on myopia control treatments rebound effect in two databases, PubMed and Web of Science, was performed according to the PRISMA statement. The search period was between 15 June 2023 and 30 June 2023. The Cochrane risk of bias tool was used to analyse the quality of the selected studies. Results: A total of 11 studies were included in this systematic review. Unifying the rebound effects of all myopia control treatments, the mean rebound effect for axial length (AL) and spherical equivalent refraction (SER) were 0.10 ± 0.07 mm [−0.02 to 0.22] and −0.27 ± 0.2 D [−0.71 to −0.03] after 10.2 ± 7.4 months of washout, respectively. In addition, spectacles with highly aspherical lenslets or defocus incorporated multiple segments technology, soft multifocal contact lenses and orthokeratology showed lower rebound effects compared with atropine and lowlevel light therapy, with a mean rebound effect for AL and SER of 0.04 ± 0.04 mm [0 to 0.08] and −0.13 ± 0.07 D [−0.05 to −0.2], respectively. Conclusions: It appears that the different treatments for myopia control produce a rebound effect after their cessation. Specifically, optical treatments seem to produce less rebound effect than pharmacological or light therapies. However, more studies are required to confirm these results. KEYWORDS atropine, DIMS/HAL spectacles, dualfocus contact lens, extended depth of focus contact lens, lowlevel light therapy, orthokeratology, rebound effect | 271 SÁNCHEZTENA etal. educational level.7–9 Hyperopic peripheral retinal defocus has also been reported as a risk factor for myopia progression.10 Therefore, new optical designs that generate myopic peripheral retinal defocus have emerged to control myopia progression, such as spectacles with highly aspherical lenslets (HALs)11,12 or defocus incorporated multiple segments (DIMS) technology,13 orthokeratology (Ortho- K)14 and soft multifocal contact lenses (CLs).15,16 However, these designs may induce optical aberrations affecting visual quality.17 Regarding pharmacological treatments, low concentration atropine is an effective and safe drug in slowing myopia progression.18 In addition, it can be also considered as a viable option for combination therapy with any of the optical treatments to enhance the efficacy of myopia control.19 Recently, new light therapy devices, such as lowlevel light therapy (LLLT) seem to achieve promising results for myopia control.20 Therefore, the longterm efficacy, as well as the possible rebound effects of these treatments, are an important area of study. Rebound effect is defined as the greater myopic progression that occurs after cessation of myopia control treatment, with the participant ultimately reaching the same level of myopia observed in a child of the same age and with similar environmental factors who did not receive any myopia control treatment.21 Although several studies have evaluated the efficacy and safety of different myopia control treatments,11–16,18,20 there is no systematic review analysing the changes in axial length (AL) and spherical equivalent refraction (SER) after the cessation of myopia control treatments. Therefore, the purpose of this systematic review was to evaluate the rebound effect of different myopia control treatments. Through this review, a comprehensive overview of the current evidence on myopic rebound effect is provided, enabling evidencebased decisionmaking and guiding future research directions. METHODS Data sources and search strategy This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA).22,23 We identified 1242 articles published before 29 September 2023 through the following databases: PubMed, Web of science and Scopus. The data search strategy with Boolean operators was as follows: (myopia control OR slowing myopia) AND (myopia progression OR rebound effect) AND (atropine OR dual focus contact lens OR MiSight contact lens OR extended depth of focus [EDOF] contact lens OR orthokeratology OR spectacles lenses OR defocus incorporated multiple segments spectacles OR DIMS spectacles OR highly aspherical lenslets OR HAL spectacles OR lowlevel light therapy OR LLLT OR red light). The references of the retrieved articles were reviewed to identify other related studies if they met the