The Effect of Repeated Low-Level Red-Light Therapy on Myopia Control and Choroid

Abstract

Purpose: To investigate the long-term effects of repeated low-level red light (RLRL) therapy on the axial length (AL), spherical equivalent (SE), and choroidal parameters.

Methods: Two hundred eight myopic eyes were recruited. The RLRL group included 100 eyes, whereas the control group included 108 eyes. Throughout the one-year follow-up period, changes in AL and SE were recorded for both groups. The RLRL group underwent additional choroidal imaging, and changes in choroidal thickness (CT), choroidal vascularity (CV), and choriocapillaris luminal area (CLA) were assessed before and after RLRL therapy.

Results: During the follow-up period, the changing trends in AL and SE differed significantly between the RLRL and control groups. In the RLRL group, AL decreased at three and six months (both P < 0.05) and returned to pretreatment values at 12 months (P = 0.453). In contrast, AL increased significantly throughout the follow-up period (three, six, and 12 months) in the control group (all P < 0.001). The SE increased significantly during the entire follow-up period in the RLRL group (all P < 0.001), whereas it decreased significantly in the control group (all P < 0.05). Regarding choroidal parameters, significant improvements were observed in CT, CV and CLA throughout the follow-up period (all P < 0.05), and changes in most choroidal parameters were significantly correlated with changes in AL and SE during the follow-up period (all P < 0.05). Furthermore, AL, SE, and most choroidal parameters showed significant correlations between changes at three and 12 months (all P < 0.05).

Conclusions: RLRL therapy significantly improved choroidal blood perfusion and circulation, which may explain the observed slowing or reversal of myopia progression in the RLRL group. Thus RLRL therapy may be a novel and effective method for controlling myopia. Furthermore, the short-term effect of photobiomodulation therapy (i.e., changes at three months) can be used to predict the long-term effects (i.e., changes at 12 months).

Translational Relevance: In this study, RLRL therapy showed a significant control effect on the development of axial length and spherical equivalent. RLRL therapy also promoted the choroidal blood perfusion and circulation. RLRL therapy could be a novel and effective method for myopia control.

Introduction

It is predicted that by 2050, 49.8% of the global population will suffer from myopia, and 9.8% will experience high myopia.¹ Myopia progression continues until the age of 16 years in Asian children.² The prevalence of myopia is particularly high in East and Southeast Asia, with 80% to 90% of young adults affected and 10% to 20% of these individuals having high myopia.^1,3 Myopia is characterized by increased axial length (AL) and is associated with certain complications, such as macular degeneration, retinal detachment, and glaucoma, which can potentially result in blindness.^4–7 Therefore myopia may significantly contribute to global vision impairment. 

Certain effective interventions for preventing and controlling myopia have been proposed, including orthokeratology and atropine. However, their efficacy rates range from 30% to 60%,^8,9 and their clinical application is restricted by factors such as age and degree of myopia.¹⁰ Moreover, these treatments also have corresponding disadvantages. For instance, individuals with myopia using orthokeratology are at risk of complications, including microbial keratitis, corneal infiltration, and corneal staining, with incidence rates ranging from 3.8% to 29.0%.¹¹ The long-term use of atropine may lead to side effects such as photophobia, rebound myopia, reduced accommodation, and drug resistance.^9,12,13 Therefore further exploration of new mechanisms and treatments for preventing and controlling myopia is required. 

Outdoor activity is widely accepted as a preventive method for myopia, with light exposure playing a key role.¹⁴ The protective effect of outdoor activity may be associated with higher ambient illumination and the spectral composition of the light.¹⁵ Indoor light sources, such as tungsten bulbs or light-emitting diodes, differ in spectral composition from sunlight, which could contribute to myopia progression.¹⁶ Recently, a novel photobiomodulation therapy called repeated low-level red light (RLRL) was introduced for myopia control.^10,17–23 This therapy uses 650 nm red light to provide sufficient energy to stimulate the tissue without damaging adjacent areas.²⁴ RLRL may improve hypoxia and inhibit inflammation.^24,25 It has the potential to treat various ophthalmologic diseases, including age-related macular degeneration, amblyopia, diabetic retinopathy, retinopathy of prematurity, and methanol-induced retinal damage.^26–29 Previous studies have also suggested that RLRL could control the progression of myopia.^{10,17,19,25,30} Therefore RLRL may be an effective and safe treatment option for myopia. 

