BlueCross and BlueShield of Montana Medical Policy/Codes
Confocal Laser Endomicroscopy (CLE) (Optical Endomicroscopy)
Chapter: Medicine: Tests
Current Effective Date: October 25, 2013
Original Effective Date: October 25, 2013
Publish Date: July 25, 2013
Description

Confocal laser endomicroscopy (CLE) is a new endoscopic modality developed to obtain very high-resolution images of the mucosal layer of the GI tract. CLE is based on tissue illumination with a low-power laser with subsequent detection of the fluorescence light reflected from the tissue through a pinhole.  The term confocal refers to the alignment of both illumination and collection systems in the same focal plane.  The laser light is focused at a selected depth in the tissue of interest and reflected light is then refocused onto the detection system by the same lens. Only returning light refocused through the pinhole is detected.  The light reflected and scattered at other geometric angles from the illuminated object or refocused out of plane with the pinhole is excluded from detection. (1) 

CLE is one of several novel methods that provide real-time, high-resolution imaging at a micronscale via endoscopes. CLE and similar technologies are often termed “virtual biopsy” as they are noted to mimic the images seen in conventional histology. However, the imaging of living tissue allows more than just practical convenience; it also permits imaging of living tissue such as active capillary circulation, cellular death, and vascular and endothelial translocation, thus extending beyond what is capable in traditional biopsy.  Immediate potential applications of CLE are to guide biopsy sampling in Barrett’s esophagus and inflammatory bowel disease surveillance, evaluation of colorectal polyps, and intraductal imaging of the pancreas and bile duct. (2)

At least two CLE systems have received FDA clearance.  According to the U.S. Food and Drug Administration (FDA)  pre-market summary letter (K042740), "the Pentax Confocal Laser System is a required accessory for legally marketed video endoscopes equipped with a confocal laser imaging module.  The system is intended to allow confocal laser imaging of the internal microstructure of tissues in the anatomical track assessed by the endoscope."  The FDA premarket notification letter (K061666) for the F-600 System (Cellvizio® Confocal Miniprobe™) indicates this device is a "confocal laser system that is intended to allow confocal laser imaging of the internal microstructure of tissues in the anatomical tract, i.e., GI or respiratory, accessed by the endoscope."

Policy

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.

Investigational

Blue Cross and Blue Shield of Montana (BCBSMT) considers confocal laser endomicroscopy (CLE) (optical endomicroscopy) experimental, investigational and unproven for all indications.

Rationale

A review from Carignan and Yagi 2012 (4) noted “Optical diagnostic technologies are emerging as clinically useful tools with the potential to set a new standard for real-time diagnosis. New imaging techniques enable visualization of high-resolution, cross-sectional images and offer the opportunity to guide biopsy, allowing maximal diagnostic yields and appropriate staging without the limitations and risks inherent with current random biopsy protocols. However, the ability of these techniques to achieve widespread adoption in clinical practice depends on future research designed to improve accuracy and allow real-time data transmission and storage, thereby linking pathology to the treating physician.”

A randomized controlled trial (RCT) published in 2009 by Dunbar et al. (5) concluded that “CLE with targeted biopsy significantly improves the diagnostic yield for endoscopically inapparent BE neoplastic compared to a standard endoscopy with a random-biopsy protocol.  CLE with targeted biopsy also greatly reduces the number of biopsies needed per patient and allows some patients without neoplasia to completely forgo mucosal biopsy.”   The authors note “our study shows that in vivo imaging with CLE and targeted mucosal biopsy of imaging abnormalities is superior to standard endoscopy with four-quadrant random biopsy for detection of endoscopically inapparent neoplasia in Barrett’s esophagus.  The number of biopsies required to make a diagnosis was significantly lower and the diagnostic yield for neoplasia was higher, suggesting that CLE may assist the endoscopist with taking smarter biopsies.”  The authors also note “his study demonstrates how CLE can enable more selective sampling of the mucosa, without the need for the gastroenterologist to replace the pathologist and that future studies will need to evaluate the clinical impact of in vivo diagnosis with CLE on the immediate endoscopic treatment of BE with associated neoplasia.”