inclusion criteria. Study selection All 1242 articles identified through the search strategy were considered and analysed. Duplicate studies were removed by DistillerSR software (disti llersr. com). The remaining studies underwent additional screening stages, which included title, abstract and fulltext screening. Studies unrelated to the topic were excluded from the review during title and abstract screening. Fulltext screening studies that did not include myopia control therapy rebound effect were also excluded. These studies were reviewed by two investigators (ABS and JMSG) who selected them according to the inclusion and exclusion criteria. The inclusion criteria were as follows: prospective randomised controlled trials (RCTs), as well as posthoc analyses of RCTs reporting new findings on the myopia control therapy rebound effect. Exclusion criteria included non- English publications and unindexed journals. There were no restrictions placed on the country in which the study was performed, the followup period, the sample size or results of the studies. Quality assessment and data extraction Data from each study were collected and summarised independently in tables designed by two researchers (ABS and JMSG). The following information was obtained from each article: (1) author and date of publication (year), (2) study design, (3) mean followup of all patients in the whole procedure (expressed in months), (4) number of patients, (5) mean age of the patients (expressed in years), (6) patient sex (female/male), (7) number of eyes involved, (8) inclusion criteria of the studies, (9) study group intervention, (10) control group intervention, (11) washout period of myopia control therapy and (12) conflicts of interest. Regarding the results of the studies, the following data were collected: (13) AL (expressed in millimetres, mm); (14) SER with cycloplegia (expressed in dioptres, D) and (15) the Key points • A rebound effect can be observed after the discontinuation of different myopia control treatments. • Optical treatments seem to produce less rebound effect than pharmacological or light therapies. However, the latter treatments seem to achieve better control of myopia progression. • Being aware of the rebound effect of myopia control treatments could help healthcare professionals and patients plan for continued myopia treatment effectively and choose the most suitable treatment option. 14751313, 2024, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/opo.13277 by Universidad De Sevilla, Wiley Online Library on [03/06/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 272 | REBOUND PHENOMENON IN MYOPIA CONTROL authors' judgement expressed by commenting in favour or against the myopia control therapy. Data synthesis was performed according to the Cochrane guideline for synthesis without metaanalysis (SWiM).24 Baseline and last visit values for all these variables were collected in the myopia control therapy group. Intragroup clinical outcomes were defined as ‘Last visit (LV) − Baseline (B) differences’. Myopia control therapy rebound effects were defined as ‘(Intragroup difference cessation groupLV − B) − (Intragroup difference continuation groupLV − B)’. Mean ± standard deviations for each variable were calculated to report intragroup clinical outcomes and myopia control therapy rebound effect. Specifically, the mean AL and SER rebound effect was calculated through the rebound effect reported in each study. The literature that remained after fulltext screening was examined to assess the quality of the studies. To avoid the risk of bias, two authors created a synopsis based on the Cochrane risk of bias tool,24 which includes the following items: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants and personnel, (4) blinding of outcome assessment, (5) incomplete outcome data, (6) selective reporting and (7) other sources of bias. A third nonblinded assessor decided the quality of the studies when disagreements occurred between the two assessors. To present a clear and comprehensive visualisation of the risk of bias across included studies, we used the Risk of Bias Visualisation (Robvis) tool. Robvis produces colourcoded, easy- to- interpret plots that represent the risk of bias assessments for individual studies as well as summary assessments across studies. Each domain assessed by the Cochrane risk of bias tool was represented in the Robvis plot, allowing for a quick but thorough understanding of the quality of the evidence included in this review. RESULTS Study characteristics The study selection process of this systematic review is presented with a flow chart diagram (Figure1). The design of the included studies was prospective RCTs published between 2013 and 2023. This systematic review included 1704 eyes FIGURE 1 Flow chart study selection process according to the PRISMA statement. 