In a new study published in The Lancet, investigators assessed if stereotactic radiotherapy (SRT) could reduce the number of anti-VEGF injections required for a patient’s treatment without sacrificing visual acuity (VA).
Give me some background first.
Age-related macular degeneration (AMD) impacts 8% of adults globally.
Wet or neovascular (nAMD) is the less common form of AMD and is noted as:
- Always late-stage
- Typically resulting in faster vision loss
- Causing symptoms such as:
- Blind spots in vision
- Straight lines appearing wavy or crooked
- Blurry area appearing near the center of vision
Why investigate the potential of radiotherapy for nAMD?
While repeated anti-VEGF injections are a treatment option for nAMD, it is usually associated with patient burden and an annual estimated cost of $10.7 billion globally.
Thus: Previous studies led the researchers to hypothesize the potential of radiation therapy. "Radiation mitigates many of the pathogenic processes that cause nAMD, and therefore has clinical potential, but the mode of delivery alters efficacy,” they stated.
Now, talk about the study.
Researchers conducted a randomized, double-masked, sham-controlled trial at 30 (unnamed) hospitals located in the United Kingdom (UK).
They randomly assigned patients in a 2:1 ratio to 16-Gray (Gy)—a unit of measure for radiation amounts—SRT delivered utilizing a robotically-controlled device or sham SRT that was stratified by treatment center.
Who was included in the study?
A total of 411 participants enrolled in the study from Jan 1, 2015, through Dec 27, 2019, comprised of:
- 274 participants randomly assigned to the 16-Gy SRT group
- 137 in the sham SRT group
- 240 (58%) females
- 171 (42%) males
What were the inclusion criteria?
Participants were required to:
- Be aged 50+
- Have had chronic active nAMD
- At least three previous anti-VEGF injections
- With at least one in the last 4 months
How was the study conducted?
Outcomes of the study were:
Primary outcome:
- Number of intravitreal ranibizumab injections required over 2 years
- Tested for superiority (fewer injections)
Main secondary outcome:
- Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) at 2 years
- Tested for non-inferiority (five-letter margin)
Primary analysis:
- Utilized the intention-to-treat principle
Who was included in the final analysis?
The final analysis included:
- 241 participants in the 16-Gy SRT
- 118 participants in the sham group
- 409 patients treated and formed the safety population
- Two patients misallocated to sham treatment received 16-Gy SRT.
Findings?
- SRT group received a mean of 10.7 injections (SD 6.3) over 2 years compared to 13.3 injections (5.8) with sham
- Reduction of 2.9 injections after adjusting for treatment center (95% Confidence interval [CI] –4.2 to –1.6, p<0.0001)
- SRT group best-corrected visual acuity (BCVA) change was non-inferior to sham
- Adjusted mean letter loss difference between groups, –1.7 letters (95% CI –4.2 to 0.8)
- Fewer ranibizumab injections offset the cost of SRT, saving a mean of £565 per participant
- 95% CI –332 to 1483
Tell me more.
- Adverse event rates were similar across groups
- However, reading center-detected microvascular abnormalities occurred in 77 SRT-treated eyes (35%) and 13 (12%) sham-treated eyes
- Overall, eyes with microvascular abnormalities tended to have better best-corrected VA than those without
Limitations?
The COVID-19 pandemic may have influenced the primary endpoint of the study as compliance shortly after the pandemic was compromised and missed or delayed visits occurred, which may have resulted in fewer ranibizumab retreatments.
The authors noted that the study results only extended to a year and were unsure if the safety and benefits of SRT extend beyond this period.
Additionally, it was unknown whether anti-VEGF agents other than ranibizumab would provide similar benefits as seen in the study. For a full overview of limitations, see the full clinical study.
Expert opinion?
The authors noted that wide implementation of SRT could lessen patient burden and reduce the global cost of delivering nAMD treatment.
They stated, “SRT could potentially avoid 1.8 million anti-VEGF injections per year globally across all high-income countries.”
Take home.
The findings suggest that SRT may reduce ranibizumab treatment burden without compromising vision.