- Email: [email protected]
Management of optic neuritis
VOLUME
SURVEY OF OPHTHALMOLOGY
THERAPEUTIC
20.
NUMBER
5.
MARCH-APRIL
1976
REVIEW
PHILIP P. ELLIS, EDITOR
Management ROBERT
S. HEPLER,
of Optic Neuritis
M.D.
Department of Ophthalmology and the Jules Stein Eye Institute, School of Medicine, University of California, Los Angeles
Abstract. To improve understanding and effectiveness of therapy in optic nerve disease, various causes of so-called optic neuritis should be identified when possible. The
clinical characteristics of demyelinating optic neuropathy can be contrasted with those of ischemic optic neuropathy, nutritional optic neuropathy, true optic nerve inflammation (e.g., luetic), optic nerve infiltration with tumor, and compression neuropathy caused by adjacent tumor. Radiologic studies and other means of investigating patients with optic neuritis are reviewed. Arguments in favor of, and against, treatment of presumed demyelinating optic neuritis are presented along with representative corticosteroid treatment regimens. The natural tendency toward spontaneous improvement of optic neuritis makes the effect of treatment difficult to assess. (Surv Opbthalmol
20 (5): 350-357,
1976)
Key Words: cortisone multiple sclerosis optic nerve optic neuritis periocular injections - steroids l
l
l
l
t has been observed of the practice of medicine that where several differing therapies are proposed for a given disease, one should be suspicious of all. Certainly this applies to the historical treatment of optic neuritis, including the present therapy as well as past. In a recent review Lieberman lists the following, all of which have been recommended at one time or another within the past forty years in the United States: opening of the bowels, sweating by hot-air baths, merhistamines, cury, iodides, multivitamins, nicotinic acid, amyl nitrite inhalation, IV sodium nitrite, IM atropine, IM acetylcholine, typhoid vaccine, surgical decompression of the optic canal, paranasal sinus drainage, and shrinkage of nasal mucosa.
I
350
Will corticosteroids, advanced for the treatment of optic neuritis by Woods’ in 1951, eventually join mercury, iodides, and the others in the list of discarded remedies? There are two major reasons for the continuing confusion which surrounds optic neuritis therapy. One pertains to the acknowledged great tendency for patients with optic neuritis to improve spontaneously, regardless of, or even despite, what is done to help them. The need for well controlled studies of drug effectiveness which take into adequate account the strong tendency toward spontaneous improvement has yet to be met, although some investigations have attempted to fill this need. Unfortunately, one still encounters reports of procedures and thera-
THERAPEUTIC REVIEW
peutic agents enthusiastically recommended because the authors have used the agents in some patients, many of whom have gotten better. The concerned physician should distrust these endorsements until there is scientifically valid evidence that such patients, untreated, would not have fared as well ultimately as those who were. The other major reason for confusion lies in varying definitions of optic neuritis. Some physicians, particularly those who observed and wrote some time ago, used the term so broadly as to encompass almost any process which interferes with optic nerve function. Thus, broadly defined, optic neuritis might include such disparate entities as ischemic optic neuropathy in the elderly, luetic optic neuritis, and the toxic optic neuropathies (so called tobacco/alcohol/prison camp amblyopias). Clinical observations based upon such different entities as these, calling them all “optic neuritis,” could only be confusing and this is reflected in the literature. Others have defined optic neuritis in a very narrow sense, meaning to implicate demyelination of the optic nerve, such as occurs in multiple sclerosis. Optic neuritis, as used in this review, refers to this usually idiopathic form of common optic neuropathy unless another meaning is clearly indicated. In a specific patient, optic neuritis may or may not be associated with more generalized multiple sclerosis. Therapeutic aspects of certain other optic neuropathies will be considered briefly, even though these should not be confused with the term optic neuritis as used here. Clinical Features of Optic Neuritis Truly abrupt onset of decreased vision (as contrasted with a sudden discovery of reduced vision) is the usual presenting chief complaint. Visual function declines to its lowest point within hours to a few days. Usually there is associated pain, which may begin concurrently with, shortly after, or a few hours or days before outset of the visual disturbance. The pain varies from entirely absent to severe. There are recorded instances in which pain brought the patient to the physician even before vision declined. The pain characteristically is made worse by ocular movement, and sometimes the globe is tender to palpation. With rare exception, signs and symptoms are uniocular at any given time. The physician observes a significant reduction
351
in vision, with acuity often as low as 20/200 and in severe cases, bare light perception or even no light perception. The corresponding visual field defect is a central scotoma. Important additional clues of optic nerve dysfunction include impaired color vision and an afferent pupillary defect. The patient reports that a light shining in the affected eye is much less bright than is the same light shining in the unaffected eye. In most cases of optic neuritis, there is no visible abnormality of the optic nerve head on funduscopy. Occasionally, when the area of optic nerve involvement is presumed to be more anteriorly situated, the disc is swollen and hyperemic and may have associated cells in adjacent vitreous observed by biomicroscopy. The implications of optic neuritis are basically similar, whether involvement is posterior in the nerve (retrobulbar neuritis), or sufliciently anterior to cause disc swelling (papillitis). Some feel that