Quality Management System in Clinical Digital Pathology Operations at a Tertiary Cancer Center.

Digital pathology workflows can improve pathology operations by allowing reliable and fast retrieval of digital images, digitally reviewing pathology slides, enabling remote work and telepathology, use of computer-aided tools, and sharing of digital images for research and educational purposes. The need for quality systems is a prerequisite for successful clinical-grade digital pathology adoption and patient safety. In this article, we describe the development of a structured digital pathology laboratory quality management system (QMS) for clinical digital pathology operations at Memorial Sloan Kettering Cancer Center (MSK). This digital pathology-specific QMS development stemmed from the gaps that were identified when MSK integrated digital pathology into its clinical practice. The digital scan team in conjunction with the Department of Pathology and Laboratory Medicine quality team developed a QMS tailored to the scanning operation to support departmental and institutional needs. As a first step, systemic mapping of the digital pathology operations identified the prescan, scan, and postscan processes; instrumentation; and staffing involved in the digital pathology operation. Next, gaps identified in quality control and quality assurance measures led to the development of standard operating procedures and training material for the different roles and workflows in the process. All digital pathology-related documents were subject to regulatory review and approval by departmental leadership. The quality essentials were developed into an extensive Digital Pathology Quality Essentials framework to specifically address the needs of the growing clinical use of digital pathology technologies. Using the unique digital experience gained at MSK, we present our recommendations for QMS for large-scale digital pathology operations in clinical settings.

Clinical Validation of Stimulated Raman Histology for Rapid Intraoperative Diagnosis of Central Nervous System Tumors.

Stimulated Raman histology (SRH) is an ex vivo optical imaging method that enables microscopic examination of fresh tissue intraoperatively. The conventional intraoperative method uses frozen section analysis, which is labor and time intensive, introduces artifacts that limit diagnostic accuracy, and consumes tissue. SRH imaging allows rapid microscopic imaging of fresh tissue, avoids tissue loss, and enables remote telepathology review. This improves access to expert neuropathology consultation in both low- and high-resource practices. We clinically validated SRH by performing a blinded, retrospective two-arm telepathology study to clinically validate SRH for telepathology at our institution. Using surgical specimens from 47 subjects, we generated a data set composed of 47 SRH images and 47 matched whole slide images (WSIs) of formalin-fixed, paraffin-embedded tissue stained with hematoxylin and eosin, with associated intraoperative clinicoradiologic information and structured diagnostic questions. We compared diagnostic concordance between WSI and SRH-rendered diagnoses. Also, we compared the 1-year median turnaround time (TAT) of intraoperative conventional neuropathology frozen sections with prospectively rendered SRH-telepathology TAT. All SRH images were of sufficient quality for diagnostic review. A review of SRH images showed high accuracy in distinguishing glial from nonglial tumors (96.5% SRH vs 98% WSIs) and predicting final diagnosis (85.9% SRH vs 93.1% WSIs). SRH-based diagnosis and WSI-permanent section diagnosis had high concordance (κ = 0.76). The median TAT for prospectively SRH-rendered diagnosis was 3.7 minutes, approximately 10-fold shorter than the median frozen section TAT (31 minutes). The SRH-imaging procedure did not affect ancillary studies. SRH generates diagnostic virtual histologic images with accuracy comparable to conventional hematoxylin and eosin-based methods in a rapid manner. Our study represents the largest and most rigorous clinical validation of SRH to date. It supports the feasibility of implementing SRH as a rapid method for intraoperative diagnosis complementary to conventional pathology laboratory methods.

Increasing access to pathology services in low- and middle-income countries through innovative use of telepathology.

INTRODUCTION: In low- and middle-income countries (LMICs), surgical care can be limited by access to pathology services. In Uganda, the pathologist-to-population ratio is less than 1 to 1 million people. The Kyabirwa Surgical Center in Jinja, Uganda, created a telepathology service in collaboration with an academic institution in New York City. This study demonstrated the feasibility and considerations of implementing a telepathology model to supplement the critical pathology needs of a low-income country. METHODS: This was a retrospective, single-center study of an ambulatory surgery center with pathology capability using virtual microscopy. The remote pathologist (also known as a telepathologist) controlled the microscope and reviewed histology images transmitted across the network in real time. In addition, this study collected demographics, clinical histories, the surgeon's preliminary diagnoses, and the pathology reports from the center's electronic medical record. RESULTS: Nikon's NIS Element Software was used as a dynamic, robotic microscopy model with a video conferencing platform for communication. An underground fiber optic cable established Internet connectivity. After a two-hour tutorial session, the lab technician and pathologist were able to proficiently use the software. The remote pathologist read (1) pathology slides with inconclusive reports from external pathology labs, and (2) tissues labeled by the surgeon as suspicious for malignancy, which belonged to patients who lacked financial means for pathology services. Between April 2021 and July 2022, tissue samples of 110 patients were examined by a telepathologist. The most common malignancies on histology were squamous cell carcinoma of the esophagus, ductal carcinoma of the breast, and colorectal adenocarcinoma. CONCLUSION: With the increasing availability of video conference platforms and network connections, telepathology is an emerging field that can be used by surgeons in LMICs to improve access to pathology services, confirming histological diagnosis of malignancies to ensure appropriate treatment.

