The role of choroidal thickness in myopia development, is early detection possible?

As myopia incidence is increasing worldwide, it is important to understand the mechanisms underlying its development. An early detection of myopia would not only improve its management but would also prevent all the clinical consequences of high myopia, namely maculopathy, retinal detachment, and choroidal neovascularization. In this context, the prospective of identifying a biomarker for myopia development seems appealing, and this article will explore the possibility of considering the choroid as such.

Myopia incidence is increasing worldwide, and this makes it a public health concern (Liu et al., 2021; Pascolini & Mariotti, 2012). The clinical consequences of this condition could be severe, mostly in the case of high myopia, which raises the risk of developing clinical conditions such as myopic maculopathy, retinal detachment, and choroidal neovascularization. Recently, literature started to focus on the potential role of the choroid in this process, opening the doors to a new research topic that could lead to the identification of a biomarker for myopia development and potentially to new management and prevention strategies.

Choroidal thickness and its connection with myopia

The choroid is a highly vascular structure, whose high blood flow nourishes the outer retina thus supporting normal ocular functions (Nickla & Wallman, 2010; Zhang et al., 2024). The thickness of this structure can be altered by factors such as age (Nickla & Wallman, 2010), time of the day (Chakraborty et al., 2018; Stone et al., 2004), accommodation (Mallen et al., 2006), and physical activity (Read & Collins, 2011; Stone et al., 2004). But most importantly, this structure can alter its thickness in response to visual stimuli, defocus being one (Read et al., 2010).

Since the first studies on myopia were conducted in 1990s, it was noted that hyperopic defocus exposure resulted in increase in axial length, choroidal thinning and myopia development (Read et al., 2018). This led to the hypothesis that an active thinning mechanism can be involved in addition to the passive stretch induced by axial elongation (Liu et al., 2021). Particularly, the cohort study titled “Changes in Choroidal Thickness Varied by Age and Refraction in Children and Adolescents: a 1 Year Longitudinal Study” carried out by Xiong and associates (2020), analysed choroidal thickness in children and adolescents (10,9 ± 3,1 average age) during a one-year observational period. The follow up exams conducted on the same population one year later, revealed that children aged between 6 and 9 years presented a more marked central foveal thinning (mean reduction 9 μm) compared to subjects aged from 10 to 13 and from 14 to 18 (mean reduction of 3 μm). Moreover, subjects who developed a myopic shift showed a mean reduction in choroidal thickness of -8 ± 22 μm, particularly evident on subjects aged between 6 and 9 years (12 μm), compared to subjects aged between 10 and 13 years (5 μm) and from 14 to 18 years (4 μm). When no myopic shift occurred, choroidal thickness variations were minimal (2 ± 22 μm). By evidencing that subjects newly developing myopia aged between 6 and 9 years experience the greatest thinning in choroid, these results suggest that the choroid could play an important role in myopia development, but most importantly, that early infancy is the most crucial period for myopia interventions. (Liu et al., 2021; Xiong et al., 2020a.)

The cross-sectional study titled “Choroidal Thickness Profiles in Myopic Eyes of Young Adults in the Correction of Myopia Evaluation Trial Cohort” conducted by Harb and associates (2015), showed regional variations in choroidal thickness in highly myopic subjects, that resulted to be thinner in the nasal area. This suggests that defocus related factors such as axial elongation and myopia development can influence choroidal thickness, suggesting that choroidal thickness modifications induced by defocus can play a relevant role in myopia development. (Harb et al., 2015.)

Choroidal blood flow and myopia

Choroidal blood flow seems to be affected by myopia too, in fact, studies examining subjects with high myopia observed the presence of thinner choroids, alterations in vessel layer and capillary networks. Moriyama et al. (2007), highlighted thinning and loss of the large-vessel choroidal layer, Alshareef et al (2017) showed similar results for the medium vessel choroidal layer. Moreover, the choriocapillaris also showed a thinning and a reduced density in subjects affected by high myopia. (Alshareef et al., 2017; Moriyama et al., 2007; Quaranta et al., 1996.)