14751313, 2024, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/opo.13277 by Universidad De Sevilla, Wiley Online Library on [03/06/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 273 SÁNCHEZTENA etal. from 1704 patients with a mean age of 10.5 ± 0.9 years. The sex distribution was 797 females (46.7%) and 907 males (53.2%). Patient followup ranged from 1225,26 to 72 months,27 with a mean followup of 26.1 ± 16.7 months. Regarding study group intervention, different myopia control therapies were used, such as atropine,26,28–30 soft multifocal CL,16,25 DIMS/ HAL spectacles,27,31 Ortho- K32 and LLLT.33,34 Concerning the control group intervention, placebo,26,28–30 singlevision spectacles27,31–35 and singlevision CL25 were used. The washout period of myopia control therapies ranged from 1 month36 to 30 months,27 with a mean washout period of 10.2 ± 7.4 months. Six studies reported no conflicts of interest (CoI),16,26,28,29,32,34 while five studies reported CoI by the authors.25,27,30,31,33 More detailed study characteristics and myopia control therapies are presented in Table1. Outcomes Regarding efficacy outcomes, 11 studies reported a rebound effect after cessation of different myopia control therapies.25–35 From these 11 studies, 6 reported data for both subgroups, one that stopped the myopia control treatment (cessation group) and another that continued the myopia control treatment (continuation group).16,25,27,29,31,33 For the other five studies, the values of the continuation group have been estimated as the mean values through the treatment period, adjusted to the followup period of the cessation group (Last visit − baseline visit) × (cessation period/treatment period).26,28,30,32,34 Intragroup clinical outcomes and rebound effect are presented in Table2. AL and SER values were found to be higher in the cessation groups compared with the groups that continued myopia control treatment. In a comprehensive assessment encompassing all types of myopia control therapies, mean continuation subgroup AL was 0.13 ± 0.1 mm [−0.08 to 0.30]. However, the mean cessation subgroup AL was 0.23 ± 0.11 mm [0 to 0.40]. These results suggest a mean rebound effect for the AL variable of 0.10 ± 0.07 mm [−0.02 to 0.22]. In refraction terms, mean continuation subgroup SER was −0.22 ± 0.19 D [−0.48 to 0.30]. However, the mean cessation subgroup was −0.49 ± 0.2 D [−0.91 to −0.2]. This implies a mean rebound effect for the SER variable of −0.27 ± 0.2 D [−0.71 to −0.03]. To better understand the average rebound effect based on the myopia control treatment, the data were segregated into five different techniques as shown in Table3. Spectacles with HAL or DIMS technology, soft multifocal CLs and Ortho- K showed lower rebound effects compared to atropine and LLLT, with a mean rebound effect in terms of AL and SER of 0.04 ± 0.04 mm [0 to 0.08] and −0.13 ± 0.07 D [−0.05 to −0.2], respectively. Risk of bias The risk of bias summary of the included studies is presented in Figure2. Risk of bias assessment was classified into three evidence level groups: (1) studies with a low risk of bias (Chia etal.,28 Wei etal.,30 Chen etal.,34 Sankaridurg etal.,31 Weng etal.,25 Yam etal.,29 Lam etal.27 and Medghalchi etal.26); (2) studies with an unclear risk of bias (Xiong etal.33) and (3) studies with a high risk of bias (Ruiz- Pomeda etal.16 and Zhu etal.32). The overall risk of bias summary of the domains used in each study is presented in Figure3. The items used to assess the risk of bias showed an overall low risk of bias (75%). Therefore, no study was excluded due to risk of bias. The Robvis tool (brist ol. ac. uk/ popul ation - healt hscien ces/ proje cts/ robis/ robis - tool/ ) was used to create risk of bias assessment figures.37 DISCUSSION Several treatments are currently used to control myopia progression.38 Although the selection of myopia control treatment is an individualised process that considers a variety of environmental and genetic factors,7–9 none of these treatments have been able to stop myopia progression completely.39 This lack of efficacy may be due to a natural slowing of myopia progression with increasing age, as well as the fact that approximately 80% of myopes do not progress to high myopia.9 In addition, a high percentage rebound effect, that varied across studies, was observed when these treatments were discontinued.33,34 Therefore, this systematic review aimed to report the changes in AL and SER after cessation of the different myopia control treatments. Spectacles Undercorrection of myopia was inaccurately used to control myopia progression.40 These treatments were thought to reduce the accommodative lag, which has been traditionally associated with myopia and its progression.41 As expected, they did not achieve satisfactory results.41,42 Currently, new spectacles designs incorporating HAL or DIMS technology in the midperipherical portion of the spectacles seem to be effective in slowing myopia progression.11–13 However, rebound effects were seen after discontinuation of the spectacle lenses. Sankaridurg et al.31 measured the rebound effect 6 months after treatment with HAL spectacles in children with a mean age of 1.1 ± 1.6 years. They reported an important rebound effect, noting that the increase in AL was three times higher in the group that stopped the treatment. On the other hand, Lam etal.27 reported that after cessation of DIMS spectacle wear, myopia continued to progress at the same rate as when they were worn, with a 24% rapid increase in AL in the group that stopped the treatment. In this investigation, the study was longer, measuring the rebound effect for 2.5 years, after 3.5 years of treatment. Therefore, children who ceased treatment were, 14751313, 2024, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/opo.13277 by Universidad De Sevilla, Wiley Online Library on [03/06/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 274 | REBOUND PHENOMENON IN MYOPIA CONTROL TABLE 1 Summary of included studies. Author (Year) Design F/UaPatients (TG/CG) Ageb (TG/CG) Sex (F/M) Eyes Inclusion criteria (SER, D) Intervention Control Washout periodaCoI Chia etal. (2013)28 DM MN 24 347/NR NR (11.7 ± 1.5/NR) 170/177 347 ≥−2.00 Atropine (0.01%, 0.1% and 0.5%) Placebo 12 No Ruiz- Pomeda etal. (2021)16 UM MN 36 31/24 12.3 ± 1.6 (13 ± 1.2/11.9 ± 1.3) NR 55 −0.75 to −4.00 Soft multifocal CL (Dualfocus) Single vision spectacles 12 No Wei etal. (2022)30 DM MN 24 65/68 9.6 ± 1.6 (9.9 ± 1.6/9.2 ± 1.6) 65/68 133 −1.00 to −6.00 Atropine (0.01%) Placebo 12 Yes Chen etal. (2022)34 SM MN 15 46/40 8.9 ± 1.6 (9 ± 1.9/8.9 ± 1.2) 34/52 86 −0.75 to −6.00 Lowlevel light therapy (635 nm) Single vision spectacles 3No Sankaridurg etal. (2022)31 DM MN 19 54/65 11.1 ± 1.6 (11.2 ± 1.6/10.9 ± 1.7) 54/65 119 −0.75 to −4.75 HAL spectacles Single vision spectacles 6Yes Weng etal. (2022)25 SM MN 12 65/30 10.8 ± 1.5 (10.8 ± 1.6/10.9 ± 1.5) 48/47 95 −0.75 to −3.50 Soft multifocal CL (Dualfocus and EDOF) Single vision CL 6 Yes Xiong etal. (2022)33 SM MT 24 63/51 10.6 ± 2.3 (10.4 ± 1.5/10.8 ± 3) 61/53 114 −1.00 to −5.00 Lowlevel light therapy (650 nm) Single vision spectacles 12 Yes Yam etal. (2022)29 DM MT 36 254/72 10.9 ± 1.8 (10.7 ± 1.7/11.1 ± 1.9) 145/181 326 ≥−1.00 Atropine (0.01%, 0.025% and 0.05%) Placebo 12 No Lam etal. (2023)27 DM MT 72 50/40 10.1 ± 1.5 (9.8 ± 1.5/10.4 ± 1.6) 47/43 90 −1.00 to −5.00 DIMS spectacles Single vision spectacles 30 Yes Medghalchi etal. (2023)26 DM MN 12 40/20 11.1 ± 3.5 (10.6 ± 3.5/12 ± 3.6) 32/35 60 −2.00 to−6.00 Atropine (0.01% and 0.1%) Placebo 6No Zhu etal. (2023)32 SM MN 13 142/137 9.2 ± 1.5 (9.2 ± 1.3/9.2 ± 1.7) 141/138 279 −1.00 to −5.00 Ortho- K Single vision spectacles 1No Abbreviations: CG, control group; CL, contact lens; CoI, conflicts of interest; D, dioptres; DIMS; defocus incorporated multiple segments; DM, doublemasked; EDOF, extended depth of focus; F, female; F/U, followup; HAL, highly aspheric lenslets; M, male; MN, monocentric; MT, multicentre; NR, not reported; SER, spherical equivalent refraction; SM, singlemasked; TG, treatment group; UM, unmasked. aExpressed as months. bExpressed as mean ± standard deviation, years. 