Confocal Laser Endomicroscopy

POLICY NUMBER

A.2.01.87

DESCRIPTION

Confocal laser endomicroscopy (CLE), also known as confocal fluorescent endomicroscopy and optical endomicroscopy, allows in vivo microscopic imaging of cells during endoscopy. Confocal laser endomicroscopy is proposed for a variety of purposes, especially as a real-time alternative to biopsy/polypectomy and histopathologic analysis during colonoscopy and for targeting areas to undergo biopsy in patients with inflammatory bowel disease or Barrett esophagus.

Confocal laser endomicroscopy (CLE), also known as confocal fluorescent endomicroscopy and optical endomicroscopy, allows in vivo microscopic imaging of the mucosal epithelium during endoscopy. The process uses light from a low-power laser to illuminate tissue and, subsequently, the same lens detects light reflected from the tissue through a pinhole. The term confocal refers to having both illumination and collection systems in the same focal plane. Light reflected and scattered at other geometric angles that are not reflected through the pinhole is excluded from detection, which dramatically increases the resolution of CLE images.

To date, two CLE systems have been cleared by the U.S. Food and Drug Administration (FDA). One is an endoscope-based system with a confocal probe incorporated onto the tip of a conventional endoscope. The other is a probe-based system; the probe is placed through the biopsy channel of a conventional endoscope. The depth of view is up to 250 µm with the endoscopic system and about 120 mm with the probe-based system. A limited area can be examined; no more than 700 µm in the endoscopic-based system and less with the probe-based system. As pointed out in review articles, the limited viewing area emphasizes the need for careful conventional endoscopy to target the areas for evaluation. Both CLE systems are optimized using a contrast agent. The most widely used agent is intravenous fluorescein, which is FDA-approved for ophthalmologic imaging of blood vessels when used with a laser scanning ophthalmoscope.

Unlike techniques such as chromoendoscopy (see the Chromoendoscopy as an Adjunct to Colonoscopy medical policy), which are primarily intended to improve the sensitivity of colonoscopy, CLE is unique in that it is designed to characterize the cellular structure of lesions immediately. Confocal laser endomicroscopy can thus potentially be used to make a diagnosis of polyp histology, particularly in association with screening or surveillance colonoscopy, which could allow for small hyperplastic lesions to be overlooked rather than removed and sent for histologic evaluation. Using CLE would reduce risks associated with biopsy and reduce the number of biopsies and histologic evaluations.

Another potential application of CLE technology is targeting areas for biopsy in individuals with Barrett esophagus undergoing surveillance endoscopy. CLE would be proposed as an alternative to the current standard approach, recommended by the American Gastroenterological Association, which is that individuals with Barrett esophagus who do not have dysplasia undergo endoscopic surveillance every 3 to 5 years. The American Gastroenterological Association has further recommended that random 4-quadrant biopsies every 2 cm be taken with white-light endoscopy in individuals without known dysplasia.

Other potential uses of CLE under investigation include better diagnosis and differentiation of conditions such as gastric metaplasia, lung cancer, and bladder cancer.

As noted, limitations of CLE systems include a limited viewing area and depth of view. Another issue is the standardization of systems for classifying lesions viewed with CLE devices. Although there is currently no internationally accepted classification system for colorectal lesions, 2 systems have been used in a number of studies conducted in different countries. These include the Mainz criteria for endoscopy-based CLE devices and the Miami classification system for probe-based CLE devices. Lesion classification systems are less developed for non-gastrointestinal lesions viewed by CLE devices (e.g., those in the lung or bladder). Another challenge is the learning curve for obtaining high-quality images and classifying lesions. Several studies, however, have found that the ability to acquire high-quality images and interpret them accurately can be learned relatively quickly; these studies were specific to colorectal applications of CLE.