The hypothesis of a relationship between choroidal vascularization and myopia and hyperopia is supported by Esmaeelpour et al (2014) and Tan et al. (2014). Based on these studies, myopia seems to be accompanied by thinner choroidal vessel layers. Given the importance of the choroid for retinal health, changes in choroidal density and thickness could contribute to refractive errors development. This highlights the importance of further investigations for a better understanding of this mechanism. (Esmaeelpour et al., 2014; Tan et al., 2014.)

The evidence collected from these studies suggests that the relationship between choroidal blood flow modification and choroidal thickness variations may be causal. However, the mechanism ruling this relationship is still unknown. (Fitzgerald et al., 2002; Kim et al., 2012; Kinoshita et al., 2016; Liu et al., 2021; Sogawa et al., 2012; S. Zhang et al., 2019). Further investigations would allow a better understanding of the interplay between these two elements and their implication for myopia development.

Choroid as a biomarker for myopia development

Literature seems to confirm the relevance of choroidal thickness changes in myopia development. Particularly, Xiong et al. (2020) detected a higher choroidal thinning in subjects newly developing myopia (NDM) than persistently non-myopic (PNM) and persistently myopic (PM) subjects, and this suggests that something relevant occurs during myopia onset. In fact, as proved by Iribarren et al. 2012 and Xiang et al. 2012, during the year preceding myopia onset there is an acceleration of myopia progression, axial elongation, and lens power loss. The pronounced choroidal thinning in NDM subjects can potentially be related to an imbalance between physiological growth and axial elongation, since choroidal thickness has a negative association with axial length, which is a factor commonly associated to myopia progression. (Iribarren et al., 2012; Xiang et al., 2012; Xiong et al., 2020.)

Hyperopic defocus seems to encourage choroidal thinning which causes a weakening of the structure and a reduction of the resistance of the eye and potentially facilitates axial elongation, thus contributing to myopia development. Monitoring choroidal thickness may be fundamental for myopia management strategies, and further research is necessary to clarify the mechanisms through which defocus influences choroidal and ocular dynamics. However, additional studies are necessary to clarify this mechanism, and longitudinal studies with wider and more homogeneous sample size including diverse demographic groups would ensure a greater reliability of the findings. Additionally, extended follow up periods would allow a deeper observation of the long-term effects of defocus on choroidal thickness and myopia development.

Choroid and Innovation in Myopia Management

The importance of this topic for the optometric field is strictly related to the necessity to understand the mechanisms underlying myopia development. The identification of a biomarker for myopia development would certainly be an effective way to develop new strategies to prevent and manage myopia in a more effective way. This work aims to contribute to the initiatives that aim to shape a future in which myopia diffusion can be mitigated through new approaches. Further research would potentially enrich the clinical practice of optometrists for multiple reasons, namely allowing the development of new personalized preventive strategies. If choroid is identified as a biomarker for myopia development it would be possible to preventively treat it, moreover, by integrating the OCT examination on their routine, optometrists could evaluate the risk of myopia development, reduce the incidence of the clinical implications related to high myopia, and lastly, to study innovative treatments for myopia management.

Giulia Sciotto
Studies Clinical Optometry in Oulu University of Applied Sciences

The text is based on the Master's Thesis:
 
Sciotto, G., Andersson, R., & Juustila, T. (2024). The Impact of Defocus Induced-Choroidal Thickness Changes on Myopia Onset [Master's Thesis, Oulu University of Applied Sciences, Clinical Optometry]. Theseus. https://urn.fi/URN:NBN:fi:amk-2024112229458

References

Alshareef, R. A., Khuthaila, M. K., Januwada, M., Goud, A., Ferrara, D., & Chhablani, J. (2017). Choroidal vascular analysis in myopic eyes: evidence of foveal medium vessel layer thinning. International Journal of Retina and Vitreous, 3(1), 28. https://doi.org/10.1186/s40942-017-0081-z

