CAM 90329

Eyelid Thermal Pulsation for the Treatment of Dry Eye Syndrome

Category:Other   Last Reviewed:August 2019
Department(s):Medical Affairs   Next Review:August 2020
Original Date:August 2013    

Description
The LipiFlow Thermal Pulsation System is a treatment option for meibomian gland dysfunction. Meibomian gland dysfunction is recognized as the major cause of dry eye syndrome. The LipiFlow System applies heat to the palpebral surfaces of the upper and lower eyelids directly over the meibomian glands, while simultaneously applying graded pulsatile pressure to the outer eyelid surfaces, thereby expressing the meibomian glands.

For individuals who have dry eye symptoms consistent with meibomian gland dysfunction who receive eyelid thermal pulsation, the evidence includes 3 randomized controlled trials (RCTs), a nonrandomized comparison study, and longer term follow-up of patients from RCTs and observational studies. Relevant outcomes are symptoms, morbid events, and functional outcomes. 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. The evidence is insufficient to determine the effects of the technology on health outcomes.

Background
Dry Eye Syndrome 
Dry eye syndrome (DES), 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. DES is considered a significant public health problem. It is estimated to affect between 14% and 33% of the population worldwide.1,2 The prevalence of DES increases with age, especially in postmenopausal women. It is estimated that DES affects more than 7 million Americans older than 40 years of age,1 and approximately 1 to 4.3 million Americans between 65 and 84 years of age.3 Prevention and treatment of DES are expected to be of greater importance as the population ages.

Treatment
Current treatment options for Meibomian gland dysfunction 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 (eg, antibiotics, topical corticosteroids) to mitigate infection and inflammation of the eyelids.4,5 These treatment options, however, have shown limited clinical efficacy. 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.5 While the symptoms of DES often improve with treatment, the disease usually is not curable and may lead to substantial patient and physician frustration. Dry eyes can be a cause of visual morbidity and may compromise results of corneal, cataract, and refractive surgery. Inadequate treatment of DES may result in increased ocular discomfort, blurred vision, reduced quality of life, and decreased productivity.

Regulatory Status
The LipiFlow® System (assigned the generic name of eyelid thermal pulsation system) was cleared by FDA in June 2011.6 FDA classified the LipiFlow® System into class II (special controls) to provide a “reasonable assurance of safety and effectiveness” of the device. The LipiFlow® System is identified by FDA “as an electrically powered device intended for use in the application of localized heat and pressure therapy to the eyelids. The device is used in adult patients with chronic cystic conditions of the eyelids, including meibomian gland dysfunction (MGD), also known as evaporative dry eye or lipid deficiency dry eye.” FDA product code: ORZ.

Policy
Eyelid thermal pulsation therapy to treat dry eye syndrome is considered INVESTIGATIONAL.  

Policy Guidelines
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.

Benefit Application
Blue Card®/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all U.S. Food and Drug Administration (FDA)-approved devices, drugs or biologics may not be considered investigational, and, thus, these devices may be assessed only on the basis of their medical necessity.

Rationale  
Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function---including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical uses of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Dry Eye Syndrome 
Clinical Context and Purpose
The purpose of eyelid thermal pulsation in patients who have dry eye syndrome (DES) is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is; does the use of eyelid thermal pulsation in patients who have DES improve net health outcomes?

The following PICOTS were used to select literature to inform this review.

Patients
The relevant population(s) of interest are patients with DES. DES is often classified into the aqueous-deficient subtype or the evaporative subtype, although classification is not mutually exclusive. DES is a multifactorial disease of the ocular surface that may require a combination approach to treatment. Meibomian gland dysfunction (MGD), characterized by changes in gland secretion with or without concomitant gland obstruction, is recognized as the most common cause of evaporative dry eye and may also play a role in aqueous-deficient dry eye.

Interventions
The treatment being considered is the use of eyelid thermal pulsation. The LipiFlow Thermal Pulsation System is a device developed to relieve MGD. This device heats 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 conjunctival 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

Comparators
The following practices are currently being used to treat DES; 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 (eg, antibiotics, topical corticosteroids) to mitigate infection and inflammation of the eyelids.

Outcomes
The general outcomes of interest are symptoms, change in disease status, functional outcomes and quality of life.

Timing
Follow-up of at least 6 months would be desirable to assess outcomes.

Setting
Thermal pulsation is provided in the outpatient setting.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:  

  1. To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
  2. In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
  3. To assess longer term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

Studies with duplicative or overlapping populations were excluded.

Comparative studies of eyelid thermal pulsation for the treatment of dry eye syndrome include 3 RCTs and 1 nonrandomized comparative study of the LipiFlow System (see Table 1). In the multicenter RCT by Lane et al (2012), controls crossed over to treatment after 2 weeks; therefore, only the 2-week follow-up is available (see Table 2).7 Results at 2 weeks showed statistically significant improvements in the primary and secondary outcome measures. Trial limitations included the short-term follow-up (2 weeks) for the primary comparative outcomes, lack of masking, and lack of intention-to-treat analysis. In addition, the control intervention did not include massage along with the warm compress, which is a common treatment for meibomian gland dysfunction.

