Evolution of Geographic Atrophy in Participants Treated with Ranibizumab for Neovascular Age-Related Macular Degeneration

Abstract

Purpose To evaluate the risk factors, incidence, and rate of progression of geographic atrophy (GA) in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab. Design Post-hoc analysis of a prospective clinical study. Participants 69 participants with nAMD in at least one eye. Methods Participants were prospectively treated in the study eye with 0.5 mg intravitreal ranibizumab. Study eyes received 4 monthly injections followed by pro re nata injections until a fluid-free macula was achieved on optical coherence tomography. Risk factors assessed included baseline demographics, treatment, and ocular characteristics on imaging. Eyes were evaluated on fundus autofluorescence (FAF) for GA. The rate of GA area growth in study and fellow eyes was analyzed by linear regression of square-root transformed areas. Main Outcome Measures Development of new-onset GA and rate of GA area growth measured on ocular imaging, including FAF images of the study eyes. Results Sixty-nine participants (mean age 78.8±7.8 years) with an average of 40.0±13.6 months of follow-up were analyzed. Twenty-two of 69 study eyes (32%) were treatment naïve. During their first year of the study, participants received an average of 9.2±3.3 injections in the study eye. Of 63 study eyes with quality baseline images, 22 (35%) had pre-existing GA. Of the remaining 41 eyes, 7 (17%) developed new-onset GA during study follow-up. Those who developed new GA were older (all ≥79 years old) and had received fewer study injections on average (6.9 vs. 10.4 injections at 1 year) compared to those who did not develop new GA. Of the 12 treatment naïve study eyes without GA at baseline, 1 (8.3%) developed new GA during the study. In 21 study eyes with quantifiable GA area, eyes with GA present at baseline (16/21) enlarged by 0.34±0.26 mm/year, compared to 0.19±0.12 mm/year in eyes developing new-onset GA (5/21). Conclusions While 17% of study eyes without GA present at baseline receiving ranibizumab developed new GA, the role of ranibizumab in the development of GA is unclear. Further prospective longitudinal studies are required to determine the eyes most at risk of developing GA in the setting of anti-VEGF treatment.

Anti–Vascular Endothelial Growth Factor Use and Atrophy in Neovascular Age-Related Macular Degeneration

“…Two publications reported atrophy outcomes using CFP, FA, and spectral-domain (SD) OCT from IVAN (The Inhibition of VEGF in Age-related choroidal Neovascularisation; Current Controlled Trials ISRCTN92166560). 10,27 Over 2 years, 30% of eyes demonstrated GA. 10 An analysis of 11,13e24 Color fundus photography and fluorescein angiography* HARBOR 12,25,26 Color fundus photography and fluorescein angiography IVAN 10,27 Color fundus photography, fluorescein angiography, and OCT RESPONSE 28 Color fundus photography, fluorescein angiography, SD OCT, FAF, and infrared imaging SEVEN-UP 29,30 Fluorescein angiography and FAF y TREX-AMD 31,32 SD OCT, FAF, and infrared imaging Chang et al (2015) 33 Color fundus photography and fluorescein angiography, FAF, and SD OCT Saito et al (2017) 34 Color fundus photography and short-wavelength autofluorescence Thavikulwat et al (2017) 35 Color fundus photography, fluorescein angiography, FAF, and SD OCT Zandi et al (2017) 36 FAF and SD OCT Mantel et al (2018) 37 Color fundus photography, fluorescein angiography, FAF, and SD OCT Mantel et al (2018) 38 Color fundus photography, fluorescein angiography, FAF, and SD OCT 13 Cohort study within CATT (N ¼ 1030; patients who completed 2 yrs of follow-up)…”

A Review of Macular Atrophy of the Retinal Pigment Epithelium in Patients with Neovascular Age-Related Macular Degeneration: What is the Link? Part II

“…The reported figures show that the highest MA incidence was within the first year of the study. Thavikulwat et al [40], Sadda et al [27], Li et al [47] and Sitnilska et al [48] reported percentages of MA incidence within the first year of 85%, 75%, 65% and 50%, respectively. Over a follow-up period of 4 years, Domalpally also noted that most new occurrences of MA were within the initial 2 years [49].…”

“…For some studies the expressed percentage was out of the group of study eyes that had no atrophy at the start of the study, whilst for others it was out of the whole cohort of study eyes. For some studies, eyes with baseline MA were excluded from either the analysis or from the whole study [14,21,27,35,36,40,46,48,51], others excluded eyes that did not develop MA by the end of the study [50], while the majority of the remaining reports included eyes with and without MA at baseline and also with and without MA at end of study.…”

“…CATT excluded eyes with baseline MA from the analysis [14], and so did others [35,46,48,51], and in another report CATT excluded eyes with subfoveal GA at baseline [21], and others have followed as well [36,40]. Again, Sadda et al also excluded eyes with subfoveal atrophy at baseline, yet atrophy immediately within, adjacent and nonadjacent to CNV lesions (active or regressed) was included [27].…”

“…SEVEN-UP [15][16][17], Kumar et al [30], Thavikulwat et al [40] and Wons et al [44] all included treatment non-naive eyes. Also, SEVEN-UP [15][16][17] and Kumar et al [30] included eyes that received photodynamic therapy, laser photocoagulation or steroid intravitreal treatments during the follow-up period.…”