Optical Coherence Tomography of the Middle Ear

Number: 0928

Policy

Aetna considers optical coherence tomography (OCT) for the assessment and management of the middle ear experimental and investigational because the effectiveness of this approach has not been established.

Background

Optical coherence tomography (OCT) is a non-invasive, non-contrast imaging technology which uses near-infrared light to produce high-resolution cross-sectional images. OCT was developed as a technique enabling high-resolution, real-time and in-situ imaging of tissue microstructure without the need for tissue excision and processing (Popescu, 2011). OCT technology is now emerging as a diagnostic tool for imaging the auditory system. Analogous to ultrasound by measuring the intensity of infrared light rather than acoustical waves, it is suggested that OCT could be a useful tool to see through the tympanic membrane into the middle ear without requiring surgical manipulation, and to help diagnose diseases associated with the tympanic membrane and middle ear (Cho et al., 2015; Pitris et al., 2001).

Monroy et al. (2017) conducted a prospective observational case series in which optical coherence tomography (OCT) tracking was used to observe 25 pediatric patients diagnosed with chronic or recurrent otitis media perioperatively. Patients were followed before and throughout their treatment. Following OCT imaging, patient records were observed for an additional 6 months in follow-up. At each time point (preop, intraop, postop), the tympanic membrane (at the light reflex region) and directly adjacent middle-ear cavity were observed in vivo with a handheld OCT probe and portable system. Imaging results were compared with clinical outcomes to correlate the clearance of symptoms in relation to changes in the image-based features of infection. OCT images of most all participants showed the presence of additional infection-related biofilm structures during their initial consultation visit and similarly for patients imaged intraoperatively before myringotomy. Patients with no recurrence of infectious symptoms had no additional structures visible in OCT images during the postoperative visit. OCT image findings suggest surgical intervention consisting of myringotomy and tympanostomy tube placement provides a means to clear the middle ear of infection-related components, including middle-ear fluid and biofilms. Furthermore, the authors concluded that OCT was demonstrated as a rapid diagnostic tool to prospectively monitor patients in both outpatient and surgical settings.

Park et al. (2017) conducted a prospective study to examine the tympanic membranes (TMs) of 120 patients with middle ear conditions using a handheld optical coherence tomography-based otoscope (860 nm central wave length, 15 μm axial resolution, 15 μm lateral resolution, and 7 mm scanning range using relay lens). Both OCT and oto-endoscope images were compared according to the clinical characteristics such as perforation, retraction, and postoperative healing process. The objective grade about the thickness of perforation margins and the accurate information about the extent of TM retraction that was not distinguishable by oto-endoscopic exam could be identified using this system. The postoperative healing process of TMs could be also followed using the OCT device. The authors concluded that their findings suggest that the handheld OCT device would be another useful application.

Cho et al. (2015) report on the application of optical coherence tomography (OCT) for the diagnosis and evaluation of otitis media (OM). They evaluated 39 patients who were diagnosed with OM via standard otoendoscopic examination and audiological tests between July and October 2012. Six volunteers with normal tympanic membrane (TM) on otoendoscopy were also included, with OCT images used as a control. Of the 39 patients, OCT images were acquired from 16 patients (41.0%). The most common cause of failure to acquire an image was a narrow or curved external auditory canal (n=5). Other causes were the presence of obstacles, such as profuse otorrhea (n=3), cholesteatoma material (n=4), and cerumen (n=7), and poor compliance (n=4). OCT could not be obtained for the three patients with chronic OM with cholesteatomas. Despite the benefits such as noninvasiveness, lack of radiation, high resolution and ability to use outpatient, the authors report some limitations, such as, difficulty securing a light pathway for the OCT device, and the diagnostic efficiency of otoendoscopy. The authors concluded that their evaluation suggests that a handheld OCT otoscope can be applied clinically to otology, and that OCT has the potential to facilitate diagnosis of OM; however, further clinical trials are necessary.