Chakraborty, R., Ostrin, L. A., Nickla, D. L., Iuvone, P. M., Pardue, M. T., & Stone, R. A. (2018). Circadian rhythms, refractive development, and myopia. Ophthalmic and Physiological Optics, 38(3), 217–245. https://doi.org/10.1111/opo.12453

Esmaeelpour, M., Kajic, V., Zabihian, B., Othara, R., Ansari-Shahrezaei, S., Kellner, L., Krebs, I., Nemetz, S., Kraus, M. F., Hornegger, J., Fujimoto, J. G., Drexler, W., & Binder, S. (2014). Choroidal Haller’s and Sattler’s Layer Thickness Measurement Using 3-Dimensional 1060-nm Optical Coherence Tomography. PLoS ONE, 9(6), e99690. https://doi.org/10.1371/journal.pone.0099690

Fitzgerald, M. E. C., Wildsoet, C. F., & Reiner, A. (2002). Temporal Relationship of Choroidal Blood Flow and Thickness Changes during Recovery from Form Deprivation Myopia in Chicks. Experimental Eye Research, 74(5), 561–570. https://doi.org/10.1006/exer.2002.1142

Harb, E., Hyman, L., Gwiazda, J., Marsh-Tootle, W., Zhang, Q., Hou, W., Norton, T. T., Weise, K., Dirkes, K., Zangwill, L. M., Deng, L., Grice, K., Fortunato, C., Weber, C., Beale, A., Kern, D., Bittinger, S., Ghosh, D., Smith, R., … Taylor, C. (2015). Choroidal thickness profiles in myopic eyes of young adults in the correction of myopia evaluation trial cohort. American Journal of Ophthalmology, 160(1), 62–71.e2. https://doi.org/10.1016/j.ajo.2015.04.018

Iribarren, R., Morgan, I. G., Chan, Y. H., Lin, X., & Saw, S. M. (2012). Changes in lens power in Singapore Chinese children during refractive development. Investigative Ophthalmology and Visual Science, 53(9), 5124–5130. https://doi.org/10.1167/iovs.12-9637

Kim, M., Kim, S. S., Kwon, H. J., Koh, H. J., & Lee, S. C. (2012). Association between Choroidal Thickness and Ocular Perfusion Pressure in Young, Healthy Subjects: Enhanced Depth Imaging Optical Coherence Tomography Study. Investigative Opthalmology & Visual Science, 53(12), 7710. https://doi.org/10.1167/iovs.12-10464

Kinoshita, T., Mitamura, Y., Shinomiya, K., Egawa, M., Iwata, A., Fujihara, A., Ogushi, Y., Semba, K., Akaiwa, K., Uchino, E., Sonoda, S., & Sakamoto, T. (2016). Diurnal variations in luminal and stromal areas of choroid in normal eyes. British Journal of Ophthalmology, 101, 360–364. https://doi.org/10.1136/bjophthalmol-2016-308594

Liu, Y., Wang, L., Xu, Y., Pang, Z., & Mu, G. (2021). The influence of the choroid on the onset and development of myopia: from perspectives of choroidal thickness and blood flow. Acta Ophthalmologica, 99(7), 730–738. https://doi.org/10.1111/aos.14773

Mallen, E. A. H., Kashyap, P., & Hampson, K. M. (2006). Transient axial length change during the accommodation response in young adults. Investigative Ophthalmology and Visual Science, 47(3), 1251–1254. https://doi.org/10.1167/iovs.05-1086

Moriyama, M., Ohno-Matsui, K., Futagami, S., Yoshida, T., Hayashi, K., Shimada, N., Kojima, A., Tokoro, T., & Mochizuki, M. (2007). Morphology and Long-term Changes of Choroidal Vascular Structure in Highly Myopic Eyes with and without Posterior Staphyloma. Ophthalmology, 114(9). https://doi.org/10.1016/j.ophtha.2006.11.034

