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| Management of Dry Eye Syndrome | |
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| Description: |
Dry eye syndrome, dry eye disease, or dysfunctional tear syndrome, either alone or in combination with other conditions, is a frequent cause of ocular irritation that leads patients to seek ophthalmologic care. It is estimated to affect between 5% and 50% of the population worldwide (Stapleton, 2017). Based on data from 2013, an estimated 16.4 million Americans have dry eye syndrome (Farrand, 2017). The prevalence of dry eye syndrome increases with age, especially in postmenopausal women. For both sexes, prevalence is more than 3 times higher in individuals 50 years of age or older compared to those 18 to 49 years of age. Meibomian gland dysfunction (MGD) is considered to be the most common cause of dry eye syndrome (Blepharitis. American Academy of Ophthalmology Cornea/External Disease Panel, 2018).
In a 2022 meta-analysis of 3 United States studies, the prevalence of dry eye ranged from 5% to 14% with an estimated pooled prevalence of 8%. The prevalence of MGD ranged from 10% to 55%. Over a 5-year period, the incidence of dry eye was 3% among individuals aged 18 years and older, and 8% among those aged 68 years and older (McCann, 2022). Prevention and treatment of dry eye syndrome are expected to be of greater importance as the population ages.
Risk Factors
Risk factors for DES include (AAO, 2018):
DES has been classified into two general groups: decreased tear production (resulting in aqueous deficient DES) and abnormal meibomian gland physiology (resulting in evaporative DES). However, it is now believed that both mechanisms are present in most patients, although one may be predominant. For all patients, tear film hyperosmolarity and subsequent ocular surface inflammation lead to the variety of symptoms and signs associated with DES.
Causes
Decreased tear production: Impaired lacrimal tear production can be caused by any form of lacrimal gland destruction or dysfunction. The reduced volume of aqueous fluid leads to hyperosmolarity of the tear film and subsequently the ocular surface, which incites inflammation of the ocular surface cells.
1. Deficiency of aqueous tear production can be subclassified into two subtypes:
2. Increased evaporative loss:
Excessive water loss from the ocular surface leads to tear film instability and a cycle of tear hyperosmolarity and lacrimal functional unit inflammation. It is most caused by meibomian gland dysfunction, also known as posterior blepharitis, in which the accessory lacrimal glands responsible for the lipid component of the tear film are dysfunctional. In a normally functioning eye, the nature of the mucin allows even spreading of the tear film to form a membrane, and the lipid layer provides a barrier to minimize evaporation of tears. Abnormalities of the lipid layer are associated with a higher rate of tear film evaporation. Structural abnormalities of eyelid position or decreased blink function also increase evaporation of the tear film by increasing the area or the time of tear film exposure. Lastly, topical medicated or preserved eye drop use, chronic contact lens wear, and ocular allergy syndromes can cause ocular surface irritation and increased tear film evaporation.
Symptoms in DES result from activation of sensory nerves of the ocular surface, either due to tear hyperosmolarity, the presence of inflammatory mediators, or hypersensitivity of the sensory nerves. Common eye complaints may include:
Diagnosis
There is no single diagnostic test or set of tests to confirm or rule out DES. Examples of methods often used to evaluate ocular surface include, but are not limited to:
1. Meibography: Is the imaging and study of the morphology (structure and function) of meibomian glands. Near-infrared dual imaging uses reflective and transilluminated light purportedly to improve meibography techniques (i.e., reduce time and discomfort) and enhance results.
Treatments
Current treatment options for MGD include physical expression to relieve the obstruction, administration of heat (warm compresses) to the eyelids to liquefy solidified meibomian gland contents, eyelid scrubs to relieve external meibomian gland orifice blockage, and medications (e.g., antibiotics, topical corticosteroids) to mitigate infection and inflammation of the eyelids (Blepharitis, 2018; Nichols, 2011; Blackie, 2010; Dry Eye Syndrome, 2018). These treatment options, however, have shown limited clinical efficacy, and often require a trial-and-error approach. For example, physical expression can be very painful given the amount of force needed to express obstructed glands. Warm compress therapy can be time-consuming and labor intensive, and there is limited evidence that medications relieve MGD (Blackie, 2010). While the symptoms of dry eye syndrome often improve with treatment, the disease usually is not curable and may lead to substantial patient and physician frustration (Blepharitis, 2018; Dry Eye Syndrome, 2018). Dry eyes can be a cause of visual morbidity and may compromise results of corneal, cataract, and refractive surgery. Inadequate treatment of dry eye syndrome may result in increased ocular discomfort, blurred vision, reduced quality of life, and decreased productivity.
Autologous Eye Drops (e.g., Autologous Serum Tears)
Autologous eye drops (autologous serum tears) have been proposed for dry eye syndrome (DES) and are made by mixing the individual's serum with other substances. There is not strong evidence for long-term or significant benefit over artificial tears and access to these eye drops, and the cost are additional barriers to its use. Additional large, high quality RTCs are needed in different severities of dry eye and using standardized questionnaires to measure participant-reported outcomes and objective clinical tests as well as objective biomarkers to assess the benefit of autologous eye drops (autologous serum tear) therapy for (DES). The evidence is insufficient to determine that the technology results in an improvement in the net health outcomes.
Electrothermal Heat (e.g., TearCare System)
The TearCare system is intended as an alternative to warm compresses to reduce dry eye syndrome (DES) symptoms caused by meibomian gland blockages. The system comprises four components: a smart hub to control thermal energy emission, a charger for the hub, two pairs of single-use thermal emitters (SmartLid devices), and a single use, blunt-tipped, tweezer-like device (Clearance Assistant).
An optometrist or ophthalmologist delivers the TearCare treatment during an office visit. The clinician applies the SmartLid devices to the individual's upper and lower eyelids over the meibomian glands and activates the hub. The connected emitters heat the eyelids to 41 degrees Celsius to 45 degrees Celsius for 12 minutes. During treatment, individuals keep their eyes open and blink normally; blinking is intended to help clear meibomian gland obstructions and relubricate eyes. After removing emitters, the clinician applies a drop of 0.5% tetracaine to each eye and expresses any remaining meibomian gland blockages from the individuals’ eyelids using the Clearance Assistant.
Intense Pulsed Light (IPL)
Intense Pulsed Light (IPL) therapy delivers bursts of light at specific wavelengths. The light energy is converted to heat. IPL therapy has been suggested as a treatment for dry eye syndrome (DES).
Intraductal Probing (e.g., Maskin Device)
Intra-ductal probing is performed using local or topical anesthetic and introduces a thin stainless-steel wire probe into the meibomian gland orifices to forcefully expel any obstructing material and restore patency.
Thermal Pulsation System
The LipiFlow Thermal Pulsation System (TearScience) is a new device developed to address the limitations of current treatment options to relieve MGD. This device is designed to heat the palpebral surfaces of both the upper and lower eyelids, while applying graded pulsatile pressure to the outer eyelid surfaces. The LipiFlow System is composed of a disposable ocular component and a handheld control system. Following application of a topical anesthetic, the heated inner portion of the LipiFlow eyecup is applied to the conjunctiva! surface of the upper and lower eyelids. The outer portion of the device covers the skin surface of the upper and lower eyelids. The device massages the eyelids with cyclical pressure from the base of the Meibomian glands in the direction of the gland orifices, thereby expressing the glands during heating. It is proposed that a single 12-minute session is at least as effective as twice daily lid warming and massage over 3 months.
Regulatory Status
In 2020 the FDA cleared the TrueTear Intranasal Tear Neurostimulator (Allergan, K193589, August 2020, Product code QBR). This device type is intended to temporarily increase tear production using neurostimulation to improve dry eye symptoms. The intranasal electrostimulation device for dry eye symptoms is a handheld device with two electroconductive tips that are inserted into the nasal cavity during neurostimulation. The disposable tips are made of rigid biocompatible USP Class VI plastic, and the conductive tips are made of silicone hydrogel. Additional hardware components include a reusable base, charging station, and cover. The base has two buttons that allow the user to select the stimulation level (device is locked from use after a predetermined amount of stimulation has been triggered). The device is powered by a rechargeable battery.
In 2022 the FDA cleared the iTear100 (Olympic Ophthalmics, K213623, March 2022. Product code QKV). This device type is a non-implantable device intended to increase tear production by mechanical stimulation via a battery-operated handheld electromechanical actuator with a vibratory tip, and software controller. The device activates tear production through stimulation of the nasolacrimal reflex. Stimulation mechanically activates external nasal nerve and initiates the nasolacrimal reflex, resulting in tear secretion. To produce the intended effect, the vibratory tip of the device should be applied to the lateral aspect of the nose for several seconds.
