Purpose: To investigate the efficacy and safety of repeated low-level red-light (RLRL) therapy combined with orthokeratology among children who, despite undergoing orthokeratology, exhibited an axial elongation of at least 0.50 mm over 1 year. Design: Multicenter, randomized, parallel-group, single-blind clinical trial (ClinicaTrials.gov identifier, NCT04722874). Participants: Eligible children were 8-13 years of age with a cycloplegic spherical equivalent refraction of -1.00 to -5.00 diopters at the initial orthokeratology fitting examination and had annual axial length (AL) elongation of ≥0.50 mm despite undergoing orthokeratology. Forty-eight children were enrolled from March 2021 through January 2022, and the final follow-up was completed in March 2023. Methods: Children were assigned randomly to the RLRL therapy combined with orthokeratology (RCO) group or to the orthokeratology group in a 2:1 ratio. The orthokeratology group wore orthokeratology lenses for at least 8 hours per night, whereas the RCO group received daily RLRL therapy twice daily for 3 minutes in addition to orthokeratology. Main outcome measures: The primary outcome was AL change measured at 12 months relative to baseline. The primary analysis was conducted in children who received the assigned intervention and completed at least 1 follow-up after randomization using the modified intention-to-treat principle. Results: Forty-seven children (97.9%) were included in the analysis (30 in the RCO group and 17 in the orthokeratology group). The mean axial elongation rate before the trial was 0.60 mm/year and 0.61 mm/year in the RCO and orthokeratology groups, respectively. After 12 months, the adjusted mean AL changes were -0.02 mm (95% confidence interval [CI], -0.08 to +0.03 mm) in the RCO group and 0.27 mm (95% CI, 0.19-0.34 mm) in the orthokeratology group. The adjusted mean difference in AL change was -0.29 mm (95% CI, -0.44 to -0.14 mm) between the groups. The percentage of children achieving an uncorrected visual acuity of more than 20/25 was similar in the RCO (64.3%) and orthokeratology (65.5%) groups (P = 0.937). Conclusions: Combining RLRL therapy with orthokeratology may offer a promising approach to optimize axial elongation control among children with myopia. This approach also potentially allows children to achieve satisfactory visual acuity, reducing daytime dependence on corrective eyewear. Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Introduction: The purpose of this study was to explore the effects of repeated low-level red-light (RLRL) therapy on the structure and vasculature of the choroid and retina in Chinese children with premyopia. Methods: This study was a single-center randomized clinical trial. A total of 94 children with premyopia (- 0.50 D < spherical equivalent [SE] ≤ + 0.75 D) were randomly assigned to either the RLRL therapy or control group. Follow-up visits were planned at 1, 3, 6, 9, and 12 months. Optical coherence biometry was used to measure axial length (AL) and anterior segment parameters. Choroidal thickness (CT), retinal thickness (RT), superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), choriocapillaris perfusion area (CCPA), and choroidal vessel volume (CVV) were measured by optical coherence tomography angiography, centered on the foveal, parafoveal (ParaF), and perifoveal (PeriF) regions. Results: The thickening of the choroid was observed across the entire macular region at different time points in the RLRL therapy group. Relative to the baseline measurement, foveal CT significantly increased at the 1-month follow-up with RLRL therapy, with a mean (± standard deviation [SD]) adjusted change of 16.96 ± 19.87 μm. The greatest magnitude of foveal CT changes was observed at the 3-month visit (an increase of 19.58 ± 20.59 μm), with a slight reduction in the extent of foveal CT increase at the 6-month visit (an increase of 15.85 ± 23.77 μm). The second greatest CT increase was observed at the 9-month visit (an increase of 19.57 ± 35.51 μm), after which the extent of CT increase gradually decreased until the end of the study at the 12-month visit (an increase of 11.99 ± 32.66 μm). We also observed a significant increase in CT in the ParaF and PeriF areas in the RLRL group over 12 months. In contrast, CT across the entire macular region in the control group significantly decreased throughout the follow-up visits (all P < 0.05). Regarding the vascular parameters of the choroid, significant increases in CVV were observed primarily in the ParaF and PeriF regions of the choroid in the RLRL group. In comparison, the control group exhibited decreases in CVV throughout the entire area. Furthermore, notable elevations in CCPA were detected in the PeriF area of the choroid in the RLRL group during the 1-month (an increase of 0.40 mm2), 3-month (an increase of 0.25 mm2), and 12-month visits (an increase of 0.42 mm2) (all P < 0.05). In addition, no notable differences were observed between the groups regarding foveal RT and retinal vascular parameters throughout the 12 months (P > 0.05). Notably, RLRL therapy achieved a notable reduction in SE shift by 73.8%, a substantial decrease in AL change by 67.9%, and a significant reduction in myopia incidence by 45.1% within 1 year. Conclusion: Our study demonstrated a significant increase in CT and flow in the RLRL-treated eyes throughout the 12-months of the study. Combined with its reduction in spherical equivalent progression and axial elongation, RLRL could be used as an effective therapy for preventing progression in premyopes.

