Practice Guidelines for Ocular Telehealth-Diabetic Retinopathy, Third Edition

The following are examples of training linked to a QA protocol:

• Standardized training for imager, imager trainers, readers, and reader trainers.¹⁴⁰

• Structured, self-study, pretraining of imager and reader to provide baseline background knowledge.

• Structured curriculum with defined endpoints and criteria-based demonstrated proficiency.

• Provisional certification followed by full certification based on experience with a minimum number of telemedicine studies over a defined period of time. Experience should demonstrate required levels of proficiency documented by quality review of a fixed number of cases.

• Time-limited certification of imagers and readers. Recertification should be based on the period since last clinical encounter (recency), number of clinical encounters over a period of time (currency), and proficiency as documented by formal review. Ocular telehealth programs should create certification methods that are defined and relevant to the program.

Ongoing sampling of imager and reader performance by criteria-based review should be performed with a periodicity that satisfies local policy and regulatory requirements for the OS and DS. A review of trends in fallout from outcome analyses can be used to assess:

• Proficiency.

• Opportunities for program improvement.

• Need for changes in initial or recurring training.

• Need for additional training of an imager or reader.

• Evidenced-based reprivileging of licensed readers.

CE is an important component of any QA/CQI program and a key method for ensuring current competency.¹⁴¹ CE should be dynamic and sensitive to patient and staff’s changing needs. The following are considerations in selecting specific CE:

• Adjust CE content by end-to-end program testing through data sampling and outcome analysis.

• Adjust CE program to maintain relevance to the specific population served by the program.

• Deliver CE in formats to achieve desired outcome with maximum efficiency and effectiveness. Format examples include periodic self-study curriculum with pre- and poststudy testing, newsletters, and e-mail “Tips of the Day.” A variety of interactive CE sessions using telehealth technology are available, such as group-based or one-on-one case reviews, morbidity and mortality conferences, and conferences patterned on clinical pathological conference concepts.

Similar guidance comes from broadly distributed programs outside the United States. The U.K. National Screening Committee adopted digital photography in 2000 for a systematic national risk reduction program.¹⁶ Their model incorporates trained professionals, recorded outcomes, targets and standards, QA, and promotion to increase screening rates. Criteria and minimal/achievable standards were proposed for each QA objective.¹⁵⁵ Other ongoing QA programs are publishing measures and outcomes. For example, a U.K. diabetes center regraded a percentage of images to determine appropriateness of referrals for clinic examination.¹⁵⁶ Other programs have reported outcomes measuring image quality, intragrader reliability, and percentage of grader-generated reports within 48 h of grading images.¹⁵⁷

Appendix A7. Customer Support

Telemedicine programs will require ongoing support to remedy hardware and software malfunctions. Programs may find it appropriate to consider the following example of an ocular telehealth program three-level help desk.

Level 1

This is the entry point for most/all initial support requests. Support staff can satisfy routine image acquisition issues and entry-level troubleshooting of software and data transmission. If the request for support is determined to be outside level 1 scope, the call is triaged to the level 2 or level 3 help desk.

Level 2

For more complex software and data transmission issues, a second level support is needed to provide solutions that are more technically complex, but not requiring software or network engineer intervention. The level 2 support staff sometimes is a bridge between levels 2 and 3 services. This is a function that typically evolves over time as the level 2 staff becomes more experienced with the operational idiosyncrasies of the technology.

Level 3

A third level support is needed for troubleshooting and resolving proprietary technology or particularly complex network issues. This support usually involves the imaging device and associated technology, and diagnostic software (camera backs, relay lenses, imaging and reading software applications, etc.).

Help desk response expectations should be prioritized to the program impact level of the exception raising the request for support. The following table provides examples of impact-level stratification and resolution timelines (Table 5).

Appendix A8. Reimbursement

The reimbursement landscape is highly dynamic, and has substantial state, regional, and payer differences. Failure to attend to these changing differences appropriately can result in failed reimbursement and in some instances, costly penalties. For these reasons, programs should seek expert council to ensure compliance with the requirements of a particular payer and locale. Telehealth Resource Centers (TRCs) are an excellent source of regional-specific information on reimbursement issues. (www.telehealthresourcecenter.org/reimbursement) At the time of publication, there was active legislative debate pertaining to expansion of Tmed-DR reimbursement, with emphasis on CPT codes and protocols. Programs should contact their regional TRC for current specifics on DR ocular telehealth reimbursement in their state or region (www.telehealthresourcecenter.org/who-your-trc).

CPT¹⁵⁸ provides several category 1 codes that can be used by telemedicine programs for DR screening or diagnosis (Tmed-DR). The specific code(s) for a particular program depends upon the state, regional, payer, and program characteristics. The following CPT codes are available within these constraints.

Medicare

CPT 92227: remote imaging for detection of retinal disease (e.g., retinopathy in a patient with diabetes) with analysis and report under physician supervision, unilateral or bilateral.

CPT 92228: remote imaging for monitoring and management of active retinal disease (e.g., DR) with physician review, interpretation and report, and unilateral or bilateral.

These remote retinal imaging codes, introduced in 2011, allow for detection of retinal disease (92227) and the monitoring and management of active retinal disease (92228). The codes specifically address the clinical application of telemedicine modalities for DR. The providers who might use these codes are primary care providers, imaging centers, optometrists, and ophthalmologists.

The primary differences between the codes are based upon professional interpretation of the images, and presence of clinically evident DR. CPT 92227 does not require a professional interpretation, whereas CPT 92228 does. CPT 92227 describes a screening service provided by a technician with physician supervision (level of supervision not specified), which may or may not identify retinal disease, whereas CPT 92228 is an assessment of existing retinal disease for remote management. Since CPT 92228 requires interpretation by a licensed independent provider (LIP), it is a greater service than 92227 in both scope and value. Medicare covers CPT 92228 because this service is performed “… for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.”¹⁵⁹

However, screening services are usually considered to be noncovered in the absence of a statutory provision to the contrary (e.g., glaucoma screening). Several Medicare Administrative Contractors (MACs) have published local coverage determinations on this topic, so programs should check their MACs for further details.

These codes have been problematic since their inception, since they poorly define the role of Tmed-DR, do not satisfy the most common telemedicine use cases for DR, and undervalued services provided by DR telemedicine applications.¹⁶⁰

In its protest, the ATA noted that the CPT 92227 definition does not reflect the large majority of actual DR remote retinal imaging programs, and that CPT 92228 does not reflect the complexity of care associated with DR remote imaging. Since CPT 92227 applies to programs with technical (non-LIP) readings, it assigns zero relative value units (RVUs) to physicians’ work. CPT 92228 significantly undervalues the physician’s responsibility and care. ATA also expressed concern that CPT 92228 restricts reimbursement to only patients with active retinal disease. Importantly, this prevents qualifying programs from reimbursement for population surveillance since the presence of retinopathy in new patients cannot be predetermined without a retinal examination. Total RVUs assigned to these new codes are markedly less than the previously used CPT 92250 (fundus photography), although similar equipment, staff, and physician effort are involved.