Eyelid thermal pulsation systems (FDA product code: ORZ) cleared by the U.S. Food and Drug Administration (FDA) are summarized in below. There are other office-based devices that deliver constant rather than pulsed heat to the eyelid (for example, MiBoFlow/MiBo Thermoflo, Blephasteam).
Coding
There is a CPT category III code specific to this treatment:
0207T: Evacuation of meibomian glands, automated, using heat and intermittent pressure, unilateral.
Effective in July 2013, there is a CPT category III code for tear film imaging (e.g., LipiView Ocular Surface Interferometer), which is being marketed for use with this treatment:
0330T: Tear film imaging, unilateral or bilateral, with interpretation and report. (may be utilized for LipiView Ocular Surface Interferometer)
This procedure may also be billed with the following CPT category III codes:
0507T Near-infrared dual imaging (i.e., simultaneous reflective and trans-illuminated light) of meibomian glands, unilateral or bilateral, with interpretation and report
0563T Evacuation of meibomian glands, using heat delivered through wearable, open-eye eyelid treatment devices and manual gland expression, bilateral (may be used utilized for TearCare)
Of note, 0207T may be reported for a unilateral procedure and 0563T for bilateral procedure.
17999 Unlisted procedure, skin, mucous membrane and subcutaneous tissue (maybe utilized for Intense Pulsed Light (e.g., IPL))
67999 Unlisted procedure, eyelids (may be utilized for iLux Thermal Pulsation System or Systane iLux2 Thermal Pulsation System)
68810 Probing of nasolacrimal duct, with or without irrigation (may be utilized for Intraductal probing [e.g., Maskin Device])
68811 Probing of nasolacrimal duct, with or without irrigation; requiring general anesthesia (may be utilized for Intraductal probing [e.g., Maskin Device])
68899 Unlisted procedure, lacrimal system (may be utilized for Autologous eye drops (e.g., autologous serum tears)
92499 Unlisted ophthalmological service or procedure (may be utilized for TrueTear, iTEARJ 00, iLux Thermal Pulsation System or Systane iLux2 Thermal Pulsation System)
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Policy/ Coverage: |
Coverage policy #2013009, Eyelid Thermal Pulsation for the Treatment of Dry Eye Syndrome, was combined with this policy effective October 1, 2023. For dates of service prior to October 1, 2023, if a hard copy of policy #2013009 is needed, please email: codespecificinquiry@arkbluecross.com
Effective October 1, 2023
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
Diagnostic tests for the diagnosis of dry eye syndrome do not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes. This includes but is not limited to the following:
For members with contracts without Primary Coverage Criteria, diagnostic tests for the diagnosis of dry eye syndrome are considered Not Medically necessary or are investigational and are not covered. Not Medically Necessary or investigational services are specific contract exclusions in most member benefit certificates of coverage. This includes but is not limited to the following:
Therapies for the treatment of dry eye syndrome (DES) due to decreased tear production and/or increased evaporation loss do not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness. This includes but is not limited to the following:
For members with contracts without Primary Coverage Criteria, therapies for the treatment of dry eye syndrome (DES) due to decreased tear production and/or increased evaporation loss are considered Not Medically Necessary or are investigational and are not covered. Not Medically Necessary or investigational services are specific contract exclusions in most member benefit certificates of coverage. This includes but is not limited to the following:
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| Rationale: |
Autologous Eye Drops (e.g., Autologous Serum Tears)
In vitro cell culture experiments showed that corneal epithelial cell morphology and function are better maintained by serum than by pharmaceutical tear substitutes. Clinical cohort studies have reported the successful use of serum for severe dry eyes and persistent epithelial defects. Studies generally show improvement in the short-term; however, improvement in symptoms over longer periods of follow-up has not been demonstrated. Protocols to prepare autologous serum eye drops and the concentrations used vary considerably between studies.
Pan et al (2017), in a Cochrane Systematic Review, evaluated the efficacy and safety of autologous serum eye drops given alone or in combination with artificial tears as compared with artificial tears alone, saline, placebo or no treatment for adults with dry eye. Five eligible RCTs were found, for a total of 92 participants, that compared autologous serum versus artificial tears or saline in individuals with dry eye of various origins. The certainty of evidence was assessed as being low or very low because of lack of reporting of quantitative data for most outcomes and unclear or high risk of bias among trials. Overall, investigators reported inconsistency in possible benefits of autologous serum for improving participant‐reported symptoms and other objective clinical measures. The investigations felt there might be some benefit in symptoms with autologous serum compared with artificial tears in the short‐term but found no evidence of an effect after 2 weeks of treatment. Well‐planned, large, high‐quality RCTs were recommended.
Shtein et al (2020) prepared an analysis on behalf of the American Academy of Ophthalmology. A literature search was performed and 10 studies of the use of autologous 3 serum-based eye drops for severe dry eye disease and 4 studies of persistent epithelial defect were reviewed. Several studies showed good effectiveness, with some improvement in symptoms, signs, or both. Eight studies reported improved symptoms for severe dry eye disease, and all noted improvement in at least 1 clinical sign. For persistent epithelial defects, all the studies showed improvement, with 3 of the 4 demonstrating an improvement rate of more than 90%. Adverse events were rare. The reviewers concluded that although autologous serum-based tears may be effective in the treatment of severe dry eye and persistent epithelial defect, conclusions are limited owing to the absence of controlled trials.
Large, high-quality randomized controlled studies are needed to determine the role of serum eye drops in the treatment of dry eyes.
Electothermal Heat (e.g., TearCare System)
Badawi (2019) reported on a study which was a 6-month extension of an initial 6-month, prospective, single-center, randomized pilot clinical trial whose results were previously reported. This extension study was conducted in full accordance with the tenets of the Declaration of Helsinki and US Food and Drug Administration regulations for the protection of human subjects in medical research. Only a subset of patients, those who had received the investigational TearCare® treatment in the initial study, were enrolled in this extension study and were retreated with the TearCare® treatment and followed for another 6 months. There are some limitations to this extension study. For example, this was a single-treatment, single-investigator study. As a result, it was not possible to mask subjects or the investigator. Also, the sample size was 12 subjects who had previously undergone a TearCare treatment. A larger, multi-center randomized, and masked, prospective trial is currently being planned. A larger study will enhance the evidence base for the use of TearCare® in the treatment ofDED. While previous trials, such as the LipiFlow trial, followed treated patients up to 1 month, this trial followed patients up to 13 months. Patients received a treatment at entry and then at 7 months. Objective and subjective end points improved in a repeatable fashion. In other words, the signs and symptoms of DED improved in patients up to 13 months. Further studies comparing TearCare® to other treatments are currently being prepared. Based on the statistically significant improvement in the signs and symptoms of DED following a second treatment with the TearCare® system observed in this extension study, repeated application appears to provide additional benefit to patients with DED. Larger, multicenter, randomized, prospective trials are planned to further evaluate this treatment for DED.
The system is currently undergoing clinical trials. The evidence is insufficient to determine the technology results in an improvement in the net health outcomes.
Intense Pulsed Light (IPL)
Leng et al. (2021) completed a systematic review and meta-analysis, examined the safety and efficacy of IPL for the treatment of MGD. Randomized clinical trials and cohort studies comparing IPL+ meibomian gland expression (MGX) or IPL alone with control groups were included. The weighted MD (WMD) was calculated to analyze the OSDI score and SPEED score, and the SMD was calculated to analyze the TBUT. Heterogeneity was quantified by the 12-statistic ranging from O to 100 %, and a random effects model was used in this meta-analysis. All analyses were performed by RevMan 5.3. All p values were calculated by the t-test, and p values were regarded as statistically significant at p
< 0.05. The Cochrane Collaboration's tool for assessing risk of bias was used to identify and evaluate bias in the literature. A total of 9 studies with a total of 539 patients were included; 8 studies examined TBUT, 6 examined OSDI scores, and 4 examined SPEED scores. IPL combined with MGX showed superiority regarding the TBUT (SMD 2.33, 95 % CI: 1.04 to 3.61), and OSDI scores (WMD 11.93, 95 % CI: - 17.10 to - 6.77), with high heterogeneity. The SPEED scores were not significantly different. The authors concluded that IPL combined with MGX may be a safe and effective treatment for MGD, however, it could not improve all symptoms; IPL alone was not superior to MGX. The efficacy was also affected by the number and average frequency of treatments. The efficacy of IPL may decrease within 6 months after the last treatment, so it should be considered a long term adjuvant therapy combined with MGX. When patients received 3 or 4 treatments (once every 3 to 4 weeks), a return visit at 6 months after the last treatment was needed.
