---
title: "Diabetic retinopathy regression rates in very mild and mild NPDR in an IHS teleophthalmology cohort"
id: "plos-one-2-rates-of-nonproliferative-diabetic-retinopathy-npdr-regression-among-patients"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-2-rates-of-nonproliferative-diabetic-retinopathy-npdr-regression-among-patients"
content_type: "clinical_feed_article"
specialty: "Endocrinology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052"
published_at: "2026-10-16T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Diabetic retinopathy regression rates in very mild and mild NPDR in an IHS teleophthalmology cohort
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-2-rates-of-nonproliferative-diabetic-retinopathy-npdr-regression-among-patients
- **Specialty:** [Endocrinology](https://medichelpline.com/clinical-feed/endocrinology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052)
- **Published At:** 2026-10-16T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Investigators performed a retrospective, longitudinal cohort analysis of Indian Health Service teleophthalmology records to quantify **diabetic retinopathy** (DR) regression among patients with baseline very mild or mild nonproliferative DR (**NPDR**). - Baseline exams were from 2015 with follow-up exams up to 36 months; the average interval between baseline and final follow-up was 22.8 ± 7.9 months. The source reported that baseline HbA1c values were substituted with follow-up values or the cohort mean when missing. - The analytic sample comprised 2,348 patients with very mild NPDR and 705 with mild NPDR who had a graded follow-up exam within 6–36 months; initial pool before follow-up exclusions was larger (5,735 patients met selection criteria). - For patients with very mild NPDR at baseline, the proportion who regressed to no DR was 0.47 (95% CI 0.45–0.50); any progression occurred in 0.27 of that group. For mild NPDR at baseline, any regression (to very mild or no DR) was 0.36 (95% CI 0.33–0.40) and progression proportion was 0.34 (95% CI 0.30–0.38). - Multivariable logistic regression showed higher **HbA1c** and insulin use were independently associated with lower odds of DR regression in both baseline-severity groups; longer diabetes duration decreased odds of regression only in the very mild NPDR subgroup. - Model-based predicted probabilities demonstrated a declining chance of regression as **HbA1c** rose, and consistently lower probabilities for patients on insulin versus oral agents at equivalent **HbA1c** values (examples reported in the source: at HbA1c 8%, predicted regression ~61% with oral agents vs ~49% with insulin for very mild NPDR). - Imaging predominantly used nonmydriatic ultra-widefield imaging (UWFI) and standardized ETDRS-based grading by certified optometrists with ophthalmologist oversight; 6.9% of follow-up exams could not be graded and were excluded from outcome calculations. - The study identified more frequent reversal than progression among very mild NPDR patients, and emphasized glycemic control and behavioral risk factor modification in diabetic eye care. The source noted study limitations including retrospective design, follow-up ascertainment bias, substitution for missing HbA1c, and limited follow-up window (6–36 months).
## Clinical Analysis & Structured Key Points
[ Skip to main content ](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#main-content) Advertisement * [plos.org](https://plos.org/) * [Create account](https://community.plos.org/registration/new) * [Sign in](https://journals.plos.org/user/secure/login?page=%2Fplosone%2Farticle%3Fid%3D10.1371%2Fjournal.pone.0361052) * * About * Browse * Publish * [](https://journals.plos.org/plosone/ "PLOS One") * Search [advanced search](https://journals.plos.org/plosone/search) * [Browse Topics](https://journals.plos.org/plosone/subjectAreaBrowse) Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click [here](https://github.com/PLOS/plos-thesaurus/blob/master/README.md "Link opens in new window"). [](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052) [](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052) * 0 [Save](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0361052#savedHeader) [Total Mendeley and Citeulike bookmarks.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0361052#savedHeader) * 0 [Citation](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0361052#citedHeader) [Paper's citation count computed by Dimensions.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0361052#citedHeader) * 23 [View](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0361052#viewedHeader) [PLOS views and downloads.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0361052#viewedHeader) * 0 [Share](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0361052#discussedHeader) [Sum of Facebook, Twitter, Reddit and Wikipedia activity.