Currently, CPT 92227 and CPT 92228 are the only dedicated telemedicine codes available for DR screening/diagnosis. Given the restriction in these CPT code definitions, one possible approach is their combined and selective use by a single program. In this use case, a program could use technology and operations satisfying CPT 92227 for annual screening of patients with DR. Those patients shown to have clinically evident DR below the referral threshold are eligible for reimbursement through a “92228” program on subsequent periodic examinations. Those patients without DR could be screened annually using the “92227” program component. The concerns raised by the ATA have not yet been addressed.

Medicaid

Coverage, coding, and valuation of Tmed-DR are state dependent. Programs should contact their state Medicaid office to determine Tmed-DR coverage, appropriate codes and comments, and other billing particulars for their program. In general, the reimbursement for Medicaid is 10–20% lower than the same service covered by Medicare.

Commercial Insurance Carrier

Many private and commercial carriers reimburse DR Tmed-DR using CPT code 92250 (Fundus Photography with interpretation and report), 92227, and 92228. Some allow use of the level II HCPCS code, S0625 (Retinal Telescreening by Digital Imaging of Multiple Different Fundus Areas to Screen for Vision-Threatening Conditions). Some carriers reimburse for the service but require pupil dilation. Owing to this variation among carriers, each must be contacted to determine the requirements for reimbursement.

Tmed-DR may be reimbursed as a single complete service, or fractionated into defined components. A global procedure contains both professional and technical components. Suffixes applied to certain Tmed-DR CPT codes provide for splitting reimbursement to separate providers based upon the performed component.

• 26: The professional component represents the supervision and interpretation of a procedure provided by the physician or other health care professional. It is identified by appending modifier 26 to the procedure code.

• TC: The technical component represents the cost of the equipment, supplies, and personnel to perform the procedure. It is identified by appending modifier TC to the procedure code.

• A global service includes both professional and technical components. The global service is identified by reporting the eligible code without modifier 26 or TC.

Other Financial Factors

Logistic Efficiencies

Geographic disparities in care can result in access to care issues that are costly in terms of time, transportation, and missed opportunity. Telemedicine can close these distances electronically with a possible overall savings in costs to the patient and health care system.

Disease/Complication Prevention

Increasing the surveillance rate of DR through telemedicine contributes to increased treatment and reduction in retinal complications and related vision loss.^161,162 This reduction can result in significant health care savings through cost avoidance.^163,164 In principle, this is the predominate business case for Tmed-DR, but the U.S. health care model limits its use in most cases since the primary care provider supporting the program is not the immediate recipient of the cost avoidance benefits. This shortcoming is somewhat offset by the trend of pay-for-performance incentives.

Resource Utilization

Some DR telehealth programs have shown to be less costly and more effective than conventional retinal examinations for the detection of DR.¹⁶⁵ In addition, use of telehealth-DR may allow a reduction in the overall cost of care with the same or expanded scope of services through the retasking of costly human resources. However, depending on the structure and business model of health care system and reimbursement methods used, these cost savings may not provide benefit to all providers and programs participating in the telehealth-DR service.²¹

Appendix A9. Telemedicine for Glaucoma: Guidelines and Recommendations

Kenman Gan, MD,^1,2 Yao Liu, MD, MS,³ Brian Stagg, MD, MS,⁴ Siddarth Rathi, MD, MBA,⁵ Louis R. Pasquale, MD,⁶ and Karim Damji, MD, MBA¹

¹Department of Ophthamology and Visual Sciences, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

²Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, Canada.

³Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin.

⁴John Moran Eye Center, University of Utah, Salt Lake City, Utah.

⁵NYU Langone Health, New York, New York.

⁶Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York.

Background

Glaucoma is the leading cause of irreversible blindness worldwide, estimated to affect >60 million people.¹⁶⁶ This condition is clinically defined as a group of progressive optic neuropathies having characteristic patterns of visual field loss. In the United States, the prevalence of glaucoma ranges from 2% among those aged 40–49 years and increases with age to 8% or more among those aged 80 years or older.¹⁶⁷ The estimated yearly direct cost for glaucoma management in the United States exceeds $2.9 billion.¹⁶⁸

Current diagnostic and treatment guidelines for glaucoma are informed by several large multicenter clinical trials.^169,170 Glaucoma care guidelines are not as standardized as those for DR, which allow for significant regional and provider variability in glaucoma diagnosis and management.¹⁷⁰ It is important to note that other areas of medicine—including psychiatry and primary care—have flexible practice guidelines, which have not been a barrier to the successful large-scale uptake of telemedicine in these fields.

Introduction

Teleglaucoma is a growing field with great promise for increasing patient access to high-quality cost-effective glaucoma care by leveraging new telecommunications and diagnostic technologies. Many of the telehealth principles underlying teleglaucoma programs are shared with those in teleretinal programs for DR. In this appendix, we review some additional considerations and practice recommendations for teleglaucoma programs.

Discussion

Definition and Literature Review

Glaucoma is a chronic lifelong disease for which patients are monitored at clinic visits occurring one or more times yearly. Access to glaucoma specialists is becoming more limited as the prevalence of glaucoma is expected to increase dramatically with our aging populations.^166,171 Advances in telecommunications and diagnostic technologies have allowed for the development of teleglaucoma programs, wherein key glaucoma measures are collected from a patient at an OS and then transmitted to a DS provider for interpretation. Teleglaucoma has the potential to increase access to glaucoma care by improving efficiency and decreasing the need for long-distance travel for patients.¹⁷² There is an emerging body of literature to support teleglaucoma programs.^173–187 In addition to these published reports, there are also many active clinical teleglaucoma programs.

Kotecha et al. reported using teleglaucoma to decrease the amount of time patients spent during each clinic visit.¹⁸⁸ Another study found that approximately three-quarters of glaucoma suspects evaluated remotely did not require in-person follow-up examination.¹⁸⁶ A cost-effectiveness analysis found that teleglaucoma was more cost-effective than in-person examination for glaucoma screening.¹⁸⁹ Patients participating in teleglaucoma programs report comparable satisfaction with in-person examinations.¹⁹⁰ A number of teleretinal programs have published high rates of incidental detection of glaucomatous-appearing optic nerves and suspected glaucoma is a major contributor to clinical referrals in teleretinal diabetic screening.^191,192

Types of Teleglaucoma Programs

The extent to which a given teleglaucoma program can support various types of use cases depends greatly on the resources available as well as the training and comfort level of the providers. We define a “Full Scope” teleglaucoma program as one with sufficient resources to provide not only glaucoma screening but also diagnosis and treatment monitoring. The types of teleglaucoma programs can be described on the following spectrum of use cases.

