Latest Review Date: April 2024

Category: Vision

POLICY:

Retinal telescreening with digital imaging and manual grading of images may be considered medically necessary as a screening technique for the detection of diabetic retinopathy.

Digital retinal imaging with image interpretation by artificial intelligence software that is approved by the U.S. Food and Drug Administration (e.g. IDX-DR, EyeArt) may be considered medically necessary for the screening of diabetic retinopathy.

Retinal telescreening is considered investigational for all other indications, including the monitoring and management of disease in individuals diagnosed with diabetic retinopathy.

DESCRIPTION OF PROCEDURE OR SERVICE:

Retinopathy screening and risk assessment with digital imaging systems are proposed as an alternative to conventional dilated fundus examination in diabetic individuals. Digital imaging systems use a digital fundus camera to acquire a series of standard field color images and/or monochromatic images of the retina of each eye. Captured digital images may be transmitted via the Internet to a remote center for interpretation, storage, and subsequent comparison.

Diabetic Retinopathy

Diabetic retinopathy is the leading cause of blindness among adults aged 20 to 74 years in the United States. The major risk factors for developing diabetic retinopathy are duration of diabetes and severity of hyperglycemia. After 20 years of disease, almost all patients with Type 1 and more than 60% of patients with Type 2 diabetes will have some degree of retinopathy. Other factors that contribute to the risk of retinopathy include hypertension and elevated serum lipid levels.

Diabetic retinopathy progresses, at varying rates, from asymptomatic, mild nonproliferative abnormalities to proliferative diabetic retinopathy, with new blood vessel growth on the retina and posterior surface of the vitreous. The two most serious complications for vision are diabetic macular edema and proliferative diabetic retinopathy. At its earliest stage (non-proliferative retinopathy), the retina develops microaneurysms, intraretinal hemorrhages, and focal areas of retinal ischemia. With the disruption of the blood-retinal barrier, macular retinal vessels become permeable, leading to exudation of serous fluid and lipids into the macula (macular edema). As the disease progresses, retinal blood vessels are blocked, triggering the growth of new and fragile blood vessels (proliferative retinopathy). The new blood vessels that occur in proliferative diabetic retinopathy may fibrose and contract, resulting in tractional retinal detachments with significant vision loss. Severe vision loss with proliferative retinopathy arises from vitreous hemorrhage. Moderate vision loss can also arise from macular edema (fluid accumulating in the center of the macula) during the proliferative or nonproliferative stages of the disease. Although proliferative disease is the main cause of blinding in diabetic retinopathy, macular edema is more frequent and is the leading cause of moderate vision loss in people with diabetes.

Treatment

With early detection, diabetic retinopathy can be treated with modalities that can decrease the risk of severe vision loss. Tight glycemic and blood pressure control is the first line of treatment to control diabetic retinopathy, followed by laser photocoagulation for patients whose retinopathy is approaching the high-risk stage. Although laser photocoagulation is effective at slowing the progression of retinopathy and reducing visual loss, it causes collateral damage to the retina and does not restore lost vision. Focal macular edema (characterized by leakage from discrete microaneurysms on fluorescein angiography) may be treated with focal laser photocoagulation, while diffuse macular edema (characterized by generalized macular edema on fluorescein angiography) may be treated with grid laser photocoagulation. Corticosteroids may reduce vascular permeability and inhibit vascular endothelial growth factor production, but are associated with serious adverse events including cataracts and glaucoma, with damage to the optic nerve. Corticosteroids can also worsen diabetes control. Vascular endothelial growth factor inhibitors (e.g., ranibizumab, bevacizumab, pegaptanib), which reduce permeability and block the pathway leading to new blood vessel formation (angiogenesis), are also used for the treatment of diabetic macular edema and proliferative diabetic retinopathy.