prognosis for visual recovery is poorer, and association with multiple sclerosis less, with papillitis than with retrobulbar neuritis. In distinction from earlier, higher estimates, Percy et a1.6 propose that the likelihood of eventually developing frank multiple sclerosis after one episode of idiopathic optic neuritis is 17%. Many cases of optic nerve dysfunction are erroneously attributed to idiopathic optic unfortunate neuritis: this is particularly because there is practical importance in identifying some of the entities which might masquerade. One such category is tumor arising close to the sella turcica and gradually compromising visual function first in one eye, then in the second eye. This can occur in any age group. While the discovery of reduced vision may be sudden, the actual loss is characteristically gradual and is usually painfree. There is no spontaneous improvement after the abrupt loss, which is so typical of the course of true optic neuritis patients. Careful examination of the second, presumably asymptomatic eye, often shows beginning abnormalities of visual function, such as a subtle temporal field defect not expected in the patient with optic neuritis. Ischemic optic neuropathy is another entity which should not be confused with optic neuritis. Unless there is underlying collagenvascular disease or some other reason for a young person to develop disturbance of blood flow, ischemic optic neuropathy occurs in the elderly person, particularly if there is
352
Surv
Ophthalmal
20
(5)
March-April
1976
longstanding hypertension, diabetes mellitus, or generalized arteriosclerosis. While the onset of visual loss in ischemic optic neuropathy is sudden, there is characteristic pale swelling of the nerve head, which serves as a major differentiating feature. It is desirable to recognize cases of optic nerve ischemia in the middle-aged and elderly and thereby avoid the confusing implications of optic neuritis in this age group.
.
Evaluation of Patient with Optic Neuritis The goals of medical investigation of the patient with optic neuritis are to: (1) look for neurological signs and symptoms which might implicate generalized demyelinating disease (multiple sclerosis); (2) find other generalized medical causes for acute optic nerve dysfunction, i.e. collagen vascular disease; (3) rule out local tumors as the cause of visual loss, i.e. parachiasmal meningioma; and (4) determine suitability for steroid therapy, if recommended, by considering the possibility of coexistent diabetes mellitus, gastric ulcer, tuberculosis, or significant mental disorder. These goals are carried out well by obtaining: (1) General medical and neurologic assessment, by a general physician, internist, or neurologist, depending upon local custom and availability of consultant; (2) complete blood count, sedimentation rate, two-hour postprandial blood sugar, chest x-ray; (3) cerebrospinal fluid examination for total protein and protein electrophoresis (elevated gamma globulin, during the acute phase of optic neuritis, is a helpful clue toward probable MS.); and (4) skull x-ray series, interpreted by a radiologist experienced in neuroradiological studies. After obtaining the above and either instituting or not instituting therapy, it is essential to follow the patient. Although other causes for optic nerve dysfunction, even compressive tumors, may demonstrate a remitting course occasionally, this spontaneous improvement is so much a feature of ordinary optic neuritis as to provide valuable confirmation of one’s presumed diagnosis. The improvement to be expected will usually be very evident within four to eight weeks, as contrasted with the stable to steady downhill course observed with parachiasmal tumors. If there is doubt clinically about the
HLPLLR
diagnosis of optic neuritis, and particularly if there is failure to improve in visual function, then additional studies are to be considered. Especially useful in ruling out intracranial tumors compromising the optic nerves is high quality laminography (polytomography) of the optic canals and sella turcica. A recent development useful in the safe, noninvasive study of intracranial structures and spaces is computerized axial tomography (EMI scan). However, the EMI scan is relatively less successful in outlining small parachiasmal masses than it is in finding abnormalities elsewhere in the head. In relatively exceptional, confusing cases, neurosurgical consultation and pneumoencephalography with polytomography are used to provide the best possible neuroradiologic clearance of the parachiasmal regions. It should be emphasized that the great majority of optic neuritis cases do not need, and should not receive invasive neuroradiologic procedures such as angiography and pneumoencephalography. These latter studies should be reserved for truly worrisome diagnostic puzzles. What is demyelination? The normal optic nerve is made up of at least a million axons connecting the retinal recipient elements with synapses in the lateral geniculate bodies. Each axon is insulated by a coat of protein-lipid substances called myelin which enhances the rapid conduction of nerve impulses. In demyelination, the insulating myelin is lost from the axon, which may appear entirely intact microscopically, but fail to function conductively in a normal manner. Descriptions of acutely demyelinated optic nerve lesions observed pathologically are hard to find, since patients rarely die in conjunction with an acute optic neuritis. However, one can make inferences of what is probably going on in such optic nerves from descriptions of demyelinating plaques observed elsewhere in the central nervous system. The breakdown of myelin liberates sudanophilic globules which are phagocytized by microglia, these becoming distended by fatty breakdown products. The microglia accumulate in large perivascular aggregates, Local edema accumulates near the focal lesion. Later on, astroglia replace microglia to form the discrete plaques of gliosis observed in the brains of patients who have had generalized multiple sclerosis.