(2020) Cote et al. reported MGD is the major cause of evaporative DED, which is the more prevalent form of dry eye disease; IPL therapy, involving treatment of the skin near the eyelids, has emerged as a potential treatment for MGD. In a Cochrane review, these researchers examined the safety and effectiveness of IPL for the management dry eye disease resulting from MGD. They searched CENTRAL, Medline (Ovid), Embase Ovid and 3 trial registers for eligible clinical trials on August 1, 2019. There were no restrictions on publication status, date, or language. These investigators included RCTs studying the safety or effectiveness of IPL for treating MGD. Outcome measures included the change from baseline in subjective dry eye symptoms, adverse events (AEs), changes to lipid layer thickness, TBUT, tear osmolarity, eyelid irregularity, eyelid telangiectasia, meibomian gland orifice plugging, meibomian gland drop-out, 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. They reached consensus on any disagreements by discussion; and summarized the overall certainty of the evidence using the GRADE Working Group approach. These investigators included 3 RCTs, 1 from New Zealand, 1 from Japan and 1 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 randomized 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 9 months; none of the trials were at low risk of bias in all 7 domains. The first authors of 2 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 3rd included trial. All 3 trials evaluated the effect of IPL on dry eye symptoms, quantified using the SPEED questionnaire. Pooling data from 2 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% CI: -2.56 to 1.89; F = 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 favor 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, thus, these researchers were uncertain regarding 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 were currently unclear. For sodium fluorescein TBUT, 2 studies indicated that there may be an improvement in favor 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). These investigators were uncertain of the effect of IPL on non-invasive TBUT (MD 5.51 seconds, 95 % CI: 0.79 to 10.23; MD 3.20, 95 % CI: 3.09 to 3.31 seconds; 2 studies; 140 eyes total; very low-certainty evidence). For tear osmolarity, 1 study indicated that there may be an improvement in favor of IPL (MD -7.00 mOsmol/L, 95 % CI: -12.97 to -1.03; 56 eyes; low-certainty evidence). The researchers were 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). These investigators were 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 3 months of follow-up (p = 0.409), and a second study reported data favoring IPL (MD -1.00 units, 95 % CI: -1.07 to -0.93 units; 172 eyes in total; very low-certainty evidence). They considered the incidence of AEs at the study endpoint, as a measure of safety. As most trials did not specifically report AEs, the safety of IPL as a treatment for MGD could also not be determined with any certainty. Very low-certainty results from individual studies suggested 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). The authors concluded that this systematic review found a scarcity of RCT evidence relating to the safety and effectiveness 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 AEs, 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 safety and effectiveness of IPL for treating MGD. They intend to update this review when results from the trials become available.
Arita and Fukuoka (2020) examined currently available non-pharmaceutical treatment modalities for MGD. A detailed search of the PubMed and Medline databases was carried out to identify original articles in English that have examined such non pharmaceutical therapies in patients with this condition. Conventional therapies such as application of a warming compress, the practice of lid hygiene, and manual expression of meibomian glands as well as more technologically advanced approaches such as intra ductal probing, thermal pulsation, and IPL therapy were included in the review. The authors noted that neither subjects nor investigators were masked to treatment allocation in the studies of intra-ductal probing performed to-date indicating that caution should be exercised in drawing conclusions from their findings. The follow-up periods of the studies were also relatively short, with the result that data on the long-term safety and efficacy of this invasive technique are lacking. The authors concluded additional large scale RCTs are also needed to provide more information such as the specific indications best suited to each treatment modality, the efficacy of such approaches in combination with pharmaceutical-based therapy, and the mechanisms of action of some of the more technologically advanced systems.
Liu and colleagues (2020) noted that MGD is frequently encountered by eye care practitioners. It is characterized by obstruction of the Meibomian glands and/or alterations in the consistency of glandular secretions. At present, no definitive treatment exists for this condition. In a systematic review and meta-analysis, these researchers examined the efficacy of intense pulsed light (IPL) therapy in the management of MGD. Databases including Embase, PubMed, Cochrane Central, Medline and Google Scholar were systematically searched to identify clinical trials that evaluated the efficacy of IPL in the treatment of MGD. Outcome measures were described as the standardized mean difference (SMD). The fixed- or random-effects model was selected for analysis based on the Cochrane 12 values representing heterogeneity. Publication bias was visually inspected using Begg's funnel plot. Data were synthesized from 4 RCTs comprising 122 subjects in the IPL group and 120 subjects in the control group. Pooled analysis indicated no statistically significant difference in the SPEED scores between the 2 groups [SMD -0.16 (95 % CI: -0.41 to 0.10)]; but a significant increase in Non-Invasive Tear Break-Up Time (NIBUT) scores in the IPL group (SMD, 0.90; 95 % CI: 0.40 to I .40).
The authors concluded that the findings of study did not provide any conclusive evidence for the efficacy of IPL therapy in the management of MGD. The analysis indicated that IPL therapy may result in an improvement of objective NIBUT scores but had no effect on subjective SPEED scores. They stated given the limited number of studies performed to-date, there is a need for more prospective, well-designed RCTs with a larger sample size to provide further evidence on the efficacy of IPL therapy.
Summary of Evidence: Intense Pulsed Light (IPL)
While study results of intense pulsed light therapy treatment for dry eye syndrome (DES) caused by meibomian gland dysfunction (MGD) may be promising, further multi-center randomized clinical trials (RCTs) with a larger sample, treatment comparison groups to assess long-term effectiveness and safety are needed. The evidence is insufficient to determine the technology results in an improvement in the net health outcomes.
Intraductal Probing (e.g., Maskin Device)
Arita et al. (2021) noted that treatment options for MGD have increased greatly with the recent advent of nonpharmaceutical treatments-since the International Workshop on Meibomian Gland Dysfunction in 2011. Selection of a treatment for MGD is currently based on the stage classification proposed at the 2011 workshop. Such stage classification is itself based on a comprehensive evaluation of subjective symptoms, lid margin abnormalities (plugging, vascularity), meibum grade, and degree of ocular surface staining. However, it is often difficult to select a treatment method according to this complicated classification in the clinic. Moreover, it is unclear at what stage nonpharmaceutical treatment options, such as intraductal probing, thermal pulsation therapy, and intense pulsed light, should be performed.
Fallah and Loer (2021) examined the effect of VTPT (vectored thermal pulsation treatment) for the treatment of MGD on objective measures of LLT and tear osmolarity. A total of 100 patients with MGD were recruited to participate. At their initial visit, baseline study parameters were recorded, and VTPT was administered. At the 2- to 3- month follow-up visit, the study parameters were reevaluated. Subjective symptoms were evaluated using the OSDI questionnaire; LLT was measured using an ocular surface interferometer. Tear osmolarity was calculated using impedance measurement of tear fluid collected from the eyelid margin. A total of 96 patients (192 eyes) completed the follow-up. Mean improvement in OSDI was 5.6 points (9 5% CI: -9.0 to -2.1, p = 0.002). There was no significant change in tear osmolarity (mean change -1.6 mOsrn/L, 9 5% C:-4.7 to+ 1.3 mOsrn/L, p = 0.3). There was no significant change in LLT (mean change -4.3 nm, 95 % CI: -9.1 to
+0.5 nm, p = 0.08). The authors concluded that the hypothesis that VTPT would decrease tear osmolarity and increase LLT was not substantiated. Although they detected significant improvement in subjective symptoms, the improvement was smaller than the improvements reported in previous studies. They stated these findings suggested the current understanding of the effects of VTPT is incomplete.
Arita and Fukuoka (2020) examined currently available non-pharmaceutical treatment modalities for MGD. A detailed search of the PubMed and Medline databases was carried out to identify original articles in English that have examined such non pharmaceutical therapies in patients with this condition. Conventional therapies such as application of a warming compress, the practice of lid hygiene, and manual expression of meibomian glands as well as more technologically advanced approaches such as intra ductal probing, thermal pulsation, and IPL therapy were included in the review. The authors noted that neither subjects nor investigators were masked to treatment allocation in the studies of intra-ductal probing performed to-date indicating that caution should be exercised in drawing conclusions from their findings. The follow-up periods of the studies were also relatively short, with the result that data on the long-term safety and efficacy of this invasive technique are lacking. Furthermore, in most studies, probing was not compared with standard treatments in the clinical setting such as eyelid warming, lid hygiene, or meibomian gland expression; thus, further studies without potential bias are needed to confirm the safety and efficacy of this procedure. The author's concluded that additional large-scale RCTs are also needed to provide more information such as the specific indications best suited to each treatment modality, the efficacy of such approaches in combination with pharmaceutical-based therapy, and the mechanisms of action of some of the more technologically advanced systems.
