Journal of Neuro-Ophthalmology, December 1988, Volume 8, Issue 4

Recurrent anterior ischemic optic neuropathy in young adults.

Anterior ischemic optic neuropathy (AION) is primarily a disease of middle and late life. When it affects the young patient, AION is often due to a specific underlying disease process predisposing to vasculopathy. Reported here are two patients with AION in whom no evidence of associated disease was found. The tendency for recurrent attacks of disc ischemia distinguishes this clinical entity from the more common idiopathic form of AION of older individuals. Hypotheses regarding possible etiology are discussed.

Journal of Clinical Neuro-ophthalmology 8(4): 239-246, 1988. © 1988 Raven Press, Ltd., New York Recurrent Anterior Ischemic Optic Neuropathy in Young Adults Latif M. Hamed, M.D., Valerie Purvin, M.D., and Michael Rosenberg, M. D. Anterior ischemic optic neuropathy (AlaN) is primarily a disease of middle and late life. When it affects the young patient, AlaN is often due to a specific underly­ing disease process predisposing to vasculopathy. Re­ported here are two patients with AlaN in whom no evidence of associated disease was found. The tendency for recurrent attacks of disc ischemia distinguishes this clinical entity from the more common idiopathic form of AlON of older individuals. Hypotheses regarding pos­sible etiology are discussed. Key Words: Anterior Ischemic Optic Neuropathy­Young adults. From the Departments of Ophthalmology (L.M.H., V.P.) and Neurology (V.P.), Indiana University Medical Center; Midwest Eye Institute, Indianapolis, Indiana (V.P.); and Department of Ophthalmology, Northwestern University, Chicago, Illinois (M.R.). Dr. Harned is a neuro-ophthalmology fellow at Bascom Palmer Eye Institute. Address correspondence and reprint requests to Valerie Pur­Yin, M.D., Midwest Eye Institute, 1800 North Capitol Avenue, Indianapolis, IN 46202, U.S.A. 239 Anterior ischemic optic neuropathy (AlaN) is a common cause of sudden visual loss. It is generally divided into arteritic and arteriosclerotic (idio­pathic) subgroups. The idiopathic variety shows an eventual bilaterality of -40%, but repeated at­tacks in a previously affected eye are rare (1). When it affects young patients, AlaN is often as­sociated with a specific predisposing disorder. The idiopathic variety shows a notable predilection for older individuals. Three young patients with recurrent idiopathic AlaN have been recently described (2). We report two additional patients with AlaN who had no other discemable ocular or systemic disorder. One patient manifested recurrent attacks in each eye over a period of 36 years. CASE REPORTS Case 1 A 36-year-old right-handed man suffered an ep­isode of sudden painless loss of vision in the right eye in January 1984. Four days later, optic disc swelling was noted by an ophthalmologist. The results of an evaluation, including complete blood count (CBC), anti-nuclear antibodies (ANA), blood chemistries, erythrocyte sedimentation rate (ESR), lipid profile, fluorescent treponemal antibody ab­sorption test (FTA-ABS), and computed tomogra­phy scan of the brain and orbits, were normal. The patient received a 3-week course of oral pred­nisone without improvement. Examination 1 month after onset revealed normal visual acuity and color vision bilaterally, and a mild right affer­ent pupillary defect. Goldmann visual field testing demonstrated an inferior altitudinal nerve fiber bundle field defect in the right eye and a normal field in the left eye (Fig. 1). The left optic disc was normal; the right revealed superior segmental pal- 240 I. M. HAMED ET AI. 270 LEFT RIGHT FIG. 1. Case 1. Goldmann perimetry demonstrates a lower altitudinal nerve fiber bun­dle field defect in the right eye. lor. Blood pressure was 126/70 mm Hg. The results of a complete physical examination, carotid ultra­sonography, and an echocardiogram were normal. The patient was stable until September 1984, when he noted sudden onset of blurred vision in the left eye. Visual acuity was 20/20 in each eye. The superior pole of the left optic disc was dif-fusely swollen, with abnormal small vessels and blurred superior margin; the remaining portion of the disc appeared normal (Fig. 2). As associated inferior altitudinal field defect was present on Goldmann perimetry (Fig. 3). Fluorescein angiog­raphy revealed dilated capillaries on the superior surface of the left optic disc, which leaked pro- F~C. 2. Cdse 1. 