Title: Pachydrusen in Fellow Eyes Predict Response to Aflibercept Monotherapy in Patients with Polypoidal Choroidal Vasculopathy

Abstract

We investigated whether responses to as-needed intravitreal aflibercept injections (IAIs) for polypoidal choroidal vasculopathy (PCV) differed among patients based upon drusen characteristics in fellow eyes. 110 eyes from 110 patients with PCV received 3 monthly IAI and thereafter Pro re nata (PRN) IAI over 12 months. Patients were classified into 4 groups depending on fellow eye findings. Group 1 (n = 16): pachydrusen; Group 2 (n = 45): no drusen; Group 3 (n = 35): soft drusen; Group4 (n = 14) PCV/scarring. Best-corrected visual acuity improved at 12 months in all groups, but not significantly in Group 1 and Group 4; however, visual improvement was similar among the groups after adjusting baseline confounders. Group 1 had a significantly lower percentage of eyes needing retreatment (all p < 0.001; Group 1: 16.7%; Group 2: 50.8%; Group 3: 80%; Group 4: 85.7%). The mean number of retreatments was least in Group 1 among the groups (all p-value < 0.003; Group 1: 0.50 ± 1.32; Group 2: 1.73 ± 2.08; Group 3:2.71 ± 1.99; Group 3: 2.71 ± 2.16). Patients with pachydrusen in fellow eyes were less likely to require additional IAI following the loading dose and may be ideal candidates for aflibercept monotherapy in their first year.

Keywords: as-needed aflibercept therapy; pachydrusen; polypoidal choroidal vasculopathy; treatment burden.

Figure 1

An eighty-year-old male patients with polypoidal choroidal vasculopathy. (A). Color fundus photography showed hemorrhagic pigment epithelial detachment in the right eye. On the indocyanine green angiography (ICGA), polypoidal lesion and branching vascular network was seen in the right eye. (B). A vertical OCT scan through the fovea showed subretinal fluid and pigment epithelial detachment. (C). Color fundus photography showed soft drusen surrounded by a white square in the left eye. On the ICGA, the soft drusen exhibited hypofluorescent in the left eye. (D). A vertical OCT scan through the soft drusen showed retinal pigment epithelial bump (red arrow).

Figure 2

A seventy-three-year-old male patient with polypoidal choroidal vasculopathy. (A). Color fundus photography showed scattered yellowish drusenoid deposits around the macular in both eyes and exudation in the macular in the right eye. (B). On the early phase of ICGA, polypoidal lesion was seen in the macula in the right eye. (Left image). On the late phase of ICGA, hyperfluorescence was seen in the area corresponding to scattered yellowish drusenoid deposits in both eyes. (Middle and left image) (C). A horizontal OCT scan through the fovea showed exudation including subretinal fluid and fibrin in the right eye. Subfoveal choroidal thickness was 375 µm in the right eye. (D). A horizontal OCT scan through the yellowish deposits showed drusenoid deposits (as indicated by a red arrow) in the left eye.

Figure 3

Changes of best-corrected visual acuity (BCVA) from initial treatment according to the groups. In pachydrusen group, BCVA improved from 0.26 ± 0.32 (baseline) to 0.17 ± 0.19 (p = 0.276), 0.13 ± 0.20 (p = 0.11), 0.089 ± 0.16 (p = 0.054), 0.10 ± 0.20 (p = 0.081) at 3 months, 6 months, 9 months, and 12 months, respectively. In no drusen group, BCVA improved from 0.39 ± 0.38 (baseline) to 0.31 ± 0.34 (p = 0.023), 0.24 ± 0.32 (p = 3.8×10^-6), 0.21 ± 0.29 (p = 8.25×10^-8), 0.19 ± 0.28 (p = 4.8×10^-7) at 3 months, 6 months, 9 months, and 12 months, respectively. In soft drusen group, BCVA improved from 0.35 ± 0.29 (baseline) to 0.31 ± 0.35 (p = 0.016), 0.27 ± 0.31 (p = 9.8×10^-3), 0.27 ± 0.34 (p = 0.043), 0.29 ± 0.35 (p = 0.14) at 3 months, 6 months, 9 months, and 12 months, respectively. In PCV/Scarring group, BCVA improved from 0.31 ± 0.35 (baseline) to 0.17 ± 0.19 (p = 0.086), 0.15 ± 0.20 (p = 0.019), 0.14 ± 0.16 (p = 0.074), 0.14 ± 0.14 (p = 0.054) at 3 months, 6 months, 9 months, and 12 months, respectively.

Figure 4

Changes of central retinal thickness (CRT) from initial treatment according to the groups. In pachydrusen group, CRT significantly decreased from 408 ± 171 (baseline) to 190 ± 98, 185 ± 82, 190 ± 86, 202 ± 113 at 3 months, 6 months, 9 months, and 12 months, respectively. (all p-value < 0.001) In no drusen group, CRT significantly decreased from 373 ± 160 (baseline) to 202 ± 81, 210 ± 71, 215 ± 75, 218 ± 85 at 3 months, 6 months, 9 months, and 12 months, respectively. (all p-value < 0.001) In soft drusen group, CRT significantly decreased from 406 ± 210 (baseline) to 196 ± 69, 240 ± 113, 229 ± 114, 236 ± 122 at 3 months, 6 months, 9 months, and 12 months, respectively. (all p-value < 0.001) In PCV/Scarring group, CRT significantly decreased from 434 ± 132 (baseline) to 242 ± 99, 254 ± 114, 245.0 ± 84, 234 ± 83 at 3 months, 6 months, 9 months, and 12 months, respectively. (all p-value < 0.05).

Figure 5

Changes of subfoveal choroidal thickness (SCT) from initial treatment according to the groups. In pachydrusen group, SCT significantly decreased from 325 ± 114 (baseline) to 296 ± 108, 298 ± 120, 305 ± 119, 298 ± 118 at 3 months, 6 months, 9 months, and 12 months, respectively. (all p-value < 0.05) In no drusen group, SCT significantly decreased from 235 ± 92 (baseline) to 204 ± 82, 210 ± 89, 206 ± 83, 211 ± 88 at 3 months, 6 months, 9 months, and 12 months, respectively. (all p-value < 0.0001) In soft drusen group, SCT significantly decreased from 200 ± 76 (baseline) to 170 ± 77, 165 ± 72, 171 ± 72, 166 ± 67 at 3 months, 6 months, 9 months, and 12 months, respectively. (all p-value < 0.01) In PCV/Scarring group, SCT significantly decreased from 260 ± 114 (baseline) to 239 ± 100, 235 ± 93, 241 ± 97, 225 ± 89 at 3 months, 6 months, 9 months, and 12 months, respectively. (all p-value < 0.05).

Figure 6

Kaplan–Meier estimator showing retreatment-free proportion after initial treatment according to the groups. Retreatment-free proportion at 12 months was 83.3% (13/16), 41.2% (19/45), 20% (7/35), 14.3% (2/14) in pachydrusen group, no drusen group, and PCV/ Scarring group, respectively. Retreatment-free period was significantly longer in pachydrusen group compared to other groups. (all p-value < 0.001). Mean number of additional injections was significantly smaller in Group 1 (0.5 ± 1.32) compared with other groups. (Group 2: 1.73 ± 2.08, p = 7.5×10^-3; Group 3: 2.71 ± 1.99, p = 1.4×10^-4; Group 4: 2.71 ± 2.16, p = 4.0×10^-4).