Ocular safety evaluation of blue light scleral cross-linking in vivo in rhesus macaques

  • Yu Li
  • Chong Liu
  • Mingshen Sun
  • Xiaotong Lv
  • Mengmeng Wang
  • Xuan Jiao
  • Li Zhang
  • Ningli Wang
  • Fengju ZhangEmail author
Basic Science



To investigate the safety of blue light scleral cross-linking (SXL) by evaluating changes in biological parameters in the retina and choroid in the eyes of rhesus macaques (Macaca mulatta).


Fifteen 3-year-old macaques (30 eyes) were randomly divided into three groups (n = 5). SXL was performed via riboflavin (0.5%) and blue light (460 nm) at the location of the equatorial sclera. Right eyes served as experimental eyes, and left eyes as control eyes. One quadrant of each right eye was irradiated in group A, two quadrants of each right eye and one quadrant of each left eye were irradiated in group B, and two quadrants of each right eye were irradiated in group C. Optical coherence tomography, optical coherence tomography angiography, and flash electroretinography (f-ERG) examinations were performed at baseline and 1 week, 1 month, 3 months, and 6 months after SXL. Additionally, retinal tissue alterations were detected via transmission electron microscopy at 1 week postoperatively.


There were no significant differences between experimental eyes and control eyes in retinal thickness, vessel density of retinal superficial capillary plexus, and choroid thickness in any of the groups at any of the time points investigated (p > 0.05). Significant reductions in f-ERG parameters were detected 1 week postoperatively in the experimental eyes of groups A and C (p < 0.05), but they gradually recovered, and there was no significant difference 1 month postoperatively (p > 0.05). Ultrastructural changes were evident in the retinal layers of SXL eyes. In group B, there were no significant differences between the right and left eyes at any of the follow-up time points investigated.


Blue light SXL can cause transient retina damage. The f-ERG parameters reductions and retinal ultrastructural changes were found at early stage, even though there were not significant changes in retinal thickness, vessel density of retinal superficial capillary plexus, and choroid thickness after blue light SXL. The long-term intraocular safety of the blue light SXL technique should be investigated further.


Blue light Cross-linking ERG Rhesus monkey Sclera Safety 



The authors thank Dr. Jing Li for her expert technical assistance with the measurement and analysis of intraocular pressure and optical coherence tomography parameters during the study.


This study was supported by grants from the National Natural Science Foundation of China (numbers 81570877 and 81873682; and the 215 High-Level Talent Fund of Beijing Health Government (number 2013-2-023;

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval for animal experiments

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yu Li
    • 1
  • Chong Liu
    • 1
  • Mingshen Sun
    • 1
  • Xiaotong Lv
    • 1
  • Mengmeng Wang
    • 2
  • Xuan Jiao
    • 1
  • Li Zhang
    • 1
  • Ningli Wang
    • 1
  • Fengju Zhang
    • 1
    Email author
  1. 1.Beijing Tongren Eye Center, Beijing Tongren HospitalCapital Medical University, Beijing Ophthalmology & Visual Sciences Key LabBeijingChina
  2. 2.Hebei Ophthalmology Key Lab, Hebeisheng Eye HospitalXingtaiChina

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