- Email: [email protected]
Ocular and Orbital Toxicity After Intracarotid Cisplatin Therapy
508
October, 1993
AMERICAN JOURNAL OF OPHTHALMOLOGY
September 1992, visual acuity was 20/30, and there was no vitreous activity. Organ transplantation and subsequent immunosuppression are associated with an increased incidence of malignancy. I A number of lymphoproliferative disorders may occur after transplant, with B-celllymphoma the commonest. The mechanism for this is not understood, but Epstein-Barr virus has been implicated. Lymphomas develop quicker after transplantation in patients treated with cyclosporine," but less often involve the central nervous system. Intraocular malignant B-cell lymphoma is rare, with involvement usually occurring in the form of primary lymphoma of the central nervous system. In many cases, tumor cells in the vitreous masquerade as intraocular inflammation. Bilateral disease occurs in 80%, with central nervous system lymphoma developing in 15% to 80% of patients. Although lymphoma (reticulum cell sarcoma) has been documented in a renal transplant patient with an unresponsive vitreitis," there has been a report of posttransplant intraocular lymphoma as a result of cyclosporine immunosuppression.' This event occurred in a cardiac transplant patient in whom the diagnosis was made at autopsy. Benign lymphoproliferation, in the form of bilateral iris tumors associated with a granulomatous iridocyclitis, has also been described in a liver transplant patient on a regimen of cyclosporine.'
References 1. Penn, I., Hammond, A., Brettschneider, L., and Starzl. T. E.: Malignant lymphomas in transplantation patients. Transplant. Proc. 1: 106, 1969. 2. Cockburn, I. T. R., and Krupp, P.: The risk of neoplasms in patients treated with cyclosporine A. J. Autoimmun. 2:723, 1989. 3. Ziemianski, M. c.. Godfrey, W. A., Lee, K. Y., and Sabates, F. N.: Lymphoma of the vitreous associated with renal transplantation and immunosuppressive therapy. Ophthalmology 87:596, 1980. 4. Johnson, B. L.: Intraocular and central nervous system lymphoma in a cardiac transplant recipient. Ophthalmology 99:987,1992. 5. Brodsky, M. c.. Casteell, H., Barber, L. D., Kletz!, M., and Roleson, G. J.: Bilateral iris tumors in an immunosuppressed child. Surv. Ophthalmol. 36:217, 1991.
Ocular and Intracarotid
Orbital Toxicity After Cisplatin Therapy
Curtis E. Margo, M.D., and F. Reed Murtagh, M.D. Departments of Ophthalmology (C.E.M.) an~ Neuroradiology (F.R.M.), University of South Florida, College of Medicine.
Inquiries to Curtis E. Margo, M.D., University of South Florida, 12901 Bruce Downs Blud., MDe Box 21, Tampa,
FL 33612.
Intracarotid cisplatin is used to treat a variety of malignant tumors of the head and neck."! Neural, retinal, and ocular vaso-occlusive side effects are common,':' but there is some evidence that severe ocular toxicity can be avoided by infusion distal to the ophthalmic artery." We treated a patient who received a supraophthalmic artery infusion of cisplatin who~e ipsilateral eye and orbit sustained a severe tOXIC injury. A 39-year-old woman with a grade 3 (glioblastoma multiforme) astrocytoma noted pain in her left eye at the end of a 25-minute intracarotid infusion of cisplatin (90 mg). The 0.038mm Tracker catheter (Target Therapuetics, San Jose, California) was placed in the left carotid artery above the branch of the ophthalmic artery and immediately below the bifurcation of the anterior and middle cerebral arteries. Mild pain persisted after treatment. Ocular examination 20 hours later disclosed visual acuity of 20/20 in each eye. Results of the examination were normal except for mild, diffuse episcleral vascular injection of the left eye. The next day, vision in the left eye decreased dramatically over several hours, orbital pain intensified, and the left eyelids began to swell. Examination four days after infusion disclosed no light perception in the left eye. The left eyelids were erythematous and swollen (Fig. 1). The left pupil was 6 mm and did not react to light. The left eye had no motility. Corneal sensation was decreased. The anterior chamber was shallow and the lens-iris diaphragm was pushed forward by a peripheral choroidal effusion. Intraocular pressure was 28 mm Hg. The retina was white except for a pink macular reflex. The right eye and orbit were normal. After the po.ssibility of mucormycosis was excluded, the patient was treated with 250 mg of methylprednisolone sodium succinate, intravenously every six hours, and anticoagulated with intravenous heparin sulfate. A magnetic resonance scan
Vol. 116, No.4
Letters to The Journal
Fig. 1 (Margo and Murtagh). The patient four days after cisplatin infusion looking in right gaze. The left eye has no motility. There is left proptosis. The eyelids are swollen and erythematous, and the conjunctiva is chemotic.
