MACULAR ISCHEMIA ASSOCIATED WITH IMATINIB MESYLATE THERAPY FOR CHRONIC MYELOID LEUKEMIA Daniel B. Roth, MD, Sara Akbari, MD, PHARMD, Anna Rothstein, MD
Purpose: Imatinib mesylate (Gleevec, East Hanover, NJ) is a drug approved for the treatment of patients with Philadelphia chromosome–positive chronic myeloid leukemia (CML) or Kit-positive gastrointestinal stromal tumors. A case of ischemic maculopathy associated with imatinib mesylate therapy is reported. Methods: A 62-year-old woman with a 16-year history of CML was treated with imatinib mesylate, initially at a daily dose of 400 mg that was decreased to 300 mg due to systemic side effects. Several weeks after beginning imatinib mesylate therapy, she developed blurred vision (greater in the left eye than in the right eye). Results: Fundus examination of both eyes revealed retinal telangiectasia with intraretinal hemorrhages and perifoveal retinal telangiectasia. Fluorescein angiography showed macular ischemia (greater in the left eye than in the right eye). Late perifoveal leakage was present surrounding the macular ischemic zone. Visual acuity was reduced to 20/30 in the right eye and 20/100 in the left eye, which did not improve over 10 months of follow-up. Conclusion: Imatinib mesylate may be associated with ischemic maculopathy that can severely compromise vision. It may be necessary for patients receiving this therapy to be monitored for associated visual symptoms and funduscopic abnormalities. RETINAL CASES & BRIEF REPORTS 3:161–164, 2009
From the Department of Ophthalmology, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey.
70% of patients surveyed through a retrospective review conducted at the Oregon Health and Science University Cancer Institute.2 Epiphoria is another common ophthalmic side effect noted by patients. Both of these side effects can be treated medically, rarely requiring surgical intervention.2 In a premarketing trial of imatinib mesylate for treatment of Kit-positive gastrointestinal stromal tumors, conjunctival hemorrhage was also found to occur, although infrequently, perhaps due to its thrombocytopenic effects.1 Current review of the literature revealed a case of macular edema in a patient with CML who was treated with imatinib mesylate.3 In addition, a case of optic neuritis associated with imatinib mesylate treatment was recently reported.4 Notably, both macular edema and optic neuritis resolved upon drug discontinuation.3,4 Corneal toxicity associated with imatinib mesylate has also been reported, but the frequency, reversibility, and severity have not been characterized.5 Cystoid macular edema is an infrequent ocular side effect, which has been seen in two separate cases.6,7 Although
F
irst approved in May 2000, imatinib mesylate (Gleevec STI-571) is used in the treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) and Kit-positive gastrointestinal stromal tumors. Imatinib mesylate competitively inhibits Philadelphia chromosome– encoded tyrosine kinase and thereby prevents tumor proliferation.1 Since its introduction into the postmarketing arena, adverse event data have emerged through case studies, Medwatch US Food & Drug Administration reporting, and postmarketing reviews. In particular, periorbital edema associated with imatinib mesylate treatment has been reported. This was observed in The authors have no proprietary interest in the materials presented in this report. Reprint requests: Daniel Roth, MD, Retina Vitreous Center, CAB, 4th Floor, 125 Paterson Street, New Brunswick, NJ 08901; e-mail: [email protected]
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visual loss improved upon discontinuation of imatinib mesylate, there is concern for secondary irreversible visual loss if this therapy is continued.6 In our survey of the literature and the US Food & Drug Administration Web site, we did not find any reports of macular ischemia associated with imatinib mesylate. We describe a patient with CML who was treated with imatinib mesylate who had retinal microvascular angiopathy, a previously unreported adverse effect of this treatment. Case Report A 62-year-old woman with a 16-year history of CML treated previously with busulfan was treated with imatinib mesylate in an attempt to reverse her Philadelphia chromosome mutation. CML entered remission after several weeks of this treatment. At a daily dose of 400 mg, she developed side effects of lower-extremity bone pain, gastrointestinal upset, diarrhea, anemia, left external ear bleeding, and severe bilateral conjunctivitis. Treatment was continued at a decreased daily dose of 300 mg, but she reported shooting eye pain and seeing a “central gray spot” out of the left eye. Notably, the patient had no visual symptoms or pertinent ocular signs at ocular examinations before initiation of imatinib mesylate therapy. Ocular symptoms began several weeks after beginning imatinib