Screening

Screening for glaucoma refers to the systematic evaluation of asymptomatic persons for evidence of glaucomatous damage.¹⁹³ In 2013, the U.S. Preventive Services Task Force concluded “the current evidence is insufficient to assess the balance of benefits and harms of screening for primary open-angle glaucoma in adults.”¹⁹⁴ However, subsequent studies have suggested that screening in populations at high risk for glaucoma is effective.^195,196 A systematic review of teleglaucoma screening estimated its sensitivity as 83.2% and specificity as 79.0%.¹⁹³

Diagnostic consultation

Teleglaucoma can also be used to provide specialist consultation from a distance to reduce patient travel.^186,197 Verma and coauthors reported that 69% of teleglaucoma patients referred for suspected glaucoma could be managed by the referring primary eye care provider and did not require in-person evaluation by a specialist.¹⁸⁶

Long-term treatment monitoring

Teleglaucoma can also be used for follow-up monitoring after initiation of treatment. “Virtual Glaucoma Clinics” described in the United Kingdom use teleglaucoma for long-term treatment monitoring.^174,187,188 In these clinics, “stable” patients are followed through virtual review of glaucoma testing with in-person visits only when necessary.¹⁸⁸ Kashiwagi et al. have described a slit-lamp camera system to accurately monitor delegation of postoperative care to nonglaucoma specialists after glaucoma surgery.¹⁹⁸

Key Components of Teleglaucoma Programs

Additional key components in establishing teleglaucoma programs include the following.

Patient history

Important components of the patient history include any ocular and visual symptoms, demographics, ocular history (including the use of any eye medications, last eye examination and recommended follow-up, and previous diagnosis of DR), medical history, and family history (e.g., first-degree relatives with glaucoma and the severity of their disease).

Equipment

Equipment needs for each teleglaucoma program depend on the program’s goals, provider preferences, patient population, and the availability of community resources. Some important components may include:

Software

Clinical decision-making for glaucoma requires the complex synthesis of a variety of measures over time. Thus, it is important for software to enable time-efficient clinical workflows. Several companies offer glaucoma-focused software programs that allow providers to rapidly evaluate multiple components of longitudinal patient data, often viewed concurrently within a single screen (e.g., Zeiss Forum; Carl Zeiss Meditec and Care1 Telemedicine Network, British Columbia, Canada). AI software for image analysis may play a role in the future of teleglaucoma.²¹⁶

Personnel

Skilled providers, technical, and administrative staff support are needed for both collecting and reviewing the complex data needed for teleglaucoma programs. The personnel and/or providers at the OS(s) play an important role in ensuring high-quality data collection, detailed patient history taking, and, in some cases, appropriate patient education and counseling. Counseling topics can range from providing general information about glaucoma diagnosis to detailed discussions regarding medication adherence, the assessment of medication-related side effects, and the risks and benefits of various treatment options. Interdisciplinary collaborations between providers at the OS and DS can be beneficial in providing a high level of teleglaucoma care.^186,197

Providers at the DS can perform consultations either in real time or using a store-and-forward model. Either option may be acceptable with sufficiently detailed documentation and instructions communicated to the patient and personnel at the OS. Personnel involved in administrative and information technology support are often closely linked with the DS/central site. A dedicated program coordinator can be invaluable for ensuring the smooth operation of teleglaucoma programs.

Financial

Start-up and ongoing maintenance costs associated with teleglaucoma programs are generally much higher than those of teleretinal programs due to extensive equipment, software, and personnel requirements already described. A recent systematic review found that the mean reported cost of establishing a teleglaucoma screening program ranged from $89,703 to $123,164.¹⁹³ Although teleglaucoma screening requires substantial resources, a follow-up study estimated that using telemedicine to screen for glaucoma was more cost-effective than in-person examinations, with predicted savings of $27,460 per quality-adjusted life year (QALY).¹⁸⁹

Teleglaucoma programs in Canada and Australia have obtained reimbursement.^177,217 Reimbursement to offset technical and personnel costs are important for encouraging sustained utilization of these services.²¹⁷ Further advances in technology may make teleglaucoma programs more affordable in the future.

Implementation

Owing to the high equipment, personnel, and financial start-up costs associated with teleglaucoma, it may be beneficial for providers to implement a collaborative model of care. Some implementation models include:

Special mention should be made for “Digitally Integrated Visits,” a specific implementation of In-House Telemedicine, wherein glaucoma patients have a subset of clinic visits reserved solely for the purpose of glaucoma testing, such as visual fields, performed by technical personnel without seeing the provider at the same visit. The provider then reviews the test results and may respond by making changes to the patient’s care plan. This system reduces the number of in-person provider visits while ensuring provider oversight of the patient’s care. It is important that the patient and technical personnel have the option to escalate patient care to in-person visits with the provider when requested.

Conclusions

Teleglaucoma has tremendous potential to improve patient access to high-quality cost-effective glaucoma care. We have reviewed some special considerations needed to address the complexity of providing guideline-concordant glaucoma care. A wide spectrum of teleglaucoma implementations is currently used around the world. The growing body of literature and experience from active teleglaucoma programs will continue to inform further development of these programs. We anticipate that teleglaucoma will have an increasingly important public health impact through expanding access to the high-quality care for glaucoma patients worldwide.

Disclosure Statement

K.G. is the Ophthalmology Director of Care 1 Inc.; L.R.P. is a consultant to Verily, Eyenovia, Bausch + Lomb, Nicox and Emerald Bioscience.

Funding Information

Y.L. was funded in part by an institutional grant from Research to Prevent Blindness to the Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, and by National Institutes of Health K23 EY026518.

B.S. is supported in part by an Unrestricted Grant from Research to Prevent Blindness, New York, NY, to the Department of Ophthalmology & Visual Sciences, University of Utah.

L.R.P. was funded in part by a grant from the National Eye Institute.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Research to Prevent Blindness.

Appendix A10. Telemedicine for Retinopathy of Prematurity

Christopher J. Brady, MD, MHS,¹ Samantha D’Amico, MS,² and J. Peter Campbell, MD, MPH³

¹Division of Ophthalmology, Department of Surgery, Larner College of Medicine, University of Vermont Medical Center, Burlington, Vermont.

²Division of Ophthalmology, Department of Surgery, University of Vermont Medical Center, Burlington, Vermont.

³Casey Eye Institute, Oregon Health and Science University, Portland, Oregon.