Digital Photography and Transmission Systems for Retinal Imaging

A number of photographic methods have been evaluated that capture images of the retina to be interpreted by expert readers, who may or may not be located proximately to the patient. Retinal imaging can be performed using digital retinal photographs with (mydriatic) or without (non-mydriatic) dilation of the pupil. One approach is mydriatic standard field 35-mm stereoscopic color fundus photography. Digital fundus photography has also been evaluated as an alternative to conventional film photography and has become the standard in major clinical trials. Digital imaging has the advantage of easier acquisition, transmission, and storage. Digital images of the retina can also be acquired in a primary care setting and evaluated by trained readers in a remote location, in consultation with retinal specialists.

KEY POINTS:

The most recent literature review was updated through February 20, 2024.

Summary of Evidence

For individuals who have diabetes without known diabetic retinopathy who receive digital retinal imaging with optometrist or ophthalmologist image interpretation, the evidence includes systematic reviews and an RCT. Relevant outcomes include test validity, change in disease status, and functional outcomes. Data from systematic reviews have demonstrated there is concordance between direct ophthalmoscopy and grading by mydriatic or non-mydriatic photography and remote evaluation. An RCT that compared a telemedicine screening program with traditional surveillance found that patients who were randomized to the telemedicine arm were more likely to undergo screening (95% vs. 44%). There is limited direct evidence related to visual outcomes for patients evaluated with a strategy of retinal telescreening. However, given evidence from the Early Treatment Diabetic Retinopathy Study (EDTRS) that early retinopathy treatment improves outcomes, coupled with studies showing high concordance between the screening methods used in Early Treatment Diabetic Retinopathy Study (EDTRS), and an RCT demonstrating higher uptake of screening with a telescreening strategy, a strong chain of evidence can be made that telescreening is associated with improved health outcomes. Digital imaging systems have the additional advantages of short examination time and the ability to perform the test in the primary care physician setting. For individuals who cannot or would not be able to access an eye care professional at the recommended screening intervals, the use of telescreening has a low-risk and is very likely to increase the likelihood of retinopathy detection. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have diabetes without known diabetic retinopathy who receive digital retinal imaging with automated image interpretation, the evidence includes prospective studies comparing the validity of automated scoring of digital images to human image grading. Relevant outcomes are test validity, change in disease status, and functional outcomes. Early detection of diabetic retinopathy is critical to vision preservation. The primary benefit of an automated screening system is to increase the rate of screening for a population that is seeing substantially increased rates of diabetes. A 2021 study found wide variability in diagnostic performance across seven different artificial intelligence algorithms, indicating that each marketed software needs to be evaluated separately, in a diverse population, and with the specific camera and dilation specified. The version of the software, which can change frequently, is also key to evaluating performance characteristics. The pivotal study for the IDx-DR system met its predefined threshold when compared to the criterion standard of expert photography and image evaluation from a centralized site. The EyeArt® versions 2.0 and 2.1.0 artificial intelligence software have been evaluated in a prospective pivotal trial and two large non-concurrent trials (30,000 and 100,000 encounters) in patients who had previously been screened as part of diabetic retinopathy screening programs. When used as an alternative to human grading, the sensitivity to detect diabetic retinopathy was above 90%. Detection of retinopathy (sensitivity) is the most critical feature for referral to an eye care specialist, and is highest in patients who have treatable disease. Annual screening would detect retinopathy as the disease progresses, mitigating the impact of false negatives. Automated annual screening at the same time as a routine diabetes check-up will improve health outcomes of patients with diabetes by increasing the rate of screening in accordance with the annual screening recommendation, thereby allowing earlier detection and treatment of diabetic retinopathy. This method minimizes delays in screening patients with diabetes, reduces strains on a limited resource of eye care specialists, and encourages referral to specialists for patients who screen positive for retinopathy. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

American Academy of Ophthalmology

A 2019 preferred practice pattern from the American Academy of Ophthalmology has provided the following on screening for diabetic retinopathy: “The purpose of an effective screening program for diabetic retinopathy is to determine who needs to be referred to an ophthalmologist for close follow-up and possible treatment and who may simply be screened annually. Some studies have shown that screening programs using digital retinal images taken with or without dilation may enable early detection of diabetic retinopathy along with an appropriate referral.”

