Central visual dysfunction with disc swelling

SURVEY OF OPHTHALMOLOGY

VOLUME 26. NUMBER I

l

JULY-AUGUST

1981

CLINICAL CHALLENGES RONALD M. BURDE AND PAUL HENKIND, EDITORS

Central Visual Dysfunction

With Disc Swelling

RONALD M. BURDE, M.D., JOHN L. KELTNER, M.D., NEIL R. MILLER, M.D., AND JOHN W. GITTINGER, JR., M.D.

Departments of Ophthalmology, .Neurology and Neurological Surgery, Washington University School of Medicme, St. Louu, Missouri, Departments of Ophlhalmology, Neurology and Neurological Surgery, Universi!y of Califorma, Davis, California, The Wilmer Ophthalmological Institute, Johns Hopkms Uniuerszty, Baltimore, Maryland, and Departmcnl of Ophthalmology, Tt&.Nez England Medical Center, Boston, Massachusetts

Abstract. A healthy

17-year-old white male suffered sudden painless onset of visual loss in the right eye had a cecocentral scotoma, marked disc swelling with hyperemia and flameshaped hemorrhages, and subretinal fluid extending into the macular area. The authors each consider the differential diagnosis, indications for treatment, the natural course, and the likelihood of association with various systemic diseases. (Surv Ophthalmol 26:43-48, 1981) eye. The affected

Key words. central visual dysfunction disc swelling 0 multiple sclerosis

corticosteroids optic neuropathy l

l

disease

*

tion with pupillary escape in the right eye directly and by swinging flashlight. Brightness appreciation in his right eye was approximately 50% of that in his left eye, and the left eye demonstrated central color desaturation. Kinetic visual fields demonstrated a cecocentral scotoma in the right eye (Fig. 1). Fundus examination of the right eye demonstrated marked disc swelling with hyperemia and flame-shaped hemorrhages (Fig. 2.A). There was subretinal fluid extending into the macular area with an early star figure in the nasal Henle layer (Fig. 2.B). The left fundus was normal.

A 17-year-old white male presented with the complaint of sudden onset of visual loss in his right eye two days before being referred to the Neuro-Ophthalmology Consult Office at Washington University Medical Center. The patient did not complain of pain associated with eye movements or photopsias. The remainder of his past ocular and medical history was entirely negative, as were his review of systems, family history, and social history. OCULAR

* demyelinating

EXAMINATION

What is your diagnosis? What laboratory tests and radiologic order, if any? Is any treatment warranted?

Ocular examination revealed a visual acuity of 20/200 in the right eye (not improved with refraction) and 20/20 in the left eye. Both pupils were equal, round and reactive to light and accommoda43

studies would you

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LEFT Fig. 1. Kinetic visual fields demonstrating

DIAGNOSTIC TESTS AND COURSE Laboratory results indicated that CBC, heterophile agglutinin, ANA, total complement and Cs level and FTA-ABS were all normal. Radiographic studies, including anterior-posterior (AP) and lateral as well as sinus series, were normal. No treatment was instituted. Four weeks later visual acuity in the involved eye was 20/30 with correction. Color desaturation and a decrease in brightness perception were still present in the right eye, but all evidence of an afferent pupillary defect was gone. Kinetic visual fields showed a marked decrease in central depression, and the fundus examination demonstrated marked diminution in the disc swelling with resolution of the macular involvement except for some minimal residue in Henle’s fiber layer.

Comments Comments. John L. Keltner, M.D., Departments of Ophthalmology, Neurology and Neurological Surgery, University of California at Davis, Davis, California. This history and ocular findings are most consistent with an acute optic neuropathy. This type of optic neuropathy is termed “acute idiopathic papillitis” which represents an intraocular form of optic neuritis or demyelinating disease. Papillitis is most commonly seen in children.a4 Pain on motion of the eye is frequently seen with retrobulbar neuritis. Positive visual

RIGHT a cecocentral scotoma in the right eye.