Recent studies have shown the importance of the choroid's structure, function, and blood flow in the progression of myopia. Decreased choroidal thickness and blood flow may lead to remodeling of the scleral extracellular matrix, which can further promote ocular growth.^31–36 In addition to hypoxia, inflammation is also an important factor in myopia progression.³⁷ The efficacy of RLRL in controlling myopia is believed to be due to its effects on improving choroidal thickness, blood flow, oxidative stress, and inflammation.^{10,17,19,25,30} However, no previous study has measured both choroidal thickness (CT), choroidal vascularity (CV), and choriocapillaris luminal area (CLA) before and after RLRL. Thus this study aims to comprehensively assess RLRL-induced changes in choroidal parameters by measuring CT, CV, and CLA in the foveal and parafoveal regions before and after RLRL treatment. To achieve this, we used optical coherence tomography (OCT) and OCT angiography (OCTA). Additionally, spherical equivalent (SE) and axial length (AL) measurements were recorded for both the RLRL and control groups throughout the study period. 

Material and Methods

Participants

This prospective study was conducted at the Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China between February 2021 and December 2022. This study was registered with the Chinese Clinical Trial Registry (https://www.chictr.org.cn/) (registration no. ChiCTR2100043085) and approved by the Ethics Committee of Tongji Hospital (TJ-IRB20210140). The study adhered to the tenets of the Declaration of Helsinki. The guardians of the enrolled participants provided written informed consent before participation. 

The inclusion criteria were as follows: (1) ages between six and 12 years; (2) SE ≤ −0.50 diopters (D) based on cycloplegic optometry (1% cyclopentolate instilled 30 and 25 minutes before optometry); (3) absence of other ocular and systemic diseases (e.g., strabismus, amblyopia, hypertension, diabetic mellitus); (4) willingness to sign an informed consent form. The exclusion criteria were as follows: (1) previous and current treatment with atropine, orthokeratology, rigid gas permeable (RGP) lenses, soft contact lenses, pirenzepine, and defocus lenses; (2) secondary myopia; (3) history of ocular surgery or trauma; (4) history of refractive surgery.^36,38 

Study Procedures

A total of 232 eyes from 116 children were included in this study. Participants were assigned to either the RLRL group or the control group based on their willingness to receive RLRL treatment. There were 57 children in the RLRL group and 59 in the control group. Among them, 12 participants (seven from the RLRL group and five from the control group) did not meet the follow-up criteria and were excluded from the study. Consequently, 208 eyes from 104 children completed the follow-up: 50 participants with 100 eyes in the RLRL group and 54 participants with 108 eyes in the control group. All study participants were instructed to wear appropriate single spectacles during the daytime. The RLRL group received additional therapy with a desktop light therapy device (Eyerising; Suzhou Xuanjia Optoelectronics Technology, Jiangsu, China) twice daily, three minutes per session. The interval between sessions was at least four hours. The device, classified as Class 1 according to IEC 60825-1:2014, provided an illuminance level of approximately 1600 lx, with a power of 0.287 mW, directed through a 4-mm pupil to the fundus, and emitted light at a wavelength of 650 ± 10 nm. The follow-up periods were three, six, and 12 months. RLRL therapy was administered at home under the supervision of parents or guardians. The device included an automated diary function that recorded treatment sessions and monitored patient compliance, with reminder messages sent to parents, guardians, and trial managers if fewer than eight sessions per week were completed.¹⁷ No specific interventions were conducted in the control group apart from the use of single spectacles. 

All study participants underwent AL (AL-Scan; NIDEK Co., Ltd. Gamagori, Aichi, Japan) and SE measurements before the study and at three, six, and 12 months after participation. The RLRL group also had choroid imaging performed using the enhanced depth imaging model of Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). During scanning with Spectralis OCT, follow-up mode was conducted in advance to ensure that the scans at each visit were in the same position. To minimize bias from circadian rhythms, OCT scans were performed by the same investigator between 9:00 AM and 12:00 noon at baseline and during the three-, six-, and 12-month follow-ups. Participants were instructed to avoid any physical activity or work for one hour before each study visit. 

Myopia Control Rate

Based on a previous study,³⁹ the myopia control rate was defined as the percentage of lower AL/greater SE compared to baseline values during the follow-up period. Additionally, the effect size of the treatment was calculated using the following formula: Effect Size = (Mean change of RLRL group − Mean change of control group)/Mean change of control group. 