mesylate therapy, with progressive vision loss of 3 months’ duration. She also had subconjunctival hemorrhages bilaterally after 2 months of therapy, which resolved on their own over the proceeding few weeks. Her medical history included hypertension, well controlled with enalapril treatment. The patient had previously undergone extensive medical evaluation for diabetes mellitus, hyperlipidemia, and coronary artery disease and did not have any of the aforementioned conditions. In addition, she had no history of other atherosclerotic counterparts, including peripheral vascular disease, myocardial infarction, and abdominal aortic aneurysm. However, she did have a mild stroke ⬇17 years ago, which left her with no permanent sequelae. Other medication included epoetin alfa for anemia of unclear etiology. The patient had not previously received other chemotherapeutic agents or radiotherapy. Her only allergy was to penicillin. She smoked 1 pack per day for 10 years but discontinued smoking 15 years ago. No alcohol use was reported. Family history was also noncontributory. The patient presented to us after receiving imatinib mesylate therapy for 4 months. At this time, ocular examination revealed visual acuity of 20/30 in the right eye and 20/100 in the left eye. Intraocular pressure was 12 mmHg in both eyes. Pupillary examination results, confrontational visual fields, and color vision were within normal limits. Amsler grid testing revealed trace nasal metamorphopsia in the right eye and more significant central and nasal metamorphopsia in the left eye. Slit lamp examination revealed normal lids, lashes, conjunctiva, and cornea and trace nuclear sclerotic cataracts in both eyes. Fundus examination of the right eye revealed retinal telangiectasia in the superior macula with scattered intraretinal hemorrhages. Fundus examination of the left eye revealed several cotton-wool spots superiorly with mild thickening of the macular region and 360° of perifoveal retinal telangiectasia and intraretinal hemorrhages (Fig. 1). Photographs of the fundus before initiation of imatinib mesylate therapy were not available. However, fundus examination before initiation of this treatment demonstrated no fundus abnormalities. Fluorescein angiography revealed macular ischemia with perifoveal capillary nonperfusion and capillary dropout, which was
Fig. 1. A, Red-free fundus photograph of the right eye, revealing telangiectatic vessels in the paramacular region, seen mostly in the superior macula. Several intraretinal hemorrhages are evident along the terminal vessels. B, Red-free fundus photograph of the left eye revealing several cotton-wool spots superiorly with mild thickening of the macular region and 360° of perifoveal retinal telangiectasia and intraretinal hemorrhages. A flame hemorrhage is evident along the superotemporal arcade. The foveal avascular zone is enlarged when compared with that in the right eye.
greater in the left eye than in the right eye. In the late phase of the fluorescein angiogram, there was late perifoveal leakage, which was greater in the left eye than in the right eye (Fig. 2). There was moderate disk staining in the late phases of the fluorescein angiogram. This may have been due to ischemia-related fluorescein accumulation in the optic nerve similar to that seen in anterior ischemic optic neuropathy,8 because the telangiectatic vessels seen in the early phases of the fluorescein angiogram extended to and around the optic disks. Determination of complete blood cell count of a blood specimen obtained at the time of presentation showed a mild decrease in erythrocyte count, hemoglobin level, and hematocrit and increased mean cell volume (MCV), mean cell hemoglobin (MCH), and red cell distributive width (RDW) values. Leukocyte and platelet counts were within normal limits. CML entered and remained in remission while she was receiving therapy with imatinib mesylate. This treatment was discontinued after 4 months, and therapy was switched back to busulfan. The
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Fig. 2. A, Fluorescein angiogram of the right eye at 47 seconds revealed macular ischemia with perifoveal capillary nonperfusion, capillary dropout, and dilated capillary terminal bulbs. B, In the late phase of the fluorescein angiogram of the right eye at 10 minutes, diffuse perifoveal leakage is noted. Late disk staining is noted. C, Fluorescein angiogram of the left eye at 32 seconds revealed more extensive macular ischemia with perifoveal capillary nonperfusion, capillary dropout, and dilated capillary terminal bulbs. A patch of capillary nonperfusion is seen superiorly, corresponding to the area of cotton-wool spot formation. D, In the late phase of the fluorescein angiogram of the left eye at 10 minutes, extensive diffuse perifoveal leakage is noted with central ischemia still evident. Late disk staining is noted.