phenomena (phosphenes) appear to be related to optic nerve involvement in patients with optic neuritis and multiple sclerosis.” The absence of pain on motion of the eye or photopsias does not exclude the diagnosis of idiopathic papillitis or optic neuritis. The differential diagnosis in a 17-year-old with this type of acute optic neuropathy might include acute uveitis, vasculitis (collagen vascular disease), vasculopathies (ischemic optic neuropathy, migraine, diabetes), inflammatory lesions (syphilis, sinusitis, and other infectious processes), exogeneous drugs or toxins, and finally compressive optic neuropathy. A uveitis or other inflammatory lesion such as pars planitis usually has a chronic course, and increased inflammatory activity would be found in the vitreous and at the pars plana. A vasculitis would demonstrate other systemic signs as well as an increased erythrocyte sedimentation rate, abnormal ANA, and abnormal serum complement. Vascular events such as occur in diabetes, migraine or ischemic optic neuropathy would be unusual in this age group and with this type of presentation. Drugs or exogenous toxins affecting only one eye would also be unusual. Sinus disease, syphilis or other types of infectious processes should have other accompanying signs and symptoms. A compressive optic neuropathy has a much longer time course with progressive visual loss. Optic atrophy or chronic disc edema rather than an acutely swollen optic nerve with a macular star would be expected. This is a healthy young man; therefore, unless new neuro-

CLINICAL

CHALLENGES

45

and swollen right disc with flame-

Fq. ZB. Early “hemi” star figure in the nasal Henle layer.

logic or ophthalmologic features develop, any of these diagnostic considerations would appear to be very unlikely. In 1979, Cohen and associates’ published an excellent prospective study of 60 patients with uncomplicated optic neuritis who were followed for at least five years (mean 7.1 years). Seventeen patients (28%) developed definite multiple sclerosis; 4 patients (7%) developed probable or possible multiple sclerosis; and 6 of the 17 patients (35%) who developed multiple sclerosis did so within the first year. During the acute attack of optic neuritis, the vision remained 20/40 or better in 13 of the patients, 20/50 to 20/200 in 23 patients, and less than 20/200 in 24 patients. The initial and final visual acuities, as well as the fundus appearance, were unrelated to the eventual development of multiple sclerosis. Twentyfive percent of these patients experienced clinical recurrence of optic neuritis. Statistically, there was an increased risk of multiple sclerosis with clinical recurrence, and therefore it would appear that recurrent attacks of optic neuritis would portend a greater risk for the subsequent development of multiple sclerosis. Compston and coworker? studied 146 patients who presented with optic neuritis without evidence of multiple sclerosis. These patients were assessed between one month and 23 years after the onset of their optic neuritis. Fifty-eight patients (40%) developed multiple sclerosis. Three factors were associated with the

development of multiple sclerosis: (1) a positive typing for HLA antigen - BTlOl; (2) winter onset of initial attack of optic neuritis and a BTlOl-positive patient; and (3) recurrent attacks of optic neuritis. Percy,s’ in 1972, in a prospective analysis of 24 idiopathic cases of optic neuritis reported the subsequent development of multiple sclerosis in 17%. In 1976, Kahana and associatesPa showed that the risk of optic neuritis developing into multiple sclerosis was highest in those who were the youngest when the optic neuritis developed, and that about 30% of these patients with optic neuritis would develop multiple sclerosis within 10 years of its onset. Depending on which series one reads and how long the patient has been followed, there appears to be a moderate chance that patients will develop a demyelinating disease following an attack of optic neuritis. Of the patients in the series by Cohen and associate? who did develop multiple sclerosis, the course appeared to be benign, at least during the short period of observation. In trying to compare these various published reports which show a great variation in the attack rate of multiple sclerosis after optic neuritis, epidemiologic factors - including where the patient was born, how long he/she lived in that environment, and whether he/she moved early in life all have a bearing on the attack rate of multiple sclerosis. We do not know if the same viruses which might cause multiple sclerosis in Boston, Massachusetts, are

Fig. ZA. Hyperemic

shaped hemorrhages.