Kheirkhah et al. (2020) noted obstructive MGD can be refractory to medical therapy. Intra-ductal meibomian gland (MG) probing may offer a potential therapeutic approach for these patients, but no randomized trials have been conducted to-date. In a randomized, double-masked, single-center, sham-controlled clinical trial, the researchers examined clinical changes after intraductal MG probing for patients with refractory obstructive MGD. A total of 42 patients with refractory obstructive MGD associated with lid tenderness were included in this trial. Enrolled patients received one of the following treatments: MG probing plus post-procedural topical sulfacetamide/ prednisolone ointment (Blephamide); MG probing plus post-procedural lubricating ointment (GenTeal); or sham probing plus GenTeal ointment. The probing was performed on the upper lids of both eyes. Primary outcome measures were symptoms as measured by OSDI and Symptom Assessment iN Dry Eye (SANDE), as well as TBUT; and secondary outcome measures were other clinical signs. Safety of the procedure was also assessed by examining the treatment-related AEs. At baseline and 4 weeks after the procedure a masked observer examined the following outcome measures: symptom questionnaires, including OSDI and SANDE, upper lid tenderness, lid margin telangiectasia, corneal fluorescein staining, conjunctiva} lissamine green staining, TBUT, Schirmer's test, and meibomian glands yielding liquid secretion (MGYLS). Compared to baseline, the MG probing/Blephamide group showed significant improvements in both OSDI and SANDE scores and the MG probing/GenTeal group demonstrated a significant improvement only in SANDE score. In contrast, the Sham/GenTeal group did not show any statistically significant changes in symptoms. There were no statistically significant changes in clinical signs in any group at the 4-week visit, except for improvement of lid tenderness in the sham probing group. The authors concluded that MG probing/Blephamide
® resulted in a significant improvement in symptoms in patients with refractory obstructive MGD without any significant effect on clinical signs.
Moreover, these researchers stated that larger studies are needed to determine the effectiveness of MG probing.
Maskin and Testa (2018) noted in a retrospective study, examined the impact of meibomian gland probing (MGP) on meibomian gland (MG) area from the upper lids of patients with O-MGD. This trial compared pre-MGP/post-MGP non-contact infrared meibography results in patients with O-MGD, viewing signs of MG growth within total measurement field. Post-MGP meibography of 34 lids (19 patients, greater than or equal to 4.5 to less than or equal to 12 months' follow-up) showed 41.2 % with MG growth; 10 lids had meibographies suitable for analysis, showing significant collective (116 glands) increase in mean individual glandular area (MIGA) of 4.87 % (p = 0.0145); 4 of 10 lids independently showed significant increase in MIGA, ranging from 10.70 % to 21.13 % (p< 0.0001, p = 0.0277, p = 0.0292, p = 0.0345), while 6 did not. At greater than 12 and less than 25 months' follow-up, 16 lids (9 additional patients) had follow-up showing 25% with signs of MG growth. Analysis of 3 lids showed a significant collective (33 glands) increase in MIGA of 11.19 % (p = 0.0004); 2 of 3 lids independently showed significant increase in MIGA of 13.73 % and 20.00 % (p = 0.0097, p = 0.0001). Collectively, for all 13 analyzed lids (149 glands), there was a significant increase of 6.38% in total glandular area (p = 0.0447) and a significant increase of 6.23 % in MIGA (p = 0.0003). The authors reported MGP was associated with increased MG tissue area and growth of atrophied MGs as viewed on meibography; MGP provided unequivocal physical proof of a patent meibum outflow tract through the natural orifice and may promote glandular growth in part by direct mechanical establishment of a patent duct/orifice system. Moreover, the authors noted future research is needed to study these post-MGP meibography changes in a randomized controlled clinical trial (RCT).
Summary of Evidence: Intraductal Probing (e.g., Maskin Device)
While study results of intraductal Probing (e.g., Maskin Device) for dry eye syndrome (DES) caused by meibomian gland dysfunction (MGD) may be promising, further multi center randomized clinical trials (RCTs) with a larger sample and treatment comparison groups are needed to assess long-term effectiveness and safety. The evidence is insufficient to determine the technology results in an improvement in the net health outcomes.
Intranasal Neurostimulation (e.g., TrueTear and iTear100)
Ji et al. (2020) completed a multicenter, open-label, single-arm clinical trial that included adult patients with DED with a Schirmer score of <10 mm in at least one eye. Enrolled subjects were instructed to apply the study device at least twice per day for 30 seconds bilaterally to the external nasal nerve. After the initial baseline visit, patients were followed up at days 3, 14, 30, 90, and 180. The primary efficacy endpoint was the Schirmer index (change from unstimulated to stimulated tear production as measured by the Schirmer test) at day 30. The major secondary endpoint was the change in symptoms of DED at day 30 evaluated using the Ocular Surface Disease Index (OSDI). A total of 101 subjects evaluated at day 30 had a mean Schirmer index of 9.4 mm (95% confidence interval [CI], 7.4-11.3), and the baseline OSDI improved by an average of 14.4 (95% CI, 11.1-17.7). Both endpoints were highly statistically and clinically significant at all time points. There were two mild unanticipated adverse events related to the device.
The safety and efficacy of the iTEAR device observed in this study support its indication for treating DED. Further data are needed to assess long-term effectiveness and safety. One limitation of this study is the absence of a control or sham group; however, the primary endpoint of immediate tear production onto a Schirmer strip is not likely to be affected by placebo or Hawthorne effect. Indeed, a separate single-day study (unpublished) showed that a sham device that made noise but did not impart energy to the skin did not result in any tear production above the basal tearing on the Schirmer strip. The OSDI and other symptom scores are susceptible to Hawthorne and placebo types of effects. The OSDI has been validated over many years and a decrease of >8 and certainly
>13 is widely accepted as evidence of clinical benefit. The meibomian gland expression score and the increase in basal tears were not expected benefits at the outset of the study based on available data for the ITN. These endpoints are newer to studies of DED; therefore, future studies will utilize a control to further understand the clinical effect size.
Pang and colleagues (2019) conducted a systematic review and meta-analysis of randomized controlled trials that compared the efficacy of VTPT and WCT in treating DED. The primary outcome was the gland function. The secondary outcomes were the tear breakup time, Schirmer test, tear osmolarity, lipid layer thickness, Standard Patient Evaluation for Eye Dryness, and the improvement of subjective symptoms as assessed by using the Ocular Surface Disease Index. PubMed, Embase, Cochrane Library, and ClinicalTrials.gov registries were searched for studies published before July 2018. They stated that MGD is the main cause of DED and is traditionally managed using warm compress treatment (WCT). Vectored TPT (VTPT) is a novel method for treating DED. This study consisted of 4 trials with 385 patients. Significantly greater improvement was observed in meibomian gland function (MD: 2.19; 95 % CI: 0.95 to 3.43), TBUT [MD: 1.08; 95 % CI: 0.06 to 2.1O)], and SPEED [MD: -2.76; 95 % CI: -4.22 to -1.30)] at 2 to 4 weeks in the VTPT group than in the WCT group. A significantly greater decrease in OSDI was observed at 2 to 4 weeks [MD: -8.61; 95 % CI: -13.62 to -3.61) and 3 months [MD: -6.92; 95 % CI: -11.95 to -1.89) in the VTPT group than in the WCT group. The authors concluded that a single 12-min VTPT was more effective than traditional WCT in treating DED either in objective or subjective measurements and recommended choosing an appropriate treatment after shared decision-making.
Senchyna et al. (2018) completed a prospective, multicenter, randomized-sequence, subject-masked, cross-over study. Subjects with dry eye disease were exposed to the CAE and when the ocular discomfort score (ODS) threshold measured with the Ora Calibra® Ocular Discomfort Scale was reached, subjects performed either the intranasal or extranasal application, administered in a randomized sequence, for ~3 minutes. The eye dryness score (EDS, assessed with a visual analog scale) and ODS were measured every five minutes during CAE exposure including prior to and following TrueTear application. The primary effectiveness measure was the change in EDS from the measure immediately prior to TrueTear application to the measure immediately following application. The primary safety measure was device-related adverse events (AEs). 185 subjects (mean age 59 y, 74.6% female) were enrolled; 143 (77.3%) performed both
applications and completed the study. Mean change in EDS (standard error [SE]) from pre- to post-application was significantly greater with intranasal (-16.5 [1.7]) than extranasal application (- 3.1 [1.7]) (LS mean difference [SE], 13.4 [2.0]; p<.0001; ANOVA). Mean decrease in ODS score in the analysis eye from pre-to post-application was also significantly greater with intranasal application (-0.93 [0.08]) than extranasal application (-0.34 [0.08]) (LS mean difference [SE], 0.60 [0.10]; p<.0001; ANOVA). Only one AE was reported: transient mild epistaxis. In conclusion, intranasal application of TrueTear during CAE exposure resulted in statistically significant improvements in eye dryness and ocular discomfort compared with the control application of the device. TrueTear demonstrated a good safety profile; there were no serious adverse events, and no subject discontinued the study because of an adverse event. By increasing tear production and reducing DED symptoms, TrueTear represents a promising new management strategy for DED.
