Medical Policies - Other

Digital Imaging Software For Analyzing Time Series Retinal Images


Effective Date:11-01-2018



Use of computer software to animate and analyze a time series of retinal images (e.g., MatchedFlicker®) is considered experimental, investigational and/or unproven for any indication, including but not limited to monitoring disease progression.


The retina is a thin layer of tissue on the inside back wall of the eye, containing millions of light-sensitive cells and other nerve cells that receive and organize visual information. The retina sends information to the brain through the optic nerve, enabling visual acuity. Retinal diseases can affect the area of the retina that serves the central vision. The goal of retinal disease treatment is to stop or slow disease progression and preserve, improve or restore vision (1)

Regulatory Status

In 2009, the United States (U.S.) Food and Drug Administration (FDA) approved MatchedFlicker® (eyeIC, Narbeth, PA.) as a 510(k) class II device. (2) MatchedFlicker is a digital image, computer software program that is utilized to animate and analyze a time series of retinal images of the same object, taken at different points in time, and then generates a superimposed view. The areas of change present between the two images appear as a flickering motion. The flickering motion highlights the small changes between the two images. This technology was developed to aide in the evaluation and progression of retinal conditions such as glaucoma, diabetic retinopathy, retinopathy of prematurity and nevi. (2) Currently the gold standard is analyses by a side-by-side comparison of serial mono or stereo-photographs. (3)

MatchedFlicker® imaging software is regulated by the FDA as a picture archiving and communications system. (2) It is substantially equivalent to other legally marketed digital imaging software, including but not limited to the following devices:

1. NAVIS (K013694) manufactured by Nidek, Inc. (4);

2. Retasure (K071299) manufactured by Digital Healthcare, Inc. (5);

3. IMAGEnet (K082364) manufactured by Topcon Corp (6).

Product code NFJ.


This policy was created in January 2015 and updated with literature searches of the MedLine database. The following includes a summary of key literature to date through September 31, 2017.

In 2009, Cymbor et al. evaluated the degree of concordance among examiners in judging glaucomatous progression between serial optic nerve head photos using digital image flicker comparison versus the traditional side-by-side photograph comparison method. The secondary comparison was to determine if flicker was quicker than side-by-side comparison. A total of 29 eyes were selected from patient records. Fourteen eyes showed various degrees of glaucomatous structural change among photos, while the remaining 15 eyes had no glaucomatous structural change. Three masked optometrists experienced in glaucoma management graded whether the photos represented glaucomatous change or no change when viewing photos randomly assigned to side-by-side or flicker comparison. Among multiple graders, flicker comparison gave moderate agreement, whereas side-by-side analysis gave fair agreement. The difference in time between the 2 methods was not statistically significant. The study concluded that Flicker is a unique, easy to learn, and an accurate way to view serial optic nerve head photographs, although additional research is needed to determine if flicker comparison is a useful tool in the clinical management of structural glaucoma progression. (7)

In 2012, Myung and colleagues measured the accuracy and speed for detection of vascular progression in retinopathy of prematurity (ROP) from serial images. Two strategies were compared in a prospective comparative study: static side-by-side presentation and dynamic flickering of superimposed image pairs. Fifteen de-identified, wide-angle retinal image pairs were taken from infants. Image pairs representing vascular disease progression were taken ≥1 week apart, and control images without progression were taken on the same day. Dynamic flickering pairs were created by digital image registration. Ten experts independently reviewed each image pair on a secure website using both strategies, and were asked to identify progression or state that images were identical. Accuracy and speed were measured, using examination date and ophthalmoscopic findings as a reference standard. Using static images, experts were accurate in a mean (%) ± standard deviation (SD) of 11.4 of 15 (76%) ± 1.7 image pairs. Using dynamic flickering images, experts were accurate in a mean (%) ± SD of 11.3 of 15 (75%) ± 1.7 image pairs. There was no significant difference in accuracy between these strategies (P = .420). Diagnostic speed was faster using dynamic flickering (24.7 ± 8.3 seconds) vs static side-by-side images (40.3 ± 18.3 seconds) (P = .002). Experts reported higher confidence when interpreting dynamic flickering images (P = .001). The study determined that retinal imaging provides objective documentation of vascular appearance, with potentially improved ability to recognize ROP progression compared to standard ophthalmoscopy. Speed of identifying vascular progression was faster by review of dynamic flickering image pairs than by static side-by-side images. There was no difference in accuracy. (8)

