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

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Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusions

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.

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References

  1. Tran HDM, Tran YH, Tran TD, Jong M, Coroneo M, Sankaridurg P (2018) A review of myopia control with atropine. J Ocul Pharmacol Ther 34(5). https://doi.org/10.1089/jop.2017.0144

  2. Holden B, Sankaridurg P, Smith E, Aller T, Jong M, He M (2014) Myopia, an underrated global challenge to vision: where the current data takes us on myopia control. Eye (London, England) 28(2):142–146. https://doi.org/10.1038/eye.2013.256

    Article  CAS  Google Scholar 

  3. Li SM, Liu LR, Li SY, Ji YZ, Fu J, Wang Y, Li H, Zhu BD, Yang Z, Li L, Chen W, Kang MT, Zhang FJ, Zhan SY, Wang NL, Mitchell P, Anyang Childhood Eye Study G (2013) Design, methodology and baseline data of a school-based cohort study in Central China: the Anyang Childhood Eye Study. Ophthalmic Epidemiol 20(6):348–359. https://doi.org/10.3109/09286586.2013.842596

    Article  CAS  PubMed  Google Scholar 

  4. McMonnies CW (2016) An examination of the relation between intraocular pressure, fundal stretching and myopic pathology. Clin Exp Optom 99(2):113–119. https://doi.org/10.1111/cxo.12302

    Article  PubMed  Google Scholar 

  5. Balparda K, Maldonado MJ (2017) Corneal collagen cross-linking A review of its clinical applications. Arch Soc Esp Oftalmol 92(4):166–174. https://doi.org/10.1016/j.oftal.2016.10.004

    Article  CAS  PubMed  Google Scholar 

  6. Wollensak G, Spoerl E (2004) Collagen crosslinking of human and porcine sclera. J Cataract Refract Surg 30(3):689–695. https://doi.org/10.1016/j.jcrs.2003.11.032

    Article  PubMed  Google Scholar 

  7. Wollensak G, Iomdina E, Dittert DD, Salamatina O, Stoltenburg G (2005) Cross-linking of scleral collagen in the rabbit using riboflavin and UVA. Acta Ophthalmol Scand 83(4):477–482. https://doi.org/10.1111/j.1600-0420.2005.00447.x

    Article  CAS  PubMed  Google Scholar 

  8. Wang M, Zhang F, Qian X, Zhao X (2012) Regional biomechanical properties of human sclera after cross-linking by riboflavin/ultraviolet A. J Refract Surg 28(10):723–728. https://doi.org/10.3928/1081597x-20120921-08

    Article  PubMed  Google Scholar 

  9. Wollensak G, Iomdina E (2009) Long-term biomechanical properties of rabbit sclera after collagen crosslinking using riboflavin and ultraviolet a (UVA). Acta Ophthalmol 87(2):193–198. https://doi.org/10.1111/j.1755-3768.2008.01229.x

    Article  CAS  PubMed  Google Scholar 

  10. Kimball EC, Nguyen C, Steinhart MR, Nguyen TD, Pease ME, Oglesby EN, Oveson BC, Quigley HA (2014) Experimental scleral cross-linking increases glaucoma damage in a mouse model. Exp Eye Res 128:129–140. https://doi.org/10.1016/j.exer.2014.08.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang M, Zhang F, Liu K, Zhao X (2015) Safety evaluation of rabbit eyes on scleral collagen cross-linking by riboflavin and ultraviolet A. Clin Exp Ophthalmol 43(2):156–163. https://doi.org/10.1111/ceo.12392

    Article  CAS  PubMed  Google Scholar 

  12. Sun M, Zhang F, Ouyang B, Wang M, Li Y, Jiao X, Zhang L, Wang N (2018) Study of retina and choroid biological parameters of rhesus monkeys eyes on scleral collagen cross-linking by riboflavin and ultraviolet A. PLoS One 13(2):e0192718. https://doi.org/10.1371/journal.pone.0192718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Iseli HP, Spoerl E, Wiedemann P, Krueger RR, Seiler T (2008) Efficacy and safety of blue-light scleral cross-linking. J Refract Surg 24(7):S752–S755

    Article  PubMed  Google Scholar 

  14. Roberts JE (2001) Ocular phototoxicity. J Photochem Photobiol B 64(2–3):136–143

    Article  CAS  PubMed  Google Scholar 

  15. Miao Zhang YZ, Zhang F, Zhang X, Wang M (2015) Efficacy of blue-light cross-linking on human scleral reinforcement. Optometry & Vision Science 92(8):873–878

    Article  Google Scholar 

  16. Savastano MC, Lumbroso B, Rispoli M (2015) In vivo characterization of retinal vascularization morphology using optical coherence tomography angiography. Retina (Philadelphia, Pa) 35(11):2196–2203

