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Macular cone cell mosaic metrics in myopia: severity evaluation and diagnostic efficiency using adaptive optics fundus camera

Eye (2026)Cite this article

Subjects

Abstract

Objectives

To quantify macular cone cell mosaic metrics in patients with varying degrees of myopia and explore its link to myopia severity using an adaptive optics (AO) fundus camera.

Methods

A total of 76 age- and gender-matched patients with varying degrees of myopia (pre-myopia, low, moderate, and high) were recruited. Macular cone cell mosaic metrics (density, spacing, regularity, dispersion) were quantified via adaptive optics (AO) imaging, including correlations between AO-derived parameters and clinical indicators (spherical equivalent refraction, axial length) and predictive efficacy of AO metrics for myopia severity evaluated through receiver operating characteristic (ROC) curve analysis.

Results

As spherical equivalent refraction (SER) decreased, cone density (r = 0.65) and regularity (r = 0.38) significantly declined, while spacing (r = –0.65) and dispersion (r = –0.40) increased (all P < 0.001). Axial length (AL) was negatively correlated with density (r = –0.62) and regularity (r = –0.39), and positively correlated with spacing (r = 0.61) and dispersion (r = 0.38) (all P < 0.001). Predictive efficacy analysis based on AO-derived parameters revealed the highest AUROC value in the HM group (0.96), followed by Pre-M (0.86), LM (0.82), and MM (0.65) groups, indicating that AO metrics demonstrated superior early identification capability for HM severity.

Conclusions

The AO fundus camera enables noninvasive evaluation of macular cone cell mosaic metrics, revealing strong correlations between density, regularity, spacing, dispersion, and myopia severity. These metrics demonstrate potential as biomarkers for evaluating myopic changes, with AO showing enhanced diagnostic efficacy in high myopia.

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Fig. 1: Cone cell mosaic in the ROI2 (superior) region of myopic groups.
Fig. 2: Cell distribution characteristics of myopic groups.
Fig. 3: Correlations and diagnostic ROC analysis.
Fig. 4: ROC curves for cone cell mosaic by myopia severity.

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Data availability

The datasets generated and analysed during the current study are available from the corresponding author on reasonable request. The data are not publicly available due to privacy or ethical restrictions.

References

  1. Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, et al. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology. 2016;123:1036–42.

    Article  PubMed  Google Scholar 

  2. Modjtahedi BS, Abbott RL, Fong DS, Lum F, Tan D, Task Force on Myopia. Reducing the global burden of myopia by delaying the onset of myopia and reducing myopic progression in children: the academy’s task force on myopia. Ophthalmology. 2021;128:816–26.

    Article  PubMed  Google Scholar 

  3. Morgan IG, Ohno-Matsui K, Saw SM. Myopia. Lancet. 2012;379:1739–48.

    Article  PubMed  Google Scholar 

  4. He HL, Liu YX, Chen XY, Ling SG, Qi Y, Xiong Y, et al. Fundus tessellated density of pathologic myopia. Asia Pac J Ophthalmol (Philos. 2023;12:604–13.

    Article  CAS  Google Scholar 

  5. Jones D, Luensmann D. The prevalence and impact of high myopia. Eye Contact Lens. 2012;38:188–96.

    Article  PubMed  Google Scholar 

  6. Wang Y, Ye J, Shen M, Yao A, Xue A, Fan Y, et al. Photoreceptor degeneration is correlated with the deterioration of macular retinal sensitivity in high myopia. Invest Ophthalmol Vis Sci. 2019;60:2800–10.

    Article  PubMed  Google Scholar 

  7. Ho WC, Kee CS, Chan HH. Myopia progression in children is linked with reduced foveal mfERG response. Invest Ophthalmol Vis Sci. 2012;53:5320–5.

    Article  PubMed  Google Scholar 

  8. Chen JC, Brown B, Schmid KL. Delayed mfERG responses in myopia. Vis Res. 2006;46:1221–9.

    Article  PubMed  Google Scholar 

  9. Zhang B, Li N, Kang J, He Y, Chen XM. Adaptive optics scanning laser ophthalmoscopy in fundus imaging, a review and update. Int J Ophthalmol. 2017;10:1751–8.