patient was reexamined 18 days after the initial visit. She reported resolution of ocular pain but continued to have a central scotoma without change of vision in the left eye. CML continued to stay in remission over 10 months of follow-up. Over the 10-month follow-up, there was no ocular pain, but there was no improvement in visual acuity, with persistent central scotoma in the left eye and minimal resolution of perifoveal capillary nonperfusion, which was greater in the left eye than in the right eye. Although retinal hemorrhages resolved slowly over the 10 months, retinal ischemia and telangiectasias persisted despite discontinuation of imatinib mesylate treatment.
Discussion Imatinib mesylate is a possible contributing factor to the development of macular ischemia in the patient with CML described here. After several weeks of imatinib mesylate therapy, the patient developed a central scotoma that expanded over the next 3 months before discontinuation of this therapy. Visual symptoms developed shortly after institution of imatinib mesylate therapy, suggesting an association between macular ischemia and imatinib mesylate. Although leukemia can potentially incite retinal ischemia by microvascular occlusion,9 the temporal sequence of symptoms after imatinib mesylate administration and the fact that CML was in remission at the time make leukemia-induced microvascular occlusion a less likely possi-
bility. Bilateral evidence of macular ischemia suggests that an isolated thromboembolic phenomenon was a less likely mechanism as well. Underlying vasculopathic conditions should also be considered in the genesis and progression of macular ischemia. The patient’s history of hypertension, although controlled with enalapril therapy, may have placed the patient at risk for developing macular ischemia. This risk is heightened when hypertension occurs alongside other accompanying conditions, including hyperlipidemia, diabetes mellitus, vasculitis, connective tissue disorder, and underlying atherosclerosis. Notably, this patient did not have diabetes mellitus or a history of hyperlipidemia. Her history of stroke does suggest a possible underlying atherosclerotic process, increasing her risk for an ischemic event in the retina as well. However, fundus examination before imatinib mesylate therapy did not reveal atherosclerotic changes. In addition, the gradual and progressive nature of the visual loss does not seem to support the occurrence of a cerebrovascular event. Because she had a remote smoking history, having quit 15 years ago, this also is not a major player in the observed ocular events. It is important to note that the patient did not receive busulfan treatment
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for several months before the development of ocular symptoms. In addition, to our knowledge, there is no cited association of busulfan with either macular ischemia or retinal hemorrhages noted in the literature. Review of the current literature revealed no previous reports of macular ischemia associated with imatinib mesylate therapy. Retinal hemorrhage occurred in one patient as noted at the Oregon Health and Science University Cancer Institute, which conducted a review of data for patients with CML who received imatinib mesylate therapy in past clinical studies.2 However, this hemorrhage occurred with no other accompanying retinal findings.2 This newly observed macular ischemia and its possible association with imatinib mesylate is an important consideration for patients receiving this therapy. Clinicians will need to distinguish the inciting etiology and contributing factors for patients with CML who develop macular ischemia, including leukemia itself and underlying vasculopathic conditions. With further postmarketing surveillance, the association of macular ischemia with imatinib mesylate will be better elucidated, and the role it plays in the clinical approach to patients with CML will be better defined. It may be necessary for patients taking this medication to be followed by an ophthalmologist on a regular basis to avoid severe capillary nonperfusion. Monitoring for visual symptoms of central vision loss, possibly with Amsler grid
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testing, may be warranted for patients with leukemia who receive imatinib mesylate therapy. Key words: imatinib mesylate (Gleevec), chronic myeloid leukemia, toxic, maculopathy, ischemia, intraretinal hemorrhage. References 1. 2.
