Growth of Geographic Atrophy in the Comparison of Age-related Macular Degeneration Treatments Trials

Abstract

Purpose To evaluate the growth of geographic atrophy (GA) during anti-VEGF therapy. Design Cohort within clinical trial. Participants Patients included in the Comparison of Age-related Macular Degeneration (AMD) Treatments Trials (CATT) Methods Participants were randomly assigned to injections of ranibizumab or bevacizumab and to a 2-year dosing regimen of monthly or pro re nata (PRN), or to monthly for 1 year and PRN the following year. Digital color photographs and fluorescein angiograms at baseline, 1 and 2 years were evaluated for GA and the total area of GA was measured by two graders masked to treatment; differences were adjudicated. Multivariate linear mixed models of the annual change in the square root of the area included baseline demographic, treatment, and ocular characteristics on imaging as candidate risk factors. Main outcome measures GA growth rate. Results Among 1185 participants, 86 (7.3%) had GA at baseline, 120 (10.1%) developed GA during year 1 and 36 (3.0%) during year 2. Among 194 eyes evaluable for growth, the rate was 0.43 (standard error [SE]: ±0.03) mm/year. In multivariate analysis, the growth rate was 0.37 mm/year in eyes receiving bevacizumab and 0.49 mm/year in eyes receiving ranibizumab (difference 0.11, 95% Confidence Interval [CI]: (0.01, 0.22); p=0.03). Growth rate did not differ between eyes treated monthly and PRN (p=0.85). Eyes with subfoveal CNV lesions had a lower growth rate than eyes with non-subfoveal CNV lesions (difference 0.12, CI: 0.01, 0.22; p=0.03). Eyes with GA farther from the fovea had higher growth rates by 0.14 (CI: 0.01, 27) mm/year for every mm farther from the fovea. The growth rate was 0.58 mm/year for eyes with predominantly classic lesions, 0.41 mm/year for eyes with minimally classic lesions, and 0.30 mm/year for eyes with occult only lesions (p<0.01). The growth rate in eyes having a fellow eye with GA was higher by 0.13 (CI: 0.01, 0.24; p=0.03) mm/year than in eyes without GA in the fellow eye. Eyes with epiretinal membrane had a higher growth rate than eyes without epiretinal membrane (difference 0.16, CI: (0.03, 0.30; p=0.02). Conclusion GA growth depends on several ocular factors. Ranibizumab may accelerate GA growth.

Risk of geographic atrophy in age-related macular degeneration patients treated with intravitreal anti-VEGF agents

“…3 The CATT cohort consisted of 1185 patients with AMD-related CNV, but patients with foveal centre GA were excluded. Morphologic features of the study eyes were evaluated as in the previous study, and whereas GA detected at baseline was considered as 'prevalent GA', GA at years 1 or 2 or both was considered as 'incident GA'.…”

“…1 Retrospective data analysed from multicentre clinical trials demonstrate the necessity of long term followup of patients treated with anti-vascular endothelial growth factor (anti-VEGF) agents, both to monitor long-term visual outcomes and also to evaluate safety of this therapy with respect to the risk of developing GA. [2][3][4] Recently, phase III clinical trials have begun to evaluate treatment for geographic atrophy (the parallel CHROMA and SPECTRI studies, ClinicalTrials.gov Identifier: NCT02247479 and NCT02247531, respectively).…”

What Is the Best Neovascular Age-related Macular Degeneration Treatment Regime for 2016?

“…Concerns about overinjection leading to a higher rate or endophthalmitis or as-of-yet-to-be-confirmed progression of atrophy steers clinicians away from this approach. 12,13 Likewise, the significant burden to patients, carers and healthcare professionals make this approach impractical for many. The 2-monthly fixed-dosing arm (after three initiation doses in the first year) reduced this injection and visit burden considerably.…”

Long-term effects of intravitreal ranibizumab treatment on retinal ganglion cell complex and choroidal thickness

“…While some of them are related with intravitreal injection procedure, somes are directly related with anti-VEGF drugs. More recently, a novel complicationduring anti-VEGF therapy which is termed as ''retinal atrophy'' has become a current issue [5] still there is a conflict on the definition of the atrophy, it can be described as the atrophy of retina pigment epithelium (RPE) and choriocapillaries that is similar to the appearence of de novo geographic atrophy (GA) [6]. Besides, we know that VEGF inhibition also leads to nonperfusion of vessels in the choroid plexus [7], afterwards choriocapillaries and RPE degeneration occurs [8].…”

“…Besides, we know that VEGF inhibition also leads to nonperfusion of vessels in the choroid plexus [7], afterwards choriocapillaries and RPE degeneration occurs [8]. A great number of studies investigated the association between anti-VEGF treatment and RPE-choroidal atrophy by using fundus autofluorescence (FAF) or near-infrared autofluorescence, fluorescein angiogram and/or optical coherence tomography (OCT) imagings [6,[9][10][11][12][13][14][15][16]. However, there is limited study in the literature looking at the difference in retinal layers thicknesses in neovascular and nonneovascular AMD patients in order to determine the plausible effect of anti-VEGF treatment [17][18][19].…”