with gadolinium showed enhancement of the left optic nerve, choroid, and mild enlargement of all recti muscles. There was no evidence of cavernous sinus thrombosis on magnetic resonance scan. The anterior chamber deepened gradually as the choroidal effusion diminished; an exudative retinal detachment developed over the next week. Eyelid and orbital inflammation subsided. Vision did not return and ocular ductions were severely limited in all fields of gaze. One month later, the fundus showed profound loss of the retinal vasculature and widespread degenerative changes of the retinal pigment epithelium (Fig. 2). The ocular and orbital reactions to cisplatin in this patient differ from previously reported complications by the presence of uveal effusion, exudative retinal detachment, enlarged recti muscles, and inflammation of soft tissue. Miller and associates" described a patient with a cavernous sinus syndrome, without signs of orbital inflammation, after intracarotid infusion of cisplatin. Ophthalmoplegia occurred several days after the second intracarotid infusion; visual acuity deteriorated to light perception over four weeks without signs of uveal effusion or retinal detachment. We are unsure why our patient sustained such a severe reaction to cisplatin at this dose and rate of infusion. Placement of the infusion catheter above the ophthalmic artery does not guarantee that the ipsilateral eye and orbit will be
509
Fig. 2 (Margo and Murtagh). The left fundus one month after cisplatin infusion. There is profound loss of the retinal arterioles and venules. The macula is thickened and hemorrhagic. There are marked pigmentary changes in the retinal pigment epithelium.
protected from the potentially blinding side effects of cisplatin."
References 1. Maiese, K., Walker, R. W., Gargan, R., and Victor, J. D.: Intra-arterial cisplatin-associated optic and otic toxicity. Arch. Neurol. 49:83,1992. 2. Kupersmith, M. J., Seiple, W. H., Hclopigian, K., Noble, K., Hiesiger, E., and Warren, F.: Maculopathy caused by intra-arterially administered cisplatin and intravenously administered carmustine. Am. J. Ophthalmol. 113:435, 1992. 3. Miller, D. F., Bay, J. W., Lederman, R. J., Purvis, J. D., Rogers, L. R. E., and Tomsak, R. L.: Ocular and orbital toxicity following intracarotid injection of BCNU (carmustine) and cisplatinum for malignant gliomas. Ophthalmology 92:402, 1985. 4. Kupersmith, M. J., Frohman, L. P., Choi, I. 5., Foo, 5. H., Hiessinger, E., Berenstein, A., Wise, A., Carr, R. E., and Ransohoff, J.: Visual system toxicity following intra-arterial chemotherapy. Neurology 38:284, 1988. 5. Shimarnura, Y., Chikama, M., Tanimoto, T., Kawakami, Y., and Tsutsumi, A.: Optic nerve degeneration caused by supra ophthalmic carotid artery infusion with dsplatin and ACNU. J. Neurosurg. 72:285, 1990.
October, 1993
AMERICAN JOURNAL OF OPHTHALMOLOGY
September 1992, visual acuity was 20/30, and there was no vitreous activity. Organ transplantation and subsequent immunosuppression are associated with an increased incidence of malignancy. I A number of lymphoproliferative disorders may occur after transplant, with B-celllymphoma the commonest. The mechanism for this is not understood, but Epstein-Barr virus has been implicated. Lymphomas develop quicker after transplantation in patients treated with cyclosporine," but less often involve the central nervous system. Intraocular malignant B-cell lymphoma is rare, with involvement usually occurring in the form of primary lymphoma of the central nervous system. In many cases, tumor cells in the vitreous masquerade as intraocular inflammation. Bilateral disease occurs in 80%, with central nervous system lymphoma developing in 15% to 80% of patients. Although lymphoma (reticulum cell sarcoma) has been documented in a renal transplant patient with an unresponsive vitreitis," there has been a report of posttransplant intraocular lymphoma as a result of cyclosporine immunosuppression.' This event occurred in a cardiac transplant patient in whom the diagnosis was made at autopsy. Benign lymphoproliferation, in the form of bilateral iris tumors associated with a granulomatous iridocyclitis, has also been described in a liver transplant patient on a regimen of cyclosporine.'
References 1. Penn, I., Hammond, A., Brettschneider, L., and Starzl. T. E.: Malignant lymphomas in transplantation patients. Transplant. Proc. 1: 106, 1969. 2. Cockburn, I. T. R., and Krupp, P.: The risk of neoplasms in patients treated with cyclosporine A. J. Autoimmun. 2:723, 1989. 3. Ziemianski, M. c.. Godfrey, W. A., Lee, K. Y., and Sabates, F. N.: Lymphoma of the vitreous associated with renal transplantation and immunosuppressive therapy. Ophthalmology 87:596, 1980. 4. Johnson, B. L.: Intraocular and central nervous system lymphoma in a cardiac transplant recipient. Ophthalmology 99:987,1992. 5. Brodsky, M. c.. Casteell, H., Barber, L. D., Kletz!, M., and Roleson, G. J.: Bilateral iris tumors in an immunosuppressed child. Surv. Ophthalmol. 36:217, 1991.
Ocular and Intracarotid
Orbital Toxicity After Cisplatin Therapy
Curtis E. Margo, M.D., and F. Reed Murtagh, M.D. Departments of Ophthalmology (C.E.M.) an~ Neuroradiology (F.R.M.), University of South Florida, College of Medicine.
