Low-dose atropine is widely used in myopia management – but does iris color influence how well it works? A new post-hoc meta-analysis published in Eye suggests that while safety-related ocular effects appear consistent across eye colors, treatment efficacy at the lowest dose may differ.
The study pooled individual-level data from three randomized controlled trials – MOSAIC, WA-ATOM, and the Pediatric Eye Disease Investigator Group’s Myopia Treatment Study – encompassing children aged 5–16 years. Investigators compared outcomes in participants with brown versus non-brown (blue/green/hazel) irides treated with atropine 0.01% or 0.05%.
One longstanding concern is that lighter irides may experience greater side effects due to lower melanin binding of atropine. However, the analysis found little evidence to support this concern.
This finding reinforces the tolerability of low-dose atropine across diverse populations – an important consideration given increasing global uptake for myopia.
Where the study becomes more provocative is in efficacy outcomes. At 24 months, children with non-brown irides treated with atropine 0.01% showed significantly less myopia progression compared with placebo, including a reduction in spherical equivalent progression of +0.17D and axial elongation of −0.09 mm.
In contrast, no significant treatment effect was observed in children with brown irides at the same concentration. Axial growth in the brown iris group treated with 0.01% atropine closely mirrored that seen in placebo groups.
This raises the possibility that atropine 0.01% could be less effective in darker irides – an observation that could have practical implications in ethnically diverse populations.
Interestingly, the iris color–related differences were not observed with atropine 0.05%. In the MOSAIC extension phase, no significant variation in axial length or refractive outcomes was seen between iris color groups at the higher dose.
One proposed explanation relates to pharmacokinetics. Atropine is known to bind to melanin in the iris, potentially reducing the amount that reaches the posterior segment. In darker irides, greater sequestration in the anterior segment could limit therapeutic concentrations at the retina, choroid, or sclera – particularly at lower doses. Higher concentrations may overcome this threshold effect.
While intriguing, the authors emphasize that these findings are exploratory. The analysis was post-hoc and not powered to detect subgroup differences, and variability between trials – including formulation differences – may have influenced results. Moreover, previous studies in predominantly Asian populations (with largely brown irides) have demonstrated efficacy with 0.01% atropine, suggesting that iris color alone is unlikely to fully explain treatment response.
Nonetheless, the study raises an important clinical question: should atropine dosing be tailored based on patient characteristics such as iris color? While it is too early to change practice, the data support consideration of higher concentrations – such as 0.05% – in patients who show limited response to 0.01% drops.
