Relationship between retinal fluid and visual acuity in patients with exudative age-related macular degeneration treated with intravitreal aflibercept using a treat-and-extend regimen: subgroup and post-hoc analyses from the ALTAIR study

Abstract

Purpose: To explore the relationship between retinal fluid status and best-corrected visual acuity (BCVA) in patients treated with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) in the ALTAIR study.

Methods: Outcomes were investigated according to overall fluid status at week 16 (predefined) and the relationship between any fluid, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment with BCVA at baseline, and weeks 16, 52, and 96 (post-hoc). The analyses involved treatment-naïve patients (N = 246) with exudative age-related macular degeneration (AMD), aged ≥ 50 years with BCVA of 73-25 Early Treatment Diabetic Retinopathy Study letters, who participated in the ALTAIR study.

Results: The mean (standard deviation) change in BCVA from baseline to week 52 was + 10.6 (10.9) and + 6.5 (16.0) letters in patients without and with fluid at week 16, respectively; and to week 96 was + 9.1 (14.3) and + 4.3 (16.1) letters in patients without and with fluid at week 16, respectively. The last injection interval was 16 weeks in 33.6% and 2.0% (week 52), and 62.9% and 17.6% (week 96) of patients without or with fluid at week 16, respectively. At baseline, 35.7% of patients had IRF and 85.2% of patients had SRF, which decreased to 11.8% (IRF) and 31.7% (SRF) of patients, 8.5% (IRF) and 18.7% (SRF), and 6.5% (IRF) and 20.7% (SRF) at weeks 16, 52, and 96, respectively. Presence of IRF at all timepoints was associated with poorer BCVA than if IRF was absent, while the presence of SRF was not associated with poorer BCVA compared with the absence of SRF.

Conclusion: IVT-AFL T&E dosing was effective at clearing fluid regardless of fluid type in ~ 80% of patients with exudative AMD. Patients without fluid at week 16 had numerically better BCVA than those with fluid at week 16. Over 60% of patients without fluid at week 16 achieved the maximum treatment interval of 16 weeks by study end, compared with < 20% of patients with fluid at week 16. IRF (weeks 16, 52, 96), although evident in a small number of patients, was associated with poorer BCVA, whereas SRF was not.

Trial registration: ClinicalTrials.gov Identifier: NCT02305238.

Keywords: Aflibercept; Exudative age-related macular degeneration; Ophthalmology; Post-hoc; Treat-and-extend.

Conflict of interest statement

M.O.: grants and personal fees—AbbVie Japan, Inc., Alcon Pharma K.K. (Japan), Allergan, B.L.J Ltd., Bayer Yakuhin, Ltd. (Japan), Chengdu Kanghong Biotechnology Co., Ltd., Chugai, HOYA, Kowa, Novartis Pharma K.K., Otsuka Pharmaceuticals, Pfizer Pharmaceuticals K.K, Santen Pharmaceuticals Co., Ltd., and Senju Pharmaceutical Co., Ltd., Topcon, during the conduct of the study.

A.A.O.: personal fees—Allergan Japan, Astellas Japan, Bayer Healthcare AG, Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Otsuka Pharmaceutical Co., Ltd, and Senju Pharmaceutical Co., Ltd.; grants and personal fees—Bayer Yakuhin Ltd. (Japan), Novartis Pharma KK (Japan), and Santen Pharmaceutical Co., Ltd, during the conduct of the study; and personal fees—AbbVie Japan, Inc., Kowa Co., Ltd., and Mitsubishi Tanabe Pharma Corporation, outside of the submitted work.

K.S.: employee—Bayer Yakuhin Ltd., Japan.

T.M. and S.-C.C.M.: employees—Bayer AG, Berlin, Germany.

K.T.: grants and personal fees—Alcon Japan, Allergan Japan, Bayer Yakuhin, Ltd. (Japan), HOYA, Kowa, Kyowa Kirin Co., Ltd., Nitto Medic, Novartis Pharma, Ono, Otsuka Pharmaceuticals, Santen Pharmaceuticals Co., Ltd., and Senju Pharmaceutical Co., Ltd during the conduct of the study.

