Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Vitrectomy and ILM peeling in rhesus macaque: pitfalls and tips for success

Abstract

Background

The non-human primate (NHP) model is ideal for pre-clinical testing of novel therapies for human retinal diseases due to its similarity to the human visual system. However, intra-ocular delivery of gene therapy or cell transplantation to the retina gets hampered by the sticky vitreous body and poorly permeable inner limiting membrane (ILM) in primates. Although vitrectomy and ILM peeling are commonly performed in patients, many pitfalls exist in carrying out these procedures in the rhesus macaque, which have not been reported previously.

Methods

We summarised common surgical pitfalls after performing vitrectomy and ILM peeling in four eyes of two rhesus macaques (one male and one female). We provided corresponding hands-on technical tips based on our surgical experience and literature search. Orbital CT scans were compared between adult rhesus macaques and humans. High-resolution surgical videos were recorded to demonstrate each critical surgical step.

Results

Due to size difference, poor post-operative compliance, and high-standard requirements of a controlled experiment, there were eleven common surgical pitfalls during vitrectomy and ILM peeling in rhesus macaque. Falling into these pitfalls may produce discomfort, add fatigue, cause surgical complications, or even lead to the exclusion of the NHP from an experimental group.

Conclusion

Recognition and circumvention of these pitfalls during vitrectomy and ILM peeling in NHP are essential. By focusing on these surgical pitfalls, we can better carry out preclinical tests of novel therapies for retinal diseases in the NHP model.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Pitfalls and tips 1–5.
Fig. 2: Small palpebral fissure in the rhesus macaque.
Fig. 3: Scheme of PVD under microscopic surgical view.
Fig. 4: Scheme of ILM peeling under microscopic surgical view.
Fig. 5: Retinal photography and OCT images after surgery.

Similar content being viewed by others

Data availability

Data available within the article or its supplementary materials.

References

  1. Picaud S, Dalkara D, Marazova K, Goureau O, Roska B, Sahel JA. The primate model for understanding and restoring vision. Proc Natl Acad Sci USA. 2019;116:26280–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Peng YR, Shekhar K, Yan W, Herrmann D, Sappington A, Bryman GS, et al. Molecular classification and comparative taxonomics of foveal and peripheral cells in primate retina. Cell. 2019;176:1222–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Jeffery G, Levitt JB, Cooper HM. Segregated hemispheric pathways through the optic chiasm distinguish primates from rodents. Neuroscience. 2008;157:637–43.

    Article  CAS  PubMed  Google Scholar 

  4. Friedli L, Rosenzweig ES, Barraud Q, Schubert M, Dominici N, Awai L, et al. Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates. Sci Transl Med. 2015;7:302ra134.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Peynshaert K, Devoldere J, Minnaert AK, De Smedt SC, Remaut K. Morphology and composition of the inner limiting membrane: species-specific variations and relevance toward drug delivery research. Curr Eye Res. 2019;44:465–75.

    Article  CAS  PubMed  Google Scholar 

  6. Zhang KY, Johnson TV. The internal limiting membrane: Roles in retinal development and implications for emerging ocular therapies. Exp Eye Res. 2021;206:108545.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tshilenge KT, Ameline B, Weber M, Mendes-Madeira A, Nedellec S, Biget M, et al. Vitrectomy before intravitreal injection of AAV2/2 vector promotes efficient transduction of retinal ganglion cells in dogs and nonhuman primates. Hum Gene Ther Methods. 2016;27:122–34.

    Article  CAS  PubMed  Google Scholar 

  8. Peynshaert K, Devoldere J, De Smedt SC, Remaut K. In vitro and ex vivo models to study drug delivery barriers in the posterior segment of the eye. Adv Drug Deliv Rev. 2018;126:44–57.

    Article  CAS  PubMed  Google Scholar 

  9. Johnson TV, Bull ND, Hunt DP, Marina N, Tomarev SI, Martin KR. Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma. Investigative Ophthalmol Vis Sci. 2010;51:2051–9.

    Article  Google Scholar 

  10. Gamlin PD, Alexander JJ, Boye SL, Witherspoon CD, Boye SE. SubILM injection of AAV for gene delivery to the retina. Methods Mol Biol. 2019;1950:249–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Nguyen CL, Oh LJ, Wong E, Francis IC. Povidone-iodine 3-minute exposure time is viable in preparation for cataract surgery. Eur J Ophthalmol. 2017;27:573–6.