    PubMed  PubMed Central  Google Scholar 

  10. Cristescu IE, Baltă F, Zăgrean L. Cone photoreceptor density in type I diabetic patients measured with an adaptive optics retinal camera. Rom J Ophthalmol. 2019;63:153–60.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Soliman MK, Sadiq MA, Agarwal A, Sarwar S, Hassan M, Hanout M, et al. High-resolution imaging of parafoveal cones in different stages of diabetic retinopathy using adaptive optics fundus camera. PLoS One. 2016;11:e0152788.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Antonetti DA, Silva PS, Stitt AW. Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat Rev Endocrinol. 2021;17:195–206.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Legras R, Gaudric A, Woog K. Distribution of cone density, spacing and arrangement in adult healthy retinas with adaptive optics flood illumination. PLoS One. 2018;13:e0191141.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yang Y, Wang J, Jiang H, Yang X, Feng L, Hu L, et al. Retinal microvasculature alteration in high myopia. Invest Ophthalmol Vis Sci. 2016;57:6020–30.

    Article  PubMed  Google Scholar 

  15. Zhang S, Zhang G, Zhou X, Xu R, Wang S, Guan Z, et al. Changes in choroidal thickness and choroidal blood perfusion in guinea pig myopia. Invest Ophthalmol Vis Sci. 2019;60:3074–83.

    Article  PubMed  CAS  Google Scholar 

  16. He HL, Liu YX, Liu H, Zhang X, Song H, Xu TZ, et al. Deep learning-enabled vasculometry depicts phased lesion patterns in high myopia progression. Asia Pac J Ophthalmol (Philos). 2024;13:100086.

    Article  Google Scholar 

  17. Wu Q, Chen Q, Lin B, Huang S, Wang Y, Zhang L, et al. Relationships among retinal/choroidal thickness, retinal microvascular network and visual field in high myopia. Acta Ophthalmol. 2020;98:e709–e714.

    Article  PubMed  Google Scholar 

  18. Lejoyeux R, Benillouche J, Ong J, Errera MH, Rossi EA, Singh SR, et al. Choriocapillaris: fundamentals and advancements. Prog Retin Eye Res. 2022;87:100997.

    Article  PubMed  Google Scholar 

  19. Nishida Y, Fujiwara T, Imamura Y, Lima LH, Kurosaka D, Spaide RF. Choroidal thickness and visual acuity in highly myopic eyes. Retina. 2012;32:1229–36.

    Article  PubMed  Google Scholar 

  20. Flores-Moreno I, Ruiz-Medrano J, Duker JS, Ruiz-Moreno JM. The relationship between retinal and choroidal thickness and visual acuity in highly myopic eyes. Br J Ophthalmol. 2013;97:1010–3.

    Article  PubMed  Google Scholar 

  21. Wu H, Zhang G, Shen M, Xu R, Wang P, Guan Z, et al. Assessment of choroidal vascularity and choriocapillaris blood perfusion in anisomyopic adults by SS-OCT/OCTA. Invest Ophthalmol Vis Sci. 2021;62:8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Yang J, Ouyang X, Fu H, Hou X, Liu Y, Xie Y, et al. Advances in biomedical study of the myopia-related signaling pathways and mechanisms. Biomed Pharmacother. 2022;145:112472.

    Article  PubMed  CAS  Google Scholar 

  23. Chinese Optometric Association, Chinese Ophthalmological Society, Ophthalmology and Optometry Committee, Ophthalmologists Association, Chinese Doctor Association, Ophthalmology and Optometry Group, Ophthalmologic Committee, Chinese Non-Government Medical Institutions Association, Eye Refractive Error Prevention and Control Group of the Cross-Straits Medical Exchange Association, Commission of Ophthalmology, Ophthalmology Branch of Chinese Geriatrics Society. Expert Consensus on Prevention and Control of High Myopia (2023). Chin J Optom Ophthalmol Vis Sci. 2023;25:401–7. https://doi.org/10.3760/cma.j.cn115909-20230509-00147.

