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A case of bilateral optic neuropathy in a patient on tacrolimus (FK506) therapy after liver transplantation
3. Albertazzi A, Di Paolo B, Spisni C, Mastropasqua L, Gallenga PE. Intraocular pressure (IOP) changes induced by regular dialysis treatment (RDT). Life Support Syst 1985;1(suppl 3):91–95. 4. Burn RA. Intraocular pressure during haemodialysis. Br J Ophthalmol 1973;57:511–513.
November 1998. He had a history of IgM myeloma but otherwise was in good health, with no atherosclerotic risk factors. In January 1999, he noted the sudden onset of painless blurred vision and inferior visual field impairment in his left eye. Over several days, the field impairment worsened. He denied any headache, jaw claudications, diplopia, or other neurologic or ophthalmologic complaints and had no clinical or laboratory signs of graft versus host reaction. He no longer drank alcohol and never smoked. He had been taking tacrolimus (Prograf), 4 mg twice daily, since his transplantation and was never treated with cyclosporine. Neuro-ophthalmologic examination on January 11, 1999, revealed visual acuity to be 20/20 in the right eye and 20/100 in the left eye. The patient identified 9.5 of 10 Hardy–Rand–Rittler pseudoisochromatic plates (Richmond International, Inc, Boca Raton, Florida) on the right eye and three of 10 on the left eye. Static visual fields on Humphrey perimeter (Humphrey Instruments, Inc, San Leandro, California) showed a superior arcuate visual field defect on the right eye and a dense inferior attitudinal defect on the left eye. Pupils were 4 mm bilaterally. The left pupil was less reactive to light than the right eye, and there was a left, relative afferent pupillary defect. Motility, intraocular tensions, and slit-lamp examination were normal. The right optic disk was mildly swollen with a cup:disk ratio of 0.1. The left disk was diffusely swollen and pale with no hemorrhages or exudates. Retinal vessels were mildly attenuated bilaterally. No retinal infiltrates or vitreous cells were noted. Laboratory investigations included negative serum studies for syphilis. Blood studies for toxoplasmosis and Bartonella henselae were negative, as were multiple blood cultures. The patient was mildly anemic and the Westergren sedimentation rate was 38 mm/hr. There was no evidence of hyperviscosity or coagulopathy. Magnetic resonance imaging of the brain and orbits with and without gadolinium contrast showed some subcortical ischemic changes. Spinal tap revealed opening pressure of 158 mm of water with two white cells, six red cells, glucose 73 mg/dl, and protein 50 mg/dl. Spinal fluid cytology, Venereal Disease Research Laboratory (VDRL), and cultures, including cytomegalovirus, fungi, and mycobacteria cultures, were negative. Several days after initial neuro-ophthalmologic examination, the patient complained of deterioration of vision in his left eye. Visual acuity on January 18, 1999, was unchanged, but visual field examination showed that the visual field defect in the left eye now included the superior visual field (Figure 1). The disk appearance was unchanged bilaterally. The tacrolimus was discontinued, and mycophenolate mofetil (Cellcept; Syntex Puerto Rico, Inc., Humacao, Puerto Rico) and aspirin were instituted. The patient showed no laboratory or clinical signs of transplant rejection.
A Case of Bilateral Optic Neuropathy in a Patient on Tacrolimus (FK506) Therapy After Liver Transplantation Paul W. Brazis, MD, James R. Spivey, MD, James P. Bolling, MD, and Jeffrey L. Steers, MD PURPOSE: To report a case of bilateral optic neuropathy in
a patient receiving tacrolimus (FK 506, Prograf; Fujisawa USA, Inc, Deerfield, Illinois) for immunosuppression after orthotropic liver transplantation. METHOD: Case report. In a 58-year-old man receiving tacrolimus after orthotropic liver transplantation, serial neuro-ophthalmologic examinations and laboratory studies were performed. RESULTS: The patient had episodic deterioration of vision in both eyes, with clinical features resembling ischemic optic neuropathies. Deterioration of vision occurred despite discontinuation of the tacrolimus. CONCLUSION: Tacrolimus and other immunosuppressive agents may be associated with optic nerve toxicity. (Am J Ophthalmol 2000;129:536 –538. © 2000 by Elsevier Science Inc. All rights reserved.)