3.
4.
5. 6.
7.
8. 9.
Gleevec [Package Insert]. East Hanover, NJ: Novartis Pharmaceuticals; 2006. Fraunfelder FW, Solomon J, Druker BJ, et al. Ocular side effects associated with imatinib mesylate (Gleevec). J Ocul Pharmacol Ther 2003;19:371–375. Kusumi E, Arakawa A, Kami M, et al. Visual disturbance due to retinal edema as a complication of imatinib. Leukemia 2004;18:1138–1139. Govind Babu K, Attili VS, Bapsy PP, Anupama G. Imatinibinduced optic neuritis in a patient of chronic myeloid leukemia. Int Ophthalmol 2007;27:43–44. Fraunfelder F. Corneal toxicity from topical ocular and systemic medications. Cornea 2006;25:1133–1138. Georgalas I, Pavesio C, Ezra E. Bilateral cystoid macular edema in a patient with chronic myeloid leukaemia under treatment with imatinib mesylate: report of an unusual side effect. Graefes Arch Clin Exp Ophthalmol 2007;245:1585– 1586. Masood I, Negi A, Dua HS. Imatinib as a cause of cystoid macular edema following uneventful phacoemulsification surgery. J Cataract Refract Surg 2005;31:2427–2428. Hayreh SS. Anterior ischemic optic neuropathy. V. Optic disc edema an early sign. Arch Ophthalmol 1981;99:1030–1040. Piermarocchi S, Segato T, Bertoja H, et al. Branch retinal vein occlusion: the pathogenic role of blood viscosity. Ann Ophthalmol 1990;22:303–311.
Purpose: Imatinib mesylate (Gleevec, East Hanover, NJ) is a drug approved for the treatment of patients with Philadelphia chromosome–positive chronic myeloid leukemia (CML) or Kit-positive gastrointestinal stromal tumors. A case of ischemic maculopathy associated with imatinib mesylate therapy is reported. Methods: A 62-year-old woman with a 16-year history of CML was treated with imatinib mesylate, initially at a daily dose of 400 mg that was decreased to 300 mg due to systemic side effects. Several weeks after beginning imatinib mesylate therapy, she developed blurred vision (greater in the left eye than in the right eye). Results: Fundus examination of both eyes revealed retinal telangiectasia with intraretinal hemorrhages and perifoveal retinal telangiectasia. Fluorescein angiography showed macular ischemia (greater in the left eye than in the right eye). Late perifoveal leakage was present surrounding the macular ischemic zone. Visual acuity was reduced to 20/30 in the right eye and 20/100 in the left eye, which did not improve over 10 months of follow-up. Conclusion: Imatinib mesylate may be associated with ischemic maculopathy that can severely compromise vision. It may be necessary for patients receiving this therapy to be monitored for associated visual symptoms and funduscopic abnormalities. RETINAL CASES & BRIEF REPORTS 3:161–164, 2009
From the Department of Ophthalmology, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey.