Nickla, D. L., & Wallman, J. (2010). The multifunctional choroid. Progress in Retinal and Eye Research, 29(2), 144–168. https://doi.org/10.1016/j.preteyeres.2009.12.002

Pascolini, D., & Mariotti, S. P. (2012). Global estimates of visual impairment: 2010. British Journal of Ophthalmology, 96(5), 614–618. https://doi.org/10.1136/bjophthalmol-2011-300539

Quaranta, M., Arnold, J., Coscas, G., Francais, C., Quentel, G., Kuhn, D., & Soubrane, G. (1996). Indocyanine Green Angiographic Features of Pathologic Myopia. American Journal of Ophthalmology, 122(5), 663–671. https://doi.org/10.1016/S0002-9394(14)70484-2

Read, S. A., & Collins, M. J. (2011). The short-term influence of exercise on axial length and intraocular pressure. Eye, 25(6), 767–774. https://doi.org/10.1038/eye.2011.54

Read, S. A., Collins, M. J., Woodman, E. C., & Cheong, S.-H. (2010). Axial Length Changes During Accommodation in Myopes and Emmetropes. Optometry and Vision Science: Official Publication of American Academy of Optometry, 87(9), 656–662. https://doi.org/10.1097/opx.0b013e3181e87dd3

Read, S. A., Pieterse, E. C., Alonso-Caneiro, D., Bormann, R., Hong, S., Lo, C. H., Richer, R., Syed, A., & Tran, L. (2018). Daily morning light therapy is associated with an increase in choroidal thickness in healthy young adults. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-26635-7

Sogawa, K., Nagaoka, T., Takahashi, A., Tanano, I., Tani, T., Ishibazawa, A., & Yoshida, A. (2012). Relationship Between Choroidal Thickness and Choroidal Circulation in Healthy Young Subjects. American Journal of Ophthalmology, 153(6), 1129-1132.E1. https://doi.org/10.1016/j.ajo.2011.11.005

Stone, R. A., Quinn, G. E., Francis, E. L., Ying, G.-S., Flitcroft, D. I., Parekh, P., Brown, J., Orlow, J., & Schmid, G. (2004). Diurnal Axial Length Fluctuations in Human Eyes. Investigative Ophthalmology & Visual Science, 45(1), 63–70. https://doi.org/10.1167/iovs.03

Tan, C. S. H., Cheong, K. X., Lim, L. W., & Li, K. Z. (2014). Topographic variation of choroidal and retinal thicknesses at the macula in healthy adults. British Journal of Ophthalmology, 98(3), 339–344. https://doi.org/10.1136/bjophthalmol-2013-304000

Xiang, F., He, M., & Morgan, I. G. (2012). Annual changes in refractive errors and ocular components before and after the onset of myopia in Chinese children. Ophthalmology, 119(7), 1478–1484. https://doi.org/10.1016/j.ophtha.2012.01.017

Xiong, S., He, X., Zhang, B., Deng, J., Wang, J., Lv, M., Zhu, J., Zou, H., & Xu, X. (2020). Changes in Choroidal Thickness Varied by Age and Refraction in Children and Adolescents: A 1-Year Longitudinal Study. American Journal of Ophthalmology, 213, 46–56. https://doi.org/10.1016/j.ajo.2020.01.003

Zhang, S., Zhang, G., Zhou, X., Xu, R., Wang, S., Guan, Z., Lu, J., Srinivasalu, N., Shen, M., Jin, Z., Qu, J., & Zhou, X. (2019). Changes in Choroidal Thickness and Choroidal Blood Perfusion in Guinea Pig Myopia. Investigative Ophthalmology & Visual Science, 60(8), 3074–3083. https://doi.org/10.1167/iovs.18-26397

Zhang, W., Kaser-Eichberger, A., Fan, W., Platzl, C., Schrödl, F., & Heindl, L. M. (2024). The structure and function of the human choroid. Annals of Anatomy, 254. https://doi.org/10.1016/j.aanat.2024.152239