'Trlt:: :>U ....t::IIUI d~.... t::(;t of me left OptiC OISC IS elevated, with dilated abnormal vessels and blurred superior margin. ANTERIOR ISCHEMIC OPTIC NEUROPATHY 270 LEFT RIGHT FIG. 3. Case 1. Goldmann visual fields demonstrate an inferior altitudinal field defect in both eyes, with some additional constriction superior-temporally in the left eye. 241 fusely on late views (Fig. 4). The inferior part of the optic disc and the retinal vasculature were spared. The edema resolved in several weeks, with resid­ual segmental pallor superiorly. In April 1985, the patient again noted sudden onset of cloudy vision in the left eye, involving previously clear areas of the visual field. Visual acuity was 20/20 in the right eye and 20/30 in the left eye. The superior aspect of the left optic disc was pale, while the entire inferior aspect was FIG. 4. Case 1. Venous-phase fluorescein angiogram shows late staining of dilated abnormal vessels in in­volved quadrant. The inferior aspect of the disc ap­pears normal. markedly swollen and hyperemic (Fig. 5). Gold­mann perimetry revealed corresponding involve­ment of the superior portion of the field (Fig. 6). Fluorescein angiography of the left disc revealed the inferior portion to have dilated capillaries with marked leakage on late views (Fig. 7). The superior portion of the optic disc remained dark throughout the angiogram, corresponding to the area of atro­phy from the previous attack in 1984. Case 2 A 59-year old right-handed man had suffered recurrent episodes of sudden, painless visual loss in each eye for 36 years. The first episode affected the left eye in 1949, when he was 23 years old. A lower arcuate nerve-fiber bundle visual field defect was documented in the left eye. The next attack, in 1952, again affected the left eye. Examination dis­closed further extension of the inferior visual field loss in the left eye. In 1960, he noted sudden blurred vision in the right eye. Evaluation at the Mayo Clinic revealed right optic disc edema with splinter hemorrhages, and moderate pallor of the left optic disc. Perimetry revealed an inferior nasal nerve-fiber bundle visual field defect in each eye. The results of an extensive work-up, including medical and neurological examination, CBC, uri­nalysis, ESR, syphilis serology, chest and skull ra­diographs, lumbar puncture, spinal fluid analysis, and protein electrophoresis, were normal. A diag­nosis of vascular optic neuritis was made, and the patient was discharged with instructions to take nicotinic acid, 100 mg daily. I Clin Neuro-ophthalmol. Vol. 8. No.4, 1988 242 L. M. HAMED ET AL. FIG. 5. Case 1. The inferior aspect of the left optic disc is elevated, with dilated abnormal vessels and blurred margin. The superior aspect is now pale. The patient did well until November 1965, when he suffered a similar episode involving the right eye with extension of the inferior field defect in that eye. A course of adrenocorticotropin hormone (ACTH) therapy was administered without any improvement in vision. He was stable until June 26, 1985, when he noted some pressure sensation behind the right eye. Two days later, he noticed decreased vision in the temporal visual field of the right eye. This seemed to progress for a few days but then re­mained stable. The results of a blood count, ESR, glucose, vitamin B]2 and folate levels, and comput­erized tomography of the head and orbits were normal. He was given prednisone, 60 mg/day from July 2 to July 12, 1985, without improvement. He was first seen in the Indiana University neuro­ophthalmology clinic on July 18, 1985. Visual acu­ity was 20/15 in each eye. He identified 15/15 pseu­doisochromatic plates in the right eye and 13/15 in the left. The pupils were 5 mm each and briskly reactive to light, with a trace left relative afferent defect. Goldmann perimetry revealed an absolute inferior altitudinal defect in each eye (Fig. 8). Oc­ular motility and the results of biomicroscopy and applanation tonometry were normal. The superior aspect of