American Diabetes Association

In 2020 the American Diabetes Association updated its position statements on standards of medical care for diabetes. Included in the guidelines were specific recommendations for initial and subsequent screening examinations for retinopathy:

• "Adults with Type 1 diabetes should have an initial eye examination by an ophthalmologist or optometrist within five years after the onset of diabetes. (B)"
• "Patients with Type 2 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist at the time of the diabetes diagnosis. (B)"
• "Eye examinations should occur before pregnancy or in the first trimester in patients with preexisting Type 1 or Type 2 diabetes, and then these patients should be monitored every trimester and for one year postpartum as indicated by the degree of retinopathy. (B)"
• "If there is no evidence of retinopathy for one or more annual eye exams and glycemia is well controlled, then screening every one to two years may be considered. (B)"
• "Programs that use retinal photography (with remote reading or use of a validated assessment tool) to improve access to diabetic retinopathy screening can be appropriate screening strategies for diabetic retinopathy. Such programs need to provide pathways for timely referral for a comprehensive eye examination when indicated. (B)"

"Artificial intelligence systems that detect more than mild diabetic retinopathy and diabetic macular edema authorized for use by the FDA represent an alternative to traditional screening approaches. However, the benefits and optimal utilization of this type of screening have yet to be fully determined."

American Telemedicine Association

In 2020, the American Telemedicine Association (ATA) updated their guidelines on the clinical, technical, and operational performance standards for ocular telehealth for diabetic retinopathy. Recommendations were based on reviews of evidence, medical literature, professional consensus, and a review that included open public comment. The guidelines stated that Early Treatment Diabetic Retinopathy Study 30°, stereo 7-standard field, color 35-mm slides have been the gold standard for evaluating diabetic retinopathy, but with the migration away from film photography, digital retinal images have become the norm for major clinical trials. ATA recommends that telehealth programs for diabetic retinopathy should demonstrate an ability to compare favorably with Early Treatment Diabetic Retinopathy Study film or digital photography as reflected in κ values for agreement of diagnosis, false-positive and false-negative readings, positive predictive value, negative predictive value, and sensitivity and specificity of referral thresholds.

 The ATA notes limitations in sensitivity and specificity of smartphone platforms with a lack of standardization and a short product life cycle that create significant operational issues. Portable handheld imaging devices may suffer from some of the same limitations. ATA considers computer algorithms to enhance digital retinal image quality or provide automated identification of retinal pathology to be emerging technologies.

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Diabetic Retinopathy Detection and Tracking System, DigiScope, Fundus AutoImager, ImageNet Digital Imaging System, Inoveon, IRIS Intelligent Retinal Imaging System, iScan,  Visual Pathways, VISUPAC Digital Imaging System. , RetinaVue, EyeSuite Imaging, Retinalyze, IDX-DR, EyeArt

APPROVED BY GOVERNING BODIES:

Several digital camera and transmission systems (see the tables below for examples) have been cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. Digital image storage and data communication systems that are designed to be utilized with a variety of cameras have also been cleared for marketing by the FDA. FDA product codes: HKI and NFJ

Many artificial intelligence analysis systems are in use around the world. As of January 2022, two have received marketing clearance from the FDA (Table 1). In 2018, the FDA gave de novo clearance for the automated retinal analysis system (IDx-DR®) that uses artificial intelligence (DEN180001). IDx-DR is indicated "for use by health care providers to automatically detect more than mild diabetic retinopathy in adults diagnosed with diabetes who have not been previously diagnosed with diabetic retinopathy. IDx-DR is indicated for use with the Topcon NW400." EyeArt® retinal analysis software (Eyenuk) received marketing clearance through the FDA's 510(k) pathway in 2020. It is indicated for use with the Canon CR-2 AF and Canon CR-2 Plus AF cameras in both primary care and eye care settings. Use of automated retinal analysis of images (Table 2) obtained with other cameras would be considered off-label. FDA product code: PIB

Table 1. Examples of Digital Camera and Transmission Systems Cleared by FDA for Retinal Telescreening

FDA: Food and Drug Administration.