© 2021. The Author(s).

Figures

Fig. 1

The proportion of patients with a last treatment interval up to week 96 of 8, 10, 12, 14, or 16 weeks and mean (SD) last treatment interval in A patients without fluid at week 16 and B patients with fluid at week 16 according to IVT-AFL adjustment regimen in the full analysis set (N = 246).a,b,c The last treatment interval was calculated based on the last two doses received (overall, 227 patients completed week 52 of treatment and 212 patients completed week 96). aFluid status was assessed by the investigator based on the presence or absence of any new or persistent fluid (on OCT); bFluid status was unknown in the IVT-AFL-2 W adjustment group (n = 1); cTwo adjustment groups are combined (IVT-AFL-2 W and IVT-AFL-4 W). IVT-AFL, intravitreal aflibercept; IVT-AFL-2 W, IVT-AFL 2-week adjustment; IVT-AFL-4 W, IVT-AFL 4-week adjustment; OCT, optical coherence tomography; SD, standard deviation

Fig. 2

Mean (SD) absolute and mean (95% CI) change in BCVA (ETDRS letters) from baseline to week 96 in patients without and with fluid at week 16a,b in the full analysis set (N = 246), with last observation carried forward. aFluid status was assessed by the investigator based on the presence or absence of any new or persistent fluid (on OCT); bTwo adjustment groups are combined (IVT-AFL-2 W and IVT-AFL-4 W); fluid status was unknown in the IVT-AFL-2 W group (n = 1). BCVA, best-corrected visual acuity; CI, confidence interval; ETDRS, Early Treatment Diabetic Retinopathy Study; IVT-AFL, intravitreal aflibercept; IVT-AFL-2 W, intravitreal aflibercept with 2-week adjustment; IVT-AFL-4 W, intravitreal aflibercept with 4-week adjustment; OCT, optical coherence tomography; SD, standard deviation

Fig. 3

Mean (SD) absolute and mean (95% CI) change in CRT (μm) from baseline to week 96 in patients without and with fluid at week 16a,b in the full analysis set (N = 246), with last observation carried forward. aFluid status was assessed by the investigator based on the presence or absence of any new or persistent fluid (on OCT); bTwo adjustment groups are combined (IVT-AFL-2 W and IVT-AFL-4 W); fluid status was unknown in the IVT-AFL-2 W group (n = 1). CI, confidence interval; CRT, central retinal thickness; IVT-AFL, intravitreal aflibercept; IVT-AFL-2 W, intravitreal aflibercept with 2-week adjustment; IVT-AFL-4 W, intravitreal aflibercept with 4-week adjustment; OCT, optical coherence tomography; SD, standard deviation

Fig. 4

The proportion of patients with A IRF or B SRF at each timepoint from baseline to week 96a,b in the full analysis set (N = 246), with last observation carried forward. aFluid status was assessed by the investigator based on the presence or absence of any new or persistent fluid (on OCT); bTwo adjustment groups are combined (IVT-AFL-2 W and IVT-AFL-4 W); IRF and SRF fluid status was unknown in n = 2 at baseline and in n = 5 at week 8. IRF, intraretinal fluid; IVT-AFL, intravitreal aflibercept; IVT-AFL-2 W, intravitreal aflibercept with 2-week adjustment; IVT-AFL-4 W, intravitreal aflibercept with 4-week adjustment; OCT, optical coherence tomography; SRF, subretinal fluid

Fig. 5

Mean absolute BCVA (ETDRS letters) and 95% confidence intervals at mandatory study visits at weeks 0, 16, 52, and 96 in A patients without or with any foveal or non-foveal fluid,aB patients without or with any foveal or non-foveal IRF, C patients without or with any foveal or non-foveal SRF, and D patients without or with any foveal or non-foveal PED. Full analysis set (N = 246).b,c The number underneath each bar represents the number of patients in each group at each study visit. aIncludes IRF and SRF only; bMissing for each fluid compartment at baseline (n = 2); cUnknown for IRF at baseline (n = 3). BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; IRF, intraretinal fluid; PED, pigment epithelial detachment; SRF, subretinal fluid