Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.
Blue Cross and Blue Shield of Montana (BCBSMT) considers eyelid thermal pulsation therapy (which may include the use of the LipiView® for diagnosis and/or the LipiFlow® for treatment) experimental, investigational and unproven for all indications including but not limited to dry eye syndrome.
This policy was created in August 2013 with a search of the MEDLINE database conducted through May 2013. Following is a summary of the key literature.
Five publications were identified on the LipiFlow System for treatment of meibomian gland dysfunction (MGD). The initial publication of this device by Korb and Blackie, based on findings of a case report on meibomian gland assessment following treatment in a 39-year old Caucasian woman, reported outcomes at 3 months of follow-up; (9) a second publication by the same group of investigators on this patient reported findings at 7 months of follow-up. (10) Funding for these publications was provided by the manufacturer of the device (TearScience Inc., Morrisville, NC). The third publication (also manufacturer-funded) by Freidland and colleagues was a feasibility study reporting on findings from 14 adult patients treated with this device for obstructive MGD. (11)
The remaining two publications were based on the results of a randomized clinical trial of this device for the treatment of MGD. The primary analysis by Lane and colleagues reported outcomes up to 1-month follow-up, (6) and a follow-up analysis by Griener reported outcomes at 9 months of follow-up in a sub-cohort of patients. (7) The primary analysis was a prospective, open-label, randomized, crossover multi-center clinical trial undertaken to evaluate the safety and effectiveness of the LipiFlow® System compared to a standardized form of warm compress therapy (iHeat Warm Compress (WC) System, Advanced Vision Research, Woburn, MA) for adults with MGD. (6) As with previous reports, this randomized clinical trial by Lane and colleagues was funded by TearScience Inc. (Morrisville, NC), the manufacturer of the LipiFlow® System. (6)
In the randomized clinical trial (RCT) by Lane and colleagues, 139 adult patients from 9 participating sites (8 U.S. sites, and 1 site in India) were randomized to either the LipiFlow® System (n=69) or WC control (n=70). (6) These patients had reported dry eye symptoms in the past 3 months, had a Standard Patient Evaluation for Eye Dryness (SPEED) score of 6 or greater, and had evidence of meibomian gland obstruction on ophthalmologic examination. Subjects in the LipiFlow® group received a single 12-minute LipiFlow® treatment and were reexamined at day one, 2 weeks and at 4 weeks of follow-up. Patients in the control group received a single 5-minute iHeat® warm compress treatment with instructions to perform the same treatment daily for 2 weeks. At 2 weeks, the control patients crossed over (LipiFlow® Crossover) and received the LipiFlow® treatment. The primary outcome measures were MG assessments performed using a hand-held Meibomian Gland Evaluator. Each of 15 glands was scored on a 0-3 rating scale, resulting in a numerical score from 0-45. The second primary outcome measure was tear break-up time (TBUT) in seconds, measured by the Dry Eye Test Method. Secondary outcome measures included dry eye symptoms measured by 2 standardized instruments, the SPEED score, and the Ocular Surface Disease Index (OSDI). Device-related adverse events were also reported, primarily treatment-related pain and discomfort. The main analyses were performed on a per-protocol basis, and not by intention to treat.
The primary comparison of treatment outcomes was performed at 2 weeks following treatment. At this time point, there were significantly greater improvements for the LipiFlow group on all of the primary and secondary outcome measures. (6) For the MG assessment, there was an improvement of 7.9 points in the LipiFlow® group compared to 0.5 points in the WC group (p<0.0001). The mean change in TBUT was 1.5 seconds in the LipiFlow® group versus 0.1 seconds in the WC group (p=0.0017). For the dry eye symptoms, there was improvement for the LipiFlow® group of 6.2 points on the SPEED scale and 14.7 points on the OSDI scale, compared to changes in the WC group of 3.5 points on the SPEED scale (p<0.0001) and 8.1 points on the OSDI scale (p=0.0004). The percent of patients with at least a 50% improvement in symptoms was 43% in the LipiFlow group versus 11% in the WC group (p value NR). There was no difference in patients-reported pain or discomfort between treatments.
In a follow-up analysis of this trial by Greiner, this improvement in both MG secretion and TBUT was maintained at 9 months in a sub-cohort of 21 adult patients participating in a U.S. single-site. However, this follow-up analysis did not include a control group, and so there were only single-arm results available for patients treated with LipiFlow®. (7)
This RCT indicates that one treatment with LipiFlow® may result in greater short-term improvement in MG dysfunction and dry eye symptoms compared to WC. Limitations of the trial include the short-term time period (2 weeks) for the primary comparative outcomes, and the lack of analysis by intention to treat. The clinical significance of the outcome measures was not assessed, particularly the minimal important clinical difference on the symptom scales. In addition, the comparator used, warm compresses as one relevant alternative treatment, but other modalities such as manual MG expression are also available. The durability of the treatment effect is not defined because the follow-up data did not include treatment with control.