Table 2. Automated Analysis Systems

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP:  Special benefit consideration may apply.  Refer to member’s benefit plan. 

CURRENT CODING:

CPT Codes:

REFERENCES:

1. Abramoff, MD, Lavin, PT, Birch, M, Shah, N, Folk, JC. Pivotal trial of an autonomous AI-based diagnostic system for detection of diabetic retinopathy in primary. npj Digital Medicine (2018) 1:39; doi: 10.1038/s41746-018-0040-6.
2. American Academy of Ophthalmology. Diabetic Retinopathy Preferred Practice Pattern. 2019. www.aao.org/preferred-practice-pattern/diabetic-retinopathy-ppp.
3. American Diabetes Association. Standards of Medical Care in Diabetes-2020 Abridged for Primary Care Providers. Clin Diabetes. Jan 2020; 38(1): 10-38.
4. American Telemedicine Association. Telehealth practice recommendations for diabetic retinopathy. 2011. Available online at: www.americantelemed.org/practice/standards/ata-standards-guidelines/telehealth-practice-recommendations-for-diabetic-retinopathy.
5. Bhaskaranand M, Ramachandra C, Bhat S, et al. The Value of Automated Diabetic Retinopathy Screening with the EyeArt System: A Study of More Than 100,000 Consecutive Encounters from People with Diabetes. Diabetes Technol Ther. Nov 2019; 21(11): 635-643.
6. Bragge P, Gruen RL, Chau M et al. Screening for Presence or Absence of Diabetic Retinopathy: A Meta-analysis. Arch Ophthalmol 2011; 129(4):435-44.
7. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. May 1991; 98(5 Suppl): 823-33.
8. Garg S, Davis RM. Diabetic retinopathy screening update. Clin Diabetes. 2009;27(4):140-145
9. Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. May 1991; 98(5 Suppl): 786-806.
10. Heydon P, Egan C, Bolter L, et al. Prospective evaluation of an artificial intelligence-enabled algorithm for automated diabetic retinopathy screening of 30 000 patients. Br J Ophthalmol. Jun 30 2020.
11. Horton MB, Brady CJ, Cavallerano J, et al. Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy, Third Edition. Telemed J E Health. Apr 2020; 26(4): 495-543.
12. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
13. Ipp E, Liljenquist D, Bode B, et al. Pivotal Evaluation of an Artificial Intelligence System for Autonomous Detection of Referable and Vision-Threatening Diabetic Retinopathy. JAMA Netw Open. Nov 01 2021; 4(11): e2134254.
14. Kim TN, Aaberg MT, Li P, et al. Comparison of automated and expert human grading of diabetic retinopathy using smartphone-based retinal photography. Eye (Lond). Jan 2021; 35(1): 334-342.
15. Kinyoun JL, Martin DC, Fujimoto WY et al. Ophthalmoscopy versus fundus photographs for detecting and grading diabetic retinopathy. Invest Ophthalmol Vis Sci 1992; 33(6):1888-93.
16. Lee AY, Yanagihara RT, Lee CS, et al. Multicenter, Head-to-Head, Real-World Validation Study of Seven Automated Artificial Intelligence Diabetic Retinopathy Screening Systems. Diabetes Care. Jan 05 2021.
17. Mansberger SL, Sheppler C, Barker G, et al. Long-term comparative effectiveness of telemedicine in providing diabetic retinopathy screening examinations: a randomized clinical trial. JAMA Ophthalmol. May 2015; 133(5):518-525.
18. Moss SE, Klein R, Kessler SD et al. Comparison between ophthalmoscopy and fundus photography in determining severity of diabetic retinopathy. Ophthalmology 1985; 92(1):62-7.
19. Shi L, Wu H, Dong J, et al. Telemedicine for detecting diabetic retinopathy: a systematic review and meta-analysis. Br J Ophthalmol. Jun 2015; 99(6):823-831.
20. U.S. Food and Drug Administration. EyeArt 510(k) Summary (K200667). August 3, 2020. Available at: www.accessdata.fda.gov/cdrh_docs/pdf20/K200667.pdf.