Image Analysis

Structural OCT was performed with horizontal and vertical scan lines centered on the fovea (Spectralis OCT; Heidelberg Engineering). Choroidal images were processed using ImageJ version 1.53 (NIH, Bethesda, MD, USA). CT was defined as the distance from the retinal pigment epithelium (RPE)–Bruch's membrane complex to the choroid–sclera interface.^36,40,41 Measurements were taken at the fovea in both horizontal and vertical scans, as well as at specific distances from the fovea: 500, 1000, 1500, and 2000 µm nasal and temporal in horizontal scans (N500, N1000, N1500, N2000, T500, T1000, T1500, T2000), and 500, 1000, 1500, and 2000 µm superior and inferior in vertical scans (S500, S1000, S1500, S2000, I500, I1000, I1500, I2000) (Fig. 1). Subfoveal CT (SFCT) was calculated as the average of the horizontal and vertical SFCT measurements. 

Figure 1.

 

The measurements of CT. (A) The representative structural OCT image. (B) The choroidal thickness measurements in vertical scan. (C) The choroidal thickness measurements in horizontal scan.

To compare CV before and after RLRL therapy, image binarization was performed using ImageJ software. The total choroidal area (TCA) was chosen from the outer boundary of the RPE-Bruch's membrane layer to the choroid–sclera interface. The measurement areas were the areas between 500 µm nasal from the fovea and 500 µm temporal from the fovea (horizontal 1000), between 1000 µm nasal from the fovea and 1000 µm temporal from the fovea (horizontal 2000), between 1500 µm nasal from the fovea and 1500 µm temporal from the fovea (horizontal 3000), between 2000 µm nasal from the fovea and 2000 µm temporal from the fovea (horizontal 4000), between 500 µm superior from the fovea and 500 µm inferior from the fovea (vertical 1000), between 1000 µm superior from the fovea and 1000 µm inferior from the fovea (vertical 2000), between 1500 µm superior from the fovea and 1500 µm inferior from the fovea (vertical 3000), and between 2000 µm superior from the fovea and 2000 µm inferior from the fovea (vertical 4000). The TCA was chosen as the region of interest using a polygon selection tool and introduced into the region of interest (ROI) manager. The image was converted to an eight-bit format for applying the Niblack auto local threshold tool and then reconverted to RGB with the luminal area (LA) highlighted using a color threshold tool. This was added to the ROI manager. To determine the LA within the TCA polygon, areas from the ROI manager were merged using the “AND” operation. The final area was introduced into the ROI manager, and the stromal area (SA) was obtained by subtracting the LA from the TCA^36,42 (Fig. 2, Supplementary Table S1). 

Figure 2.

 

The measurements of CV. (A, C, E) the structural OCT image. (B, D, F) The binarized OCT image.

OCTA images were acquired using Spectralis OCTA. En face angiograms of the choriocapillaris slab (the layer between the basal border of the RPE–Bruch's membrane complex and approximately 20 µm beneath it) were processed to remove project artifacts from retinal vessels. The CLA was measured using a threshold binarization algorithm to detect flow signals.^34,36,43 The CLA measurements were performed within four concentric rings centered on the fovea, with diameters of 0.5, 1, 1.5, and 2 mm. The specific areas measured included 0 to 0.5 mm from the fovea (0-0.5 sum), 0 to 1 mm from the fovea (0-1 sum), 0 to 1.5 mm from the fovea (0-1.5 sum), 0 to 2 mm from the fovea (0-2 sum), 0.5 to 1 mm from the fovea (0.5-1 sum), 0.5 to 1.5 mm from the fovea (0.5-1.5 sum), 0.5 to 2 mm from the fovea (0.5-2 sum), 1 to 1.5 mm from the fovea (1-1.5 sum), 1 to 2 mm from the fovea (1-2 sum), and 1.5 to 2 mm from the fovea (1.5-2 sum). The OCTA images were maintained in their native form without adjustments to brightness or contrast. Image analysis was conducted using ImageJ software. The “round selection tool” was used to create concentric rings with diameters of 0.5, 1, 1.5, and 2 mm centered on the fovea. These rings were added to the ROI manager and merged using the “AND” operation. The image was converted to eight-bit format for applying the Phansalkar auto local threshold tool, then reconverted to RGB with the CLA highlighted using a color threshold tool, and added to the ROI manager. To evaluate CLA within the en face choriocapillaris, all areas from the ROI manager were merged using the “AND” operation³⁶ (Fig. 3, Supplementary Table S1). 

Figure 3.

 

The measurements of CLA. (A) OCTA scan region centering on fovea. (B, E–N) The measurement ranges of CLA. (C, D) Structural OCT image combined with flow OCT image with choriocapillaris segmentation lines.