Summary of Evidence: Intranasal Neurostimulation (e.g., TrueTear and iTEARl00)
For individuals who suffer from dry eye syndrome Intranasal Neurostimulation (e.g., TrueTear and iTEARl00) is a promising intervention, however, further randomized clinical trials (RCTs) are needed to include a presence of a control or sham groups to assess long-term effectiveness and safety. The evidence is insufficient to determine that the technology results in an improvement in the net health outcomes.
Thermal Pulsation System
Park et al. (2021) investigated the use of preoperative VTP on meibomian gland dysfunction in subjects prior to cataract surgery. Outcomes were measured by TBUT, Oxford corneal staining score, and LLT. OSDI and Dry Eye Questionnaires (DEQ) were also assessed. The authors also reported on meibomian gland atrophy, degree of gland expressibility, and quality of gland secretions. Participants were followed for 3 months. Analysis included 60 participants in the VTP treatment group and 48 participants in the control group (those who did not receive VTP prior to cataract surgery). In the control group, the authors report a decrease in meibomian gland expressibility, worsened quality of meibomian gland secretions, decreased LLT, and worsened corneal staining. The VTP treatment group showed improved patency of meibomian glands, improved meibum quality, increased TBUT, and reduced corneal staining. OSDI and DEQ questionnaires reported an improvement in subjective outcomes. While these studies report improvements after using VTP prior to cataract surgery, there remains a lack of comparison of VTP to conventional treatment to assess improved health outcomes using an automated process.
Zhao et al. (2021) reported the efficacy of preoperative VTP therapy for individuals prior to cataract surgery. Participants were followed for 3 months after treatment. The primary outcome measure was an improvement in MGYLS. Efficacy was measured using symptoms of dry eye, LLT, tear break up time (TBUT), corneal staining, SIT, MGYLS, and meibomian gland dropout. There were 32 participants previously diagnosed with meibomian gland dysfunction enrolled. Each participant received VTP on one eye. Of the 32 participants, 16 had cataract surgery following VTP and 16 received only VTP and did not have surgery. Scores from a questionnaire of ocular symptoms decreased in both those who had cataract surgery and those who did not have surgery. There were no significant changes in SIT and corneal staining between VTP surgery group and the VTP non-surgery group. LLT values were stable for the 3-month follow-up time. The authors reported a significant difference in TBUT in the surgical group when comparing the eye that received VTP to the eye that didn't receive VTP at week I and I-month exams (4.47 ± 2.77 vs 3.44 ± 2.23 and 4.72 ± 2.78 vs 3.44 ± 2.24 respectively). There was an increase seen in MGYLS from baseline to the I-week visit in the VTP surgery group. There continued to be in increase in meibomian gland function at 3 months, but no difference was seen in the VTP non-surgery group. The authors report improvement in MGYLS after using VTP in both the surgery group and non-surgery group but acknowledge limitations to the study including no relief of subjective symptoms by the participants who underwent cataract surgery and improvement of symptoms in those who did not have surgery. The authors also note the SPEED questionnaire was not good at differentiating
symptomatic and asymptomatic participants and recommend larger multicenter studies to confirm the results. There is also lack of comparison of automated VTP treatment to a manual process.
Hura et al. (2020) completed a retrospective, single-blinded cohort study noting visible meibomian gland structure was evaluated at baseline and at 1-year in treatment (30 patients, 48 eyes) and control (13 patients, 22 eyes) groups. Meibography images were captured using dynamic meibomian imaging. Images were assessed using a novel morphometric analysis technique and analyzed for change in area of VGS (pixels). Additional outcomes measured include tear break up time, corneal staining, tear osmolarity, matrix metalloproteinase-9 (MMP-9), meibography grading, and meibomian gland evaluation. As high as 69% of eyes in the treatment group showed an improvement in VGS versus 27% of eyes in the control group. As high as 31% of eyes in the treatment group showed a decline in VGS versus 73% of eyes in the control group. TBUT (p = 0.0001), corneal staining (p = 0.0063), and meibomian gland evaluation scores (p = 0.0038) all significantly improved after VTP treatment. However, SPEED scores, MMP- 9, tear osmolarity, and meiboscale scores were not significantly improved I-year post treatment. The author's concluded morphometric analysis protocol of meibography provides clinically meaningful information that is undetectable with the standard semiquantitative method of grading meibomian gland structure. This is the first report indicating that gland structure may increase post-VTP relative to untreated controls, thus presenting significant implications regarding benefits and timing of VTP therapy. The described protocol is currently more appropriate for research than for clinical practice.
Li et al. (2020) completed an interventional study by reported on the use of LipiFlow to treat OMGD (n=25 participants) and HMGD (n=25 participants), evaluating the efficacy over a 12-week period. Efficacy was assessed using SPEED scores, OSDI scores, Schirmer I test (SIT), noninvasive keratographic breakup time (NIKBUT), tear meniscus height (TMH), lipid layer thickness (LLT), and partial blink rate (PBR). Compared to baseline, the SPEED and OSDI scores decreased in both OMGD and HMGD groups after 12 weeks. In both groups, mean NIKBUT and TMH increased at the 4-week point, and gradually decreased until the 12-week point. SIT improved in both groups at 4 weeks then gradually decreased until the 12-week point. LLT peaked at 4 weeks and gradually decreased in both groups. The PBR also decreased in both groups. There was overall improvement in both groups following treatment, however there was greater improvement noted in the OMGD group compared to the HMGD group. While this study shows improvement in participants with both OMGD and HMGD, lack of a control group makes it difficult to determine efficacy of an automated process compared to a manual process for treatment of meibomian gland dysfunction.
Tauber (2020) reported a single-center RCT comparing the LipiFlow System to twice daily administration of lifitegrast ophthalmic solution 5% in patients with inflammatory MGD (N=50; 25 patients per group). The co-primary outcomes were change in eye discomfort and tear lipid layer thickness from baseline to day 42. Results demonstrated that changes in the eye discomfort scores were significantly greater in the group that received lifitegrast, while changes in lipid layer thickness did not reach statistical significance between groups. Trial limitations included lack of masking, attrition in the lifitegrast group (3 patients discontinued therapy), and selection of patients that had both MGD and inflammation (results may have differed in populations with MGD without inflammation).
Hagen et al. (2018) completed a prospective, randomized, parallel-group study looked at 28 participants with moderate-to-severe meibomian gland dysfunction. The participants were randomized to receive either doxycycline treatment (n=14) or VTP (using the LipiFlow System). The oral doxycycline was given daily for 3 months and the VTP was given once in a single bilateral 12-minute procedure. Any adjunctive treatment (for example, artificial tears, fish oil supplements, lid scrubs, and warm compresses) was continued if it had been used for at least 3 months prior to the doxycycline or VTP. Primary endpoint was evaluation of dry eye symptoms using a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED]) and meibomian gland function assessed by counting the number of glands yielding liquid secretion (meibomian glands yielding liquid secretion [MGYLS]), tear breakup time, and corneal and conjunctiva! staining. In the doxycycline group, 2 participants discontinued their treatment due to intolerance to study medication. In the VTP group, 1
participant was lost to follow-up. These participants were not included in the final analysis. In the VTP group, the SPEED scores, MGYLS and tear breakup time were improved from their baseline levels. There was also improvement in the corneal and conjunctiva! staining. In the doxycycline group, SPEED scores, MGYLS and conjunctiva! stain improved significantly from the pretreatment levels, but improvement in tear breakup time and corneal stain did not reach statistical significance. While the results show improvement using the VTP compared to the oral doxycycline, there was no comparison of the VTP to a conventional method of lid warming and massage. Additional larger studies are necessary with comparison of the automated process to a manual process to determine efficacy of the automated process.
Blackie et al. (2016) completed a 2-stage multicenter RCT, evaluated treatment effects of the LipiFlow System for patients with MGD and dry eye symptoms. The first stage involved the open-label evaluation of treatment effects over the short term. Trialists compared the single, in-office, LipiFlow treatment with conventional treatments consisting of warm compress and eyelid hygiene control therapy, conducted twice daily for 3 months. Significant treatment effects relative to controls were observed for OSDI scores and meibomian gland secretion score (higher scores reflect less dysfunction). The second stage involved an observational crossover study to evaluate the long-term effects (from 3 to 12 months) of a single session using the LipiFlow System or in combination with other conventional treatments when considered necessary. Sustained treatment effects for the single LipiFlow treatment compared with the combination treatment subgroups were observed over the long-term for OSDI scores, but not for meibomian gland secretion scores. Trial limitations included lack of masking and lack of massage combined with warm compression, the usual treatment approach. The clinical significance of the 17- to 22-point improvement in OSDI scores observed across treatment and controls may be relatively small because final OSDl scores indicated that patients in both groups improved from severe disease to mild disease (treatment) or moderate disease (controls). The lack of blinding might also have led to an
overestimation of the treatment effect of LipiFlow.
