Chemo Fog pp 113-118 | Cite as

Chemotherapy-Related Visual System Toxicity

  • Robert B. Raffa
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 678)


Most, if not all, of the studies that report cognitive impairments in patients who have been treated with cancer chemotherapy also report deficits involving the visual system (e.g., visual-spatial function or visual memory). The visual system seems like a likely susceptible target of cytotoxic drugs. Therefore, some portion of the vision-related cognitive deficits of chemo fog/chemo brain might result from a direct action of the drugs or from site/site interaction between effects on the visual system and other critical brain regions. This chapter is a succint summary of a more expanded review.


Visual System Ocular Side Ocular Toxicity Keratoconjunctivitis Sicca International Breast Cancer Study Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Raffa RB, Tallarida RJ. Effects on the visual system might contribute to some of the cognitive deficits of cancer chemotherapy-induced ‘chemo-fog’. J Clin Pharm Ther, in press.Google Scholar
  2. 2.
    Wieneke MH, Dienst ER. Neuropsychological assessment of cognitive functioning following chemotherapy for breast cancer. Psycho-Oncology 1995; 4:61–66.CrossRefGoogle Scholar
  3. 3.
    Brezden CB, Phillips K-A, Abdolell M et al. Cognitive function in breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 2000; 18:2695–2701.PubMedGoogle Scholar
  4. 4.
    Schagen SB, van Dam FSAM, Muller MJ et al. Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer 1999; 85:640–650.PubMedCrossRefGoogle Scholar
  5. 5.
    van Dam FSAM, Schagen SB, Muller MJ et al. Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy. J Natl Cancer Inst 1998; 90:210–218.PubMedCrossRefGoogle Scholar
  6. 6.
    Raffa RB, Tallarida RJ. Effects on the visual system might contribute to some of the cognitive deficits of cancer chemotherapy-induced ‘chemo-fog’. J Clin Pharm Ther, in press.Google Scholar
  7. 7.
    Lezak M. Neuropsychological Assessment. 2nd ed. New York: Oxford University Press, 1993.Google Scholar
  8. 8.
    Delis DC, Kramer JH, Kaplan E et al. CVLT Research Edition Manual. New York: The Psychological Association, 1987.Google Scholar
  9. 9.
    Fraunfelder FT, Meyer SM. Ocular toxicity of anineoplastic agents. Ophthalmology 1983; 90:1–3.PubMedCrossRefGoogle Scholar
  10. 10.
    Imperia PS, Lazarus HM, Lass JH. Ocular complications of systemic cancer chemotherapy. Survey Ophthalmol 1989; 34:209–230.CrossRefGoogle Scholar
  11. 11.
    AL-Tweigeri T, Nabholtz J-M, Mackey JR. Ocular toxicity and cancer chemotherapy. Cancer 1996; 78:1359–1373.PubMedCrossRefGoogle Scholar
  12. 12.
    Schmid KE, Kornek GV, Scheithauer W et al. Update on ocular complications of systemic cancer chemotherapy. Survey Ophthalmol 2006; 51:19–40.CrossRefGoogle Scholar
  13. 13.
    Gianni L, Panzini I, Li S et al. International Breast Cancer Study Group (IBCSG). Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer: results from International Breast Cancer Study Group trials. Cancer 2006; 106:505–513.PubMedCrossRefGoogle Scholar
  14. 14.
    Jack MK, Hicks JD. Ocular complications in high-dose chemoradiotherapy and marrow transplantation. Ann Ophthalmol 1981; 13:709–711.PubMedGoogle Scholar
  15. 15.