T
HE RECENT SUCCESS OF ORTHOTROPIC LIVER TRANS-
plantation in the management of irreversible liver disease has been achieved in part by advances in immunosuppressive therapy. Tacrolimus (FK506, Prograf; Fujisawa USA, Inc, Deerfield, Illinois) is a relatively new immunosuppressive agent that inhibits cytokine synthesis and blocks T-cell development. Although cortical blindness associated with bilateral occipital white matter lesions, similar to that reported with cyclosporine immunosuppression, has been documented as a potential side effect of tacrolimus therapy,1,2 we are unaware of any reports of optic neuropathy associated with the use of this agent. We report a patient who developed bilateral optic neuropathy as a possible complication of tacrolimus therapy. ● CASE REPORT:
A 58-year-old man underwent liver transplantation for end-stage, alcoholic-related cirrhosis in Accepted for publication Nov 13, 1999. From the Departments of Neurology (P.W.B.), Gastroenterology and Hepatology, (J.R.S.), Ophthalmology (J.P.B.), and Transplantation Surgery (J.L.S.), Mayo Clinic-Jacksonville, Jacksonville, Florida. Inquiries to Paul W. Brazis, MD, Department of Neurology, Mayo Clinic-Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224; fax: (904) 953-7233.
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AMERICAN JOURNAL
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OPHTHALMOLOGY
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FIGURE 1. Static visual field examination by Humphrey perimeter on January 18, 1999. Left eye is on the left, and right eye is on the right. MD ⴝ mean deviation; SITA ⴝ Swedish Interactive Thresholding Algorithm (standard strategy).
FIGURE 2. Subsequent static visual field examination on June 23, 1999.
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should be aware of potential optic nerve toxicity of immunosuppressive agents.
Neuro-ophthalmologic examination on February 10, 1999, revealed visual acuity to be 20/40 in the right eye and 5/200 in the left eye. The visual fields were unchanged. The right disk was mildly swollen, and the left disk was now atrophic and pale. The patient was reexamined on March 24, 1999. Although he noted no change in his vision, visual fields on the right had significantly deteriorated with evidence for a cecocentral scotoma and upper and lower arcuate defects. Visual acuity was 20/40 in the right eye and 5/200 in the left eye. He identified 10 of 10 pseudoisochromatic plates on the right eye, but only one of 10 on the left eye. The right pupil was now less reactive to light than before, although there was still evidence of a left relative afferent pupillary defect. Both disks were atrophic. The patient has had no further deterioration of vision. On June 23, 1999, examination revealed visual acuity of 20/20 in the right eye and 5/200 in the left eye. Visual field examination on the right showed dense, inferior attitudinal defect with some impairment of central vision, and left visual field showed diffuse impairment, especially inferiorly (Figure 2). Bilateral optic atrophy was noted. The patient developed bilateral optic neuropathies while on tacrolimus therapy. The pallid disk swelling and altitudinal visual field defects suggest the possibility of bilateral anterior ischemic optic neuropathies, although the progressive course is atypical. However, the patient had no arteriosclerotic risk factors or other predisposing factors for optic nerve ischemia, except his mild anemia and the small cup:disk ratio of the optic nerves. We suggest that the bilateral optic neuropathies may be related to the tacrolimus therapy. Tacrolimus, like cyclosporine, may have a direct neurotoxic effect, resulting in axonal swelling, increased water content, and edema of neural tissues3. A vascular mechanism has also been postulated for the neurotoxic effects of these immunosuppressive agents.3,4 Prostocyclin–thromboxane interactions are modified by cyclosporine, possibly as a result of augmentation of thromboxane A2 generation, and this may result in vasoconstriction and tissue ischemia. Thus, tacrolimus-induced ischemia may have been the mechanism of the anterior ischemic optic neuropathies. We are unaware of other cases of optic neuropathy with tacrolimus therapy. However, optic nerve abnormalities have been described with cyclosporine therapy.5 In a review by Avery and associates5 of eight cases of bilateral optic disk edema associated with cyclosporine therapy, six of the cases had increased intracranial pressure, suggesting that the disk edema was papilledema because of pseudotumor cerebri induced by the cyclosporine. However, in two patients, spinal opening pressures were normal and the disk swelling may have been because of direct optic nerve toxicity of the immunosuppressive agent. In conclusion, our patient’s optic neuropathy may well have been related to the tacrolimus therapy. Clinicians
538
AMERICAN JOURNAL
REFERENCES
1. Shutter LA, Green JP, Newman NJ, Hooks MA, Gordon RD. Cortical blindness and white matter lesions in a patient receiving FK506 after liver transplantation. Neurology 1993; 43:2417–2418. 2. Steg RE, Kessinger A, Wszolek ZK. Case report: cortical blindness and seizures in a patient receiving FK 506 after bone marrow transplantation. Bone Marrow Transplant 1999;23: 959 –962. 3. Stein DP, Lederman RJ, Vogt DP, Carey WD, Broughan TA. Neurological complications following liver transplantation. Ann Neurol 1992;31:644 – 649. 4. Wilson SE, de Groen PC, Aksamit AJ, Weisner RH, Garrity JA, Krom RAF. Cyclosporin A-induced reversible cortical blindness. J Clin Neuro-Ophthalmol 1988;8:215–220. 5. Avery R, Jabs DA, Wingard JR, Vogelsang G, Saral R, Santos G. Optic disc edema after bone marrow transplantation: possible role of cyclosporine toxicity. Ophthalmology 1991; 98:1294 –1301.
