Impact of macular fluid volume fluctuations on visual acuity during anti-VEGF therapy in eyes with nAMD

Abstract

Objectives: To study the effect of repeated retinal thickness fluctuations during the anti-VEGF therapy maintenance phase in neovascular age-related macular degeneration (nAMD).

Methods: Data were extracted from electronic medical records of 381 nAMD patients, aged ≥50 years; baseline VA ≥33 and ≤73 letters; ≥24 months' follow-up and ≥2 optical coherence tomography (OCT) measurements. OCT scans were analysed using an artificial intelligence algorithm that quantified the volumes of intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED) and central subfield thickness (CSFT). IRF, SRF and PED were summed to obtain total fluid (TF). The standard deviation (SD) of IRF, SRF, PED, CSFT and TF was computed and categorised into quartiles (SD-Q). Relationships between SD-Qs for each OCT feature and VA change was tested using generalised estimating equations and linear regression.

Results: By Month 24, compared to SD-Q1, eyes in SD-Q2, SD-Q3, and SD-Q4 for IRF, SRF, PED, CSFT and TF showed greater VA losses. Eyes in SD-Q4 of TF were 9.4 letters worse compared to eyes in Q1 (95% Confidence Interval: -12.9 to -6.0). The frequency of clinic visits with IRF and SRF present on OCT scans by quartiles of CSFT was lower in eyes with least fluctuation (Q1) compared to eyes with the most fluid fluctuation (Q4) (median [IQR] IRF: 0.3 [0.0-0.7] versus 0.8 [0.5-1.0]; SRF: 0.0 [0.0-0.5] versus 0.6 [0.3-1.0]).

Conclusions: Greater fluctuations in retinal fluid volumes during the maintenance phase of anti-VEGF treatment in nAMD is associated with worse VA by 2 years.

Fig. 1. Representative B scan segmented using the NOA algorithm.

The ILM and the hyperreflective RPE band are outlined in green. Two foci of intraretinal fluid are shown delineated in red. Subretinal fluid lying between the RPE band and the outer limits of the photoreceptor layer is seen in orange. ILM, inner limiting membrane; RPE, retinal pigment epithelium.

Fig. 2. GEE models of forest plots of adjusted mean change in VA from Month 3 to Month 24 by SD quartile relative to uartile 1 for each OCT marker of lesion activity.

VA changes for Q1 to Q4 for the OCT markers IRF (a), SRF (b), PED (c), CSFT (d), and total fluid (sum of IRF + SRF + PED) (e). The standard deviation for each OCT marker of lesion activity was calculated from all available visits. Point estimates for VA change with 95% CI are shown at Month 24. CI, confidence interval; CSFT, central subfield thickness; GEE, generalised estimating equation; IRF, intraretinal fluid; OCT, optical coherence tomography; PED; pigment epithelial detachment; SD, standard deviation; SRF, subretinal fluid; VA, visual acuity.