THERAPEUTIC REVIEW
Arguments in Favor of and Against Steroid Therapy Those who favor the use of corticosteroid therapy cite the following arguments (followed by appropriate rebuttals): 1. There is a theoretical basis for using an agent (cortisone) known to reduce edema and inflammation. This argument is nicely summarized by Lubow and Adams’ as follows: The initial cause of the demyelinating lesion in the optic nerve remains beyond our grasp, but the secondary structural changes with edema compression, ischemia, and further disorganization of myelin and axon fibers are characteristic of severe brain swelling and may be reversed by large quantities of steroids used for only a few days. Photographs of disc edema in acute papillitis after one and two days of treatment confirm this response. It seems reasonable to anticipate that rapid resolution of the lesion will produce a smaller scar with less axonal impairment for future function. For just this reason, it is important to judge the rate of improvement with treatment as compared to the natural course of the disease, not just the final visual acuity after one month or one year.
353
probably the best published efforts attempting to show a beneficial effect of steroids. By these authors’ own acknowledgment, their data in 25 treated and 25 untreated patients showed no statistical significance in ultimate visual acuity between the two groups, measured at one year. They did, however, demonstrate a more rapid improvement by the eighth day of treatment, which would have to be evaluated against the risks and side effects of therapy with ACTH or corticosteroids.)Bv7 (Additional evidence in rebuttal is provided in the large collaborative study of Rose et al.* who concluded that “Short term, high dosage use of ACTH hastened the evidences of improvement of symptoms and signs, but it cannot be stated from the data of this study that the ultimate extent of improvement was greater than that attained by placebo . . . The results of this study provide no basis for a recommendation for the use of ACTH as a long-term treatment for MS patients.“)
4. There is much pressure to “do something,” particularly when visual impair(Rebuttal: It isn’t known that edema ment is severe, or when the second eye is inand/or inflammation play any role in the volved. The steroid agents not only provide a pathologic changes of optic neuritis. The highly visible “doing something” which imedema compression and ischemia mechanism is conjectural in the case of the optic nerves, presses the patient, but they often provide a effect which counters whatever may occur elsewhere in the central euphoria-inducing patient concern with the illness. nervous system. If edema and inflammation (Rebuttal: It is an abdication of a do play a significant role in optic neuritis, one physician’s responsibility in the scientific should reasonably expect impressive benefit practice of medicine to use medication not from steroid therapy instead of the debatable improvement observed. It is the final visual shown to benefit the disease being treated, when there are potentially acuity after one month [or more ap- particularly awesome side effects of that treatment. As to propriately, after several months] which is the euphoria, some patients respond with a important ultimately, not the speed of the imdangerous degree of euphoria, or with depresprovement.) sion severe enough to precipitate suicide soon 2. Empirical observation indicates that after initiation of therapy.) steroids work. (Rebuttal: This seems to depend upon who is making the observations.) 3. Statistical studies already published prove the beneficial effects. (Rebuttal: As indicated earlier, all such studies having to do with multiple sclerosis, and optic neuritis in particular, contain the inherent difficulties of interpretation which stem from the natural tendencies toward marked spontaneous improvement of these diseases. Probably 90% of optic neuritis patients return to visual acuity of at least 20/40. The papers of Rawson et al.7 are
5. Steroid therapy is so widespread an approach to the treatment of optic neuritis as to constitute a legally significant “standard of care in the community.” (Rebuttal: This argument is an appeal to “everyone else is doing it” and is unworthy of scientific medicine. Fortunately, while most physicians probably treat optic neuritis with steroids in one form or another, there are enough who do not do so, and enough thoughtful analysis in the literature opposing steroid therapy, to maintain a dialogue on the subject.)
