The relationship between serum zinc levels and myopia: a comment on an article by Burke N et al

I read with enthusiasm the article by Burke et al. I congratulate the authors, for this beautifully written paper on a very interesting and important topic. The main purpose of the authors was to explore associations between serum zinc levels and myopia. Whilst the authors recognise that their study has some limitations, there are novel methodological suggestions that will be useful for the future research. Firstly, results of many studies highlight the importance of considering several biomarkers when assessing zinc status, namely erythrocyte zinc, 24-h urinary zinc excretion, linoleic acid: Dihomo-γ-linolenic acid ratio and hair zinc levels. Looking at their Table 1, The ‘myopic group’ had significantly higher body mass index compared to that of the ‘non-myopic group’, while no significant difference was found in mean serum zinc levels between the two groups. This is in contrast to other Korean studies. Furthermore, serum zinc concentrations in the study by Burke et al. were only determined in single spot serum samples, which may not be reflective of long term zinc status, even if mean serum zinc level was a reliable biomarker, considering that there is no zinc stores in humans. Future studies may choose to use repeated zinc measurements plus semi-quantitative food frequency questionnaires which are already validated and available for zinc status, or preferably use a combination of the abovementioned methods. Secondly, many non-ophthalmic and game-changing variables are associated with disc size change and other morphological parameters associated with myopia, such as the serum lipids, dietary factors (particularly lutein, zeaxanthin, and omega-3 fatty acids), medications (such as lipid-lowering agents), genetic susceptibility, body mass index, age, sex, diseases (such as diabetes, obesity, and hypertension); among which only a few are addressed by Burke et al. Thirdly, axial length measurement is a critical parameter when determining myopia. Burke et al. have not measured this variable, and thus it should be difficult from their methodology to judge whether the results are valid. Current and future studies are advised to not only measure this critical parameter, but also, if axial lengths are shorter than 23.60 mm and longer than 25.55 mm, adjust the measured circumpapillary retinal nerve fibre layer thickness to account for ocular magnification during spectral-domain optical coherence tomography. Fourthly, and most importantly, recent studies demonstrate that there are different myopia phenotypes within a population, which may differentially interact with parameters of interest. Thereby, future studies need to take this important point into consideration when enrolling participants. Lastly, there is a high possibility of interaction/and or effect mediation in such studies. For instance, changes in optic disc size and Bruch’s membrane are a function of macular pigment optical density, which in turn is a function of dietary carotenoid intake. Thus, for future investigations, a mediation analysis – preferably causal mediation analysis – is recommended to support the conclusions. A full citation of all the publications and all the variables, pathways and mechanisms was beyond the scope of this letter, due to the space limits, but can be easily found in online medical resources.