Journal of Neuro-Ophthalmology, September 1985, Volume 5, Issue 3

Amaurosis fugax and retinal vasculitis associated with methamphetamine inhalation.

A 26-year-old male drug abuser developed amaurosis fugax followed by retinal vasculitis in the right eye after nasal inhalation of methamphetamine. He gradually recovered, but required prolonged systemic corticosteroid therapy. We believe that the amaurosis fugax was due to drug-induced vasospasm and that the retinal vasculitis was a drug-induced hypersensitivity vasculitis.

J. Clin. Neuro-ophthalmol. 5: 169-176,1985 <D 1985 Raven Press, New York Amaurosis Fugax and Retinal Vasculitis Associated with Methamphetamine Inhalation HAROLD E. SHAW, JR., M.D. JEFFREY G. LAWSON, M.D. R. DOYLE STULTING, M.D., Ph.D. Abstract A 26-year-old male drug abuser developed amau­rosis fugax followed by retinal vasculitis in the right eye after nasal inhalation of methamphet­amine. He gradually recovered, but required pro­longed systemic corticosteroid therapy. We believe that the amaurosis fugax was due to drug-induced vasospasm and that the retinal vasculitis was a drug-induced hypersensitivity vasculitis. Introduction Numerous medical complications of illicit drug use have been documented, but specific ocular complications have been reported infre­quently . To our knowledge, this is the first re­port of amaurosis fugax and retinal vasculitis associated with nasal inhalation of methamphet­amine. Case Report A 26-year-old white male was seen with a his­tory of 8-12 episodes of transient loss of vision in the right eye over the previous 18 hours. Each of the episodes was associated with a vague prodromal tingling sensation on the right side of his head followed by total or near total loss of vision in the right eye lasting 1-2 minutes. Each episode resolved completely and ther.e were no other associated symptoms. ApproXI­mately 36 hours prior to the onset of the visual disturbances he had sniffed methamphetamine mixed with mannitol through his right nostril. The patient had a long history of drug abuse From the Departments of Ophthalmology and Medicine, Greenville Hospital System, GreenvIlle, South CarolIna (HES, }GL); and the Department of Ophthalmology, Emory University Clinic, Atlanta, GeorgIa (RDS). Write for reprints to: Harold E. Sha~, Jr., M.D., 7-B Cleve­land Court, Greenville, South Carohna 29607. September 1985 which included numerous classes of illicit drugs. He smoked marijuana and drank alcohol heavily and used intranasal cocaine and oral amphetamines occasionally, but he had not used drugs intravenously for several years. He had not recently used cocaine intranasally. Twelve years previously he had a left pyelo­plasty for hydronephrosis. On three occasions he was treated for gonorrhea. His sexual con­tacts were strictly heterosexual. His general and ocular health had been good otherwise. Ocular examination on February 15, 1983, re­vealed 20/20 visual acuity in each eye. Confron­tation and tangent screen visual field testing, external, pupillary, motility, slit lamp, and di­lated ophthalmoscopic examinations were normal. Tensions by applanation were 18 mm of mercury in each eye. The patient was ob­served and after several hours he experienced sudden loss of vision with no light perception in the right eye. During the episode indirect ophthalmoscopy revealed generalized attenua­tion of the retinal arterioles in the right eye which lasted 45-60 seconds. As he began re­gaining vision, the retinal arterioles pulsated briefly and then returned to their normal cal­iber. No emboli were seen. Vision returned to 20/20 with no residual abnormal findings at that time (Fig. 1). Over the next 24 hours he expe­rienced several more brief episodes at amau­rosis in the right eye and then became asymp­tomatic. Three days later he awakened with per­sistent blurred vision in the right eye. Upon reexamination on February 21, his visual acuity was still 20/20 in each eye. Ophthalmoscopic ex­amination revealed prepapillary vitreous cells, mild optic disc edema, irregular venous. dilata­tion, and fluffy white penvenous depOSits and sheathing in the posterior pole of the right eye (Fig. 2). The retinal periphery was normal. ~ fluorescein angiogram showed segmental pen­venous leakage in the right eye (Fig. 3). The left eye was normal. General physical examination 169 Methamphetamine Inhalation (b) Figure la and lb. Ocular iundi iollowing amaurotic attack in the right eye. Note normal appearance in both eyes. disclosed no abnormalities. Treatment was started with prednisone 80 mg daily. A complete blood count, urinalysis, erythro­cyte sedimentation rate, biochemical profile, an­tinuclear antibodies, rheumatoid factor, hepa­titis B antigen, serum