CENTRAL SEROUS CHORIORETINOPATHY ASSOCIATED WITH THE USE OF EPHEDRA Kristine K. Pierce, MD,* R. Gary Lane, MD†
Purpose: To report three cases of central serous chorioretinopathy (CSC) likely related to the use of body-building products containing ephedra. Methods: Observational case series of three patients who presented with signs and symptoms of CSC. All cases had ocular coherence tomography and fluorescein angiograms to confirm the diagnosis. All admitted to current or previous use of ephedra containing products for body building. No patient had a history of current or prior use of steroids. Results: The first patient presented in 2005 with a 7-month history of bilateral CSC. On careful history, the patient admitted to the use of ephedra during body-building exercises. After discontinuation of the ephedra, his CSC resolved. The second and third patients presented in 2007. Both had pigmented epithelial detachments in both eyes secondary to CSC and atrophic changes suggestive of old, resolved CSC. The second patient had admitted to the use of ephedra 3 years previously and Patient 3 was currently using an ephedra-containing body-building product. After Patient 3 discontinued the ephedra, his CSC too resolved. Conclusion: We report three cases of CSC related to the use of ephedra-containing products. All three cases were chronic, atypical, and bilateral in nature with two of three cases resolving after the discontinuation of the ephedra. This may be related to the sympathomimetic properties of ephedra as reported by Michael et al for pseudoephedrine. Given these findings, we suggest that questioning about ephedra products become standard when taking histories in suspected CSC cases. RETINAL CASES & BRIEF REPORTS 3:376 –378, 2009
From the Departments of *Ophthalmology and †Vitreoretinal Surgery, Wilford Hall Medical Center, San Antonio, Texas.
was rediscovered by body builders as a potent stimulant to increase energy and to burn fat during workouts.5 It has been shown to have serious side effects to include hypertension, palpitations, arrhythmias, cardiac arrest, and myocardial infarctions.4,5 In 2004, ephedra was banned from the U.S. commercial market as a result of safety concerns; however, it is still widely available through the Internet.6 Central serous chorioretinopathy (CSC) is a serous neural retinal detachment usually in the macular region and/or the posterior pole.7 It has often been correlated with type A personality traits, migraines, smoking, antibiotics, antihistamines, and corticosteroids.7 To the authors’ knowledge, however, there has been no known association with ephedra use and CSC. We present a case series of three patients with chronic, recurrent CSC likely related to the use of body-building supplements containing ephedra.
E
phedra is an alkaloid derived of ephedrine and pseudoephedrine, which are potent sympathomemetics.1 It has been used as a therapeutic herb by the Chinese for over 5,000 years to alleviate symptoms of lung and bronchial constriction, water retention, and sweating.2,3 In 1924, physicians in the United States began using the supplement for similar conditions.4 At the end of the 20th century, ephedra None of the authors have financial interests in this report. No grants or funds were used for this study. Reprint requests: Kristine K. Pierce, MD, Department of Ophthalmology, Wilford Hall Medical Center, 2200 Bergquist Drive, Lackland AFB, San Antonio, TX 78236; e-mail: [email protected]
376
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CSC ASSOCIATED WITH EPHEDRA USE
Fig. 1. Patient 1 fundus photographs with inset OCT of the macula.
Case Reports Patient 1 A 31-year-old black man presented in June 2005 with a 7-month history of a black spot in his central vision in both eyes. Ocular and medical history were negative for steroid use, nasal inhalers, smoking, antihistamines, and so on. Social history revealed the patient to be a body builder with current use of ephedra. Visual acuity was 20/60 in both eyes without correction with no improvement on manifestation. Ocular examination was significant for an exudative retinal detachment in both eyes just overlying the macula. His left eye also revealed yellow deposits just inferior to the temporal arcade. Optical coherence tomography (OCT) revealed a large amount of subretinal fluid in the right eye and subretinal fluid within the fovea in the left eye (Figure 1). Fluorescein angiography (FA) revealed the classic “smokestack” in the right eye and a hot spot near the disk in the left eye. Polypoidal choroidal neovascularization was unlikely given his age as well as no evidence clinically with a contact lens nor on FA of subretinal polyplike structures. The patient was instructed to discontinue all supplements including ephedra. Given his job requirements and change of duty station to Germany in the next 6 weeks, he underwent photodynamic therapy in the left eye to help with resolution of the “hot spot” located near the disk. On follow up at 6 months in Landstuhl, Germany, by optometry, his vision had returned to 20/25 in both eyes. In February 2006, 1 month later, his vision dropped to 20/60 in the left eye secondary to recurrent CSC likely secondary to new use of flonase. He currently has 20/20 in the right eye and 20/60 in the left eye with permanent visual impairment in the left eye as a result of his CSC.
