Sudden Retinal Manifestations of Intranasal Cocaine and Methamphetamine Abuse R. Trent Wallace, M.D., Gary C. Brown, M.D., W i l l i a m B e n s o n , M.D., and Arunan S i v a l i n g h a m , M.D. We examined two patients who had sudden decrease in vision after intranasal cocaine or methamphetamine abuse. A 38-year-old woman with a history of systemic arterial hypertension developed a central retinal artery occlusion four hours after intranasal use of cocaine. A 26-year-old woman had blurred vision and intraretinal hemorrhages shortly after using methamphetamine nasally. The adrenomimetic response and sudden increase in blood pressure associated with the intranasal use of these drugs may have contributed to the retinal vascular manifestations observed in these patients. W E TREATED two patients with sudden retinal vascular complications related to nasal drug abuse.
L.E.: 20/30. The anterior segment was normal in each eye, as was the intraocular pressure. A right afferent pupillary defect was present. Examination of the right fundus showed dif fuse retinal whitening in the posterior pole, with a foveal cherry-red spot and vascular at tenuation consistent with a sudden central reti nal artery occlusion (Fig. 1). No arterial emboli were seen. The left fundus was normal. An anterior chamber paracentesis was imme diately performed and 500 mg of acetazolamide was administered intravenously. The patient was hospitalized for carbogen therapy (breath ing a mixture of 95% oxygen and 5% carbon dioxide for ten minutes every two hours). Results of diagnostic studies, including echocardiography, carotid ultrasonography, and de termination of packed cell volume, were all normal. Fluorescein angiography performed
Case Reports Case 1 A 38-year-old woman had painless loss of vision in her right eye four hours after using cocaine intranasally. She had a history of sys temic arterial hypertension, and was currently being treated with oral propranolol, 80 mg, two times per day, and nifedipine, 10 mg, four times per day. She had no history of migraine head aches. At initial examination, her blood pres sure was 208/114 mm Hg and her pulse rate was 72 beats per minute. No history of intrave nous drug abuse was elicited. Her visual acuity was R.E.: hand motions and Accepted for publication May 13, 1992. From the Retina Service, Wills Eye Hospital, Jefferson Medical College, Thomas Jefferson University, Philadel phia, Pennsylvania. Reprint requests to Gary C. Brown, M.D., 910 E. Willow Grove Ave., Philadelphia, PA 19118.
158
Fig. 1 (Wallace and associates). Case 1. The right fundus demonstrates macular whitening and a foveal cherry-red spot characteristic of a central retinal artery occlusion.
©AMERICAN JOURNAL OF OPHTHALMOLOGY
114:158-160,
AUGUST,
1992
Vol. 114, No. 2
Retinal Manifestations of Cocaine and Methamphetamine
Fig. 2 (Wallace and associates). Case 1. Intravenous fluorescein angiogram of the right eye at 37 seconds after antecubital injection shows a delay in retinal arterial filling, as demonstrated by a leading edge of dye in the proximal arteries.
159
Fig. 3 (Wallace and associates). Case 2. The left fundus shows multiple intraretinal hemorrhages.
Discussion the next day showed a markedly prolonged arteriovenous transit time, as well as late stain ing of the optic nerve (Fig. 2). Case 2 A 26-year-old woman had blurred vision and a spot in front of her left eye for five days at initial examination. Her medical history was unremarkable. She noticed the visual change in her left eye several hours after using metham phetamine nasally. She had no history of intra venous drug abuse. Her visual acuity was 20/20 in each eye. The intraocular pressure and the anterior segment were normal in each eye. The right fundus was normal. Examination of the left fundus disclosed mul tiple intraretinal hemorrhages and dilated veins (Fig. 3). Fluorescein angiography dis closed normal choroidal filling and a normal arteriovenous transit time. There were multiple blocking defects that corresponded to the intra retinal hemorrhages in the fluorescein angio gram (Fig. 4). Results of neurologic examina tion were normal and the patient denied any residual headaches. There was no late staining of the retinal veins or intraretinal leakage of dye.