Syed et al. believed optic disc hemorrhages are associated with active glaucomatous neurodegeneration and ongoing visual field loss. The goal was to determine whether automated alternation flicker enhances the detection of disc hemorrhages in serial images from patients with glaucoma when compared to side-by-side photographic evaluation and single-image display. Serial sets of optic nerve photographs of 394 eyes from 234 patients followed for glaucoma at the authors' institutions were included in this study. Eyes with disc hemorrhages were graded for difficulty level and randomized along with non-disc hemorrhages. The images were controlled into one of three groups (automated alternation flicker, side-by-side or single image). Seven graders viewed all images and assessed for the presence or absence of disc hemorrhages. The sensitivity of automated alternation flicker for disc hemorrhages detection (0.878) was higher than side-by-side (0.705; p=0.002) and single photographs (0.757; p=0.01). There was no specificity difference between pairs of presentation groups (all p≥0.7). Syed and colleagues determined that automated alternation flicker is a more sensitive method for disc hemorrhage detection than the current clinical standard and may have an important role in the management of glaucoma. (9)

In 2014, Marlow et al. wanted to highlight changing features over time within a single static image through the auto-alignment and subtraction of serial optic nerve photographs. Subtraction maps were generated from auto-aligned (EyeIC, Narbeth, PA) baseline and follow-up images using Adobe Photoshop software. They demonstrated progressive retinal nerve fibre layer (RNFL) defects, optic disc hemorrhage (DH), neuroretinal rim loss (RL) and peripapillary atrophy (PPA). A masked glaucoma specialist identified features of progression on subtraction map first, then assessed feature strength by comparison with original images using alternation flicker. Control images with no progression and parallax-only images (as determined by flicker) were included. Eighty eyes of 67 patients were used to generate subtraction maps that detected glaucoma progression in 87% of DH (n = 28, sensitivity (Se) 82%, specificity (Sp) 98%) and 84% of PPA (n = 30, Se 80%, Sp 98%) cases. The lowest rate of detection was seen with RL at 67% (n = 31, Se 65%, Sp 100%). The subtraction technique was most sensitive for detecting parallax (n = 39, Se 98%, Sp 94%). Features of glaucoma progression appeared equally strong in flicker and subtraction images, but parallax was often enhanced on subtraction maps. Among control images selected for absence of features of glaucomatous change (n = 9) in original flicker images, no features were detected on subtraction maps. Auto-alignment and subtraction of serial optic nerve photographs reliably detect features of glaucoma progression with a single static image. Parallax identification may also be facilitated. Auto-alignment and subtraction of serial optic nerve photographs may prove especially useful in education and printed publications when dynamic imaging is not feasible. (10)