each optic disc was markedly pale (Fig. 9), with total absence of the adjacent nerve fiber layer. The patient's past medical history was unre­markable. Specifically, there was no history of hy­pertension, diabetes, or vascular disease. Family history was positive for Huntington's disease in his father, a sister, and an aunt. His only current medication was nicotinic acid, 100 mg three times per day. Blood pressure was 130/80 mm Hg. The results of general medical and neurological exam­inations were entirely normal. Additional tests, in­cluding VORL, FTA-ABS, serum protein electro­phoresis, anti-DNA antibodies, complement lev­els, rheumatoid factor, angiotensin converting enzyme, and tuberculin skin test were unremark­able. The patient has been followed up since the last episode without any further recurrences. The optic discs, visual acuities, and visual fields have remained unchanged. DISCUSSION The clinical features of AION have been well characterized (3,4). This disorder typically pre­sents as sudden monocular visual loss without pain or premonitory transient visual phenomena. The visual deficit is usually maximal at onset, but a minority of cases may show early progression. Vi­sual field defects are most often altitudinal or ar­cuate, three times more common inferiorly than superiorly, and often involve fixation. The optic disc shows a characteristic pallid swelling, often in ANTERIOR ISCHEMIC OPTIC NEUROPATHY 270 LEFT RIGHT FIG. 6. Case 1. Goldmann perimetry demonstrates progression of the visual field defect in the left eye, now showing extensive involvement of the superior aspect of the field. Compare with Fig. 3. 243 a segmental distribution corresponding to the vi­sual field defect, with frequent peripapillary splin­ter hemorrhages. Disc edema resolves within weeks to months, leaving pallor of the involved portion of the nerve head. The resulting visual def­icit rarely improves significantly. Most cases of AlaN are seen in middle-aged and elderly patients and can be divided into two groups: those due to giant cell arteritis, and a larger group of idiopathic cases presumed due to arteriosclerosis. When AlaN occurs in a young pa- FIG. 7. Case 1. The inferior one-half of the left optic disc shows profuse leakage in this venous-phase flu­orescein angiogram. The atrophic superior aspect of the disc remains dark. tient it is often due to a specific underlying condi­tion predisposing to vascular insufficiency, such as diabetes mellitus (1,5,6), accelerated hypertension (7,8), severe preeclampsia (9), migraine (10--12), optic disc drusen (13-15), acute blood loss (16-17), acute intermittent porphyria (18), the collagenoses (19), favism (20), or use of oral contraceptives (21). The pathophysiology of idiopathic AlaN is not completely understood. Hayreh's work incrimi­nated vascular occlusion of the posterior ciliary ar­teries that supply the disc in a segmental fashion (22-24). However, the occurrence of the condition in otherwise healthy patients without demonstra­ble evidence of vascular disease elsewhere, the predilection for the superior aspect of the optic disc (3,4), and the absence of vertical segmental disc infarcts despite the usual vertical segmenta­tion of the ciliary vasculature are difficult to ex­plain on a purely vaso-occlusive basis. Recent re­ports demonstrating significantly smaller cup/disc ratios in fellow eyes of patients with unilateral AlaN than in normal subjects suggest that under­lying structural features of the papilla may predis­pose to disc infarction (25-28). The crowding that results from a small scleral canal may render axons more vulnerable to mechanical damage as they traverse the compact lamina cribrosa. Thus, a pri­mary ischemic event may lead to swelling and in­farction in a predisposed individual, but to merely asymptomatic, reversible edema in one without such a predisposition. Three patients under the age of 30 with recur­rent optic neuropathy and disc swelling were re- I Clin Neuro-ophthalmol, Vol. 8, No.4, 1988 244 L. M. HAMED ET AL. 270 LEFT FIG. 8. Case 2. Goldmann perimetry shows absolute bundle field defect in each eye. 270 RIGHT lower altitudinal nerve fiber ported by Dutton and Burde (2). The clinical fea­tures in their three patients were quite typical of idiopathic AION of older individuals, except for the frequent recurrence of attacks. One patient had three separate attacks, one had five, and the other had seven attacks, eventually involving both eyes in each patient. In contrast, typical idiopathic AION almost never recurs in an affected eye. While the recurrence rate in the fellow eye is esti­mated to be 40%, a repeat attack in the same eye is exceedingly rare. In a review of the literature, Lavin and Ellenberger (29) found only five cases of recurrent AION and added one of their own. Beck et al. (30) described an additional four cases, al­though in three of the four, the interval between the two attacks was 3 weeks or less. The reason for this apparent immunity from re­current ischemia is not entirely clear, but several theories have been advanced. A patient with a vi­sual deficit in an eye already affected may be less FIG. 9. Case 2. The superior aspect of the right optic disc demonstrates marked pallor. The left disc appeared similar. ANTERIOR ISCHEMIC OPTIC NEUROPATHY TABLE 1. Summary of clinical data 245 Age of No. of Vision Vision Visual field defect Visual field defect Case onset Sex attacks RE LE RE LE 1 36 M 3 20/20 20/20 Inferior altitudinal Inferior altitudinal 2 23 M 6 20/15 20/15 Inferior altitudinal Inferior altitudinal 3 27 F 7 Light perception 20/20 Inferior altitudinal Inferior altitudinal 4" 23 M 3 20/25 20/20 Horizontal hourglass Superior arcuate defect constriction 5" 17 M 5 20/20 20/20 Inferior altitudinal Marked constriction of and superior arcuate smaller isopters: defect superonasal defect " Patients of Dutton and Burde (2). likely to detect an additional superimposed decre­ment. Shunting of the blood supply of the in­farcted fibers to the surviving ones may render the latter better perfused and subsequently more im­mune from further attacks of ischemia (30). The fine vessel proliferation noted by Smith (31) on the spared part of the optic disc following AION may represent exaggerated forms of such shunting, al­though other explanations for this "pseudo­hemangiomatous" elevation are possible. Alterna­tively, since it appears that a predisposed patient has a crowded optic nerve with a small or absent physiologic cup, it is hypothesized that the initial infarct may provide more space for the surviving fibers to swell into, thus minimizing the effect of mechanical factors that may aggravate an initially mild ischemic insult, rendering it irreversible (29). This is compatible with Hayreh's concept of "a whole range of ischemia varying from the very mild ... to an extremely severe ischemia" (32), milder cases being compatible with normal visual impulse transmission and potential reversibility. On the basis of the three cases reported by Dut­ton and Burde and our two cases, there appears to be a distinct syndrome of AION occurring in oth­erwise healthy young adults (Table 1). The average age at onset of the initial attack was 25 years, and the average number of attacks was 4.8. Each of these patients suffered abrupt loss of vision, often present upon awakening. Most attacks were pain­less, but an occasional episode was associated with a pressure sensation or discomfort in the affected eye. All were observed to have sectoral disc edema, which evolved into segmental optic disc pallor. As in the idiopathic variety, the most com­mon visual field defect was inferior altitudinal, and the defects showed no subsequent improvement. Visual acuity was remarkably preserved in most of these patients, with vision of 20/30 or better 9 of 10 eyes; the one exception was a patient of Dutton and Burde whose acuity was reduced to bare light perception. Our second patient was of particular interest in that despite six separate attacks over a 36-year period, visual acuity has remained 20/15 in each eye. Color vision in eyes with better than 201 40 vision was only minimally impaired, as deter­mined by pseudo-isochromatic plates. None of the patients had any associated systemic signs or symptoms of underlying vascular disease. Com­plete physical examinations and extensive labora­tory testing failed to reveal any associated illness. The pathogenesis of idiopathic AION in young patients is unclear. Vascular occlusion secondary to atherosclerosis, the presumed mechanism in most older patients, seems unlikely in the absence of stroke risk factors or evidence of vascular dis­ease affecting other organ systems. Another pos­sibility is some type of anomalous vascular supply to the optic disc on a congenital basis. Abnormally attenuated vessels or ones with unusual configu­ration could be prone to premature closure due to normal mechanical stresses associated with eye movements. Unfortunately, there is no pathologic material to either support or exclude this possibil­ity. A third possible mechanism is some form of vasospasm, i.e., a localized form of migraine af­fecting the posterior ciliary arteries. AION has been described secondary to migraine in patients with a background history of typical migraine (10­12). None of our patients had a history suggestive of migraine, and none of the attacks were associ­ated with any migrainous symptoms. Finally, re­current attacks of ischemic optic neuropathy was reported in association with optic disc drusen (13­15), and these may become evident in discs that initially had shown elevation without drusen (33). Careful ophthalmoscopy and computerized to­mography of the orbits effectively rule out this possibility in our patients. As in typical idiopathic AION, a combination of factors may be responsible. A form of benign optic disc vasculitis has been described in healthy young adults, in which there is essentially no visual loss despite significant disc edema. The cause of that I Clin Neuro-ophthalmol. Vol. 8. No.4. 1988 246 L. M. HAMED ET AL. syndrome, also termed the "big blind spot syndrome" is unknown. Perhaps our patients are affected by this form of vasculitis but possess optic nerve heads that are structurally vulnerable to ischemia and thus suffer optic nerve damage sec­ondary to swelling. It is quite possible that the nat­ural history of benign disc vasculitis includes re­current attacks. Since most patients are asymptom­atic, the disc edema is discovered during routine examination, and repeat attacks could easily go unnoticed. The premorbid structure of the optic disc in young patients with AlaN would be of some interest in attempts to explain it pathogene­sis. Unfortunately, the propensity to bilaterality in this disorder makes such observation difficult. This syndrome may be more common than is generally appreciated, since most young adults with acute monocular visual loss with disc edema are thought to suffer from optic neuritis. Several features are helpful in distinguishing these cases of AlaN from optic nerve inflammation. Altitudinal or arcuate visual field defects, found in all but two affected eyes in these five patients, are character­istic of AlaN and extremely unusual in optic neu­ritis, accounting for only 3 and 1.8% of patients, respectively (34). The appearance of pallid disc edema observed acutely in all but one of these pa­tients (our Case 1) is quite characteristic of infarc­tion and is distinct from the hyperemic swelling of optic neuritis. Similarly, segmental disc pallor fol­lowing resolution of edema is not a characteristic of optic neuritis. Finally, the time course of the two conditions is quite different. The abrupt onset with lack of subsequent improvement is an expected feature of disc infarction but is unusual in optic neuritis. In addition to these points that distin­guish our cases from patients with neuritis, fluo­rescein angiography in one patient was consistent with segmental disc infarction following each of two attacks (Figs. 4 and 7). REFERENCES 1. Repka MX, Savino PI. Schatz NI. et al. Clinical profile and long-term implications of anterior ischemic optic neuropa­thy. Am JOphthalmol 1983;96:478-83. 2. Dutton H, Burde RM. Anterior ischemic optic neuropathy of the young. JClin Neuro-ophthalmoI1983;3:137-46. 3. Boghen DR, Glaser JD. Ischaemic optic neuropathy; the clinical profile and natural history. Brain 1975;98:689-708. 4. Ellenberger C Jr, Keltner JL, Burde RM. Acute optic neu­ropathy in older patients. Arch Neural 1973;28:182-85. 5. Pavan PR, Aiello LM, Wafai MZ, et al. Optic disc edema in juvenile-onset diabetes. Arch OphtlzalmoI1980;98:2193-97. 6. 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