Backgroud: To investigate the safety of repetitive low-level red-light therapy (RLRLT) in children with myopia. Methods: Children with myopia were assigned to the RLRL and control groups. Axial length (AL) and spherical equivalent refraction (SER) were followed up at 3-, 6-, and 12-month. To evaluate the safety of RLRLT, at 6 and 12 months in the RLRL group, multifocal electroretinography (mfERG) and contrast sensitivity were recorded. Furthermore, optical coherence tomography was used to measure the relative reflectance of the ellipsoid zone (rEZR), photoreceptor outer segment (rPOSR), and retinal pigment epithelium (rRPER). Results: A total of 108 children completed the trial (55 in the RLRL group and 53 in the control group). After 3, 6, and 12 months, AL was shorter and SER less myopic in the RLRL group than in the control group. Regarding the safety of the RLRLT, the response density and amplitude of the P1 wave of the first ring of the mfERG increased significantly at 6 months (P = 0.001 and P = 0.017, respectively). At 6 and 12 months, contrast sensitivity at the high spatial frequency increased. Moreover, the rEZR increased significantly at 6 months (P = 0.029), the rPOSR increased significantly at 6 and 12 months (both P < 0.001), and the increase in rPOSR was greater with greater AL regression. Conclusions: Based on retinal function and structure follow-up, RLRLT was safe within 12 months. However, rEZR and rPOSR increased, the effects of this phenomenon requires further observation.

Abstract Photobiomodulation (PBM) therapy uses light of different wavelengths to treat various retinal degeneration diseases, but the potential damage to the retina caused by long-term light irradiation is still unclear. This study were designed to detect the difference between long- and short-wavelength light (650-nm red light and 450-nm blue light, 2.55 mW/cm2, reference intensity in PBM)-induced injury. In addition, a comparative study was conducted to investigate the differences in retinal light damage induced by different irradiation protocols (short periods of repeated irradiation and a long period of constant irradiation). Furthermore, the protective role of PARP-1 inhibition on the molecular mechanism of blue light-induced injury was confirmed by a gene knockdown technique or a specific inhibitor through in vitro and in vivo experiments. The results showed that the susceptibility to retinal damage caused by irradiation with long- and short-wavelength light is different. Shorter wavelength lights, such as blue light, induce more severe retinal damage, while the retina exhibits better resistance to longer wavelength lights, such as red light. In addition, repeated irradiation for short periods induces less retinal damage than constant exposure over a long period. PARP-1 plays a critical role in the molecular mechanism of blue light-induced damage in photoreceptors and retina, and inhibiting PARP-1 can significantly protect the retina against blue light damage. This study lays an experimental foundation for assessing the safety of phototherapy products and for developing target drugs to protect the retina from light damage.

Time spentoutdoorsisthe bestdefence againstshort-sightedness, but scientists are searchingfor other ways to reverse the troubling trend.

目的：系统评价重复低强度红光(RLRL)照射对儿童近视进展的控制效果。 方法：检索Medline、Embase、Cochrane Library、Web of Science、ClinicalTrial.gov和中国知网、维普全文数据库、万方数据库、中国临床试验注册中心(www.chictr.org.cn)中关于RLRL照射控制儿童近视进展的随机对照试验(RCT)，检索时限为建库起至2022年9月，补充检索灰色数据库。根据PICOS原则制定纳入和排除标准。由2位研究者独立筛选文献，提取资料并依据Cochrane风险偏倚评估工具评估纳入研究的偏倚风险后，将数据导入RevMan 5.4软件进行Meta分析。采用均值和标准差计算各研究数据的均值差和95%置信区间，比较单焦点框架眼镜联合RLRL照射治疗(试验组)与单独使用单焦点框架眼镜(对照组)干预前后等效球镜度(SE)、眼轴长度(AL)的变化值。采用GRADE系统对结局指标进行证据质量分级。 结果：检索到157篇文献，经过筛选后共纳入7项符合标准的高质量RCT研究，共1 038例儿童。Meta分析结果显示，与对照组相比，不同随访时间点(1、3、6、12、24个月)，试验组均可显著控制近视儿童SE进展，减少AL增长；随着随访时间的延长(1~24个月)，试验组控制SE进展效果越强(0.14~0.93 D)，减少AL增长效果越明显(0.07~0.48 mm)。635 nm和650 nm波长红光照射均可显著控制近视患者SE进展，减少AL增长。GRADE评级显示，SE变化量和AL变化量这2个结局指标为中等强度证据。 结论基于当前中等强度证据显示，与单独使用单焦点框架眼镜相比，联合RLRL照射对儿童近视进展的控制效果更好。

