Area of CNV Associated With Visual Acuity Loss in nAMD

Age Related Macular Degeneration, Also Called Senile Macular Degeneration. Choroidal Neovascularization. Photograph Of The Back Of Eye. (Photo By BSIP/UIG Via Getty Images)
Researchers review predictive factors of acuity loss in neovascular AMD while using anti-VEGF therapy.

A large choroidal neovascularization (CNV) area is significantly associated with either initial or secondary loss of visual acuity of ≥5 letters, despite the use of anti-vascular endothelial growth factor (VEGF) injection therapy in patients with neovascular age-related macular degeneration (AMD) according to research published in Ophthalmology Retina

Researchers conducted a post-hoc analysis of the  French Evaluation Group Avastin Versus Lucentis (GEFAL) study — a prospective, noninferiority, double-masked, randomized clinical trial ( identifier NCT01170767) — to evaluate early predictive factors of 1-year visual loss in patients with neovascular AMD treated with anti-VEGF injections with a PRN regimen. 

Patients (n=404) were randomly assigned to 1 of 2 treatment arms: either intravitreal administration of bevacizumab 1.25 mg or intravitreal ranibizumab 0.50 in 0.05 ml of solution. Each group received a loading dose period, including 3 injections at months 0, 1, and 2, and a maintenance period. Investigators chose a PRN regimen for the maintenance period. 

Reinjections were performed when patients either lost 5 or more letters since the previous visit with no atrophy or subretinal fibrosis with fluid on optical coherence tomography (OCT), when active exudation was noted on OCT, when increased CNV area or persistent leakage on angiography was seen since the previous visit, or when new or persistent subretinal or intraretinal macular hemorrhage was identified. 

The post-hoc analysis included trajectories that took into account patient visual status at 3 months and 1 year. The current analysis is based on 1-year study data who had an available best-corrected visual acuity (BCVA) reading at 3 months.

The total study population included 393 patients (mean age, 79.2±7.1 years; 67.4% women) with available month 3 BCVA. Mean BCVA at baseline was 54.9±14 letters, with a mean central macular thickness (CMT) of 357.4±116.6 µm. In 43.6% of cases, CNV type was purely occult; mean total area of CNV at baseline was 2±1.5 disc areas. 

Overall, 57.3% of patients had an absence of loss of ≥5 letters; a secondary loss of ≥5 letters after month 3 was noted in 27.7% of patients and an initial loss of ≥5 letters of BCVA was seen in 15% of patients. At month 3, mean BCVA was 62±14.5, 64.1±16.0, and 43.8±17.2 letters for each group, respectively. 

Final BCVA differed significantly between the 3 groups: 67±14.4, 49.5±20.8, and 45.5±20.9, respectively. 

At month 3, mean CMT was 247.5±66.5, 244.2±56.6, and 265±82.6 µm for each group. The final CMT differed significantly between groups. 

Across the 3 groups, baseline characteristics were comparable, excluding total CNV area which was larger in the secondary and initial loss of ≥5 letters groups. Neither baseline BCVA nor baseline CMT were “associated with a particular trajectory, nor [with] the presence of a specific fluid location or the CNV subtype.” 

Also at month 3, the presence of subretinal fluid was significantly associated with profile groups — this was not the case with intraretinal fluid. Neither CMT nor total CNV area were significantly associated with the profile group. Both intraretinal fluid (IRF) and subretinal fluid (SRF) at month 3 were identified in 36.9%, 27.5%, and 52.5% of patients in each group.  

Across the groups, the number of injections in 1 year did not differ; however, the early need for a fourth injection was associated with worse visual outcomes. Patients who had an initial loss of ≥5 letters needed this injection during the third month following the first intravitreal injection in 70.6% of cases, vs 30.6% and 48.2% in the secondary loss and absence of loss of ≥5 letters groups, respectively. 

The treatment arm — either ranibizumab or bevacizumab — was not statistically associated with any particular outcomes. 

Study limitations include the post hoc design, the need for further analysis of OCT findings that may relate to vision loss or recurrence, the short follow-up period of only 12 months, and the use of a 5-letter loss threshold, rather than the typical 15. 

“We found that a large CNV area at baseline was significantly associated with initial or secondary loss of visual acuity ≥5 letters, despite anti-VEGF injections in wet AMD,” according to the researchers. “Moreover, the presence of fluid…at [month 3] was found in patients with poorer trajectories.” 

“Further studies are needed to find other biomarkers of visual loss, especially those related to CNV subtypes, to improve follow-up and adapt treatment regimens to specific patients and diseases.” 

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures. 


Kodjikian L, Rezkallah A, Decullier E, et al; for the GEFAL study group. Early predictive factors of visual loss at 1-year in neovascular age-related macular degeneration under anti-VEGF in the GEFAL study. Ophthalmol Retina. Published online May 12, 2021. doi:10.1016/j.oret.2021.04.015