    Article  PubMed  Google Scholar 

  12. Siqueira RC, Dos Santos WF, Scott IU, Messias A, Rosa MN, Fernandes Cunha GM, et al. Neuroprotective effects of intravitreal triamcinolone acetonide and dexamethasone implant in rabbit retinas after pars plana vitrectomy and silicone oil injection. Retina. 2015;35:364–70.

    Article  CAS  PubMed  Google Scholar 

  13. Konstantinidis L, Berguiga M, Beknazar E, Wolfensberger TJ. Anatomic and functional outcome after 23-gauge vitrectomy, peeling, and intravitreal triamcinolone for idiopathic macular epiretinal membrane. Retina. 2009;29:1119–27.

    Article  PubMed  Google Scholar 

  14. Li Y, Wolf MD, Kulkarni AD, Bell J, Chang JS, Nimunkar A, et al. In situ tremor in vitreoretinal surgery. Hum Factors. 2021;63:1169–81.

    Article  PubMed  Google Scholar 

  15. Zurawski CA, McCarey BE, van Rij G, Fernandes A. Corneal biometrics of the rhesus monkey (Macaca mulatta). J Med Primatol. 1989;18:461–6.

    Article  CAS  PubMed  Google Scholar 

  16. Zamora JL. Chemical and microbiologic characteristics and toxicity of povidone-iodine solutions. Am J Surg. 1986;151:400–6.

    Article  CAS  PubMed  Google Scholar 

  17. Jiang J, Wu M, Shen T. The toxic effect of different concentrations of povidone iodine on the rabbit’s cornea. Cutan Ocul Toxicol. 2009;28:119–24.

    Article  CAS  PubMed  Google Scholar 

  18. Speaker MG, Menikoff JA. Prophylaxis of endophthalmitis with topical povidone-iodine. Ophthalmology. 1991;98:1769–75.

    Article  CAS  PubMed  Google Scholar 

  19. Warrier SK, Jain R, Gilhotra JS, Newland HS. Sutureless vitrectomy. Indian J Ophthalmol. 2008;56:453–8.

    Article  PubMed  PubMed Central  Google Scholar 

  20. López-Guajardo L, Pareja-Esteban J, Teus-Guezala MA. Oblique sclerotomy technique for prevention of incompetent wound closure in transconjunctival 25-gauge vitrectomy. Am J Ophthalmol. 2006;141:1154–6.

    Article  PubMed  Google Scholar 

  21. Yamane S, Kadonosono K, Inoue M, Kobayashi S, Watanabe Y, Arakawa A. Effect of intravitreal gas tamponade for sutureless vitrectomy wounds: three-dimensional corneal and anterior segment optical coherence tomography study. Retina. 2011;31:702–6.

    Article  PubMed  Google Scholar 

  22. Kanclerz P, Grzybowski A. Complications associated with the use of expandable gases in vitrectomy. J Ophthalmol. 2018;2018:8606494.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gupta V, Prabhakar A, Yadav M, Khandelwal N. Computed tomography imaging-based normative orbital measurement in Indian population. Indian J Ophthalmol. 2019;67:659–63.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Fernandes A, Bradley DV, Tigges M, Tigges J, Herndon JG. Ocular measurements throughout the adult life span of rhesus monkeys. Invest Ophthalmol Vis Sci. 2003;44:2373–80.

    Article  PubMed  Google Scholar 

  25. Bach A, Villegas VM, Gold AS, Shi W, Murray TG. Axial length development in children. Int J Ophthalmol. 2019;12:815–9.

    PubMed  PubMed Central  Google Scholar 

  26. Uchino E, Uemura A, Ohba N. Initial stages of posterior vitreous detachment in healthy eyes of older persons evaluated by optical coherence tomography. Arch Ophthalmol. 2001;119:1475–9.

    Article  CAS  PubMed  Google Scholar 

  27. Inoue M. Wide-angle viewing system. Dev Ophthalmol. 2014;54:87–91.

    Article  PubMed  Google Scholar 

  28. Virata SR, Kylstra JA, Singh HT. Corneal epithelial defects following vitrectomy surgery using hand-held, sew-on, and noncontact viewing lenses. Retina. 1999;19:287–90.