患者，女，12岁，近视4年，因佩戴角膜塑形镜后反复眼红、眼痒、分泌物增多1年于2022年3月12日在湖南省儿童医院就诊。患儿因变应性结膜炎病史曾双眼点用奥洛他定滴眼液和玻璃酸钠滴眼液，其母亲中度近视，否认其他眼病家族史。患儿右眼裸眼视力0.04，复方托吡卡胺滴眼液扩瞳后矫正视力－6.50 DS/－0.50 DC×5°＝0.8；左眼裸眼视力0.04，矫正视力为－5.75 DS/－1.00 DC×180°＝0.8。由于患儿曾用角膜塑形镜矫正近视且反复出现双眼结膜炎，在其监护人要求及眼底检查排除黄斑疾病后(图1)，采用红光治疗仪(型号RS-200)行单纯低强度红光重复照射疗法(repeated low-level red-light，RLRL)。仪器为Ⅱ类设备B型，光源输出功率为(2.0±0.5)mW，瞳孔直径4.0 mm状态下进入瞳孔的光功率约为0.25 mW，照射参数为AC(220±22)V，(50±1)Hz；输入功率≤30 VA。患儿每天照射双眼2次，间隔至少4 h，每次3 min。RLRL治疗1个月双眼屈光度降低约－2.00 D，更换镜片；治疗3个月矫正视力为1.0，分别于治疗后1、3个月行眼底和光学相干断层扫描(optical coherence tomography，OCT)检查，均未发现异常(图2，3)。治疗后5个月(2022年8月10日)患儿出现治疗后彩虹样后像，持续时间偶超8 min，未就诊并自行继续治疗。2022年8月30日患儿出现视力下降，咨询后建议停用RLRL并及时复诊。2022年9月3日患儿于湖南省儿童医院就诊，诉右眼眼红、畏光伴咳嗽、流涕1周，不伴发热。眼科检查见双眼结膜充血，右眼中央角膜可见片状荧光素钠染色，双眼调节和放松不足。超广角眼底成像可见黄斑中心凹圆形病灶；OCT检查示双眼中心凹视网膜外层椭圆体带欠连续，直径712 μm(图4)。屈光科与眼底病科会诊后诊断为双眼高度近视、右眼角膜炎、左眼结膜炎、双眼视网膜病变。以更昔洛韦医用凝胶、玻璃酸钠滴眼液点眼2周；甲泼尼龙片晨服，8 mg/d，连续1周；球旁注射曲安奈德注射液40 mg 1次。患者随后在中南大学湘雅二院、上海交通大学新华医院、中山大学中山眼科中心就诊，视神经磁共振成像平扫+增强检查示双侧视神经未见异常，双眼视野明显异常；多焦视网膜电图(multifocal electroretinogram，mfERG)检查示双眼1环振幅密度下降，中心反应峰消失；双眼视杆、视锥反应波振幅均轻度下降。嘱患者口服叶黄素1个月并停用RLRL。2个月后患者自觉视力逐渐恢复，2022年10月19日于湖南省儿童医院复诊，双眼矫正视力恢复至0.8，OCT成像示双眼黄斑中心凹椭圆体带完整性和连续性均恢复(图5)。给予玻璃酸钠滴眼液点眼和左旋多巴片250 mg/d口服，2022年12月21日(停用RLRL后4个月)检查角膜透明，视网膜结构完整，双眼视力未查(图6)。

近年来，低强度600~670 nm红光照射治疗近视引起了研究者们的广泛关注，国内为期1年的多中心随机对照试验发现，红光治疗可以抑制儿童的眼轴增长和近视进展，然而其作用机制及安全性尚未完全明确。纵向色差理论可以解释红光照射在雏鸡和豚鼠中表现出的延缓近视作用，然而不同物种的研究存在差异，在灵长类动物中表现出相反的结果。研究表明，红光控制近视的可能机制包括：短暂增加脉络膜血流，改善巩膜缺氧；影响视锥细胞代谢信号通路；光照强度达到一定阈值可促进视网膜分泌多巴胺；影响昼夜节律；通过细胞色素C氧化酶减少氧化应激，促进细胞修复，抑制细胞凋亡。安全性方面，研究提示红光治疗存在双剂量效应：低强度、低剂量、短时间的红光照射尚未发现安全性事件，但需警惕过度照射引起感光细胞和视网膜色素上皮细胞损伤。本文对红光照射治疗近视的临床有效性、作用机制及安全性研究进展进行综述。