Cocaine blocks the transmission of nerve impulses by inhibiting ion movement across the axonal plasma membrane. Systemically, co caine blocks the reuptake of norepinephrine from sympathetic nerve fibers, which increases the availability of norepinephrine at the postsynaptic receptor sites and results in increased vascular tone, increased heart rate, and in creased myocardial contractility. 1 After nasal administration, the user experi ences an intense stimulation after the drug is absorbed through the nasal mucosa. With the increased purity and availability of cocaine, the systemic complications from cocaine abuse have recently increased. 1,2 Methamphetamine is structurally similar to amphetamine and has adrenomimetic actions similar to cocaine. Like the amphetamines, it stimulates the release of norepinephrine from sympathetic nerve terminals, causing a sudden increase in blood pressure, myocardial contrac tility, and stimulation of the central nervous system. 3 Myocardial infarctions in young adults after cocaine use have been attributed to vascu lar spasm and the dramatic increase in sympa thetic tone. 4 Similarly, the dramatic increase in blood pressure induced by cocaine can result in
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sion from c o c a i n e u s e c o u l d also h a v e l e d to central r e t i n a l a r t e r y o b s t r u c t i o n b y c a u s i n g fibrinoid n e c r o s i s w i t h i n t h e vessels or h e m o r rhage under an atherosclerotic plaque within the central retinal artery.9 We t h e o r i z e d t h a t t h e a d r e n o m i m e t i c effect of the n a s a l m e t h a m p h e t a m i n e c o n t r i b u t e d to a s u d d e n i n c r e a s e in b l o o d p r e s s u r e a n d h e m o d y n a m i c c h a n g e s that r e s u l t e d in the i n t r a r e t i n a l h e m o r r h a g e s o b s e r v e d in our s e c o n d p a t i e n t . Retinal h e m o r r h a g e s c o u l d p o s s i b l y r e s u l t from a s u d d e n i n c r e a s e in h y d r o s t a t i c p r e s s u r e w i t h in the smaller r e t i n a l vessels, l e a d i n g to r u p ture.
References
Fig. 4 (Wallace and associates). Case 2. Fluorescein angiogram of the left fundus shows multiple blocking defects corresponding to the retinal hemorrhages.
a s u b a r a c h n o i d h e m o r r h a g e or in c e n t r a l n e r v o u s system infarction, especially in i n d i v i d u a l s w i t h p r e d i s p o s i n g c o n d i t i o n s s u c h as a r t e r i o v e n o u s m a l f o r m a t i o n s or cerebral a n e u r y s m s . 2 C e n t r a l r e t i n a l a r t e r y o c c l u s i o n s , like cere bral infarctions, are typically f o u n d in o l d e r i n d i v i d u a l s a n d are often a s s o c i a t e d w i t h sys temic arterial h y p e r t e n s i o n . 5 Many of the c e n tral r e t i n a l a r t e r y occlusions in o l d e r p e r s o n s are t h o u g h t to occur s e c o n d a r y to e m b o l i from a t h e r o m a t o u s p l a q u e s in the carotid arteries. 5 A r t e r y o c c l u s i o n s in y o u n g e r p a t i e n t s a r e m o r e c o m m o n l y associated w i t h m i g r a i n e , t r a u m a , a n d c o a g u l o p a t h i e s . 6 Vasospasm may h a v e a n i m p o r t a n t role in a r t e r y occlusions in y o u n g p e o p l e . C e n t r a l r e t i n a l a r t e r y occlusion a s s o c i ated w i t h m i g r a i n e - i n d u c e d v a s o s p a s m h a s b e e n described. 7 Similarly, arterial s p a s m m a y b e i n d u c e d b y cocaine 8 a n d may result in d e c r e a s e d ocular perfusion. This may have b e e n the m e c h a n i s m r e s p o n s i b l e for the c e n t r a l r e t i n a l a r t e r y o b s t r u c t i o n in our first p a t i e n t . Severe h y p e r t e n
1. Jaffe, J. H.: Drug addiction and drug abuse. In Gilman, A. G., Rail, T. W., Neis, A. S., and Taylor, P. (eds.): The Pharmacological Basis of Therapeutics, ed. 8. New York, Pergamon, 1990, p. 539. 2. Klonoff, D. C , Andrews, B. T., and Obana, W. G.: Stroke associated with cocaine use. Arch. Neurol. 46:989, 1989. 3. Hoffman, B. B., and Lefkowitz, R. J.: Catecholamines and sympathomimetic drugs. In Gilman, A. G., Rail, T. W., Neis, A. S-, and Taylor, P. (eds.): The Pharmacological Basis of Therapeutics, ed. 8. New York, Pergamon, 1990, p. 186. 4. Isner, J. M., Estes, M., Thompson, P. D., Costango-Nordin, M., Subramarian, R., Miller, G., Katros, G., Sweeney, K., and Sterner, W.: Acute cardiac events temporally related to cocaine abuse. N. Engl. J. Med. 315:1438, 1986. 5. Brown, G. C , and Magargal, L. E.: Central reti nal artery obstruction and visual acuity. Ophthal mology 89:14, 1982. 6. Brown, G. C , Magargal, L. E., Shields, J. A., Goldberg, R. E., and Walsh, P. N.: Retinal arterial obstruction in children and young adults. Ophthal mology 88:18, 1981. 7. Silberberg, D. H., and Laties, A. M.: Occlusive migraine. Trans. Pa. Acad. Ophthalmol. Otolaryngol. 27:34, 1974. 8. Cregler, L. L., and Mark, H.: Medical complica tions of cocaine abuse. N. Engl. J. Med. 315:1495, 1986. 9. Brown, G. C : Retinal arterial obstructive dis ease. In Ryan, S. J. (ed.): Retina, vol. 2. St. Louis, C. V. Mosby, 1989, p. 403.