70% of patients surveyed through a retrospective review conducted at the Oregon Health and Science University Cancer Institute.2 Epiphoria is another common ophthalmic side effect noted by patients. Both of these side effects can be treated medically, rarely requiring surgical intervention.2 In a premarketing trial of imatinib mesylate for treatment of Kit-positive gastrointestinal stromal tumors, conjunctival hemorrhage was also found to occur, although infrequently, perhaps due to its thrombocytopenic effects.1 Current review of the literature revealed a case of macular edema in a patient with CML who was treated with imatinib mesylate.3 In addition, a case of optic neuritis associated with imatinib mesylate treatment was recently reported.4 Notably, both macular edema and optic neuritis resolved upon drug discontinuation.3,4 Corneal toxicity associated with imatinib mesylate has also been reported, but the frequency, reversibility, and severity have not been characterized.5 Cystoid macular edema is an infrequent ocular side effect, which has been seen in two separate cases.6,7 Although
F
irst approved in May 2000, imatinib mesylate (Gleevec STI-571) is used in the treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) and Kit-positive gastrointestinal stromal tumors. Imatinib mesylate competitively inhibits Philadelphia chromosome– encoded tyrosine kinase and thereby prevents tumor proliferation.1 Since its introduction into the postmarketing arena, adverse event data have emerged through case studies, Medwatch US Food & Drug Administration reporting, and postmarketing reviews. In particular, periorbital edema associated with imatinib mesylate treatment has been reported. This was observed in The authors have no proprietary interest in the materials presented in this report. Reprint requests: Daniel Roth, MD, Retina Vitreous Center, CAB, 4th Floor, 125 Paterson Street, New Brunswick, NJ 08901; e-mail: [email protected]
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visual loss improved upon discontinuation of imatinib mesylate, there is concern for secondary irreversible visual loss if this therapy is continued.6 In our survey of the literature and the US Food & Drug Administration Web site, we did not find any reports of macular ischemia associated with imatinib mesylate. We describe a patient with CML who was treated with imatinib mesylate who had retinal microvascular angiopathy, a previously unreported adverse effect of this treatment. Case Report A 62-year-old woman with a 16-year history of CML treated previously with busulfan was treated with imatinib mesylate in an attempt to reverse her Philadelphia chromosome mutation. CML entered remission after several weeks of this treatment. At a daily dose of 400 mg, she developed side effects of lower-extremity bone pain, gastrointestinal upset, diarrhea, anemia, left external ear bleeding, and severe bilateral conjunctivitis. Treatment was continued at a decreased daily dose of 300 mg, but she reported shooting eye pain and seeing a “central gray spot” out of the left eye. Notably, the patient had no visual symptoms or pertinent ocular signs at ocular examinations before initiation of imatinib mesylate therapy. Ocular symptoms began several weeks after beginning imatinib mesylate therapy, with progressive vision loss of 3 months’ duration. She also had subconjunctival hemorrhages bilaterally after 2 months of therapy, which resolved on their own over the proceeding few weeks. Her medical history included hypertension, well controlled with enalapril treatment. The patient had previously undergone extensive medical evaluation for diabetes mellitus, hyperlipidemia, and coronary artery disease and did not have any of the aforementioned conditions. In addition, she had no history of other atherosclerotic counterparts, including peripheral vascular disease, myocardial infarction, and abdominal aortic aneurysm. However, she did have a mild stroke ⬇17 years ago, which left her with no permanent sequelae. Other medication included epoetin alfa for anemia of unclear etiology. The patient had not previously received other chemotherapeutic agents or radiotherapy. Her only allergy was to penicillin. She smoked 1 pack per day for 10 years but discontinued smoking 15 years ago. No alcohol use was reported. Family history was also noncontributory. The patient presented to us after receiving imatinib mesylate therapy for 4 months. At this time, ocular examination revealed visual acuity of 20/30 in the right eye and 20/100 in the left eye. Intraocular pressure was 12 mmHg in both eyes. Pupillary examination results, confrontational visual fields, and color vision were within normal limits. Amsler grid testing revealed trace nasal metamorphopsia in the right eye and more significant central and nasal metamorphopsia in the left eye. Slit lamp examination revealed normal lids, lashes, conjunctiva, and cornea and trace nuclear sclerotic cataracts in both eyes. Fundus examination of the right eye revealed retinal telangiectasia in the superior macula with scattered intraretinal hemorrhages. Fundus examination of the left eye revealed several cotton-wool spots superiorly with mild thickening of the macular region and 360° of perifoveal retinal telangiectasia and intraretinal hemorrhages (Fig. 1). Photographs of the fundus before initiation of imatinib mesylate therapy were not available. However, fundus examination before initiation of this treatment demonstrated no fundus abnormalities. Fluorescein angiography revealed macular ischemia with perifoveal capillary nonperfusion and capillary dropout, which was
Fig. 1. A, Red-free fundus photograph of the right eye, revealing telangiectatic vessels in the paramacular region, seen mostly in the superior macula. Several intraretinal hemorrhages are evident along the terminal vessels. B, Red-free fundus photograph of the left eye revealing several cotton-wool spots superiorly with mild thickening of the macular region and 360° of perifoveal retinal telangiectasia and intraretinal hemorrhages. A flame hemorrhage is evident along the superotemporal arcade. The foveal avascular zone is enlarged when compared with that in the right eye.