14751313, 2024, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/opo.13277 by Universidad De Sevilla, Wiley Online Library on [03/06/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 275 SÁNCHEZTENA etal. on average, 14 years of age at the beginning of the follow- up period, finishing the study with a mean age of 16 years. The extension of treatment and the different ages of the participants clearly influence these variations in the results of the two studies. This result seems to indicate that the centring of these spectacle designs plays a crucial role in controlling myopia progression.43 In addition, it is important to perform a thorough evaluation of candidates for this treatment to ensure that they will wear the spectacles for a significant period of the day.44 Soft multifocal contact lenses Centredistance multifocal CLs have been studied extensively for myopia control.40 Several studies have reported that high add power multifocal CLs achieve greater slowing of myopia progression.45–47 However, these participants presented with poorer visual acuity and contrast sensitivity.48 Therefore, new CL designs, such as the dualfocus and EDOF CLs, have been developed for myopia control, obtaining promising results.15,16 Regarding the possible rebound effect, Ruiz- Pomeda etal.16 reported a low rebound effect after cessation of dualfocus CL wear during 12 months of followup. Higher rebound values were reported by Weng etal.25 with dualfocus and EDOF 6 months after discontinuation. Again, these rebound higher values, as seen with myopia control spectacles, could be due to differences in ages between the studies, with mean ages at the beginning of the followup TABLE 2 Intragroup difference outcomes and rebound effect. Author (Year) Myopia control treatment Rebound effectc F/A Continuation Cessation AL, mm SER, D AL, mm SER, D AL, mm SER, D Chia etal. (2013)28 Intragroup differencea0.19 −0.23 0.24 −0.59 0.05 −0.36 F Ruiz- Pomeda etal. (2021)16 Intragroup differenceb0.16 −0.37 0.22 −0.46 0.06 −0.09 F Wei etal. (2022)30 Intragroup differencea0.30 −0.48 0.39 −0.78 0.09 −0.3 F Chen etal. (2022)34 Intragroup differencea0.003 0.013 0.16 −0.2 0.157 −0.213 F Sankaridurg etal. (2022)31 Intragroup differenceb0.06 −0.2 0.17 −0.33 0.11 −0.13 F Weng etal. (2022)25 Intragroup differenceb (EDOF CL) 0.06 −0.26 0.15 −0.3 0.09 −0.04 F Intragroup differenceb (dualfocus CL) 0.08 −0.23 0.14 −0.26 0.06 −0.03 F Xiong etal. (2022)33 Intragroup differenceb0.12 −0.2 0.42 −0.91 0.3 −0.71 F Yam etal. (2022)29 Intragroup differenceb (atropine 0.05%) 0.17 −0.28 0.33 −0.68 0.16 −0.4 F Intragroup differenceb (atropine 0.025%) 0.20 −0.35 0.29 −0.57 0.09 −0.22 F Intragroup differenceb (atropine 0.01%) 0.24 −0.38 0.29 −0.56 0.05 −0.18 F Lam etal. (2023)27 Intragroup differenceb0.25 −0.30 0.31 −0.48 0.06 −0.18 F Medghalchi etal. (2023)26 Intragroup differencea−0.08 0.3 0.14 −0.33 0.22 −0.63 F Zhu etal. (2023)32 Intragroup differencea0.018 NR 0NR −0.018 NR F Abbreviations: A, against; AL, axial length; CL, contact lens; D, dioptres; EDOF, extended depth of focus; F, in favour; NR, not reported; SER, spherical equivalent refraction with cycloplegic. aEstimation has been done with the treatment group as (Last visit − baseline visit) × (cessation period/treatment period), the authors did not report values for a group that continued the study. bDefined as Last visit − Baseline. cDefined as (intragroup difference cessation groupLast visit − Baseline) − (intragroup Difference continuation groupLast visit − Baseline). TABLE 3 Mean rebound effect of different myopia control treatments. Myopia control treatment Rebound effectaWashout period (months)AL, mm SER, D Lowlevel light therapy (n = 109) 0.23 ± 0.07 −0.46 ± 0.25 7.5 ± 4.5 Atropine (n = 706) 0.11 ± 0.06 −0.35 ± 0.15 10.5 ± 2.6 DIMS/HAL spectacles (n = 104) 0.08 ± 0.03 −0.2 ± 0.03 18 ± 12 Dualfocus CL (n = 96) 0.07 ± 0.01 −0.05 ± 0.03 9 ± 3 Ortho- Kb (n = 142) −0.018 NR 1 Abbreviations: AL, axial length; CL, contact lens; D, dioptres, DIMS, defocus incorporated multiple segments; HAL, highly aspherical lenslets; NR, not reported; Ortho- K, orthokeratology; SER, spherical equivalent refraction with cycloplegic. aDefined as (Intragroup difference cessation groupLast visit − Baseline) − (Intragroup difference continuation groupLast visit − Baseline). bThe rebound effect after Ortho- K cessation was evaluated by one study. Therefore, mean ± standard deviation could not be calculated. 