354
Surv Ophthalmol 20 (5) March-April
1976
Recommended Steroid Therapy Regimens The basic aim of corticosteroid therapeutic regimens is to provide enough corticosteroid agent to influence the optic nerve lesion without inducing unacceptable side effects. These side effects are generally well known, and need not be emphasized here. It is worth mentioning, however, that the common belief that a brief trial of steroids has no serious harmful effects is not always true. There are reported instances of fatal GI bleeding, severe psychosis, aseptic necrosis of the femur, activation of latent tuberculosis, and other serious side effects which have arisen from only a few weeks’ therapy with corticosteroids. Hence, the need continues to assess the patient’s general medical status, and to balance this against the best available steroid administration program. Whatever the treatment plan, it is generally agreed that the greatest possible effect is begun by commencing therapy immediately. The following are representative recommended approaches to steroid therapy, in detail, as suggested in recent publications. ACTH given parenterally has the advantage of not suppressing the adrenal glandular output. Poskanzer, in communication with Wray, expresses the viewpoint that ACTH may be more efficacious than synthetic corticosteroids such as prednisone. The disadvantages of ACTH administration include the need for hospitalization during at least the initial phases, and the requirement for multiple percutaneous injections, to which some patients object. A representative treatment schedule, as proposed by Wray,” is as follows: ACTH 20 units/cc. 80 units IV q 6-8 hours in 500 cc of 5% Dextrose in water for three days. Then ACTH gel (40 units/cc.) IM 40 units q 12 hours for seven days, then the dose is reduced by 10 units every three days as follows: 35 units bid x three days 30 units bid x three days 50 units qd x three days 40 units qd x three days 30 units qd x three days 20 units qd x three days
20 units qod x three days For patients who can’t or won’t enter the hospital, and for those to whom avoidance of multiple injections is important, orally administered agents such as prednisone are available. These have high potency, rapid and
HEPLER
total absorption, and relatively low salt retention properties. The evidence that ACTH administration provides more beneficial effect than prednisone is meager indeed, and certainly prednisone is far less costly and more convenient for patient and physician alike. A representative treatment schedule for prednisone is as follows: 100 mgm day 1 80 mgm day 2 60 mgm day 3-5 30 mgm day 6-7 At the end of the first week of therapy the response can be assessed and therapy either continued on a slowly tapering dosage, or if there has been no indication of beneficial effect, the prednisone can be simply discontinued. Lubow and Adams’ recommend intensive treatment with massive dosages of steroids (200 mgm of prednisone per day) for 36-72 hours, which they believe is effective in aborting an acute attack of optic neuritis. They believe that prolonged treatment is not indicated in this disorder. Hopefully, the patient receiving either ACTH or corticosteroids such as prednisone will be evaluated medically prior to instituting therapy, and followed during therapy by a general physician or internist. Occasionally, however, the ophthalmolpgist may have to fill at least part of the role of If this occurs, the general physician. ophthalmologist should remember the importance of: 1. Good history taking of past medical events including diabetes mellitus, peptic ulcer, tuberculosis, psychosis or depression, drugs used (aspirin, anticoagulants, digitalis). 2. Baseline chest x-ray and, possibly, skin tests. 3. Complete blood count and stool guiac. 4. Antacids (maalox or equivalent, 1 ounce two hours after meals and at bedtime). 5. Potassium supplement - eat bananas, oranges, tomatoes, and consider added potassium supplement. 6. Tapering steroid effect - if steroids are given, then discontinued within a two-week period, no significant endogenous adrenal suppression occurs. However, if steroid administration is prolonged, then the terminal phases of tapering should be carried out gradually to give the adrenal glands a chance to resume functioning. Furthermore, the
THERAPEUTIC REVIEW
355
patient and the family should be instructed that in the event of accident, surgery, or serious illness within a year of the termination of steroid therapy, physicians caring for the patient must be alerted to the past steroid therapy in order to provide supplementation. of repository Sub-Tenon’s injection steroids has obvious theoretical advantages in delivering large dosage to the region of the eye while minimizing the effects of systemic steroids. Despite the enthusiastic endorsement of persuasive advocates, proof of effectiveness is lacking. Severe side effects of this route of delivery have included perforations of the globe (several reported instances, and the number unreported can only be guessed), and severe steroid-induced glaucoma. For those who wish to utilize sub-Tenon’s injection, the following technique is recommended by Smith et al.O*lo A sterile, disposable 1 ml tuberculin syringe with a 27 gauge, l/2 inch needle is used. (One ml of triamcinolone acetonide aqueous suspension
sub-Tenon’s injection. The author prefers brief, initially intensive (100 mgm per day for two days, then taper) administration of prednisone for a one-week period in most such patients. If the indications for treatment are strong and if there are serious contraindications to systemic steroid administration, repository steroids given sub-Tenon’s injection may be offered to the patient. 5. It is a serious mistake to raise the possibility of multiple sclerosis in conversation with the patient or in medical reports. If the patient really has multiple sclerosis, this would be far better explained by a neurologist (who should evaluate the patient anyway, partitularly if there are signs or historical events to suggest disseminated disease). If the patient doesn’t go on to develop multiple sclerosis, the ophthalmologist has done an enormous disservice by even raising the issue, needlessly placing the patient under a cloud. The consulting neurologist can also advise
[Kenalog IM] is loaded into the syringe). The lower lid is gently wiped with an alcohol sponge, the patient is instructed to look up and to the opposite side, and the injection is given through the lower lid at the junction of the outer and middle thirds in the same direction as for a routine retrobulbar anesthetic. The needle is pushed snugly to its base, and the medication is injected moderately slowly. Covering the eye for about 30 minutes until the bolus of the drug is absorbed is helpful in avoiding transient diplopia. A semipressure eye patch can be applied for one to two hours if desired. The effect of the injection usually lasts for one to two weeks . . .
regarding limitation of exercise, exposure to heat, d esirability of moving to a cooler climate, and other practical aspects of care for the patient with multiple sclerosis.