Visual-spatial dimension integration in digital pathology education enhances anatomical pathology learning.

Literature review demonstrated a surprising lack of publications on digital e-learning pathology resources for senior medical undergraduates and interns. An interactive Digital Pathology Repository (iDPR) integrating two- and three-dimensional (2D, 3D) high-resolution anatomical pathology images with correlated digital histopathology was developed. The novel iDPR was rigorously evaluated using mixed methods to assess pathology knowledge gains (pre- and post-tests), quality impact analysis (questionnaire), user feedback (focus group discussions) and user visual behaviour (eye gaze tracking analysis of 2D/ 3D images).Exposure to iDPR appeared to improve user pathology knowledge, as observed by significantly increased test scores on topic-related quizzes (n = 69, p < 0.001). In addition, most users were highly satisfied with the key design elements of the iDPR tool. Focus group discussion revealed the iDPR was regarded as a relevant online learning resource, although some minor technical issues were also noted. Interestingly, visual behaviour trends indicated that specific diagnostic pathological lesions could be correctly identified faster in 3D images, when compared to 2D images.The iDPR offers promise and potential in pathology education for senior clinical students and interns, gauging from both qualitative and quantitative positive user feedback. With incorporation of image annotations and interactive functionality, and with further technology development, this would prove a useful tool for diagnostic pathology and telepathology. As images with added visual-spatial dimension can provide enhanced detail and aid more rapid diagnosis, future applications of the iDPR could include virtual reality or holographic images of anatomical pathology specimens.

Validation of a digital pathology system including remote review during the COVID-19 pandemic.

Remote digital pathology allows healthcare systems to maintain pathology operations during public health emergencies. Existing Clinical Laboratory Improvement Amendments regulations require pathologists to electronically verify patient reports from a certified facility. During the 2019 pandemic of COVID-19 disease, caused by the SAR-CoV-2 virus, this requirement potentially exposes pathologists, their colleagues, and household members to the risk of becoming infected. Relaxation of government enforcement of this regulation allows pathologists to review and report pathology specimens from a remote, non-CLIA certified facility. The availability of digital pathology systems can facilitate remote microscopic diagnosis, although formal comprehensive (case-based) validation of remote digital diagnosis has not been reported. All glass slides representing routine clinical signout workload in surgical pathology subspecialties at Memorial Sloan Kettering Cancer Center were scanned on an Aperio GT450 at ×40 equivalent resolution (0.26 µm/pixel). Twelve pathologists from nine surgical pathology subspecialties remotely reviewed and reported complete pathology cases using a digital pathology system from a non-CLIA certified facility through a secure connection. Whole slide images were integrated to and launched within the laboratory information system to a custom vendor-agnostic, whole slide image viewer. Remote signouts utilized consumer-grade computers and monitors (monitor size, 13.3-42 in.; resolution, 1280 × 800-3840 × 2160 pixels) connecting to an institution clinical workstation via secure virtual private network. Pathologists subsequently reviewed all corresponding glass slides using a light microscope within the CLIA-certified department. Intraobserver concordance metrics included reporting elements of top-line diagnosis, margin status, lymphovascular and/or perineural invasion, pathology stage, and ancillary testing. The median whole slide image file size was 1.3 GB; scan time/slide averaged 90 s; and scanned tissue area averaged 612 mm2. Signout sessions included a total of 108 cases, comprised of 254 individual parts and 1196 slides. Major diagnostic equivalency was 100% between digital and glass slide diagnoses; and overall concordance was 98.8% (251/254). This study reports validation of primary diagnostic review and reporting of complete pathology cases from a remote site during a public health emergency. Our experience shows high (100%) intraobserver digital to glass slide major diagnostic concordance when reporting from a remote site. This randomized, prospective study successfully validated remote use of a digital pathology system including operational feasibility supporting remote review and reporting of pathology specimens, and evaluation of remote access performance and usability for remote signout.

