Author: David Sarraf (United States)
Co-authors: Arshad M. Khanani, SriniVas R. Sadda, Andrew Chang, David T. Wong, Anne-Sophie Kempf, Insaf Saffar
Purpose
To investigate the effect of retinal pigment epithelial detachment (PED) thickness (i.e., height) and variability on best corrected visual acuity (BCVA) over 96 weeks of follow-up in anti-VEGF treated patients with neovascular age-related macular degeneration (nAMD).
Setting/Venue
Post hoc treatment-agnostic analysis of the pooled cohorts of the 96-week, randomized, double-masked, multicentre Phase III clinical trials HAWK (NCT02307682) and HARRIER (NCT02434328) of nAMD patients treated with either brolucizumab 6 mg or aflibercept 2 mg (n=1396 patients).
Methods
Optical coherence tomography images from anti-VEGF treated patients in the pooled HAWK and HARRIER (H&H) studies were assessed for the maximum PED thickness across the macula at baseline through to Week 96. The impact of PED thickness on BCVA outcomes was assessed by comparing BCVA change from baseline to Week 96 in the subgroups of patients with either less than 200 µm or ≥200 µm PED thickness at baseline and at Week 12 (the first visit when the full effect of the three loading injections could be observed). The impact of PED fluctuations on change in BCVA from baseline to Week 96 was evaluated by grouping the H&H cohort into four PED variability quartiles (Qv1–4) based on PED variability expressed as PED thickness standard deviation (SD) for each patient from Week 12 to Week 96. Furthermore, the association between PED thickness and the presence of other retinal fluids was probed by grouping the H&H cohort into four quartiles based on PED thickness (Qh1–4) at Week 48 (time of primary endpoint) and assessing the presence of intraretinal fluid (IRF) and subretinal fluid (SRF) in these quartiles at that specific time point.
Results
Patients with baseline PED thickness less than 200 µm (n=870) gained (mean ± standard error) 8.0±0.4 and 7.0±0.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline at Weeks 48 (p=0.0003) and 96 (p=0.004), respectively, versus 5.5±0.6 and 4.6±0.6 ETDRS letters for patients with baseline PED thickness ≥200 µm (n=513). Patients with Week 12 PED thickness less than 200 µm (n=1138) gained 7.5±0.4 and 6.5±0.4 ETDRS letters from baseline at Weeks 48 (p=0.03) and 96 (p=0.04), respectively, versus 5.5±0.9 and 4.3±1.0 ETDRS letters for patients with Week 12 PED thickness ≥200 µm (n=215). BCVA gains from baseline were lower for patients in the quartile Qv4, which had the highest variability (Week 48 ETDRS letter gains: Qv1: 7.1±0.7; Qv2: 8.4±0.7; Qv3: 8.1±0.7; Qv4: 5.0±0.7; Week 96 ETDRS letter gains: Qv1: 6.2±0.8; Qv2: 7.9±0.8; Qv3: 7.2±0.8; Qv4: 3.3 ±0.8). Compared with patients in Qh1, Qh2–4 patients showed a steadily increasing association (odds ratio [95% confidence interval]) of PED thickness with presence of both IRF (Qh2: 1.5 [0.9; 2.5]; Qh3: 1.9 [1.2; 3.2]; Qh4: 3.9 (2.4; 6.2]) and SRF (Qh2: 1.6 [1.0; 2.6]; Qh3: 2.3 [1.5; 3.6]; Qh4: 5.6 (3.6; 8.6]).
Conlusions
In this pooled, treatment-agnostic HAWK and HARRIER post hoc analysis, BCVA outcomes over 96 weeks were better in patients with PED thickness less than 200 µm at baseline or at Week 12 compared with patients with PED thickness ≥200 µm. Greater fluctuations in PED thickness from Week 12 through Week 96 were also associated with lower BCVA gains at Week 96, and increasing PED thickness at Week 48 was associated with an increasing presence of IRF and SRF, especially in the group with the greatest PED thickness. The results of this analysis therefore indicate that lower and less variable PED thickness is associated with reduced disease activity and improved visual outcomes in nAMD patients treated with anti-VEGF. PED thickness may thus represent a surrogate of neovascular activity.
Financial Disclosure
Consultant for Amgen, Bayer, Genentech, Iveric Bio, Novartis, Optovue; Research grants from Amgen, Genentech, Heidelberg, Optovue, Regeneron, Topcon; Speaker fees from Optovue
Comments
Additional Co-authors: 7. Shuhan Tang - Novartis Pharma AG, Basel, Switzerland 8. Ramin Tadayoni - Department of Ophthalmology, Université de Paris, AP-HP, Lariboisière, Saint Louis and Rothschild Foundation Hospitals, Paris, France