POLICY HISTORY:

Medical Policy Group, October, 2012 (4)

Medical Policy Administration Committee, October 2012

Available for comment October 24 through December 10, 2012

Medical Policy Group, October, 2013 (4): Updated Key Points, added Practice and Position statement, updated References.  No changes to the policy statement at this time.

Medical Policy Panel October 2014

Medical Policy Group, October 2014 (1): Update to Key Points and References. No changes in Policy.

Medical Policy Group, November 2015:  2015 Annual Coding update. Added code 0380T to Current Coding.

Medical Policy Panel, April 2016

Medical Policy Group, April 2016 (6): Update to Description, Key Points, Key Words, Approved by Governing Bodies, & References. No change in policy statement.

Medical Policy Panel March 2017

Medical Policy Group, March 2017 (6): Updates to Key points, Governing Bodies, Practice Guidelines and References.

Medical Policy Panel, March 2019

Medical Policy Group, April 2019 (6): Updates to Key Points, Practice Guidelines, Approved by Governing Bodies and References. No change to policy statement.

Medical Policy Group, December 2019 (6): Annual Coding Update, 0380T deleted, added 92499.

Medical Policy Panel, March 2020

Medical Policy Group, April 2020 (6): Updates to Policy Statement, Key Points, Practice Guidelines, Governing Bodies, Key Words (RetinaVue, EyeSuite Imaging, Retinalyze, IDx-DR). On Draft through May 17, 2020.

Medical Policy Group, October 2020:  2021 Annual Coding Update.  Added CPT code 92229 to the Current coding section. Revised CPT code 92227 to state "Imaging of retina for detection or monitoring of disease; with remote clinical staff review and report, unilateral or bilateral" and CPT code 92228 to state "Imaging of retina for detection or monitoring of disease; with remote physician or other qualified health care professional interpretation and report, unilateral or bilateral".

Medical Policy Panel, March 2021

Medical Policy Group, March 2021 (9): Policy statement updated to extend medically necessary coverage for Digital retinal imaging with image interpretations by artificial intelligence software that is approved by the U.S. FDA (IDX-DR, EyeArt) for the screening of diabetic retinopathy, effective 4/1/2021 (change to policy statement intent).  Policy statement updated to remove “not medically necessary,” (no change to policy intent). 2021 Updates to Key Points, Description, Regulatory Status, References. Key Word added: EyeArt

Available for comment March 15, 2021 through April 29, 2021.

Medical Policy Administration Committee, April 2021.

Medical Policy Panel, March 2022

Medical Policy Group, March 2022 (9): 2022 Updates to Key Points, Description, References. Deleted Previous Coding Section that includes CPT code 0380T. Clarified abbreviations in policy statement. No change to policy statement intent.

Medical Policy Panel, March 2023

Medical Policy Group, April 2023 (9): Updates to Key Points and Benefit Application; No change to Policy Statement.

Medical Policy Panel, March 2024

Medical Policy Group, April 2024 (9): Minor update to Key Points. No new references added.  Removed previous policy statement prior to April 2021. No change in policy intent.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;
2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;
3. The technology must improve the net health outcome;
4. The technology must be as beneficial as any established alternatives;
5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and
2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and
3. Not primarily for the convenience of the patient, physician or other health care provider; and
4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.