An RCT by Finis et al (2014), which reported on outcomes prior to crossover at 3 months, found a significant effect of treatment compared with controls for the primary outcome measure (Ocular Surface Disease Index [OSDI] score), but not for any other outcome measures.8 The clinical significance of the 11.6-point improvement in OSDI score is unclear because final OSDI scores at 3 months (34.6 for LipiFlow, 40.0 for control) would still be classified as severe dry eye disease.

In a 2-stage multicenter RCT, Blackie et al (2016) evaluated treatment effects of the LipiFlow System for patients with meibomian gland function and dry eye symptoms.9 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) (see Table 2). 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 glad secretion score. 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 OSDI 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.

The nonrandomized trial by Zhao et al (2016) compared 25 patients undergoing a single LipiFlow treatment with 25 patients using warm compresses and lid massage.10 At 4 and 12 weeks, between-group outcomes were similar for symptom change, change in meibomian gland force evaluator, and tear break-up time. At 12 weeks, change in Schirmer test scores also did not differ significantly between groups.

Three other studies have evaluated long-term outcomes for some trial subjects who had undergone LipiFlow treatment. The study by Greiner (2013)11 evaluated 18 of 30 subjects from 1 site of the Lane trial (described above).7 Several outcomes remained significantly improved from baseline, but the improvements were of lower magnitude at 1 year than at 1 month. Finis et al (2014) evaluated 26 patients at 6 months after LipiFlow treatment.12 Several outcome measures remained improved 6 months after treatment. Another study of 20 patients conducted by Greiner (2016) found that most outcomes remained significantly improved up to 3 years relative to baseline.13

Table 1. Summary of Key Characteristics of Comparative Studies 

 

 

 Interventions

Study

Countries

Sites

Dates

Participants

Active

Comparator

Lane et al (2012)7

U.S.

9

Mar-May 2009

  • 69 LipiFlow
  • 70 control

Single LipiFlow treatment

Daily warm compress for 2 wk

Finis et al (2014)8

Germany

NR

Apr 2012-Jun 2013

  • 20 LipiFlow
  • 20 contro

Single LipiFlow treatment

Twice daily lid warming and massage

Zhao et al (2016)10

Singapore

1

Feb 2012-Mar 2013

  • 25 LipiFlow
  • 25 control

Single LipiFlow treatment

Twice daily lid warm compresses and massage

Blackie et al (2016)9

U.S.

9

Feb-Oct 2012

  • 101 LipiFlow
  • 99 control

Single LipiFlow treatment

Twice daily warm compress and eyelid hygiene control therapy for 3 mo

Table 2. Summary of Key Results of Comparative Studies 

Study

ΔMGS Scorea

ΔTBUT, sb

ΔOSDI Scorec

ΔSPEED Scored

Symptom Score, %

ΔSchirmer Test, mm

Lane et al (2012)

LipiFlow 

7.9

 1.5

 14.7

6.2 

 

 

Controls 

0.5 

 0.1

8.1 

3.5

 

 

 p

<0.001 

<0.001 

<0.001 

<0.001 

 

 

Finis et al (2014)8

LipiFlow 

3.0

2.0 

11.6 

2.3 

 

 

Controls 

2.5 

0.2 

0.1 

1.2 

 

 

NS 

NS 

0.029 

NS 

 

 

Zhao et al (2016)10

LipiFlow 

 

 89.2%

 

 

-30.5% 

1.0 

Controls 

 

 63.0%

 

 

-15.9% 

 -3.95

 p

 

 0.0625

 

 

 

0.55 

Blackie et al (2016)9 

LipiFlow 

11.6 

 

-23.4 

 

 

 

Controls 

4.5 

 

-17.8 

 

 

 

<0.001 

 

0.007 

 

 

 

MGS: meibomian gland secretion; NR: not reported; OSDI: Ocular Surface Disease Index; SPEED: Standard Patient Evaluation for Eye Dryness; TBUT: tear break-up time.
a The Meibomian Gland Evaluator device was developed by TearScience to evaluate gland secretion through gland expression to determine if meibomian glands are blocked.
b Practice parameters from the American Academy of Ophthalmology (2013) has indicated that a tear break-up time of <10 s is considered abnormal.3 Note that Zhao et al (2016) is reported in percent not seconds.
c The OSDI assesses the patient’s frequency and severity of dry eye symptoms in specific contexts during the week prior to the examination. The minimal clinically important difference for the OSDI ranges from 4.5-7.3 for mild or moderate disease. The overall OSDI score defines the ocular surface as normal (0-12 points) or as having mild (13-22 points), moderate (23-32 points), or severe (33-100 points) disease.14
d The SPEED questionnaire is a self-reported measure of the frequency and severity of dryness, grittiness, scratchiness, soreness, irritation, burning, watering, and eye fatigue within 3 months of examination. It was developed by TearScience and validated in a 2013 study funded by TearScience.15 In this validation study, the mean SPEED score of symptomatic subjects was 21.0 and the mean of asymptomatic subjects was 6.25.   

