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Vehicle of triamcinolone acetonide is associated with retinal toxicity and transient increase of lens density

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Abstract

Background

Intravitreal triamcinolone acetonide (TA) has been widely used as a therapeutic method for many ocular diseases, but a consensus on an appropriate safe therapeutic window of dosage for intravitreal injection, and whether vehicle of TA should be reduced or eliminated, has not yet been reached. The aim of this article is to investigate these issues.

Methods

Forty New Zealand white rabbits were divided into four experimental groups and one control group. Four or 25 mg TA, with vehicle either reduced or not, was injected into the vitreous cavity of rabbits in experimental groups. Rabbits in the control group received 0.2 ml intravitreal sterile saline solution. Intraocular pressures (IOP) were measured by a Tonopen tonometer. Values of lens density were measured by a Pentacam system. Soluble protein, total antioxidation capacity, reduced glutathione (GSH), glutathion peroxidase (GSH-px), and superoxide dismutase (SOD) in lens were measured by specific kits. ERG and pathological examinations, including light and electron microscopy of the retina, were also performed.

Results

Elevation of IOP was noted in all experimental groups after intravitreal TA (P<0.01, paired t-test). Significant increase of lens density was noticed at 1 week after intravitreal TA in the 25 mg vehicle-containing group (P<0.0001, paired t-test). Significant loss of GSH-px activity was noticed at the end of the study (P<0.05, paired t-test), while SOD activity increased (P<0.05, paired t-test). Amplitudes of ERG waves declined significantly in vehicle-containing groups (P<0.01, paired t-test) at the end of the study. Pathological examination showed obvious retinal toxicity in vehicle-containing groups.

Conclusions

Vehicle of TA should be eliminated or reduced before intravitreal injection to avoid potential retinal toxicity and transient increase in lens density.

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References

  1. Bednarek J, Wysocki H, Sowinski J (2004) Peripheral parameters of oxidative stress in patients with infiltrative Graves’ ophthalmopathy treated with corticosteroids. Immunol Lett 93(2–3):227–232

    Article  PubMed  CAS  Google Scholar 

  2. Bucher RS, Johnson MW (2005) Microbiologic studies of multiple-dose containers of triamcinolone acetonide and lidocaine hydrochloride. Retina 25(3):269–271

    Article  PubMed  Google Scholar 

  3. Bynoe LA, Weiss JN (2003) Retinal endovascular surgery and intravitreal triamcinolone acetonide for central vein occlusion in young adults. Am J Ophthalmol 135(3):382–384

    Article  PubMed  CAS  Google Scholar 

  4. Ciulla TA, Criswell MH, Danis RP, Fronheiser M, Yuan P, Cox TA, Csaky KG, Robinson MR (2003) Choroidal neovascular membrane inhibition in a laser treated rat model with intraocular sustained release triamcinolone acetonide microimplants. Br J Ophthalmol 87(8):1032–1037

    Article  PubMed  CAS  Google Scholar 

  5. Danis RP, Ciulla TA, Pratt LM, Anliker W (2000) Intravitreal triamcinolone acetonide in exudative age-related macular degeneration. Retina 20(3):244–250

    Article  PubMed  CAS  Google Scholar 

  6. Dickerson JE Jr, Dotzel E, Clark AF (1997) Steroid-induced cataract: new perspective from in vitro and lens culture studies. Exp Eye Res 65(4):507–516

    Article  PubMed  CAS  Google Scholar 

  7. Fydryk J, Jacobson E, Kurzawska O, Malecka G, Gonet B, Urasinski T, Brodkiewicz A, Bukowska H (1998) Antioxidant status of children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 12(9):751–754

    Article  PubMed  CAS  Google Scholar 

  8. Garcia-Arumi J, Boixadera A, Giralt J, Martinez-Castillo V, Gomez-Ulla F, Corcostegui B, Garcia-Arumi E (2005) Comparison of different techniques for purification of triamcinolone acetonide suspension for intravitreal use. Br J Ophthalmol 89(9):1112–1114

    Article  PubMed  CAS  Google Scholar 

  9. Gerometta R, Podos SM, Candia OA, Wu B, Malgor LA, Mittag T, Danias J (2004) Steroid-induced ocular hypertension in normal cattle. Arch Ophthalmol 122(10):1492–1497

    Article  PubMed  CAS  Google Scholar 

  10. Gillies MC, Kuzniarz M, Craig J, Ball M, Luo W, Simpson JM (2005) Intravitreal triamcinolone-induced elevated intraocular pressure is associated with the development of posterior subcapsular cataract. Ophthalmology 112(1):139–143