Inquiries to Curtis E. Margo, M.D., University of South Florida, 12901 Bruce Downs Blud., MDe Box 21, Tampa,
FL 33612.
Intracarotid cisplatin is used to treat a variety of malignant tumors of the head and neck."! Neural, retinal, and ocular vaso-occlusive side effects are common,':' but there is some evidence that severe ocular toxicity can be avoided by infusion distal to the ophthalmic artery." We treated a patient who received a supraophthalmic artery infusion of cisplatin who~e ipsilateral eye and orbit sustained a severe tOXIC injury. A 39-year-old woman with a grade 3 (glioblastoma multiforme) astrocytoma noted pain in her left eye at the end of a 25-minute intracarotid infusion of cisplatin (90 mg). The 0.038mm Tracker catheter (Target Therapuetics, San Jose, California) was placed in the left carotid artery above the branch of the ophthalmic artery and immediately below the bifurcation of the anterior and middle cerebral arteries. Mild pain persisted after treatment. Ocular examination 20 hours later disclosed visual acuity of 20/20 in each eye. Results of the examination were normal except for mild, diffuse episcleral vascular injection of the left eye. The next day, vision in the left eye decreased dramatically over several hours, orbital pain intensified, and the left eyelids began to swell. Examination four days after infusion disclosed no light perception in the left eye. The left eyelids were erythematous and swollen (Fig. 1). The left pupil was 6 mm and did not react to light. The left eye had no motility. Corneal sensation was decreased. The anterior chamber was shallow and the lens-iris diaphragm was pushed forward by a peripheral choroidal effusion. Intraocular pressure was 28 mm Hg. The retina was white except for a pink macular reflex. The right eye and orbit were normal. After the po.ssibility of mucormycosis was excluded, the patient was treated with 250 mg of methylprednisolone sodium succinate, intravenously every six hours, and anticoagulated with intravenous heparin sulfate. A magnetic resonance scan
Vol. 116, No.4
Letters to The Journal
Fig. 1 (Margo and Murtagh). The patient four days after cisplatin infusion looking in right gaze. The left eye has no motility. There is left proptosis. The eyelids are swollen and erythematous, and the conjunctiva is chemotic.
with gadolinium showed enhancement of the left optic nerve, choroid, and mild enlargement of all recti muscles. There was no evidence of cavernous sinus thrombosis on magnetic resonance scan. The anterior chamber deepened gradually as the choroidal effusion diminished; an exudative retinal detachment developed over the next week. Eyelid and orbital inflammation subsided. Vision did not return and ocular ductions were severely limited in all fields of gaze. One month later, the fundus showed profound loss of the retinal vasculature and widespread degenerative changes of the retinal pigment epithelium (Fig. 2). The ocular and orbital reactions to cisplatin in this patient differ from previously reported complications by the presence of uveal effusion, exudative retinal detachment, enlarged recti muscles, and inflammation of soft tissue. Miller and associates" described a patient with a cavernous sinus syndrome, without signs of orbital inflammation, after intracarotid infusion of cisplatin. Ophthalmoplegia occurred several days after the second intracarotid infusion; visual acuity deteriorated to light perception over four weeks without signs of uveal effusion or retinal detachment. We are unsure why our patient sustained such a severe reaction to cisplatin at this dose and rate of infusion. Placement of the infusion catheter above the ophthalmic artery does not guarantee that the ipsilateral eye and orbit will be
509
Fig. 2 (Margo and Murtagh). The left fundus one month after cisplatin infusion. There is profound loss of the retinal arterioles and venules. The macula is thickened and hemorrhagic. There are marked pigmentary changes in the retinal pigment epithelium.
protected from the potentially blinding side effects of cisplatin."
References 1. Maiese, K., Walker, R. W., Gargan, R., and Victor, J. D.: Intra-arterial cisplatin-associated optic and otic toxicity. Arch. Neurol. 49:83,1992. 2. Kupersmith, M. J., Seiple, W. H., Hclopigian, K., Noble, K., Hiesiger, E., and Warren, F.: Maculopathy caused by intra-arterially administered cisplatin and intravenously administered carmustine. Am. J. Ophthalmol. 113:435, 1992. 3. Miller, D. F., Bay, J. W., Lederman, R. J., Purvis, J. D., Rogers, L. R. E., and Tomsak, R. L.: Ocular and orbital toxicity following intracarotid injection of BCNU (carmustine) and cisplatinum for malignant gliomas. Ophthalmology 92:402, 1985. 4. Kupersmith, M. J., Frohman, L. P., Choi, I. 5., Foo, 5. H., Hiessinger, E., Berenstein, A., Wise, A., Carr, R. E., and Ransohoff, J.: Visual system toxicity following intra-arterial chemotherapy. Neurology 38:284, 1988. 5. Shimarnura, Y., Chikama, M., Tanimoto, T., Kawakami, Y., and Tsutsumi, A.: Optic nerve degeneration caused by supra ophthalmic carotid artery infusion with dsplatin and ACNU. J. Neurosurg. 72:285, 1990.