Two confocal laser endomicroscopy devices have been cleared for marketing by the FDA through the 510(k) process:

Cellvizio® (Mauna Kea Technologies) is a confocal microscopy with a fiber optic probe (i.e., a probe-based CLE system). The device consists of a laser scanning unit, proprietary software, a flat-panel display, and miniaturized fiber optic probes. The F-600 system, cleared by the FDA in 2006, can be used with any standard endoscope with a working channel of at least 2.8 mm. According to the FDA, the device is intended for imaging the internal microstructure of tissues in the anatomic tract (gastrointestinal or respiratory) that are accessed by an endoscope. The 100 series version of the system (F400-v2) was cleared by the FDA in 2015 for imaging the internal microstructure of tissues and for visualization of body cavities, organs, and canals during endoscopic and laparoscopic surgery, and has been approved for use with several miniprobes for specific indications. Confocal Miniprobes™ approved for use with the Cellvizio 100 series that are particularly relevant to this review include the GastroFlex™ and ColoFlex™ (for imaging of anatomical tracts, ie, gastrointestinal systems, accessed by an endoscope or endoscopic accessories), and the CranioFlex™ (for visualization within the central nervous system during cranial diagnostic and therapeutic procedures such as tumor biopsy and resection). In 2020, the Cellvizio 100 series system received extended FDA approval to allow for use of fluorescein sodium as a contrast agent for visualization of blood flow for all of its approved indications. Later in 2020, the Cellvizio I.V.E. system with Confocal Miniprobes was approved by the FDA as a newer version of the previously approved 100 series system, designed to reduce the system footprint and improve device usability. The two devices are otherwise equivalent and are approved for the same indications. In 2022, the Cellvizio 100 series system F800 model received extended FDA approval to allow for use of indocyanine green (ICG) and pafolacianine as contrast agents. Intravenous administration of ICG is used to perform fluorescence angiography and interstitial administration of ICG is used to perform fluorescence imaging and visualization of the lymphatic system. Intravenous administration of pafolacianine is used to perform fluorescence imaging of tissues. FDA product codes: GCJ, GWG, OWN.

Confocal Video Colonoscope (Pentax Medical) is an endoscopy-based CLE system. The EC-38 70 CILK system, cleared by the FDA in 2004, is used with a Pentax Video Processor and with a Pentax Confocal Laser System. According to the FDA, the device is intended to provide optical and microscopic visualization of and therapeutic access to the lower gastrointestinal tract. FDA product code: GCJ/FDF (endoscope and accessories). This device is no longer commercially available from the manufacturer.

Endomicroscopy Devices Cleared by the U.S. Food and Drug Administration

Related medical policies are –

• Endoscopic Radiofrequency Ablation or Cryoablation for Barrett’s Esophagus

• Chromoendoscopy as an Adjunct to Colonoscopy

• Colonoscopy, Flexible Sigmoidoscopy and CT Colonography

POLICY

Use of confocal laser endomicroscopy is considered investigational.

POLICY EXCEPTIONS

Federal Employee Program (FEP) may dictate that all 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.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting. 

POLICY HISTORY

03/21/2013: Approved by Medical Policy Advisory Committee.

03/11/2014: Policy reviewed; no changes.

02/09/2015: Policy reviewed; description updated. Policy statement unchanged.

07/13/2015: Code Reference section updated for ICD-10.

12/18/2015: Policy reviewed. Policy statement unchanged. Investigative definition updated in Policy Guidelines.

06/01/2016: Policy number A.2.01.87 added.

01/03/2017: Policy description updated regarding devices. Policy statement unchanged.

01/05/2018: Policy reviewed; no changes.

01/04/2019: Policy description updated regarding devices. Policy statement unchanged.

12/10/2019: Policy reviewed; no changes.

01/13/2021: Policy description updated regarding devices. Policy statement unchanged.

01/26/2022: Policy description updated. Policy statement unchanged.

12/15/2022: Policy description updated regarding devices. Policy statement unchanged.

12/14/2023: Policy reviewed; no changes.

01/29/2025: Policy description updated to change "patients" to "individuals." Policy statement unchanged.

SOURCE(S)

Blue Cross Blue Shield Association policy # 2.01.87 

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

Investigational Codes

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