14751313, 2024, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/opo.13277 by Universidad De Sevilla, Wiley Online Library on [03/06/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 276 | REBOUND PHENOMENON IN MYOPIA CONTROL FIGURE 2 Risk of bias summary of the included studies16,25–34 with traffic light plot. The colour of the traffic light represents the author's risk of bias judgement in each domain (D) used to assess the quality of the studies. FIGURE 3 Overall risk of bias summary of the domains with a bar plot. Bar plots represent the overall author's risk of bias judgement in each domain presented as percentages. 14751313, 2024, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/opo.13277 by Universidad De Sevilla, Wiley Online Library on [03/06/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 277 SÁNCHEZTENA etal. of 13 and 11 years in Ruiz- Pomeda etal. and Weng etal., respectively. An additional factor to consider was the duration of treatment and followup, being 2 years of treatment and 1 year of followup in Ruiz- Pomeda etal., versus 6 months of treatment and 6 months of followup in Weng etal. Nevertheless, the findings suggest that these CL designs may be effective in controlling myopia progression without experiencing a significant rebound effect. Further research is required to confirm these results. Orthokeratology In Ortho- K patients, the assessment of refractive changes is more complicated due to the corneal moulding induced by the rigid gas permeable CL. Therefore, the control of myopia progression is usually assessed through AL changes.49 Zhu etal.36 reported no significant AL changes in Ortho- K patients after 12 months of followup. In addition, no rebound effect was observed in this study, which may be explained because Ortho- K was only discontinued for 1 month. Therefore, it would be interesting to analyse the rebound effect by discontinuing treatment for a duration equal to or longer than the treatment period. However, several studies have reported an increase in AL after the cessation of Ortho- K. In addition, Swarbrick etal.,50 Li etal.51 and Wang etal.52 concluded that AL was only relatively reliable in Ortho- K patients after the washout period. Therefore, taking as a cut off AL findings measured without a washout period to assess changes after ortho- K cessation may overestimate efficacy, especially in studies that included a control group. Atropine The use of different concentrations of atropine to control myopia progression has been widely studied.18 Several investigations have demonstrated the efficacy of 1% atropine in slowing myopia progression.53–55 However, adverse effects, such as mydriasis and a high rebound effect have limited the clinical use of this dosage.56 Consequently, there has been a shift towards using atropine at much lower concentrations. Management of myopia with 0.01% and 0.05% atropine seems to be safe and effective for myopia control, producing a lower rebound effect.26,28,29,30 Chia et al.28 reported that 12 months after atropine cessation, the rebound effect was lower in participants who had received 0.01% atropine, compared with 0.5% and 0.1% concentrations. Similar results were reported by Wei et al.,30 Yam etal.29 and Medghalchi etal.,26 with no significant rebound effect 10 ± 2.8 months after cessation of 0.01% atropine. In addition, Yam etal.29 showed that younger children were more likely to exhibit a greater rebound effect than older children, which may be explained by the slower physiological myopia progression of the older children. However, it is also important to mention that growth hormone and oestrogen levels regulate muscarinic receptor activity,57–59 which may influence treatment