MacDougall et al. (2015) state that optical coherence tomography (OCT) for imaging the middle ear can present some challenges for real-time clinical use. Although OCT is noninvasive, the challenges included the need to work at a low numerical aperture, the deleterious effects of transtympanic imaging on image quality at the ossicles, sensitivity requirements for clinical fidelity of images at real-time rates, and the high dynamic-range requirements of the ear. (Abstract only)

Nguyen et al. (2013) investigated the acoustic effects of bacterial biofilms, confirmed using optical coherence tomography (OCT), in adult ears. Biofilms have been linked to chronic otitis media (OM) and OM with effusion in the middle ear. Non-invasive OCT images were collected to visualize the 2D cross-sectional structure of the middle ear, verifying the presence of a biofilm behind the TM of 5 ears. Wideband measurements of acoustic reflectance and impedance (0.2 to 6 [kHz]) were used to study the acoustic properties of ears with confirmed bacterial biofilms. Compared to known acoustic properties of normal middle ears, each of the ears with a bacterial biofilm had an elevated power reflectance in the 1 to 3 [kHz] range, corresponding to an abnormally small resistance. The authors note that their preliminary study indicates that acoustic reflectance and impedance measurements may have utility for assessment of the presence and acoustic impact of biofilms in the middle ear; however, future study of a wide range of OM-related conditions, with definitive biofilm and non-biofilm classifications, is needed.

UpToDate reviews on “Evaluation and management of middle ear trauma” (Evans and Handler, 2017), “Acute otitis media in adults” (Limb et al., 2017), “Acute otitis media in children: Diagnosis” (Wald, 2017), and “Eustachian tube dysfunction” (Poe and Hanna, 2016) do not mention use of optical coherence tomography for diagnosis or management.

In a prospective, case-series study, Monroy and colleagues (2018) characterized OM-associated structures affixed to the mucosal surface of the tympanic membrane (TM) in-vivo and in surgically recovered in-vitro samples. A total of 40 pediatric subjects scheduled for tympanostomy tube placement surgery were imaged intra-operatively under general anesthesia.  Post-myringotomy, a portable OCT imaging system assessed for the presence of any biofilm affixed to the mucosal surface of the TM.  Samples of suspected microbial infection-related structures were collected through the myringotomy incision. The sampled site was subsequently re-imaged with OCT to confirm collection from the original image site on the TM.  In-vitro analysis based on confocal laser scanning microscope (CLSM) images of fluorescence in-situ hybridization (FISH)-tagged samples and polymerase chain reaction (PCR) provided microbiological characterization and verification of biofilm activity; OCT imaging was achieved for 38 of 40 subjects (95 %).  Images from 38 of 38 (100 %) of subjects observed with OCT showed the presence of additional microbial infection-related structures; 34 samples were collected from these 38 subjects.  CLSM images provided evidence of clustered bacteria in 32 of 33 (97 %) of samples; PCR detected the presence of active bacterial DNA signatures in 20 of 31 (65 %) of samples.  The authors concluded that PCR and CLSM analysis of FISH-stained samples validated the presence of active bacteria that have formed into a middle ear biofilm that extended across the mucosal layer of the TM.  Moreover, these researchers stated that in the future, OCT could be used to rapidly and quantitatively assess for the presence of a middle ear biofilm without invasive sampling, as in the primary care office.  This capability allows for the longitudinal tracking of middle ear biofilms, specifically their formation and resolution at different stages of OM and when exposed to existing or newly developed pharmacologic or surgical treatment strategies.  The OCT system provided an imaging depth up to approximately 2 mm into tissue, even semi-transparent or highly scattering tissues such as the TM.  This capability allowed cross-sectional depth-resolved visualization and quantification of the TM and any adjacent structure in the middle ear cavity (MEC).  Since the middle ear mucosa (MEM) is known to support biofilms, these researchers are developing a swept-source OCT system to provide visualization of deeper structures within the MEC, up to a centimeter or more, including the ossicles and the MEM.