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0361052#discussedHeader) Open Access Peer-reviewed Research Article # Rates of nonproliferative diabetic retinopathy (NPDR) regression among patients with very mild or mild NPDR in an Indian Health Service teleophthalmology program, 2015 – 2020 * Sven-Erik Bursell , Contributed equally to this work with: Sven-Erik Bursell, Stephanie J. Fonda, Kaitlynn Borik, Dara Shahon Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing * E-mail: Sven.Bursell@socialeyesus.com Affiliation Estenda Solutions, Inc., Wayne, Pennsylvania, United States of America [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0009-0007-4348-6425 ](https://orcid.org/0009-0007-4348-6425 "ORCID Registry") ⨯ * Stephanie J. Fonda , Contributed equally to this work with: Sven-Erik Bursell, Stephanie J. Fonda, Kaitlynn Borik, Dara Shahon Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing Affiliation Estenda Solutions, Inc., Wayne, Pennsylvania, United States of America ⨯ * Kaitlynn Borik , Contributed equally to this work with: Sven-Erik Bursell, Stephanie J. Fonda, Kaitlynn Borik, Dara Shahon Roles Validation, Visualization, Writing – original draft, Writing – review & editing Affiliation SSM Health/Saint Louis University School of Medicine, St. Louis, Missouri, United States of America ⨯ * Jeff Stainback, Roles Methodology, Resources, Software, Validation, Visualization, Writing – review & editing Affiliation Estenda Solutions, Inc., Wayne, Pennsylvania, United States of America ⨯ * Dara Shahon Contributed equally to this work with: Sven-Erik Bursell, Stephanie J. Fonda, Kaitlynn Borik, Dara Shahon Roles Project administration, Resources, Supervision, Validation, Writing – review & editing Affiliation Phoenix Indian Medical Center, Phoenix Arizona, United States of America ⨯ # Rates of nonproliferative diabetic retinopathy (NPDR) regression among patients with very mild or mild NPDR in an Indian Health Service teleophthalmology program, 2015 – 2020 * Sven-Erik Bursell, * Stephanie J. Fonda, * Kaitlynn Borik, * Jeff Stainback, * Dara Shahon ![PLOS](https://journals.plos.org/resource/img/logo-plos-full-color.svg) x * Published: October 16, 2026 * * [Article](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052) * [Authors](https://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0361052) * [Metrics](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0361052) * [Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0361052) * [Media Coverage](http://plos.altmetric.com/details/doi/10.1371/journal.pone.0361052) * [Peer Review](https://journals.plos.org/plosone/article/peerReview?id=10.1371/journal.pone.0361052) * [Abstract](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#abstract0) * [Introduction](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#sec001) * [Methods](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#sec002) * [Results](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#sec007) * [Discussion](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#sec008) * [Acknowledgments](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#ack) * [References](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#references) * [Reader Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0361052) * [Figures](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052) ## Abstract Diabetic retinopathy (DR) regression is not regularly reported; yet understanding of its prevalence in early-stage DR may impact strategies for eye care management. This study’s primary aim was to examine DR regression in patients initially diagnosed with very mild or mild nonproliferative DR (NPDR). A secondary aim was to assess the association between retinopathy regression and diabetes therapy, diabetes duration, and Hemoglobin A1c (HbA1c). This was a retrospective, longitudinal cohort study using medical record data from the United States’s Indian Health Service’s teleophthalmology program for DR evaluation. Baseline exams occurred in 2015–2017 and follow-up (FU) exams occurred within 3 years of baseline. There were 2,348 patients included in this cohort with very mild NPDR at baseline and 705 patients with mild NPDR. For the whole sample, mean age was 56 ± 12.8 years, 55% were female, diabetes duration was 13.0 ± 9.1 years, and HbA1c was 8.8 ± 2.1%. Proportions for DR regression were 0.47 (CI = .45 − .50) (from very mild NPDR) and 0.36 (CI = 0.33–0.40) (from mild NPDR). Proportions for any DR progression were 0.27 (CI = 0.25–0.29) (from very mild NPDR) and 0.34 (CI = 0.30–0.38) (from mild NPDR). Multivariable analyses showed that lower HbA1c levels were associated with greater odds of diabetic retinopathy regression in patients with either very mild or mild baseline NPDR, whereas insulin use was associated with lower odds of regression. Shorter diabetes duration was associated with greater odds of regression only among patients with very mild NPDR at baseline. DR **r** egression was more frequent than DR progression particularly for patients initially with very mild NPDR. DR reversal was more likely in early-stage DR. Behavioral modifications such as increased physical activity and weight loss that lower HbA1c and subsequent risks for DR progression are important to emphasize in diabetic eye care. ## Figures ![Table 4](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t004) ![Table 5](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t005) ![Table 6](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t006) ![Table 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t001) ![Table 2](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t002) ![Table 3](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t003) ![Table 4](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t004) ![Table 5](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t005) ![Table 6](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t006) ![Table 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t001) ![Table 2](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t002) ![Table 