Whole-slide Imaging: Clinical Workflows and Primary Diagnosis.

Digital pathology has made great strides in recent years culminating with the approval to market devices from the Food and Drug Administration. The pathology community is now poised to begin using these systems for diagnostic purposes. This article will discuss the preparatory steps needed to implement digital pathology as well as some implementation styles that may be sufficient for a pathology department.

Whole Slide Imaging: Technology and Applications.

Pathology has benefited from advanced innovation with novel technology to implement a digital solution. Whole slide imaging is a disruptive technology where glass slides are scanned to produce digital images. There have been significant advances in whole slide scanning hardware and software that have allowed for ready access of whole slide images. The digital images, or whole slide images, can be viewed comparable to glass slides in a microscope, as digital files. Whole slide imaging has increased in adoption among pathologists, pathology departments, and scientists for clinical, educational, and research initiatives. Worldwide usage of whole slide imaging has grown significantly. Pathology regulatory organizations (ie, College of American Pathologists) have put forth guidelines for clinical validation, and the US Food and Drug Administration have also approved whole slide imaging for primary diagnosis. This article will review the digital pathology ecosystem and discuss clinical and nonclinical applications of its use.

Efficiency of Mobile Video Sharing Application (WhatsApp®) in Live Field Image Transmission for Telepathology.

Telepathology is in its nascent stages in India. Video calling applications in mobile phones can be efficiently used to transmit static and live field microscopic images hastening low cost telepathology. To evaluate the efficiency of WhatsApp® Video Calling for dynamic microscopy in distant diagnosis. Thirty haematoxylin and eosin stained slides of common pathologies were retrieved from the archives of Department of Oral Pathology and Microbiology, coded with relevant history and given to three untrained investigators. The investigators then connected a mobile phone with VOIP facility to a microscope using a custom adaptor. Dynamic fields were transferred to three independent pathologists via WhatsApp® video call. The pathologists attempted to diagnose the lesion based on the live field video over their display screen (phone). Audio quality was found to be better than that of video. In 70% of the cases, pathologists could render a diagnosis (13% gave a confirmed diagnosis, 57.7% gave a probable diagnosis). The average time taken for connecting the adaptor, connecting the call to the pathologist and then receiving the diagnosis was 9:30 min. In addition, proper history taking and staining of the tissue slides were critical to arrive at the diagnosis. WhatsApp® free VOIP facility helped untrained investigators to send the live-field pathologic fields to a specialist rendering histopathological diagnosis. The factors affecting the diagnosis included network stability, clarity of images transmitted, staining quality and contrast of nuclear details of the stain. The history, clinico-pathologic correlation, transmission of static images, training of the person transmitting the images plays a vital role in rendering accurate diagnosis. Telepathology over WhatsApp® video calling could be used as an efficient screening tool to identify suspicious lesions and follow-up critical cases.

Pathology and Telepathology Methods in the Child Health and Mortality Prevention Surveillance Network.

This manuscript describes the Child Health and Mortality Prevention Surveillance (CHAMPS) network approach to pathologic evaluation of minimally invasive tissue sampling (MITS) specimens, including guidelines for histopathologic examination and further diagnostics with special stains, immunohistochemistry, and molecular testing, as performed at the CHAMPS Central Pathology Laboratory (CPL) at the Centers for Disease Control and Prevention, as well as techniques for virtual discussion of these cases (telepathology) with CHAMPS surveillance locations. Based on review of MITS from the early phase of CHAMPS, the CPL has developed standardized histopathology-based algorithms for achieving diagnoses from MITS and telepathology procedures in conjunction with the CHAMPS sites, with the use of whole slide scanners and digital image archives, for maximizing concurrence and knowledge sharing between site and CPL pathologists. These algorithms and procedures, along with lessons learned from initial implementation of these approaches, guide pathologists at the CPL and CHAMPS sites through standardized diagnostics of MITS cases, and allow for productive, real-time case discussions and consultations.

Whole slide imaging equivalency and efficiency study: experience at a large academic center.