Patient 2 A 38-year-old white man presented in January 2007 with visual changes in the left eye. Ocular and medical history were negative
Fig. 2. Patient 2 fundus photographs with inset OCT of the macula.
for steroid use, nasal inhalers, smoking, and so on. Social history revealed body-building supplemental use to include ephedra 3 years previously. Visual acuity was 20/20 in both eyes without correction. Ocular examination was significant for a pigmented epithelial detachment (PED) temporal to the macula in the right eye and a PED centrally in the left eye. Optical coherence tomography revealed no subretinal fluid in the right eye and a small PED overlying the macula in the left eye (Figure 2). Fluorescein angiography revealed findings consistent with his OCT without current leakage.
Patient 3 A 44-year-old white man presented in July 2007 with visual changes to his right eye. Ocular and medical history were negative for steroid use, nasal inhalers, smoking, and so on. Social history revealed current use of xenadrine, which contains ephedra, for his body-building exercises. Visual acuity was 20/20 in both eyes. Ocular examination was significant for a PED temporal to the macula in the right eye and a smaller PED just superior and temporal to the macula in the left eye. Further inspection of the left eye with a macular contact lens at the slit lamp revealed a neurosensory detachment just inferior to the temporal arcade. OCT revealed PED in his temporal macula in the right eye and a temporal PED in the left eye (Figure 3). Fluorescein angiography revealed findings consistent with his OCT as well as a focal hot spot just inferior to the temporal arcade in the left eye corresponding to the area seen on slit-lamp examination. The patient was counseled to discontinue all supplements including xenadrine with complete resolution of his PED/CSC at 6-month follow up.
Discussion Signs and symptoms of CSC typically remain for only 2 to 4 weeks without treatment as recently re-
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Fig. 3. Patient 3 fundus photographs with inset OCT of the macula in the right eye and superior arcade in the left eye.
ported in 2002 by Pikkel et al.8 It has been described in patients tending to be middle-aged men with the aforementioned predisposing risk factors such as steroids and type A personality traits.8 Chronic CSC, conversely reported in up to 5% of cases, lasts more than 6 months and tends to be in patients older than 55. All cases have also been associated with some form of corticosteroid use. We present three cases of the chronic nature, however, atypical given that our patients were in the middle age group and none were using any form of corticosteroid. All had an underlying history of current or prior use of ephedra for body building. Two of three cases had complete resolution only after discontinuation of the ephedra supplements. Furthermore, all cases were bilateral and two of three also exhibited bilateral PED. In July 2003, Michael et al reported on the development of CSC after high doses of pseudoephedrine likely related to its sympathomimetic properties.9 Ephedra contains the alkaloids ephedrine and pseudoephedrine, both potent sympathomimetics. Ephedrine and pseudoephedrine act at the norepinephrine synapse causing more norepinephrine to be released from its storage vesicles. Ephedrine can also bind directly to adrenergic receptors to mimic the actions of norepinephrine.5 Sibayan et al in 2000 found that apoptosis was induced in retinal pigment epithelium cells in a time- and dose-dependent manner by epinephrine implicating this as the pathyophysiologic mechanism for the development of CSC.10 The combined effects of ephedrine and pseudoephedrine in ephedra causing cell death of the retinal pigment epithelium may account for the possible cause and atypical nature of CSC in our three patients. Such use of ephedra-containing supplements will likely be limited given the Food and Drug Administration ban of all such products for weight loss and body building in early 2004.6 On a quick Internet search, however, one may find such products outside the United States. Furthermore, two of our patients
were using the ephedra supplements up to 3 years after the ban. We believe there is a direct correlation with ephedra use and the development of a chronic and atypical course of CSC given these three patients. In conclusion, it is extremely prudent to carefully counsel our patients as well as obtain a well-defined medication history to include supplements to allow better management of CSC. We also suggest that questioning about ephedra-containing products become standard when taking histories for predisposing factors in suspected CSC cases. Key words: central serous chorioretinopathy, ephedra, ephedrine, pseudoephedrine. References 1.