3](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t003) **Citation:** Bursell S-E, Fonda SJ, Borik K, Stainback J, Shahon D (2026) Rates of nonproliferative diabetic retinopathy (NPDR) regression among patients with very mild or mild NPDR in an Indian Health Service teleophthalmology program, 2015 – 2020. PLoS One 21(10): e0361052. https://doi.org/10.1371/journal.pone.0361052 **Editor:** Yalong Dang, Sanmenxia Central Hospital, Henan University of Science and Technilogy, CHINA **Received:** February 26, 2026; **Accepted:** October 5, 2026; **Published:** October 16, 2026 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the [Creative Commons CC0](https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. **Data Availability:** The minimal data set is available at Harvard Dataverse via . **Funding:** The author(s) received no specific funding for this work. **Competing interests:** I have read the journal’s policy and the authors of this manuscript have the following competing interests: Sven-Erik Bursell: Scientific consultant for SocialEyes Corp. and Research Consultant subcontracted by the Indian Health Service Joslin Vision Network to manage and analyze the data collected for the program. Sterphanie J. Fonda: Subcontracted by the Indian Health Service Joslin Vision Network to manage and analyze the data collected for the program as Estenda Solutions Vice President of Research Initiatives. Jef Stainback: Subcontracted by the Indian Health Service Joslin Vision Network to manage and analyze the data collected for the program as Estenda Solutions Quality Assurance Manager. Dara Shahon: Employee of the Indian Health Service as Director, IHS-JVN Teleophthalmology Program at the Phoenix Indian Medical Center. ## Introduction The level of Diabetic Retinopathy (DR) is commonly used to characterize ocular microvascular complications of diabetes, the leading cause of preventable blindness amongst working-aged people [[1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref001)]. Shorter durations of diabetes, improved glycemic control, and lower blood pressure and lipid levels are implicated in reducing the risk for development and progression of DR [[2](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref002)]. A review of prior research [[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref003)] identified studies focused on prevalence, incidence and progression of DR and the risk factors associated with them. However, regression (or improvement) of DR is less frequently studied or is a secondary focus. Available studies on regression ([Table 1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone-0361052-t001)) suggest it is more likely to occur in very mild nonproliferative DR (NPDR) [[6](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref006),[19](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref019)], particularly for younger patients with hemoglobin A1c (HbA1c) levels close to normal and shorter diabetes duration [[11](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref011),[13](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref013),[16](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref016)]. Generally, the literature addressing regression focused on improvements in risk factors known to be associated with progression of DR. However, one publication [[8](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref008)] suggested that the formation of microaneurysms (MAs), a characteristic lesion for mild NPDR, was independent of glycemic control and other medical factors that affect more advanced levels of DR. [![thumbnail](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0361052.t001)](https://journals.plos.org/plosone/article/figure/image?size=medium&id=10.1371/journal.pone.0361052.t001 "Click for larger image") Download: * [PNG larger image](https://journals.plos.org/plosone/article/figure/image?download&size=large&id=10.1371/journal.pone.0361052.t001) * [TIFF original image](https://journals.plos.org/plosone/article/figure/image?download&size=original&id=10.1371/journal.pone.0361052.t001) Table 1. Published studies reporting diabetic retinopathy regression. [ https://doi.org/10.1371/journal.pone.0361052.t001](https://doi.org/10.1371/journal.pone.0361052.t001) The primary aim of this study was to investigate the occurrence of DR regression in teleophthalmology patients with initially very mild NPDR or mild NPDR. Rates of no change or stability and any progression were also determined for comparison purposes. A secondary aim was to examine the association of diabetes therapy, diabetes duration, and HbA1c with regression occurrence. Prior results on this study cohort [[20](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref020),[21](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref021)] demonstrated prevalence of any DR, any DME, and sight-threatening disease was 28.6%, 3.0%, and 3.0%. Of patients with no DR in 2015, 18.0% had mild NPDR or worse in 2016–2019, and 0.1% had PDR. Of patients with mild NPDR in 2015, 27.2% progressed to moderate NPDR or worse in 2016–2019, and 2.3% progressed to severe NPDR or worse. ## Methods ### Setting and study population This is a retrospective cohort study using de-identified medical records from the national, primary care-based Indian Health Service’s (IHS) teleophthalmology program (Data accessed 09/14/2022) in the United States. Baseline data included only patients with type 2 diabetes accessed to the program during the