Ocular toxicity of daunomycin: Effects of subdivided doses on the rabbit retina after vitreous gas compression

  • Ulrich H. Steinhorst
  • Diane L. Hatchell
  • Edward P. Chen
  • Robert Machemer
Laboratory Investigations


Daunomycin is a potent antiproliferative agent which has been shown to prevent experimental proliferative vitreoretinopathy. However, toxic effects on the rabbit retina have been reported even for the lowest effective doses. In a previous report we demonstrated that subdivided doses rather than single doses of daunomycin improves the efficacy in prevention of experimental proliferative vitreoretinopathy. To evaluate whether dose subdivision would also have an alleviating effect on drug toxicity, we administered 15 nmol daunomycin in doses of 10 nmol and 5 nmol 4 h apart into the vitreous cavity of rabbit eyes which had previously undergone vitreous gas compression. All contralateral eyes received sham treatment. Simultaneous electroretinographic recordings from both eyes on days 0, 3, 7, and 14 demonstrated a significant b-wave decline in drug-exposed eyes. Morphological studies on these eyes revealed no retinal damage. Our findings suggest that dose subdivision does not eliminate the retinal toxicity of daunomycin.


Toxicity Retina Single Dose Effective Dose Morphological Study 
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  1. 1.
    Blumenkranz MS, Hartzer MK (1989) The mechanism of action of drugs for the treatment of vitreoretinal scarring. In: Ryan SJ, Glaser BM, Michels RG (eds) Retina, vol. 3. Mosby, St. Louis, pp 401–411Google Scholar
  2. 2.
    Chandler DB, Quansah FA, Hida T, Machemer R (1986) A refined experimental model for proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 224:86–91PubMedGoogle Scholar
  3. 3.
    Gangadhar DV, Wolf BM, Tanenbaum HL (1989) NakaRushton equation parameters in electroretinogram analysis of daunomycin effects on retinal function. Doc Ophthalmol 72:61–70PubMedGoogle Scholar
  4. 4.
    Hayat MA (1981) Fixation for electron microscopy. Academic Press, New YorkGoogle Scholar
  5. 5.
    Khawly JA, Saloupis P, Hatchell DL, Machemer R (1991) Daunorubicin treatment in a refined experimental model of proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 229:464–467PubMedGoogle Scholar
  6. 6.
    Lawwill T (1972) Practical rabbit electroretinography. Am J Ophthalmol 74:135–141PubMedGoogle Scholar
  7. 7.
    Machemer R (1988) Proliferative vitreoretinopathy (PVR): a personal account of its pathogenesis and treatment. Invest Ophthalmol Vis Sci 29:1771–1784PubMedGoogle Scholar
  8. 8.
    Santana M, Wiedemann P, Kirmani M, Minckler DS, Patterson R, Sorgente N, Ryan SJ (1984) Daunomycin in the treatment of experimental proliferative vitreoretinopathy: retinal toxicity of intravitreal daunomycin in the rabbit. Graefes Arch Clin Exp Ophthalmol 221:210–213PubMedGoogle Scholar
  9. 9.
    Schindler RH, Chandler D, Thresher R, Machemer R (1982) The clearence of intravitreal triamcinolone acetonide. Am J Ophthalmol 93:415–417PubMedGoogle Scholar
  10. 10.
    Silicone Study Group (1992) Vitrectomy with silicone oil or perfluoropropane gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. II. Arch Ophthalmol 110:780–792Google Scholar
  11. 11.
    Spivey BE, Pearlman JT (1953) Day-to-day variations in the ERG of humans and rabbits. Am J Ophthalmol 55:1013–1020Google Scholar
  12. 12.
    Steinhorst UH, Chen EP, Hatchell DL, Samsa GP, Saloupis PT, Westendorf J, Machemer R (1993) Aclacinomycin A in the treatment of experimental proliferative vitreoretinopathy: efficacy and toxicity in the rabbit eye. Invest Ophthalmol Vis Sci 34:1753–1760PubMedGoogle Scholar
  13. 13.
    Steinhorst UH, Chen EP, Machemer R, Hatchell DL (1993) N,N-Dimethyladriamycin for treatment of experimental proliferative vitreoretinopathy: efficacy and toxicity on the rabbit retina. Exp Eye Res 56:489–495PubMedGoogle Scholar
  14. 14.
    Tresher R, Ehrenberg M, Machemer R (1984) Gas-mediated vitreous compression: an experimental alternative to mechanized vitrectomy. Graefes Arch Clin Exp Ophthalmol 221:192–198PubMedGoogle Scholar
  15. 15.
    Wiedemann P, Kirmani M, Santana M, Sorgente N, Ryan SJ (1983) Control of experimental massive periretinal proliferation by daunomycin: dose-response relation. Graefes Arch Clin Exp Ophthalmol 220:233–235PubMedGoogle Scholar
  16. 16.
    Wiedemann P, Sorgente N, Bekhor C, Patterson R, Tran T, Ryan SJ (1985) Daunomycin in the treatment of experimental proliferative vitreoretinopathy. Effective doses in vitro and in vivo. Invest Ophthalmol Vis Sci 26:719–725PubMedGoogle Scholar
  17. 17.
    Wiedemann P, Lemmen K, Schmiedl R, Heimann K (1987) Intraocular daunomycin for the treatment and prophylaxis of traumatic proliferative vitreoretinopathy. Am J Ophthalmol 104:10–14PubMedGoogle Scholar
  18. 18.
    Wiedemann P, Leinung C, Hilgers RD, Heimann K (1991) Daunomycin and silicone oil for the treatment of proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 229:150–152PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Ulrich H. Steinhorst
    • 1
    • 2
  • Diane L. Hatchell
    • 2
    • 3
  • Edward P. Chen
    • 2
  • Robert Machemer
    • 2
  1. 1.Augenklinik der Universität BernBernSwitzerland
  2. 2.Duke University Eye CenterDurhamUSA
  3. 3.Durham Veterans Affairs Medical CenterDurhamUSA

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