cryoglobulins, serum protein electrophoresis, fungal serologies, tox-oplasmosis titer, fluorescent treponemal anti­body absorption test, urine culture for cytomeg­alovirus, immune complex Clq binding test, Raji cell immunoassay, and C4 levels were all normal. C3 levels were decreased to 63 mg/dl (n 83-177 mg/dl). The HLA type was A26, A28, B14, and Bw53. A tuberculin skin test was non- Journal of Clinical Neuro-ophthalmology Shaw, Lawson, Stuiting lAi) (b) Figure 2a and 2b. Right fundus at onset of retinal vasculitis. Note blur­ring of optic disc. irregular venous caliber. and perivenous dl'Pllsits ,lnJ sheathing. reactive. Blood cultures showed no growth. x­ray films of the chest and sacroiliac joints showed normal findings. An echocardiogram and a computerized axial tomogram of the brain and orbits with contrast enhancement were normal. September 1985 Over a 1O-week period, the patient's ocular inflammation improved. C3 levels returned to normal. With tapering of prednisone to 10 mgt day in May, vitreous haze increased and new perivenous deposits and hemorrhages, irregu­larities of venous caliber, and focal chorioretinal 171 Methamphetamine Inhalation Figure 3. Fluorescein angiogram of right fundus. late phase. shows perivenous staining. (al Figure 4a-c. Right fundus :.1 months after onset of retinal vasculitis. Note prepapillary vitreous haze. irregular wnous caliber. and perivenous hem­orrhages and infiltratt'S. 172 Journal of Clinical Neuro-ophthalmology Shaw, Lawson, Stulting Ibl Ie) infiltrates developed in the right eye (Fig. 4). Prednisone was increased to 60 mg daily and he improved. He did well until October, when prednisone was tapered to 20 mg daily and he again developed increased vitritis, perivascu­litis, and chorioretinitis in the right eye. Pred­nisone was increased to 80 mg daily and he again improved. He was treated with a gradu­ally tapering dosage of prednisone over the next September 1985 6 months, during which time the inflammation was controlled, leaving preretinal gliosis and macular pigmentary changes in the right eye (Fig. 5). The left eye remained normal and no other systemic abnormalities developed. During that time he continued to drink alcohol and smoke marijuana, but he abstained from other drugs. Prednisone was discontinued and when the patient was last examined on April 17, 1984 173 Methamphetamine Inhalation Figure 5. Right fundus 14 months after onset of retinal vasculitis shows preretinal gliosis and macular pigment changes. There is no active in­flammation. his visual acuity ..",as 20/20 and there was no evidence of active ocular inflammation. Discussion Methamphetamine is a member of the am­phetamine group of sympathomimetic amines. It is a potent central nervous system stimulant and has been used extensively by drug abusers for its euphoric effects. A variety of psychiatric and medical complications have been attributed to methamphetamine but, to our knowledge, no complications related to intranasal methamphet­amine use have been described. I In our patient, this unconventional route of administration ap­peared to playa major role in the initiation of ocular events. Within 36 hours of recreationally inhaling methamphetamine through his right nostril he began having multiple attacks of amaurosis fugax in the right eye. The exact mechanism by which this occurred is specula­tive. Amaurosis fugax usually signifies extra­cranial carotid occlusive disease, but other causes such as migraine, cardiac disease, and collagen vascular disorders are more likely in younger patients. 2- tl No underlying systemic abnormality was identified in our patient. Blind­ness due to retinal emboli from intranasal injec­tions has been well documented, and in some cases vasospasm without emboli has been pos­tulated. 9 - 11 The anterior and posterior ethmoid- 174 al arteries are branches of the ophthalmic ar­tery and it is thought that retinal embolization occurs by retrograde flow through these anas­tomoses under the pressure of forceful intraar­terial injection. In the absence of direct intra­vascular injection, however, this mechanism seems implausible in our patient. A more likely explanation is that the amaurosis fugax resulted from vasospasm due to the sympathomimetic effects of methamphetamine. The amphet­amines are potent vasoconstrictors and diffuse vascular spasm after their ingestion have been described. 