    Article  Google Scholar 

  24. Babcock HW. The possibility of compensating astronomical seeing. Publ Astronomical Soc Pac. 1953;65:229.

    Article  Google Scholar 

  25. Dabir S, Mangalesh S, Schouten JS, Berendschot TT, Kurian MK, Kumar AK, et al. Axial length and cone density as assessed with adaptive optics in myopia. Indian J Ophthalmol. 2015;63:423–6.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Curcio CA, Sloan KR, Kalina RE, Hendrickson AE. Human photoreceptor topography. J Comp Neurol. 1990;292:497–523.

    Article  PubMed  CAS  Google Scholar 

  27. Baird, Saw PN, Lanca SM, Guggenheim C, Smith JA, Iii EL, et al. Myopia. Nat Rev Dis Prim. 2020;6:99.

    Article  PubMed  Google Scholar 

  28. Cui M, Zhu Z, Gao Y, Zong X, Li S, Liu J, et al. Research on the predictive performance of using ROC curve to evaluate axial length for myopia in children and adolescents. BMC Ophthalmol. 2025;25:195.

    Article  Google Scholar 

  29. Liu R, Xuan M, Wang DC, Xiao O, Guo XX, Zhang J, et al. Using choroidal thickness to detect myopic macular degeneration. Int J Ophthalmol. 2024;17:317–23.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Pang CE, Sarraf D, Freund KB. Extreme choroidal thinning in high myopia. Retina. 2015;35:407–15.

    Article  PubMed  Google Scholar 

  31. Gupta P, Cheung CY, Saw S, Koh V, Tan M, Yang A, et al. Choroidal thickness does not predict visual acuity in young high myopes. Acta Ophthalmol. 2016;94:e764–e765.

    Article  Google Scholar 

  32. Zhou Y, Song M, Zhou M, Liu Y, Wang F, Sun X. Choroidal and retinal thickness of highly myopic eyes with early stage of myopic chorioretinopathy: tessellation. J Ophthalmol. 2018;2018:2181602.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zhang Y, Zhong Y, Mao W, Zhang Z, Zhou Y, Li H, et al. Clinical features evaluation of myopic fundus tessellation from OCTA and MfERG. Photodiagnosis Photodyn Ther. 2025;52:104493.

  34. Sui J, Li H, Bai Y, He Q, Sun Z, Wei R. Morphological characteristics of the foveal avascular zone in pathological myopia and its relationship with macular structure and microcirculation. Graefes Arch Clin Exp Ophthalmol. 2024;262:2121–33.

    Article  PubMed  Google Scholar 

  35. McBrien NA. Regulation of scleral metabolism in myopia and the role of transforming growth factor-beta. Exp Eye Res. 2013;114:128–40.

    Article  PubMed  CAS  Google Scholar 

  36. Jobling AI, Nguyen M, Gentle A, McBrien NA. Isoform-specific changes in scleral transforming growth factor-beta expression and the regulation of collagen synthesis during myopia progression. J Biol Chem. 2004;279:18121–6.

    Article  PubMed  CAS  Google Scholar 

  37. Jiang B, Wu ZY, Zhu ZC, Ke GJ, Wen YC, Sun SQ. Expression and role of specificity protein 1 in the sclera remodeling of experimental myopia in guinea pigs. Int J Ophthalmol. 2017;10:550–4.

    PubMed  PubMed Central  Google Scholar 

  38. Qian YS, Chu RY, Hu M, Hoffman MR. Sonic hedgehog expression and its role in form-deprivation myopia in mice. Curr Eye Res. 2009;34:623–35.

    Article  PubMed  CAS  Google Scholar 

  39. Chen M, Qian Y, Dai J, Chu R. The sonic hedgehog signaling pathway induces myopic development by activating matrix metalloproteinase (MMP)-2 in Guinea pigs. PLoS One. 2014;9:e96952.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Liu YX, Sun Y. MMP-2 participates in the sclera of guinea pig with form-deprivation myopia via IGF-1/STAT3 pathway. Eur Rev Med Pharm Sci. 2018;22:2541–8.