Greiner et al. (2016) completed a prospective, cohort, observational, single-center study design, signs (meibomian gland secretion [MGS] scores and tear film breakup time [TBUT]) and symptoms (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation of Eye Dryness [SPEED] questionnaires) were determined in 20 patients (40 eyes) with MGD and dry eye symptoms at baseline (BL), 1 month, and 3 years post-TPS treatment using LipiFlow. Meibomian gland secretion scores increased from BL (4.5±0.8) to 1 month (12.0±1.1, P<0.001). Improvement persisted at 3 years (18.4±1.4) relative to BL (P:<0.001). Meibomian gland secretion scores in all regions of the lower eyelid were improved over BL at 1 month (nasal [P:<0.001], central [P:<0.001], temporal [P:<0.01]) and 3 years (nasal [P:<0.001], central [P:<0.001], temporal [P:<0.001]). TBUT increased from BL (4.1±0.4) to 1 month (7.9±1.4, P:<0.05) but was not significantly different than BL at 3 years (4.5±0.6, P>0.05). The OSDI scores decreased from BL (26.0±4.6) to
1 month (14.7±4.3, P:<0.001) but returned to BL levels at 3 years (22.5±5.4, P>0.05). The SPEED scores decreased from BL (13.4±1.0) to 1 month (6.5±1.3, P:<0.001), and this improvement persisted at 3 years (9.5±1.6, P:<0.001). The author's concluded thermal pulsation may be a uniquely efficacious treatment option for DED secondary to MGD in that a single 12-min procedure is associated with significant improvement in MGS and SPEED scores for up to 3 years.
Summary of Evidence: The LipiFlow Thermal Pulsation System
For individuals who have dry eye syndrome (DES) who receive LipiFlow eyelid thermal pulsation, the evidence includes randomized controlled trials (RCTs,) nonrandomized comparison study, and longer- term follow-up of patients from RCTs and observational studies. The trials do not provide strong evidence of long-term efficacy. Two RCTs have demonstrated positive findings for most outcome measures over the short term (up to 3 months). Observational studies have shown sustained treatment effects for most outcomes up to 3 years. The nonrandomized study showed similar outcomes for eyelid thermal pulsation and standard treatment. Further randomized clinical trials (RCTs) are needed to include trials with longer follow-up to assess long-term effectiveness and safety. The evidence is insufficient to determine that the technology results in an improvement in the net health outcomes.
Practice Guidelines and Position Statements
In 2018, the American Academy of Ophthalmology updated preferred practice patterns guidelines on dry eye syndrome (AAO DES, 2018). These guidelines list "In-office, physical heating and expression of the meibomian glands (including device-assisted therapies, such as LipiFlow, or intense pulse light treatment)" as 1 of several step-up treatments for patients who do not respond to conventional management, including the elimination of environmental factors and offending medications, dietary modifications, ocular lubricants, and lid hygiene and warm compresses.
In 2018, the American Academy of Ophthalmology updated preferred practice patterns guidelines on blepharitis (AAO Blepharitis, 2018). These guidelines cover the 3 clinical subcategories of blepharitis: staphylococcal, seborrheic, and meibomian gland dysfunction (posterior blepharitis specifically affects the meibomian glands). The following statements are made relevant to thermal pulsation treatment:
"There are also several in-office procedural treatments available that may theoretically unclog the inspissated meibomian gland orifices using intense pulsed light (IPL) or mechanical means (e.g., microblepharoexfoliation of the eyelid margin, meibomian gland probing, and/or devices using thermal pulsation). Although there have been industry-sponsored studies, independent, randomized, masked clinical trials have yet to be performed to assess efficacy of these costly, primarily fee-for-service treatments."
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Results of a systematic review were reported that informed an 'Ophthalmic Technology Assessment' commissioned by the American Academy of Ophthalmology(Tao, 2023).
The review was designed to assess the efficacy and safety of thermal pulsation in improving signs or symptoms of MGD and dry eye compared with no therapy or conventional (nonthermal pulsation) therapy such as warm compress or eyelid hygiene. The literature search was performed in March 2023. For each study, the quality of study methodology was rated according to the American Academy of Ophthalmology’s guidelines. 8 studies were rated as providing level I evidence (well-designed and well-conducted randomized controlled trials and systematic reviews) and 3 studies were rated as providing level II evidence (well-designed cohort studies and nonrandomized controlled cohort or follow-up trials).All included studies evaluated the LipiFlow device. The review did not include a meta-analysis. The authors stated that 9/11 of the studies reported greater efficacy with LipiFlow compared to standard warm compress therapy and eyelid hygiene. In general, improvements were detected in both subjective and objective metrics of MGD within 1 to 12 months of thermal pulsation treatment compared with nontreatment. The authors noted that durability beyond several months is uncertain.
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2025. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
In a 2024 Cochrane review, Pucker et al. evaluated the effectiveness of LipiFlow for treating dry eye disease and the safety of this treatment compared to sham and/or other treatments for MGD (Pucker, 2024). Across thirteen RCTs, published through October 2022, a total of 1155 participants were randomized, with each study ranging from 28 to 236 participants. Of these trials, six took place in the USA, three in China, two in Thailand, one in France, and one in Italy. Eight trials were single-center, four were multicenter, and one did not specify the number of centers involved. The participants consisted of 66% females, ranging in age from 19 to 86 years. The LipiFlow treatment was assessed as a stand-alone intervention against basic warm compresses in five trials, a thermostatic device in another five, an oral intervention in one trial, and topical dry eye medications in another. Additionally, one trial evaluated LipiFlow combined with an eyelid hygiene product versus eyelid hygiene products alone.
Five trials compared the efficacy of LipiFlow with the application of a basic warm compress, varying in duration and frequency. Only one trial included the addition of eyelid massage to the warm compress regimen. The analysis of symptom scores using the OSDI and the SPEED questionnaires revealed inconsistent results, showing no significant difference in symptoms between LipiFlow and warm compresses after 4 weeks. Furthermore, there was an absence of evidence indicating any significant difference in meibomian gland expression, meibum quality, or TBUT when comparing LipiFlow to basic warm compresses. Similarly, another five trials contrasted LipiFlow with thermostatic devices. The analysis at 4 weeks revealed that thermostatic devices managed to reduce OSDI scores by a mean difference (MD) of 4.59 (95% confidence interval [CI] 1.23 to 7.95; I2=0, p =.007; 553 participants; very low certainty evidence) compared to LipiFlow. Additionally, when LipiFlow combined with eyelid hygiene was compared to eyelid hygiene alone, no significant differences in signs or symptoms were observed at any evaluated time point. In a single trial, LipiFlow was compared against a topical dry eye disease medication, lifitegrast 5%. The trial suggested that lifitegrast 5% might enhance meibomian gland expression scores more effectively than LipiFlow by day 42 (MD
−1.21, 95% CI
−2.37 to
−0.05; 50 participants; low certainty evidence), utilizing a MGES from 0 to 8. Another trial compared LipiFlow with an oral intervention, doxycycline, revealing that LipiFlow might significantly improve SPEED scores over doxycycline at 3 months (MD
−4.00, 95% CI
−7.33 to
−0.67; 24 participants; very low certainty evidence). No other notable differences in signs or symptoms were observed between LipiFlow and doxycycline at 3 months. Additionally, no other statistically significant differences in symptoms or signs were identified in any other analyses conducted during this review within the 4 week timeframe. No trial reported any intervention-related, vision-threatening adverse events. LipiFlow shows comparable efficacy to other commonly used dry eye disease treatments in terms of signs and symptoms. However, the best level of evidence was deemed to have a high level of bias, resulting in low to very low certainty. Additional research with adequate masking, a standardized testing methodology, and a sample representative of the MGD population is needed before any definitive conclusions can be drawn regarding comparative benefits and harms of eyelid thermal pulsation therapy.