Ongoing Clinical Trials
Three studies on the LipiFlow System for treatment of MGD currently are listed at online site ClinicalTrials.gov. (13, 14, 15)
Randomized Controlled Trial of Long-term Treatment Effectiveness for Meibomian Gland Dysfunction (MGD) and Dry Eye (NCT01521507)
This is a post-market prospective clinical trial sponsored by the manufacturer (TearScience Inc., Morrisville, NC) of the LipiFlow® System. This trial has the estimated enrollment of 200 adult patients across 8 U.S. sites. This trial is divided into 2 stages. The first stage from enrollment to 3 months is an open-label, randomized controlled design to compare the effectiveness of a single LipiFlow® System treatment to a standardized daily warm compress and eyelid hygiene control therapy with crossover LipiFlow® treatment of the control subjects at 3 months. The second stage, occurring between 3 months and 1 year, is an observational design to evaluate the effectiveness of LipiFlow® alone and in combination with other MGD and dry eye treatments over a follow-up period of 1 year. Patients will be entered into pre-specified subgroups based on the subject's self-assessment of the adequacy of symptom relief and protocol-defined criteria for additional treatment. The primary outcome measure is the mean change in total MG score between baseline to 3 months, baseline to 6 months, and baseline to 1 year of follow-up, respectively. This study is ongoing but not recruiting participants with the estimated completion date of November 2013.
Comparison of LipiFlow Treatment and a Standard Lid Hygiene Regime (NCT01769105)
This is a randomized prospective single-blind trial comparing the LipiFlow® System with a standard lid hygiene regimen for treatment of MGD. This trial, with an estimated enrollment of 40 adult patients, is being undertaken at a university center in Germany (study sponsor). The primary outcome measure is improvement of dry eye symptoms using standardized questionnaires at 3-month follow-up. This study is currently recruiting participants with the estimated completion date of April 2013.
Thermal Pulsation System for the Treatment of Meibomian Gland Dysfunction (NCT01683318)
This is an observational study designed to test the efficacy of the LipiFlow® System for treatment of MGD. This study, with an estimated enrollment of 25 adult patients, is being undertaken at the Singapore National Eye Center (study sponsor). Patients will be asked to undergo a one-time treatment with LipiFlow® and the investigators will assess for changes in tear film and lipid composition, as well as changes in the anatomy of meibomian glands up to 3 month follow-up. Additionally, dry eye symptoms will be documented in the form of questionnaires. The study investigators hypothesize that the treatment will be effective in improving clinical signs and will relieve dry eye symptoms for the patient. If the LipiFlow® System of managing MGD is found to be efficacious and safe, it will be made available to eligible patients in Singapore. This study is currently recruiting participants with the estimated completion date of October 2013.
A clinical study is underway to determine if the LipiView can provide a statistically reliable estimate of lipid layer thickness as well as tear film thickness. (12) The following study is listed online at ClinicalTrials.gov:
Investigating Abnormal Lipid Layer Thickness and Other Objective Dry Eye Parameters in Patients Seeking Blepharoplasty, and How They Change After Blepharoplasty (NCT01787942) (16)
This study is investigating if there are significant differences in lipid layer thickness (LLT) and other objective dry eye parameters in two situations: 1) patients considering blepharoplasty as compared to other patients not considering such procedures 2) patients before and after undergoing blepharoplasty. The results of these investigations can go towards establishing LLT as an important objective parameter to account for before and after blepharoplasty. Estimated study completion date: December 2013.
Further prospective RCTs are needed to assess the impact on health outcomes of the LipiView and the LipiFlow System compared to alternative options. These trials will require longer follow-up to assess durability of effect and to accurately predict the optimal frequency of treatment with the LipiFlow® System for individual patients. Based on review of the evidence to date the use of the LipiView and the LipiFlow® Thermal Pulsation System are considered experimental, investigational and unproven for dry eye disease (DED).
Practice Guidelines and Position Statements
In October 2011, the American Academy of Ophthalmology (AAO) developed a Preferred Practice Patterns Guidelines on DED. (1) In the process of developing these guidelines, an updated literature search of articles in the English language was conducted in February 2011 on the subject of dry eye, limited to English language and publication date from 2002 to the date of the search (which was prior to device approval by the FDA). The results were reviewed by the AAO Cornea/External Disease Panel and used to prepare the recommendations for these guidelines.(1) The LipiFlow System was not mentioned as a therapeutic option under their treatment recommendations for DED by disease severity level.(1)
Disclaimer for coding information on Medical Policies
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.
The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.
Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.