Acute Transient Myopia Induced by Indapamide Pierre Blain, MD, Michel Paques, MD, Pascale Massin, MD, Ali Erginay, MD, Pierre-Yves Santiago, MD, and Alain Gaudric, MD PURPOSE:
To report on a case of acute transient myopia associated with ciliochoroidal detachment induced by indapamide. METHOD: Case report. Clinical examination, ultrasonography, and fluorescein angiography were performed during the acute phase of disease and convalescence. RESULTS: After indapamide was discontinued, acute bilateral myopia, which was associated with anterior chamber shallowing and diffuse choroidal thickening, resolved spontaneously 8 days after onset. The initial angiography showed scattered islands of delayed fluorescein filling that disappeared without any permanent change by day 30. CONCLUSION: Indapamide can induce spontaneously resolving transient myopia associated with diffuse choroidal thickening. (Am J Ophthalmol 2000;129:538 –540. © 2000 by Elsevier Science Inc. All rights reserved.)
Accepted for publication Oct 22, 1999. From the Department of Ophthalmology, Hoˆpital Lariboisie`re, Assistance Publique-Hoˆpitaux de Paris, Universite´ Paris 7, Paris, France. Inquiries to Alain Gaudric, MD, 2 rue Ambroise Pare´, 75475 Paris CEDEX 10, France; fax: 33 (1) 01 49 95 64 83; e-mail: alain.gaudric@ lrb.ap-hop-paris.fr
OF
OPHTHALMOLOGY
APRIL 2000
November 1998. He had a history of IgM myeloma but otherwise was in good health, with no atherosclerotic risk factors. In January 1999, he noted the sudden onset of painless blurred vision and inferior visual field impairment in his left eye. Over several days, the field impairment worsened. He denied any headache, jaw claudications, diplopia, or other neurologic or ophthalmologic complaints and had no clinical or laboratory signs of graft versus host reaction. He no longer drank alcohol and never smoked. He had been taking tacrolimus (Prograf), 4 mg twice daily, since his transplantation and was never treated with cyclosporine. Neuro-ophthalmologic examination on January 11, 1999, revealed visual acuity to be 20/20 in the right eye and 20/100 in the left eye. The patient identified 9.5 of 10 Hardy–Rand–Rittler pseudoisochromatic plates (Richmond International, Inc, Boca Raton, Florida) on the right eye and three of 10 on the left eye. Static visual fields on Humphrey perimeter (Humphrey Instruments, Inc, San Leandro, California) showed a superior arcuate visual field defect on the right eye and a dense inferior attitudinal defect on the left eye. Pupils were 4 mm bilaterally. The left pupil was less reactive to light than the right eye, and there was a left, relative afferent pupillary defect. Motility, intraocular tensions, and slit-lamp examination were normal. The right optic disk was mildly swollen with a cup:disk ratio of 0.1. The left disk was diffusely swollen and pale with no hemorrhages or exudates. Retinal vessels were mildly attenuated bilaterally. No retinal infiltrates or vitreous cells were noted. Laboratory investigations included negative serum studies for syphilis. Blood studies for toxoplasmosis and Bartonella henselae were negative, as were multiple blood cultures. The patient was mildly anemic and the Westergren sedimentation rate was 38 mm/hr. There was no evidence of hyperviscosity or coagulopathy. Magnetic resonance imaging of the brain and orbits with and without gadolinium contrast showed some subcortical ischemic changes. Spinal tap revealed opening pressure of 158 mm of water with two white cells, six red cells, glucose 73 mg/dl, and protein 50 mg/dl. Spinal fluid cytology, Venereal Disease Research Laboratory (VDRL), and cultures, including cytomegalovirus, fungi, and mycobacteria cultures, were negative. Several days after initial neuro-ophthalmologic examination, the patient complained of deterioration of vision in his left eye. Visual acuity on January 18, 1999, was unchanged, but visual field examination showed that the visual field defect in the left eye now included the superior visual field (Figure 1). The disk appearance was unchanged bilaterally. The tacrolimus was discontinued, and mycophenolate mofetil (Cellcept; Syntex Puerto Rico, Inc., Humacao, Puerto Rico) and aspirin were instituted. The patient showed no laboratory or clinical signs of transplant rejection.
