Findings from a study published in Med compared the efficacy and safety of oral lamivudine for diabetic macular edema (DME) to bevacizumab.
Give me some background.
DME is a leading cause of vision loss among patients with diabetic retinopathy (DR), which is prevalent in over 25% of people with diabetes and affects nearly 10 million individuals in the United States.
The current standard treatment involves monthly intraocular injections of anti-vascular endothelial growth factor (VEGF) drugs.
- However: These anti-VEGF injections are invasive and can be costly and subsequently inaccessible for many patients.
Now bring in lamivudine.
Lamivudine is an inexpensive oral drug approved for viral infections—including human immunodeficiency virus (HIV)—and has shown potential for repurposing for DME in experimental models due to its ability to inhibit inflammasome activation.
Quick refresher: Inflammasomes are multiprotein complexes that coordinate inflammatory responses and normally act as sensors for infections, but they also have been implicated in the development of DME.
Now, talk about the study.
In this short-term, randomized, double-blind, placebo-controlled study, investigators enrolled 24 adults between February 2022 and September 2023.
The participant criteria: One or two eyes with center-involved DME (CI-DME) and best-corrected visual acuity (BCVA) < 69 letters (~20/50).
These participants were randomized into two groups:
- Oral lamivudine (150 mg twice daily; 10 participants, 16 eyes)
- Placebo (14 participants, 21 eyes)
Then: Patients received intravitreal bevacizumab (1.25 mg) at week 4 in addition to lamivudine and the placebo.
- Note: Comparisons to anti-VEGF drugs used synthetic controls from DRCR.net Protocol T.
Primary outcome measures: Mean changes in BCVA from baseline to weeks 4 and 8
- Secondary outcomes: Retinal thickness and adverse events
Findings?
- At week 4: BCVA improved 9.8 letters with lamivudine and decreased 1.8 letters with placebo (p < 0.001)
- At week 8: BCVA improved 16.9 letters with lamivudine and bevacizumab and 5.3 letters with placebo and bevacizumab (p < 0.001)
Anything else?
Lamivudine was associated with greater BCVA improvement than bevacizumab or ranibizumab (p < 0.05) and was not different from aflibercept (p = 0.5).
There was no significant difference in retinal thickness or adverse events between groups.
Expert opinion?
“A $20-a-month or even cheaper oral pill that improves vision as much as or more than therapy with injections into the eye that cost up to $2,000 per month could be transformative both for patients and the health care system,” explained Jayakrishna Ambati, MD, corresponding author.
“We have developed a safer version of lamivudine called K9, which blocks inflammasomes without the potential side effects of lamivudine,” he added.
Take home.
These findings suggest that oral lamivudine significantly improved vision in patients with CI-DME and appeared to enhance the effects of standard anti-VEGF injections.
This study is the starting point for a more accessible and less invasive treatment approach for DME, with the potential to benefit many patients globally.