Advertisement

A new dye based on anthocyanins from the acai fruit (Euterpe oleracea) for chromovitrectomy in humans: clinical trial results

  • Rafael R. Caiado
  • Cristiane Peris
  • Eduardo B. Rodrigues
  • Michel Eid Farah
  • André Maia
  • Octaviano MagalhãesJr
  • Eduardo Novais
  • Acácio Souza Lima-Filho
  • Mauricio MaiaEmail author
Retinal Disorders
  • 14 Downloads

Abstract

Purpose

To test the applicability of the acai dye at a 25% concentration for identifying the posterior hyaloids and internal limiting membranes (ILMs) during pars plana vitrectomy (PPV) in human eyes with macular holes (MHs).

Methods

This study included 25 patients with chronic idiopathic MHs. The exclusion criteria included glaucoma, previous significant ocular conditions, and previous ocular surgeries except uncomplicated cataract. Ten surgeons performed 23-gauge four-port PPV, phacoemulsification, posterior hyaloid detachment, ILM peeling guided by dye staining, and perfluoropropane injection. The patients remained prone for 5 days postoperatively. The patients were evaluated postoperatively after 1, 30, and 180 days. The surgeons completed a questionnaire regarding the dye’s staining abilities.

Results

The posterior hyaloids and ILMs stained purple in all eyes. The final best-corrected visual acuity improved significantly (p < 0.001) from preoperatively (1.37 ± 0.29) to 180 days postoperatively (1.05 ± 0.43). The MHs closed in 76% of eyes.

Conclusion

The acai dye at a 25% concentration identified posterior hyaloids and ILMs during PPVs in humans. Dye toxicity was unlikely.

Keywords

Acai dye Internal limiting membrane Pars plana vitrectomy Posterior hyaloid Toxicity 

Notes

Acknowledgments

Vision Institute (IPEPO) and Ophthalmos Pharmaceutical Industry.

Funding

This study was funded by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq- 402718/2013-5), Brasília, Brazil, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP – 2014/07686-8), São Paulo, Brazil.

Compliance with ethical standards

This prospective, interventional, non-randomized clinical study was registered at clinicaltrials.gov (NCT02691429). The consort flow diagram and checklist are available (Supplemental Digital Content 1). The Ethics Committee of the Federal University of São Paulo (Institutional Review Board number 466.833) and the National Brazilian Council of Research (CONEP authorization number 1.139.211) approved the study, which was conducted according to the Research Guidelines of the Association of Research in Vision Ophthalmology and the Declaration of Helsinki. To avoid BIAS during data interpretation, 10 surgeons performed 25 procedures following an aleatory protocol defined by the Ethics Committee of the Federal University of São Paulo. All patients provided informed consent regarding the benefits and risks of the surgical procedure and the new dye tested.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the UNIFESP and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

417_2018_4204_MOESM1_ESM.pdf (1.8 mb)
ESM 1 (PDF 1878 kb)
417_2018_4204_MOESM3_ESM.pdf (1 mb)
ESM 3 (PDF 1065 kb)