All analyses and measurements were performed in a blinded manner. To assess the reproducibility of our measurements, choroidal parameters were remeasured in 50 eyes by the same trained observer (M.L.). The intraclass correlation coefficient values were as follows: CT measurements ranged from 0.842 to 0.918, CV measurements ranged from 0.852 to 0.930, and CLA measurements ranged from 0.999 to 1.000. 

Statistical Analyses

All analyses were conducted using R Project (The R Foundation, Vienna, Austria) and Empowerstats (www.empowerstats.com; X&Y Solutions, Inc., Boston, MA, USA). Data are presented as mean ± standard deviation where applicable. Age distribution was tested for normality using the Shapiro–Wilk test and confirmed to be non-Gaussian. Thus the Mann–Whitney U test was used for age comparisons between groups. The χ² test was used to compare the sexes between groups. Generalized estimating equations (GEEs), which take the correlation of measurements of the two eyes of one participant into account, were used for intergroup comparison of AL, SE, baseline CT, baseline CV, and baseline CLA; comparisons of pre- and post-RLRL therapy AL, SE, CT, CV, and CLA; correlation analyses between changes in choroidal parameters and changes in AL/SE during the follow-up period; and correlation analyses between changes in AL/SE/choroidal parameters at three months and changes in AL/SE/choroidal parameters at 12 months. 

Results

Study Characteristics

As shown in Table 1, there were no significant differences in age, sex, AL, or SE between the RLRL and control groups (all P > 0.05). 

Table 1.

 

Study Characteristics

 

Changes in AL and SE in the RLRL and Control Groups During the Follow-Up Period

In the RLRL group, AL decreased significantly at three and six months after RLRL therapy (P < 0.001 and P = 0.006, respectively), but it returned to baseline at 12 months after the therapy (P = 0.453). SE increased significantly compared with baseline values at three, six, and 12 months after RLRL therapy (all P < 0.001). In contrast, AL increased, and SE decreased significantly throughout the entire follow-up period in the control group (all P < 0.05) (Table 2). 

Table 2.

 

Changes in AL and SE of RLRL and Control Groups During the Follow-Up Period

 

Myopia Control Rates of RLRL Treatment and Control Groups

As shown in Table 3, the myopia control rates based on AL for the RLRL group were 64.00%, 61.00%, and 43.00% at three, six, and 12 months, respectively. In contrast, the myopia control rates in the control group were 0.00% throughout the entire follow-up period. For SE, the myopia control rates in the RLRL group were 68.00%, 67.00%, and 62.00% at three, six, and 12 months, respectively. The control group had much lower myopia control rates of 1.85%, 2.78%, and 2.78% at three, six, and 12 months, respectively. 

Table 3.

 

Myopia Control Rates in RLRL and Control Groups

 

Changes in CT in the RLRL Group During the Follow-Up Period

In the RLRL group, all CT parameters increased significantly during the follow-up period compared to baseline values (all P < 0.001) (Fig. 4). 

Figure 4.

 

Changes in CT of RLRL group during the follow-up period. FCT, foveal choroidal thickness; I, inferior; N, nasal; S, superior; T, temporal.

Changes in the CV of the RLRL Group During the Follow-Up Period

In the RLRL group, all CV parameters increased significantly during the follow-up period compared to the baseline values (all P < 0.05) (Fig. 5). 

Figure 5.

 

Changes in CV of RLRL group during the follow-up period.

Changes in the CLA of the RLRL Group During the Follow-Up Period

In the RLRL group, all CLA parameters increased significantly during the follow-up period compared to the baseline values (all P < 0.05) (Fig. 6). 

Figure 6.

 

Changes in CLA of RLRL group during follow-up period.

The Relationships Between Changes in CT and Changes in AL/SE

Changes in all CT values were significantly correlated with changes in AL/SE at 12-month follow-up. Most CT values also showed significantly correlations with changes in AL and SE at the three- and six-month follow-ups (Table 4). 

Table 4.

 

The Relationships Between Changes in CT and Changes in AL/SE

 

The Relationships Between Changes in CV and Changes in AL/SE

For AL, changes in all CV values were significantly correlated with changes in AL at both three and 12 months of follow-up. At the six-month follow-up, only half of the CV values showed significant correlations with changes in AL. For SE, changes in all CV values were significantly correlated with changes in SE at the 12-month follow-up. At the three- and six-month follow-ups, only some of the CV values showed significant correlations with changes in SE (Table 5). 

Table 5.