12 We postulate that a similar local­ized effect might have been precipitated by in­tranasal methamphetamine. Another possible explanation, in view of subsequent develop­ments, is that the amaurosis fugax was due to vasospasm induced by vascular irritation asso­ciated with incipient retinal vasculitis. Whatever the mechanism, we believe that the time rela­tionship between drug inhalation and onset of ocular symptoms, the proximity of the nasal ab­sorption site to the ocular circulation, and the known pharmacologic properties of metham­phetamine strongly implicate this agent as the cause of amaurosis fugax in our patient. Among the complications associated with methamphetamine abuse is a necrotizing angitis which involves mainly small and medium-sized arteries and has clinical, arteriographic, and his­topathologic features strikingly similar to poly­arteritis nodosa. 13 -18 Ocular involvement has Journal of Clinical Neuro-ophthalmology been mentioned, but not well documented in some of these casesY·14 Our patient developed retinal vasculitis in the right eye within 1 week after he inhaled methamphetamine, and we were able to observe him closely over an ex­tended period of time. The differential diag­nosis of retinal vasculitis includes nonspecific uveitis, ocular sarcoidosis, collagen vascular disorders, Eales' disease, pars planitis, Behcet's disease, infectious retinochoroiditis such as syphilis and toxoplasmosis, early bacterial en­dophthalmitis, perivasculitis associated with any severe intraocular intlammation, and cho­rioretinal emboli. 1'1-23 Our patient had none of these conditions. The retinal vasculitis which we observed was primaril~' a retinal phlebitis which was concen­trated in the posterior pole of the eye and which was characterized by perivenous cuffing and sheathing, venous irregularities, retinal hem­orrhages, exudates and edema, posterior vi­tritis, and ultimately preretinal gliosis and mac­ular pigmentary changes. Early in the course of the vasculitis fluorescein angiography showed segmental leakage from retinal veins. Associ­ated with the vasculitis was a transiently de­creased C3 level. Ffytche has reviewed the clin­ical signs of retinal vasculitis and emphasized that most cases involve an immune complex dis­turbance affecting the retinal veins. 24 We believe that the findings in our patient were consistent with an immune complex mediated retinal vas­culitis precipitated by methamphetamine inha­lation. The evidence is now substantial that most vasculitis syndromes are related to deposition of immune complexes in vessel walls. 25 The con­ditions necessary for this to occur have been delineated in experimental models and involve the formation of soluble antigen-antibody com­plexes under conditions of antigen excess. In­creased vascular permeability via platelet de­rived vasoactive amines, IgE mediated reac­tions, or other mechanisms leads to the deposition of immune complexes in vessel walls. Complement is activated, and polymor­phonuclear leukocytes are attracted by chemo­taxis to the site of immune complex deposition. There the polymorphonuclear leukocytes re­lease proteolytic enzymes which cause necrosis of the vessel wall. This can result in vascular occlusion, hemorrhage, and ischemia of sur­rounding tissues. 25 - 28 The concentration of im­mune complexes in the circulation, the duration of their circulating half-life, the physical char­acteristics of the complexes, and the site of their deposition are factors which influence the re­sulting disease activity. Circulating immune complexes were not identified in our patient, September 1985 Shaw, Lawson, Stulting but that does not preclude immune complex mediated disease since complexes are often rap­idly cleared from the circulation and may not be detectable. 25 We suggest that ischemia from vaso­spasm may have increased retinal vascular permeability, leading to the localized deposition of immune complexes and subseguent vascu­litis. Although there is considerable overlap in the vasculitic syndromes, we believe that our case is best classified as a hypersensitivity vascu­litis. 25,28 The hypersensitivity vasculitis syn­dromes are thought to be initiated by immune complex deposition and characteristically in­volve small vessels. A precipitating antigen, such as a drug, can generally be identified. Signs and symptoms usually develop within 1 week to 10 days after antigen exposure. Al­though the skin is most commonly involved, hypersensitivity vasculitis can affect any organ. The condition is usually self-limited, but can recur or become chronic. Treatment consists of removal of the offending antigen and use of cor­ticosteroids in some cases, although no thera­peutic modality has universally proven efficacy. Systemic corticosteroid therapy appeared ben­eficial in our patient, but prolonged treatment was reguired. As others have pointed out in describing com­plications attributed to methamphetamine, the multiplicity of substances used by most drug abusers and the potential contamination and lack of purity of those substances make it diffi­cult to identify positivelr. a single drug as the cause of a complication. 