Assessing and Grading Diabetic Retinopathy: Updates for Ophthalmology Residents

by David RP Almeida, MD, MBA, PhD and Eric K Chin, MD
Feb 4, 2021
7 min read
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With the development of new tools for the diagnosis and management of diabetic retinopathy, it's worth returning to the evolution of the Early Treatment Diabetic Retinopathy Study (ETDRS) classification system in order to understand how ophthalmologists assess and grade diabetic retinopathy now.

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The Early Treatment Diabetic Retinopathy Study (ETDRS) classification system has evolved and, in a congruent manner, the approach for assessing and grading diabetic retinopathy severity has been modified in attempt to describe diabetic retinal disease with both accuracy and precision. Here, we review the evolution of the ETDRS classification system and the Diabetic Retinopathy Severity Scale (DRSS) and provide insights for future directions.

Historical perspective

While it began as the O’Hare Classification, the Airlie House Committee on diabetic retinopathy classification developed a comprehensive system to critically describe diabetic retinopathy and to evaluate the effect of treatment modalities.1 Specifically, the Airlie House Classification of diabetic retinopathy qualitatively and quantitatively described the status of diabetic retinopathy with fundus photography to permanently record the locations of these lesions in certain predesignated areas of the fundus1 (FIGURE 1).

FIGURE 1: Seven standard fields of the modified Airlie House Classification of diabetic retinopathy. Using the right eye as an example, Field 1 is centered on the optic nerve, Field 2 is centered on the macula and Field 3 is temporal to the macula. Field 4, 5, 6 and 7 capture the retinal mid-periphery.

FIGURE 1: Seven standard fields of the modified Airlie House Classification of diabetic retinopathy. Using the right eye as an example, Field 1 is centered on the optic nerve, Field 2 is centered on the macula and Field 3 is temporal to the macula. Field 4, 5, 6 and 7 capture the retinal mid-periphery.

In 1971, the Airlie House Classification was modified for use in the first landmark clinical trial, the Diabetic Retinopathy Study, which demonstrated significant reduction in the rates of severe vision loss in eyes treated with panretinal photocoagulation compared to untreated control eyes.2 The grading system was further modified for use in the ETDRS randomized prospective study which found the rate of moderate vision loss in eyes with clinically significant macular edema treated with macular focal laser had a relative risk reduction of 50% compared to untreated eyes.3

The ETDRS, by use of fundus photography, defined and detailed microaneurysms (MA), venous beading and narrowing, intraretinal microvascular abnormalities (IRMA),

diabetic macular edema (i.e., clinically significant macular edema). Moreover, ETDRS definitions compared with standardized fundus photographs produced the DRSS for the description of non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). TABLE 1 and FIGURE 2 summarize the ETDRS DRSS.

FIGURE 2: Early Treatment of Diabetic Retinopathy (ETDRS) standard photos 2A (top), 8A (middle) and 10a (bottom).

FIGURE 2: Early Treatment of Diabetic Retinopathy (ETDRS) standard photos 2A (top), 8A (middle) and 10a (bottom).

Disease Severity Level Clinical Findings ETDRS Definition
Mild NPDR At least 1 MA and definition not met for any other disease severity level
    MA defined as red
    spot 125μm (longest dimension) with sharp margins
Moderate NPDR
    MA and hemorrhages
    May include soft exudates, venous beading, IRMA with definition not met for any other disease severity level
    Hemorrhage defined as red spot with irregular margins and a dimension that exceeded 125μm
    Hemorrhages and/or MA ≥ standard photograph 2A
Severe NPDR
    Cotton wool spots, venous beading and IRMA in at least two of fields 4-7
    Two of cotton wool spots, venous beading, IRMA in at least two of fields 4-7, with hemorrhages in all fields 4-7 (consistent with photo 2A)
    IRMA in all of fields 4-7 and definition not met for any other disease severity level
IRMA in fields 4-7 must be ≥ photograph 8A
Non High-Risk (Early) PDR Neovascularization with definition not met for high-risk PDR
High-Risk PDR
    New vessel growth on or within 1 disc diameter of optic disc with or without vitreous or preretinal hemorrhage
    Vitreous or preretinal hemorrhage with NVD or NVE
    Neovascularization ≥ photograph 10A (one-quarter to one-third disc area)
    NVE ≥ than one-quarter disc area

TABLE 1: Summary of the diabetic retinopathy severity scale (DRSS) with associated disease severity, clinical findings and Early Treatment of Diabetic Retinopathy (ETDRS) standard photos. (NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy; MA, microaneurysms; IRMA, intraretinal microvascular abnormalities; NVD, neovascularization of the disc; NVE, neovascularization elsewhere.)

The ETDRS and DRSS evolution

The ETDRS DRSS was subsequently updated to provide a coherent but simplified approach to retinopathy level and disease severity. The summary of the ETDRS Final Scale of Diabetic Retinopathy Severity is provided in TABLE 2 and FIGURE 3.

