CYSTOID MACULAR EDEMA SECONDARY TO PACLITAXEL (ABRAXANE) Sarah M. Risard, BS, Dante J. Pieramici, MD, Melvin D. Rabena, BS
Purpose: To report a case of cystoid macular edema secondary to systemic paclitaxel. Methods: A 58-year-old man with Stage 4 metastatic cutaneous melanoma presented with decreased vision and macular edema while having minimal fluorescein leakage 7 months into a course of paclitaxel chemotherapy. The edema continued to worsen, and vision declined until paclitaxel therapy was discontinued. Six weeks after cessation of paclitaxel, the edema had completely resolved and vision returned to normal. Conclusion: Paclitaxel use can result in reversible vision loss associated with angiographically silent macular edema. RETINAL CASES & BRIEF REPORTS 3:383–385, 2009
From the California Retina Research Foundation, Santa Barbara, California.
A 58-year-old man with Stage 4 metastatic cutaneous melanoma was referred for evaluation of macular edema and decreasing vision. The patient had undergone a 7-month chemotherapeutic regimen that included paclitaxel and intravenous Avastin (Genentech Inc., South San Francisco, CA) infusions (341 mg and 1,050 mg per infusion, respectively). He first noticed steadily decreasing vision ⬃3 months before presentation. At presentation, his vision measured 20/60 and 20/80 (Snellen) in his right and left eyes, respectively. Dilated examination and fundus photographs suggested macular edema in both eyes, with no obvious epiretinal membrane or vitreomacular traction. Optical coherence tomography revealed evidence of cystic spaces with a central thickness of 500 m in the right eye and 666 m in the left eye. However, fluorescein angiography showed minimal to no leakage (Figures 1 and 2). To extend his chemotherapeutic course of treatment, he was initially managed with topical prednisolone and ketorolac QID. When the patient returned 3 weeks later, his vision had dropped to 20/70 and 20/200 in the right and left eyes, respectively, and central retinal thickness increased to 612 m and 741 m in the right and left
P
aclitaxel (Abraxane, Abraxis BioScience, LLC, Los Angeles, CA) is an antineoplastic agent, chemically similar to docetaxel. It is approved for treating ovarian and breast carcinoma and functions as an antimicrotubule agent that prevents mitotic cellular functions. The most common systemic toxic effects are fatigue, nausea, suppressed bone marrow, alopecia, peripheral neuropathy, athralgia, and myalgia.1,2 Ocular side effects include mild conjunctival chemosis, corneal epitheliopathy, corneal edema, keratitis, and photopsia.2-5 There is only one published report of paclitaxel maculopathy.1 We present a second patient with cystoid macular edema without angiographic leakage that resolved rapidly with restoration of vision after discontinuing paclitaxel.
The authors have no propriety interest in any of the products discussed in this article. Reprint requests: Dante J. Pieramici, MD, CA Retina Consultants, 515 E. Micheltorena Street, Ste. C, Santa Barbara, CA 93103; e-mail: [email protected]
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Fig. 1. Fluorescein angiograms of the right and left eyes, respectively, at initial evaluation do not show significant leakage.
eyes, respectively. At this time, we consulted with his medical oncologist to discontinue his paclitaxel therapy. Two weeks after his chemotherapy (paclitaxel) was discontinued, his vision had returned to 20/40 and 20/70 in his right and left eyes, respectively, and central retinal thickness had decreased to 353 m and 682 m in his right and left eyes, respectively. Six weeks after discontinuation of paclitaxel, best-corrected visual acuity was 20/30 and 20/50, and head central retinal thicknesses of 236 m and 254 m in his right and left eyes, respectively (Figure 2). Our patient demonstrates another compelling association between the use of paclitaxel and the occurrence of fluorescein silent macular edema. Macular edema in the absence of angiographic leakage can be seen in patients with vitreomacular interface abnormalities (epiretinal membrane, vitreomacular traction) and has been reported as a toxic reaction in patients using docetaxel, paclitaxel, and niacin.1,5-9 It is interesting that the macular edema occurred in our patient despite the concomitant use of intravenous bevacizumab. This suggests a non–
vascular endothelial growth factor–mediated mechanism for the macular edema in our case. The cause of the cystoid edema in our patient is unclear, and two main theories have been proposed based on similar anatomic findings in patients using nicotinic acid and docetaxel. One theory suggests the engorgement of Muller cells, which are responsible for maintaining osmotic gradients within the neurosensory retina.1,8-10 Another theory proposes a breakdown of the blood– ocular barrier.8,9 The latter seems less likely because no leakage was seen on the fluorescein angiography and one might expect that bevacizumab might have blunted this edema. However, selective leakage of only molecules smaller than fluorescein (molecular weight 376) might be an alternative explanation. Despite the use of paclitaxel for ⬎7 months with significant maculopathy, our patient responded rapidly and completely (subjectively) to cessation of the medication without obvious irreversible effects. Patients on this medication should monitor their vision and be referred for ocular examination if visual symptoms develop.
