Profiling neovascular age-related macular degeneration choroidal neovascularization lesion response to anti-vascular endothelial growth factor therapy using SSOCTA

Abstract

Purpose: To identify the changes in distinct vascular parameters of choroidal neovascularization (CNV) in eyes with treatment-naïve neovascular age-related macular degeneration (nAMD) during the primary response to anti-VEGF therapy using aflibercept.

Methods: Patients were prospectively followed during the first 3 months according to a standardized protocol with mandatory visits at days 7 and 14 after each anti-VEGF treatment up to day 90. Fourteen eyes were seen in addition at days 1 and 3 post-initial injection. Aflibercept was administered at baseline (BL), day 30 and 60. 6 × 6mm SSOCTA (PlexElite, Zeiss) images were acquired. Using the semi-automated AngioTool, CNV area, vessel area, vessel density (VD), the number of junctions, junctions density, total vessel length, average vessel length, total number of endpoints and lacunarity were assessed.

Results: Thirty-two consecutive patients presenting with treatment-naïve, SSOCTA-positive CNV lesions were included. Close follow-up showed a characteristic neovascular response curve with a dynamic decrease in lesion size within days and a reactive increase following 2 weeks after initial treatment. An undulating pattern was seen for all neovascular parameters except for vascular density, with variable statistical significance. Due to a flattening of the therapeutic response as early as after the second treatment, CNV lesion size and most of the related parameters had an increase in activity above baseline values at the end of the loading phase. Lesion size was the leading feature of reactivation by a mean increase of 19.3% after three monthly aflibercept injections. Subgroup analysis based on lesion size revealed a significant correlation between best-corrected visual acuity and quantitative change in lesion size over time, but not baseline size.

Conclusions: Using SSOCTA, a morphologic neovascular response pattern can be identified in anti-VEGF treatment of CNV. A synchronized early decrease and consecutive reactivation in a large spectrum of neovascular biomarkers including size and internal structure are visualized in a qualitative and quantitative manner. SSOCTA analyses allow new insights in CNV morphology changes and therapeutic response.

Keywords: SSOCTA; biomarker; choroidal neovascularization; loading phase; neovascular age-related macular degeneration.

Fig. 1

logMAR visual acuity during aflibercept loading dose.

Fig. 2

Relative choroidal neovascularization area change from baseline during aflibercept loading dose. Vertical dashed lines indicate intravitreal injections; BL = baseline (day 0); The asterisk indicates a statistically significant difference based on pixel data.

Fig. 3

The choroidal neovascularization (CNV) area as expressed by relative change form baseline. CNV reacted to aflibercept treatment with an instant decrease in size starting within 24 h continuing until day 14. BL = baseline (day 0).

Fig. 4

Median logMAR best‐corrected visual acuity change during loading dose in subgroups with in‐ or decreasing choroidal neovascularization area.

Fig. 5

Relative change from baseline shown for parameters characterizing the choroidal neovascularization area by SSOCTA: vessel density (VD), vessel area, total vessel length, total number of junctions and junctions density displayed over time (days). Vertical dashed lines indicate aflibercept treatment. Asterisks indicating significant change compared with baseline.