2. 3.
4.
5.
6. 7.
8. 9.
10.
Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833–1838. Hu SY. Ephedra (Ma-huang) in the new Chinese materia medica. Econ Bot 1969;23:346 –351. Costello JF, May CS, Paterson JW, Pickup ME. Pharmacokinetics of ephedrine in asthmatics receiving acute and chronic treatment. Br J Clin Pharmacol 1975;2:180 –181. Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance. A meta-analysis. JAMA 2003;289:1537–1545. Ma G, Bavadekar SA, Davis YM, et al. Pharmacological effects of ephedrine alkaloids on human alpha 1- and alpha 2-adrenergic receptor subtypes. J Pharmacol Exp Ther 2007; 322:214 –221. Rados C. Ephedra ban: no shortage of reasons. FDA Consum 2004;38:6 –7. Tittl MK, Spaide RF, Wong D, et al. Systemic findings associated with central serous chorioretinopathy. Am J Ophthalmol 1999;128:63– 68. Pikkel J, Beiran I, Ophir A, et al. Acetazolamide for central serous retinopathy. Ophthalmology 2002;109:1723–1725. Michael JC, Pak J, Pulido J, de Venecia G. Central serous chorioretinopathy associated with administration of sympathomimetic agents. Am J Ophthalmol 2003;136:182–185. Sibayan SA, Kobuch K, Spiegel D, et al. Epinephrine, but not dexamethoasone, induces apoptosis in retinal pigment epithelium cells in vitro: possible implications on the pathogenesis of central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol 2000;238:515–519.
Purpose: To report three cases of central serous chorioretinopathy (CSC) likely related to the use of body-building products containing ephedra. Methods: Observational case series of three patients who presented with signs and symptoms of CSC. All cases had ocular coherence tomography and fluorescein angiograms to confirm the diagnosis. All admitted to current or previous use of ephedra containing products for body building. No patient had a history of current or prior use of steroids. Results: The first patient presented in 2005 with a 7-month history of bilateral CSC. On careful history, the patient admitted to the use of ephedra during body-building exercises. After discontinuation of the ephedra, his CSC resolved. The second and third patients presented in 2007. Both had pigmented epithelial detachments in both eyes secondary to CSC and atrophic changes suggestive of old, resolved CSC. The second patient had admitted to the use of ephedra 3 years previously and Patient 3 was currently using an ephedra-containing body-building product. After Patient 3 discontinued the ephedra, his CSC too resolved. Conclusion: We report three cases of CSC related to the use of ephedra-containing products. All three cases were chronic, atypical, and bilateral in nature with two of three cases resolving after the discontinuation of the ephedra. This may be related to the sympathomimetic properties of ephedra as reported by Michael et al for pseudoephedrine. Given these findings, we suggest that questioning about ephedra products become standard when taking histories in suspected CSC cases. RETINAL CASES & BRIEF REPORTS 3:376 –378, 2009
From the Departments of *Ophthalmology and †Vitreoretinal Surgery, Wilford Hall Medical Center, San Antonio, Texas.
was rediscovered by body builders as a potent stimulant to increase energy and to burn fat during workouts.5 It has been shown to have serious side effects to include hypertension, palpitations, arrhythmias, cardiac arrest, and myocardial infarctions.4,5 In 2004, ephedra was banned from the U.S. commercial market as a result of safety concerns; however, it is still widely available through the Internet.6 Central serous chorioretinopathy (CSC) is a serous neural retinal detachment usually in the macular region and/or the posterior pole.7 It has often been correlated with type A personality traits, migraines, smoking, antibiotics, antihistamines, and corticosteroids.7 To the authors’ knowledge, however, there has been no known association with ephedra use and CSC. We present a case series of three patients with chronic, recurrent CSC likely related to the use of body-building supplements containing ephedra.