L.E.: 20/30. The anterior segment was normal in each eye, as was the intraocular pressure. A right afferent pupillary defect was present. Examination of the right fundus showed dif fuse retinal whitening in the posterior pole, with a foveal cherry-red spot and vascular at tenuation consistent with a sudden central reti nal artery occlusion (Fig. 1). No arterial emboli were seen. The left fundus was normal. An anterior chamber paracentesis was imme diately performed and 500 mg of acetazolamide was administered intravenously. The patient was hospitalized for carbogen therapy (breath ing a mixture of 95% oxygen and 5% carbon dioxide for ten minutes every two hours). Results of diagnostic studies, including echocardiography, carotid ultrasonography, and de termination of packed cell volume, were all normal. Fluorescein angiography performed
Case Reports Case 1 A 38-year-old woman had painless loss of vision in her right eye four hours after using cocaine intranasally. She had a history of sys temic arterial hypertension, and was currently being treated with oral propranolol, 80 mg, two times per day, and nifedipine, 10 mg, four times per day. She had no history of migraine head aches. At initial examination, her blood pres sure was 208/114 mm Hg and her pulse rate was 72 beats per minute. No history of intrave nous drug abuse was elicited. Her visual acuity was R.E.: hand motions and Accepted for publication May 13, 1992. From the Retina Service, Wills Eye Hospital, Jefferson Medical College, Thomas Jefferson University, Philadel phia, Pennsylvania. Reprint requests to Gary C. Brown, M.D., 910 E. Willow Grove Ave., Philadelphia, PA 19118.
158
Fig. 1 (Wallace and associates). Case 1. The right fundus demonstrates macular whitening and a foveal cherry-red spot characteristic of a central retinal artery occlusion.
©AMERICAN JOURNAL OF OPHTHALMOLOGY
114:158-160,
AUGUST,
1992
Vol. 114, No. 2
Retinal Manifestations of Cocaine and Methamphetamine
Fig. 2 (Wallace and associates). Case 1. Intravenous fluorescein angiogram of the right eye at 37 seconds after antecubital injection shows a delay in retinal arterial filling, as demonstrated by a leading edge of dye in the proximal arteries.
159
Fig. 3 (Wallace and associates). Case 2. The left fundus shows multiple intraretinal hemorrhages.
Discussion the next day showed a markedly prolonged arteriovenous transit time, as well as late stain ing of the optic nerve (Fig. 2). Case 2 A 26-year-old woman had blurred vision and a spot in front of her left eye for five days at initial examination. Her medical history was unremarkable. She noticed the visual change in her left eye several hours after using metham phetamine nasally. She had no history of intra venous drug abuse. Her visual acuity was 20/20 in each eye. The intraocular pressure and the anterior segment were normal in each eye. The right fundus was normal. Examination of the left fundus disclosed mul tiple intraretinal hemorrhages and dilated veins (Fig. 3). Fluorescein angiography dis closed normal choroidal filling and a normal arteriovenous transit time. There were multiple blocking defects that corresponded to the intra retinal hemorrhages in the fluorescein angio gram (Fig. 4). Results of neurologic examina tion were normal and the patient denied any residual headaches. There was no late staining of the retinal veins or intraretinal leakage of dye.
Cocaine blocks the transmission of nerve impulses by inhibiting ion movement across the axonal plasma membrane. Systemically, co caine blocks the reuptake of norepinephrine from sympathetic nerve fibers, which increases the availability of norepinephrine at the postsynaptic receptor sites and results in increased vascular tone, increased heart rate, and in creased myocardial contractility. 1 After nasal administration, the user experi ences an intense stimulation after the drug is absorbed through the nasal mucosa. With the increased purity and availability of cocaine, the systemic complications from cocaine abuse have recently increased. 1,2 Methamphetamine is structurally similar to amphetamine and has adrenomimetic actions similar to cocaine. Like the amphetamines, it stimulates the release of norepinephrine from sympathetic nerve terminals, causing a sudden increase in blood pressure, myocardial contrac tility, and stimulation of the central nervous system. 3 Myocardial infarctions in young adults after cocaine use have been attributed to vascu lar spasm and the dramatic increase in sympa thetic tone. 4 Similarly, the dramatic increase in blood pressure induced by cocaine can result in
160
August, 1992
AMERICAN JOURNAL OF OPHTHALMOLOGY
sion from c o c a i n e u s e c o u l d also h a v e l e d to central r e t i n a l a r t e r y o b s t r u c t i o n b y c a u s i n g fibrinoid n e c r o s i s w i t h i n t h e vessels or h e m o r rhage under an atherosclerotic plaque within the central retinal artery.9 We t h e o r i z e d t h a t t h e a d r e n o m i m e t i c effect of the n a s a l m e t h a m p h e t a m i n e c o n t r i b u t e d to a s u d d e n i n c r e a s e in b l o o d p r e s s u r e a n d h e m o d y n a m i c c h a n g e s that r e s u l t e d in the i n t r a r e t i n a l h e m o r r h a g e s o b s e r v e d in our s e c o n d p a t i e n t . Retinal h e m o r r h a g e s c o u l d p o s s i b l y r e s u l t from a s u d d e n i n c r e a s e in h y d r o s t a t i c p r e s s u r e w i t h in the smaller r e t i n a l vessels, l e a d i n g to r u p ture.