    Google Scholar 

  41. She M, Li B, Li T, Hu Q, Zhou X. Modulation of the ERK1/2-MMP-2 pathway in the sclera of guinea pigs following induction of myopia by flickering light. Exp Ther Med. 2021;21:371.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Zhao F, Zhou Q, Reinach PS, Yang J, Ma L, Wang X, et al. Cause and effect relationship between changes in scleral matrix metallopeptidase-2 expression and myopia development in mice. Am J Pathol. 2018;188:1754–67.

    Article  PubMed  CAS  Google Scholar 

  43. Wu H, Chen W, Zhao F, Zhou Q, Reinach PS, Deng L, et al. Scleral hypoxia is a target for myopia control. Proc Natl Acad Sci USA. 2018;115:E7091–E7100.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Zhao F, Zhang D, Zhou Q, Zhao F, He M, Yang Z, et al. Scleral HIF-1alpha is a prominent regulatory candidate for genetic and environmental interactions in human myopia pathogenesis. EBioMedicine. 2020;57:102878.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Xie Y, Ouyang X, Wang G. Mechanical strain affects collagen metabolism-related gene expression in scleral fibroblasts. Biomed Pharmacother. 2020;126:110095.

    Article  PubMed  CAS  Google Scholar 

  46. Elsner AE, Chui TY, Feng L, Song HX, Papay JA, Burns SA. Distribution differences of macular cones measured byAOSLO: variation in slope from fovea to periphery more pronounced than differences in total cones. Vis Res. 2017;132:62–8.

    Article  PubMed  Google Scholar 

  47. Zhang T, Godara P, Blanco ER, Griffin RL, Wang X, Curcio CA, et al. Variability in human cone topography assessed by adaptive optics scanning laser ophthalmoscopy. Am J Ophthalmol. 2015;160:290–300.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the patients for their participation in the study. They also gratefully acknowledge Tang Li from Zhitong Vision Science (Chongqing) Biotechnology Co., Ltd. for providing technical support for the AO instrumentation and valuable suggestions.

Funding

This study was supported by grants from the Science and Technology Research Programme of Chongqing Municipal Education Commission (Grant No. KJZD-K202400402), the National Natural Science Foundation of China (No. 81970832, 81371043 and 81800814).

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Author notes

  1. These authors contributed equally: Wen-Li Deng, Yan-Lai Zhang.

Authors and Affiliations

  1. The First Affiliated Hospital of Chongqing Medical University, Department of Ophthalmology, Chongqing Key Laboratory of Prevention and Treatment of Major Blinding Diseases, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China

    Ke-Yu Liu, Ju-Xian Liu, Zhou-Yu Li, Yu Yue, Chen Zeng, Qi Li, Shu-Lin Liu, Wen-Juan Wan, Wen-Li Deng & Yan-Lai Zhang

  2. University-Town Hospital of Chongqing Medical University, Department of Ophthalmology, Chongqing, China

    Ren-Yue Xiao

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Contributions

K-YL was responsible for data collection and examination, data analysis, manuscript drafting and manuscript revision. J-XL was responsible for data collection and examination. Z-YL was responsible for data collection and examination. YY was responsible for data analysis. R-YX was responsible for data collection. CZ was responsible for data collection. QL was responsible for data analysis. S-LL was responsible for manuscript revision. W-JW was responsible for manuscript revision. W-LD (guarantor) was responsible for study design, data collection, examination, data analysis, manuscript revision and supervision of the study process. Y-LZ (guarantor) was data analysis, manuscript drafting, manuscript revision and supervision of the study process. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Wen-Li Deng or Yan-Lai Zhang.

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Liu, KY., Liu, JX., Li, ZY. et al. Macular cone cell mosaic metrics in myopia: severity evaluation and diagnostic efficiency using adaptive optics fundus camera. Eye (2026). https://doi.org/10.1038/s41433-025-04171-9

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