efficacy and the rebound effect. Overall, these results appear to indicate that 0.01% atropine has the lowest rebound effect and achieves significant control of myopia progression, but further studies comparing the rebound effects of 0.01%, 0.025% and 0.05% atropine are needed. Lowlevel light therapy Red light therapy is a new approach to control myopia progression in patients with moderate myopia.20 Although the mechanism of action is not fully understood, this device emits a red light (650 nm) that seems to improve scleral hypoxia and thus prevent myopia progression.20,60 RCTs evaluating myopia control with this treatment are limited. Chen etal.34 and Xiong etal.33 reported the highest rebound effect after LLLT cessation compared with the other myopia control treatments included in this systematic review. This rebound effect may be explained by the greater control of myopia progression reported in these studies. Therefore, further investigations are needed to elucidate the mechanism of action of LLLT, as well as the minimum potency of this therapy that achieves the best control of myopia progression with the least possible rebound effect. Strengths and limitations The main strength of this systematic review is that all included studies were RCTs with an overall low risk of bias. However, this study has several limitations. First, the heterogeneity of the interventions in both groups, which complicated comparisons between the investigations. In addition, the washout period differed across studies; thus, the methodologies were not always similar. For these reasons, a metaanalysis was not performed. Second, evaluation of the rebound effect was only performed at the end of the washout period, which may have influenced the results. Therefore, larger, welldesigned, strictly blinded, multicentre RCTs with increased evaluations during the washout period are needed to determine the rebound effect of different treatments more accurately. Third, since this systematic review includes studies some 10 years apart, it is important to emphasise that the study designs will have changed over the years which could affect the outcome of our analysis. While this review offers a general understanding of the rebound effect with different myopia control treatments, it lacks any consideration as to how demographic and clinical factors such as race, baseline refractive error and parental myopia may influence treatment outcomes. Future research should aim to fill this gap by investigating the interactions between these variables and the effectiveness of different treatments, thus allowing for more personalised therapeutic strategies. 14751313, 2024, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/opo.13277 by Universidad De Sevilla, Wiley Online Library on [03/06/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 278 | REBOUND PHENOMENON IN MYOPIA CONTROL In conclusion, this study has shown that the different treatments methodologies for myopia control produce a rebound effect. In particular, spectacles with DIMS or HALs, doublefocus or EDOF CLs and Ortho- K seem to produce a lower rebound effect than atropine and LLLT. However, these latter treatments seem to achieve better control of myopia progression. Therefore, further studies are needed to confirm these results. AUTHOR CONTRIBUTIONS Miguel Ángel Sánchez- Tena: Writing – review and editing (equal). Antonio Ballesteros- Sánchez: Conceptualization (equal); data curation (equal); formal analysis (lead); methodology (lead); software (lead); visualization (lead); writing – original draft (lead). Clara Martinez- Perez: Writing – review and editing (equal). Cristina Alvarez- Peregrina: Writing – review and editing (equal). Concepción De- Hita- Cantalejo: Writing – review and editing (equal). María Carmen Sánchez- González: Writing – review and editing (equal). José- María Sánchez- González: Conceptualization (lead); data curation (equal); formal analysis (equal); methodology (equal); visualization (equal); writing – original draft (equal). CONFLICT OF INTEREST STATEMENT The authors have no financial/nonfinancial competing interest. FUNDING INFORMATION This study did not received any funding. 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