References
Fig. 4 (Wallace and associates). Case 2. Fluorescein angiogram of the left fundus shows multiple blocking defects corresponding to the retinal hemorrhages.
a s u b a r a c h n o i d h e m o r r h a g e or in c e n t r a l n e r v o u s system infarction, especially in i n d i v i d u a l s w i t h p r e d i s p o s i n g c o n d i t i o n s s u c h as a r t e r i o v e n o u s m a l f o r m a t i o n s or cerebral a n e u r y s m s . 2 C e n t r a l r e t i n a l a r t e r y o c c l u s i o n s , like cere bral infarctions, are typically f o u n d in o l d e r i n d i v i d u a l s a n d are often a s s o c i a t e d w i t h sys temic arterial h y p e r t e n s i o n . 5 Many of the c e n tral r e t i n a l a r t e r y occlusions in o l d e r p e r s o n s are t h o u g h t to occur s e c o n d a r y to e m b o l i from a t h e r o m a t o u s p l a q u e s in the carotid arteries. 5 A r t e r y o c c l u s i o n s in y o u n g e r p a t i e n t s a r e m o r e c o m m o n l y associated w i t h m i g r a i n e , t r a u m a , a n d c o a g u l o p a t h i e s . 6 Vasospasm may h a v e a n i m p o r t a n t role in a r t e r y occlusions in y o u n g p e o p l e . C e n t r a l r e t i n a l a r t e r y occlusion a s s o c i ated w i t h m i g r a i n e - i n d u c e d v a s o s p a s m h a s b e e n described. 7 Similarly, arterial s p a s m m a y b e i n d u c e d b y cocaine 8 a n d may result in d e c r e a s e d ocular perfusion. This may have b e e n the m e c h a n i s m r e s p o n s i b l e for the c e n t r a l r e t i n a l a r t e r y o b s t r u c t i o n in our first p a t i e n t . Severe h y p e r t e n
1. Jaffe, J. H.: Drug addiction and drug abuse. In Gilman, A. G., Rail, T. W., Neis, A. S., and Taylor, P. (eds.): The Pharmacological Basis of Therapeutics, ed. 8. New York, Pergamon, 1990, p. 539. 2. Klonoff, D. C , Andrews, B. T., and Obana, W. G.: Stroke associated with cocaine use. Arch. Neurol. 46:989, 1989. 3. Hoffman, B. B., and Lefkowitz, R. J.: Catecholamines and sympathomimetic drugs. In Gilman, A. G., Rail, T. W., Neis, A. S-, and Taylor, P. (eds.): The Pharmacological Basis of Therapeutics, ed. 8. New York, Pergamon, 1990, p. 186. 4. Isner, J. M., Estes, M., Thompson, P. D., Costango-Nordin, M., Subramarian, R., Miller, G., Katros, G., Sweeney, K., and Sterner, W.: Acute cardiac events temporally related to cocaine abuse. N. Engl. J. Med. 315:1438, 1986. 5. Brown, G. C , and Magargal, L. E.: Central reti nal artery obstruction and visual acuity. Ophthal mology 89:14, 1982. 6. Brown, G. C , Magargal, L. E., Shields, J. A., Goldberg, R. E., and Walsh, P. N.: Retinal arterial obstruction in children and young adults. Ophthal mology 88:18, 1981. 7. Silberberg, D. H., and Laties, A. M.: Occlusive migraine. Trans. Pa. Acad. Ophthalmol. Otolaryngol. 27:34, 1974. 8. Cregler, L. L., and Mark, H.: Medical complica tions of cocaine abuse. N. Engl. J. Med. 315:1495, 1986. 9. Brown, G. C : Retinal arterial obstructive dis ease. In Ryan, S. J. (ed.): Retina, vol. 2. St. Louis, C. V. Mosby, 1989, p. 403.