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Surv Ophthalmol

26(l) July-August

1981

the same viruses which cause multiple sclerosis in Los Angeles, California, and whether they will produce the same statistics with respect to attack rates, type of disease process, and other pertinent information to enable us to make intelligent statements with regard to any single patient. Thus, it would seem inappropriate to talk to the patient about the possibility of developing multiple sclerosis in the future. To tell a patient about this possibility may produce tremendous psychological stress for years over a disease that may never happen. If, indeed, the patient develops multiple sclerosis at some point in time, then a full discussion of the disease should ensue. In this particular patient, a laboratory evaluation might include a CBC, erythrocyte sedimentation rate, ANA, serology, fasting blood sugar, and sinus x-rays. These tests are almost invariably normal but do represent a minimum laboratory evaluation. Tests to support the diagnosis of multiple sclerosis, such as cerebrospinal fluid examination for oligoclonal bands, will not be positive early in the course of the disease process. Visually evoked potentials, particularly looking for latency changes in the opposite eye, give only inferential information. Furthermore, until an effective treatment for multiple sclerosis is available, why expend the effort to diagnose a disease which can neither be treated effectively nor prevented from progressing to a more severe form of the illness through early recognition? Papillitis and retrobulbar neuritis generally have a favorable prognosis. Visual recovery often starts in 7 to 14 days after the initial onset but may not take place for many weeks. Full recovery may take weeks or months. Earl and Martin” found that 93% of patients with optic neuritis recovered to a visual acuity of 20/30; the figure for patients under 45 years of age was 96%, and for those 45 years of age or older, was 76%. Bradley and Whitty’ reported the presence of optic disc swelling and pain was not correlated with the level of recovery. Rucke? reported that recovery of 20/30 vision occurred in 74% of patients with optic neuritis of unknown cause at the University of Michigan. Surprisingly, Cohen and associates’ reported that of 24 patients with visual acuity of 20/200 or less, 9 remained at that level. When there is a high spontaneous recovery rate in any disease process it is difficult to know if any treatment modality is effective without extremely wellcontrolled clinical trials. Even though there are many articles in the literature which attest to the effectiveness of corticosteroids in optic neuritis, few of these studies were well controlled. Bowden and coworkers,’ in 1974, in a comprehensive study of patients with optic neuritis, measured visual acuity, color vision, and visual fields, and concluded that ACTH minimally shortened the period of recovery

BURDE ET AL but did not influence the final outcome. Cohen and associates’ also found that corticosteroids did not appear to affect the final outcome in cases of optic neuritis. Bird, in a carefully controlled random study of patients with optic neuritis treated with 40 mg of retroorbital, intraconal injections of triamcinolone, found that the corticosteroids minimally reduced the recovery period but had no influence on the final visual result.’ Bird felt it was doubtful that the return of good visual acuity in two weeks, as opposed to three or four weeks, was adequate justification for the use of corticosteroids with the severe potential side effects inherent in the use of these drugs. In addition, retrobulbar injections themselves have been associated with untoward complications such as central retinal artery occlusion.‘? Thus, there is no justification for the routine use of corticosteroids or ACTH, either systemically or locally, in the treatment of optic neuritis due to intrinsic demyelination. Those patients who have bilateral optic neuritis or who already have severe loss of vision in the opposite eye probably should be treated with corticosteroids in an attempt to shorten their period of visual disability. Oral corticosteroids, 60-80 mg per day for lo-14 days, should be tried and then tapered quickly if no improvement is noted. Patients with a large inflammatory component in the vitreous may respond better than those with retrobulbar neuritis. Recent reports of manipulation of immunologic mechanisms in multiple sclerosis have raised the hope that a new approach for the treatment of this devastating disease may soon be available. High doses of predazathioprine,16~2’ antilymphocyte nisolone,12~34 and transfer factor,“~” have all been globulin, reported to produce a beneficial effect in slowing progressive disability in patients with multiple sclerosis, but the data available are not convincing. Recent work has suggested that plasma exchange may potentially be of benefit to multiple sclerosis patients.‘0~36~3e The National Multiple Sclerosis Society has formed an ad hoc working group to consider the possibility of a randomized controlled multicenter trial of plasmapheresis in multiple sclerosis patients. Until therapeutic trials or applied immunology have improved our basic understanding of the disease process, a distinction must be drawn between the valid indications for clinical experimentation (which existing trials provide) and the manner in which individual patients with multiple sclerosis should be treated.““’ Comments. Neil R. Miller, M.D., The Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland. This 17-year-old, previously healthy male presents with sudden loss of visual acuity in the right eye. His findings are that of an anterior optic neuropathy. Although young patients with migraine, diabetes