    Article  Google Scholar 

  17. Shahlaee A, Samara WA, Hsu J, Say EA, Khan MA, Sridhar J, Hong BK, Shields CL, Ho AC (2016) In vivo assessment of macular vascular density in healthy human eyes using optical coherence tomography angiography. Am J Ophthalmol 165:39–46. https://doi.org/10.1016/j.ajo.2016.02.018

    Article  Google Scholar 

  18. McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R, Bach M (2015) ISCEV standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130(1):1–12. https://doi.org/10.1007/s10633-014-9473-7

    Article  Google Scholar 

  19. McBrien NA, Norton TT (1994) Prevention of collagen crosslinking increases form-deprivation myopia in tree shrew. Exp Eye Res 59(4):475–486. https://doi.org/10.1006/exer.1994.1133

    Article  CAS  PubMed  Google Scholar 

  20. Liu S, Li S, Wang B, Lin X, Wu Y, Liu H, Qu X, Dai J, Zhou X, Zhou H (2016) Scleral cross-linking using riboflavin UVA irradiation for the prevention of myopia progression in a Guinea pig model: blocked axial extension and altered scleral microstructure. PLoS One 11(11):e0165792. https://doi.org/10.1371/journal.pone.0165792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Iseli HP, Korber N, Karl A, Koch C, Schuldt C, Penk A, Liu Q, Huster D, Kas J, Reichenbach A, Wiedemann P, Francke M (2015) Damage threshold in adult rabbit eyes after scleral cross-linking by riboflavin/blue light application. Exp Eye Res 139:37–47. https://doi.org/10.1016/j.exer.2015.07.005

    Article  CAS  PubMed  Google Scholar 

  22. Schuldt C, Karl A, Korber N, Koch C, Liu Q, Fritsch AW, Reichenbach A, Wiedemann P, Kas JA, Francke M, Iseli HP (2015) Dose-dependent collagen cross-linking of rabbit scleral tissue by blue light and riboflavin treatment probed by dynamic shear rheology. Acta Ophthalmol 93(5):e328–e336. https://doi.org/10.1111/aos.12621

    Article  CAS  PubMed  Google Scholar 

  23. Karl A, Makarov FN, Koch C, Korber N, Schuldt C, Kruger M, Reichenbach A, Wiedemann P, Bringmann A, Iseli HP, Francke M (2016) The ultrastructure of rabbit sclera after scleral crosslinking with riboflavin and blue light of different intensities. Graefes Arch Clin Exp Ophthalmol 254(8):1567–1577. https://doi.org/10.1007/s00417-016-3393-z

    Article  CAS  PubMed  Google Scholar 

  24. McBrien NA, Gentle A (2003) Role of the sclera in the development and pathological complications of myopia. Prog Retin Eye Res 22(3):307–338

    Article  CAS  PubMed  Google Scholar 

  25. Jia Y, Bailey ST, Hwang TS, McClintic SM, Gao SS, Pennesi ME, Flaxel CJ, Lauer AK, Wilson DJ, Hornegger J, Fujimoto JG, Huang D (2015) Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye. Proc Natl Acad Sci U S A 112(18):E2395–E2402. https://doi.org/10.1073/pnas.1500185112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Robson AG, Nilsson J, Li S, Jalali S, Fulton AB, Tormene AP, Holder GE, Brodie SE (2018) ISCEV guide to visual electrodiagnostic procedures. Doc Ophthalmol 136(1):1–26. https://doi.org/10.1007/s10633-017-9621-y

    Article  PubMed  PubMed Central  Google Scholar 

  27. Fisher SK, Lewis GP, Linberg KA, Verardo MR (2005) Cellular remodeling in mammalian retina: results from studies of experimental retinal detachment. Prog Retin Eye Res 24(3):395–431. https://doi.org/10.1016/j.preteyeres.2004.10.004

    Article  PubMed  Google Scholar 

  28. Barliya T, Ofri R, Sandalon S, Weinberger D, Livnat T (2017) Changes in retinal function and cellular remodeling following experimental retinal detachment in a rabbit model. J Ophthalmol 2017(4):1–14. https://doi.org/10.1155/2017/4046597

    Article  CAS  Google Scholar 

Download references

Acknowledgments

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.

Funding

This study was supported by grants from the National Natural Science Foundation of China (numbers 81570877 and 81873682; http://www.nsfc.gov.cn/) and the 215 High-Level Talent Fund of Beijing Health Government (number 2013-2-023; http://www.bjchfp.gov.cn/).

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Correspondence to Fengju Zhang.

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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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Li, Y., Liu, C., Sun, M. et al. Ocular safety evaluation of blue light scleral cross-linking in vivo in rhesus macaques. Graefes Arch Clin Exp Ophthalmol 257, 1435–1442 (2019). https://doi.org/10.1007/s00417-019-04346-7

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  • DOI: https://doi.org/10.1007/s00417-019-04346-7

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