greater in the left eye than in the right eye. In the late phase of the fluorescein angiogram, there was late perifoveal leakage, which was greater in the left eye than in the right eye (Fig. 2). There was moderate disk staining in the late phases of the fluorescein angiogram. This may have been due to ischemia-related fluorescein accumulation in the optic nerve similar to that seen in anterior ischemic optic neuropathy,8 because the telangiectatic vessels seen in the early phases of the fluorescein angiogram extended to and around the optic disks. Determination of complete blood cell count of a blood specimen obtained at the time of presentation showed a mild decrease in erythrocyte count, hemoglobin level, and hematocrit and increased mean cell volume (MCV), mean cell hemoglobin (MCH), and red cell distributive width (RDW) values. Leukocyte and platelet counts were within normal limits. CML entered and remained in remission while she was receiving therapy with imatinib mesylate. This treatment was discontinued after 4 months, and therapy was switched back to busulfan. The
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Fig. 2. A, Fluorescein angiogram of the right eye at 47 seconds revealed macular ischemia with perifoveal capillary nonperfusion, capillary dropout, and dilated capillary terminal bulbs. B, In the late phase of the fluorescein angiogram of the right eye at 10 minutes, diffuse perifoveal leakage is noted. Late disk staining is noted. C, Fluorescein angiogram of the left eye at 32 seconds revealed more extensive macular ischemia with perifoveal capillary nonperfusion, capillary dropout, and dilated capillary terminal bulbs. A patch of capillary nonperfusion is seen superiorly, corresponding to the area of cotton-wool spot formation. D, In the late phase of the fluorescein angiogram of the left eye at 10 minutes, extensive diffuse perifoveal leakage is noted with central ischemia still evident. Late disk staining is noted.
patient was reexamined 18 days after the initial visit. She reported resolution of ocular pain but continued to have a central scotoma without change of vision in the left eye. CML continued to stay in remission over 10 months of follow-up. Over the 10-month follow-up, there was no ocular pain, but there was no improvement in visual acuity, with persistent central scotoma in the left eye and minimal resolution of perifoveal capillary nonperfusion, which was greater in the left eye than in the right eye. Although retinal hemorrhages resolved slowly over the 10 months, retinal ischemia and telangiectasias persisted despite discontinuation of imatinib mesylate treatment.