    Kende G, Sirkin SR, Thomas PR et al. Blurring of vision: a previously undescribed complication of cyclophosphamide therapy. Cancer 1979; 44:69–71.PubMedCrossRefGoogle Scholar
  16. 16.
    Stevens A, Spooner D. Lacrimal duct stenosis and other ocular toxicity associated with adjuvant cyclophosphamide, methotrexate and 5-fluorouracil combination chemotherapy for early stage breast cancer. Clin Oncol 2001; 13:438–440.Google Scholar
  17. 17.
    Lee V, Bentley CR, Olver JM. Sclerosing canaliculitis after 5-fluorouracil breast cancer chemotherapy. Eye 1998; 12:343–349.PubMedCrossRefGoogle Scholar
  18. 18.
    Esmaeli B, Burnstine MA, Ahmadi MA et al. Docetaxel-induced histologic changes in the lacrimal sac and the nasal mucosa. Ophth Plas Recon Sur 2003; 19:305–308.CrossRefGoogle Scholar
  19. 19.
    Esmaeli B, Hidaji L, Adinin RB et al. Blockage of the lacrimal drainage apparatus as a side effect of docetaxel therapy. Cancer 2003; 98:504–507.PubMedCrossRefGoogle Scholar
  20. 20.
    Vizel M, Oster MW. Ocular side effects of cancer chemotherapy. Cancer 1982; 49:1999–2002.PubMedCrossRefGoogle Scholar
  21. 21.
    Rahl AHS, Hungerford JL, Ahmed AI. Ocular toxicity of desferrioxamine: light microscopic histochemical and ultrastructural findings. Brit J Ophthal 1988; 70:373–381.Google Scholar
  22. 22.
    Voest EE, Neijt JP, Keunen JE et al. Phase I study using desferrioxamine and iron sorbitol citrate in an attempt to modulate the iron status of tumor cells to enhance doxorubicin activity. Cancer Chemother Pharmacol 1993; 31:357–362.PubMedCrossRefGoogle Scholar
  23. 23.
    Khaw PT, Sherwood MB, MacKay SL et al. Five-minute treatments with fluorouracil, floxuridine and mitomycin have long-term effects on human Tenon’s capsule fibroblasts. Arch Ophthalmol 1992; 110:1150–1154.PubMedCrossRefGoogle Scholar
  24. 24.
    Stern WH, Guerin CJ, Erickson PA et al. Ocular toxicity of fluorouracil after vitrectomy. Amer J Ophthalmol 1983; 96:43–51.PubMedGoogle Scholar
  25. 25.
    Agarwal MR, Esmaeli B, Burnstine MA. Squamous metaplasia of the canaliculi associated with 5-fluorouracil: a clinicopathologic case report. Ophthalmology 2002; 109:2359–2361.PubMedCrossRefGoogle Scholar
  26. 26.
    Shapiro MS, Thoft RA, Friend J et al. 5-fluorouracil toxicity to the ocular surface epithelium. Invest Ophthalmol Vis Sci 1985; 26:580–583.PubMedGoogle Scholar
  27. 27.
    Brink HM, Beex LV. Punctal and canalicular stenosis associated with systemic fluorouracil therapy. Documenta Ophthalmologica 1995; 90:1–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Prasad S, Kamath GG, Phillips RP. Lacrimal canalicular stenosis associated with systemic 5-fluorouracil therapy. Acta Ophthalmol Scand 2000; 78:110–113.PubMedCrossRefGoogle Scholar
  29. 29.
    Bixenman WW, Nicholls JVV, Warwick OH. Oculomotor disturbances associated with 5-fluorouracil chemotherapy. Amer J Ophthalmol 1968; 83:604–608.Google Scholar
  30. 30.
    Sato Y, Morita M, Takahashi HO et al. Combined surgery, radiotherapy and regional chemotherapy in carcinoma of the paranasal sinuses. Cancer 1970; 25:571–579.PubMedCrossRefGoogle Scholar
  31. 31.
    Fishman ML, Bean SC, Cogan DG. Optic atrophy following prophylactic chemotherapy and cranial radiation for acute lymphocytic leukemia. Amer J Ophthalmol 1976; 82:571–576.PubMedGoogle Scholar