Whole slide imaging is Food and Drug Administration-approved for primary diagnosis in the United States of America; however, relatively few pathology departments in the country have fully implemented an enterprise wide digital pathology system enabled for primary diagnosis. Digital pathology has significant potential to transform pathology practice with several published studies documenting some level of diagnostic equivalence between digital and conventional systems. However, whole slide imaging also has significant potential to disrupt pathology practice, due to the differences in efficiency of manipulating digital images vis-à-vis glass slides, and studies on the efficiency of actual digital pathology workload are lacking. Our randomized, equivalency and efficiency study aimed to replicate clinical workflow, comparing conventional microscopy to a complete digital pathology signout using whole slide images, evaluating the equivalency and efficiency of glass slide to whole slide image reporting, reflective of true pathology practice workloads in the clinical setting. All glass slides representing an entire day's routine clinical signout workload for six different anatomic pathology subspecialties at Memorial Sloan Kettering Cancer Center were scanned on Leica Aperio AT2 at ×40 (0.25 µm/pixel). Integration of whole slide images for each accessioned case is through an interface between the Leica eSlide manager database and the laboratory information system, Cerner CoPathPlus. Pathologists utilized a standard institution computer workstation and viewed whole slide images through an internally developed, vendor agnostic whole slide image viewer, named the "MSK Slide Viewer". Subspecialized pathologists first reported on glass slides from surgical pathology cases using routine clinical workflow. Glass slides were de-identified, scanned, and re-accessioned in the laboratory information system test environment. After a washout period of 13 weeks, pathologists reported the same clinical workload using whole slide image integrated within the laboratory information system. Intraobserver equivalency metrics included top-line diagnosis, margin status, lymphovascular and/or perineural invasion, pathology stage, and the need to order ancillary testing (i.e., recuts, immunohistochemistry). Turnaround time (efficiency) evaluation was defined by the start of each case when opened in the laboratory information system and when the case was completed for that day (i.e., case sent to signout queue or pending ancillary studies). Eight pathologists participated from the following subspecialties: bone and soft tissue, genitourinary, gastrointestinal, breast, gynecologic, and dermatopathology. Glass slides signouts comprised of 204 cases, encompassing 2091 glass slides; and digital signouts comprised of 199 cases, encompassing 2073 whole slide images. The median whole slide image file size was 1.54 GB; scan time/slide, 6 min 24 s; and scan area 32.1 × 18.52 mm. Overall diagnostic equivalency (e.g., top-line diagnosis) was 99.3% between digital and glass slide signout; however, signout using whole slide images showed a median overall 19% decrease in efficiency per case. No significant difference by reader, subspecialty, or specimen type was identified. Our experience is the most comprehensive study to date and shows high intraobserver whole slide image to glass slide equivalence in reporting of true clinical workflows and workloads. Efficiency needs to improve for digital pathology to gain more traction among pathologists.

Being fully digital: perspective of a Dutch academic pathology laboratory.

The introduction of fast and robust whole slide scanners has facilitated the implementation of 'digital pathology' with various uses, the final challenge being full digital diagnostics. In this article, we describe the implementation process of a fully digital workflow for primary diagnostics in 2015 at the University Medical Centre in Utrecht, The Netherlands, as one of the first laboratories going fully digital with a future-proof complete digital archive. Furthermore, we evaluated the experience of the first 2 years of working with the system by pathologists and residents. The system was successfully implemented in 6 months, including a European tender procedure. Most pathologists and residents had high confidence in working fully digitally, the expertise areas lagging behind being paediatrics, haematopathology, and neuropathology. Reported limitations concerned recognition of microorganisms and mitoses. Neither the age of respondents nor the number of years of pathology experience was correlated with the confidence level regarding digital diagnostics. The ergonomics of digital diagnostics were better than those of traditional microscopy. In this article, we describe our experiences in implementing our fully digital primary diagnostics workflow, describing in depth the implementation steps undertaken, the interlocking components that are required for a fully functional digital pathology system (laboratory management, hospital information systems, data storage, and whole slide scanners), and the changes required in workflow and slide production.

Digital pathology is a practical alternative to on-site intraoperative frozen section diagnosis in thoracic surgery.