Fig. 2. Optical coherence tomography scans of the right and left eyes, respectively, after 7 months of paclitaxel therapy (top) and 6 weeks after cessation (bottom) demonstrate a reduction in edema.
CYSTOID MACULAR EDEMA SECONDARY TO PACLITAXEL
Key words: Abraxane, cystoid macular edema, maculopathy, paclitaxel, toxicity.
5.
References
6.
1. 2. 3.
4.
Joshi MM, Garretson BR. Paclitaxel maculopathy. Arch Ophthalmol 2007;125:709 –710. Tan WW, Walsh T. Ocular toxicity secondary to paclitaxel in two lung cancer patients. Med Pediatr Oncol 1998;31:177. Sua´rez F, Jockovich ME, Hernandez E, et al. Paclitaxel in the treatment of retinal tumors of LH beta-Tag murine transgenic model of retinoblastoma. Invest Ophthalmol Vis Sci 2007; 48:3437–3440. Damascelli B, Cantu´ G, Mattavello F, et al. Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007): phase II study of patients with squamous cell carcinoma of the head and neck and anal canal: preliminary evidence of
7.
8.
9.
10.
385 clinical activity. Cancer 2001;92:2592–2602. Teitelbaum BA, Tresley DJ. Cystic maculopathy with normal capillary permeability secondary to docetaxel. Optom Vis Sci 2003;80:277–279. Hofstra LS, de Vries EG, Willemse PH. Ophthalmic toxicity following paclitaxel infusion. Ann Oncol 1997;8:1053. Telander DG, Sarraf D. Cystoid macular edema with docetaxel chemotherapy and the fluid retention syndrome. Semin Ophthalmol 2007;22:151–153. Spirin MJ, Warren FA, Guyer DR, et al. Optical coherence tomography findings in nicotinic acid maculopathy. Am J Ophthalmol 2003;135:913–914. Dajani DM, Lauer AK. Optical coherence tomography findings in niacin maculopathy. Can J Ophthamol 2006;41:197– 200. Albert D, Miller J, Azar D, et al. Albert and Jakobiec’s Principles and Practice of Ophthalmology. Elsevier; 2008: 1633–1638.
Purpose: To report a case of cystoid macular edema secondary to systemic paclitaxel. Methods: A 58-year-old man with Stage 4 metastatic cutaneous melanoma presented with decreased vision and macular edema while having minimal fluorescein leakage 7 months into a course of paclitaxel chemotherapy. The edema continued to worsen, and vision declined until paclitaxel therapy was discontinued. Six weeks after cessation of paclitaxel, the edema had completely resolved and vision returned to normal. Conclusion: Paclitaxel use can result in reversible vision loss associated with angiographically silent macular edema. RETINAL CASES & BRIEF REPORTS 3:383–385, 2009
From the California Retina Research Foundation, Santa Barbara, California.
A 58-year-old man with Stage 4 metastatic cutaneous melanoma was referred for evaluation of macular edema and decreasing vision. The patient had undergone a 7-month chemotherapeutic regimen that included paclitaxel and intravenous Avastin (Genentech Inc., South San Francisco, CA) infusions (341 mg and 1,050 mg per infusion, respectively). He first noticed steadily decreasing vision ⬃3 months before presentation. At presentation, his vision measured 20/60 and 20/80 (Snellen) in his right and left eyes, respectively. Dilated examination and fundus photographs suggested macular edema in both eyes, with no obvious epiretinal membrane or vitreomacular traction. Optical coherence tomography revealed evidence of cystic spaces with a central thickness of 500 m in the right eye and 666 m in the left eye. However, fluorescein angiography showed minimal to no leakage (Figures 1 and 2). To extend his chemotherapeutic course of treatment, he was initially managed with topical prednisolone and ketorolac QID. When the patient returned 3 weeks later, his vision had dropped to 20/70 and 20/200 in the right and left eyes, respectively, and central retinal thickness increased to 612 m and 741 m in the right and left
P
aclitaxel (Abraxane, Abraxis BioScience, LLC, Los Angeles, CA) is an antineoplastic agent, chemically similar to docetaxel. It is approved for treating ovarian and breast carcinoma and functions as an antimicrotubule agent that prevents mitotic cellular functions. The most common systemic toxic effects are fatigue, nausea, suppressed bone marrow, alopecia, peripheral neuropathy, athralgia, and myalgia.1,2 Ocular side effects include mild conjunctival chemosis, corneal epitheliopathy, corneal edema, keratitis, and photopsia.2-5 There is only one published report of paclitaxel maculopathy.1 We present a second patient with cystoid macular edema without angiographic leakage that resolved rapidly with restoration of vision after discontinuing paclitaxel.
