Impact of Sub-Retinal Fluid on the Long-Term Incidence of Macular Atrophy in Neovascular Age-related Macular Degeneration under Treat & Extend Anti-Vascular Endothelial Growth Factor Inhibitors

Abstract

Sub-retinal fluid (SRF) has been discussed as a protective factor against macular atrophy in eyes with neovascular age-related macular degeneration (nAMD).To gauge the impact of SRF on macular atrophy, a database of 310 nAMD eyes was screened for eyes manifesting an SRF-only phenotype under treat & extend anti-VEGF treatment, defined as nAMD expressing CNV exudation beyond the three monthly anti-VEGF loading doses by SRF only without any signs of exudative intra-retinal fluid (IRF) for ≥3 years. incidence of macular atrophy and treatment responses were evaluated on multimodal imaging, including optical coherence tomography (OCT), blue autofluorescence (BAF) and near-infrared (NIR) confocal scanning laser ophthalmoscopy and fluorescence and indocyanine green angiography (FAG/ ICGA). In total, 27 eyes (8.7%) of 26 patients with a mean follow-up of 4.2 ± 0.9 (3-5) years met the inclusion criteria. Mean age was 72 ± 6 (range: 61-86) years. The SRF only phenotype was seen from baseline in 14 eyes (52%), and in 13 eyes (48%) after a mean 1.0 ± 1.3 (1-3) injections. In years 1 to 5, mean 7.5, 5.9, 6.1, 6.1 and 7.0 anti-VEGF injections were given (p = 0.33). Cumulative macular atrophy incidence was 11.5% at year 1, 15.4% throughout years 2 to 4, and 22.4% at year 5. In conclusion, eyes manifesting activity by SRf only in treat & extend anti-VeGf regimen for nAMD seem to exhibit rather low rates of macular atrophy during long-term follow-up. SRf might be an indicator of a more benign form of nAMD. The introduction of anti-vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (nAMD) has improved visual acuity and quality of life for millions of patients worldwide 1. In the era of anti-VEGF, the long-term maintenance of visual acuity is now challenged less by fibrovascular, and more by atrophic scars 2. Incidence and growth of macular atrophy are strongly dependent on CNV activity and resulting anti-VEGF therapy 2. CNV activity and the need for retreatment are mostly defined by the presence of macular fluid, i.e. intra-retinal fluid (IRF), sub-retinal fluid (SRF), and, less prominently, sub-pigment epithelium fluid 3. While many studies have shown a robust association of IRF with worsening visual acuity and increasing rates of macular atrophy 4-6 , subretinal fluid presence has paradoxically been shown to correlate with better visual acuity as compared to a completely dry macula, especially if located sub-foveally 7,8. The reasons for the documented beneficial effects of sub-retinal fluid on visual acuity are largely unclear. The most common hypothesis concludes that SRF presence reduces the risk of vision-threatening macular atrophy 9. Therefore, new modified treat & extend regimen tolerating SRF are currently being investigated 10. However,

Short-Term Efficacy and Safety Outcomes of Brolucizumab in the Real-Life Clinical Practice

“…In fact, according to the current paradigm, the goal of anti-VEGF treatments is to keep the retina as dry as possible, with a zero-tolerance approach to retina fluids (Schmidt-Erfurth et al, 2014), and retreatment strategies such as the treat and extend approach aim to prevent recurrences (Rufai et al, 2017;Silva et al, 2018). Some recent findings, however, paradoxically correlated the presence of SRF with better visual acuity as compared to a dry macula, hypothesizing a protective effect of SRF to vision-threatening macular atrophy (Guymer et al, 2019;Jaffe et al, 2019;Siedlecki et al, 2020). Moreover, the complete resolution of retinal fluids could also increase the long-term incidence of geographic atrophy (Grunwald et al, 2014;Grunwald et al, 2017;Sadda et al, 2018).…”

Enlargement rate of geographic atrophy before and after secondary CNV conversion with associated anti-VEGF treatment

“…Multimodal imaging was performed as needed at each visit after pupil dilation as described previously [ 10 ]. At each visit, spectral domain optical coherence tomography (SD-OCT) in volume mode (49 B-scans covering an area of 6 × 6 mm centered on the fovea), near-infrared (NIR)/blue autofluorescence (BAF) confocal laser scanning ophthalmoscopy (CSLO) were performed.…”

Impact of macular fluid features on outcomes of anti-vascular endothelial growth factor treatment for type 3 macular neovascularization

“…It is well known that IRF in neovascular AMD is associated with lower baseline VA, delayed response to anti-VEGF treatment, and poor visual outcome 16 . On the other hand, SRF is associated with better visual outcome, lower frequency of anti-VEGF injections than that in patients with IRF 10 , and lower frequency of development of macular atrophy 17 . However, these correlations between visual outcome and features of macular fluid were not observed in our cohort of patients with only type 3 MNV.…”