period of January 1,2015, to December 31,2015, and a follow-up period of January 1,2016, to December 31,2019. Eligible patients had at least 1 IHS teleophthalmology examination with the program in both periods. Data from this program has previously been used to describe DR prevalence and incidence [[20](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref020),[21](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref021)]. Briefly, the IHS teleophthalmology program is a validated American Telemedicine Association (ATA) Category 3 program [[22](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref022)] that accesses patients presenting for their primary care appointments [[23](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref023),[24](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref024)]. The program’s graders are certified and licensed optometrists who use standardized protocols to identify the Early Treatment Diabetic Retinopathy Study (ETDRS) defined clinical levels of DR severity [[25](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref025)]. An ophthalmologist provides oversight. The study was reviewed and approved by the IHS Institutional Review Board at Phoenix Indian Medical Center (IHS IRB PXR 20.08) under the exempt process (consent waived). STROBE reporting guidelines were used for this article. ### Data selection To establish a ‘baseline’, patients aged 20 + years who were imaged in 2015 and received a diagnosis of very mild or mild NPDR (ETDRS DR levels of severity 20 or 35) in one or both eyes were selected. Patients with no DR in both eyes, with a more severe level of NPDR than very mild or mild in one or both eyes, or with concurrent PDR (ETDRS levels 61, 65, 71−75, 81−85) and/or DME were excluded. The baseline period selected allowed time for patients to obtain a follow-up exam before possible disruptions to scheduling resulting from the COVID-19 public health emergency. ‘Follow-up’ (FU) exams were defined as the last available teleophthalmology exam in the medical record, for a minimum of 6 months and a maximum of 36 months. The average time between baseline and final FU visits was 22.8 ± 7.9 months. If the last FU exam could not be graded, the FU outcome also could not be determined (6.9% of patients with a FU exam had to be excluded from calculations of the outcomes). ### Measures **Assessment of DR severity**. Over 80% of the DR examinations used nonmydriatic ultra-widefield imaging (UWFI) scanning laser ophthalmoscopy (Daytona, Optos, plc, Dunfermline, United Kingdom). The UWFI protocol included non-simultaneous stereo pair 200o images from each eye, centered on the macula. The remaining examinations used low-illumination, nonmydriatic fundus photography (NMFP) digital imaging system (Topcon NW6S; Topcon Medical Systems, Inc., Paramus, NJ) with a custom digital camera back (Megavision Retinal Image Capture; Santa Barbara, CA). The NMFP protocol included three non-simultaneous stereo pair 45o (degree) images from different retinal regions and two non-simultaneous stereo pair 30o digital images of the optic disc and the macula from the retina of each eye were obtained, for an approximate total retinal coverage of 90o to 135o. These methods and their agreement with ETDRS photography have been previously described [[26](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref026),[27](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0361052#pone.0361052.ref027)]. **DR outcomes.** For the patients with very mild NPDR at baseline, the outcome had four categories based on the patients’ worst eye: regression to no DR; no change in DR; progression to mild NPDR and progression to any higher level of DR as of the patients’ last FU exam. Progression to mild NPDR was considered separately to assess whether these patients differed from those whose diagnosis at FU was still very mild NPDR. For patients with mild NPDR at baseline, the outcome had four categories based on the patients’ worst eye: regression to no DR; regression to very mild NPDR; no change in DR; and progression to any higher level of DR. For some statistical analyses, no change and any DR progression were combined into one group grouped
## Related Clinical Research

- [Olive oil before carbs and blood sugar: what the mouse study found](https://medichelpline.com/clinical-feed/medical-news-today-0-olive-oil-shot-trend-what-science-really-says-about-fat-and-glucose-response.md)
- [Cardiovascular safety of oral orforglipron versus insulin glargine in T2D at increased CV risk (AC](https://medichelpline.com/clinical-feed/pubmed-42815506.md) (DOI: 10.1016/S0140-6736(26)01865-9)
- [Self-Management Program Lowers HbA1c, eGFR, SBP, LDL-C in High-Risk DKD Patients with Type 2 Diabe](https://medichelpline.com/clinical-feed/plos-one-11-effectiveness-of-a-self-management-intervention-on-clinical-outcomes-among.md)
- [Safety comparison of imeglimin versus sitagliptin in Japanese patients with type 2 diabetes](https://medichelpline.com/clinical-feed/plos-one-8-comparative-safety-of-imeglimin-versus-sitagliptin-in-japanese-patients-with.md)
- [Model-directed insulin pump dosing for type 2 diabetes using LSTM: development and prospective eva](https://medichelpline.com/clinical-feed/medrxiv-22-a-data-driven-system-for-insulin-pump-dosing-in-type-2-diabetes-development.md)

## Navigation
- [← Back to Endocrinology Feed](https://medichelpline.com/clinical-feed/endocrinology.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.