Introduction

Retinopathy of prematurity (ROP) is a disease of the retinal vasculature that remains a leading cause of childhood blindness in the United States and abroad.^218,219 The disease affects the most severely premature and lowest birth weight infants, with 15.6% of premature newborns with hospital stays >28 days and 68% of infants with birth weights <1,251 g affected by the disease.²¹⁹

Several studies have confirmed the ability of timely treatment to prevent blindness; therefore, a simple, valid, noninvasive, and inexpensive screening examination is necessary to identify infants who are at increased risk for developing ROP.^220–223 The availability of ROP screening is a requirement for level IIIB neonatal intensive care unit (NICU) designation in the United States, which supports infants with extreme prematurity, extremely low birth weights, or severe/complex illnesses.²²⁴ Although a matter of some debate in the ophthalmic literature,^225,226 the reference standard for the screening and diagnosis of ROP is a live dilated examination by an ophthalmologist using binocular indirect ophthalmoscopy (BIO), often with scleral indentation.²²⁷

However, in many areas, there are a limited number of ophthalmologists and significant workforce limitations, including concerns about medicolegal liability, low reimbursement, and work-flow difficulties, such that few trained ophthalmologists may be available and/or willing to perform ROP screening examinations.^228–230

In addition, the significant variability that exists between examiners diagnosing ROP using BIO also suggests that the use of remote imaging and computer-based image analysis (CBIA) methods may improve accuracy and consistency of diagnosis of plus disease.^{228,231–234} A study evaluating ROP image grading by eight ROP experts found that there is poor agreement on the classification of plus disease, despite established international standards.²³¹ This disagreement suggests that treatment recommendations likely vary among providers and that some infants may be undertreated while others are over treated for ROP.²³¹

For these reasons, there has been growing interest in photographic screening and remote interpretation for ROP screening, with reports from several successful clinical implementations and research studies available in the literature. Consequently, the 2013 joint guidelines from the American Academy of Pediatrics, American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, and the American Association of Certified Orthoptists recognized the interest in remote interpretation of retinal images and allowed for the possibility of alternative screening strategies.²³⁵

Current guidelines support the use of remote digital fundus imaging to identify individuals with referral-warranted ROP (RW-ROP), but recommend that at least one BIO examination is completed before initiation of treatment or termination of ROP monitoring, as current cameras do not allow for adequate view of the peripheral retina.^229,236,237 Still, many remain skeptical of the safety and efficacy of telehealth screening as evidenced by a survey of 847 Level III NICU directors in which only 21% of NICUs used retinal imaging devices and only 30% agreed that telemedicine for ROP screening is safe.²³⁸

Background

Reports from the early 21st century documented proof-of-principle for ROP telehealth screening, but raised concerns about the technical ability of the RetCam device (Natus Medical, Inc., Pleasanton, CA) to capture images with sufficient sensitivity to replace live screening.^239,240 However, subsequent reports began to show improved diagnostic capability and low false-negative rates, which must be minimized in any ROP screening scenario given the severe consequences of even a single missed case.^241–247

Nevertheless, debate continues and most authors conclude that wide-field imaging could potentially serve as an adjunct to live screening, but ought not replace in-person examination by an ophthalmologist.^229,245,246 A 2008 systematic review likewise concluded “the evidence base is not sufficient to recommend that retinal imaging be routinely adopted by NICUs to identify infants who have serious retinopathy of prematurity.”²⁴⁸ Most guidelines continue to be hesitant about ROP telehealth screening and continue to recommend a hybrid approach, given that few large-scale outcome comparisons have been published.²³⁷

Recent Clinical Study Findings

The most recent large multicenter validation study to be published, the Telemedicine Approaches to Evaluating Acute-phase ROP Study (e-ROP), compared wide-field retinal imaging performed and interpreted by nonphysicians to examinations performed by physicians.^218,249 The e-ROP Study enrolled 1,257 infants who received a median of 3 imaging sessions and conventional live examinations at 12 sites in the United States and 1 site in Canada between 2011 and 2013. The infants had a median birth weight of 860 g and a median gestational age of 26 weeks. Approximately 44% of infants were nonwhite or did not have race information available. Any ROP was identified in 63.7% of infants and RW-ROP (plus disease, ROP in zone I or stage 3 ROP or greater)²⁴² was noted in 19.4% of infants on criterion-standard live examination.

When both eyes were analyzed together (i.e., at the level of the infant), remote grading by trained nonphysician graders had 90% sensitivity and 87% specificity. Given the prevalence of RW-ROP in this population, this conferred a 97.3% negative predictive value and 62.5% positive predictive value. Importantly, when considering only those infants ultimately treated for ROP, the sensitivity of remote imaging grading was 98.2%. Although this number is impressively high, in absolute terms, there were 3 infants out of the 162 treated who did not have RW-ROP detected on the remote imaging preceding treatment.

The e-ROP authors argued that their study supports the validity of using nonphysician imagers and graders for remote detection of RW-ROP, similar to how reading centers are structured for other ophthalmic conditions.^218,250 The authors did highlight the limitations of identifying important features of ROP and inherent variability of the criterion standard live examination as a potential weakness of the study, but also note that the possibility of missing severe ROP needs to be considered in the development of any screening program.^218,251 The e-ROP Cooperative Group found that the region of the retina where most severe disease occurs (zone I) may be best assessed by retinal images, but that the subtleties that may be seen in stage 3 ROP in zone I may currently be best identified by an experienced clinician on a live examination.²⁵¹

The Imaging and Informatics in Retinopathy of Prematurity Consortium (i-ROP) found that there was a slightly higher accuracy for diagnosis of zone III and stage 3 ROP on live examination than with imaging.²⁵² Although examinations by an experienced clinician currently remain the gold standard for ROP screening, there are weaknesses to this system to which the implementation of tele-ROP screening and automated image analysis may be the solution.

Turnaround times of 24 h or less were feasible in the e-ROP study, with >95% of images returned within that period, showing that ROP telemedicine is capable of providing timely feedback for detection of ROP.²²⁸ The biggest barriers to rapid turnaround identified were the time of submission and delays between image acquisition and uploading. Images that were submitted before 2 pm were graded much more quickly than images that were submitted later and, therefore, not graded until the next morning. The authors felt these issues could be addressed by improving technology used to select and submit images to allow images to easily be submitted at the bedside and increasing staffing at reading centers during peak demand times.

Reports of Clinical Implementations

United States

A hybrid model has been deployed at six NICUs in Northern California through the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) in which all infants meeting screening criteria are photographed according to screening guidelines and then also receive a live examination within 1 week of NICU discharge. A retrospective analysis of 6 years of follow-up between 2005 and 2011 has been published.²¹⁹ During this time, 1,216 eyes were screened, generating 26,970 retinal images. Twenty-two infants were determined to have treatment-warranted ROP (TW-ROP: zone I, any stage ROP with plus disease; zone I, stage 3 ROP with or without plus disease; zone II, stage 2 or stage 3 ROP with plus disease; any plus disease; or any stage 4 or higher disease).²²¹

All TW-ROP infants were successfully identified through photoscreening in this time period and only 1 “false-positive” case was noted in which stage 3 ROP was not felt to warrant treatment on live examination. These results translate to a sensitivity of 100%, negative predictive value of 100%, specificity of 99.8%, and positive predictive value of 95.5%. The SUNDROP authors concluded that telehealth screening can be safe, reliable, and cost-effective when coupled with committed ROP specialists to interpret images and perform live examinations when necessary.

