WE HAVE ENTERED the era of personalized medicine. From cancer research to age-related macular degeneration (AMD) treatment (Das et al, 2011), personalized medicine has emerged as a systemic clinical practice that uses innovative technologies and algorithms to revolutionize clinical decision-making and optimize treatment.

A plethora of myopia treatment modalities have become readily available in recent years. Growing research has shown that combination therapy based on individualized risk profiles is likely the next logical and inevitable phase of pediatric myopia management (Jong et al, 2021; González-Méijome et al, 2016; Wang et al, 2021; Wildsoet et al, 2019). Clinical efficacy of myopia management is conventionally rooted in dioptric measurement.

Recently, though, axial length was found to be a more objective and reliable metric (Brennan et al, 2021). In general, adjunct myopia therapy is warranted when axial length elongation exceeds the age-norm emmetropic growth (i.e., physiologic eye growth without treatment), and it can no longer be managed by a solo therapy sufficiently. While exact mechanisms remain elusive, it is postulated that combination therapy likely augments the effects of myopic defocus signals and dopamine uptakes, thereby resulting in greater axial length control (Chiang et al, 2020; Wan et al, 2018).

How do we identify patients at greater risks of axial length progression, or so-called “fast progressors?” Age of onset was found to be the strongest determinant for the rate of myopia progression (Mutti et al, 2022; Zadnik et al, 2015; Hu et al, 2020; Chua et al, 2016; and others. Full list available in the reference list below.). Indeed, juvenile-onset myopia is directly associated with a greater likelihood of progression, particularly in Asian and Southeast Asian population (Mutti et al, 2022).

In a Chinese cohort study by Hu and colleagues, Asian children who had initial onset of myopia at 7 or 8 years of age showed greater than 50% risk of developing high myopia (Hu et al, 2020). Nevertheless, Mutti and colleagues found that prior changes of myopia weakly predicts future trend of progression (Mutti et al, 2022).

Collectively, it is argued that fast progressors should begin myopia treatment as young as possible. For those cases, combination therapy is more likely warranted due to rapid and asynchronous physiologic growth of the eye.

Among all various combination approaches, orthokeratology (ortho-k) combined with low-dose atropine (AOK) is best supported by the most robust research so far (Tan et al, 2022; Kinoshita et al, 2020; Yuan et al, 2021). Nevertheless, most data are largely short-term retrospective studies and only 0.01% atropine was used exclusively. It was reported that dual therapy of AOK for two consecutive years resulted in slower axial length progression compared to monotherapy (Kinoshita et al, 2018; Kinoshita et al, 2020).

It was found that children having faster axial length progression after ortho-k treatment tended to show better control when low-dose atropine was added subsequently (Chen et al, 2010). Combination therapy is a safe and effective regimen for at-risk children, particularly for those of younger age and at a lower stage of initial myopia (Yang et al, 2022). It is important to consider potential noncompliance or withdrawal from the treatment due to added effort and commitment by combination therapy.

More work is warranted to help us understand the mechanisms and long-term impact of combination therapy for myopia management. When considering the multifaceted interactions between the current viable interventions and environmental factors, modulating effects associated with nature likely adds further complexity (Troilo et al, 2019; Wildsoet et al, 2019, Chakraborty et al, 2019.

For instance, does seasonal variation influence treatment outcomes for children undergoing a single versus dual therapy? How do late-sleepers respond, if differently, to combination therapy compared to “early birds?”

These questions bring us closer to embrace the “individualized” aspect of myopia management. When used judiciously, combination therapy would likely be used as part of the soon-to-be “standard of care” for pediatric myopia. CLS

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