The authors stated that this study had several limitations.  First, there was no control group.  No TM mucosa samples were collected for analysis from healthy pediatric subjects undergoing non-OM-related surgeries.  However, it was previously demonstrated that normal ears have no biofilms on the MEM.  Other studies similarly reported that normal ears lack biofilm-related structures, as shown in a rat model with a combination of OCT and histology and in normal adult and pediatric ears with OCT.  Second, prior to sample collection, the MEC was not aspirated to remove any effusion, and samples were not washed before being placed in fixative.  Given the numerous FISH processing steps, it was unlikely that an effusion had any significant effect on these results.  Moreover, positive CLSM images were evaluated by consistent and repeated fluorescent signal embedded within the biofilm matrix, not from the exterior of the structure.  Aspiration of any middle ear effusion (MEE) before imaging and sampling may also inadvertently remove biofilm material and confound sample collection.  Third, it was possible that some samples, once divided for PCR and FISH/CLSM, did not have active bacterial populations.  However, it was likely that in other samples, the amount of genetic material for analysis was simply limited.  Some recovered samples were small (approximately 1 mm3), and no additional culturing to expand bacterial concentration was performed.  While FISH results were able to identify single bacteria, PCR requires a minimum amount of genetic material, which may explain why some samples had no identifiable bacteria.  Furthermore, this study analyzed the 3 most common bacterial species known to cause OM, although many other bacterial strains have been identified.  Thus, these factors may explain why some samples did not confirm the hypothesis with combined PCR and CLSM/FISH imaging results.  However, when sufficient genetic material was present for 1 or both techniques, the resulting measurements were not degraded by the heterogeneous composition of these samples, which can include white and red blood cells, MEE fluid, other bacteria, and cell and biofilm fragments. 

Tan and associates (2018) evaluated the recent developments in OCT for TM and middle ear imaging and identified what further development is needed for the technology to be integrated into common clinical use.  Data sources included PubMed, Embase, Google Scholar, Scopus, and Web of Science.  A comprehensive literature search was performed for English language articles published from January 1966 to January 2018 with the keywords "tympanic membrane or middle ear", "optical coherence tomography" and "imaging".  These investigators stated that conventional imaging techniques cannot adequately resolve the microscale features of TM and middle ear, sometimes necessitating diagnostic exploratory surgery in challenging otologic pathology.  As a high-resolution non-invasive imaging technique, OCT offers promise as a diagnostic aid for otologic conditions, such as OM, cholesteatoma, and conductive hearing loss.  Using OCT vibrometry to image the nanoscale vibrations of the TM and middle ear as they conduct acoustic waves may detect the location of ossicular chain dysfunction and differentiate between stapes fixation and incus-stapes discontinuity. The capacity of OCT to image depth and thickness at high resolution allows 3-dimensional volumetric reconstruction of the ME and has potential use for reconstructive tympanoplasty planning and the follow-up of ossicular prostheses.  These researchers stated that to achieve common clinical use beyond these initial discoveries, future in-vivo imaging devices must feature low-cost probe or endoscopic designs and faster imaging speeds and demonstrate superior diagnostic utility to computed tomography (CT) and magnetic resonance imaging (MRI).  While such technology has been available for OCT, its translation requires focused development through a close collaboration between engineers and clinicians.