FIGURE 3: Photographic depiction of the abbreviated summary of the Early Treatment of Diabetic Retinopathy (ETDRS) Final Scale of Diabetic Retinopathy Severity. (NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic.)

FIGURE 3: Photographic depiction of the abbreviated summary of the Early Treatment of Diabetic Retinopathy (ETDRS) Final Scale of Diabetic Retinopathy Severity. (NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic.)

ETDRS Level Disease Severity Definition
10 No retinopathy Diabetic retinopathy absent
20 Very mild NPDR MA only
35 Mild NPDR MA plus hard exudates, soft exudates (cotton wool spots) and/or mild retinal hemorrhages
43 Moderate NPDR MA plus mild IRMA or moderate retinal hemorrhages
47 Moderate NPDR More extensive IRMA. Severe retinal hemorrhages or venous beading in 1 quadrant only
53 Severe NPDER Severe retinal hemorrhages in 4 quadrants, or venous beading in at least 2 quadrants, or moderately severe IRMA in at least 1 quadrant
61 Mild PDR NVE < 1/2 disc area in 1 or more quadrants
65 Moderate PDR NVE ≥ 1/2 disc area in 1 or more quadrants or NVD < 1/4–1/3 disc area
71-75 High-Risk PDR NVD ≥ 1/4–1/3 disc area and/or vitreous hemorrhage
81-85 Advanced PDR Fundus partially obscured

TABLE 2: Abbreviated summary of the Early Treatment of Diabetic Retinopathy (ETDRS) Final Scale of Diabetic Retinopathy Severity. (NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy; MA, microaneurysms; IRMA, intraretinal microvascular abnormalities; NVD, neovascularization of the disc; NVE, neovascularization elsewhere.)

The future of diabetic retinopathy grading

With the advent of vascular endothelial growth factor (VEGF) inhibitors and widespread widefield photography systems, the ETDRS DRSS classification of diabetic retinopathy has been criticized to be less clinically relevant.4 The ability of anti-VEGF agents to both promote anatomic resolution of diabetic macular edema and regress many of the features of diabetic retinopathy require a classification system for assessment and grading with high sensitivity and reproduceability.5

Moreover, the need to account for technological advances in imaging with respect to optical coherence tomography (OCT), OCT angiography (OCTA) and ultra-widefield imaging will create significant selective pressure to evolve the ETDRS system further.6 Concomitantly, new insights into diabetic retinal disease will require both clinicians and researchers to adapt so as to best characterize retinal changes in diabetes. 

References

  1. Goldberg MF, Fine SL. Symposium on the Treatment of Diabetic Retinopathy. Arlington: US Department of Health, Education, and Welfare; 1968. Public Health Service Publication No. 1890.
  2. The Diabetic Retinopathy Study Research Group. A Modification of the Airlie House Classification of Diabetic Retinopathy. DRS report #7. Invest Ophthalmol Vis Sci. 1981;21:210–26.
  3. Early Treatment Diabetic Retinopathy Study Research Group. Grading Diabetic Retinopathy from Stereoscopic Color Fundus Photographs - An Extension of the Modified Airlie House Classification. ETDRS Report Number 10. Ophthalmology. 1991 May; 98 (5): 786-806.
  4. Wang K, Jayadev C, Nittala MG, Velaga SB, Ramachandra CA, Bhaskaranand M, et al. Automated detection of diabetic retinopathy lesions on ultrawidefield pseudocolour images. Acta Ophthalmol. 2018 Mar;96(2):e168–73.
  5. Arcadu F, Benmansour F, Maunz A, Willis J, Haskova Z, Prunotto M. Deep learning algorithm predicts diabetic retinopathy progression in individual patients Digital Medicine (2019) 2:92.
  6. Abramoff MD, Fort PE, Han IC, Jayasundera KT, Sohn EH, Gardner TW. Approach for a Clinically Useful Comprehensive Classification of Vascular and Neural Aspects of Diabetic Retinal Disease. Invest Ophthalmol Vis Sci. 2018;59(1):519-527.
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About David RP Almeida, MD, MBA, PhD

David Almeida MD MBA PhD is a vitreoretinal eye surgeon offering a unique voice that combines a passion for ophthalmology, vision for business innovation, and expertise in ophthalmic and biomedical research. He is part of Erie Retinal Surgery, a retina-only private practice with an esteemed reputation for excellence in Pennsylvania. Dr. Almeida and Erie Retinal Surgery diagnose and treat all medical and surgical conditions of the vitreous, retina and macula.

About Eric K Chin, MD

Dr. Eric K Chin is a board certified ophthalmologist at Inland Eye Specialists in Northern California. A graduate of University of California Berkeley with a bachelor’s degree in Bioengineering, Dr. Chin received his medical degree from the Chicago Medical School. He completed his ophthalmology residency at the University of California Davis, and his surgical vitreoretinal fellowship at the University of Iowa. During his residency and fellowship, he was awarded several accolades for his teaching and research in imaging and novel treatments for various retinal diseases.


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