A similar retrospective “real-world” study from an NICU in Montana reported good outcomes in the 137 infants evaluated, 13 of whom required transfer, and 9 of those transferred ultimately required laser treatment.²⁵³ Over the 4.5 years covered by their review, the authors noted no infants progressing to stage 4 or stage 5 ROP. The investigators followed the SUNDROP protocol for their screening schedule and ensured all infants were seen for a live diagnostic examination within 2 weeks of NICU discharge.

International

Vinekar et al. reported results from 36 rural NICUs in the southern Indian state of Karnataka starting in February 2011 through February 2015, covering remote screening of 7,106 infants as part of the Karnataka Internet Assisted Diagnosis of Retinopathy of Prematurity (KIDROP) program.²⁵⁴ The overall incidence of any ROP was 22.4% and treatment-requiring ROP was 3.6%. In this report, there was no comparison with criterion standard examination. The group’s prior 2014 report examining 1,601 infants²⁵⁵ did compare nonphysician grading of images versus expert live examinations, but did not clearly report the results of this evaluation.

A national network for ROP screening was also developed and implemented in 11 NICUs in Chile.²⁵⁶ Images were taken by trained nonphysician operators using the RetCam Shuttle and were evaluated independently by two ROP experts. Of the 5,263 imaging sessions performed, 4,903 (93%) were considered good or excellent quality with evaluation of ROP possible in 98% of images. In this network, all screening and examinations were performed by telemedicine, with the exception of BIO examinations performed before treatment. Forty-two infants (4%) were referred for treatment and 98% agreement was found between the initial imaging and clinical examinations.

Lorenz et al. reported their 6-year experience with the wide-field remote screening in five NICUs in Germany.²⁵⁷ In this study, all 1,222 infants also received live examinations for comparison. The authors report that all 42 cases requiring treatment were successfully identified by telescreening with an acceptable positive predictive value of 82.4%.

In France, implementation of a telemedicine program for ROP screening resulted in an absolute 57.3% increase in the proportion of examinations completed in accordance with American Academy of Pediatrics guidelines, whereas the screening rates in the control group, which continued ROP screening using live examinations, remained unchanged.²⁵⁸ The average cost of examination in the telemedicine program was slightly more expensive (∼$22) than the standard procedure of transferring infants to a specialized center for examination by a specialist, but the authors projected that this cost would decrease as the number of examinations completed rose.²⁵⁸

Another French ROP screening program was conducted in Bordeaux between July 2009 and August 2015 and screened 419 infants using the RetCam 120.²⁵⁹ They found any ROP in 27.68% of infants. The authors felt that their exclusively telemedicine screening system was successful at identifying ROP, but did not report any data with regard to predictive values.

Skalet et al. performed a feasibility study on 26 babies in Lima, Peru.²⁶⁰ In this study, 95–97% of image sets were judged to be suitable for ROP grading.

Despite lack of full endorsement in current guidelines, remote ROP screening programs are being developed and implemented by many groups around the world.

Guidelines for Imagers

Although the use of nonphysician imagers is the foundation to the widespread use of telemedicine in ROP screening, it is imperative that imagers are appropriately trained and certified to ensure high-quality images. A team of at least two people is recommended for image acquisition: a certified retinal imager to capture images and NICU nurse to monitor the infant.²⁶¹ Initial education of imagers in the e-ROP study consisted of general training on ROP, premature infants, and image acquisition including positioning infants and maintaining comfort. On-site instruction was provided by the camera manufacturer, including hands-on training with the camera and practice with a model eye. Imagers were also trained on image selection, data entry, and export of images.

Certification in the e-ROP study consisted of knowledge assessments and a practical examination that included submitting three bilateral image sets per protocol from infants. Images were evaluated by the reading center and feedback was provided with additional image sets submitted until sufficient quality was obtained. After certification, feedback was provided to sites monthly during calls and yearly at group meetings. The authors found that it was important for imagers to frequently image a varied patient population to maintain optimal skills. The e-ROP study demonstrated a 92% success rate for nonphysician imagers providing acceptable quality images.

In addition, the KIDROP program has developed a 90-day training that is available through an e-learning platform “WISE-ROP.”^®262 Imagers read modules and complete quizzes to evaluate their progress. Video sessions and oral trainings are used to discuss the imagers’ technique and hands-on sessions are scheduled with an assigned mentor.

A rigorous training and certification program is necessary for implementation of telemedicine in ROP screening to ensure high-quality images are consistently acquired.

Imaging Systems

One of the major considerations in any ROP telemedicine program is the choice of digital imaging system. Until 2016, most reports on ROP telehealth programs used the RetCam^® system.^218,245 There are now several wide-field contact imaging systems on the market, although none have published clinical validation studies. The Visunex Panocam (Visunex Medical Systems, Inc., Fremont, CA) system has two cameras in its product line,²⁶³ a smaller portable system and a larger console system. The Phoenix ICON^® system, a contact wide-field cart-based system (Phoenix Technology Group, Pleasanton, CA), has also recently been introduced.²⁶⁴ The 3Nethra Neo^® (Forus Health, Bangalore, India), a 120° FOV, contact camera, has also recently been introduced.²⁶²

In a small pilot study of 128 premature infants from 35 NICUs, images acquired by both the Neo and RetCam were evaluated by two masked ROP specialists.²⁶⁵ The Neo was reported to have sensitivities of 97.4% and 99.3% and specificities of 81.1% and 75.6% for each grader, respectively. Since initial reporting, the study has been expanded to include 1,200 infants, but results are not yet published.

The Pictor^® (Volk Optical, Inc., Mentor, OH), a handheld noncontact fundus camera, has also been shown to be effective in screening for type 1 ROP and preplus and plus disease, despite its 45° FOV.^266,267 The Pictor was found to have 100% sensitivity by both graders and 93% and 74% specificity by each grader, respectively, when compared with clinical examinations.²⁶⁷ At ∼$10,000, the Pictor may make implementation of telemedicine ROP screening programs more widely accessible.²⁶⁷

With the introduction of new cameras to the commercial market, investigators have found entry prices to be 40–50% of the recent past prices,²⁶⁸ making remote ROP screening systems more widely accessible.

Guidelines for Reading Centers

Although current guidelines recommend that graders for telemedicine ROP screening programs be experienced ophthalmologists who have experience in bedside examination as well as interpretation of digital images, several studies have examined the efficacy of the use of nonphysician graders.²³⁷ Nonphysician graders in the e-ROP study underwent a three-phase process including training, precertification, and final certification.²⁶⁹ Phase 1 of training included lectures that covered classification of ROP, the study and grading protocol, and current ROP treatments, interactive sessions with sample images, and a visit to an NICU to observe the imaging process.