In summary, patients with optic neuritis for whom ACTH or corticosteroid therapy is contemplated should be approached with the following realizations. 1. No physician should feel that the present evidence compels treatment of optic neuritis with ACTH or corticosteroids. 2. However, most patients with this disorder are so treated at present. 3. Because the evidence is uncertain and treatment with any form of corticosteroids or ACTH carries with it risk, the patient should participate in giving medico-legally valid informed consent. 4. Even a therapeutic conservative (such as the author of this review) will treat most patients if their opti neuritis is severe, or if it occurs in their only good eye. Individual preference and local custom can determine whether to use ACTH, corticosteroids, or
patients
with
indications
of dissemination
Treatment of Other Optic Neuropathies ISCHEMIC
OPTIC NEUROPATHY
Emboli to the circulation of the optic nerve can come from carotid atheromas, from the walls of the ventricles of the heart, particularly in the presence of cardiac arrhythmia, from infrequent sources such as cardiac myxomas, and very commonly postcardiotomy, when soft platelet emboli forming on rough surfaces along the walls of the heart break loose and are carried to the small vessels supplying the optic nerve. Nonembolic categories of ischemic optic neuropathy include carotid occlusive disease in which the pathogenesis of the optic nerve change is reduced perfusion pressure in the large vessels, (rather than emboiization from them), giant cell arteritis, and intrinsic small vessel disease adjacent to or within the optic nerve, presumed to be arteriosclerotic in nature. Neurological textbooks continue to list diabetes mellitus as a cause of optic neuritis. However, most if not all of the cases presented to support this notion are probably
356
Surv Ophtholmol 20 (5) March-April
1976
unidentified ischemic optic neuritis. Hence, the situation is not one of diabetes mellitus producing an actual optic neuritis, but rather a predisposition to small vessel occlusive disease within the optic nerve blood supply induced by the diabetes mellitus. Description of the clinical presentation of ischemic optic neuropathy is beyond the scope of the present review. These features are presented in a detailed review by Burde,’ which cites (in comparison with typical optic neuritis) the elderly age group, the abrupt onset, and the characteristic pale swelling of the optic nerve head observed in the acute phase and often misinterpreted as papilledema. Particularly helpful diagnostically is a characteristic altitudinal quality of the visual field defect, which often can be correlated with pale swelling or later atrophy of the corresponding portion of the optic nerve head. The most common source of either hard or soft embolic material in the optic nerve or retinal blood supply is from an ulcerating atheroma close to the junction of the internal and external carotid arteries. The therapeutic approach for this embolic category is to remove the source of embolism, presuming that the patient’s age and general status are such as to permit consideration of modern, safe angiography and possible endarterectomy or grafting procedures. Patients with soft platelet emboli following cardiotomy are generally anticoagulated until healing is completed to lessen the number and severity of effect of further emboli. Patients with suspected ulcerating atheromas, whose general status won’t permit consideration of endarterectomy, probably should not be anticoagulated, but they may be helped by the administration of aspirin to reduce platelet cohesiveness. When giant cell arteritis is the cause of ischemic optic neuropathy, systemic steroids are indicated, to be started as soon as a markedly elevated erythrocyte sedimentation rate and the clinical setting establish the likelihood of the diagnosis. While giant cell arteritis has been reported occasionally in younger adults, it is generally a disease of the very aged. Far more cases occur in the patient over 70 years of age than in younger persons. Proven cases under the age of 60 are rare. The sedimentation rate is usually very high, not just mildly elevated. A useful rule of thumb is to realize that the sedimentation rate is
HLPLER
generally equal to the age of the patient during active phases of giant cell arteritis. The steroids should be continued until the sedimentation rate and the clinical course indicate that the disease has become quiescent, and the patient needs to be observed for indications of recurrence for at least several years. The value of temporal artery biopsy lies not just in establishing the diagnosis for academic purposes (a negative biopsy, of course, doesn’t rule out the diagnosis in this disorder in which segmental arterial involvement is the rule). It also provides means of persuading reluctant internists that the patient has a potentially blinding or lethal disease warranting continued steroid therapy until controlled. When the diagnosis of giant cell arteritis is indicated by the history, physical findings, and elevated sedimentation rate, corticosteroid therapy should be commenced at once, even before the results of the temporal artery biopsy are received. Despite early indications that diphenylhydantoin (Dilantin@) might be helpful in treating ischemic optic neuropathy, Burde’ summarizes present consensus by pointing out that Dilantins has not proven (statistically) to be efficacious. While most patients with ischemic optic neuropathy due presumably to arteriosclerosis are treated with systemic steroids, Burde points out that neither corticosteroids nor anticoagulants have proven of benefit in this condition.’ Hayreh’” reviewed the subject of ischemic optic neuropathy recently and expressed the opinion that systemically administered steroids substantially improve the visual outcome in this disorder. His recommendation is based upon evaluation of a small group of patients whose acute optic nerve disturbance is presumed to be arteriosclerotic. His conclusion that such patients are improved by steroids given while their optic nerves are still visibly swollen is being investigated further, using larger numbers of patients subjected to a double-blind, randomized study. Hopefully, additional significant data of this sort will resolve firmly the present uncertainty which many clinicians feel about the efficacy of steroid administration in ischemic optic neuropathy not due to giant cell arteritis. TOBACCO/ALCOHOL (NUTRITIONAL, CAMP, TOXIC) OPTIC NEUROPATHY
PRISON
It is beyond the scope of this review to
THERAPEUTIC REVIEW
357
References discuss the reasons why cyanide metabolism is implicated in this CategOry of optic I. gurde RM: Ischemic optic neuropathy, in neuropathy, as well as in Leber’s hereditary Neuro-Ophthalmology Symposium of the optic atrophy. The general subject has been University of Miami and the Bascom Palmer Eye Institute, Vol VII. St. Louis, CV Mosby, reviewed by Lessell.* The traditional therapy 1973. pp 38-62 recommended in these disorders has been good nutrition, supplemental vitamins, strict la. Hayreh SS: Anterior Ischemic Optic Neuropathy, New York, Springer-Verlag, 1975, pp avoidance of tobacco and alcohol (and 101-111 perhaps a wiser choice of one’s ancestors, in the case of those who suffer from Leber’s 2. Lessell S: Toxic and deficiency optic neuropathies, in Neuro-Ophthalmology Symhereditary optic atrophy). Reports in the posium of the University of Miami and the British literature suggest that one should add Bascom Palmer Eye Institute, Vol VII, St a trial of hydroxy cobalamine, the hydroxLouis, CV Mosby, 1973. pp 21-37 ylated form of vitamin B,, which has a high 3. Lieberman TW: Use or abuse of corticosteroid degree of potency compared to ordinary therapy in acute optic neuritis, in Symposium vitamin B,,. The recommended dosage is 1 on Ocular Therapy, St Louis, CV Mosby, 1974. pp 75-82 mgm parenterally, daily for seven days, then 4. Lubow M, Adams L: The changing manageweekly for an additional three months.
