Cote Sharlotta, Zhang Alexis Ceecee, Ahmadzai Victoria, Maleken Amina, Li Christine, Oppedisano Jeremy, Nair Kaavya, Busija Ljoudmila, Downie Laura E
The University of Melbourne, Department of Optometry and Vision Sciences, Parkville, Australia.
Monash University, Biostatistics Unit, Department of Epidemiology and Preventive Medicine, Melbourne, Victoria, Australia, 3000.
Cochrane Database Syst Rev. 2020 Mar 18;3(3):CD013559. doi: 10.1002/14651858.CD013559.
Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease, which is the more prevalent form of dry eye disease. Intense pulsed light (IPL) therapy, involving treatment of the skin near the eyelids, has emerged as a potential treatment for MGD.
To evaluate the effectiveness and safety of intense pulsed light (IPL) for the management dry eye disease resulting from meibomian gland dysfunction (MGD).
We searched CENTRAL, MEDLINE (Ovid), Embase Ovid and three trial registers for eligible clinical trials on 1 August 2019. There were no restrictions on publication status, date or language.
We included randomised controlled trials (RCTs) studying the effectiveness or safety of IPL for treating MGD.
Our outcomes of interest were the change from baseline in subjective dry eye symptoms, adverse events, changes to lipid layer thickness, tear break-up time (TBUT), tear osmolarity, eyelid irregularity, eyelid telangiectasia, meibomian gland orifice plugging, meibomian gland dropout, corneal sodium fluorescein staining and conjunctival lissamine green staining. Two review authors independently screened abstracts and full-text articles, extracted data from eligible RCTs and judged the risk of bias using the Cochrane tool. We reached consensus on any disagreements by discussion. We summarised the overall certainty of the evidence using the GRADE Working Group approach.
We included three RCTs, one from New Zealand, one from Japan and one from China, published between 2015 and 2019. Together, these trials enrolled 114 adults (228 eyes). Two studies used a paired-eye (inter-eye comparison) design to evaluate the effects of a sham (control) IPL treatment relative to an actual IPL treatment. One study randomised individuals to either an IPL intervention combined with meibomian gland expression (MGX), or MGX alone (standard therapy). The study follow-up periods ranged from 45 days to nine months. None of the trials were at low risk of bias in all seven domains. The first authors of two included studies were in receipt of funding from patents or the manufacturers of IPL devices. The funding sources and declaration of interests were not given in the report of the third included trial. All three trials evaluated the effect of IPL on dry eye symptoms, quantified using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Pooling data from two trials that used a paired-eye design, the summary estimate for these studies indicated little to no reduction in dry eye symptoms with IPL relative to a sham intervention (mean difference (MD) -0.33 units, 95% confidence interval (CI) -2.56 to 1.89; I² = 0%; 2 studies, 144 eyes). The other study was not pooled as it had a unit-of-analysis error, but reported a reduction in symptoms in favour of IPL (MD -4.60, 95% CI -6.72 to -2.48; 84 eyes). The body of evidence for this outcome was of very low certainty, so we are uncertain about the effect of IPL on dry eye symptoms. There were no relevant combinable data for any of the other secondary outcomes, thus the effect of IPL on clinical parameters relevant to dry eye disease are currently unclear. For sodium fluorescein TBUT, two studies indicated that there may be an improvement in favour of IPL (MD 2.02 seconds, 95% CI 0.87 to 3.17; MD 2.40 seconds, 95% CI 2.27 to 2.53; 172 eyes total; low-certainty evidence). We are uncertain of the effect of IPL on non-invasive tear break-up time (MD 5.51 seconds, 95% CI 0.79 to 10.23; MD 3.20, 95% CI 3.09 to 3.31 seconds; two studies; 140 eyes total; very low-certainty evidence). For tear osmolarity, one study indicated that there may be an improvement in favour of IPL (MD -7.00 mOsmol/L, 95% -12.97 to -1.03; 56 eyes; low-certainty evidence). We are uncertain of the effect of IPL on meibomian gland orifice plugging (MD -1.20 clinical units, 95% CI -1.24 to -1.16; 84 eyes; very low-certainty evidence). We are uncertain of the effect of IPL on corneal sodium fluorescein staining. One study reported no evidence of a difference between the IPL and sham intervention arms at three months of follow-up (P = 0.409), and a second study reported data favouring IPL (MD -1.00 units, 95% CI -1.07 to -0.93 units; 172 eyes in total; very low-certainty evidence). We considered the incidence of adverse events at the study endpoint, as a measure of safety. As most trials did not specifically report adverse events, the safety of IPL as a treatment for MGD could also not be determined with any certainty. Very low-certainty results from individual studies suggest some adverse effects that may be experienced by participants, include mild pain and burning, and the potential for partially losing eyelashes (due to clinician error).
AUTHORS' CONCLUSIONS: This systematic review finds a scarcity of RCT evidence relating to the effectiveness and safety of IPL as a treatment for MGD. Whether IPL is of value for modifying the symptoms or signs of evaporative dry eye disease is currently uncertain. Due to a lack of comprehensive reporting of adverse events, the safety profile of IPL in this patient population is also unclear. The current limitations in the evidence base should be considered by clinicians using this intervention to treat MGD, and outlined to individuals potentially undergoing this procedure with the intent of treating dry eye disease. The results of the 14 RCTs currently in progress will be of major importance for establishing a more definitive answer regarding the effectiveness and safety of IPL for treating MGD. We intend to update this review when results from these trials become available.
