Join Rishi P. Singh, MD, FASRS, and Aaron M. Miller, MD, MBA, as they discuss childhood myopia management and the most recent STAR (Study of Atropine for the Reduction of Myopia Progression) study results on this episode of Evidence Based Retina.
Dr. Miller is a fellowship-trained pediatric ophthalmologist with additional specialization in adult strabismus who practices at Houston Eye Associates.
STAR study fast facts
- Study design: Phase 3, multicenter, randomized, double-masked, placebo-controlled trial aimed at investigating SYD-101's effectiveness in slowing myopia progression in children.1
- Participants: The STAR study enrolled 847 children aged 3 to 14 at the time of treatment initiation. These children had myopia that ranged from 0.50D to 6.00D, with a mean baseline progression of 2.65D. Patients were randomized 1:1:1—vehicle (placebo), SYD-101 0.01%, or SYD-101 0.03%.2
- Duration: Participants were evaluated every 6 months for 36 months with an additional 12-month follow-up for rebound assessment.2
- Primary endpoint: In the full dataset, SYD-101 0.01% successfully achieved its primary efficacy endpoint, showing a significantly greater proportion of patients with confirmed progression of -0.75D at 36 months compared to the vehicle group (139 vs. 111 patients [Vehicle vs. 0.01%]; p=0.0226].2
- Secondary endpoint: SYD-101 0.01% achieved its primary secondary endpoint, the mean annual progression rate of myopia, in the full study population at month 36 (Vehicle: -0.38D/year vs. 0.01%: -0.30D/year, p=0.0002).2
- Additionally, there was >50% progression reduction in patients who had progressed at least 0.05D in the year prior to starting the study.2
- Safety: The study also showed an excellent safety profile. This was no surprise given decades of excellent safety demonstrated with much higher FDA-approved concentrations of atropine used for mydriasis and amblyopia.
- Relevance: Despite more than a decade of doctors’ clinical experience with compounded formulations and impressive STAR study results, no low-dose atropine formulation is currently FDA-approved. Additionally, North America and most of Africa are the last major areas of the world that still do not have a regulatory-approved low-dose atropine.
Deeper dive into low-dose atropine for myopia
Dr. Miller uses atropine for his growing myopic patient population. Atropine is a muscarinic receptor blocker that works in numerous parts of the eye, including the peripheral retina, and reduces pediatric progressive myopia over time. By using a lower concentration of atropine, side effects such as blurring and near focus effects are reduced while slowing down axial length elongation and worsening visual function.3
Longer-term, myopia increases the risk of numerous sight-threatening co-morbidities including macular maculopathy, retinal detachment, and early onset glaucoma and cataracts.4
Atropine has been studied for some time, and earlier studies such as Atropine for the Treatment of Myopia (ATOM) and Low-Concentration Atropine for Myopia Progression (LAMP) have shown its effectiveness.3
Findings from the STAR study
The more recent phase 3 STAR study by Sydnexis lasted 36 months and is the largest prospective, randomized myopia study to date.2 As mentioned above, the primary efficacy and key secondary endpoints were achieved, despite 36% of the patients in the SYD-101 0.01% group being between 16 and 18 years old, who showed minimal progression by the end of the study.2
This is important context to consider, because we have known for decades that most patients’ myopia progression starts to naturally slow down and stabilize in the later teenage years.
For SYD-101 to still hit its overall efficacy endpoints in a study population with such a large proportion of older patients reflects favorably for the drug. This also naturally begs the question of how well SYD-101 worked in patients who were actively progressing during the study.
In the pre-specified group of fast progressors (defined as patients progressing 0.5D or more in the year prior to treatment initiation), SYD-101 0.01% reduced myopia progression by >50% vs. vehicle at 3 years.2 SYD-101 demonstrated that it worked even better in the patients who needed it the most.
The impact of an FDA-approved low-dose atropine therapy on myopia management
Despite these results, the treatment has not yet received FDA approval,2 and low-dose atropine is only available through compounding pharmacies, which often produce variations in formulation, consistency, and overall manufacturing quality. These inconsistencies can affect safety, sterility, and efficacy, potentially causing varying results and adverse events for patients.5
Furthermore, compounded low-dose atropine is currently not covered by medical insurance (i.e., cash pay), and having an FDA-approved version could enhance commercial and state Medicaid insurance access, making an approved high-quality formulation more accessible to a larger number of people.