References

  1. 1.
    Burk SE, Da Mata AP, Snyder ME, Rosa RH Jr, Foster RE (2000) Indocyanine green-assisted peeling of the retinal internal limiting membrane. Ophthalmology 107:2010–2014CrossRefGoogle Scholar
  2. 2.
    Gandorfer A, Haritoglou C, Gass CA, Ulbig MW, Kampik A (2001) Indocyanine green-assisted peeling of the internal limiting membrane may cause retinal damage. Am J Ophthalmol 132:431–433CrossRefGoogle Scholar
  3. 3.
    Engelbrecht NE, Freeman J, Sternberg P Jr, Aaberg TM Sr, Aaberg TM Jr, Martin DF et al (2002) Retinal pigment epithelial changes after macular hole surgery with indocyanine green-assisted internal limiting membrane peeling. Am J Ophthalmol 133:89–94CrossRefGoogle Scholar
  4. 4.
    Maia M, Kellner L, de Juan E Jr, Smith R, Farah ME, Margalit E et al (2004) Effects of indocyanine green injection on the retinal surface and into the subretinal space in rabbits. Retina 24:80–91CrossRefGoogle Scholar
  5. 5.
    Maia M, Margalit E, Lakhanpal R, Tso MO, Grebe R, Torres G et al (2004) Effects of intravitreal indocyanine green injection in rabbits. Retina 24:69–79CrossRefGoogle Scholar
  6. 6.
    Yuen D, Gonder J, Proulx A, Liu H, Hutnik C (2009) Comparison of the in vitro safety of intraocular dyes using two retinal cell lines: a focus on brilliant blue G and indocyanine green. Am J Ophthalmol 147:251–9 e2CrossRefGoogle Scholar
  7. 7.
    Malerbi FK, Maia M, Farah ME, Rodrigues EB (2009) Subretinal brilliant blue G migration during internal limiting membrane peeling. Br J Ophthalmol 93:1687Google Scholar
  8. 8.
    Farah ME, Maia M, Rodrigues EB (2009) Dyes in ocular surgery: principles for use in chromovitrectomy. Am J Ophthalmol 148:332–340CrossRefGoogle Scholar
  9. 9.
    Chen J, Ferreira MA, Farah ME, de Carvalho AM, Alves Ferreira RE, de Moraes Filho MN et al (2013) Posterior hyaloid detachment and internal limiting membrane peeling assisted by anthocyanins from acai fruit (Euterpe oleracea) and 10 other natural vital dyes: experimental study in cadaveric eyes. Retina 33:89–96CrossRefGoogle Scholar
  10. 10.
    Peris CS, Badaro E, Ferreira MA, Lima-Filho AA, Ferreira EL, Maia A et al (2013) Color variation assay of the anthocyanins from acai fruit (Euterpe oleracea): a potential new dye for vitreoretinal surgery. J Ocul Pharmacol Ther 29(8):746–753CrossRefGoogle Scholar
  11. 11.
    Kahkonen MP, Heinonen M (2003) Antioxidant activity of anthocyanins and their aglycons. J Agric Food Chem 51:628–633CrossRefGoogle Scholar
  12. 12.
    Rahman MM, Ichiyanagi T, Komiyama T, Hatano Y, Konishi T (2006) Superoxide radical- and peroxynitrite-scavenging activity of anthocyanins; structure-activity relationship and their synergism. Free Radic Res 40:993–1002CrossRefGoogle Scholar
  13. 13.
    De Rosso VV, Moran Vieyra FE, Mercadante AZ, Borsarelli CD (2008) Singlet oxygen quenching by anthocyanin's flavylium cations. Free Radic Res 42:885–891CrossRefGoogle Scholar
  14. 14.
    Caiado RR, Peris CS, Lima-Filho AAS, Urushima JGP, Novais E, Badaro E et al (2017) Retinal toxicity of acai fruit (Euterpe Oleracea) dye concentrations in rabbits: basic principles of a new dye for chromovitrectomy in humans. Curr Eye Res 42(8):1185–1193CrossRefGoogle Scholar
  15. 15.
    Del Pozo-Insfran D, Brenes CH, Talcott ST (2004) Phytochemical composition and pigment stability of acai (Euterpe oleracea Mart.). J Agric Food Chem 52:1539–1545CrossRefGoogle Scholar
  16. 16.
    Peris CS, Caiado RR, Lima-Filho AAS, Rodrigues EB, Farah ME, Gonçalves M, et al. (2018) Analysis of anthocyanins extracted from the acai fruit (Euterpe oleracea): a potential novel vital dye for chromovitrectomy. J Ophthalmol 2018:1–9Google Scholar
  17. 17.
    Schauss AG, Wu X, Prior RL, Ou B, Huang D, Owens J et al (2006) Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleraceae mart. (acai). J Agric Food Chem 54:8604–8610CrossRefGoogle Scholar