    Article  PubMed  Google Scholar 

  11. Gillies MC, Simpson JM, Billson FA, Luo W, Penfold P, Chua W, Mitchell P, Zhu M, Hunyor AB (2004) Safety of an intravitreal injection of triamcinolone: results from a randomized clinical trial. Arch Ophthalmol 122(3):336–340

    Article  PubMed  CAS  Google Scholar 

  12. Hanta I, Kuleci S, Canacankatan N, Kocabas A (2003) The oxidant-antioxidant balance in mild asthmatic patients. Lung 181(6):347–352

    Article  PubMed  CAS  Google Scholar 

  13. Hernaez-Ortega MC, Soto-Pedre E (2004) A simple and rapid method for purification of triamcinolone acetonide suspension for intravitreal injection. Ophthalmic Surg Lasers Imaging 35(4):350–351

    PubMed  Google Scholar 

  14. Hida T, Chandler D, Arena JE, Machemer R (1986) Experimental and clinical observations of the intraocular toxicity of commercial corticosteroid preparations. Am J Ophthalmol 101(2):190–195

    PubMed  CAS  Google Scholar 

  15. Hui YN, Hu D (1999) Prevention of experimental proliferative vitreoretinopathy with daunomycin and triamcinolone based on the time course of the disease. Graefes Arch Clin Exp Ophthalmol 237(7):601–605

    Article  PubMed  CAS  Google Scholar 

  16. Jonas JB, Degenring R, Kreissig I, Akkoyun I (2004) Safety of intravitreal high-dose reinjections of triamcinolone acetonide. Am J Ophthalmol 138(6):1054–1055

    Article  PubMed  CAS  Google Scholar 

  17. Jonas JB, Hayler JK, Panda-Jonas S (2000) Intravitreal injection of crystalline cortisone as adjunctive treatment of proliferative vitreoretinopathy. Br J Ophthalmol 84(9):1064–1067

    Article  PubMed  CAS  Google Scholar 

  18. Jonas JB, Hayler JK, Sofker A, Panda-Jonas S (2001) Intravitreal injection of crystalline cortisone as adjunctive treatment of proliferative diabetic retinopathy. Am J Ophthalmol 131(4):468–471

    Article  PubMed  CAS  Google Scholar 

  19. Jonas JB, Hayler JK, Sofker A, Panda-Jonas S (2001) Regression of neovascular iris vessels by intravitreal injection of crystalline cortisone. J Glaucoma 10(4):284–287

    Article  PubMed  CAS  Google Scholar 

  20. Jonas JB, Kreissig I, Sofker A, Degenring RF (2003) Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol 121(1):57–61

    Article  PubMed  CAS  Google Scholar 

  21. Kivilcim M, Peyman GA, El-Dessouky ES, Kazi AA, Cheema R, Hegazy H (2000) Retinal toxicity of triamcinolone acetonide in silicone-filled eyes. Ophthalmic Surg Lasers 31(6):474–478

    PubMed  CAS  Google Scholar 

  22. Kosano H, Nishigori H (2002) Steroid-induced cataract: other than in the whole animal system, in the lens culture system, androgens, estrogens and progestins as well as glucocorticoids produce a loss of transparency of the lens. Dev Ophthalmol 35:161–168

    Article  PubMed  CAS  Google Scholar 

  23. Lee JW, Iwatsuru M, Nishigori H (1995) Glucocorticoid-induced cataract of developing chick embryo as a screening model for anticataract agents. J Ocul Pharmacol Ther 11(4):533–541

    Article  PubMed  CAS  Google Scholar 

  24. McCuen BW 2nd, Bessler M, Tano Y, Chandler D, Machemer R (1981) The lack of toxicity of intravitreally administered triamcinolone acetonide. Am J Ophthalmol 91(6):785–788

    PubMed  CAS  Google Scholar 

  25. Mohan R, Muralidharan AR (1989) Steroid induced glaucoma and cataract. Ind J Ophthalmol 37(1):13–16

    CAS  Google Scholar 

  26. Moshfeghi DM, Kaiser PK, Scott IU, Sears JE, Benz M, Sinesterra JP, Kaiser RS, Bakri SJ, Maturi RK, Belmont J, Beer PM, Murray TG, Quiroz-Mercado H, Mieler WF (2003) Acute endophthalmitis following intravitreal triamcinolone acetonide injection. Am J Ophthalmol 136(5):791–796

    Article  PubMed  CAS  Google Scholar 

  27. Nishimura A, Kobayashi A, Segawa Y, Sakurai M, Shirao E, Shirao Y, Sugiyama K (2003) Isolating triamcinolone acetonide particles for intravitreal use with a porous membrane filter. Retina 23(6):777–779