Purpose: To evaluate the long-term efficacy and safety of repeated low-intensity red light (RLRL) treatment for childhood myopia. Design: Systematic review and meta-analysis METHODS: We searched PubMed, Web of Science, CNKI, and Wanfang from inception to February 8, 2023. We used the RoB 2.0 and ROBINS-I tools to assess the risk of bias and then used a random-effect model to calculate the weighted mean difference (WMD) and 95% CIs. The primary outcomes were WMD in spherical equivalent refractive error (SER), WMD in axial length (AL), and WMD in subfoveal choroid thickness (SFChT). Subgroup analyses were performed to investigate the sources of heterogeneity based on variation in follow-up and study design. The Egger and Begg tests were used to assess publication bias. Sensitivity analysis was used to verify the stability. Results: This analysis included 13 studies (8 randomized controlled trials, 3 non-randomized controlled trials, and 2 cohort studies) involving 1857 children and adolescents. Eight studies met the meta-analysis criteria, and the WMD for myopia progression between RLRL and the control group was 0.68 diopters (D) per 6 months (95% CI = 0.38 to 0.97 D; I2 = 97.7%; P < .001) for SER change; -0.35 mm per 6 months (95% CI = -0.51 to -0.19 mm; I2 = 98.0%; P < .001) for AL elongation; and 36.04 µm per 6 months (95% CI = 19.61 to 52.48 µm; I2 = 89.6%; P < .001) for SFChT change. Conclusions: Our meta-analysis shows that RLRL therapy may be effective for delaying the progression of myopia. The evidence is low certainty, and larger and better randomized clinical trials with 2-year follow-ups are needed to improve the existing state of knowledge to inform medical guidelines more comprehensively.

Importance Myopia is a global concern, but effective prevention measures remain limited. Premyopia is a refractive state in which children are at higher risk of myopia, meriting preventive interventions. Objective To assess the efficacy and safety of a repeated low-level red-light (RLRL) intervention in preventing incident myopia among children with premyopia. Design, Setting, and Participants This was a 12-month, parallel-group, school-based randomized clinical trial conducted in 10 primary schools in Shanghai, China. A total of 278 children with premyopia (defined as cycloplegic spherical equivalence refraction [SER] of −0.50 to 0.50 diopter [D] in the more myopic eye and having at least 1 parent with SER ≤−3.00 D) in grades 1 to 4 were enrolled between April 1, 2021, and June 30, 2021; the trial was completed August 31, 2022. Interventions Children were randomly assigned to 2 groups after grade stratification. Children in the intervention group received RLRL therapy twice per day, 5 days per week, with each session lasting 3 minutes. The intervention was conducted at school during semesters and at home during winter and summer vacations. Children in the control group continued usual activities. Main Outcomes and Measures The primary outcome was the 12-month incidence rate of myopia (defined as SER ≤−0.50 D). Secondary outcomes included the changes in SER, axial length, vision function, and optical coherence tomography scan results over 12 months. Data from the more myopic eyes were analyzed. Outcomes were analyzed by means of an intention-to-treat method and per-protocol method. The intention-to-treat analysis included participants in both groups at baseline, while the per-protocol analysis included participants in the control group and those in the intervention group who were able to continue the intervention without interruption by the COVID-19 pandemic. Results There were 139 children (mean [SD] age, 8.3 [1.1] years; 71 boys [51.1%]) in the intervention group and 139 children (mean [SD] age, 8.3 [1.1] years; 68 boys [48.9%]) in the control group. The 12-month incidence of myopia was 40.8% (49 of 120) in the intervention group and 61.3% (68 of 111) in the control group, a relative 33.4% reduction in incidence. For children in the intervention group who did not have treatment interruption secondary to the COVID-19 pandemic, the incidence was 28.1% (9 of 32), a relative 54.1% reduction in incidence. The RLRL intervention significantly reduced the myopic shifts in terms of axial length and SER compared with the control group (mean [SD] axial length, 0.30 [0.27] mm vs 0.47 [0.25] mm; difference, 0.17 mm [95% CI, 0.11-0.23 mm]; mean [SD] SER, –0.35 [0.54] D vs –0.76 [0.60] D; difference, –0.41 D [95% CI, –0.56 to –0.26 D]). No visual acuity or structural damage was noted on optical coherence tomography scans in the intervention group. Conclusions and Relevance In this randomized clinical trial, RLRL therapy was a novel and effective intervention for myopia prevention, with good user acceptability and up to 54.1% reduction in incident myopia within 12 months among children with premyopia.