 

The Relationships Between Changes in CV and Changes in AL/SE

 

The Relationships Between Changes in CLA and Changes in AL/SE

Significant correlations were observed between changes in CLA (except for changes in the 0–0.5 sum) and changes in AL at 12-month follow-up (Table 6). 

Table 6.

 

The Relationships Between Changes in CLA and Changes in AL/SE

 

The Relationships Between Changes in AL/SE/Choroidal Parameters at Three Months and Changes in AL/SE/Choroidal Parameters at 12 Months

Except for the CT at N2000 and TCA at H1000, all other choroidal parameters showed significant correlations between changes at 3 and 12 months. Similarly, AL and SE also demonstrated significant correlations between changes at 3 and 12 months (Table 7). 

Table 7.

 

The Relationships Between Changes in AL/SE/Choroidal Parameters at Three Months and Changes in AL/SE/Choroidal Parameters at 12 Months

 

Discussion

In this study, we investigated the effects of RLRL therapy on AL, SE, and choroidal parameters. During the follow-up period, changes in AL and SE in the RLRL and control groups exhibited opposite trends. In the RLRL group, AL decreased at three and six months but returned to pretreatment values at 12 months. In contrast, AL increased significantly throughout the follow-up period (three, six, and 12 months) in the control group. Similarly, SE increased significantly in the RLRL group over the follow-up period, whereas it decreased significantly in the control group. These results suggest that RLRL can significantly slow or reverse the progression of myopia. Regarding the choroid, all choroidal parameters (CT, CV, and CLA) increased significantly during the follow-up period. This indicates that RLRL therapy could improve choroidal blood supply and circulation, which may contribute to the control of AL and SE in children. 

Photobiomodulation therapy has proven effective in delaying myopic progression in children.^{10,17,19,25,30} In the control group, the single-spectacles/focus group had an increase in AL ranging from 0.14 to 0.48 mm, the orthokeratology group had an increase in AL of 0.06 mm, and the atropine group had an increase in AL of 0.33 mm, while the photobiomodulation therapy showed a change in AL ranging from −0.06 to 0.13 mm, which was lower than that of the control groups. Regarding SE in the control group, it showed a decrease ranging from −0.97 to −0.25 D in the single-spectacles/focus group and −0.60 D in the atropine group. Meanwhile, the photobiomodulation therapy group showed a change in SE ranging from −0.20 to 0.28 D, which was higher than that of the control group (Table 8).^10,17–23 The results of the present study are similar to previous findings, with AL changes of −0.06 mm at three months, −0.06 mm at six months, and −0.02 mm at 12 months after RLRL therapy, and SE changes of 0.19 D at three months, 0.25 D at six months, and 0.28 D at 12 months. In the control group, AL changes were 0.14, 0.24, and 0.43 mm at three, six, and 12 months, respectively, whereas SE changes were −0.15, −0.41, and −0.41 D at three, six, and 12 months during the same periods. The changing trends in AL and SE were the opposite of those of the RLRL therapy and control groups. Although outdoor activities have been suggested to slow myopia progression, children with additional outdoor activities showed a decrease in SE (−1.42 D) and an increase in AL (0.95 mm) over a three-year follow-up period.⁴⁴ Therefore photobiomodulation therapy may represent a novel approach to controlling myopia. However, the long-term effects of this therapy remain unclear and require further investigation. 

Table 8.

 

Changes in Axial Length and Spherical Equivalent in Studies of Photobiomodulation Therapy

 

In this study, we not only observed changes in AL and SE but also measured changes in choroidal parameters (CT, CV, and CLA) in the RLRL therapy group. Although previous studies have reported changes in CT during photobiomodulation therapy, most of them only measured the SFCT.^{10,17–19,22} Only Tian et al.²¹ measured the CT in the foveal and parafoveal areas at nine locations. However, their follow-up was limited to six months. In contrast, our study followed up participants for 12 months and included 17 CT measurement locations, providing a more comprehensive CT dataset than previous studies. Our results are consistent with those of previous studies,^{10,17–19,21,22} indicating that photobiomodulation therapy induces an increase in CT. 

Besides the morphology of the choroid (CT), we also measured the perfusion of the choroid (CV and CLA) simultaneously, because CT alone may not adequately reflect the choroidal circulation status. Zhou et al. observed positive effects of photobiomodulation on CV, with significant increases in TCA and LA.¹⁹ Our study, which included additional CV measurements and revealed similar findings, indicated that all CV parameters increased significantly after photobiomodulation therapy. This positive effect appeared to persist throughout the 12-month follow-up. Regarding CLA, our study is the first to examine changes induced by photobiomodulation therapy. The CLA results were consistent with those for CT and CV, with significant increases at all measurement locations after RLRL therapy. Combining the CT, CV, and CLA data suggests that photobiomodulation therapy could increase choroidal blood flow and perfusion in the foveal and parafoveal areas. 