AIMS: Telepathology uses digitised image transfer to allow off-site reporting of histopathology slides. This technology could facilitate the centralisation of pathology services, which may improve their quality and cost-effectiveness. The benefits may be most apparent in frozen section reporting, in which turnaround times (TATs) are vital. We moved from on-site to off-site telepathology reporting of thoracic surgery frozen section specimens in 2016. The aim of this study was to compare TATs before and after this service change. METHODS AND RESULTS: All thoracic frozen section specimens analysed 4 months prior and 4 months following the service change were included. Demographics, operation, sample type, time taken from theatre, time received by laboratory, time reported by laboratory, TAT, frozen section diagnosis, final histopathological diagnosis and final TNM staging were recorded. The results were analysed with spss statistical software version 24. In total, there were 65 samples from 59 patients; 34 before the change and 31 after the change. Specimens included 51 lung, six lymph node, three bronchial, three chest wall and two pleural biopsies. Before the change, the median TAT was 25 min [interquartile range (IQR) 20-33 min]. No diagnoses were deferred. No diagnoses were changed on subsequent paraffin analysis. After the change, with the use of digital pathology, the median TAT was 27.5 min (IQR 21.75-38.5 min). This difference was not significant (P = 0.581). Diagnosis was deferred in one case (3.23%). There was one (3.23%) mid-case technical failure resulting in the sample having to be transported by courier, resulting in a TAT of 106 min. No diagnoses were changed on subsequent paraffin analysis. CONCLUSIONS: There was no significant difference in reporting times between digital technology and an on-site service, although one sample was affected by a technical failure requiring physical transportation of the specimen for analysis. Our study was underpowered to detect differences in accuracy.

Practice of Teledermatopathology: A Systematic Review.

INTRODUCTION: Teledermatopathology has the potential to revolutionize the practice of diagnosing skin diseases. This review provides an overview of the advantages, limitations, and future directions of teledermatopathology. METHODS: MEDLINE was searched via PubMed and Google Scholar databases for relevant articles published from 2012 to the present. Additional articles were also identified by hand-searching. RESULTS: A total of 2675 citations were identified in the initial search. Two thousand five hundred seventy-three were excluded based on duplicates and review of titles and abstracts. Eighty studies failed to meet the inclusion criteria, resulting in a total of 22 articles for analysis. Nine additional articles were hand-searched. CONCLUSIONS: Recent studies report that telepathology increases access to specialists, reduces interpretive errors and health care expenditures, improves the efficiency of workflow, and optimizes patient outcomes. It also facilitates international collaboration by widening global access to dermatopathology services and providing educational resources in underserved areas. However, the quality and regulations of digital slide imaging in teledermatopathology need to be improved.

Digital pathology in clinical use: where are we now and what is holding us back?

Whole slide imaging is being used increasingly in research applications and in frozen section, consultation and external quality assurance practice. Digital pathology, when integrated with other digital tools such as barcoding, specimen tracking and digital dictation, can be integrated into the histopathology workflow, from specimen accession to report sign-out. These elements can bring about improvements in the safety, quality and efficiency of a histopathology department. The present paper reviews the evidence for these benefits. We then discuss the challenges of implementing a fully digital pathology workflow, including the regulatory environment, validation of whole slide imaging and the evidence for the design of a digital pathology workstation.

Clinical Applications of Whole-slide Imaging in Anatomic Pathology.

The development of whole-slide imaging has paved the way for digitizing of glass slides that are the basis for surgical pathology. This transformative technology has changed the landscape in research applications and education but despite its tremendous potential, its adoption for clinical use has been slow. We review the various niche applications that initiated awareness of this technology, provide examples of clinical use cases, and discuss the requirements and challenges for full adoption in clinical diagnosis. The opportunities for applications of image analysis tools in a workflow will be changed by integration of whole-slide imaging into routine diagnosis.

The Pathologist 2.0: An Update on Digital Pathology in Veterinary Medicine.

Using light microscopy to describe the microarchitecture of normal and diseased tissues has changed very little since the middle of the 19th century. While the premise of histologic analysis remains intact, our relationship with the microscope is changing dramatically. Digital pathology offers new forms of visualization, and delivery of images is facilitated in unprecedented ways. This new technology can untether us entirely from our light microscopes, with many pathologists already performing their jobs using virtual microscopy. Several veterinary colleges have integrated virtual microscopy in their curriculum, and some diagnostic histopathology labs are switching to virtual microscopy as their main tool for the assessment of histologic specimens. Considering recent technical advancements of slide scanner and viewing software, digital pathology should now be considered a serious alternative to traditional light microscopy. This review therefore intends to give an overview of the current digital pathology technologies and their potential in all fields of veterinary pathology (ie, research, diagnostic service, and education). A future integration of digital pathology in the veterinary pathologist's workflow seems to be inevitable, and therefore it is proposed that trainees should be taught in digital pathology to keep up with the unavoidable digitization of the profession.

Enterprise Implementation of Digital Pathology: Feasibility, Challenges, and Opportunities.