E
phedra is an alkaloid derived of ephedrine and pseudoephedrine, which are potent sympathomemetics.1 It has been used as a therapeutic herb by the Chinese for over 5,000 years to alleviate symptoms of lung and bronchial constriction, water retention, and sweating.2,3 In 1924, physicians in the United States began using the supplement for similar conditions.4 At the end of the 20th century, ephedra None of the authors have financial interests in this report. No grants or funds were used for this study. Reprint requests: Kristine K. Pierce, MD, Department of Ophthalmology, Wilford Hall Medical Center, 2200 Bergquist Drive, Lackland AFB, San Antonio, TX 78236; e-mail: [email protected]
376
377
CSC ASSOCIATED WITH EPHEDRA USE
Fig. 1. Patient 1 fundus photographs with inset OCT of the macula.
Case Reports Patient 1 A 31-year-old black man presented in June 2005 with a 7-month history of a black spot in his central vision in both eyes. Ocular and medical history were negative for steroid use, nasal inhalers, smoking, antihistamines, and so on. Social history revealed the patient to be a body builder with current use of ephedra. Visual acuity was 20/60 in both eyes without correction with no improvement on manifestation. Ocular examination was significant for an exudative retinal detachment in both eyes just overlying the macula. His left eye also revealed yellow deposits just inferior to the temporal arcade. Optical coherence tomography (OCT) revealed a large amount of subretinal fluid in the right eye and subretinal fluid within the fovea in the left eye (Figure 1). Fluorescein angiography (FA) revealed the classic “smokestack” in the right eye and a hot spot near the disk in the left eye. Polypoidal choroidal neovascularization was unlikely given his age as well as no evidence clinically with a contact lens nor on FA of subretinal polyplike structures. The patient was instructed to discontinue all supplements including ephedra. Given his job requirements and change of duty station to Germany in the next 6 weeks, he underwent photodynamic therapy in the left eye to help with resolution of the “hot spot” located near the disk. On follow up at 6 months in Landstuhl, Germany, by optometry, his vision had returned to 20/25 in both eyes. In February 2006, 1 month later, his vision dropped to 20/60 in the left eye secondary to recurrent CSC likely secondary to new use of flonase. He currently has 20/20 in the right eye and 20/60 in the left eye with permanent visual impairment in the left eye as a result of his CSC.
Patient 2 A 38-year-old white man presented in January 2007 with visual changes in the left eye. Ocular and medical history were negative
Fig. 2. Patient 2 fundus photographs with inset OCT of the macula.
for steroid use, nasal inhalers, smoking, and so on. Social history revealed body-building supplemental use to include ephedra 3 years previously. Visual acuity was 20/20 in both eyes without correction. Ocular examination was significant for a pigmented epithelial detachment (PED) temporal to the macula in the right eye and a PED centrally in the left eye. Optical coherence tomography revealed no subretinal fluid in the right eye and a small PED overlying the macula in the left eye (Figure 2). Fluorescein angiography revealed findings consistent with his OCT without current leakage.
Patient 3 A 44-year-old white man presented in July 2007 with visual changes to his right eye. Ocular and medical history were negative for steroid use, nasal inhalers, smoking, and so on. Social history revealed current use of xenadrine, which contains ephedra, for his body-building exercises. Visual acuity was 20/20 in both eyes. Ocular examination was significant for a PED temporal to the macula in the right eye and a smaller PED just superior and temporal to the macula in the left eye. Further inspection of the left eye with a macular contact lens at the slit lamp revealed a neurosensory detachment just inferior to the temporal arcade. OCT revealed PED in his temporal macula in the right eye and a temporal PED in the left eye (Figure 3). Fluorescein angiography revealed findings consistent with his OCT as well as a focal hot spot just inferior to the temporal arcade in the left eye corresponding to the area seen on slit-lamp examination. The patient was counseled to discontinue all supplements including xenadrine with complete resolution of his PED/CSC at 6-month follow up.
