Fluctuations in central foveal thickness and association with vision outcomes with anti-VEGF therapy for nAMD: HARBOR post hoc analysis

Abstract

Objective: To evaluate correlations between variability in central foveal thickness (CFT) and vision with ranibizumab in a HARBOR post hoc analysis.

Methods and analysis: Patients with neovascular age-related macular degeneration (nAMD; N=1097) received monthly or as-needed (PRN) ranibizumab (0.5 or 2.0 mg) for 24 months. Fluctuation scores were used to assess CFT variability; every time CFT increased and then decreased (or vice versa), numeric value of the change was added to the score. Magnitude of change <50 µm was considered clinically insignificant and did not count towards the score. Fluctuation scores were grouped into quartiles. Least squares mean (LSM) changes in best-corrected visual acuity (BCVA) were plotted against fluctuation score quartiles for CFT, subretinal fluid (SRF) height, neurosensory retina and neurosensory retina + subretinal hyper-reflective material.

Results: Patients with lower fluctuations scores (quartiles 1-3) had greatest vision gains at month 24, with LSM changes from baseline of 9.0-10.8 and 8.7-10.6 letters in the monthly and PRN arms, respectively. Corresponding changes for quartile 4 were 6.7 and 6.5 letters, respectively. There were no differences between quartiles for association between fluctuations in SRF height and BCVA gains. There were inverse correlations between magnitude of fluctuations in neurosensory and inner retina thickness and BCVA gains for quartile 4 vs quartiles 1-3. Patients in quartiles 1 and 2 showed rapid, robust BCVA gains, whereas those in quartiles 3 and 4 had lesser responses.

Conclusions: Fluctuations in retinal thickening with ranibizumab may be associated with treatment response in patients with nAMD.

Trial registration number: NCT00891735.

Keywords: clinical trial; macula; retina; treatment medical; vision.

Conflict of interest statement

Competing interests: The author(s) have made the following disclosure(s): VS: consultant for Genentech, Inc.; MD'R, SG and SB: employees of Genentech, Inc.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Least squares mean (LSM) best-corrected visual acuity (BCVA) change from baseline at month 24 by magnitude of central foveal thickness (internal limiting membrane to retinal pigment epithelium) fluctuation, including quartiles defined by all data (monthly and as-needed (pro re nata) (PRN) pooled); (A) and quartiles defined by regimen-specific data for monthly (B) and PRN (C) patients. Error bars represent 95% CI; LSM was adjusted for baseline BCVA. The numbers of patients for each quartile in the monthly arm (B) are not equal because >25% of the monthly patients had a fluctuation score of 0.

Figure 2

Least squares mean (LSM) best-corrected visual acuity (BCVA) change from baseline at month 24 by magnitude of subretinal fluid fluctuation, with quartiles defined by all data (monthly and as-needed (pro re nata) (PRN) pooled). Quartiles 1 and 2 were combined because >50% of patients had a fluctuation score of 0. Error bars represent 95% CI; LSM was adjusted for baseline BCVA.

Figure 3

Least squares mean (LSM) best-corrected visual acuity (BCVA) change from baseline at month 24 by magnitude of fluctuation of neurosensory retina thickness (internal limiting membrane to photoreceptor outer segment representative of intraretinal fluid), with quartiles defined by all data (monthly and as-needed (pro re nata) (PRN) pooled). Quartiles 1 and 2 were combined because >50% of patients had a fluctuation score of 0. Error bars represent 95% CI; LSM was adjusted for baseline BCVA.

Figure 4

Least squares mean (LSM) best-corrected visual acuity (BCVA) change from baseline by magnitude of fluctuation of inner retina thickness (representative of intraretinal fluid + subretinal hyper-reflective material), with quartiles defined by all data (monthly and as-needed (pro re nata) (PRN) pooled). Error bars represent 95% CI; LSM was adjusted for baseline BCVA.

Figure 5

Least squares mean (LSM) change in best-corrected visual acuity (BCVA) from baseline over time by fluctuation quartile, with quartiles defined by all data (monthly and as-needed (pro re nata) pooled).