Digital pathology is becoming technically possible to implement for routine pathology work. At our institution, we have been using digital pathology for second opinion intraoperative consultations for over 10 years. Herein, we describe our experience in converting to a digital pathology platform for primary pathology diagnosis. We implemented an incremental rollout for digital pathology on subspecialty benches, beginning with cases that contained small amounts of tissue (biopsy specimens). We successfully scanned over 40,000 slides through our digital pathology system. Several lessons (both challenges and opportunities) were learned through this implementation. A successful conversion to digital pathology requires pre-imaging adjustments, integrated software and post-imaging evaluations.

The Empirical Foundations of Telepathology: Evidence of Feasibility and Intermediate Effects.

INTRODUCTION: Telepathology evolved from video microscopy (i.e., "television microscopy") research in the early 1950s to video microscopy used in basic research in the biological sciences to a basic diagnostic tool in telemedicine clinical applications. Its genesis can be traced to pioneering feasibility studies regarding the importance of color and other image-based parameters for rendering diagnoses and a series of studies assessing concordance of virtual slide and light microscopy diagnoses. This article documents the empirical foundations of telepathology. METHODS: A selective review of the research literature during the past decade (2005-2016) was conducted using robust research design and adequate sample size as criteria for inclusion. CONCLUSIONS: The evidence regarding feasibility/acceptance of telepathology and related information technology applications has been well documented for several decades. The majority of evidentiary studies focused on intermediate outcomes, as indicated by comparability between telepathology and conventional light microscopy. A consistent trend of concordance between the two modalities was observed in terms of diagnostic accuracy and reliability. Additional benefits include use of telepathology and whole slide imaging for teaching, research, and outreach to resource-limited countries. Challenges still exist, however, in terms of use of telepathology as an effective diagnostic modality in clinical practice.

The Use of Telehealth to Reduce Inequalities in Cardiovascular Outcomes in Australia and New Zealand: A Critical Review.

Telehealth, the delivery of health care services at a distance using information and communications technology, is one means of redressing inequalities in cardiovascular outcomes for disadvantaged groups in Australia. This critical review argues that there is sufficient evidence to move to larger-scale implementation of telehealth for acute cardiac, acute stroke, and cardiac rehabilitation services. For cardiovascular chronic disease and risk factor management, telehealth-based services can deliver value but the evidence is less compelling, as the outcomes of these programs are variable and depend upon the context of their implementation.

Identification of Diabetic Retinopathy and Ungradable Image Rate with Ultrawide Field Imaging in a National Teleophthalmology Program.

PURPOSE: To compare diabetic retinopathy (DR) identification and ungradable image rates between nonmydriatic ultrawide field (UWF) imaging and nonmydriatic multifield fundus photography (NMFP) in a large multistate population-based DR teleophthalmology program. DESIGN: Multiple-site, nonrandomized, consecutive, cross-sectional, retrospective, uncontrolled imaging device evaluation. PARTICIPANTS: Thirty-five thousand fifty-two eyes (17 526 patients) imaged using NMFP and 16 218 eyes (8109 patients) imaged using UWF imaging. METHODS: All patients undergoing Joslin Vision Network (JVN) imaging with either NMFP or UWF imaging from May 1, 2014, through August 30, 2015, within the Indian Health Service-JVN program, which serves American Indian and Alaska Native communities at 97 sites across 25 states, were evaluated. All retinal images were graded using a standardized validated protocol in a centralized reading center. MAIN OUTCOME MEASURES: Ungradable rate for DR and diabetic macular edema (DME). RESULTS: The ungradable rate per patient for DR and DME was significantly lower with UWF imaging compared with NMFP (DR, 2.8% vs. 26.9% [P < 0.0001]; DME, 3.8% vs. 26.2% [P < 0.0001]). Identification of eyes with either DR or referable DR (moderate nonproliferative DR or DME or worse) was increased using UWF imaging from 11.7% to 24.2% (P < 0.0001) and from 6.2% to 13.6% (P < 0.0001), respectively. In eyes with DR imaged with UWF imaging (n = 3926 eyes of 2402 patients), the presence of predominantly peripheral lesions suggested a more severe level of DR in 7.2% of eyes (9.6% of patients). CONCLUSIONS: In a large, widely distributed DR ocular telehealth program, as compared with NMFP, nonmydriatic UWF imaging reduced the number of ungradable eyes by 81%, increased the identification of DR nearly 2-fold, and identified peripheral lesions suggesting more severe DR in almost 10% of patients, thus demonstrating significant benefits of this imaging method for large DR teleophthalmology programs.