Table 1.

Limitations of the ETDRS and International DR Severity Scales and Goals for the Development of an Updated DRD Staging System.

Limitations of the ETDRS and International DR Severity Scales	Goals for the Development of an Updated DRD Staging System
Do not evaluate the neural retina	Include evaluation of neural retinal pathology in DRD to elucidate early degenerative changes that may accompany or precede vascular lesions and to determine how neural abnormalities are correlated with visual function loss
Do not visualize the peripheral retina	Understand if peripheral retina is important for predicting future outcomes in eyes with DRD, since this may change whether we should routinely evaluate peripheral nonperfusion and lesions to best stage risk of DRD worsening for research and clinical efforts
Do not include molecular, pathophysiologic or neurodegenerative changes that occur before the development of clinically evident retinopathy	Explore early changes in DRD that may lead to better characterization of preclinical abnormalities and therapeutic target development
Do not incorporate measures of systemic health	Include systemic health context (e.g. measures of glycemic control, blood pressure and blood lipids) in the DRD staging system since these influence future anatomic and visual outcomes in persons with diabetes
Not well-suited to document worsening or improvement of retinal neovascularization in eyes with PDR	Revise the PDR scale to describe key levels for both worsening and improvement of PDR. This will enable better characterization of eyes with PDR in natural history and under treatment for research and clinical purposes.
Do not address regression of DR severity in the setting of treatment	Clarify how improvement of ETDRS DR severity level during treatment with diabetes control, anti-VEGF or steroids affects outcomes to understand whether such therapies modify underlying disease
Do not adequately incorporate severity stages for DME that are currently being used to drive care and evaluation of eyes with DME	Include severity stages for DME that specify involvement of the macula since this information is now incorporated into commonly used treatment algorithms
Are not directly tied to visual outcomes other than those based on best corrected central visual acuity	Understand how additional aspects of functional vision, such as visual fields, contrast sensitivity, metamorphopsia and low luminance acuity, change in DRD. This may facilitate development of therapies addressing DRD severity levels that do not directly affect central visual acuity and provide additional registrable endpoints for regulatory approval.
Are not quantitative	Aim to develop a staging system and severity scales that can be used to quantitate DRD pathology for easier use in clinical research
Difficult to use in practice	Develop a revised staging system that is easy to use in practice

DME: diabetic macular edema; DR: diabetic retinopathy; DRD: diabetic retinal disease; ETDRS: Early Treatment Diabetic Retinopathy Study; OCT: optical coherence tomography; PDR: proliferative diabetic retinopathy