To progress to phase 2, graders were required to pass a knowledge assessment. Phase 2 included grading of an average of 15 image sets along with review and discussion of the results compared with an expert consensus generated final result. Phase 3 included grading of 100 ROP training image sets with additional images added until 85% agreement was met. Final certification consisted of 15 image sets from the e-ROP pilot submission and was earned once 80% agreement was met. If this level of agreement was not achieved, retraining was performed for 1 week and the final certification with new images was repeated. This process was repeated until 80% agreement was met. After using this system, the authors reported a weighted kappa of 0.72 for intergrader agreement for RW-ROP as well as weighted kappas ranging from 0.57 to 0.94 for intragrader agreement for RW-ROP.

Despite the current guideline recommendations for physicians to evaluate digital images, there is inconsistent training on ROP and no standardized method of assessing competency among ophthalmology residency and pediatric ophthalmology and retina fellowship programs.²⁷⁰ The Global Education Network-ROP group has created a tele-education program for ROP to further the education of physicians evaluating ROP images. The program includes a pretest, ROP tutorial on classification and management, five training chapters that each emphasize a particular category of ROP, and a post-test. This education system has been studied in two separate populations: 31 ophthalmology residents among 5 residency programs in the United States and 1 residency program in Canada and 58 ophthalmology residents and fellows from 1 program in Mexico.^270,271

Both studies found that the system was effective in improving diagnostic accuracy of ROP by ophthalmologists-in-training. Although this program has limitations, such as not tracking common errors made by trainees and not including examples of stage 4 or stage 5 ROP, the authors feel that improvements can be made and that this platform has potential to be used in a widespread manner to standardize evaluation of ROP images for both physician and nonphysician graders. Appropriate training of both physician and nonphysician graders is essential to ensure patient safety.

Automated Image Analysis

In concert with early reports of successful application of retinal photographic screening for ROP, interest in automated image analysis for image interpretation was also evident. Several earlier groups sought to determine whether the vascular tortuosity of plus disease could be segmented in an automated or semiautomated manner.^272,273

Subsequently, several groups focused on integrated grading systems. Ataer-Cansizoglu et al., who are part of the i-ROP consortium, reported on their validation study in which 77 wide-angle images were graded by a computer algorithm “developed to extract tortuosity and dilation features from arteries and veins.”²⁷⁴ The algorithm grades were compared with a reference standard diagnosis generated by combining three independent expert image grades with the diagnosis rendered during a live BIO examination. The investigators found that their system was 95% accurate for the classification of preplus and plus disease, which compared favorably with the individual accuracy of the expert grades and was substantially higher than the mean accuracy of 31 nonexperts.

The i-ROP consortium also evaluated the methods physicians currently use when diagnosing ROP to further understand what may work best in an automated system. They found that ROP experts consider tortuosity of both arteries and veins and also consider areas outside the central retina when diagnosing plus disease, contrary to the International Classification of Retinopathy of Prematurity standards.²³³ They found that the performance of the i-ROP CBIA performed better than 9 of 11 experts in the study with 95% accuracy for diagnosis of plus disease when using a larger FOV than recommended and considering all vessels.²³³

Abbey et al. have also recently reported their validation of the ROPtool system.²⁷⁵ For this study, 335 fundus photographs were collaboratively assessed by a panel of three ROP experts to generate the criterion standard grade. Each quadrant was graded on a 5-point scale that incorporated tortuosity and dilatation. If any quadrant was graded as questionable or worse, then the image was classified as abnormal. The ROPtool system calculates the tortuosity of a single vessel within each quadrant and the value for the second most tortuous segment is defined as the tortuosity score for that eye. Dilation was also assessed, but this did not improve their model accuracy and was not presented.

The authors then examined multiple diagnostic set points through ROC. Optimizing sensitivity and including unreadable images as diseased, ROPtool had a sensitivity of 96% and specificity of 64%. The clinical utility of the proxy of tortuosity used as the criterion standard for this validation was not discussed.

More recently, deep learning, where CBIA systems have been trained to automatically recognize and evaluate images, has been used for ROP screening.^276,277 Deep learning allows the system to continually learn and re-evaluate its process autonomously and consists of multiple layers of algorithms that data flow through to form neural networks.²⁷⁷ CNNs have to be trained through exposure to a large number and variety of pathological and normal images to then apply a series of filters to produce the desired output, which in this case would be diagnosis or classification of ROP.^277,278

The i-ROP consortium has developed a deep learning algorithm, which has shown a high accuracy for identifying plus disease.²⁷⁸ The system was trained using a set of 5,511 retinal images that had been obtained as part of the i-ROP study and a reference standard diagnosis established by three trained graders and one expert clinical examiner. The system was able to diagnose plus disease on an independent set of 100 images with 93% sensitivity and 94% specificity and preplus disease or worse with 100% sensitivity and 94% specificity. The algorithm out-performed six of eight ROP experts and all prior computer-based imaging analysis systems in ROP without the need for manual segmentation.²⁷⁸

After the algorithm was trained to recognize plus disease, the authors also tested its ability to identify diagnostic categories and overall disease severity. After analysis of 4,861 images, they found that the system could accurately detect clinically significant ROP with 94% sensitivity and a 99.7% negative predictive value based on posterior pole fundus photographs alone.²⁷⁶

Wang et al. also developed two deep neural networks, Id-Net and Gr-Net, which were, respectively, designed for the identification and grading of ROP.²⁷⁹ Id-Net achieved a sensitivity of 96.62% and specificity of 99.32% for identification of any ROP, and Gr-Net achieved 88.46% sensitivity and 92.31% specificity for grading of ROP severity, which was comparable with three expert graders.

Zhang et al. have also evaluated three general-purposed deep neural networks (AlexNet, GoogLeNet, and VGG16) using a transfer learning workflow with 17,801 images to identify ROP.²⁸⁰ They found that VGG16 achieved the best performance on a test set of 1,742 images and found that this performance was comparable with that of five pediatric ophthalmologists.

The use of CBIA systems in ROP screening could help improve the accuracy and consistency of diagnosis of ROP.

Safety of Retinal Imaging in ROP

Although many remain skeptical of the safety of remote ROP imaging and grading of images,²³⁸ several studies have reported low frequencies of AEs associated with retinal imaging. In the e-ROP study, one-third of AEs were reported to have probably or definitely been related to BIO (4 AEs) or contact imaging (18 AEs).²⁸¹ Based on the low frequency of AEs (65 AEs reported >4,238 visits) and serious AEs (none) reported in the e-ROP study, the authors considered both BIO and imaging to be safe methods of ROP screening.²⁸¹

Prakalapakorn et al., who have examined the use of the Pictor noncontact fundus camera, also found that safety events (clinically significant bradycardia, tachycardia, oxygen desaturation, or apnea) occurred after 5.8% of clinical examinations and after 0.8% of imaging sessions.²⁸² Because the noncontact camera did not require a use of a lid speculum or contact with the cornea, the authors felt that the process was less stressful for infants.

Despite the survey finding in which only 30% of NICU directors felt that telemedicine for ROP screening was safe, studies evaluating AEs surrounding the use of ROP imaging have so far found low incidences of AEs.