Sadri et al conducted a randomized (assessor-masked) trial (NCT05162261) to determine the efficacy and safety of thermo-mechanical action compared to LipiFlow in MGD (Sadri, 2024). Participants, recruited between 2022 and 2023 across 5 US centers, who had OSDI scores between 23 and 79 and fluorescein TBUT of less than 10 seconds in each eye, were treated with either bilateral thermo-mechanical action (TMA) using the Tixel device (Novoxel) or thermal pulsation (TP) with LipiFlow. The TMA cohort underwent three treatment sessions two weeks apart, while the TP group received a single session. Primary efficacy outcomes, including TBUT and OSDI, were assessed at baseline, at the 4-week mark, and 12 weeks post the final treatment session. Among the 106 participants (53 per group), TBUT showed significant improvements (p less than .001), increasing by 3.0 ± 3.2 and 3.1 ± 4.3 seconds after TMA, and 2.7 ± 2.7 and 3.3 ± 3.6 seconds after TP, at Week 4 and Week 12, respectively. Notably, the change in TBUT for TMA was proven to be non-inferior to TP (linear mixed-effects model, p less than .001). OSDI improved by 26.4 ± 21.1 and 28.6 ± 22.4 after TMA and 18.8 ± 21.0 and 21.9 ± 18.5 after TP, at Week 4 and Week 12, respectively. No device-related adverse events occurred in either group.
Ayres et al. conducted a randomized (assessor-masked) controlled superiority trial (SAHARA, NCT04795752) to determine the efficacy and safety of TearCare (TC, Sight Sciences) in comparison to topical cyclosporine 0.05% (CsA) for addressing dry eye disease in adults (Ayres, 2023).,The trial enlisted 345 participants (172 in the TC group and 173 in the CsA group, recruited between 2021 and 2022) across 19 ophthalmic and optometric clinics in 11 US states. Primary efficacy outcomes were changes from baseline in TBUT and OSDI at 6 months, with safety evaluations including adverse events, best corrected visual acuity, intraocular pressure, and slit-lamp observations. TBUT improved at all time points in both groups (p less than .0001), with TC demonstrating a notably greater enhancement compared to CsA (p =.0006). The OSDI also exhibited significant improvement in both groups at all time points (p less than .0001), though no significant differences were observed between the two treatment arms. Both therapies were largely safe and well-tolerated. Of the 19 treatment-emergent adverse events recorded in each group (constituting 11%), only 2 in the TC group (1%) and 8 in the CsA group (5%) were adjudged as related to the study treatment. All related adverse events were rated as mild (n=9) or moderate (n=1) in severity.
In 2023, the American Academy of Ophthalmology (AAO) updated preferred practice pattern guidelines on dry eye syndrome. These guidelines list thermal pulsation devices as a second-stage option for treatment of dry eye disease (Amescua, 2024).
In 2023, the AAO updated preferred practice pattern guidelines for blepharitis (Lin, 2024). These guidelines indicate that multiple industry-sponsored studies have demonstrated that a single vectored thermal pulsation (VTP) treatment can be effective at improving meibomian gland function and reducing dry eye symptoms for a year or more post procedure. However, there have been no independent RCTs confirming or refuting these industry-sponsored studies.
"There are several in-office procedural treatments available that may improve the inspissated meibomian gland orifices using intense pulsed light (IPL) or theoretically unclog the meibomian glands by mechanical means (e.g., microblepharoexfoliation of the eyelid margin, meibomian gland probing, and/or devices using thermal pulsation). Although there have been industry-sponsored studies, independent, randomized clinical trials have yet to be performed to assess efficacy or superiority of any one of these treatments over another. [moderate quality, discretionary recommendation]"
2026 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2026. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Ben Ephraim Noyman et al conducted a systematic review of 45 studies that compared device-based MDG treatment to conservative therapy (Ben Ephraim Noyman, 2025). Of the 45 studies, 9 evaluated LipiFlow, 2 evaluated iLux, and 2 evaluated TearCare. For TBUT, none of the thermal pulsation devices had a significant effect compared to conservative treatment. Similarly, none of the MGD symptom scores were significantly different between thermal pulsation devices and conservative treatment.
Ayres et al published phase 2 results of the SAHARA study (a 6-month extension of SAHARA), which involved a single dose of TearCare in patients who had previously received CsA for 6 months (n=322 eyes) (Ayres, 2023). After crossover to TearCare, TBUT improved to 6.6 +/- 3.2 seconds at 3 months and 6.1 +/- 2.8 seconds at 6 months (both p less than .001 vs. baseline). There was no improvement in ODSI scores at 3 months, but there was a significant change in ODSI scores at 6 months (p less than .0001 vs. baseline).
Hovanesian et al published results of phase 3 of the SAHARA study (long-term follow-up) (Hovanesian, 2025). A total of 166 patients were followed for 24 months. Retreatment with TearCare was allowed if TBUT decreased to within 2 seconds of baseline and if OSDI scores increased by 15 points from the prior visit; 32 patients required additional treatment at a median time of 8 months. Improvements from baseline in all efficacy parameters was maintained until 24 months in the remaining 134 patients.
In 2023, the AAO updated preferred practice pattern guidelines on dry eye syndrome. These guidelines list thermal pulsation devices as a second-stage option for treatment of dry eye disease (Amescua, 2024). First-line treatment includes eyelid hygiene, warm compresses, and ocular lubrication. Other second-line treatment options include topical secretagogues, topical immunomodulators (such as cyclosporine), liftegrast, and short-term topical antibiotics and/or corticosteroids (for blepharitis).
The Tear Film & Ocular Surface Society is an industry-sponsored international organization that hosts periodic workshops on the topic of dry eye syndrome (Jones, 2025). The management and therapy report of the latest dry eye workshop (DEWS) was published in 2025; the document includes a conflict of interest disclosure, but there is no description of the literature review methodology or system of evidence grading. For patients with a lipid-based dry eye etiology or with dry eye caused by meibomian gland dysfunction, the report concludes that the efficacy of lid heating devices is supported by randomized, placebo-controlled trials and are one of several treatment options. No recommendations are made for a preferred thermal pulsation device, but the report does comment on comparative efficacy. Regarding LipiFlow, non-industry sponsored studies have found that LipiFlow has similar efficacy as warm compresses and eyelid hygiene. Regarding iLux, the report states that it has statistically similar efficacy as LipiFlow. Regarding TearCare, a randomized study found similar efficacy between TearCare and LipiFlow overall, but patients with more severe symptoms did better with TearCare.
Some currently ongoing or unpublished trials that might influence this review are listed below.
Ongoing:
Unpublished:
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| References: |
Akpek, E. K., et al.(2018) Dry Eye Syndrome Preferred Practice Pattern®. Ophthalmology. doi:10.1016/j.ophtha.2018.10.023