A Case of Bilateral Optic Neuropathy in a Patient on Tacrolimus (FK506) Therapy After Liver Transplantation Paul W. Brazis, MD, James R. Spivey, MD, James P. Bolling, MD, and Jeffrey L. Steers, MD PURPOSE: To report a case of bilateral optic neuropathy in
a patient receiving tacrolimus (FK 506, Prograf; Fujisawa USA, Inc, Deerfield, Illinois) for immunosuppression after orthotropic liver transplantation. METHOD: Case report. In a 58-year-old man receiving tacrolimus after orthotropic liver transplantation, serial neuro-ophthalmologic examinations and laboratory studies were performed. RESULTS: The patient had episodic deterioration of vision in both eyes, with clinical features resembling ischemic optic neuropathies. Deterioration of vision occurred despite discontinuation of the tacrolimus. CONCLUSION: Tacrolimus and other immunosuppressive agents may be associated with optic nerve toxicity. (Am J Ophthalmol 2000;129:536 –538. © 2000 by Elsevier Science Inc. All rights reserved.)
T
HE RECENT SUCCESS OF ORTHOTROPIC LIVER TRANS-
plantation in the management of irreversible liver disease has been achieved in part by advances in immunosuppressive therapy. Tacrolimus (FK506, Prograf; Fujisawa USA, Inc, Deerfield, Illinois) is a relatively new immunosuppressive agent that inhibits cytokine synthesis and blocks T-cell development. Although cortical blindness associated with bilateral occipital white matter lesions, similar to that reported with cyclosporine immunosuppression, has been documented as a potential side effect of tacrolimus therapy,1,2 we are unaware of any reports of optic neuropathy associated with the use of this agent. We report a patient who developed bilateral optic neuropathy as a possible complication of tacrolimus therapy. ● CASE REPORT:
A 58-year-old man underwent liver transplantation for end-stage, alcoholic-related cirrhosis in Accepted for publication Nov 13, 1999. From the Departments of Neurology (P.W.B.), Gastroenterology and Hepatology, (J.R.S.), Ophthalmology (J.P.B.), and Transplantation Surgery (J.L.S.), Mayo Clinic-Jacksonville, Jacksonville, Florida. Inquiries to Paul W. Brazis, MD, Department of Neurology, Mayo Clinic-Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224; fax: (904) 953-7233.
536
AMERICAN JOURNAL
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OPHTHALMOLOGY
APRIL 2000
FIGURE 1. Static visual field examination by Humphrey perimeter on January 18, 1999. Left eye is on the left, and right eye is on the right. MD ⴝ mean deviation; SITA ⴝ Swedish Interactive Thresholding Algorithm (standard strategy).
FIGURE 2. Subsequent static visual field examination on June 23, 1999.
VOL. 129, NO. 4
BRIEF REPORTS
537
should be aware of potential optic nerve toxicity of immunosuppressive agents.