Discussion Imatinib mesylate is a possible contributing factor to the development of macular ischemia in the patient with CML described here. After several weeks of imatinib mesylate therapy, the patient developed a central scotoma that expanded over the next 3 months before discontinuation of this therapy. Visual symptoms developed shortly after institution of imatinib mesylate therapy, suggesting an association between macular ischemia and imatinib mesylate. Although leukemia can potentially incite retinal ischemia by microvascular occlusion,9 the temporal sequence of symptoms after imatinib mesylate administration and the fact that CML was in remission at the time make leukemia-induced microvascular occlusion a less likely possi-
bility. Bilateral evidence of macular ischemia suggests that an isolated thromboembolic phenomenon was a less likely mechanism as well. Underlying vasculopathic conditions should also be considered in the genesis and progression of macular ischemia. The patient’s history of hypertension, although controlled with enalapril therapy, may have placed the patient at risk for developing macular ischemia. This risk is heightened when hypertension occurs alongside other accompanying conditions, including hyperlipidemia, diabetes mellitus, vasculitis, connective tissue disorder, and underlying atherosclerosis. Notably, this patient did not have diabetes mellitus or a history of hyperlipidemia. Her history of stroke does suggest a possible underlying atherosclerotic process, increasing her risk for an ischemic event in the retina as well. However, fundus examination before imatinib mesylate therapy did not reveal atherosclerotic changes. In addition, the gradual and progressive nature of the visual loss does not seem to support the occurrence of a cerebrovascular event. Because she had a remote smoking history, having quit 15 years ago, this also is not a major player in the observed ocular events. It is important to note that the patient did not receive busulfan treatment
164
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for several months before the development of ocular symptoms. In addition, to our knowledge, there is no cited association of busulfan with either macular ischemia or retinal hemorrhages noted in the literature. Review of the current literature revealed no previous reports of macular ischemia associated with imatinib mesylate therapy. Retinal hemorrhage occurred in one patient as noted at the Oregon Health and Science University Cancer Institute, which conducted a review of data for patients with CML who received imatinib mesylate therapy in past clinical studies.2 However, this hemorrhage occurred with no other accompanying retinal findings.2 This newly observed macular ischemia and its possible association with imatinib mesylate is an important consideration for patients receiving this therapy. Clinicians will need to distinguish the inciting etiology and contributing factors for patients with CML who develop macular ischemia, including leukemia itself and underlying vasculopathic conditions. With further postmarketing surveillance, the association of macular ischemia with imatinib mesylate will be better elucidated, and the role it plays in the clinical approach to patients with CML will be better defined. It may be necessary for patients taking this medication to be followed by an ophthalmologist on a regular basis to avoid severe capillary nonperfusion. Monitoring for visual symptoms of central vision loss, possibly with Amsler grid
●
2009
●
VOLUME 3
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NUMBER 2
testing, may be warranted for patients with leukemia who receive imatinib mesylate therapy. Key words: imatinib mesylate (Gleevec), chronic myeloid leukemia, toxic, maculopathy, ischemia, intraretinal hemorrhage. References 1. 2.
3.
4.
5. 6.
7.
8. 9.
Gleevec [Package Insert]. East Hanover, NJ: Novartis Pharmaceuticals; 2006. Fraunfelder FW, Solomon J, Druker BJ, et al. Ocular side effects associated with imatinib mesylate (Gleevec). J Ocul Pharmacol Ther 2003;19:371–375. Kusumi E, Arakawa A, Kami M, et al. Visual disturbance due to retinal edema as a complication of imatinib. Leukemia 2004;18:1138–1139. Govind Babu K, Attili VS, Bapsy PP, Anupama G. Imatinibinduced optic neuritis in a patient of chronic myeloid leukemia. Int Ophthalmol 2007;27:43–44. Fraunfelder F. Corneal toxicity from topical ocular and systemic medications. Cornea 2006;25:1133–1138. Georgalas I, Pavesio C, Ezra E. Bilateral cystoid macular edema in a patient with chronic myeloid leukaemia under treatment with imatinib mesylate: report of an unusual side effect. Graefes Arch Clin Exp Ophthalmol 2007;245:1585– 1586. Masood I, Negi A, Dua HS. Imatinib as a cause of cystoid macular edema following uneventful phacoemulsification surgery. J Cataract Refract Surg 2005;31:2427–2428. Hayreh SS. Anterior ischemic optic neuropathy. V. Optic disc edema an early sign. Arch Ophthalmol 1981;99:1030–1040. Piermarocchi S, Segato T, Bertoja H, et al. Branch retinal vein occlusion: the pathogenic role of blood viscosity. Ann Ophthalmol 1990;22:303–311.