SUMMARY OF EVIDENCE
For individuals who have dry eye symptoms consistent with meibomian gland dysfunction who receive eyelid thermal pulsation, the evidence includes 3 RCTs, a nonrandomized comparison study, and longer term follow-up of patients from RCTs and observational studies. Relevant outcomes are symptoms, morbid events, and functional outcomes. 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. The evidence is insufficient to determine the effects of the technology on health outcomes. 

PRACTICE GUIDELINES AND POSITION STATEMENTS
In 2013, the American Academy of Ophthalmology published preferred practice patterns guidelines on dry eye syndrome.3 A number of treatment options were recommended. The use of thermal pulsation treatment devices was not mentioned.  

U.S. PREVENTIVE SERVICES TASK FORCE RECOMMENDATIONS
Not applicable. 

ONGOING AND UNPUBLISHED CLINICAL TRIALS
Some currently unpublished trials that might influence this review are listed in Table 3.

Table 3. Summary of Key Trials 

NCT No. Trial Name Planned Enrollment Completion Date

Unpublished

NCT02894658

LipiFlow Versus Warm Compresses in Parkinson’s Disease 25 Jan 2020 (suspended)

NCT: national clinical trial.
 ª Denotes industry-sponsored or cosponsored trial.

References 

  1. Fiscella RG. Understanding dry eye disease: a managed care perspective. Am J Manag Care. Dec 2011;17(Suppl 16):S432-439. PMID 22435675
  2. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. Apr 2007;5(2):75-92. PMID 17508116
  3. American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern Guidlines. Dry Eye Syndrome. San Francisco, CA: American Academy of Ophthalmology; 2013.
  4. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. Mar 2011;52(4):1922-1929. PMID 21450913
  5. Blackie CA, Korb DR, Knop E, et al. Nonobvious obstructive meibomian gland dysfunction. Cornea. Dec 2010;29(12):1333-1345. PMID 20847669
  6. Medical devices; ophthalmic devices; classification of the eyelid thermal pulsation system. Final rule. Fed Regist. Aug 19 2011;76(161):51876-51878. PMID 21894651
  7. Lane SS, DuBiner HB, Epstein RJ, et al. A new system, the LipiFlow, for the treatment of meibomian gland dysfunction. Cornea. Apr 2012;31(4):396-404. PMID 22222996
  8. Finis D, Hayajneh J, Konig C, et al. 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
  9. Blackie CA, Coleman CA, Holland EJ. 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
  10. Zhao Y, Veerappan A, Yeo S, et al. Clinical trial of thermal pulsation (Lipiflow) in meibomian gland dysfunction with preteatment meibography. Eye Contact Lens. Nov 2016;42(6):339-346. PMID 26825281
  11. Greiner JV. Long-term (12-month) improvement in meibomian gland function and reduced dry eye symptoms with a single thermal pulsation treatment. Clin Experiment Ophthalmol. Aug 2013;41(6):524-530. PMID 23145471
  12. Finis D, Konig C, Hayajneh J, et al. Six-month effects of a thermodynamic treatment for MGD and implications of meibomian gland atrophy. Cornea. Dec 2014;33(12):1265-1270. PMID 25321941
  13. Greiner JV. 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
  14. Miller KL, Walt JG, Mink DR, et al. Minimal clinically important difference for the Ocular Surface Disease Index. Arch Ophthalmol. Jan 2010;128(1):94-101. PMID 20065224
  15. Ngo W, Situ P, Keir N, et al. Psychometric properties and validation of the Standard Patient Evaluation of Eye Dryness questionnaire. Cornea. Sep 2013;32(9):1204-1210. PMID 23846405

Coding Section

Codes Number Description
CPT 0207T

Evacuation of meibomian glands, automated, using heat and intermittent pressure, unilateral

ICD-9 Diagnosis  

Investigational for all diagnoses

ICD-10-CM (effective 10/01/15)  

Investigational for all diagnoses

  H04.121-H04.129

Dry eye syndrome code range

ICD-10-PCS (effective 10/01/15)  

ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this procedure.

Type of Service    
Place of Service    

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2014 Forward     

08/01/2019 

Annual review, no change to policy intent. Updating background, rationale and references. 

08/13/2018 

Annual review, no change to policy intent. Updating background, rationale and references. 

08/24/2017 

Annual review, no change to policy intent. Updating description, rationale and references. 

08/10/2016 

Annual review, no change to policy intent. Updating rationale and references. 

08/11/2015 

Annual review, no change to policy intent. Updated background, description, rationale and references. Added guidelines and coding.

08/04/2014

Annual review. Updated background, description, regulatory status, rationale and references. No change to policy intent. 


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