睑板腺功能障碍（MGD）是蒸发型干眼疾病的主要病因，而蒸发型干眼疾病是更为常见的干眼类型。强脉冲光（IPL）疗法，即对眼睑附近皮肤进行治疗，已成为一种治疗MGD的潜在方法。
评估强脉冲光（IPL）治疗睑板腺功能障碍（MGD）所致干眼疾病的有效性和安全性。
我们于2019年8月1日检索了Cochrane中心对照试验注册库（CENTRAL）、MEDLINE（Ovid）、Embase（Ovid）以及三个试验注册库，以查找符合条件的临床试验。对发表状态、日期或语言均无限制。
我们纳入了研究IPL治疗MGD有效性或安全性的随机对照试验（RCT）。
我们感兴趣的结局指标包括主观干眼症状较基线的变化、不良事件、脂质层厚度变化、泪膜破裂时间（TBUT）、泪液渗透压、眼睑不规则度、眼睑毛细血管扩张、睑板腺开口堵塞、睑板腺缺失、角膜荧光素钠染色和结膜丽丝胺绿染色。两位综述作者独立筛选摘要和全文文章，从符合条件的RCT中提取数据，并使用Cochrane工具判断偏倚风险。我们通过讨论就任何分歧达成了共识。我们使用GRADE工作组方法总结了证据的总体确定性。
我们纳入了三项RCT，一项来自新西兰，一项来自日本，一项来自中国，发表于2015年至2019年之间。这些试验共纳入了114名成年人（228只眼）。两项研究采用配对眼（眼内比较）设计，以评估假手术（对照）IPL治疗相对于实际IPL治疗的效果。一项研究将个体随机分为IPL干预联合睑板腺按摩（MGX）组或单独MGX组（标准治疗）。研究随访期为45天至9个月。所有三项试验在所有七个领域均未处于低偏倚风险。两项纳入研究中的第一作者接受了IPL设备专利或制造商的资助。第三项纳入试验的报告中未提及资金来源和利益声明。所有三项试验均使用干眼标准患者评估（SPEED）问卷评估了IPL对干眼症状的影响。汇总两项采用配对眼设计的试验数据，这些研究的汇总估计表明，相对于假手术干预，IPL对干眼症状的减轻作用很小或没有减轻（平均差（MD）-0.33单位，95%置信区间（CI）-2.56至1.89；I² = 0%；2项研究，144只眼）。另一项研究未进行汇总，因为存在分析单位错误，但报告称症状减轻有利于IPL（MD -4.60，95%CI -6.72至-2.48；84只眼）。该结局的证据质量非常低，因此我们不确定IPL对干眼症状的影响。对于其他次要结局，没有相关的可合并数据，因此目前尚不清楚IPL对与干眼疾病相关的临床参数的影响。对于荧光素钠TBUT，两项研究表明可能有利于IPL（MD 2.02秒，95%CI 0.87至3.17；MD 2.40秒，95%CI 2.27至2.53；共172只眼；低质量证据）。我们不确定IPL对非侵入性泪膜破裂时间的影响（MD 5.51秒，95%CI 0.79至10.23；MD 3.20，95%CI 3.09至3.31秒；两项研究；共140只眼；极低质量证据）。对于泪液渗透压，一项研究表明可能有利于IPL（MD -7.00 mOsmol/L，95% -12.97至-1.03；56只眼；低质量证据）。我们不确定IPL对睑板腺开口堵塞的影响（MD -1.20临床单位，95%CI -1.24至-1.16；84只眼；极低质量证据）。我们不确定IPL对角膜荧光素钠染色的影响。一项研究报告称，在随访三个月时，IPL组和假手术干预组之间没有差异的证据（P = 0.409），另一项研究报告的数据有利于IPL（MD -1.00单位，95%CI -1.07至-0.93单位；共172只眼；极低质量证据）。我们将研究终点时不良事件的发生率作为安全性的衡量指标。由于大多数试验未具体报告不良事件，因此也无法确定IPL作为MGD治疗方法的安全性。个别研究的极低质量结果表明，参与者可能会经历一些不良反应，包括轻度疼痛和烧灼感，以及睫毛部分脱落的可能性（由于临床医生操作失误）。
本系统评价发现，关于IPL作为MGD治疗方法的有效性和安全性，随机对照试验证据不足。目前尚不确定IPL对于改善蒸发型干眼疾病的症状或体征是否有价值。由于缺乏对不良事件的全面报告，IPL在该患者群体中的安全性也不明确。使用这种干预措施治疗MGD的临床医生应考虑现有证据的局限性，并向可能接受该治疗以治疗干眼疾病的个体说明情况。目前正在进行的14项随机对照试验的结果对于确定IPL治疗MGD的有效性和安全性将具有重要意义。我们打算在这些试验结果可用时更新本综述。
