Current and Emerging Management of NPDR

Treatment of nonproliferative diabetic retinopathy (NPDR) can prevent progression and may be 90% effective in preventing severe vision loss.¹ If left untreated, vision loss from diabetic retinopathy can lead to a substantial economic burden on patients, their families, and society.¹ NPDR treatment goals include vision preservation and improvement, in addition to a reduction in the rate of retinopathy progression, vitreous hemorrhage, and macular edema.² The overall management strategy should be individualized to maximize vision benefits and minimize side effects while considering systemic issues and NPDR severity.²

Multidisciplinary management and working with the patient’s primary care provider is the ideal way to treat people with NPDR, including incorporating a healthy diet and regular exercise into their daily routines.¹

For instance, two critical modifiable risk factors associated with developing diabetic retinopathy are blood glucose levels and blood pressure.¹ Most people with diabetes should aim for a target HbA1c of 7% or lower.¹ Increases in HbA1c often increase the risk of developing diabetic macular edema (DME).¹ Studies also show that maintaining near-normal blood pressure levels is important to reducing retinopathy progression.¹ Lowering serum lipids may also play a role in improving DR.¹

Many people with NDPR may not need ocular treatment but can improve with systemic management of their glucose, blood pressure, and other metabolic factors.¹ However, treatments with lasers, anti-VEGF agents, or intravitreal corticosteroids may also be considered in appropriate situations.¹

People with mild to moderate NPDR and no DME can typically be monitored without ocular treatment. However, they should be re-examined every 6-12 months because the 4-year risk of developing DME can be as high as 23%.¹ The 5-year progression rate of moderate NPDR to PDR is a worrisome 50%, so close monitoring is needed to allow for the appropriate transition from observation to treatment.³

Signs of severe NPDR should prompt follow-up every 3 months, or even more frequently if DME is present.⁴ Regardless of DME, studies show that the risk of progression to proliferative diabetic retinopathy (PDR) over 5 years is approximately 44% for people with moderate NPDR, 66% for moderately severe NPDR, and 75% to 90% for severe NPDR or worse.³ After only 1 year, about one in four eyes with moderate NPDR and more than half of those with severe NPDR will worsen to PDR.³

It is vital to consider proactive rather than reactive management of NPDR.⁵ Waiting to start therapy until after the development of sight-threatening conditions such as PDR and DME may not be the best option for the patient; once neovascularization develops, the risk of vision loss increases dramatically.^1,5 By treating NPDR before PDR or DME develop, ophthalmologists may prevent retinopathy progression and worse visual outcomes.^1,5

Laser panretinal photocoagulation (PRP)
Laser PRP decreases the risk of severe vision loss in people with severe NPDR and high-risk factors such as poor compliance with follow-up, impending cataract extraction or pregnancy, and blind or advanced DR in the fellow eye.^1,4 People with very severe NPDR or worse have approximately a 50% chance of worsening to PDR within 1 year.¹

Anti-vascular endothelial growth factor (anti-VEGF)
Studies suggest that treating moderate to severe NPDR with anti-VEGF in some people can improve signs of retinopathy and delay progression from severe NPDR to PDR.^5,8 The two primary anti-VEGF therapies that are FDA-approved to treat any degree of NPDR are ranibizumab and aflibercept.³Data from the Protocol S, RISE/RIDE, VIVID/VISTA, and PANORAMA trials show that these anti-VEGF therapies can help eyes with any level of DR, with or without DME.³ Eyes with more advanced NPDR respond particularly well to anti-VEGF therapy, with approximately 80% showing regression of retinopathy severity.³

DME is another facet of diabetic retinopathy that may run a concurrent or independent course with NPDR. It can be a significant source of visual impairment for patients and may need ocular therapy. Focal macular laser was the mainstay of center-involving DME treatment; however, intravitreal anti-VEGF injections have moved to the forefront and are now first-line therapy for DME.⁹

In addition to ranibizumab and aflibercept, faricimab has been FDA-approved to treat DME (YOSEMITE/RHINE).^10,11 Additionally, higher molar concentration aflibercept (8mg) has been FDA-approved for the treatment of DR and DME (PHOTON).¹² Some ophthalmologists also use bevacizumab off-label for retinal edema.¹⁰

Many patients respond well to anti-VEGF agents, improving 1-3 lines or more on the Snellen vision chart.¹⁰ Unfortunately, up to 40% of people experience persistent DME, although, even in these cases, a substantial portion have shown ≥2 lines of improvement in clinical trial settings.¹⁰

Alternative treatments
Alternative treatments may be considered if the DME does not respond after 3-6 monthly intravitreal injections.⁹ Laser therapy may be initiated after 6 months of anti-VEGF treatment. Intravitreal injections or implants of steroids may also improve retinal thickening and visual acuity.¹⁰ However, long-term results have not been as promising as either laser therapy or anti-VEGF agents.¹⁰

Diabetic Retinopathy (DR) Main Page

Nonproliferative Diabetic Retinopathy (NPDR)

Proliferative Diabetic Retinopathy (PDR)

Infographic Summaries of DR Trials

Reading and Resources

HD Visual Learning

Clinical Exchange

References

Lim JI, Kim SJ, Bailey ST, et al. Diabetic Retinopathy Preferred Practice Pattern^®. Ophthalmology. 2025;132(4):P75-P162.
Fraser CE, D’Amico DJ, Shah, AR. Diabetic retinopathy: Prevention and treatment. In: Nathan DM, Trobe J, and Mulder JE, eds. UpToDate. https://www.uptodate.com/contents/diabetic-retinopathy-prevention-and-treatment
Yonekawa Y, Modi YS, Kim LA, et al;. American Society of Retina Specialists Clinical Practice Guidelines: Management of nonproliferative and proliferative diabetic retinopathy without diabetic macular edema. J Vitreoretin Dis. 2020;4:125-135.
Wong TY, Sun J, Kawasaki R, et al. Guidelines on diabetic eye care: The International Council of Ophthalmology recommendations for screening, follow-up, referral, and treatment based on resource settingsOphthalmology. 2018;125:1608-1622.
Wykoff CC. Management of Diabetes-Related Retinopathy. In: Prevention and Management of Diabetes-Related Eye Disease. American Diabetes Association; May 2019.11-16. https://www.ncbi.nlm.nih.gov/books/NBK544520/
American Academy of Ophthalmology^® (AAO). Diabetic Retinopathy-Asia. ONE^® Network. October 2016. https://www.aao.org/topic-detail/diabetic-retinopathy-asia
Thomson JT. Intravitreal injection of anti-VEGF drug. Retina Image Bank. 2017;27125. https://imagebank.asrs.org/file/27125/intravitreal-injectionBrown DM, Wykoff CC, Boyer D, et al. Evaluation of intravitreal aflibercept for the treatment of severe nonproliferative diabetic retinopathy: Results from the PANORAMA randomized clinical trial. JAMA Ophthalmol. 2021;139:946-955.
Figueira J, Henriques J, Carneiro Â, et al. Guidelines for the management of center-involving diabetic macular edema: Treatment options and patient monitorization. Clin Ophthalmol. 2021;15:3221-3230.
Jacoba CM, Mitzner MG, Vavallerano J, et al. Diabetic Macular Edema. AAO^®. EyeWiki^®. https://eyewiki.org/Diabetic_Macular_Edema
Wykoff CC, Abreu F, Adamis AP, et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): Two randomised, double-masked, phase 3 trials. Lancet. 2022;399:741-755.
News release. 8/18/23 (https://investor.regeneron.com/news-releases/news-release-details/eylea-hd-aflibercept-injection-8-mg-approved-fda-treatment-wet).