Added Benefits Seen With Early Initiation of Anti-VEGF Agents for Diabetic Retinopathy

Charles C. Wykoff, MD, PhD


May 26, 2016

In This Article

A New Threshold for Treatment Initiation

According to the World Health Organization's just-released first Global Report on Diabetes, approximately 1 in 12 (8.5%) adults globally have diabetes mellitus.[1] Consequently, both diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are increasing in prevalence and remain major causes of visual acuity (VA) loss, accounting for approximately 2.6% of cases of global blindness in 2010.[1,2]

For decades, development of clinically significant DME or PDR represented a threshold for initiating ocular-specific treatment, with laser-based modalities being the cornerstone management strategy for both. Macular laser treatment for DME reduces the risk for progressive visual loss by about 50%,[3] and application of appropriate panretinal photocoagulation (PRP) for PDR dramatically reduces the risk for severe vision loss.[4]

Despite their proven value, laser treatments have limitations and possible untoward effects. Macular laser treatment for DME appears to be ineffective at substantially improving mean VA,[5,6,7] and PRP can lead to peripheral visual field defects, night-vision impairment, and reduction of contrast sensitivity. Furthermore, PRP can be incompletely effective in some eyes, with supplemental PRP required in 45% of eyes and a subsequent need for vitrectomy in approximately 5%.[8,9]

Antibody-based pharmacologic agents administered directly into the eye via intravitreal injection block the activity of vascular endothelial growth factor A (VEGF). These agents have revolutionized the treatment of DME and PDR over the past 10 years, shifting the management paradigm in many cases from laser-based modalities to medical options. Randomized, controlled, phase 3 trials have demonstrated that the US Food and Drug Administration (FDA)-approved anti-VEGF agents aflibercept (Eylea®; Regeneron) and ranibizumab (Lucentis®; Genentech), as well as off-label bevacizumab (Avastin®; Genentech), can be remarkably effective for the treatment of both center-involved DME leading to VA loss[6,7,10] and less severe stages of PDR.[9]

Recent data from multiple sources collectively indicate that initiating ocular-specific treatments at earlier stages of diabetic retinopathy (DR) may be warranted. The driver of this shift toward timelier treatment initiation is the apparent clinical relevance of earlier stages of DR to our patients' well-being. Specifically, DR itself, even in the absence of DME or PDR, appears to have a significant effect on patients' visual lives.

DR severity is quantified using the Diabetic Retinopathy Severity Scale (DRSS).[11] This scale has established prognostic value: Worsening of two or more steps on the DRSS is associated with an increased risk for subsequent vision loss.[12]

In the population-based Los Angeles Latino Eye Study, 1064 of 7789 self-identified Latino adults had diabetes and underwent ocular examinations as well as detailed health-related quality-of-life (HRQOL) assessments. Results of this large cohort analysis supported prior observations that patients with DR have a measurable decline in HRQOL early in the disease process, well before the standard threshold for initiation of ocular-specific DR treatments. The correlation between decreasing HRQOL and increasing DR severity was significant (P<.001) for all QOL subscales considered, including driving difficulties, vision-related dependency, and vision-related mental health. There appeared to be a significant negative trend in HRQOL measures when both eyes were affected with just moderate nonproliferative DR (NPDR) (level 43), which continued to decline as DR severity increased.[13]


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