Elsevier

Ophthalmology

Volume 121, Issue 6, June 2014, Pages 1237-1245
Ophthalmology

Original article
Morphologic Parameters Relevant for Visual Outcome During Anti-Angiogenic Therapy of Neovascular Age-Related Macular Degeneration

https://doi.org/10.1016/j.ophtha.2013.12.029Get rights and content

Purpose

To identify the effects of anti-angiogenic therapy in neovascular age-related macular degeneration (AMD) in respect to morphologic type and time course and to identify prognostic factors for visual outcome on the basis of standardized optical coherence tomography (OCT) analysis.

Design

Subanalysis of a prospective, 12-month, multicenter, phase IIIb trial (Efficacy and Safety of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration [EXCITE]).

Participants

A total of 353 treatment-naïve patients with subfoveal choroidal neovascularization (CNV) receiving quarterly or monthly ranibizumab therapy.

Methods

Patients were randomized to receive 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised a loading phase of 3 consecutive monthly injections followed by a 9-month maintenance phase of monthly or quarterly injections. Best-corrected visual acuity (BCVA) was measured using the Early Treatment Diabetic Retinopathy Study protocol, and retinal morphology was assessed by Stratus OCT (Carl Zeiss Meditec, Dublin, CA). Imaging data were evaluated by certified examiners of the Vienna Reading Center using a standardized protocol.

Main Outcome Measures

The BCVA was measured using ETDRS charts and retinal morphology was assessed by OCT.

Results

During the loading phase, there was a significant correlation between a reduction in central retinal thickness and an increase in BCVA (P < 0.001), which decreased during the maintenance phase in all treatment arms. The proportion of patients showing retinal morphologic changes, such as intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment epithelial detachments (PEDs), decreased significantly in all groups (P < 0.001), more intensively in the 0.5 mg quarterly than in both 0.3 mg groups. Intraretinal cysts resolved most rapidly followed by SRF, whereas PED decreased at a slower rate and intensity. Patients with IRC at baseline had lower BCVA levels that remained lower over the entire study period, whereas recurrence of IRC during follow-up showed no additional negative effect on function. Baseline SRF had no effect on visual recovery; however, recurrence of SRF during follow-up showed a tendency for an additional negative effect on function (P = 0.06). Baseline PED showed a negative influence on visual outcome only in combination with IRC and SRF.

Conclusions

There is a distinct response pattern and time course of morphologic parameters associated with anti-vascular endothelial growth factor therapy in neovascular AMD. Specific alterations, such as IRC, SRF, and PED, as baseline or follow-up features are significantly influencing the potential for visual gain.

Section snippets

Study Design

The EXCITE study was designed as a 1-year, randomized, double-masked, active-controlled, multicenter, phase IIIb study in patients with subfoveal CNV secondary to AMD, comparing the efficacy and safety of quarterly dosing regimens of ranibizumab in 2 different dosages with a monthly dosing regimen during the maintenance phase, that is, from month 3 onward.

Eligible patients were randomly assigned in a 1:1:1 ratio to any of the following 3 double-masked treatment arms (Fig 1): loading dose of 3

Patients

A total of 353 patients at 59 study sites were randomized for treatment with the study medication. The study was completed by 106 patients in the ranibizumab 0.3 mg quarterly group (arm A), 95 patients in the ranibizumab 0.5 mg quarterly group (arm B), and 103 patients in the ranibizumab 0.3 mg monthly group (arm C). The patients' disposition, baseline and ocular disease characteristics, treatment exposure, adverse events, BCVA, and CRT time course and contrast sensitivity analysis in the 3

Discussion

In the present investigation, change in overall CRT and individual morphologic parameters (IRC, SRF, PED) were documented in a quantitative and qualitative manner and correlated with functional outcomes during a 12-month follow-up. Datasets from a prospective multicenter trial offering a direct comparison between a continuous immediate re-treatment strategy and a discontinuous delayed regimen allowing exacerbation of morphologic alteration were analyzed. Certified graders of an independent

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      Indeed, the presence of SRF at baseline was an independent negative predictor of final BCVA in the multivariate model (P = 0.008). The role of SRF and IRF as possible outcome predictors was intensively analyzed in previous papers.19,21,29–32 Several studies reported that baseline IRF is associated with poorer outcomes in nAMD patients,29–32 whereas baseline SRF predicts good visual outcomes in patients receiving anti-VEGF therapy33.

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    The data presented in this paper are the result of independent sub-analysis of the EXCITE study conducted by the VRC without any financial support. The Department of Ophthalmology at the Medical University of Vienna served as a clinical site in the EXCITE study and received regular recompensation for contract research. The sponsor or funding organization had no role in the design or conduct of this research.

    Financial Disclosure(s): The author(s) have made the following disclosure(s): U.M.S.-E. was a principal investigator in the EXCITE trial. C.S. is the director of the VRC, which performed the OCT data analysis during the EXCITE study.

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