The authors have no propriety interest in any of the products discussed in this article. Reprint requests: Dante J. Pieramici, MD, CA Retina Consultants, 515 E. Micheltorena Street, Ste. C, Santa Barbara, CA 93103; e-mail: [email protected]
383
384
RETINAL CASES & BRIEF REPORTSℜ
●
2009
●
VOLUME 3
●
NUMBER 4
Fig. 1. Fluorescein angiograms of the right and left eyes, respectively, at initial evaluation do not show significant leakage.
eyes, respectively. At this time, we consulted with his medical oncologist to discontinue his paclitaxel therapy. Two weeks after his chemotherapy (paclitaxel) was discontinued, his vision had returned to 20/40 and 20/70 in his right and left eyes, respectively, and central retinal thickness had decreased to 353 m and 682 m in his right and left eyes, respectively. Six weeks after discontinuation of paclitaxel, best-corrected visual acuity was 20/30 and 20/50, and head central retinal thicknesses of 236 m and 254 m in his right and left eyes, respectively (Figure 2). Our patient demonstrates another compelling association between the use of paclitaxel and the occurrence of fluorescein silent macular edema. Macular edema in the absence of angiographic leakage can be seen in patients with vitreomacular interface abnormalities (epiretinal membrane, vitreomacular traction) and has been reported as a toxic reaction in patients using docetaxel, paclitaxel, and niacin.1,5-9 It is interesting that the macular edema occurred in our patient despite the concomitant use of intravenous bevacizumab. This suggests a non–
vascular endothelial growth factor–mediated mechanism for the macular edema in our case. The cause of the cystoid edema in our patient is unclear, and two main theories have been proposed based on similar anatomic findings in patients using nicotinic acid and docetaxel. One theory suggests the engorgement of Muller cells, which are responsible for maintaining osmotic gradients within the neurosensory retina.1,8-10 Another theory proposes a breakdown of the blood– ocular barrier.8,9 The latter seems less likely because no leakage was seen on the fluorescein angiography and one might expect that bevacizumab might have blunted this edema. However, selective leakage of only molecules smaller than fluorescein (molecular weight 376) might be an alternative explanation. Despite the use of paclitaxel for ⬎7 months with significant maculopathy, our patient responded rapidly and completely (subjectively) to cessation of the medication without obvious irreversible effects. Patients on this medication should monitor their vision and be referred for ocular examination if visual symptoms develop.
Fig. 2. Optical coherence tomography scans of the right and left eyes, respectively, after 7 months of paclitaxel therapy (top) and 6 weeks after cessation (bottom) demonstrate a reduction in edema.
CYSTOID MACULAR EDEMA SECONDARY TO PACLITAXEL
Key words: Abraxane, cystoid macular edema, maculopathy, paclitaxel, toxicity.
5.
References
6.
1. 2. 3.
4.
Joshi MM, Garretson BR. Paclitaxel maculopathy. Arch Ophthalmol 2007;125:709 –710. Tan WW, Walsh T. Ocular toxicity secondary to paclitaxel in two lung cancer patients. Med Pediatr Oncol 1998;31:177. Sua´rez F, Jockovich ME, Hernandez E, et al. Paclitaxel in the treatment of retinal tumors of LH beta-Tag murine transgenic model of retinoblastoma. Invest Ophthalmol Vis Sci 2007; 48:3437–3440. Damascelli B, Cantu´ G, Mattavello F, et al. Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007): phase II study of patients with squamous cell carcinoma of the head and neck and anal canal: preliminary evidence of
7.
8.
9.
10.
385 clinical activity. Cancer 2001;92:2592–2602. Teitelbaum BA, Tresley DJ. Cystic maculopathy with normal capillary permeability secondary to docetaxel. Optom Vis Sci 2003;80:277–279. Hofstra LS, de Vries EG, Willemse PH. Ophthalmic toxicity following paclitaxel infusion. Ann Oncol 1997;8:1053. Telander DG, Sarraf D. Cystoid macular edema with docetaxel chemotherapy and the fluid retention syndrome. Semin Ophthalmol 2007;22:151–153. Spirin MJ, Warren FA, Guyer DR, et al. Optical coherence tomography findings in nicotinic acid maculopathy. Am J Ophthalmol 2003;135:913–914. Dajani DM, Lauer AK. Optical coherence tomography findings in niacin maculopathy. Can J Ophthamol 2006;41:197– 200. Albert D, Miller J, Azar D, et al. Albert and Jakobiec’s Principles and Practice of Ophthalmology. Elsevier; 2008: 1633–1638.