1 -15 Whether the ocular events in our patient were due to the direct ef­fect of methamphetamine or whether other factors might have been involved cannot be de­termined with absolute certainty. The circum­stantial evidence is strong; however, metham­phetamine taken intranasally can cause serious ocular conseguences. References 1. Yatsu, F. M., Wesson, D. R., and Smith, D. E.: Amphetamine abuse. In Medical Aspects of Drug Ahl/se, R. W. Richter, Ed. Harper & Row, Pub­lishers, Hagerstown, Maryland, 1975, pp. 50-56. 2. Walsh, F. B., and Hoyt, W. F.: Clil/ical Nel/ro-oph­thalmology (3rd ed.). Williams & Wilkins, Balti­more, 1969, pp. 1671- 1672; 1806. 3. Kearns, T. P.: Ophthalmology and the carotid ar­tery. Am. J. Ophthalmol. 88: 714-722, 1979. 4. Caltrider, N. D., Irvine, A. R., Kline, H. J., and Rosenblatt, A.: Retinal emboli in patients with mitral valve prolapse. Am. f. Ophthalmol. 90: 534­539, 1980. 5. Lesser, R. L., Heinemann, M. H., Borowski, H., 175 Methamphetamine Inhalation and Cohen, L. S.: Mitral valve prolapse and amaurosis fugax. ,. Clill. Ncuro-ophthalmol. 1: 153- lhO, IYH I. 6. Shaw, H. E., Osher, R. H., and Smith, J. L.: Amaurosis fugax associated with SC hemoglo­binopathy and lupus erythematosus. Am. f. 0l'hthollllol, 87: 2HI-2H5, 1979. 7. Glaser, J. S.: Topical diagnosis: Prechiasmal vi­sual pathways. In Clillical Ophthalmology, Vol. 2, T. D. Duane and E. A. Jaeger, Eds. Harper & Row, Publishers, Philadelphia, 1982, chap. 5, pp.6-9. 8. Troost, B. T.: Migraine. In Clinical Ophthalmology, Vol. 2, T. D. Duane and E. A. Jaeger, Eds. Harper & Row, Publishers, Philadelphia, 1982, chap. 19, pp. 11-12. 9. Byers, B.: Blindness secondary to steroid injec­tions into the nasal turbinates. Arch. Ophthalmol. 97: 79-80, 1979. 10. Evans, D. E., Zahorchak, J. A., and Kennerdell, J. S.: Visual loss as a result of primary optic nerve neuropathy after intranasal corticosteroid injec­tions. Am, f. Ophthalmol. 90: 641-644,1980. 11. Mabry, R. L.: Visual loss after intranasal corti­costeroid injection. Arch, Otolaryngol. 107: 484­486, 1981. 12. Bowen, J. S., Davis, G. B., Kearney, T. E., and Bardin, J.: Diffuse vascular spasm associated with 4-bromo-2, 5-dime-thoxyamphetamine ingestion. JAMA 249: 1477-1479, 1983. 13. Citron, B. P., Halpern, M., McCarron, M., Lund­berg, G. D., McCormick, R., Pincus, 1. J., Tatter, D., and Haverback, B. J.: Necrotizing angiitis as­sociated with drug abuse. N. Engl. f. Med. 283: 1003-1011,1970. 14. Halpern, M., and Citron, B. P.: Necrotizing an­giitis associated with drug abuse. AJR 111: 663­671, 1971. 15. Margolis, M. T., and Newton, T. H.: Metham­phetamine ("speed") arteritis. Neuroradiology 2: 179-182,1971. . 16. Rumbaugh, C. L., Bergeron, R. T., Fang, H. C. H., and McCormick, R.: Cerebral angio- 176 graphic changes in the drug abuse patient. Ra­diology 101: 335-344, 1971. 17. Rumbaugh, C. L., Bergeron, R. T., Scanlan, R. L., Teal, J. S., Segall, H. D., Fang, H. C. H., and McCormick, R.: Cerebral vascular changes secondary to amphetamine abuse in the experi­mental animal. Radiology 101: 345-351, 1971. 18. Yu, Y. J., Cooper, D. R., Wellenstein, D. E., and Black, B.: Cerebral angiitis and intracerebral hem­orrhage associated with methamphetamine abuse. f. Neurosurg. 58: 109-111, 1983. 19. Duke-Elder, S., and Dobree, J. H.: Diseases of the retina. In System of Ophthalmology, Vol. 10, S. Duke-Elder, Ed. C. V. Mosby, St. Louis, 1967, pp. 218-233. 20. Wise, G. N., Dollery, C. T., and Henkind, P.: The Retinal Circulation. Harper & Row, Hagerstown, Maryland, 1971, p. 208. 21. Yanoff, M., and Fine, B. S.: Ocular Pathology. A Text and Atlas, Harper & Row, Hagerstown, Maryland, 1975, p. 73. 22. Patrinely, J. R., Green, W. R., and Randolph, M. E.: Retinal phlebitis with chorioretinal em­boli. Am. f. Ophthalmol. 94: 49-57, 1982. 23. Packer, A. J., Weingeist, T. A., and Abrams, G. W.: Retinal periphlebitis as an early sign of bacterial endophthalmitis. Am. f. Ophthalmol. 96: 66-71, 1983. 24. Ffytche, T. J.: Retinal vasculitis: A review of the clinical signs. Trans. Ophthal. Soc. U.K. 97: 457­461, 1977. 25. Fauci, A. S., Haynes, B. F., and Katz, P.: The spectrum of vasculitis: Clinical, pathologic, im­munologic, and therapeutic considerations. Ann. Intern. Med. 89: 660-676, 1978. 26. Cochrane, C. G.: Mechanisms involved in the deposition of immune complexes in tissues. f. Exp. Med. 134: 75s-89s, 1971. 27. Cochrane, C. G., and Koffler, D.: Immune com­plex disease in experimental animals and man. Adt'. ImmwlOl. 16: 185-264, 1973. 28. Moor~, P: M., and Cupps, T. R.: Neurological complications of vasculitis. Ann. Neurol. 14: 155­167, 1983. Journal of Clinical Neuro-ophthalmology