Discussion Signs and symptoms of CSC typically remain for only 2 to 4 weeks without treatment as recently re-
378
RETINAL CASES & BRIEF REPORTSℜ
●
2009
●
VOLUME 3
●
NUMBER 4
Fig. 3. Patient 3 fundus photographs with inset OCT of the macula in the right eye and superior arcade in the left eye.
ported in 2002 by Pikkel et al.8 It has been described in patients tending to be middle-aged men with the aforementioned predisposing risk factors such as steroids and type A personality traits.8 Chronic CSC, conversely reported in up to 5% of cases, lasts more than 6 months and tends to be in patients older than 55. All cases have also been associated with some form of corticosteroid use. We present three cases of the chronic nature, however, atypical given that our patients were in the middle age group and none were using any form of corticosteroid. All had an underlying history of current or prior use of ephedra for body building. Two of three cases had complete resolution only after discontinuation of the ephedra supplements. Furthermore, all cases were bilateral and two of three also exhibited bilateral PED. In July 2003, Michael et al reported on the development of CSC after high doses of pseudoephedrine likely related to its sympathomimetic properties.9 Ephedra contains the alkaloids ephedrine and pseudoephedrine, both potent sympathomimetics. Ephedrine and pseudoephedrine act at the norepinephrine synapse causing more norepinephrine to be released from its storage vesicles. Ephedrine can also bind directly to adrenergic receptors to mimic the actions of norepinephrine.5 Sibayan et al in 2000 found that apoptosis was induced in retinal pigment epithelium cells in a time- and dose-dependent manner by epinephrine implicating this as the pathyophysiologic mechanism for the development of CSC.10 The combined effects of ephedrine and pseudoephedrine in ephedra causing cell death of the retinal pigment epithelium may account for the possible cause and atypical nature of CSC in our three patients. Such use of ephedra-containing supplements will likely be limited given the Food and Drug Administration ban of all such products for weight loss and body building in early 2004.6 On a quick Internet search, however, one may find such products outside the United States. Furthermore, two of our patients
were using the ephedra supplements up to 3 years after the ban. We believe there is a direct correlation with ephedra use and the development of a chronic and atypical course of CSC given these three patients. In conclusion, it is extremely prudent to carefully counsel our patients as well as obtain a well-defined medication history to include supplements to allow better management of CSC. We also suggest that questioning about ephedra-containing products become standard when taking histories for predisposing factors in suspected CSC cases. Key words: central serous chorioretinopathy, ephedra, ephedrine, pseudoephedrine. References 1.
2. 3.
4.
5.
6. 7.
8. 9.
10.
Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833–1838. Hu SY. Ephedra (Ma-huang) in the new Chinese materia medica. Econ Bot 1969;23:346 –351. Costello JF, May CS, Paterson JW, Pickup ME. Pharmacokinetics of ephedrine in asthmatics receiving acute and chronic treatment. Br J Clin Pharmacol 1975;2:180 –181. Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance. A meta-analysis. JAMA 2003;289:1537–1545. Ma G, Bavadekar SA, Davis YM, et al. Pharmacological effects of ephedrine alkaloids on human alpha 1- and alpha 2-adrenergic receptor subtypes. J Pharmacol Exp Ther 2007; 322:214 –221. Rados C. Ephedra ban: no shortage of reasons. FDA Consum 2004;38:6 –7. Tittl MK, Spaide RF, Wong D, et al. Systemic findings associated with central serous chorioretinopathy. Am J Ophthalmol 1999;128:63– 68. Pikkel J, Beiran I, Ophir A, et al. Acetazolamide for central serous retinopathy. Ophthalmology 2002;109:1723–1725. Michael JC, Pak J, Pulido J, de Venecia G. Central serous chorioretinopathy associated with administration of sympathomimetic agents. Am J Ophthalmol 2003;136:182–185. Sibayan SA, Kobuch K, Spiegel D, et al. Epinephrine, but not dexamethoasone, induces apoptosis in retinal pigment epithelium cells in vitro: possible implications on the pathogenesis of central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol 2000;238:515–519.