American Academy of Ophthalmology. Dry Eye Syndrome, Preferred Practice Pattern Guideline 2018. http://www.aao.org/preferred-practice-pattern/dry-eye syndrome-ppp-2018 AmericanAcademyOphthalmology (AAO).(2021) Ophthalmic Technology Assessment. Autologous serum-based eye drops for treatment of ocular surface disease. http://www.aao.org. Published September 2019. Accessed September 16, 2021. Amescua G, Ahmad S, Cheung AY, et al.(2024) Dry Eye Syndrome Preferred Practice Pattern. Ophthalmology. Apr 2024; 131(4): P1-P49. PMID 38349301 Arita R, Fukuoka S.(2020) Non-pharmaceutical treatment options for meibomian gland dysfunction. Clin Exp Optorn. 2020;103(6):742-755 Arita, R. et al.(2020) Proposed Algorithm for Management of Meibomian Gland Dysfunction Based on Noninvasive Meibography. Journal of clinical medicine vol. 10,165. 27 Dec. 2020, doi:10.3390/jcm10010065. Ayres BD, Bloomenstein MR, Loh J, et al.(2024) Improved Signs and Symptoms of Dry Eye Disease for Restasis Patients Following a Single Tearcare Treatment: Phase 2 of the SAHARA Study. Clin Ophthalmol. 2024; 18: 1525-1534. PMID 38827771 Badawi, David.(2019) "TearCare® system extension study: evaluation of the safety, effectiveness, and durability through 12 months of a second TearCare® treatment on subjects with dry eye disease." Clinical ophthalmology (Auckland, N.Z.) vol. 13 189-198. 22 Jan. 2019, doi:10.2147/OPTH.S191588. Ben Ephraim Noyman D, Chan CC, Teichman JC, et al.(2025) Dry Eye Disease Management Via Technological Methods: A Systematic Review and Network Meta-analysis. Ophthalmol Ther. Aug 2025; 14(8): 1917-1954. PMID 40601205 Blackie CA, Coleman CA, Holland EJ.(2016) The sustained effect (12 months) of a single-dose vectored thermal pulsation procedure for meibomian gland dysfunction and evaporative dry eye. Clin Ophthalmol. Jul 26 2016; 10:1385-1396. PMID 27555745 Blackie CA, Korb DR, Knop E, et al.(2010) Nonobvious obstructive meibomian gland dysfunction. Cornea. Dec 2010; 29(12): 1333-45. PMID 20847669 Blackie, CA, et al.(2018) A single vectored thermal pulsation treatment for meibomian gland dysfunction increases mean comfortable contact lens wearing time by approximately 4 hours per day. Clin Ophthalmol. 2018;12:169-183. PubMed: 29398904 Blepharitis.(2018) American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern Guidelines. San Francisco, CA: American Academy of Ophthalmology; 2018. C. Mun, et al.(2019) A Phase I/II PlaceboControlled Randomized Pilot Clinical Trial of Recombinant Deoxyribonuclease (DNase) Eye Drops Use in Patients With Dry Eye Disease. A Phase I/II PlaceboControlled Randomized Pilot Clinical Trial of Recombinant Deoxyribonuclease (DNase) Eye Drops Use in Patients With Dry Eye Disease. Christenson-Akagi, KJ.(2018) Comparison of a single-dose vectored thermal pulsation procedure with a 3- month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction. Clin Ophthalmol. 2018;12:161-168. PubMed: 29398903 Cote S, et al.(2020) Intense pulsed light (IPL) therapy for the treatment of meibomian gland dysfunction. Cochrane Database Syst Rev. 2020;3(3):CD013559. Dry Eye Syndrome.(2018) American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern Guidelines. San Francisco, CA: American Academy of Ophthalmology; 2018. Farrand KF, Fridman M, Stillman IO, et al.(2017) Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older. Am J Ophthalmol. Oct 2017; 182: 90-98. PMID 28705660 Finis D, et al.(2014) Evaluation of an automated thermodynamic treatment (LipiFlow(R)) system for meibomian gland dysfunction: a prospective, randomized, observer-masked trial. Ocul Surf. Apr 2014;12(2):146-154. PMID 24725326 Finis D, et al.(2014) Factors influencing the measurement of tear film lipid layer thickness with interferometry. Klin Monbl Augenheilkd. 2014;231(6):603-610. Fiscella RG.(2011) Understanding dry eye disease: a managed care perspective. Am J Manag Care. Dec 2011;17 Suppl 16:S432-439. PMID 22435675 Geerling, G et al.(2017) Emerging strategies for the diagnosis and treatment of meibomian gland dysfunction: Proceedings of the OCEAN group meeting. The Ocular Surface. 15. 10.1016/j.jtos.2017.01.006. Greiner N.(2016) Effects of a single thermal pulsation system treatment on meibomian gland function and dry eye symptoms. Eye Contact Lens. Mar 2016; 42(2):99-107. PMID 26222095 Hovanesian J, Ayres BD, Bloomenstein MR, et al.(2025) Durability of the TearCare treatment effect in subjects with dry eye disease: Stage 3 of the Sahara randomized controlled trial. Optom Vis Sci. Aug 01 2025; 102(8): 495-504. PMID 40719437 Hura AS, et al.(2020) Visible Meibornian Gland Structure Increases After Vectored Thermal Pulsation Treatment in Dry Eye Disease Patients with Meibornian Gland Dysfunction. Clin Ophthalmoll. 2020; 14: 4287-4296. PMID 33324034. Ji, Marco H et al.(2020) Novel Extranasal Tear Stimulation: Pivotal Study Results. Translational vision science & technology vol. 9,12 23. 17 Nov. 2020, doi:10.1167/tvst.9.12.23 Jie Y., et al.(2019) Evaluation of incomplete blinking as a measurement of dry eye disease. Ocul Surf, 17(3), 440-446. doi:10.1016/j.jtos.2019.05.007. Jones L, Craig JP, Markoulli M, et al.(2025) TFOS DEWS III: Management and Therapy. Am J Ophthalmol. Nov 2025; 279: 289-386. PMID 40467022 Kheirkhah A, et al.(2020) A randomized, sham-controlled trial intraductal meibomian gland probing w or wo topical antibiotic/steroid for obstructive meibomian gland dys. Ocul Surf. 2020;18(4):852-856. Lane SS, DuBiner HB, Epstein RJ, et al.(2012) A new system, the LipiFlow, for the treatment of Meibomian gland dysfunction. Cornea. Apr 2012;31(4):396-404. PMID 22222996 Leng X, et al. (2021) Intense pulsed light for meibomian gland dysfunction: A systematic review and meta-analysis. Graefes Arch Clin Exp Ophthalmol. 2021;259(1):1-10 Maskin SL, Testa WR.(2018) Growth of meibomian gland tissue after intraductal meibomian gland probing in patients with obstructive meibomian gland dysfunction. Br J Ophthalmol. 2018;102(1):59-68. Maskin SL.(2010) Intraductal rneibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction. Cornea. 2010;29(10):1145-1152. McCann P, et al.(2022) Prevalence and Incidence of Dry Eye and Meibomian Gland Dysfunction in the United States: A Systematic Review and Meta-analysis. JAMA Ophthalmol. 2022;140(12):1181-1192. doi:10.1001/jamaophthalmol.2022.4394 Miller KL, et al.(2010) Minimal clinically important difference for the ocular surface disease index. Arch Ophthalmoll. Jan 2010; 128(1): 94-101. PMID 20065224 National Eye Institute: Dry Eye Eye https://nei.nih.gov/leam-about-eye-health/eye conditions-and-diseases/dry-eye. Ngo W, et al.(2013) Psychometric properties and validation of the Standard Patient Evaluation of Eye Dryness questionnaire. Cornea. Sep 2013; 32(9): 1204-10. PMID 23846405. Nichols KK, Foulks GN, Bron AJ, et al.(2011) The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. Mar 30 2011; 52(4): 1922-9. PMID 21450913 Oydanich M, et al.(2019) Effects of Omega-3 Supplementation on Exploratory Outcomes in the Dry Eye Assessment and Management Study. Ophthalmology. 2020 Jan;127(1):136-138. doi: 10.1016/j.ophtha.2019.07.009. Epub 2019 Jul 25. Pan Q et al.(2017) Autologous serum eye drops for dry eye. Cochrane Database Syst Rev,. 2017, 2:CD009327. Doi:10.1002/14651858.CD009327.pub3. Pan Q, et al.(2013) Autologous serum eye drops for dry eye. Cochrane Database Syst Rev. 2013, 8:CD009327. doi: 10.1002/14651858.CD009327.pub2. Park J, Yoo et al.(2021) Effects of LipiFlow treatment prior to cataract surgery: a prospective, randomized, controlled study: LipiFlow prior to cataract surgery. Arn J Ophthalmoll. 2021 May 13:S0002-9394(21)00267-1. Online ahead of print. Senchyna M., et al.(2018) Effect of TrueTear on Dry Eye Symptoms During Exposure to a Controlled Adverse Environment. Invest. Ophthalmoll. Vis. Sci. 2018;59(9):918. Shtein RN, et al.(2020) Autologous serum-based eye drops for treatment of ocular surface disease: a report by the American Academy of Ophthalmology. Ophthalmology. Jan 2020;127(1):128-133 Silbert JA, Bitton E, Bhagat K.(2019) Advances in Diagnosis and Management of Dry Eye Disease. Advances in Ophthalmology and Optometry 2019 Aug;(4):13-38. doi: https://doi.org/10.1016/j.yaoo.2019.04.002.Epub 2019 May 23 Simsek C, et. al.(2018) Current management and treatment of dry eye disease. . Turk J Ophthalmol 2018 Dec;48{6): 309-313. PMID 30605938 Stapleton F, et al.(2017) TFOS DEWS II Epidemiology Report. Ocul Surf. Jul 2017; 15(3): 334-365. PMID 28736337. Tauber J.(2020) A 6-week prospective, randomized single-masked study of Lifitegrast Ophthalmic Solution 5% versus thermal pulsation procedure for treatment of inflammatory rneibomian gland dysfunction. Cornea 2020 Apr;39(4):403-407. PMID 31895884. TearCare (Sight Sciences, Inc.) for Treating Dry Eye Disease. Health Tech Assessment (Product Brief) March 16, 2022. Ecri.com The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Workshop Ocul Surf. Apr 2007;5(2):75-92. PMID 17508116 TrueTear Intranasal Tear Neurostimulator (Allergan plc) for Treating Moderate to Severe Dry Eye Syndrome. March 16, 2022. Ecri.com Zhao AV, et al.(2015) Intra-observer and inter-observer repeatability of ocular surface interferometer in measuring lipid layer thickness. BMC Ophthalmol 2015 May;15:53. Zhao Y, et al.(2016) Clinical trial of thermal pulsation (Lipiflow) in meibomian gland dysfunction with pretreatment meibography. Clinical trial of thermal pulsation (Lipiflow) in meibomian gland dysfunction with pretreatment meibography. Zhao Y, Li J, Xue K, et al.(2021) Preoperative management of MGD with vectored thermal pulsation before cataract surgery: a prospective, controlled clinical trial. Sernin Ophthalmoll. 2021; 36(1-2):2-8. |
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