Can Anti-VEGF Therapy Benefit Macular Vessel Density?

Anti-vascular endothelial growth factor (VEGF) therapy may be useful for patients with retinal nonperfusion, as the treatment does not exacerbate the nonperfusion, according to a study published in JAMA Ophthalmology.

Anti-vascular endothelial growth factor (VEGF) therapy may be useful for patients with retinal nonperfusion, as the treatment does not exacerbate the nonperfusion, according to a study published in JAMA Ophthalmology.

In individuals with diabetes, proliferative diabetic retinopathy (PDR), and its associated complications, are a common cause of vision loss. Panretinal photocoagulation has historically been the standard of treatment for PDR, but the process can be associated with adverse effects like decreased night vision and worsening of coexisting diabetic macular edema (DME).

“Although previous studies have evaluated the association between anti—VEGF factor therapy and macular vessel density, they were confounded by the presence of macular edema, which may be associated with artifacts and segmentation errors in optical coherence tomography angiography (OCTA),” authors write.

In this secondary analysis of a randomized clinical trial, researchers aim to evaluate the association of intravitreal aflibercept with changes in macular vascular density using OCTA in patients with PDR and without DME.

The Intravitreal Aflibercept for Retinal Nonperfusion in Proliferative Diabetic Retinopathy (RECOVERY) clinical trial ran from August 1, 2016 to June 31, 2017 and included 40 eyes of 40 patients with PDR without DME.

Over the course of 12 months 20 patients received 2 mg of aflibercept injections monthly or quarterly (n = 20). The current post-hoc analysis included the eyes of 32 patients, with 16 in each cohort. Average patient age was around 48 years old while the majority (53.1%) were male.

Baseline analyses revealed a median glycated hemoglobin level of 8.75% (95% CI, 8.62%-10.21%), while the median duration of diabetes was 16.01 years (95% CI, 13.19-18.96 years).

Researchers found:

  • Average (standard deviation [SD]) central retinal thickness in all eyes decreased from 262.68 (29.42) μm (95% CI, 205-306 μm) to 231.31 (25.75) μm (95% CI, 159-270 μm) after treatment (P &thinsp;<&thinsp;.001)
  • Average central retinal thickness in the monthly cohort decreased from 263.58 (33.66) μm (95% CI, 205-302 μm) to 225.84 (29.92) μm (95% CI, 159-256 μm) after treatment (P&thinsp; =&thinsp; .003)
  • In the quarterly cohort, the average decrease in mean central retinal thickness was not statistically significant (P&thinsp; =&thinsp; .06)
  • Average total scan vascular density for the superficial vascular complex was 42.28% (4.03%; 95% CI, 40.63%-43.93%) at baseline and 39.64% (4.01%; 95% CI, 37.91%-41.37%) at month 12 (P &thinsp;= &thinsp;.69)
  • For the deep vascular complex, the average vascular density was 48.42% (4.99%; 95% CI, 46.36%-50.47%) at baseline and 45.69% (4.63%; 95% CI, 43.69%-47.70%) at month 12 (P&thinsp; =&thinsp; .40)
  • For the choriocapillaris, the average vascular density was 64.42% (3.36%; 95% CI, 63.04%-65.81%) at baseline and 62.55% (4.79%; 95% CI, 60.48%-64.62%) at month 12 (P&thinsp; = &thinsp;.16)

Overall, analyses showed no difference in vascular density parameters between the 2 injection arms after 12 months.

“Because nonperfusion is expected to progress in diabetic retinopathy, this finding may represent a beneficial association between anti—VEGF therapy and macular vascular density,” researchers write.

Authors note the mechanism by which VEGF can lead to retinal ischemia is not certain while the analysis results appear to support the association of anti-VEGF therapy with slowed development of additional areas of nonperfusion.

Findings also suggest that “progressive nonperfusion and ischemia are not the underlying mechanism responsible for retinal layer thinning.”

The small sample size poses a limitation to the analysis, in addition to the limited central 3mm2 area of the retina observed. This excluded the possibility of determining significant changes in vessel density over time in peripheral regions of the eye.

“During 1 year, we did not observe a change in central macular vessel density in eyes of patients with PDR without apparent DME treated with monthly or quarterly aflibercept therapy,” authors conclude. “Future studies with larger widefield OCTA are needed to confirm whether these observations extend to more peripheral regions of the retina.”


Alagorie AR, Nittala MG, Velaga S, et al. Association of intravitreal aflibercept with optical coherence tomography angiography vessel density in patients with proliferative diabetic retinopathy: A secondary analysis of a randomized clinical trial. JAMA Ophthalmol. Published online June 25, 2020. doi:10.1001/jamaophthalmol.2020.2130