Jeon and co-workers (2019) noted that Doppler OCT (DOCT) is useful for both, the spatially resolved measurement of the TM oscillation and high-resolution imaging.  These investigators demonstrated a new technique capable of providing real-time two-dimensional (2D) Doppler OCT image of rapidly oscillatory latex mini-drum and in-vivo rat TM and ossicles.  Using DOCT system, the oscillation of sample was measured at frequency range of 1- to 4-kHz at an output of 15 W.  After the sensitivity of the DOCT system was verified using a latex mini-drum consisting of a 100 μm-thick latex membrane, changes in displacement of the umbo and contacted area between TM and malleus in normal and pathologic conditions were measured.  The oscillation cycles of the mini-drum for stimulus frequencies were 1.006 kHz for 1-kHz, 2.012 kHz for 2-kHz, and 3.912 kHz for 4-kHz, which meant that the oscillation cycle of the mini-drum became short in proportional to the frequency of stimuli.  The oscillation cycles of umbo area and the junction area in normal TM for frequencies of the stimuli showed similar integer ratio with the data of latex mini-drum for stimuli less than 4-kHz.  In the case of MEM condition, the Doppler signal showed a tendency of attenuation in all frequencies, which was prominent at 1-kHz and 2-kHz.  The TM vibration under sound stimulation with frequencies from 1-kHz to 4-kHz in normal and pathologic conditions was demonstrated using signal demodulation method in in-vivo condition.  The OCT technology could be helpful for functional and structural assessment as an optional modality.  This preliminary study used a signal de-modulation method to demonstrate TM vibration under sound stimulation at frequencies of 1-, 2-, and 4-kHz in a normal ear and an ear under simulated pathological condition in-vivo and implemented 3D reconstruction of the TM vibration under sound stimulation.  The difference between the oscillation pattern at low-frequency and high-frequency was identified, but further study is needed to validate this method and its results.  These researchers stated that they will conduct detailed studies on abnormal models and further animal and human experiments.

Monroy and colleagues (2019) stated that the diagnosis and treatment of OM is a significant burden on the healthcare system.  Diagnosis relies on observer experience via otoscopy, although for non-specialists or inexperienced users, accurate diagnosis can be difficult.  In past studies, OCT has been used to quantitatively characterize disease states of OM, although with the involvement of experts to interpret and correlate image-based indicators of infection with clinical information.  These investigators presented a flexible and comprehensive framework that automatically extracts features from OCT images, classifies data, and presents clinically relevant results in a user-friendly platform suitable for point-of-care (POC) and primary care settings.  This framework was used to test the discrimination between OCT images of normal controls, ears with biofilms, and ears with biofilms and MEM.  Predicted future performance of this classification platform returned promising results (90 %+ accuracy) in various initial tests.  The authors stated that with integration into patient healthcare workflow, users of all levels of medical experience may be able to collect OCT data and accurately identify the presence of middle ear fluid and/or biofilms.

These researchers stated that “Currently, there is no accepted method to identify the presence of middle ear biofilms (MEBs), although it is likely that biofilms increase the opacity of the TM during infection.  In this study, the development of the “Normal”, “Biofilm”, and “Fluid and Biofilm” states was made possible by observing the image-based features in OCT data in this and past studies.  It was observed that subjects with more severe cases of OM have MEF in addition to an accompanying MEB.  This raises additional questions about the pathogenesis of MEB during OM; questions that are beyond the scope of this present study.  OCT, however, could be one tool that provides a quantitative identification of biofilms and fluid, and in addition, provide further characterization of the purulence or scattering of the fluid.  In this and prior studies, it is common to identify a biofilm layer and middle ear fluid in subjects with more severe cases of OM.  As infections progress, any MEF becomes more purulent and optically scattering, depending on the duration of the infection.  This is likely due to increasing amounts of immune cell activity and biofilm dispersal within the MEC.  Clinicians do not currently diagnose or treat middle ear biofilms as there is no accepted diagnostic tool, nor established or tested/verified treatment regimen.  With these limitations in mind, this platform may offer the immediate potential to identify the presence of MEF and MEB, as well as enable new and expanded capabilities in the future.  The use of machine learning (ML) analysis to classify OCT images from subjects with OM can provide a means to automatically classify data and provide a probable diagnostic outcome.  When an image is successfully collected, a combined OCT + ML platform could ensure the user would have a minimum baseline skill for detecting diagnostic markers for OM.  In its current form, this platform is intended to supplement the assessment of the numerous quantitative details within the data and apparent in tissue, and integrate statistical measures to help guide decision making.  In turn, with an accurate diagnosis, it may then be possible to provide the most appropriate and effective treatment for the current state of infection.  This platform is not intended to replace clinical expertise, but offers the potential for further research and clinical investigations before being validated as an approved technology for clinical decision making”.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :
CPT codes not covered for indications listed in this CPB:
0485T - 0486T	Optical coherence tomography (OCT) of middle ear, with interpretation and report

The above policy is based on the following references: