CENTRAL RETINAL ARTERY OCCLUSION RICHARD E. APPEN, M.D.,
SHIRLEY H. WRAY, M.D.,
DAVID G. COGAN,
AND
M.D.
Boston, Massachusetts
Von Graefe1 described the classic clinical picture of an acute occlusion of the central retinal artery (CRA) in 1859. He pointed out the early ophthalmoscopic findings that he observed in a man who had suddenly lost vision in his right eye seven days previously. Von Graefe described the pale disk, attenu ated arteries and veins, and the cloudy retina that produced the macular cherry-red spot (kirsch-rother Fleck). A few days later, he noted segmental flow in this patient's retinal vessels that gradually improved, but without recovery of visual acuity. He deduced that the blindness and ophthalmoscopic signs were the result of obstruction of the retinal circu lation, and concluded that the cause in this man, who had aortic valve disease, was an embolus blocking the CRA. Many subsequent reports discussing the etiology and sequelae of retinal vascular dis ease2"6 have been misleading because the au thors combined venous and branch arterial occlusions with acute CRA occlusions de spite their differences in onset, course, and etiology. What has remained unclear over the years is the relationship between CRA occlu sions and coexisting cerebral and extracranial vascular disease and cardiovascular disorders. The risk of a cerebral stroke or involvement of the second eye has not been clarified. For this reason, we undertook a retrospective study of patients with CRA occlusion to de termine the incidence of subsequent cerebrovascular accidents or a second CRA occlusion, From the Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. This study was supported by a grant from The Seeing Eye, Inc., Morristown, New Jersey. This study was presented in part at the Uni versity of Wisconsin Ophthalmology Alumni Meeting, Sept. 6, 1974. Reprint requests to Richard E. Appen, M.D., Department of Ophthalmology, University Hos pitals, 1300 University Ave., Madison, WI 53706.
unsuspected underlying carotid artery dis ease, cardiac valvular disease, or other medical disorders that might cause CRA occlusion. PATIENTS
At least one of us diagnosed 64 cases of acute CRA occlusion between 1945 and 1973. The etiology of the 54 patients in this study was apparent at the initial examination or follow-up information was later obtained. Follow-up examination was performed by one of us or by the patient's ophthalmologist, optometrist, or the Massachusetts Eye and Ear Infirmary Clinic. Questionnaires were also sent to the patients to supplement the physicians' reports. RESULTS
The ages of the 54 patients at the onset of the CRA occlusion ranged from 17 to 84 years, averaging 54.3 years, with a median of 57 years. Fifty-seven percent of the pa tients were men. The - right eye was involved in 55,% of the patients. The preponderance of men has been found in previous studies, but the average age at onset has been con siderably older.3'5'7 Ten patients in our group were under 40 years of age at the onset of the ocular arterial occlusion. Because of the differences in the incidence and type of vascular disease in young and older patients, we elected to divide our patient material into two groups for analysis: patients older than 40 years of age, and patients under 40 years of age. Older patients with CRA occlusion— Forty-four patients were included in the group over 40 years of age. The age of onset ranged from 40 to 84 years (Table 1), with an average of 60.7 years (median of 59 years), an age more comparable to that of prior reports. 3 ' 5 ' 7 Fifty-five percent of the patients were men. The right eye was in-
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375
TABLE 1 PATIENTS OVER 40 YEARS OF AGE AT ONSET OF CRA OCCLUSION* Case, Age at Onset, Sex
E
Date of Onset (mo/yr)
Duration of Follow-Up (yrs)
4/1949
3D
Associated Disease at Onset Alcoholism; simultaneous left hemiparesis with CRAO; died of unknown cause, 1952 DM; hypertension; syphilis; sickle trait DM; ASVD
1.40, F
R.E.
2. 64, M
L.E.
4/1969
3. 82, M
L.E.
10/1963
4. 71, F
R.E.
10/1967
5
5, 46, M
R.E.
6/1955
17D
6, 51. M
L.E.
9/1945
17D
7. 65. M
R.E.
2/1966
None
8. 41, F
R.E.
8/1965
Systemic lupus erythematosus
9. 65, M 10, 67, M
R.E. R.E.
7/1964 6/1972
7mo 2JD
9 1
None RHD with MS; died of CHF, 1/1972 Syphilis
11. 54, M
R.E.
1/1972
18 mo
12, 63. M
R.E.
10/1972
3mo
13, 71, M 14, 54, M 15, 44, M
L.E. L.E. L.E.
11/1960 S/1968 2/1959
13 5 SD
16, 61, F
L.E.
10/1961
8D
Right ICA stenosis General ASVD; old occipital infarct; CRAO at angiography Occurred after closure of Pop pen clamp for aneurysm Calcified aortic valve with LVH AS None RHD with Al, AS; died of CHF. 1964 RHD with AS, AI. MR
17. 59, F
R.E.
1/1966
7
None
18. 79. M 19. 57, M 20. 45, F 21. 52. M 22. 58, M 23. 57, M
R.E. L.E. R.E. L.E. R.E. L.E.
10/1972 5/1961 1/1959 3/1949 2/1973 6/1962
10 mo 12 14 3D 6mo 18moD
24, 61, F
L.E.
12/1966
6D
25, 65. M 26. 69, M
R.E. R.E.
4/1972 9/1968
18 mo 4D
27, 70, F
R.E.
1/1962
6D
28, 67, F
L.E.
10/1962
9D
29, 30, 31, 32,
54, F 58, M 82, F 84. M
L.E. R.E. R.E. R.E.
10/1965 10/1951 12/1971 10/1969
33, 68. F 34. 44. M
L.E. R.E.
2/1973 4/1967
8 4} 2 4 6mo 5
AS RHD with MR. MS RHD with AS. AI, MS AS AS with CHF Hypertension; history of left hemiparesis, 1954; died of MI, 12/1963 Hypertension; died of cere bral hemorrhage. 1/1973 Hypertension; alcoholism Hypertension: died of corpus callosum glloblastoma, 5/1972 Hypertension; died of un known cause, 5/1968 + STS: hypertension; history of severe asthma; died of unknown cause, 1/1972 Hypertension Hypertension; CHF Hypertension History of MI; cardiac pacer placed 5/1969 Cardiac arrhythmia Sickle cell-thalassemia hemoglobinopathy
Subsequent Cerebrovascular Acddentt
Second Eye Involved
+ ; died of left cerebral infarct, 11/1969 + ; died with aphasia, right hemiparesis, 5/1966 + ; left hemiparesis, 6/1972 + ; left hemiparesis. 1969 + ; loss of R.E. visual acuity, right hemiplegia 2 wks after L.E. occlusion + ; loss of left ear hear ing, 1966; right ear, 1973 + ; had right hemiplegia 1 day after R.E. CRAO
+ : R.E.. 1955; L.E., 1959 + ; L.E., 1961; R.E., 1964 + ;R.E„ 1/1966: L.E., BRAO, 12/1966
+ ; unknown
* Definitions include AI. aortic insufficiency: AS, aortic stenosis; ASVD. atherosclerotic vascular disease: BRAO, branch retinal artery occlusion; CHF. congestive heart failure; CRAO, central retinal artery occlusion: D, followed up until death: DM. diabetes mellitus: ESR. erythrocyte sedimentation rate; ICA. internal carotid arterj': LVH. left ventricular hypertrophy; MI, myocardial Infarction: MR, mitral régurgitation; MS, mitral stenosis; RHD. rheumatic heart disease; and STS, serologie test for syphilis. f -f- indicates evidence of cerebrovascular accident.
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MARCH, 197S
TABLE 1 (Continued) Case, Age at Onset, Sex
Eye
Date of Onset (mo/yr)
Duration of Follow Up (yrs)
35, 74, F
L.E.
11/1968
5
36, 61, F
R.E.
3/1968
5i
37, 57, F 38, 52, F
L.E. R.E.
9/1961 11/1957
11
39, 56, F 40, 64, F 41, 51, M 42, 54, M 43, 74, F
L.E. R.E. R.E. R.E. R.E.
8/1964 4/1969 8/1962 1/1969 5/1967
44, 61, F
L.E.
6/1958
8D
9 4 11 4 6moD
Associated Disease at Onset
Subsequent Cerebrovascular Accidentt
Second Eye Involved
Temporal arteritis, biopsy specimen positive; ESR, 78 mm/hr Temporal arteritis, biopsy specimen negative; ESR, 68 mm/hr Idiopathic vasculitis None; DM 1 mo later; died of CHF 8 yrs later None ; doing well at follow-up None; doing well at follow-up None; doing well at follow-up None; doing well at follow-up None; died of pulmonary edema in 11/1967 None; doing well at follow-up
volved in 59% of the cases. After an aver age follow-up of 6.1 years, 15 patients (34%) had died. The follow-up of the 29 survivors was 6.2 years. There was no sig nificant difference in the average age at on set of those dead or those still alive at followup. CEREBROVASCULAR ACCIDENT—Eight of
the 44 patients ( 18%) had a cerebrovascular accident. In one case (Case 1), a contralateral hemiparesis occurred simultaneously with the CRA occlusion. Unfortunately, ophthalmodynamometry, auscultation for carotid bruits, and angiography were not performed in 1949 when this patient was studied. In three other patients, a subsequent contralateral hemiparesis developed seven months (Case 2), 29 months (Case 3), and five years (Case 4) after the CRA occlusion, suggesting that the cerebral stroke repre sented extension of disease in the extracranial internal carotid artery. In two of these three patients, however, there was evidence of wide spread systemic vascular disease. Carotid angiography was not performed in these three patients. The remaining four patients had a stroke, one presumably embolie from heart disease. A 46-year-old man (Case 5) with rheu matic mitral stenosis had a CRA occlu sion of his right eye in June 1955, and a left hemiparesis six years later. A 51-year-old man (Case 6) had syphilitic arteritis, the
apparent cause of a CRA occlusion of his left eye, followed two weeks later by a right hemiparesis and loss of vision in his right eye. He died 17 years later of an unknown cause. The third patient in this group was a 65-year-old man (Case 7) with a CRA oc clusion of his right eye in February 1966, sudden loss of hearing (attributed to internal auditory artery occlusion) of the left ear that same year, and of the right ear seven years later. A 41-year-old woman (Case 8) had a remarkable history of separate episodes of phlebitis, idiopathic thrombocytopenic purpura, pulmonary embolism, and myocardial infarctions—all complications of sys temic lupus erythematosus. She then devel oped right hemiparesis and aphasia, with loss of visual acuity of the right eye, coma, and choreiform movements of the left limbs several hours later. Having been maintained on continuous anticoagulants, she had re covered well neurologically eight years later except for permanent blindness of the right eye. The neurologic dysfunction was the re sult of a hypercoagulable state related to her underlying disease. CAROTID ARTERY DISEASE—Five of the 44
patients (11%) had ipsilateral carotid artery disease associated with a CRA occlusion; three had no cerebral signs or symptoms. One (Case 9) was a 65-year-old man seen in July 1964, who had, in addition to a CRA occlusion of the right eye, a bright
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CENTRAL RETINAL ARTERY OCCLUSION
cholesterol plaque in the right fundus, de creased ophthalmodynamometry in the right eye, and bilateral carotid bruits. Carotid angiography revealed 90% stenosis of the right internal carotid artery, and 15% steno sis of the left internal carotid artery. In January 1965, he underwent right carotid endarterectomy. His right eye was enucleated five months after the occlusion because of glaucoma, but histologie examination did not permit clarification of the mechanism for the occlusion (thrombotic vs. embolie). In November 1970, he was evaluated elsewhere because of ill-defined visual impairment of his left eye, and repeat angiography re vealed severe stenosis of the left internal carotid artery with a normal right carotid system. He therefore underwent left carotid endarterectomy in December 1970. In Sep tember 1971, a retinal detachment of the left eye was observed, possibly providing the explanation for his visual complaints prior to the second endarterectomy. These were the only neurologic complications in a nineyear follow-up since the initial CRA occlu sion. Another patient (Case 1) had had amaurosis fugax prior to the onset of simultaneous CRA occlusion and contralateral hemiparesis. In two patients, the CRA occlusions were iatrogenic. In one (Case 10), the event oc curred during carotid angiography when an embolus, probably originating from an atheromatous segment of the stenotic intracavernous portion of the ipsilateral internal carotid artery, blocked the CRA. In the other patient (Case 11), an ipsilateral CRA occlusion occurred two days after the final turn of a Poppen clamp applied to the right common carotid artery in treating a right anterior communicating artery aneurysm. A fifth patient (Case 2) had a low retinal diastolic pressure on the left side. Ophthal modynamometry was performed when a right hemiparesis occurred seven months after a CRA occlusion of the left eye. Of these five patients with carotid artery disease, three had had amaurosis fugax prior to
CRA occlusion, and two had visible retinal emboli. RETINAL EMBOLI—Six patients had
an
embolus visible in the retinal vessels at the time of the CRA occlusion. Two patients (Cases 9 and 10) had stenotic internal carotid disease. Two others (Cases 12 and 13) had aortic stenosis. Another patient (Case 4) with an embolus developed a con tralateral hemiparesis five years after the CRA occlusion. The sixth patient (Case 14) was unchanged five years later. BILATERAL
CRA
OCCLUSION—Bilateral
CRA occlusion has rarely been reported*·9 but it occurred in three patients in this older group. Two of these patients (Cases 15 and 16) had known rheumatic heart disease, and the other had syphilitic arteritis (Case 6). A fourth patient had a branch artery occlusion in the second eye (Case 17) and the cause was presumably embolie. CARDIAC
VALVULAR
DISEASE—Ten
of
these patients (Cases 5,12,13,15,16, and 1822) had evidence of significant cardiac valvu lar disease involving the aortic valve in eight and the mitral valve in four patients (both valves in some). Two of the patients with rheumatic valvular disease experienced bi lateral CRA occlusion. Six of the ten pa tients with valvular disease had the occlusion in the right eye, the same frequency as in the 34 patients without valvular disease (21/34 or 62%). Amaurosis fugax was an infrequent symptom in this group. Only two of the ten patients with valvular disease had had episodes of transient monocular blurring prior to the total occlusion, as opposed to 11 of the 34 (33%) patients without valvular disease, and to three of the five patients with carotid artery stenosis. Only one of the ten patients with valvular disease had hyperten sion (160/100 or higher; or systolic pres sure above 200 mm H g ; or a history of hypertension and currently under therapy) ; whereas, of the 34 patients without valve disease, ten (30%) had hypertension. ASSOCIATED MEDICAL DISORDERS—A num-
AMERICAN JOURNAL OF OPHTHALMOLOGY
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MARCH, 1975
(Case 4) sustained a left hemiplegia five years after the ocular vascular accident. Of the other two, one (Case 44) was doing well seven years after the CRA occlusion, and the other (Case 17) had had a transient branch artery occlusion in her good eye 11 months after the original CRA occlusion, but was unchanged and doing well six years after that. Of the four with normal choles terol levels, two had cardiac valve disease, one had syphilitic arteritis, and the fourth had generalized atherosclerosis.
ber of the patients had an associated medical disorder, generally related to systemic vascu lar disease or abnormal blood coagulability. Eleven of the 44 had hypertension; three had prior myocardial ischemie disease; and three had other atherosclerotic vascular dis ease. Two (Cases 2 and 34) had hemoglobinopathies, and three (Cases 2, 6, and 28) had positive serologie tests for syphilis. One (Case 8) had a presumptive hypercoagulopathy as a complication of systemic lupus erythematosus. Two patients (Cases 35 and 36) had typical temporal arteritis revealed by biopsy specimen in one. One (Case 37) had systemic vasculitis unrelated to temporal arteritis. Only three patients (Cases 2, 3, and 38) had diabetes mellitus. Of the nine patients tested, five (Cases 4, 17, 23, 24, and 44) had serum cholesterol levels of 250 mg/100 ml or higher. Of the five patients with hypercholesterolemia, three had no other associated abnormalities, one was hypertensive, and the other had gen eralized arteriosclerotic vascular disease; at follow-up, two patients (Cases 23 and 24) had died of vascular disease 18 months and six years after the occlusion. One patient
No ASSOCIATED DISEASE—Seven patients
(16%) had no associated disease at the time of onset of CRA occlusion. After an aver age follow-up of 6.1 years, five were doing well. The other two had had debilitating vascular accidents, resulting in death from cardiac failure in one and in bilateral deaf ness due to occlusions of the internal audi tory arteries in the other. Younger patients with CRA occlusion— Ten patients under 40 years of age had CRA occlusion (Table 2 ) . The average age was 25.8 years, ranging from 17 to 39 years of age. Seven of the patients were men. Four of the occlusions involved the right eye. The
TABLE 2 PATIENTS UNDER 40 YEARS OF AGE AT ONSET OF CRA OCCLUSION*
Duration of Follow-Up (yrs)
Eyet
Date of Onset (mo/yr)
27, F 18, M 30, M 20, M 17, M 18, F 39, M
L.E. R.E. L.E. R.E. L.E. L.E. R.E.
8/1951 7/1962 2/1959 11/1959 12/1966 6/1964 8/1961
52, 31, F
R.E.
3/1972
1J
53, 19, M 54, 39, M
L.E. L.E.
7/1972 10/1971
1 2
Case, Age at Onset, Sex 45, 46, 47, 48, 49, 50, 51,
22 11 14 14 6 9 mo 1|D
Associated Disease at Onset
No disease; pregnant; well at follow-up No disease ; vigorous dancing; well at follow-up None; doing well at follow-up None; doing well at follow-up Left àtrial myxomat Marian's syndrome with MR Polycythemia with atrial fibrillation, CHF; died of pulmonary embolism, 2/1963 Presumed hypercoagulopathy, on oral anovulatory agent Orbital compressive syndrome while stuporous Hypertension; traumatic paraplegia
* Definitions include CHF, congestive heart failure; CRAO, central retinal artery occlusion; D, followed up until death ; and MR, mitral régurgitation f Fellow eyes did not become involved. t Subsequent cerebrovascular accident; simultaneous right hemiparesis with central retinal artery occlusion, L.E.
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follow-up period ranged from one to 22 years, and averaged 8.2 years (median of six years) excluding the patient who was dead at follow-up. CEREBROVASCULAR ACCIDENT—One of
the
ten younger patients had a subsequent stroke. The patient, a 17-year-old boy (Case 49), was admitted with fever and a holo systolic cardiac murmur initially attributed to bacterial endocarditis. He developed simultaneous embolie occlusion of the left CRA and the left middle cerebral artery and, two weeks later, bilateral occlusions of the femoral arteries as complications of a left atrial myxoma. CAROTID ARTERY DISEASE—None of
the
ten patients in this younger group had extracranial carotid artery disease. RETINAL EMBOLI—Retinal emboli were not observed in any of these patients. BILATERAL CRA OCCLUSION—None of the
ten younger patients had bilateral CRA oc clusion. CARDIAC VALVULAR DISEASE—Three of
the ten patients had cardiac disease. One pa tient developed an initially unsuspected atrial myxoma. An 18-year-old woman (Case 50) had Marian's syndrome and mitral insuffi ciency. The third patient was a 39-year-old man with polycythemia, myocardial ischemie disease, and atrial fibrillation. ASSOCIATED MEDICAL DISORDERS—Three
of the ten patients had other disorders. One was a 39-year-old man (Case 54) with mild hypertension of 160/100. A 31-year-old woman had presumptive hypercoagulopathy (Case 52). Following a CRA occlusion and auscultation of a holosystolic cardiac mur mur, she underwent cardiac catheterization. She occluded the brachial artery at the site of entry of the catheter eight hours, two days, and nine months after the study, re quiring endarterectomy on each occasion. Otherwise, she was doing well 1^2 years after the original CRA occlusion. A 19year-old man (Case 53) had a monocular CRA occlusion after prolonged orbital com pression due to his face resting against his
379
knees while in a drug-induced stupor. No
ASSOCIATED DISEASE—Four patients
had no apparent cause for CRA occlusion at initial evaluation. One of them (Case 45) was pregnant at the time of the occlusion, but she had uncomplicated pregnancies and was well at follow-up 22 years later. An other patient (Case 46) was vigorously dancing the twist in a contest (which he won) when he noticed a flash of light and loss of vision in his right eye. He was well 11 years later. Two other patients (Cases 47 and 48), with no related condition or ac tivity at onset, were well and unchanged 14 years later. DISCUSSION
The significance of a CRA occlusion clearly depends on its pathogenesis. In the mid-1800s, embolism was stressed as the usual cause but in the early 1900s, throm bosis of the CRA was thought to be the usual mechanism. Even in recent series of CRA occlusions, embolism was the stated cause in only two of 62 cases,3 in two of 26 cases,2 and in two of 117 cases.5 Most recently, emphasis is shifting back to em bolism as the more frequent mechanism, especially arising as platelet conglomerates or atherosclerotic fragments from plaques in the carotid arteries. 8-10 Most histologie re ports have described emboli,10-16 though two reports depict probable thromboses.5'17 Be cause of the rarity in obtaining a specimen soon after the occlusion if there is no other active disease process, many cases due to thrombosis are never examined histologically. The present series provides support for the proponents of embolism, since ten (23%) of the 44 older patients had significant car diac valvular disease, and five (11%) had associated internal carotid artery disease. Both embolism and thrombosis seem to be frequent causes of CRA occlusions. Throm bosis seems to be the more likely explanation in the older patient, especially the one with hypertension or hyperlipidemia, or both, or with other evidence of atherosclerotic vascu-
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AMERICAN JOURNAL OF OPHTHALMOLOGY
lar disease. Because of the many variables involved and the relative lack of histologie documentation, no data could be obtained from the present series to support or refute this hypothesis. However, careful medical evaluation of the cardiovascular system and the carotid arteries (auscultation for bruits, palpation of the facial pulses, search for emboli in the retinal vessels, ophthalmodynamometry, and angiography when sug gested by the previous findings) is indicated in all patients with occlusion of the CRA. Magnification angiography may even reveal unsuspected disease in the ophthalmic artery in some cases. Through this study, we planned to de termine whether the ocular vascular accident presaged a later, more devastating cerebrovascular accident, or involvement of the second eye. Liversedge and Smith3 in 1962 noted that three of approximately 50 patients developed neurologic symptoms, approxi mately 20 months after CRA occlusion. Lorentzen7 noted that six of 37 patients ( 16% ) developed contralateral neurologic symptoms after an average follow-up of eight years. In the present series, only eight of the 44 older patients (18%) had developed a cerebrovascular accident after an average followup of over six years, and in only two was it clearly related to disease of the ipsilateral carotid vessels in the neck. This low inci dence of stroke complicating CRA occlusion might be explained by the marked difference in the caliber of the blood vessels involved. A clinical stroke is associated with occlusion of large caliber cerebral vessels ; whereas, the CRA is a small vessel equivalent to terminal cortical vessels on the surface of the brain. Microemboli of sufficient size to block the CRA may also escape into the cerebral circulation and occlude small caliber cerebral vessels without producing neurologic signs or symptoms. Pathologic verification of silent cerebral microemboli in cases of CRA oc clusion should be sought in future autopsy material. Because subsequent stroke was rare in this and other series studied, prophylactic
MARCH, 1975
use of long-term anticoagulants is discour aged in patients with an acute CRA occlu sion. Bilateral CRA occlusion is evidently rare. The 37 patients described by Lorentzen7 and the 26 cases of Ellis and associates2 evi denced no bilateral occlusions. Karjalainen 5 documented less than six examples of 181 combined branch and central retinal artery occlusions. Embolie occlusion is the likely mechanism, occurring in two patients with rheumatic heart disease in the present study. One patient with syphilitic arteritis experi enced involvement in the fellow eye two weeks after an otherwise typical CRA oc clusion in the first eye. Therefore, an opti mistic prognosis for vision in the fellow eye is justified in nonembolic and noninflamma tory CRA occlusions. Associated medical diseases have been stressed in reports of patients with CRA occlusions,2'3·5 and the present series con firms a relationship with atherosclerotic cardiovascular disease and with hypertension. Less frequent medical diagnoses in the pres ent series include hyperlipidemia (five pa tients), syphilis (three patients), diabetes mellitus (three patients), temporal arteritis (two patients), hemoglobinopathies (two pa tients), and systemic lupus erythematosus (one patient). Of the patients under 40 years of age, there were definite explanations for the ocu lar vascular disturbances in six patients. These included a particularly noteworthy case of unsuspected atrial myxoma and two other cases of heart disease. There were isolated cases of presumptive hypercoagulability, hypertension, and orbital compression syndrome.18 The investigation of young pa tients with CRA occlusion must include ex tensive cardiac studies including an echocardiogram or cardiac catheterization, or both to screen for the presence of atrial myxoma, in addition to hématologie and sys temic disease studies. Four of the younger patients had no apparent etiology initially, and all four remain in good health after a
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CENTRAL RETINAL ARTERY OCCLUSION
relatively long follow-up. In the young patient for whom no cause can be found, a guardedly optimistic prognosis seems reasonable. SUMMARY
Data regarding the etiology and subse quent course of 54 patients with an occlusion of the central retinal artery included the following: of 44 patients over 40 years of age at the time of the central retinal artery occlusion, eight (18%) had cerebrovascular accidents, but only two patients (5%) had a stroke clearly related to the vessels involv ing the affected central retinal artery. Five patients (11%) had occlusive disease of the ipsilateral internal carotid artery; two of these had cerebral involvement later or simultaneously. Ten of the older patients had cardiac valvular disease and presumed embolie occlusion of the central retinal artery. Associated medical disorders were common. Of the ten patients under 40 years of age, six occlusions were secondary to atrial myxoma, mitral insufficiency with Marian's syndrome, polycythemia, hypercoagulopathy, hypertension, and orbital compression. Four had no apparent etiology at onset and were in good health many years later. ACKNOWLEDGMENT
We thank H. V. Appen for translating von Graefe's original paper into English. REFERENCES
1. Von Graefe, A. : Ueber Embolie der Arteria centralis retinae als Ursache plötzlicher erblindung. Albrecht von Graefe's Arch. Ophthalmol. 5:136, 1859. 2. Ellis, C. J., Hamer, D. B., Hunt, R. W., Lever, A. F., Lever, R. S., Peart, W. S., and Walker,
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S. M. : Medical investigation of retinal vascular occlusion. Br. Med. J. 2:1093, 1964. 3. Liversedge, L. A., and Smith, V. H. : Neuromedical and ophthalmic aspects of central retinal artery occlusion. Trans. Ophthalmol. Soc. U. K. 82:571, 1962. 4. Hill, D. W. : Studies in retinal vascular acci dents. Ann. R. Coll. Surg. Engl. 43:287, 1968. 5. Karjalainen, K. : Occlusion of the central retinal artery and retinal branch arterioles. Acta Ophthalmol. 109(Suppl.) :9, 1971. 6. Kollarits, C. R., Lubow, M., and Hissong, S. L. : Retinal stroke. 1. Incidence of carotid atheromata. J.A.M.A. 222:1273, 1972. 7. Lorentzen, S. E. : Occlusion of the central retinal artery. A follow-up. Acta Ophthalmol. 47:690, 1969. 8. Walsh, F. B., and Hoyt, W. F.: Clinical Neuroophthalmology. Baltimore, Williams and Wilkins, 1969, pp. 1824-28. 9. Cogan, D. G. : Ophthalmic Manifestation of Systemic Disease. Philadelphia, W. B. Saunders, 1974, pp. 102-126. 10. Wolter, J. R. : Double embolism of the cen tral retinal artery and one long posterior ciliary artery followed by secondary hemorrhagic glau coma. Am. J. Ophthalmol. 73:651, 1972. 11. Manschot, W. A. : Embolism of the central retinal artery originating from an endocardial myxoma. Am. J. Ophthalmol. 48:381, 1959. 12. Cogan, D. G., Kuwabara, T., and Moser, H. : Fat emboli in the retina following angiography. Arch. Ophthalmol. 71:308, 1964. 13. Zimmerman, L. : Embolism of the central re tinal artery. Arch. Ophthalmol. 73:822, 1965. 14. Penner, R., and Font, R. L. : Retinal em bolism from calcified vegetations of aortic valve. Arch. Ophthalmol. 81:565, 1969. 15. Jampol, L. M., Wong, A. S., and Albert, D. M. : Atrial myxoma and central retinal artery occlusion. Am. J. Ophthalmol. 75:242, 1973. 16. Anderson, J. D., and Lubow, M. : Atrial myxoma as a source of retinal embolization. Am. J. Ophthalmol. 76:769, 1973. 17. Dahrling, B. E. : The histopathology of early central retinal artery occlusion. Arch. Ophthalmol. 73:506, 1965. 18. Hollenhorst, R. W., Svien, H. J., and Benoit, C. F.: Unilateral blindness occurring during anes thesia for neurosurgical operation. Arch. OpHthalmol. 52:819, 1954.
SHIRLEY H. WRAY, M.D.,
DAVID G. COGAN,
AND
M.D.
Boston, Massachusetts
Von Graefe1 described the classic clinical picture of an acute occlusion of the central retinal artery (CRA) in 1859. He pointed out the early ophthalmoscopic findings that he observed in a man who had suddenly lost vision in his right eye seven days previously. Von Graefe described the pale disk, attenu ated arteries and veins, and the cloudy retina that produced the macular cherry-red spot (kirsch-rother Fleck). A few days later, he noted segmental flow in this patient's retinal vessels that gradually improved, but without recovery of visual acuity. He deduced that the blindness and ophthalmoscopic signs were the result of obstruction of the retinal circu lation, and concluded that the cause in this man, who had aortic valve disease, was an embolus blocking the CRA. Many subsequent reports discussing the etiology and sequelae of retinal vascular dis ease2"6 have been misleading because the au thors combined venous and branch arterial occlusions with acute CRA occlusions de spite their differences in onset, course, and etiology. What has remained unclear over the years is the relationship between CRA occlu sions and coexisting cerebral and extracranial vascular disease and cardiovascular disorders. The risk of a cerebral stroke or involvement of the second eye has not been clarified. For this reason, we undertook a retrospective study of patients with CRA occlusion to de termine the incidence of subsequent cerebrovascular accidents or a second CRA occlusion, From the Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. This study was supported by a grant from The Seeing Eye, Inc., Morristown, New Jersey. This study was presented in part at the Uni versity of Wisconsin Ophthalmology Alumni Meeting, Sept. 6, 1974. Reprint requests to Richard E. Appen, M.D., Department of Ophthalmology, University Hos pitals, 1300 University Ave., Madison, WI 53706.
unsuspected underlying carotid artery dis ease, cardiac valvular disease, or other medical disorders that might cause CRA occlusion. PATIENTS
At least one of us diagnosed 64 cases of acute CRA occlusion between 1945 and 1973. The etiology of the 54 patients in this study was apparent at the initial examination or follow-up information was later obtained. Follow-up examination was performed by one of us or by the patient's ophthalmologist, optometrist, or the Massachusetts Eye and Ear Infirmary Clinic. Questionnaires were also sent to the patients to supplement the physicians' reports. RESULTS
The ages of the 54 patients at the onset of the CRA occlusion ranged from 17 to 84 years, averaging 54.3 years, with a median of 57 years. Fifty-seven percent of the pa tients were men. The - right eye was involved in 55,% of the patients. The preponderance of men has been found in previous studies, but the average age at onset has been con siderably older.3'5'7 Ten patients in our group were under 40 years of age at the onset of the ocular arterial occlusion. Because of the differences in the incidence and type of vascular disease in young and older patients, we elected to divide our patient material into two groups for analysis: patients older than 40 years of age, and patients under 40 years of age. Older patients with CRA occlusion— Forty-four patients were included in the group over 40 years of age. The age of onset ranged from 40 to 84 years (Table 1), with an average of 60.7 years (median of 59 years), an age more comparable to that of prior reports. 3 ' 5 ' 7 Fifty-five percent of the patients were men. The right eye was in-
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375
TABLE 1 PATIENTS OVER 40 YEARS OF AGE AT ONSET OF CRA OCCLUSION* Case, Age at Onset, Sex
E
Date of Onset (mo/yr)
Duration of Follow-Up (yrs)
4/1949
3D
Associated Disease at Onset Alcoholism; simultaneous left hemiparesis with CRAO; died of unknown cause, 1952 DM; hypertension; syphilis; sickle trait DM; ASVD
1.40, F
R.E.
2. 64, M
L.E.
4/1969
3. 82, M
L.E.
10/1963
4. 71, F
R.E.
10/1967
5
5, 46, M
R.E.
6/1955
17D
6, 51. M
L.E.
9/1945
17D
7. 65. M
R.E.
2/1966
None
8. 41, F
R.E.
8/1965
Systemic lupus erythematosus
9. 65, M 10, 67, M
R.E. R.E.
7/1964 6/1972
7mo 2JD
9 1
None RHD with MS; died of CHF, 1/1972 Syphilis
11. 54, M
R.E.
1/1972
18 mo
12, 63. M
R.E.
10/1972
3mo
13, 71, M 14, 54, M 15, 44, M
L.E. L.E. L.E.
11/1960 S/1968 2/1959
13 5 SD
16, 61, F
L.E.
10/1961
8D
Right ICA stenosis General ASVD; old occipital infarct; CRAO at angiography Occurred after closure of Pop pen clamp for aneurysm Calcified aortic valve with LVH AS None RHD with Al, AS; died of CHF. 1964 RHD with AS, AI. MR
17. 59, F
R.E.
1/1966
7
None
18. 79. M 19. 57, M 20. 45, F 21. 52. M 22. 58, M 23. 57, M
R.E. L.E. R.E. L.E. R.E. L.E.
10/1972 5/1961 1/1959 3/1949 2/1973 6/1962
10 mo 12 14 3D 6mo 18moD
24, 61, F
L.E.
12/1966
6D
25, 65. M 26. 69, M
R.E. R.E.
4/1972 9/1968
18 mo 4D
27, 70, F
R.E.
1/1962
6D
28, 67, F
L.E.
10/1962
9D
29, 30, 31, 32,
54, F 58, M 82, F 84. M
L.E. R.E. R.E. R.E.
10/1965 10/1951 12/1971 10/1969
33, 68. F 34. 44. M
L.E. R.E.
2/1973 4/1967
8 4} 2 4 6mo 5
AS RHD with MR. MS RHD with AS. AI, MS AS AS with CHF Hypertension; history of left hemiparesis, 1954; died of MI, 12/1963 Hypertension; died of cere bral hemorrhage. 1/1973 Hypertension; alcoholism Hypertension: died of corpus callosum glloblastoma, 5/1972 Hypertension; died of un known cause, 5/1968 + STS: hypertension; history of severe asthma; died of unknown cause, 1/1972 Hypertension Hypertension; CHF Hypertension History of MI; cardiac pacer placed 5/1969 Cardiac arrhythmia Sickle cell-thalassemia hemoglobinopathy
Subsequent Cerebrovascular Acddentt
Second Eye Involved
+ ; died of left cerebral infarct, 11/1969 + ; died with aphasia, right hemiparesis, 5/1966 + ; left hemiparesis, 6/1972 + ; left hemiparesis. 1969 + ; loss of R.E. visual acuity, right hemiplegia 2 wks after L.E. occlusion + ; loss of left ear hear ing, 1966; right ear, 1973 + ; had right hemiplegia 1 day after R.E. CRAO
+ : R.E.. 1955; L.E., 1959 + ; L.E., 1961; R.E., 1964 + ;R.E„ 1/1966: L.E., BRAO, 12/1966
+ ; unknown
* Definitions include AI. aortic insufficiency: AS, aortic stenosis; ASVD. atherosclerotic vascular disease: BRAO, branch retinal artery occlusion; CHF. congestive heart failure; CRAO, central retinal artery occlusion: D, followed up until death: DM. diabetes mellitus: ESR. erythrocyte sedimentation rate; ICA. internal carotid arterj': LVH. left ventricular hypertrophy; MI, myocardial Infarction: MR, mitral régurgitation; MS, mitral stenosis; RHD. rheumatic heart disease; and STS, serologie test for syphilis. f -f- indicates evidence of cerebrovascular accident.
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MARCH, 197S
TABLE 1 (Continued) Case, Age at Onset, Sex
Eye
Date of Onset (mo/yr)
Duration of Follow Up (yrs)
35, 74, F
L.E.
11/1968
5
36, 61, F
R.E.
3/1968
5i
37, 57, F 38, 52, F
L.E. R.E.
9/1961 11/1957
11
39, 56, F 40, 64, F 41, 51, M 42, 54, M 43, 74, F
L.E. R.E. R.E. R.E. R.E.
8/1964 4/1969 8/1962 1/1969 5/1967
44, 61, F
L.E.
6/1958
8D
9 4 11 4 6moD
Associated Disease at Onset
Subsequent Cerebrovascular Accidentt
Second Eye Involved
Temporal arteritis, biopsy specimen positive; ESR, 78 mm/hr Temporal arteritis, biopsy specimen negative; ESR, 68 mm/hr Idiopathic vasculitis None; DM 1 mo later; died of CHF 8 yrs later None ; doing well at follow-up None; doing well at follow-up None; doing well at follow-up None; doing well at follow-up None; died of pulmonary edema in 11/1967 None; doing well at follow-up
volved in 59% of the cases. After an aver age follow-up of 6.1 years, 15 patients (34%) had died. The follow-up of the 29 survivors was 6.2 years. There was no sig nificant difference in the average age at on set of those dead or those still alive at followup. CEREBROVASCULAR ACCIDENT—Eight of
the 44 patients ( 18%) had a cerebrovascular accident. In one case (Case 1), a contralateral hemiparesis occurred simultaneously with the CRA occlusion. Unfortunately, ophthalmodynamometry, auscultation for carotid bruits, and angiography were not performed in 1949 when this patient was studied. In three other patients, a subsequent contralateral hemiparesis developed seven months (Case 2), 29 months (Case 3), and five years (Case 4) after the CRA occlusion, suggesting that the cerebral stroke repre sented extension of disease in the extracranial internal carotid artery. In two of these three patients, however, there was evidence of wide spread systemic vascular disease. Carotid angiography was not performed in these three patients. The remaining four patients had a stroke, one presumably embolie from heart disease. A 46-year-old man (Case 5) with rheu matic mitral stenosis had a CRA occlu sion of his right eye in June 1955, and a left hemiparesis six years later. A 51-year-old man (Case 6) had syphilitic arteritis, the
apparent cause of a CRA occlusion of his left eye, followed two weeks later by a right hemiparesis and loss of vision in his right eye. He died 17 years later of an unknown cause. The third patient in this group was a 65-year-old man (Case 7) with a CRA oc clusion of his right eye in February 1966, sudden loss of hearing (attributed to internal auditory artery occlusion) of the left ear that same year, and of the right ear seven years later. A 41-year-old woman (Case 8) had a remarkable history of separate episodes of phlebitis, idiopathic thrombocytopenic purpura, pulmonary embolism, and myocardial infarctions—all complications of sys temic lupus erythematosus. She then devel oped right hemiparesis and aphasia, with loss of visual acuity of the right eye, coma, and choreiform movements of the left limbs several hours later. Having been maintained on continuous anticoagulants, she had re covered well neurologically eight years later except for permanent blindness of the right eye. The neurologic dysfunction was the re sult of a hypercoagulable state related to her underlying disease. CAROTID ARTERY DISEASE—Five of the 44
patients (11%) had ipsilateral carotid artery disease associated with a CRA occlusion; three had no cerebral signs or symptoms. One (Case 9) was a 65-year-old man seen in July 1964, who had, in addition to a CRA occlusion of the right eye, a bright
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CENTRAL RETINAL ARTERY OCCLUSION
cholesterol plaque in the right fundus, de creased ophthalmodynamometry in the right eye, and bilateral carotid bruits. Carotid angiography revealed 90% stenosis of the right internal carotid artery, and 15% steno sis of the left internal carotid artery. In January 1965, he underwent right carotid endarterectomy. His right eye was enucleated five months after the occlusion because of glaucoma, but histologie examination did not permit clarification of the mechanism for the occlusion (thrombotic vs. embolie). In November 1970, he was evaluated elsewhere because of ill-defined visual impairment of his left eye, and repeat angiography re vealed severe stenosis of the left internal carotid artery with a normal right carotid system. He therefore underwent left carotid endarterectomy in December 1970. In Sep tember 1971, a retinal detachment of the left eye was observed, possibly providing the explanation for his visual complaints prior to the second endarterectomy. These were the only neurologic complications in a nineyear follow-up since the initial CRA occlu sion. Another patient (Case 1) had had amaurosis fugax prior to the onset of simultaneous CRA occlusion and contralateral hemiparesis. In two patients, the CRA occlusions were iatrogenic. In one (Case 10), the event oc curred during carotid angiography when an embolus, probably originating from an atheromatous segment of the stenotic intracavernous portion of the ipsilateral internal carotid artery, blocked the CRA. In the other patient (Case 11), an ipsilateral CRA occlusion occurred two days after the final turn of a Poppen clamp applied to the right common carotid artery in treating a right anterior communicating artery aneurysm. A fifth patient (Case 2) had a low retinal diastolic pressure on the left side. Ophthal modynamometry was performed when a right hemiparesis occurred seven months after a CRA occlusion of the left eye. Of these five patients with carotid artery disease, three had had amaurosis fugax prior to
CRA occlusion, and two had visible retinal emboli. RETINAL EMBOLI—Six patients had
an
embolus visible in the retinal vessels at the time of the CRA occlusion. Two patients (Cases 9 and 10) had stenotic internal carotid disease. Two others (Cases 12 and 13) had aortic stenosis. Another patient (Case 4) with an embolus developed a con tralateral hemiparesis five years after the CRA occlusion. The sixth patient (Case 14) was unchanged five years later. BILATERAL
CRA
OCCLUSION—Bilateral
CRA occlusion has rarely been reported*·9 but it occurred in three patients in this older group. Two of these patients (Cases 15 and 16) had known rheumatic heart disease, and the other had syphilitic arteritis (Case 6). A fourth patient had a branch artery occlusion in the second eye (Case 17) and the cause was presumably embolie. CARDIAC
VALVULAR
DISEASE—Ten
of
these patients (Cases 5,12,13,15,16, and 1822) had evidence of significant cardiac valvu lar disease involving the aortic valve in eight and the mitral valve in four patients (both valves in some). Two of the patients with rheumatic valvular disease experienced bi lateral CRA occlusion. Six of the ten pa tients with valvular disease had the occlusion in the right eye, the same frequency as in the 34 patients without valvular disease (21/34 or 62%). Amaurosis fugax was an infrequent symptom in this group. Only two of the ten patients with valvular disease had had episodes of transient monocular blurring prior to the total occlusion, as opposed to 11 of the 34 (33%) patients without valvular disease, and to three of the five patients with carotid artery stenosis. Only one of the ten patients with valvular disease had hyperten sion (160/100 or higher; or systolic pres sure above 200 mm H g ; or a history of hypertension and currently under therapy) ; whereas, of the 34 patients without valve disease, ten (30%) had hypertension. ASSOCIATED MEDICAL DISORDERS—A num-
AMERICAN JOURNAL OF OPHTHALMOLOGY
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MARCH, 1975
(Case 4) sustained a left hemiplegia five years after the ocular vascular accident. Of the other two, one (Case 44) was doing well seven years after the CRA occlusion, and the other (Case 17) had had a transient branch artery occlusion in her good eye 11 months after the original CRA occlusion, but was unchanged and doing well six years after that. Of the four with normal choles terol levels, two had cardiac valve disease, one had syphilitic arteritis, and the fourth had generalized atherosclerosis.
ber of the patients had an associated medical disorder, generally related to systemic vascu lar disease or abnormal blood coagulability. Eleven of the 44 had hypertension; three had prior myocardial ischemie disease; and three had other atherosclerotic vascular dis ease. Two (Cases 2 and 34) had hemoglobinopathies, and three (Cases 2, 6, and 28) had positive serologie tests for syphilis. One (Case 8) had a presumptive hypercoagulopathy as a complication of systemic lupus erythematosus. Two patients (Cases 35 and 36) had typical temporal arteritis revealed by biopsy specimen in one. One (Case 37) had systemic vasculitis unrelated to temporal arteritis. Only three patients (Cases 2, 3, and 38) had diabetes mellitus. Of the nine patients tested, five (Cases 4, 17, 23, 24, and 44) had serum cholesterol levels of 250 mg/100 ml or higher. Of the five patients with hypercholesterolemia, three had no other associated abnormalities, one was hypertensive, and the other had gen eralized arteriosclerotic vascular disease; at follow-up, two patients (Cases 23 and 24) had died of vascular disease 18 months and six years after the occlusion. One patient
No ASSOCIATED DISEASE—Seven patients
(16%) had no associated disease at the time of onset of CRA occlusion. After an aver age follow-up of 6.1 years, five were doing well. The other two had had debilitating vascular accidents, resulting in death from cardiac failure in one and in bilateral deaf ness due to occlusions of the internal audi tory arteries in the other. Younger patients with CRA occlusion— Ten patients under 40 years of age had CRA occlusion (Table 2 ) . The average age was 25.8 years, ranging from 17 to 39 years of age. Seven of the patients were men. Four of the occlusions involved the right eye. The
TABLE 2 PATIENTS UNDER 40 YEARS OF AGE AT ONSET OF CRA OCCLUSION*
Duration of Follow-Up (yrs)
Eyet
Date of Onset (mo/yr)
27, F 18, M 30, M 20, M 17, M 18, F 39, M
L.E. R.E. L.E. R.E. L.E. L.E. R.E.
8/1951 7/1962 2/1959 11/1959 12/1966 6/1964 8/1961
52, 31, F
R.E.
3/1972
1J
53, 19, M 54, 39, M
L.E. L.E.
7/1972 10/1971
1 2
Case, Age at Onset, Sex 45, 46, 47, 48, 49, 50, 51,
22 11 14 14 6 9 mo 1|D
Associated Disease at Onset
No disease; pregnant; well at follow-up No disease ; vigorous dancing; well at follow-up None; doing well at follow-up None; doing well at follow-up Left àtrial myxomat Marian's syndrome with MR Polycythemia with atrial fibrillation, CHF; died of pulmonary embolism, 2/1963 Presumed hypercoagulopathy, on oral anovulatory agent Orbital compressive syndrome while stuporous Hypertension; traumatic paraplegia
* Definitions include CHF, congestive heart failure; CRAO, central retinal artery occlusion; D, followed up until death ; and MR, mitral régurgitation f Fellow eyes did not become involved. t Subsequent cerebrovascular accident; simultaneous right hemiparesis with central retinal artery occlusion, L.E.
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CENTRAL RETINAL ARTERY OCCLUSION
follow-up period ranged from one to 22 years, and averaged 8.2 years (median of six years) excluding the patient who was dead at follow-up. CEREBROVASCULAR ACCIDENT—One of
the
ten younger patients had a subsequent stroke. The patient, a 17-year-old boy (Case 49), was admitted with fever and a holo systolic cardiac murmur initially attributed to bacterial endocarditis. He developed simultaneous embolie occlusion of the left CRA and the left middle cerebral artery and, two weeks later, bilateral occlusions of the femoral arteries as complications of a left atrial myxoma. CAROTID ARTERY DISEASE—None of
the
ten patients in this younger group had extracranial carotid artery disease. RETINAL EMBOLI—Retinal emboli were not observed in any of these patients. BILATERAL CRA OCCLUSION—None of the
ten younger patients had bilateral CRA oc clusion. CARDIAC VALVULAR DISEASE—Three of
the ten patients had cardiac disease. One pa tient developed an initially unsuspected atrial myxoma. An 18-year-old woman (Case 50) had Marian's syndrome and mitral insuffi ciency. The third patient was a 39-year-old man with polycythemia, myocardial ischemie disease, and atrial fibrillation. ASSOCIATED MEDICAL DISORDERS—Three
of the ten patients had other disorders. One was a 39-year-old man (Case 54) with mild hypertension of 160/100. A 31-year-old woman had presumptive hypercoagulopathy (Case 52). Following a CRA occlusion and auscultation of a holosystolic cardiac mur mur, she underwent cardiac catheterization. She occluded the brachial artery at the site of entry of the catheter eight hours, two days, and nine months after the study, re quiring endarterectomy on each occasion. Otherwise, she was doing well 1^2 years after the original CRA occlusion. A 19year-old man (Case 53) had a monocular CRA occlusion after prolonged orbital com pression due to his face resting against his
379
knees while in a drug-induced stupor. No
ASSOCIATED DISEASE—Four patients
had no apparent cause for CRA occlusion at initial evaluation. One of them (Case 45) was pregnant at the time of the occlusion, but she had uncomplicated pregnancies and was well at follow-up 22 years later. An other patient (Case 46) was vigorously dancing the twist in a contest (which he won) when he noticed a flash of light and loss of vision in his right eye. He was well 11 years later. Two other patients (Cases 47 and 48), with no related condition or ac tivity at onset, were well and unchanged 14 years later. DISCUSSION
The significance of a CRA occlusion clearly depends on its pathogenesis. In the mid-1800s, embolism was stressed as the usual cause but in the early 1900s, throm bosis of the CRA was thought to be the usual mechanism. Even in recent series of CRA occlusions, embolism was the stated cause in only two of 62 cases,3 in two of 26 cases,2 and in two of 117 cases.5 Most recently, emphasis is shifting back to em bolism as the more frequent mechanism, especially arising as platelet conglomerates or atherosclerotic fragments from plaques in the carotid arteries. 8-10 Most histologie re ports have described emboli,10-16 though two reports depict probable thromboses.5'17 Be cause of the rarity in obtaining a specimen soon after the occlusion if there is no other active disease process, many cases due to thrombosis are never examined histologically. The present series provides support for the proponents of embolism, since ten (23%) of the 44 older patients had significant car diac valvular disease, and five (11%) had associated internal carotid artery disease. Both embolism and thrombosis seem to be frequent causes of CRA occlusions. Throm bosis seems to be the more likely explanation in the older patient, especially the one with hypertension or hyperlipidemia, or both, or with other evidence of atherosclerotic vascu-
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AMERICAN JOURNAL OF OPHTHALMOLOGY
lar disease. Because of the many variables involved and the relative lack of histologie documentation, no data could be obtained from the present series to support or refute this hypothesis. However, careful medical evaluation of the cardiovascular system and the carotid arteries (auscultation for bruits, palpation of the facial pulses, search for emboli in the retinal vessels, ophthalmodynamometry, and angiography when sug gested by the previous findings) is indicated in all patients with occlusion of the CRA. Magnification angiography may even reveal unsuspected disease in the ophthalmic artery in some cases. Through this study, we planned to de termine whether the ocular vascular accident presaged a later, more devastating cerebrovascular accident, or involvement of the second eye. Liversedge and Smith3 in 1962 noted that three of approximately 50 patients developed neurologic symptoms, approxi mately 20 months after CRA occlusion. Lorentzen7 noted that six of 37 patients ( 16% ) developed contralateral neurologic symptoms after an average follow-up of eight years. In the present series, only eight of the 44 older patients (18%) had developed a cerebrovascular accident after an average followup of over six years, and in only two was it clearly related to disease of the ipsilateral carotid vessels in the neck. This low inci dence of stroke complicating CRA occlusion might be explained by the marked difference in the caliber of the blood vessels involved. A clinical stroke is associated with occlusion of large caliber cerebral vessels ; whereas, the CRA is a small vessel equivalent to terminal cortical vessels on the surface of the brain. Microemboli of sufficient size to block the CRA may also escape into the cerebral circulation and occlude small caliber cerebral vessels without producing neurologic signs or symptoms. Pathologic verification of silent cerebral microemboli in cases of CRA oc clusion should be sought in future autopsy material. Because subsequent stroke was rare in this and other series studied, prophylactic
MARCH, 1975
use of long-term anticoagulants is discour aged in patients with an acute CRA occlu sion. Bilateral CRA occlusion is evidently rare. The 37 patients described by Lorentzen7 and the 26 cases of Ellis and associates2 evi denced no bilateral occlusions. Karjalainen 5 documented less than six examples of 181 combined branch and central retinal artery occlusions. Embolie occlusion is the likely mechanism, occurring in two patients with rheumatic heart disease in the present study. One patient with syphilitic arteritis experi enced involvement in the fellow eye two weeks after an otherwise typical CRA oc clusion in the first eye. Therefore, an opti mistic prognosis for vision in the fellow eye is justified in nonembolic and noninflamma tory CRA occlusions. Associated medical diseases have been stressed in reports of patients with CRA occlusions,2'3·5 and the present series con firms a relationship with atherosclerotic cardiovascular disease and with hypertension. Less frequent medical diagnoses in the pres ent series include hyperlipidemia (five pa tients), syphilis (three patients), diabetes mellitus (three patients), temporal arteritis (two patients), hemoglobinopathies (two pa tients), and systemic lupus erythematosus (one patient). Of the patients under 40 years of age, there were definite explanations for the ocu lar vascular disturbances in six patients. These included a particularly noteworthy case of unsuspected atrial myxoma and two other cases of heart disease. There were isolated cases of presumptive hypercoagulability, hypertension, and orbital compression syndrome.18 The investigation of young pa tients with CRA occlusion must include ex tensive cardiac studies including an echocardiogram or cardiac catheterization, or both to screen for the presence of atrial myxoma, in addition to hématologie and sys temic disease studies. Four of the younger patients had no apparent etiology initially, and all four remain in good health after a
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CENTRAL RETINAL ARTERY OCCLUSION
relatively long follow-up. In the young patient for whom no cause can be found, a guardedly optimistic prognosis seems reasonable. SUMMARY
Data regarding the etiology and subse quent course of 54 patients with an occlusion of the central retinal artery included the following: of 44 patients over 40 years of age at the time of the central retinal artery occlusion, eight (18%) had cerebrovascular accidents, but only two patients (5%) had a stroke clearly related to the vessels involv ing the affected central retinal artery. Five patients (11%) had occlusive disease of the ipsilateral internal carotid artery; two of these had cerebral involvement later or simultaneously. Ten of the older patients had cardiac valvular disease and presumed embolie occlusion of the central retinal artery. Associated medical disorders were common. Of the ten patients under 40 years of age, six occlusions were secondary to atrial myxoma, mitral insufficiency with Marian's syndrome, polycythemia, hypercoagulopathy, hypertension, and orbital compression. Four had no apparent etiology at onset and were in good health many years later. ACKNOWLEDGMENT
We thank H. V. Appen for translating von Graefe's original paper into English. REFERENCES
1. Von Graefe, A. : Ueber Embolie der Arteria centralis retinae als Ursache plötzlicher erblindung. Albrecht von Graefe's Arch. Ophthalmol. 5:136, 1859. 2. Ellis, C. J., Hamer, D. B., Hunt, R. W., Lever, A. F., Lever, R. S., Peart, W. S., and Walker,
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S. M. : Medical investigation of retinal vascular occlusion. Br. Med. J. 2:1093, 1964. 3. Liversedge, L. A., and Smith, V. H. : Neuromedical and ophthalmic aspects of central retinal artery occlusion. Trans. Ophthalmol. Soc. U. K. 82:571, 1962. 4. Hill, D. W. : Studies in retinal vascular acci dents. Ann. R. Coll. Surg. Engl. 43:287, 1968. 5. Karjalainen, K. : Occlusion of the central retinal artery and retinal branch arterioles. Acta Ophthalmol. 109(Suppl.) :9, 1971. 6. Kollarits, C. R., Lubow, M., and Hissong, S. L. : Retinal stroke. 1. Incidence of carotid atheromata. J.A.M.A. 222:1273, 1972. 7. Lorentzen, S. E. : Occlusion of the central retinal artery. A follow-up. Acta Ophthalmol. 47:690, 1969. 8. Walsh, F. B., and Hoyt, W. F.: Clinical Neuroophthalmology. Baltimore, Williams and Wilkins, 1969, pp. 1824-28. 9. Cogan, D. G. : Ophthalmic Manifestation of Systemic Disease. Philadelphia, W. B. Saunders, 1974, pp. 102-126. 10. Wolter, J. R. : Double embolism of the cen tral retinal artery and one long posterior ciliary artery followed by secondary hemorrhagic glau coma. Am. J. Ophthalmol. 73:651, 1972. 11. Manschot, W. A. : Embolism of the central retinal artery originating from an endocardial myxoma. Am. J. Ophthalmol. 48:381, 1959. 12. Cogan, D. G., Kuwabara, T., and Moser, H. : Fat emboli in the retina following angiography. Arch. Ophthalmol. 71:308, 1964. 13. Zimmerman, L. : Embolism of the central re tinal artery. Arch. Ophthalmol. 73:822, 1965. 14. Penner, R., and Font, R. L. : Retinal em bolism from calcified vegetations of aortic valve. Arch. Ophthalmol. 81:565, 1969. 15. Jampol, L. M., Wong, A. S., and Albert, D. M. : Atrial myxoma and central retinal artery occlusion. Am. J. Ophthalmol. 75:242, 1973. 16. Anderson, J. D., and Lubow, M. : Atrial myxoma as a source of retinal embolization. Am. J. Ophthalmol. 76:769, 1973. 17. Dahrling, B. E. : The histopathology of early central retinal artery occlusion. Arch. Ophthalmol. 73:506, 1965. 18. Hollenhorst, R. W., Svien, H. J., and Benoit, C. F.: Unilateral blindness occurring during anes thesia for neurosurgical operation. Arch. OpHthalmol. 52:819, 1954.
