Khurana RN, Chang L, Day BM, Ghanekar A, Stoilov I. Timing of Peak Vision Gains in Patients with Neovascular Age-Related Macular Degeneration Treated with Ranibizumab. Ophthalmol Retina. 2020;4(8):760-766. doi:10.1016/j.oret.2020.02.011
It is widely accepted that the treatment of neovascular age-related macular degeneration (nAMD) includes intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents; however, the “art” of determining and optimizing treatment schedules in patients is often based on empiricism and physician preference. Additionally, the decision to switch to a different anti-VEGF agent is often guided by a patient’s response to a specific anti-VEGF agent in the first few months of treatment. More studies are needed to determine the optimal time to switch anti-VEGF agents in the clinical setting. As such, the purpose of this study was to determine whether time to peak response to an anti-VEGF agent (in this study ranibizumab) was predictive of an end increase in BCVA. Additionally, this study examined whether patient baseline clinical characteristics were predictive of time to peak BCVA.
This report is an exploratory analysis of results from HARBOR. To summarize, HARBOR was a phase 3, multicenter, double-blinded, randomized, controlled trial that assessed the safety and efficacy of ranibizumab for treatment of nAMD. Patients received either 0.5 mg or 2 mg of ranibizumab monthly or PRN (after 3 monthly loading doses). The inclusion criteria for the HARBOR study were patients greater than 50 years old with treatment naïve subfoveal nAMD. The primary outcome of interest in this trial was the mean change in BCVA from baseline to month 12. The current study is a post-hoc analysis of the data from HARBOR. The purpose of this analysis was to determine individual patients’ time to achieve greatest BCVA gain which was defined as “peak vision”. Subsequently, the authors analyzed whether this time to peak vision was predictive of 1) the degree of change in peak BCVA and 2) the final BCVA achieved at study end at 24 months. Early peakers were defined as patients whose BCVA peaked between day 7 and month 6 and late peakers were patients whose BCVA peaked month 7 onwards (7 months- 12 months, 13 months- 18 months, 19months-24 months).
Of the 1,097 patients enrolled in HARBOR, 474 patients receiving PRN treatment and 469 patient receiving monthly injections were included in this post hoc analysis Since the results from HARBOR showed no significant dose-dependent response to ranibizumab, the patient data for two doses were pooled while the dosing schedules (monthly versus PRN) were kept separate. Additionally, this analysis evaluated a few baseline demographic variables and clinical characteristics (such as presence of sub-retinal or intra-retinal fluid, atrophy, fibrosis, RPE tears etc) as potentials predictors of time to peak BCVA.
The results showed that a large portion of the study population (64% of the PRN group, 70% of the monthly group) peaked late (after >6 months of treatment). At the study end in 24 months, the early peakers on average lost vision (monthly, -1.9 ETDRS letters; PRN, -1.6 ETDRS letters), while the late peakers actually gained vision (monthly, 10.2-18.7 ETDRS letters; PRN 8.5-17.7 ETDRS letters). Additionally, none of the baseline clinical variables assessed were found to correlate with the different outcomes between the early and late peakers.
Overall, this post hoc analysis shows that it is difficult to predict visual outcomes in the first 3-6 months following initiation of treatment. Continued treatment with the same agent (in this study, ranibizumab) holds promise for vision gain in the long run even though the patient may be a “late peaker.” However, these suggestions are based on a post-hoc analysis. As the authors mention, further studies are needed to validate these findings.
Mehnaz Khan, MD