Our Publications

MTM Vision Co-Scientific Director Jennifer K. Sun, M.D., M.P.H., of the Department of Ophthalmology at Harvard Medical School and the Beetham Eye Institute at Joslin Diabetes Center, co-authored an article titled “Diabetic Retinopathy in Youths – A Potential Unappreciated Public Health Catastrophe,” recently published in JAMA Ophthalmology. Sun’s co-authors include Julie Rosenthal, M.D., M.S., from the Department of Ophthalmology and Visual Sciences at the W.K. Kellogg Eye Center, University of Michigan, and Risa M. Wolf, M.D., from the Division of Pediatric Endocrinology at Johns Hopkins University School of Medicine. The article highlights the concerning rise of diabetic retinopathy (DR) in youths, a condition traditionally considered rare in this population. Recent data from the SEARCH and TODAY studies revealed alarming rates of DR among youths with diabetes, with 52% of those with type 1 diabetes and up to 55% with youth-onset type 2 diabetes showing signs of the disease after a relatively short duration of 7.5 to 12 years.

The report, “Data Harmonization, Standardization, and Collaboration for Diabetic Retinal Disease (DRD) Research: Report From the 2024 Mary Tyler Moore Vision Initiative (MTM Vision) Workshop on Data,” was recently published by TVST, an ARVO Journal. The “Workshop on Data” discussed best practices and specific considerations for building a comprehensive, shareable MTM Vision data lake by standardizing and harmonizing clinical data and ocular ’omics analyses. Standardization of data collection, common data elements, and data interoperability were emphasized alongside federated learning approaches to promote data sharing and collaboration while maintaining data privacy and security. Integrating molecular data with other multimodal data types was recognized as a promising strategy for leveraging machine learning, and AI approaches to advance therapeutics development and improve treatment outcomes for DRD patients. Partnerships with the National Eye Institute, part of the National Institutes of Health, foundations, and industry were deemed vital for successfully implementing these initiatives. The report was led by Amitha Domalpally, MD, PhD, with contributors including Ward Fickweiler, MD; S. Robert Levine, MD; Kerry E. Goetz; PhDc; Brian L. VanderBeek; MD, MPH, MSCE; Aaron Lee, MD; Jeffrey M. Sundstrom, MD, PhD; Dorene Markel, MS, MHSA; Jennifer K. Sun, MD, MPH.

The article explains Diabetic Retinal Disease (DRD) as a primary complication of diabetes and a top cause of vision loss in the active workforce. It proposes that DRD should be viewed as a type of sensory neuropathy or neurovascular degeneration. The focus of existing treatments is on late-stage DRD, with therapies predominantly targeting vascular endothelial growth factor (VEGF). The authors discuss the evolution in the understanding of DRD’s pathogenesis and highlight the need for innovative approaches in clinical assessments, trial frameworks, and the identification of new therapeutic targets. They underscore the necessity of expediting the creation and evaluation of novel treatments through the “Restoring Vision Moonshot” initiative, emphasizing a strategy to fill knowledge gaps. The ultimate ambition is to both preserve and restore vision in individuals with diabetes. The authors contributing to this perspective include S. Robert Levine, MD, Przemyslaw Sapieha, PhD, Sanjoy Dutta,PhD, Jennifer K. Sun, MD, MPH, and Thomas W. Gardner, MD, MS.

Published the report of the 2022 MTM Vision Clinical Endpoints Workshop in Translational Vision Science and Technology (TVST) (an ARVO journal): Gardner TW. Report from the 2022 Mary Tyler Moore Vision Initiative Diabetic Retinal Disease Clinical Endpoints Workshop. Transl Vis Sci Technol. 2023;12(11):33.

The article by Marie E. Wistrup Torm, MD, and colleagues explores the challenges and recent advances in understanding and treating Diabetic Retinal Disease (DRD), a significant cause of vision impairment globally. Present treatments are effective at later, vision-threatening stages, yet gaps exist in comprehending early DRD mechanisms. Novel retinal imaging methods have enhanced DRD staging precision beyond the traditional Diabetic Retinopathy Severity Scale. Moreover, current clinical studies offer insights into optimizing metabolic control to reduce DRD risks. However, therapies are partially successful, underscoring the necessity for research on the underlying mechanisms affecting the neurovascular retina and treatment innovations. The article also highlights the unexplained variability in DRD progression among patients with similar metabolic profiles. Emphasizing the need for patient-centered research, the paper calls for an inclusive focus on patient experiences of visual disabilities and the impact of treatments.

In a thought-provoking editorial, leading experts including Jennifer K. Sun, MD, MPH and Lloyd Paul Aiello, MD, PhD, argue for a refresh of the diabetic retinopathy (DR) severity scales. Highlighting the inadequacies of conventional systems like the ETDRS, which miss crucial aspects like neurodegeneration and diabetic macular edema (DME), the authors advocate for a nuanced, multidimensional approach. Leverages in imaging and AI tech signal the need for an updated system that can enhance early disease detection and patient management. Integral to this advancement is a coordinated effort from all stakeholders for the system’s development and clinical validation, as underscored by Michael D. Abràmoff, MD, PhD, and fellow contributors.

In a comprehensive review, notable experts including Adam R. Glassman, MS, Ted Maddess, PhD, FNAI, and Leonard A. Levin, MD, along with a team of specialists, dive into the assessment of visual function for individuals with diabetes and diabetic retinal disease. The collaborative work of Darrell E. Baskin, MD, Mitchell Brigell, PhD, and others within Mary Tyler Moore Vision Initiative’s Visual Function Working Group offers new perspectives. It aims to refine measurement techniques, setting the stage for enhanced diagnostic and treatment strategies in diabetic eye care.