In addition to recording changes in choroidal parameters during the follow-up period, we analyzed the correlations between changes in choroidal parameters and changes in AL/SE. We found significant correlations between changes in most choroidal parameters and changes in AL and SE at three, six, and 12 months, indicating a close relationship between choroidal changes and AL/SE changes. This result further implies that photobiomodulation therapy could improve choroidal blood flow and perfusion in the foveal and parafoveal areas, potentially contributing to the observed changes in AL/SE and thus delaying myopia progression. Although these correlations suggest that targeting the choroid could be a promising strategy for myopia control, our study only identifies associations. The exact mechanism through which photobiomodulation therapy affects myopia control requires further investigation. 

The choroid has various functions, including nourishing the retina and adjusting the refractive state through changes in CT.⁴⁵ Choroidal thinning may precede axial changes in myopia,^46,47 and changes in CT could be early indicators of myopia progression.²⁵ Photobiomodulation therapy may increase choroidal blood flow and perfusion, thereby improving ischemia and hypoxia in the sclera, conditions that are closely associated with axial elongation.^34,36 In addition, a thickened choroid can decrease the AL by pushing the retina forward.¹⁰ Moreover, photobiomodulation therapy may enhance mitochondrial function by promoting the oxidation of cytochrome C, which increases mitochondrial oxygen utilization, mitochondrial membrane sensitivity, and mitochondrial permeability. This process helps dissociate nitric oxide from cytochrome C and boosts ATP production, potentially reducing oxidative stress and further delaying myopia progression.^48,49 In addition, other studies have indicated that photobiomodulation therapy could reduce the levels of interferon γ and tumor necrosis factor α, inhibit the production of prostaglandin E2, and reduce the expression of cyclooxygenase 1 mRNA, which may also contribute to controlling myopia progression.^50,51 

Retinal hypoxia may also contribute to myopia progression by inducing oxidative stress through the generation of excessive reactive oxygen species, which can alter retinal dopamine and nitric oxide levels, further promoting myopia progression.⁵² By increasing choroidal perfusion and circulation, photobiomodulation therapy may improve retinal hypoxia, potentially contributing to the control of myopia. 

In addition, we also performed correlation analysis between changes at 3 months and changes at 12 months for AL, SE, and choroidal parameters, to investigate the prediction effect of changes at 3 months. The results showed that AL, SE, and all choroidal parameters, except for CT of N2000 and TCA of H1000, showed significant correlations between changes at three and 12 months. This indicates that the short-term effect of photobiomodulation therapy (i.e., changes at three months) can be used to predict the long-term effects (i.e., changes at 12 months). The consistency between short-term and long-term changes in AL, SE, and choroidal parameters underscores the potential of early measurements to forecast long-term results. 

Regarding the safety of photobiomodulation therapy, no retinal damage was observed in this study, aligning with most previous studies with follow-up periods ranging from six to 24 months.^17–19 However, a recent study reported a case of retinal damage after RLRL therapy.⁵³ Therefore further investigation into the safety of RLRL is required. 

This study has certain limitations. First, it was a single-center study conducted in a Chinese population. Multicenter studies in different geographic regions and populations are needed to provide more comprehensive evidence regarding the efficacy of photobiomodulation therapy for myopia control and its impact on choroidal parameters. Second, the follow-up period was limited to 12 months, and longer-term studies are required to assess the sustainability of the therapy's effects. Third, changes in ocular parameters (AL, SE, and choroidal parameters) after cessation of photobiomodulation therapy were not evaluated. Fourth, although we investigated choroidal changes in the foveal and parafoveal areas, peripheral choroidal changes were not observed. 

In conclusion, photobiomodulation therapy can slow or reverse the progression of myopia in children, making it a novel and effective method for controlling myopia. Moreover, this therapy could improve choroidal blood perfusion and circulation, which might potentially be one reason for the myopia control induced by the photobiomodulation therapy. 

Acknowledgments

Supported by the National Natural Science Foundation of China (Grant No. 82000893, 81800821). 

Disclosure: Y. Liu, None; M. Zhu, None; X. Yan, None; M. Li, None; Y. Xiang, None