Volumetric fluid analysis of fixed monthly anti-VEGF treatment in patients with neovascular age-related macular degeneration

Abstract

Aim: To evaluate visual outcomes and changes in fluid after administering monthly anti-vascular endothelial growth factor (VEGF) injections to treat neovascular age-related macular degeneration (nAMD) with subretinal fluid (SRF) and pigment epithelial detachment (PED).

Methods: This prospective study included eyes with nAMD previously treated with as-needed anti-VEGF injections. The patients were treated with six monthly intravitreal injections of ranibizumab. Quantitative volumetric segmentation analyses of the SRF and PED were performed. The main outcome measures included best-corrected visual acuity (BCVA), and SRF and PED volumes.

Results: Twenty eyes of 20 patients were included in this study. At the 6-month follow-up, BCVA and PED volume did not change significantly (P=0.110 and 0.999, respectively) but the mean SRF volume decreased from 0.53±0.82 mm³ at baseline to 0.08±0.23 mm³ (P=0.002). The absorption rate of the SRF volume was negatively correlated with the duration of previous anti-VEGF treatment (P=0.029). Seven of the 20 eyes (35%) showed a fluid-free macula and significant improvement in BCVA (P=0.036) by month 6.

Conclusion: Quantifying the SRF can precisely determine the patient's responsiveness to anti-VEGF treatment of nAMD.

Keywords: anti-vascular endothelial growth factor treatment; drug tolerance; neovascular age-related macular degeneration; persistent subretinal fluid; volumetric fluid analysis.

Figure 1. Manual segmentation of SRF and PED to determine the volume using the Iowa Reference Algorithm

A: Raw scan image; B: Boundaries of SRF and PED are manually delineated, as shown in green and red lines, respectively; C, D: Three-dimensional visualization of SRF and PED, with the calculated SRF and PED volumes. SRF: Subretinal fluid; PED: Pigment epithelial detachment.

Figure 2. Mean changes in best-corrected visual acuity (BCVA, ETDRS letters; A), pigment epithelial detachment (PED) volume (B), subretinal fluid (SRF) volume (C) and central macular thickness (CMT; D) during the 6-month period of monthly ranibizumab injections in patients with neovascular age-related macular degeneration with persistent fluid

The changes in the SRF and CMT were significant (linear mixed model, P=0.002 and P<0.001, respectively). ETDRS: Early Treatment Diabetic Retinopathy Study scale for visual acuity; M0: Baseline; M1: Month 1; M2: Month 2; M3: Month 3; M4: Month 4; M5: Month 5; M6: Month 6. ^aP<0.05; error bars represent the standard error.

Figure 3. Representative example showing the usefulness of quantitative assessment of subretinal fluid (SRF) volume in evaluating the response to anti-VEGF treatment

A 73-year-old man with neovascular age-related macular degeneration (nAMD) was treated with monthly intravitreal anti-VEGF injections. After three injections, the raster image of spectral domain-optical coherence tomography revealed persistent SRF. The change in SRF height after 3mo was not prominent. This patient may have been considered to have refractory nAMD if conventional qualitative methods, which are based on whether the macula is fluid-free after three anti-VEGF injections, were applied. However, evaluation of SRF volume by manual segmentation revealed a slow reduction in this measure. After three more anti-VEGF injections, the SRF was completely absorbed.