CLINICAL

CHALLENGES

mellitus or other systemic vasculopathies may develop an anterior ischemic optic neuropathy,28 this patient is otherwise healthy. In addition, the finding of a cecocentral scotoma is extremely rare in ischemic disease.2 Compressive optic neuropathies usually present with slowly progressive visual loss, rather than sudden visual 10~s.~’ In this setting, the most likely explanation is an inflammatory process involving the optic nerve, presumably located anterior to the lamina cribrosa; i.e., an anterior optic neuritis or papillitis. In many cases of optic neuritis, whether anterior or retrobulbar, deep orbital pain - both sharp and dull - may precede or occur coincident with the visual loss; however, this is by no means always the case. A macular star figure is often seen in patients with anterior optic neuritis following viral illnesses;” however, this is not a specific finding and occurs whenever there is significant leakage from disc vessels. I do not feel that any laboratory tests or x-rays are mandatory in this case. In view of the fact that inflammation of the paranasal sinuses may rarely be associated with optic neuritis,” I would certainly not object to a skull series with views of the paranasal sinuses. Although patients with connective tissue disease, syphilis, and various systemic viral infections may develop an anterior optic neuritis,‘~2g~s” with this patient’s negative past medical history I would think that the yield from serologic studies would be low. I certainly would not perform any further extensive tests. I specifically feel that a lumbar puncture has no place in the workup of an otherwise asymptomatic patient with an optic neuritis. It has been my experience that anterior optic neuritis is quite uncommonly associated with the ultimate development of multiple sclerosis. Although signs and symptoms of multiple sclerosis may develop within several months to several years in up to 50% of patients who first present with optic neuritis,6~8*22 I see no particular reason to perform any invasive studies looking for multiple sclerosis in the absence of a positive neurologic history and in view of the fact that there is neither a preventive, nor a curative, agent for the disease. To date, no treatment has been shown to be effective in causing resolution of optic neuritis. The use of retrobulbar injections of ACTH and triamcinolone have been found in controlled studies to have no effect when compared to the natural history of the disease process itself.20 In view of the potential side effects of corticosteroids, I do not treat such patients. It should be mentioned, however, that when one speaks of “resolution” of optic neuritis, one is limited by the clinical and electrophysiological studies at hand. It is possible that the studies now being used to detect optic nerve dysfunction are not sensitive enough to detect differences between treated and untreated patients. In the future, new techniques may show that corticosteroid treatment is effective in reducing the

47

degree of visual fiber damage suffered by a patient during an episode of optic neuritis. Nevertheless, until and unless such information is forthcoming, I would not recommend the use of corticosteroids in a routine case of optic neuritis, either anterior or retrobulbar. Comments. John W. Gittinger, Jr., M.D., Department of Ophthalmology, Tufts-New England Medical Center, Boston, Massachusetts. I agree with Drs. Miller and Keltner that this is most likely a case of idiopathic optic neuritis. Because of the ophthalmoscopically obvious inflammation, neuroradiological studies are not as important as in the more commonly encountered retrobulbar neuritis, an entity sometimes mimicked by compressive neuropathy. Serological studies to look for an altered immune system are interesting but do not affect initial management. A papillitis with macular exudates, as described here, has variously been called pseudo-albuminous stellate retinitis2’ or simply Leber’s stellate maculopathy, the papillomacular form of optic neuritis,’ and neuroretinitis. Duke-Elder lists a differential diagnosis for this variant of optic neuritis,” most of which has been covered in Drs. Keltner and Miller’s discussions. Neuroretinitis has also been associated with mononucleosis.18 It should not be confused with papillophlebitis (an entity with its own nosological problems),” where vision usually remains near normal and retinal exudation is absent. Certain malignant optic nerve tumors produce disc swelling and exudates, usually in a blind eye and not involving the macula.21 I am a nontreater of optic neuritis unless the temporarily reduced acuity represents a major disability for the affected individual, as in bilateral disease. I admit to occasionally violating this principle when the visual loss is very severe, although I have no systematic basis for this exception. Papillitis or neuroretinitis, as has been pointed out, have a predilection for young people and for bilaterality. My impression is that this is also the group where a recent viral illness is most frequently identified, although this was not true in the case presented here. There is some indication, then, that this optic neuropathy is separable from retrobulbar optic neuritis, but the overlap between the two groups is probably significant enough to prevent a conclusion as to the eventual prognosis in an individual case. Concluding Comments. Ronald M. Burde, M.D., Departments of Ophthalmology, Neurology, and Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri. At the end of his discussion, Dr. Miller broached a very important topic. The use of the term, “recovery,”

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in retrobulbar

neuritis or papillitis does not imply a return anatomically or physiologically to the premorbid state. What is implied is that the commonly used clinical parameters of visual function (i.e., Snellen acuity and kinetic visual fields) have improved so that they fall within a statistical norm. There is clinically evident damage to the nerve fiber bundles by careful direct ophthalmoscopy as well as measurable change in visual evoked response latency. The implications are anatomically and physiologically obvious, but at the moment, not directly applicable. The afferent visual system is anatomically redundant, and patients who sustain what appears to be substantial dropout of nerve fiber bundles can have “normal” visual function as routinely measured. The optic nerve, on the other hand, transmits a myriad of coded material that we do not routinely measure, e.g., color saturation, brightness appreciation, spatial and temporal information, etc. Each individual who has had optic nerve damage seems to have these systems affected in a different manner. The implications of this are not clear.

13. 14. 15. 16.

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18. 19. 20.

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