In 2016, Schaefer et al. (11) compared the accuracy and speed of using the computerized MatchedFlicker software program to evaluate glaucomatous optic disc change against the traditional gold standard of manually examining stereoscopic disc photographs. Two resident ophthalmologists and 1 glaucoma fellow independently evaluated 140 image pairs from 100 glaucomatous/ocular hypertensive patient eyes using a handheld stereo viewer and the MatchedFlicker program. Fifty patients progressed to glaucoma as determined by the Ocular Hypertension Treatment Study (OHTS) Optic Disc Reading Group and the OHTS Endpoint Committee in the OHTS, and 50 more had photographs taken a few minutes apart, which were negative controls with no progression. Twenty photograph pairs from each group were duplicated to determine reviewer variability. Photographs were examined in alternating blocks of 70 photograph pairs for each method, with the starting viewing method randomized. Reviewer accuracy and time to review for each method were measured. Using the handheld stereo viewer, the reviewers correctly identified progression or non-progression in 76.0% of the slide pairs. Using the MatchedFlicker software, 87.6% were correctly identified (P = .011). Evaluator speed averaged 34.1 seconds per image pair with the stereo viewer verses 24.9 seconds with the MatchedFlicker (P = .044). Overall, Flicker was significantly more specific but less sensitive than stereo slides. Trainees appeared more reluctant to identify glaucoma progression from slides than from Flicker. For the 2 less experienced trainees Flicker was significantly more accurate. The prospective evaluation concluded that the MatchedFlicker software had a greater accuracy and was quicker to perform than using a handheld stereoscopic viewer.

Professional Guidelines and Position Statements

There are no professional guidelines and position statements that would likely influence this review.

Summary of Evidence

The role of computer software to animate and analyze a time series of retinal images to monitor disease progression of glaucoma and/or other retinal diseases has not been established. To date, there is insufficient evidence in the published, peer-reviewed scientific literature to establish improved health outcomes using this technology. Additional high quality randomized controlled trials with larger number of subjects are needed to evaluate the long-term safety and efficacy of this treatment modality.


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Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

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1. Mayoclinic. Diseases and conditions: Retinal Disease. Available at <> (accessed October 23, 2017).

2. FDA - Medical Devices: 510(k) summary: EyeIC’s Matchedflicker® Device (k090266). Food and Drug Administration - Center for Devices and Radiologic Health (May 6, 2009). Available at <> (accessed October 23, 2017).

3. Öhnell H, Heijl A, Brenner L, et al. Structural and functional progression in the Early Manifest Glaucoma Trial. Ophthalmology. 2016 Jun; 123(6): 1173–1180.

4. FDA - Medical Devices: 510(k) summary: NAVIS (k013694). Food and Drug Administration - Center for Devices and Radiologic Health (November 19, 2002). Available at <> (accessed October 23, 2017).

5. FDA - Medical Devices: 510(k) summary: Retasure (k071299). Food and Drug Administration - Center for Devices and Radiologic Health (August 31, 2007). Available at <> (accessed October 23, 2017).

6. FDA - Medical Devices: 510(k) summary: IMAGEnet (K082364). Food and Drug Administration - Center for Devices and Radiologic Health (September 30,2008). Available at <> (accessed October 23, 2017).

7. Cymbor M, Lear L, Mastrine M, et al. Concordance of flicker comparison versus side-by-side comparison in glaucoma. Optometry 2009; 80(8):437-41. PMID 19635435

8. Myung et al. Evaluation of vascular disease progression in retinopathy of prematurity using static and dynamic retinal images. Am. J. Ophthalmol. 2012; 153(3):544-551. PMID 22019222

9. Syed ZA, Radcliffe NM, De Moraes CG, et al, Automated alternation flicker for the detection of optic disc hemorrhages. Acta Ophthalmology. 2012 November; 90(7):645-50. PMID 21288309

10. Marlow et al. A novel optic nerve photograph alignment and subtraction technique for the detection of structural progression in glaucoma. Acta Ophthalmologica 2014 June; 92(4); e267-72. PMID 24460623

11. Schaefer J, Lukowski Z, Meyer A, et al. Comparing glaucomatous disc change using stereo disc viewing and the MatchedFlicker software program in ophthalmologists-in-training. Am J Ophthalmol. 2016 July; 167:88-95. PMID 27038890

Policy History:

11/1/2018 Reviewed. No changes.
12/15/2017 Document updated with literature review. Coverage unchanged.
12/1/2016 Reviewed. No changes.
1/1/2015 New medical document. Use of computer software to animate and analyze a time series of retinal images (e.g. Matchedflicker®) is considered experimental, investigational and/or unproven for any indication, including but not limited to monitoring disease progression.

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