  32. 32.
    Margileth DA, Poplack DG, Pizzo PA et al. Blindness during remission in two patients with acute lymphoblastic leukemia: a possible complication of multimodality therapy. Cancer 1977; 39:58–61.PubMedCrossRefGoogle Scholar
  33. 33.
    Boogerd W, Moffie D, Smets LA. Early blindness and coma during intrathecal chemotherapy for meningeal carcinomatosis. Cancer 1990; 65:452–457.PubMedCrossRefGoogle Scholar
  34. 34.
    Carter WH Jr, Wampler GL, Stablein DM et al. Drug activity and therapeutic synergism in cancer treatment. Cancer Res 1982; 42:2963–2971.PubMedGoogle Scholar
  35. 35.
    Greco WR, Park HS, Rustum YM. Application of a new approach for the quantitation of drug synergism to the combination of cis-diamminedichloroplatinum and 1-β-D-arabinofuranosylcytosine. Cancer Res 1990; 50:5318–5327.PubMedGoogle Scholar
  36. 36.
    Raymond E, Djelloul S, Buquet-Fagot C et al. Synergy between the nonclassical thymidylate synthase inhibitor AG337 (Thymitaq) and cisplatin in human colon and ovarian cancer cells. Anti-Cancer Drugs 1996; 7:752–757.PubMedCrossRefGoogle Scholar
  37. 37.
    Hsieh TC, Wu JM. Suppression of cell proliferation and gene expression by combinatorial synergy of EGCG, resveratrol and gamma-tocotrienol in estrogen receptor-positive MCF-7 breast cancer cells. Internatl J Oncol 2008; 33:851–859.Google Scholar
  38. 38.
    Shuhendler AJ, O’Brien PJ, Rauth AM et al. On the synergistic effect of doxorubicin and mitomycin C against breast cancer cells. Drug Metabol Drug Interact 2007; 22:201–233.PubMedCrossRefGoogle Scholar
  39. 39.
    Pentheroudakis G, Razis E, Athanassiadis A et al. Paclitaxel-carboplatin combination chemotherapy in advanced breast cancer: accumulating evidence for synergy, efficacy and safety. Med Oncol 2006; 23:147–160.PubMedCrossRefGoogle Scholar
  40. 40.
    McGill TJ, Douglas RM, Lund RD et al. Quantification of spatial vision in the Royal College of Surgeons rat. Invest Ophthalmol Visual Sci 2004; 45:932–936.CrossRefGoogle Scholar
  41. 41.
    Tallarida RJ, Jacob LS. The Dose-Response Relation in Pharmacology. New York: Springer-Verlag, 1979.CrossRefGoogle Scholar
  42. 42.
    Tallarida RJ, Murray RB. Manual of Pharmacologic Calculations With Computer Programs. 2nd ed. New York: Springer-Verlag, 1987.Google Scholar
  43. 43.
    Tallarida RJ, Raffa RB, McGonigle P. Principles in General Pharmacology. New York: Springer-Verlag, 1988.CrossRefGoogle Scholar
  44. 44.
    Tallarida RJ. Drug Synergism and Dose-Effect Data Analysis. Boca Raton: CRC/Chapman-Hall, 2000.CrossRefGoogle Scholar
  45. 45.
    Tallarida RJ. Perspectives in pharmacology: An overview of drug combination analysis with isobolograms. J Pharmacol Exp Ther 2006; 319:1–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Tallarida RJ. Interactions between drugs and occupied receptors. Pharmacol Thera 2007; 113:197–209.CrossRefGoogle Scholar
  47. 47.
    Raffa RB, Stone DJ, Tallarida RJ. Discovery of self-synergistic spinal/supraspinal antinociception produced by acetaminophen (paracetamol). J Pharmacol Exp Ther 2000; 295:291–294.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  • Robert B. Raffa
    • 1
  1. 1.Department of Pharmaceutical SciencesTemple University School of PharmacyPhiladelphiaUSA

Personalised recommendations