    Article  CAS  PubMed  Google Scholar 

  29. Sheng Lim K, Garg A, Cheng J, Muthusamy K, Beltran-Agullo L, Barton K. Comparison of short-term postoperative hypotony rates of 23-gauge vs 25-gauge needles in formation of the scleral tract for Baerveldt tube insertion into the anterior chamber. J Curr Glaucoma Pr. 2018;12:36–9.

    Article  Google Scholar 

  30. Ho LY, Garretson BR, Ranchod TM, Balasubramaniam M, Ruby AJ, Capone A Jr, et al. Study of intraocular pressure after 23-gauge and 25-gauge pars plana vitrectomy randomized to fluid versus air fill. Retina. 2011;31:1109–17.

    Article  PubMed  Google Scholar 

  31. Inoue Y, Kadonosono K, Yamakawa T, Uchio E, Watanabe Y, Yanagi Y, et al. Surgically-induced inflammation with 20-, 23-, and 25-gauge vitrectomy systems: an experimental study. Retina. 2009;29:477–80.

    Article  PubMed  Google Scholar 

  32. Sedova A, Steiner I, Matzenberger RP, Georgopoulos M, Scholda C, Kriechbaum KF, et al. Comparison of safety and effectiveness between 23-gauge and 25-gauge vitrectomy surgery in common vitreoretinal diseases. PLoS One. 2021;16:e0248164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sawada T, Kakinoki M, Sawada O, Kawamura H, Ohji M. Closure of sclerotomies after 25- and 23-gauge transconjunctival sutureless pars plana vitrectomy evaluated by optical coherence tomography. Ophthalmic Res. 2011;45:122–8.

    Article  PubMed  Google Scholar 

  34. Barth H, Crafoord S, Arner K, Ghosh F. Inflammatory responses after vitrectomy with vitreous substitutes in a rabbit model. Graefes Arch Clin Exp Ophthalmol. 2019;257:769–83.

    Article  CAS  PubMed  Google Scholar 

  35. Chen W, Mo W, Sun K, Huang X, Zhang YL, Song HY. Microplasmin degrades fibronectin and laminin at vitreoretinal interface and outer retina during enzymatic vitrectomy. Curr Eye Res. 2009;34:1057–64.

    Article  CAS  PubMed  Google Scholar 

  36. Grinton M, Steel DH. Cochrane Corner: Ocriplasmin-why isn’t it being used more? Eye (Lond). 2019;33:1195–7.

    Article  PubMed  Google Scholar 

  37. Gandorfer A, Rohleder M, Sethi C, Eckle D, Welge-Lüssen U, Kampik A, et al. Posterior vitreous detachment induced by microplasmin. Invest Ophthalmol Vis Sci. 2004;45:641–7.

    Article  PubMed  Google Scholar 

  38. Wassmer SJ, Carvalho LS, György B, Vandenberghe LH, Maguire CA. Exosome-associated AAV2 vector mediates robust gene delivery into the murine retina upon intravitreal injection. Sci Rep. 2017;7:45329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The sponsor or funding organisation had no role in the design or conduct of this research. We thank MJEditor (www.mjeditor.com) for language editing.

Funding

National Key R&D Program of China [2021YFA1101200]. National Key R&D Program of China [2016YFC1101200]. National Natural Science Foundation of China [81770926;81800842]. Key R&D Program of Zhejiang Province [2019C03009; 2021C03065]. Key R&D Program of Wenzhou Eye Hospital [YNZD1201902]. National Key R&D Program of China [2019YFC0119300].

Author information

Authors and Affiliations

Authors

Contributions

Conceptualisation: YZ, QP; Data curation: YZ, SL, ML; Formal Analysis: SL, ML, HP, LW, YM; Funding acquisition: YZ, WW; Methodology: YZ, QP; Visualisation: YZ, QP, SL, ML. Writing – original draft: YZ, QP, SL, ML; Writing – review & editing: YZ, QP, WW.

Corresponding authors

Correspondence to Wencan Wu or Yikui Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

The research followed the principles of the Declaration of Helsinki, and was approved by the ethics committees of Wenzhou Eye Hospital, Wenzhou Medical University (Ethics ID number: KYK (2017) 53). Patient consents from three male adults were obtained before analysis of their orbital CT scan data in this study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pan, Q., Lu, S., Li, M. et al. Vitrectomy and ILM peeling in rhesus macaque: pitfalls and tips for success. Eye 37, 2257–2264 (2023). https://doi.org/10.1038/s41433-022-02327-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41433-022-02327-5

Search

Quick links