This scholarly review, authored by the Cellular Mechanisms Working Group of the Mary Tyler Moore Vision Initiative, thoroughly investigates preclinical and clinical data to unravel the fundamental and cellular underpinnings influencing diabetic retinal disease (DRD). Eminent researchers, including M. Elizabeth Hartnett, MD, Lloyd Paul Aiello MD, PhD, and colleagues like Ward Fickweiler, MD, PhD, Anthony P. Adamis, MD, and others, dissect insights that may be critical for the future refinement of the DRD staging system. This collaborative effort aims to translate complex biological mechanisms into actionable criteria for DRD assessment and management.

The review, authored by the dynamic assembly of the Systemic Health Working Group from the Mary Tyler Moore Vision Initiative, embarks on a scholarly expedition to scrutinize the relationship between systemic health factors and diabetic retinal disease (DRD) staging. The expertise of Helen Colhoun, MD, Joe Mellor, PhD, Anita Jeyam, PhD, and their colleagues sheds light on how these factors could potentially forecast the initiation and advancement of DRD and the disease’s reaction to therapeutic interventions. Their findings aim to bolster the predictive accuracy and clinical refinement of DRD staging protocols, heralding a new era of personalized medicine in managing diabetic eye conditions.

Under the expert guidance of Professor Tien Yin Wong, MD, the Vascular Working Group of the Mary Tyler Moore Vision Initiative conducted a meticulous review penned by Tien-En Tan, MBBS (Hons), FRCOphth, to dissect and enhance the existing methodologies for capturing retinal imaging in diabetic eye disease. This critical analysis seeks to modernize disease classification, shed light on the current gaps, and proffer strategic recommendations for advancement. The review is a cornerstone for the DRD Staging System Update Effort, furthering MTM Vision’s commitment to pioneering efforts in diabetic eye disease research and management.

Led by Roomasa Channa, MD, and Michael Abramoff, MD, PhD, this comprehensive review evaluates the literature surrounding biomarkers for diagnosing diabetic retinal disease (DRD), particularly diabetic retinal neurodegeneration and diabetic macular edema. It acknowledges the strides made in retinal diagnostic technology and patient data acquisition but highlights a persistent over-reliance on conventional color fundus photography for DRD staging. The review calls attention to the urgent need for clear protocols to incorporate findings from emerging diagnostic approaches into routine clinical management. This scholarly work represents a significant contribution from the Diabetic Retinal Neurodegeneration and Macular Edema working group of the Mary Tyler Moore Vision Initiative global collaborative initiative to refine DRD Staging guidelines.

The review by Stela Vujosevic, MD, PhD, and the Quality of Life Working Group of the Mary Tyler Moore Vision Initiative critically evaluates patient-reported outcome measures (PROMs) for assessing quality of life in diabetic retinal disease (DRD). It underscores how vital psychometric properties of PROMs are in reflecting the various severity levels of an updated DRD staging system. The study assesses a range of PROMs, including generic, vision-specific, and DRD-specific tools, proposing areas for further improvement. The work forms part of  MTM Vision’s DRD Staging System Update Effort. MTM Vision leads this update with funding support from  Breakthrough T1D (formerly JDRF) and the Mary Tyler Moore and S. Robert Levine, MD Charitable Foundation.

In their scholarly review, Jessica H. Eisma, Jennifer E. Dulle, and Patrice E. Fort PhD, MS explore diabetic retinopathy (DR), the primary diabetes-induced cause of blindness in adults. They critically assess the transition from animal models to human donor tissue analyses to understand the vascular, inflammatory, and neurodegenerative components of DR. Recognizing limitations in animal studies, they emphasize data from human pathology to gain deeper insight into DR mechanisms, particularly in the context of non-proliferative (NPDR) and proliferative (PDR) stages. The review underscores the complexity of DR’s molecular mechanisms and advocates for additional research integrating both animal and human studies for a comprehensive understanding of the disease.

This study by Patrice Fort PhD, MS et. al explored the relationship between lipid changes and the severity of diabetic retinopathy (DR) by examining retinal tissues from human donors with varying degrees of DR and serum samples from American Indians with type 2 diabetes. Lipidomic analysis using mass spectrometry revealed a decrease in complex lipids like long-chain acylcarnitines and other lipid classes such as diacylglycerols, triacylglycerols, and ceramides in the retinas of individuals with DR, suggesting impaired synthesis of these lipids and mitochondrial fatty acid β-oxidation. In the serum samples, there was a similar decrease in long-chain acylcarnitines, accompanied by an increase in certain triacylglycerols, indicating systemic lipid alterations parallel to those in the retina. These findings imply that the synthesis of complex lipids and fatty acid metabolism are disrupted in DR, with these changes reflected in both the retina and the bloodstream. This research was supported by several NIH grants, The Thomas Beatson Foundation; and the JDRF Center for Excellence.

This publication by Haitao Liu, PhD, et.al investigates the role of Akt2 signaling in the development of diabetic retinopathy (DR), a primary cause of blindness. The study utilized human tissues and genetically modified mice, including those with RPE-specific conditional knockout (cKO) and knock-in (KI) of Akt2. Researchers found that Akt1 and Akt2 have opposing activities in the retinal pigment epithelium (RPE) of diabetic donors and mice. Deleting Akt2 in diabetic mice led to fewer retinal complications by increasing Akt1 activity, which reduced vascular damage, cytokine release, and immune cell infiltration by affecting the GSK3β/NF-κB pathway. Surprisingly, overexpressing Akt2 had no impact. The findings suggest that enhancing Akt1 in the RPE could be a new strategy for DR treatment.