    Article  PubMed  Google Scholar 

  28. Park CH, Jaffe GJ, Fekrat S (2003) Intravitreal triamcinolone acetonide in eyes with cystoid macular edema associated with central retinal vein occlusion. Am J Ophthalmol 136(3):419–425

    Article  PubMed  CAS  Google Scholar 

  29. Patteau F, Bourcier T, Naacke H, Allahdadi H, Borderie V, Laroche L (2003) [Posterior subcapsular cataract in a case of ulcerative colitis treated with corticosteroid enema]. J Fr Ophtalmol 26(8):834–836

    PubMed  CAS  Google Scholar 

  30. Pescosolido N, Miccheli A, Manetti C, Iannetti GD, Feher J, Cavallotti C (2001) Metabolic changes in rabbit lens induced by treatment with dexamethasone. Ophthalmic Res 33(2):68–74

    Article  PubMed  CAS  Google Scholar 

  31. Rechtman E, Allen VD, Danis RP, Pratt LM, Harris A, Speicher MA (2003) Intravitreal triamcinolone for choroidal neovascularization in ocular histoplasmosis syndrome. Am J Ophthalmol 136(4):739–741

    Article  PubMed  CAS  Google Scholar 

  32. Singh IP, Ahmad SI, Yeh D, Challa P, Herndon LW, Allingham RR, Lee PP (2004) Early rapid rise in intraocular pressure after intravitreal triamcinolone acetonide injection. Am J Ophthalmol 138(2):286–287

    Article  PubMed  Google Scholar 

  33. Spandau UH, Derse M, Schmitz-Valckenberg P, Papoulis C, Sagstetter BU, Stiefvater K, Jonas JB (2005) Triamcinolone acetonide concentration after filtration of the solvent agent. Am J Ophthalmol 139(4):712–713

    Article  PubMed  CAS  Google Scholar 

  34. Sutter FK, Gillies MC (2003) Pseudo-endophthalmitis after intravitreal injection of triamcinolone. Br J Ophthalmol 87(8):972–974

    Article  PubMed  CAS  Google Scholar 

  35. Sutter FK, Simpson JM, Gillies MC (2004) Intravitreal triamcinolone for diabetic macular edema that persists after laser treatment: three-month efficacy and safety results of a prospective, randomized, double-masked, placebo-controlled clinical trial. Ophthalmology 111(11):2044–2049

    Article  PubMed  Google Scholar 

  36. Weinreb RN, Bloom E, Baxter JD, Alvarado J, Lan N, O’Donnell J, Polansky JR (1981) Detection of glucocorticoid receptors in cultured human trabecular cells. Invest Ophthalmol Vis Sci 21(3):403–407

    PubMed  CAS  Google Scholar 

  37. Wenk EJ, Hernandez MR, Weinstein BI, Gordon GG, Dunn MW, Southren AL (1982) Glucocorticoid receptor binding in bovine lens. Invest Ophthalmol Vis Sci 22(5):599–605

    PubMed  CAS  Google Scholar 

  38. Wingate RJ, Beaumont PE (1999) Intravitreal triamcinolone and elevated intraocular pressure. Aust N Z J Ophthalmol 27(6):431–432

    Article  PubMed  CAS  Google Scholar 

  39. Wordinger RJ, Clark AF (1999) Effects of glucocorticoids on the trabecular meshwork: towards a better understanding of glaucoma. Prog Retin Eye Res 18(5):629–667

    Article  PubMed  CAS  Google Scholar 

  40. Yeung CK, Chan KP, Chan CK, Pang CP, Lam DS (2004) Cytotoxicity of triamcinolone on cultured human retinal pigment epithelial cells: comparison with dexamethasone and hydrocortisone. Jpn J Ophthalmol 48(3):236–242

    Article  PubMed  CAS  Google Scholar 

  41. Yeung CK, Chan KP, Chiang SW, Pang CP, Lam DS (2003) The toxic and stress responses of cultured human retinal pigment epithelium (ARPE19) and human glial cells (SVG) in the presence of triamcinolone. Invest Ophthalmol Vis Sci 44(12):5293–5300

    Article  PubMed  Google Scholar 

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Correspondence to Jiang Yanrong.

Additional information

This study was supported by the 985 Fund of Peking University, Beijing.

The authors have no financial interest in any instruments or drugs mentioned in this study.

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Kai, W., Yanrong, J. & Xiaoxin, L. Vehicle of triamcinolone acetonide is associated with retinal toxicity and transient increase of lens density. Graefe's Arch Clin Exp Ophthalmo 244, 1152–1159 (2006). https://doi.org/10.1007/s00417-005-0251-9

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  • DOI: https://doi.org/10.1007/s00417-005-0251-9

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