Costs of Remote ROP Screening

A major barrier to implementation of telemedicine in general is the high startup cost. Within ocular telehealth, the retinal cameras needed for imaging premature infants are costlier than the nonmydriatic devices used to image adults with diabetes, but costs are decreasing with the release of new cameras, such as the Neo, and expansion to nontraditional cameras, such as the Pictor.

Several cost-effectiveness analyses have been published exploring different scenarios for ROP screening. Jackson et al. performed a cost–utility analysis of telemedicine and standard ophthalmoscopy compared with no treatment from a third-party perspective.²⁸³ This group found that the cost per QALY gained was $3,193 for telehealth screening compared with $5,617 with standard ophthalmoscopy.

Varying several aspects within the simulation generated wide variations from their base case (up to $18,989 per QALY gained for telehealth and $27,215 for ophthalmoscopy), but the interventions remained below the previously described threshold of a highly cost-effective intervention of $50,000/QALY. Because the perspective chosen for this analysis (third-party payer) does not include the costs of acquiring the retina cameras and telehealth connectivity, the results are valuable in convincing policy makers and insurers of the value of the intervention, but do not necessarily speak of the viability of establishing a telehealth program for hospitals.

Castillo-Riquelme et al. likewise performed a cost-effectiveness of retinal photographs screening for ROP in the United Kingdom.²⁸⁴ This simulation study compared five different screening strategies and used a health system perspective. The investigators estimated that the current methods cost GBP 321 to screen one infant and that if a specialist nurse were to travel among NICUs to capture and interpret images, this would be substantially less expensive (GBP 172 per infant or GBP 201 if the images were transmitted for ophthalmologist review).

Other methods explored in their simulation would be more expensive: use of a standard camera with NICU nurses acquiring and interpreting the images (GBP 371) or transmitting the images for ophthalmologist review (GBP 390). Throughout the sensitivity analysis, the least expensive method was largely unchanged, unless the cost of the visiting nurse was almost at the extreme high end of the sensitivity range or the specificity of nurse interpretation was 40% or less (99% was used in the base case). Of note, if the sensitivity dipped slightly <90%, the standard examination strategy was noted to be “cost-effective.” The authors suggest that development of a portable imaging solution could dramatically change the cost-effectiveness landscape. The results may be difficult to apply to other settings without a national health system.

Makkar et al. noted that implementing telemedicine examinations for ROP in a level II NICU reduced costs associated with transport, decreased the length of hospitalization, and decreased the use of higher levels of care than needed.²⁸⁵ They also noted that the current telemedicine reimbursement rate for digital retinal examinations does not cover the cost of required effort (∼1 h of total processing time for each infant imaged).

Conclusions

As the preceding discussion illustrates, the ocular telehealth paradigm for ROP is different from remote screening for DR as discussed in the body of these guidelines. The population at risk is hospitalized low-birth weight premature infants, so the technical aspects of image acquisition need to account for the NICU environment and the anatomy of the neonatal eye. For ROP, the burden of screening largely falls on the providers and health systems rather than on patients to present for opportunistic screening. Perhaps the most critical difference is the time course of vision loss and prognosis for eyes in which the ROP diagnosis is not made in a timely manner. Unlike in DR, very high sensitivities for vision-threatening disease must be achieved because the risk of near-term potentially permanent vision loss is unacceptably high.

In addition to the challenges posed by ROP for effective ocular telehealth, there are opportunities that are unique to ROP. Because the screenings are done in a controlled environment, universal coverage of screening should be far easier to achieve than in DR, and technical issues with equipment may be easier to deal with in the NICU environment with access to hospital IT and biomedical engineering departments. DR telehealth screening programs sometimes are met with resistance from primary eye care providers as the programs can be seen as a threat to patient volumes and revenue streams. ROP screenings, in contrast, are often a challenge for hospitals to find appropriate coverage and could provide more convenience to treating providers rather than “competition.”

Finally, there may be medical–legal benefits to photo-documentation of ROP examination findings, particularly if there are automated aids to image classification or decision support within the grading software.

Any ROP screening implementation using telehealth should follow the screening recommendations of the major societies of the region.²³⁵ Retinal images must be of sufficient quality to allow a grader to make an accurate determination of the ROP status. Different groups have used different diagnostic set points as already discussed, so any program must validate to their predetermined level of disease severity, analogous to the recommendations made in the body of this document for DR.

The majority of research to date has used contact wide-field imaging, but research is ongoing to determine the value of noncontact posterior pole imaging to detect plus disease to screen for RW-ROP.²⁸⁶ Because the volume of babies requiring imaging in a given center may be lower than what is seen in DR screening, deliberate efforts should be taken so that imagers maintain skills. Further technical guidance is provided in a 2015 Joint Technical Report of the American Academy of Pediatrics, the American Academy of Ophthalmology, and the American Association of Certified Orthoptists.²²⁹

Disclosure Statement

J.P.C. receives grant support from Genentech, and is listed on a preliminary patent application related to deep learning technology for ROP screening.

Funding Information

C.J.B. was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P20GM103644. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. S.D. was supported in part by the Elliot W. Shipman Professorship Fund. J.P.C. was supported by National Institutes of Health grants R01EY19474, P30EY10572, and K12EY27720 (Bethesda, MD), National Science Foundation grant SCH-1622679 (Arlington, VA), and unrestricted departmental funding and a Career Development Award (JPC) from Research to Prevent Blindness (New York, NY).

Appendix A11. Telemedicine for Age-Related Macular Degeneration

Christopher J. Brady, MD, MHS,¹ and Seema Garg, MD, PhD²

¹Division of Ophthalmology, Department of Surgery, Larner College of Medicine, University of Vermont Medical Center, Burlington, Vermont.

²Department of Ophthalmology, University of North Carolina, School of Medicine, Chapel Hill, North Carolina.

Introduction

AMD is the leading cause of vision loss in the United States.²⁸⁷ As such, the disease presents an appropriate target for ocular telehealth interventions. Unlike DR, there is no consensus about the utility of population screening for AMD.²⁸⁸ Some groups have found value by adding screening for AMD to existing DR screening programs,^289,290 but others have not found screening programs for AMD to be cost-effective.²⁹¹ Several groups have investigated the feasibility and validity of telehealth programs for AMD. Owing to the uncertainty of the role of screening for AMD, several groups have explored other telehealth paradigms for this disease.

Clinical Feasibility

Although the official gold standard for DR diagnosis is seven-field, ETDRS stereoscopic fundus photography, the benchmark for the diagnosis of AMD remains a combination of clinical examination, and fluorescein angiography and OCT. Therefore, several groups have sought to validate the use of fundus photographs for the diagnosis of AMD through the detection of characteristic lesions of AMD (drusen, hyperpigmentation, CNVM, and geographic atrophy [GA]). Specifically as it relates to the presence of CNVM, a retrospective analysis of stereoscopic images of 127 fellow eyes from the Macular Photocoagulation Study correctly identified all 30 eyes that developed CNVM as defined by the fluorescein angiogram.²⁹²

To determine the accuracy of diagnosing AMD with monoscopic images alone, Scholl et al. at Moorfields Eye Hospital compared digitized color, mydriatic, monoscopic images with stereoscopic 35 mm slides and found an agreement of 83–93% for the presence or absence of intermediate drusen depending on the macular subfield examined.²⁹³ Furthermore, they found agreement of 94–96% for GA and 94–98% for CNVM.