Neuro-ophthalmologic examination on February 10, 1999, revealed visual acuity to be 20/40 in the right eye and 5/200 in the left eye. The visual fields were unchanged. The right disk was mildly swollen, and the left disk was now atrophic and pale. The patient was reexamined on March 24, 1999. Although he noted no change in his vision, visual fields on the right had significantly deteriorated with evidence for a cecocentral scotoma and upper and lower arcuate defects. Visual acuity was 20/40 in the right eye and 5/200 in the left eye. He identified 10 of 10 pseudoisochromatic plates on the right eye, but only one of 10 on the left eye. The right pupil was now less reactive to light than before, although there was still evidence of a left relative afferent pupillary defect. Both disks were atrophic. The patient has had no further deterioration of vision. On June 23, 1999, examination revealed visual acuity of 20/20 in the right eye and 5/200 in the left eye. Visual field examination on the right showed dense, inferior attitudinal defect with some impairment of central vision, and left visual field showed diffuse impairment, especially inferiorly (Figure 2). Bilateral optic atrophy was noted. The patient developed bilateral optic neuropathies while on tacrolimus therapy. The pallid disk swelling and altitudinal visual field defects suggest the possibility of bilateral anterior ischemic optic neuropathies, although the progressive course is atypical. However, the patient had no arteriosclerotic risk factors or other predisposing factors for optic nerve ischemia, except his mild anemia and the small cup:disk ratio of the optic nerves. We suggest that the bilateral optic neuropathies may be related to the tacrolimus therapy. Tacrolimus, like cyclosporine, may have a direct neurotoxic effect, resulting in axonal swelling, increased water content, and edema of neural tissues3. A vascular mechanism has also been postulated for the neurotoxic effects of these immunosuppressive agents.3,4 Prostocyclin–thromboxane interactions are modified by cyclosporine, possibly as a result of augmentation of thromboxane A2 generation, and this may result in vasoconstriction and tissue ischemia. Thus, tacrolimus-induced ischemia may have been the mechanism of the anterior ischemic optic neuropathies. We are unaware of other cases of optic neuropathy with tacrolimus therapy. However, optic nerve abnormalities have been described with cyclosporine therapy.5 In a review by Avery and associates5 of eight cases of bilateral optic disk edema associated with cyclosporine therapy, six of the cases had increased intracranial pressure, suggesting that the disk edema was papilledema because of pseudotumor cerebri induced by the cyclosporine. However, in two patients, spinal opening pressures were normal and the disk swelling may have been because of direct optic nerve toxicity of the immunosuppressive agent. In conclusion, our patient’s optic neuropathy may well have been related to the tacrolimus therapy. Clinicians
538
AMERICAN JOURNAL
REFERENCES
1. Shutter LA, Green JP, Newman NJ, Hooks MA, Gordon RD. Cortical blindness and white matter lesions in a patient receiving FK506 after liver transplantation. Neurology 1993; 43:2417–2418. 2. Steg RE, Kessinger A, Wszolek ZK. Case report: cortical blindness and seizures in a patient receiving FK 506 after bone marrow transplantation. Bone Marrow Transplant 1999;23: 959 –962. 3. Stein DP, Lederman RJ, Vogt DP, Carey WD, Broughan TA. Neurological complications following liver transplantation. Ann Neurol 1992;31:644 – 649. 4. Wilson SE, de Groen PC, Aksamit AJ, Weisner RH, Garrity JA, Krom RAF. Cyclosporin A-induced reversible cortical blindness. J Clin Neuro-Ophthalmol 1988;8:215–220. 5. Avery R, Jabs DA, Wingard JR, Vogelsang G, Saral R, Santos G. Optic disc edema after bone marrow transplantation: possible role of cyclosporine toxicity. Ophthalmology 1991; 98:1294 –1301.
Acute Transient Myopia Induced by Indapamide Pierre Blain, MD, Michel Paques, MD, Pascale Massin, MD, Ali Erginay, MD, Pierre-Yves Santiago, MD, and Alain Gaudric, MD PURPOSE:
To report on a case of acute transient myopia associated with ciliochoroidal detachment induced by indapamide. METHOD: Case report. Clinical examination, ultrasonography, and fluorescein angiography were performed during the acute phase of disease and convalescence. RESULTS: After indapamide was discontinued, acute bilateral myopia, which was associated with anterior chamber shallowing and diffuse choroidal thickening, resolved spontaneously 8 days after onset. The initial angiography showed scattered islands of delayed fluorescein filling that disappeared without any permanent change by day 30. CONCLUSION: Indapamide can induce spontaneously resolving transient myopia associated with diffuse choroidal thickening. (Am J Ophthalmol 2000;129:538 –540. © 2000 by Elsevier Science Inc. All rights reserved.)
Accepted for publication Oct 22, 1999. From the Department of Ophthalmology, Hoˆpital Lariboisie`re, Assistance Publique-Hoˆpitaux de Paris, Universite´ Paris 7, Paris, France. Inquiries to Alain Gaudric, MD, 2 rue Ambroise Pare´, 75475 Paris CEDEX 10, France; fax: 33 (1) 01 49 95 64 83; e-mail: alain.gaudric@ lrb.ap-hop-paris.fr
OF
OPHTHALMOLOGY
APRIL 2000