Long-term anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration: the LATAR study. Report 1: ten-year, real-world outcomes.

Written by: Vlad Matei, MD

August 2021

Spooner K, Fraser-Bell S, Hong T, et al. Long-term anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration: the LATAR study. Report 1: ten-year, real-world outcomes. Ophthalmology Retina 2021;5(6):511-518.

Neovascular age-related macular degeneration (nAMD) is one of the most common and debilitating diseases encountered by retinal specialists. Anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections have been the mainstay of nAMD treatment for over a decade, and multiple clinical trials and real-world retrospective studies have suggested that a higher number of anti-VEGF injections given at consistent intervals results in better long-term visual outcomes in most nAMD patients. However, there are very few studies with more than 5 years of patient follow-up to inform our prognosis for nAMD patients, which is complicated by the relentless atrophic component of AMD. The authors of the present study set out to shed further light on nAMD outcomes with a longer-term, real-world study.

This was a retrospective chart review of all consecutive patients diagnosed with nAMD and started on anti-VEGF intravitreal injections in a single Australian private retina practice between 2006-2009. Patients with prior anti-VEGF or surgical therapy for AMD, fewer than 3 injections in the first year of therapy, or with comorbid macular diseases were excluded. Until 2012, only ranibizumab was used, and after 2012 aflibercept was also used. Although treatment frequency was at the discretion of the treating physicians, through 2008 patients were treated with a monthly anti-VEGF regimen, and from late 2008 onwards increasingly more patients were transitioned to a treat-and-extend regimen, with patients rarely having injections less often than 12 weeks. The primary outcome was the difference in corrected or pinhole visual acuity (VA; determined by Snellen chart and converted to ETDRS for analysis) between the initial treatment visit and a visit at least 10 years later.

Ten-year follow-up data was available for 293 eyes, comprising only about one quarter of the sample of patients initially found by the authors’ medical records search. The mean baseline characteristics of the 10-year patients included age of 75 years, about 20/80 mean baseline VA, female sex in about 60%, Caucasian race in nearly 95%, and type 1 and type 2 macular neovascularization (MNV) in 45% and 41% of patients, respectively. The mean follow-up length of these patients was 11.5 years. The mean number of injections received by the eyes for which 10-year follow-up data was available was 58.

After a median VA gain of 9 letters within the first year of anti-VEGF treatment, the VA gradually declined over time to a final mean VA that was about the same as the baseline VA (a mean change of 1.3 letters). However, the proportion of eyes with 20/40 or better VA increased from 29% at baseline to 35% at 10 years, while the proportion of eyes with 20/200 or worse vision increased from 14 to 17%. Eyes with poor baseline VA (20/200 or worse) gained about one line of vision by the final follow-up date. Younger age and a greater number of injections were associated with more long-term VA improvement. Although 10-year eyes and eyes who were lost to follow-up earlier than 10 years had similar baseline VA, eyes lost to follow-up had less VA gains by the time of treatment dropout, despite a similar number of injections between the two groups.

The mean central macular thickness (CMT) in all eyes decreased by nearly 100 microns to nearly normal levels and remained near this lower number over the 10 years of follow-up. At the final visit, 35% of eyes still had fluid on OCT (⅔ with intraretinal fluid and ⅓ with subretinal fluid). By the final visit, macular atrophy had developed in 59% and subretinal fibrosis had developed in 43%, without any association between the number of injections and the development of macular atrophy.

Overall, this study suggests that, on average, patients with nAMD can at least maintain their VA over 10 years of follow-up, provided that patients continue to receive anti-VEGF injections. The decline in VA despite the stably reduced CMT is in line with the suspicion that progression of the dry component of AMD is one of the main causes of continued VA decline in nAMD patients. While dry AMD is still not within our control, the frequency and consistency of anti-VEGF treatment of nAMD is, and this study echoes other studies in suggesting that undertreatment in the real world is the other major cause of long-term vision loss in nAMD.

This study is limited by its retrospective nature, lack of standardized treatment protocols, and the fact that 10-year follow-up data was not available for many patients who seemed to be trending towards worse VA outcomes. However, its 10-year span of data for a relatively large number of patients make it an important contribution to the AMD literature. Until an option for a longer-term, sustained nAMD treatment modality is widely available, we can quote data from this study to our patients (and to ourselves) when the number of injections and visits starts to take a toll on patients’ motivation to continue treatment.