  18. 18.
    Jang YP, Zhou J, Nakanishi K, Sparrow JR (2005) Anthocyanins protect against A2E photooxidation and membrane permeabilization in retinal pigment epithelial cells. Photochem Photobiol 81:529–536CrossRefGoogle Scholar
  19. 19.
    Rizzo S, Savastano A, Bacherini D, Savastano MC (2017) Vascular features of full-thickness macular hole by OCT angiography. Ophthalmic Surg Lasers Imaging Retina 48:62–68CrossRefGoogle Scholar
  20. 20.
    Hood DC, Bach M, Brigell M, Keating D, Kondo M, Lyons JS et al (2012) ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol 124:1–13CrossRefGoogle Scholar
  21. 21.
    McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R et al (2015) ISCEV standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130:1–12CrossRefGoogle Scholar
  22. 22.
    Badaro E, Furlani B, Prazeres J, Maia M, Lima AA, Souza-Martins D et al (2014) Soluble lutein in combination with brilliant blue as a new dye for chromovitrectomy. Graefes Arch Clin Exp Ophthalmol 252:1071–1078CrossRefGoogle Scholar
  23. 23.
    Maia M, Furlani BA, Souza-Lima AA, Martins DS, Navarro RM, Belfort R Jr (2014) Lutein: a new dye for chromovitrectomy. Retina 34:262–272CrossRefGoogle Scholar
  24. 24.
    Rodrigues EB, Costa EF, Penha FM, Melo GB, Bottos J, Dib E et al (2009) The use of vital dyes in ocular surgery. Surv Ophthalmol 54:576–617CrossRefGoogle Scholar
  25. 25.
    Henrich PB, Priglinger SG, Haritoglou C, Josifova T, Ferreira PR, Strauss RW et al (2011) Quantification of contrast recognizability during brilliant blue G- and indocyanine green-assisted chromovitrectomy. Invest Ophthalmol Vis Sci 52:4345–4349CrossRefGoogle Scholar
  26. 26.
    Caiado RR, Moraes-Filho MN, Maia A, Rodrigues EB, Farah ME, Maia M (2014) State of the art in chromovitrectomy. Rev Bras Oftalmol 73:363–376CrossRefGoogle Scholar
  27. 27.
    Rodrigues EB, Maia M, Meyer CH, Penha FM, Dib E, Farah ME (2007) Vital dyes for chromovitrectomy. Curr Opin Ophthalmol 18:179–187CrossRefGoogle Scholar
  28. 28.
    Rodrigues EB, Penha FM, de Paula Fiod Costa E, Maia M, Dib E, Moraes M Jr et al (2010) Ability of new vital dyes to stain intraocular membranes and tissues in ocular surgery. Am J Ophthalmol 149:265–277CrossRefGoogle Scholar
  29. 29.
    Tari SR, Vidne-Hay O, Greenstein VC, Barile GR, Hood DC, Chang S (2007) Functional and structural measurements for the assessment of internal limiting membrane peeling in idiopathic macular pucker. Retina 27:567–572CrossRefGoogle Scholar
  30. 30.
    Lim JW, Cho JH, Kim HK (2010) Assessment of macular function by multifocal electroretinography following epiretinal membrane surgery with internal limiting membrane peeling. Clin Ophthalmol 4:689–694CrossRefGoogle Scholar
  31. 31.
    Chatziralli IP, Theodossiadis PG, Steel DHW (2018) Internal limiting membrane peeling in macular hole surgery; why, when, and how? Retina 38:870–882CrossRefGoogle Scholar
  32. 32.
    Eckardt C, Eckardt U, Groos S, Luciano L, Reale E (1997) Removal of the internal limiting membrane in macular holes Clinical and morphological findings. Ophthalmologe 94:545–551CrossRefGoogle Scholar
  33. 33.
    Mester V, Kuhn F (2000) Internal limiting membrane removal in the management of full-thickness macular holes. Am J Ophthalmol 129:769–777CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Rafael R. Caiado
    • 1
  • Cristiane Peris
    • 1
  • Eduardo B. Rodrigues
    • 1
  • Michel Eid Farah
    • 1
  • André Maia
    • 1
  • Octaviano MagalhãesJr
    • 1
  • Eduardo Novais
    • 1
  • Acácio Souza Lima-Filho
    • 1
    • 2
  • Mauricio Maia
    • 1
    • 3
    Email author return OK on get
  1. 1.Vision Institute, Department of OphthalmologyFederal University of São PauloSão PauloBrazil
  2. 2.Ophthalmos Pharmaceutical IndustrySão PauloBrazil
  3. 3.Brazilian Institute of Fight Against BlindnessSão PauloBrazil

Personalised recommendations