An international multicenter randomized controlled trial of probe-based CLE in Barrett’s was published in September 2011.  (6)  It concluded:  “Probe based CLE combined with HD-WLE [high-definition white light endoscopy] significantly improved the ability to detect neoplasia in BE patients compared with HD-WLE.  This may allow better informed decisions to be made for the management and subsequent treatment of BE patients.”

American Gastroenterological Association (AGA) 2011 Medical Position Statement on the Management of Barrett’s Esophagus (7)

"For the routine endoscopic evaluation of Barrett’s esophagus, the use of chromoendoscopy or electronic chromoendoscopy or advanced imaging techniques such as confocal laser endomicroscopy is not necessary.  These technologies may be helpful in guiding the performance of biopsies in patients who are known to have dysplasia and in patients who have mucosal irregularities detected by white light endoscopy. Quality of Evidence: Low".

The American Society for Gastrointestinal Endoscopy (ASGE) 2009 notes that CLE is being studied as a possible valued addition to conventional endoscopy, as a means of in vivo optical biopsy enabling realtime histological examination of the superficial layer of the GI tract.   ASGE states: “Additional studies are needed to determine how confocal fluorescent endomicroscopy will affect the practice of screening, surveillance, and early diagnosis of benign, premalignant, and malignant lesions of the GI tract.” (1)

Ongoing Trials

A large prospective international multicenter study “Confocal Endomicroscopy for Improved Diagnosis of Barrett's Esophagus and Early Esophageal Cancer (CEBE Study)” -  NCT01124214, (8) is underway to assess the performance characteristics of CLE in patients with Barrett’s and associated neoplasia.  Estimated study completion date is January 2013.  It is noted that this study will validate single center studies supporting the routine use of EM for screening and surveillance of Barrett’s esophagitis.

Summary

Although confocal laser endomicroscopy shows promise, more studies are needed to determine its impact on overall health outcomes. Further evidence is needed to support that CLE provides additional information beyond that of high-resolution white light endoscopy.  In addition, specialized equipment and/or training that may not be available outside of specialty centers.

Coding

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. 

ICD-9 Codes

Experimental, investigational and unproven for all indications.

ICD-10 Codes

Experimental, investigational and unproven for all indications.

Procedural Codes: 43206, 43252, 88375
References
  1. Report on Emerging Technology, Confocal laser Endomicroscopy; The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee Gastrointestinal Endoscopy  Volume 70, No. 2 : 2009
  2. Ussui, V., Wallace, M., Confocal Endomicroscopy of Colorectal Polyps, Gastroenterology Research and Practice Volume 2012 (2012), Article ID 545679, pages 1-6.
  3. U.S. Food and Drug Administration (FDA) , 510(k )Summary - Pentax Confocal Laser System K042740 and Cellvizio® (-Gl, -LUNG) with Confocal Miniprobe' (Coloflex,
  4. Gastroflex, Alveoflex) K061666. (Accessed on 11/6/2012)
  5. Carignan CS, Yagi Y, Optical endomicroscopy and the road to real-time, in vivo pathology: present and future" Diagn Pathol. 2012 Aug 13; 7(1):98.
  6. Dunbar KB, Okolo P, Montgomery E, Canto MI. Confocal laser endomicroscopy in Barrett’s esophagus and endoscopically inapparent Barrett’s neoplasia: a prospective, randomized, double-blind, controlled, crossover trial. Gastrointest Endosc 2009; 70: 645-654
  7. Sharma P, Meining AR, Real-time increased detection of neoplastic tissue in Barrett's esophagus with probe-based confocal laser endomicroscopy: final results of an international multicenter, prospective, randomized, controlled trial. Gastrointest Endosc. 2011 Sep; 74(3):465-72.
  8. American Gastroenterological Association (AGA) 2011 Medical Position Statement on the Management of Barrett’s Esophagus Gastroenterolgy 2011;140:1084–1091
  9. Confocal Endomicroscopy for Improved Diagnosis of Barrett's Esophagus and Early Esophageal Cancer (CEBE Study), Clinical trial NCT01124214.  Available at www.clinicaltrials.gov (Accessed on 11/7/2012)
History
July 2013  New 2013 BCBSMT medical policy.  Confocal laser endomicroscopy (CLE) (optical endomicroscopy) is considered experimental, investigational and unproven for all indications. 
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Confocal Laser Endomicroscopy (CLE) (Optical Endomicroscopy)