ment of acute optic neuritis, in Symposium of
OPTIC
NEUROPATHY
INFILTRATIVE
the University of Miami Palmer Eye Institute, Vol
DUE TO
ent knowledge
of optic nerve disease
and its
treatment dictate humility in our therapeutic approach.
the
Bascom
Mosby, 1972. pp 44-50 Percy A, Nobrega ST, Kurland LT: Optic sclerosis. Arch and multiple neuritis
TUMOR
Optic nerve involvement with infiltrative lymphoma or metastatic tumor is often remarkably sensitive to irradiation, even when the primary tumor itself would not be expected to be responsive. Patients with optic nerve impairment due to this cause are subject to rapidly progressive decrease in vision, for instance, passing from normal acuity to bare light perception over the course of a few days. Despite their limited long term life expectancy, they are likely to be very distressed by their loss of vision which may well be reversed with externally delivered irradiation given in well tolerated dosage. Radiation therapists in major medical centers are acquainted with the recommended treatment factors. In summary, management of the optic neuropathies begins with identification of the probable etiologic/diagnostic category, followed by selection of therapy appropriate _ _. -. _. . ” to that category of disease. The limits ot pres-
and
VI, St Louis, CV
Ophthalmol
87:135-139,
1972
Rawson MD, Liversedge LA: Treatment of retrobulbar neuritis with corticotrophin. Lancet
2:222-224,
1969
Rawson MD, Liversedge LA, Goldfarb G: Treatment of acute retrobulbar neuritis with corticotrophin. Lancet 2:1044-1046, 1966 Rose AS, Kuzma JW, Kurtzke JF, et al: Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs. placebo. Neurology 9.
20: l-59,
1970
Smith JL, McCrary JA, Bird AC, et al: SubTenon steroid injection for optic neuritis.
Trans Am Acad Ophthalmol Otolaryngol 74:1249-1253, 1970 IO. Smith JL: Editor’s Note, in Symposium of the University of Miami and the Bascom Palmer Eye Institute, Vol. VI, St. Louis, CV Mosby,
1972. p 49 Il. Wray SH: The treatment of optic neuritis. Sight Saving Rev: 5-13, Spring, 1972 Reprint requests should be addressed to Dr. Robert Hepler, Jules Stein Eye Institute, University of California
California 90024.
at LOS Angeles,
LOS Angeles,
SURVEY OF OPHTHALMOLOGY
THERAPEUTIC
20.
NUMBER
5.
MARCH-APRIL
1976
REVIEW
PHILIP P. ELLIS, EDITOR
Management ROBERT
S. HEPLER,
of Optic Neuritis
M.D.
Department of Ophthalmology and the Jules Stein Eye Institute, School of Medicine, University of California, Los Angeles
Abstract. To improve understanding and effectiveness of therapy in optic nerve disease, various causes of so-called optic neuritis should be identified when possible. The
clinical characteristics of demyelinating optic neuropathy can be contrasted with those of ischemic optic neuropathy, nutritional optic neuropathy, true optic nerve inflammation (e.g., luetic), optic nerve infiltration with tumor, and compression neuropathy caused by adjacent tumor. Radiologic studies and other means of investigating patients with optic neuritis are reviewed. Arguments in favor of, and against, treatment of presumed demyelinating optic neuritis are presented along with representative corticosteroid treatment regimens. The natural tendency toward spontaneous improvement of optic neuritis makes the effect of treatment difficult to assess. (Surv Opbthalmol
20 (5): 350-357,
1976)
Key Words: cortisone multiple sclerosis optic nerve optic neuritis periocular injections - steroids l
l
l
l
t has been observed of the practice of medicine that where several differing therapies are proposed for a given disease, one should be suspicious of all. Certainly this applies to the historical treatment of optic neuritis, including the present therapy as well as past. In a recent review Lieberman lists the following, all of which have been recommended at one time or another within the past forty years in the United States: opening of the bowels, sweating by hot-air baths, merhistamines, cury, iodides, multivitamins, nicotinic acid, amyl nitrite inhalation, IV sodium nitrite, IM atropine, IM acetylcholine, typhoid vaccine, surgical decompression of the optic canal, paranasal sinus drainage, and shrinkage of nasal mucosa.
