Ocular and systemic risk factors for higher retreatment need with intravitreal anti-VEGF for neovascular age-related macular degeneration

Poster Details

First Author: M.Zola SWITZERLAND

Co Author(s):    J. De Azevedo   L. Marchionno   C. Bergin   F. Behar-Cohen   I. Mantel                 

Abstract Details


To investigate the associations between the need for retreatment with anti-VEGF for neovascular age-related macular degeneration (nAMD) and a number of ocular and systemic factors, using a variable dosing regimen Observe-and-Plan over 2 years.


Post hoc 2-year analysis of two analogue prospective clinical research protocols using the same variable dosing treatment regimen with either ranibizumab or Aflibercept.


Both prospective clinical protocols (ranibizumab or Aflibercept) used the Observe-and-Plan, an interval based, variable dosing regimen for treatment of nAMD over a period of two years. The number of injections was recorded, along with multiple ocular and systemic baseline characteristics, as well as the Month 3 characteristics. These included age, gender, medication, cardiovascular disorders, arterial hypertension, smoking history, best corrected visual acuity (BCVA), lesion type, lesion size, geographic atrophy (GA), pigment epithelium detachment (PED), central retinal thickness (CRT), choroidal thickness, axial length, intraretinal fluid, subretinal fluid, subretinal hyperreflective material, reticular pseudodrusen, soft drusen, epiretinal membrane and vitreomacular adhesion. Univariate analysis was used to identify significant association between number of injections and clinical characteristics. Those parameters with p<0.2 in univariate analysis were included in the stepwise multivariate regression model.


220 eyes of 197 patients were included (mean age 79.9 years, 69% female). The mean number of anti-VEGF injections required was 14.2 over 2 years, the interquartile range was 10 to 18 injections. Univariate analysis indicated that the number of anti-VEGF injections was associated with higher PED at baseline and Month 3 (p<0.0001, p<0.0001), thicker CRT at baseline and Month 3 (p 0.04, p<0.0001) (adjusted for OCT type), higher amount of subretinal fluid (p 0.042), smaller GA at baseline (p 0.023), and the study (including differences in drug, OCT type and investigator team) (p 0.04). Additional factors (p<0.2) included into the multivariate model were angiographic CNV type, the choroidal thickness (adjusted for age and axial length), age, body mass index, and antidepressant medication. After multivariate linear regression (adjusting for age, axial length and study related differences), the following factors were observed to be independently associated with the number of anti-VEGF injections: PED at Month 3 (p<0.0001), CRT at baseline (p 0.03), and antidepressant medication (p 0.01). The study related differences (team, OCT and drug type) were not significantly associated with the number of injections (p 0.38).


This post hoc evaluation of 2 analogue prospective treatment studies indicates that the number of injections needed over 2 years is positively correlated with baseline CRT, 3 months PED, and antidepressant medication. CRT may be related to the amount of VEGF secretion by the lesion. PED that has not responded after the loading dose of 3 anti-VEGF injections may induce rapid sub- or intraretinal fluid recurrences requiring retreatment. Antidepressant medication is a new finding which may be related to its VEGF mediated effect. Further investigations are needed to better characterize the influence of systemic medication on need for retreatment.

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