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. 2019 Aug 1;137(8):914-920.
doi: 10.1001/jamaophthalmol.2019.1947.

Incidence of New Choroidal Neovascularization in Fellow Eyes of Patients With Age-Related Macular Degeneration Treated With Intravitreal Aflibercept or Ranibizumab

Ravi Parikh  1   2   3 , Robert L Avery  4 , Namrata Saroj  5 , Desmond Thompson  5 , K Bailey Freund  1   2
Affiliations

Incidence of New Choroidal Neovascularization in Fellow Eyes of Patients With Age-Related Macular Degeneration Treated With Intravitreal Aflibercept or Ranibizumab

Ravi Parikh et al. JAMA Ophthalmol. .

Abstract

Importance: Incidence of conversion to neovascular age-related macular degeneration (nAMD) in untreated fellow eyes of patients who are treated for nAMD in 1 eye with anti-vascular endothelial growth factor agents provides important prognostic information to clinically manage patients.

Objective: To investigate the association of treatment assignment (intravitreal aflibercept vs ranibizumab) and baseline characteristics with fellow eye conversion to nAMD in the VEGF (Vascular Endothelial Growth Factor) Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) studies.

Design, setting, and participants: This post hoc analysis of the VIEW 1 and VIEW 2 studies (randomized, double-masked, active-controlled, multicenter, 96-week, phase 3 trials comparing the efficacy and safety of intravitreal aflibercept in 2457 patients with treatment-naive eyes with nAMD) analyzed a subgroup of participants treated for nAMD in 1 eye who had untreated fellow eyes without neovascularization at baseline. All participants in the VIEW studies were included in 1 of 4 groups: ranibizumab, 0.5 mg, every 4 weeks; aflibercept, 2 mg, every 4 weeks; aflibercept, 0.5 mg, every 4 weeks; or aflibercept, 2 mg, every 8 weeks after 3 injections at 4-week intervals. Data collection in the VIEW studies occurred from July 2007 to August 2011; the data analysis presented in this report took place from April 2016 to November 2018.

Interventions: Patients received no treatment in the fellow eyes unless after conversion to nAMD, when any treatment approved by heath authorities was given per the investigators' discretion.

Main outcomes and measures: Incidence of conversion to nAMD in patients with untreated fellow eyes that had not had clinical signs of neovascularization at baseline.

Results: A total of 1561 participants were included in this analysis. At 96 weeks, 375 patients (24.0%) experienced cases of conversion to neovascular disease in the fellow eye, including 107 of the 399 individuals who received ranibizumab, 0.5 mg, every 4 weeks; 93 of the 387 individuals who received aflibercept, 2 mg, every 4 weeks; 84 of the 387 individuals who received aflibercept, 0.5 mg, every 4 weeks; and 91 of the 388 individuals who received aflibercept, 2 mg, every 8 weeks after 3 doses at 4-week intervals. The rates were 18.1, 16.2, 14.7, and 16.0 per 100 patient-years at risk at week 96, respectively. On multivariate analysis, fellow eye conversion was associated with increasing patient age (per 10 years) at baseline (hazard ratio [HR], 1.20 [95% CI, 1.05-1.36]), female sex (HR, 1.32 [95% CI, 1.06-1.63]), intraretinal fluid in the study eye at baseline (HR, 1.28 [95% CI, 1.02-1.61]), and increasing choroidal neovascularization lesion size (per 10 mm2) in the study eye at baseline (HR, 1.29 [95% CI, 1.06-1.57]). Rates of fellow eye conversion were similar with either of the treatments.

Conclusions and relevance: In this secondary analysis of randomized clinical trial data, patients with active nAMD in 1 eye appeared to have a high risk for fellow eye conversion. Such patients should be monitored closely.

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Conflict of interest statement

Conflict of Interest: Dr Avery reported personal fees from Allergan, Alimera, Amgen, Bausch & Lomb, Ocular Therapeutix, Iridex, RegenXbio, Santen, Genentech, and Eyepoint; personal fees and stock from Novartis and Regeneron; and stock in Replenish outside the submitted work. In addition, Dr Avery has a patent on retinal drug delivery issued and licensed. Dr Saroj was an employee of Regeneron at the time of the study and is currently a paid consultant for Regeneron; Dr Saroj is also a consultant for Aerie, Adverum, Allegro, Apellis, RegenxBio, and SamaCare and is an equity owner of Allegro, Pr3vent, and SamaCare, outside the submitted work. Dr Thompson reports personal fees from Regeneron during the conduct of the study. Dr Freund reported personal fees from Zeiss, Novartis, Optovue, Allergan, and Heidelberg Engineering; grants from Regeneron; and grants and personal fees from Genentech/Roche during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Patient Disposition From the Original Studies Through the Current Post Hoc Analysis
0.5q4 Indicates intravitreal aflibercept, 0.5 mg, every 4 weeks; 2q4, intravitreal aflibercept, 2 mg, every 4 weeks; 2q8, intravitreal aflibercept, 2 mg, every 8 weeks after 3 initial monthly injections; IAI indicates intravenous aflibercept injections; Rq4, intravitreal ranibizumab, 0.5 mg, every 4 weeks; VIEW, VEGF (Vascular Endothelial Growth Factor) Trap-Eye: Investigation of Efficacy and Safety in Wet AMD.
Figure 2.
Figure 2.. Time to First Conversion to Neovascular Age-Related Macular Degeneration in Fellow Eye at 12 and 24 Months
Hazard ratios compare all dosages of intravitreal aflibercept with intravitreal ranibizumab. 0.5q4 Indicates intravitreal aflibercept, 0.5 mg, every 4 weeks; 2q4, intravitreal aflibercept, 2 mg, every 4 weeks; 2q8, intravitreal aflibercept, 2 mg, every 8 weeks after 3 initial monthly injections; AMD, age-related macular degeneration; NA, not applicable; PYR, patient-years at risk; Rq4, intravitreal ranibizumab, 0.5 mg, every 4 weeks.
Figure 3.
Figure 3.. Multivariate Analysis of Baseline Factors Associated With Choroidal Neovascularization Conversion in Fellow Eye at Month 24
0.5q4 Indicates intravitreal aflibercept, 0.5 mg, every 4 weeks; 2q4, intravitreal aflibercept, 2 mg, every 4 weeks; 2q8, intravitreal aflibercept, 2 mg, every 8 weeks after 3 initial monthly injections; Rq4, intravitreal ranibizumab, 0.5 mg, every 4 weeks.
See this image and copyright information in PMC

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