I
350
Will corticosteroids, advanced for the treatment of optic neuritis by Woods’ in 1951, eventually join mercury, iodides, and the others in the list of discarded remedies? There are two major reasons for the continuing confusion which surrounds optic neuritis therapy. One pertains to the acknowledged great tendency for patients with optic neuritis to improve spontaneously, regardless of, or even despite, what is done to help them. The need for well controlled studies of drug effectiveness which take into adequate account the strong tendency toward spontaneous improvement has yet to be met, although some investigations have attempted to fill this need. Unfortunately, one still encounters reports of procedures and thera-
THERAPEUTIC REVIEW
peutic agents enthusiastically recommended because the authors have used the agents in some patients, many of whom have gotten better. The concerned physician should distrust these endorsements until there is scientifically valid evidence that such patients, untreated, would not have fared as well ultimately as those who were. The other major reason for confusion lies in varying definitions of optic neuritis. Some physicians, particularly those who observed and wrote some time ago, used the term so broadly as to encompass almost any process which interferes with optic nerve function. Thus, broadly defined, optic neuritis might include such disparate entities as ischemic optic neuropathy in the elderly, luetic optic neuritis, and the toxic optic neuropathies (so called tobacco/alcohol/prison camp amblyopias). Clinical observations based upon such different entities as these, calling them all “optic neuritis,” could only be confusing and this is reflected in the literature. Others have defined optic neuritis in a very narrow sense, meaning to implicate demyelination of the optic nerve, such as occurs in multiple sclerosis. Optic neuritis, as used in this review, refers to this usually idiopathic form of common optic neuropathy unless another meaning is clearly indicated. In a specific patient, optic neuritis may or may not be associated with more generalized multiple sclerosis. Therapeutic aspects of certain other optic neuropathies will be considered briefly, even though these should not be confused with the term optic neuritis as used here. Clinical Features of Optic Neuritis Truly abrupt onset of decreased vision (as contrasted with a sudden discovery of reduced vision) is the usual presenting chief complaint. Visual function declines to its lowest point within hours to a few days. Usually there is associated pain, which may begin concurrently with, shortly after, or a few hours or days before outset of the visual disturbance. The pain varies from entirely absent to severe. There are recorded instances in which pain brought the patient to the physician even before vision declined. The pain characteristically is made worse by ocular movement, and sometimes the globe is tender to palpation. With rare exception, signs and symptoms are uniocular at any given time. The physician observes a significant reduction
351
in vision, with acuity often as low as 20/200 and in severe cases, bare light perception or even no light perception. The corresponding visual field defect is a central scotoma. Important additional clues of optic nerve dysfunction include impaired color vision and an afferent pupillary defect. The patient reports that a light shining in the affected eye is much less bright than is the same light shining in the unaffected eye. In most cases of optic neuritis, there is no visible abnormality of the optic nerve head on funduscopy. Occasionally, when the area of optic nerve involvement is presumed to be more anteriorly situated, the disc is swollen and hyperemic and may have associated cells in adjacent vitreous observed by biomicroscopy. The implications of optic neuritis are basically similar, whether involvement is posterior in the nerve (retrobulbar neuritis), or sufliciently anterior to cause disc swelling (papillitis). Some feel that prognosis for visual recovery is poorer, and association with multiple sclerosis less, with papillitis than with retrobulbar neuritis. In distinction from earlier, higher estimates, Percy et a1.6 propose that the likelihood of eventually developing frank multiple sclerosis after one episode of idiopathic optic neuritis is 17%. Many cases of optic nerve dysfunction are erroneously attributed to idiopathic optic unfortunate neuritis: this is particularly because there is practical importance in identifying some of the entities which might masquerade. One such category is tumor arising close to the sella turcica and gradually compromising visual function first in one eye, then in the second eye. This can occur in any age group. While the discovery of reduced vision may be sudden, the actual loss is characteristically gradual and is usually painfree. There is no spontaneous improvement after the abrupt loss, which is so typical of the course of true optic neuritis patients. Careful examination of the second, presumably asymptomatic eye, often shows beginning abnormalities of visual function, such as a subtle temporal field defect not expected in the patient with optic neuritis. Ischemic optic neuropathy is another entity which should not be confused with optic neuritis. Unless there is underlying collagenvascular disease or some other reason for a young person to develop disturbance of blood flow, ischemic optic neuropathy occurs in the elderly person, particularly if there is
352
Surv
Ophthalmal
20
(5)
March-April
1976
longstanding hypertension, diabetes mellitus, or generalized arteriosclerosis. While the onset of visual loss in ischemic optic neuropathy is sudden, there is characteristic pale swelling of the nerve head, which serves as a major differentiating feature. It is desirable to recognize cases of optic nerve ischemia in the middle-aged and elderly and thereby avoid the confusing implications of optic neuritis in this age group.