Pirbhai et al. conducted a prospective comparison of mydriatic monoscopic color fundus photographs with conventional clinical evaluation and fluorescein angiography.²⁹⁴ In this study, the diagnoses rendered on the basis of the monoscopic images were 89.2% sensitive and 85.7% specific. Clinical recommendations based on the monoscopic images corresponded to the gold standard clinical examination 80.3% of the time. The kappa statistic is frequently used to test inter-rater reliability and can range from −1.0 to 1.0. In this study, the kappa was 0.59, which the authors concluded was evidence of good agreement.²⁹⁴

In another study, Duchin et al.²⁹⁵ compared nonmydriatic fundus images with a conventional clinical dilated fundus examination with a retina specialist. In 94 eyes of 47 patients,²⁹⁵ they found sensitivity for referable AMD (Age-Related Eye Disease Study [AREDS] grading level 3 or greater) to be 84–88% and specificity of 81% between their two expert graders. Of note, the authors used their existing telemedicine infrastructure for DR screening.

Clinical Experience

To expand upon feasibility studies, several groups have implemented ocular telehealth programs for AMD. In a randomized controlled trial, participants referred for possible or established neovascular AMD were randomly assigned to either conventional clinical examination or image acquisition and remote interpretation at an ocular telehealth site.²⁹⁶ Data collected included best-corrected visual acuity, intraocular pressure, color fundus photographs (mydriatic status not specified in publication, but clarified as dilated by senior article author, Dr. Thomas Sheidow, pers. comm., February 9, 2018) and OCT.

These data were transmitted to retina specialists at a tertiary referral site. They found no delay in presentation for care in the telescreening group, but did note increased interval between detection and reinitiation of therapy in participants with established AMD. They did not detect any adverse outcomes in terms of visual acuity attributable to this delay in this small study.

Another in situ study was performed by De Bats et al. in Lyon, France.²⁹⁷ In this study, 1,022 individuals were screened for known presence of AMD and absence of comorbidity that would preclude AMD management, of whom 683 were eligible and interested in participating. Nonmydriatic color photographs were then taken at two community health examination centers and then transmitted for grading by an ophthalmologist. Images were gradable in 80% of the 1,363 images acquired, and AMD was diagnosed in 178 eyes. There was no gold standard assessment of participants in this study.

As in DR, ROP, and other retinal conditions, there is growing interest in the use of AI systems for image processing and interpretation.²⁹⁸ Such systems may allow for more rapid/instantaneous grading of images with accuracy similar to expert human grading. Investigators have used a variety of public and private data sets including the Singapore Integrated Diabetic Retinopathy Screening Programme¹³⁶ and the AREDS^299,300 to train deep learning algorithms to identify features of AMD on color fundus photographs. Other groups have likewise used deep learning approaches to identify AMD on OCT images.^301,302 At the time of this writing, no AI system is FDA approved for AMD.

Remote Monitoring

Several groups have looked to other telehealth paradigms beyond store-and-forward remote screening/detection, such as remote monitoring. Andonegui et al. sought to determine whether ancillary testing performed without a live examination could allow clinicians to reach a similar assessment and plan to that diagnostic decisions based on a live examination.³⁰³ In this study, 201 participants with exudative AMD who had received a minimum of three prior ranibizumab injections initially had a live examination with spectral domain OCT (SD-OCT), fundus photography, and visual acuity measurements. Antivascular endothelial growth factor (VEGF) retreatment decisions were made based on this live examination and recorded.

At least 4 weeks later, the ancillary data were anonymized and randomly distributed to the same two retina physicians who had seen them previously. A retreatment decision was then rendered and recorded based on this “remotely acquired” clinical data, simulating a telehealth encounter. The same treatment decision was reached in 90% of cases, with 8% of patients receiving “false-positive” (i.e., the remote decision was to retreat, but the live decision was to defer), and 1% receiving a “false-negative” (i.e., the remote decision was to defer, but the live decision was to treat).

Moving further away from remote image acquisition and transmission, Azzolini et al. sought to determine whether an e-health decision support tool could help general ophthalmologists follow AMD patients without referral.³⁰⁴ General ophthalmologists could enter in patient age, visual acuity, Amsler grid results, presence of macular hemorrhage, and fellow eye status. A risk score for active exudation is calculated, and the general provider can directly schedule with a retinal provider in instances of high risk. A comparison of consecutive patients undergoing usual care was also established.

During the study period, 360 patients with known AMD were examined within the network. Of these, 310 were judged high risk of disease progression, and referred for a live examination. Of these, 276 received intravitreal anti-VEGF therapy. There was less of a delay before initiating therapy in the “network” as compared with the usual care patients, and all providers judged the system to be “good” or “very good.” The validation of risk score is listed as “unpublished data” and the 50 patients with low-risk scores were not examined in this study.

Another approach at remote monitoring using a consumer device was explored in the AREDS 2 study.³⁰⁵ In this study, participants with nonexudative AMD at high risk for developing choroidal neovascularization (CNV) were randomized to either use the ForeseeHome device daily at home or to standard-of-care symptom monitoring. The device tests macular visual field using hyperacuity techniques, and sent an alert to investigators if a substantial change was noted. During a prespecified interim analysis, a statistically significant smaller decline in visual acuity was noted at the time of diagnosis of active CNV in the ForseeHome group as compared with standard-of-care monitoring. For this reason, early termination for efficacy was recommended. After FDA approval of the device, a cost-effectiveness analysis from a federal government perspective found that home telemonitoring of patients at high risk for CNV was cost-effective compared with biannual in-person examination.³⁰⁶

Conclusions

Across a range of studies, then, numerous different ocular telehealth strategies have been tested for AMD. Because of the lack of well-defined high-risk population, merely extending existing DR screening pathways to screen for AMD is not currently in use, nor recommended. Ocular telehealth for AMD is likely to require expansion of the remote screening tool kit of a network-connected nonmydriatic fundus camera to include technologies such as OCT and possibly OCT angiography. As new strategies are tested in high-quality studies, and as the population ages, and the burden of AMD increases, there will likely be opportunities for remote monitoring, either through teleconsultation with general medical providers or optometric or general ophthalmologic providers, or through consumer facing home monitoring. Indeed, finding solutions to the challenges of remote detection and management of AMD may allow for the generalization of ocular telehealth methods to a number of different conditions, and may help usher the field away from a disease-specific paradigm.

Disclosure Statement

No competing financial interests exist.

Funding Information

C.J.B. was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P20GM103644. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.