.
Evaluation of Patient with Optic Neuritis The goals of medical investigation of the patient with optic neuritis are to: (1) look for neurological signs and symptoms which might implicate generalized demyelinating disease (multiple sclerosis); (2) find other generalized medical causes for acute optic nerve dysfunction, i.e. collagen vascular disease; (3) rule out local tumors as the cause of visual loss, i.e. parachiasmal meningioma; and (4) determine suitability for steroid therapy, if recommended, by considering the possibility of coexistent diabetes mellitus, gastric ulcer, tuberculosis, or significant mental disorder. These goals are carried out well by obtaining: (1) General medical and neurologic assessment, by a general physician, internist, or neurologist, depending upon local custom and availability of consultant; (2) complete blood count, sedimentation rate, two-hour postprandial blood sugar, chest x-ray; (3) cerebrospinal fluid examination for total protein and protein electrophoresis (elevated gamma globulin, during the acute phase of optic neuritis, is a helpful clue toward probable MS.); and (4) skull x-ray series, interpreted by a radiologist experienced in neuroradiological studies. After obtaining the above and either instituting or not instituting therapy, it is essential to follow the patient. Although other causes for optic nerve dysfunction, even compressive tumors, may demonstrate a remitting course occasionally, this spontaneous improvement is so much a feature of ordinary optic neuritis as to provide valuable confirmation of one’s presumed diagnosis. The improvement to be expected will usually be very evident within four to eight weeks, as contrasted with the stable to steady downhill course observed with parachiasmal tumors. If there is doubt clinically about the
HLPLLR
diagnosis of optic neuritis, and particularly if there is failure to improve in visual function, then additional studies are to be considered. Especially useful in ruling out intracranial tumors compromising the optic nerves is high quality laminography (polytomography) of the optic canals and sella turcica. A recent development useful in the safe, noninvasive study of intracranial structures and spaces is computerized axial tomography (EMI scan). However, the EMI scan is relatively less successful in outlining small parachiasmal masses than it is in finding abnormalities elsewhere in the head. In relatively exceptional, confusing cases, neurosurgical consultation and pneumoencephalography with polytomography are used to provide the best possible neuroradiologic clearance of the parachiasmal regions. It should be emphasized that the great majority of optic neuritis cases do not need, and should not receive invasive neuroradiologic procedures such as angiography and pneumoencephalography. These latter studies should be reserved for truly worrisome diagnostic puzzles. What is demyelination? The normal optic nerve is made up of at least a million axons connecting the retinal recipient elements with synapses in the lateral geniculate bodies. Each axon is insulated by a coat of protein-lipid substances called myelin which enhances the rapid conduction of nerve impulses. In demyelination, the insulating myelin is lost from the axon, which may appear entirely intact microscopically, but fail to function conductively in a normal manner. Descriptions of acutely demyelinated optic nerve lesions observed pathologically are hard to find, since patients rarely die in conjunction with an acute optic neuritis. However, one can make inferences of what is probably going on in such optic nerves from descriptions of demyelinating plaques observed elsewhere in the central nervous system. The breakdown of myelin liberates sudanophilic globules which are phagocytized by microglia, these becoming distended by fatty breakdown products. The microglia accumulate in large perivascular aggregates, Local edema accumulates near the focal lesion. Later on, astroglia replace microglia to form the discrete plaques of gliosis observed in the brains of patients who have had generalized multiple sclerosis.
THERAPEUTIC REVIEW
Arguments in Favor of and Against Steroid Therapy Those who favor the use of corticosteroid therapy cite the following arguments (followed by appropriate rebuttals): 1. There is a theoretical basis for using an agent (cortisone) known to reduce edema and inflammation. This argument is nicely summarized by Lubow and Adams’ as follows: The initial cause of the demyelinating lesion in the optic nerve remains beyond our grasp, but the secondary structural changes with edema compression, ischemia, and further disorganization of myelin and axon fibers are characteristic of severe brain swelling and may be reversed by large quantities of steroids used for only a few days. Photographs of disc edema in acute papillitis after one and two days of treatment confirm this response. It seems reasonable to anticipate that rapid resolution of the lesion will produce a smaller scar with less axonal impairment for future function. For just this reason, it is important to judge the rate of improvement with treatment as compared to the natural course of the disease, not just the final visual acuity after one month or one year.
353
probably the best published efforts attempting to show a beneficial effect of steroids. By these authors’ own acknowledgment, their data in 25 treated and 25 untreated patients showed no statistical significance in ultimate visual acuity between the two groups, measured at one year. They did, however, demonstrate a more rapid improvement by the eighth day of treatment, which would have to be evaluated against the risks and side effects of therapy with ACTH or corticosteroids.)Bv7 (Additional evidence in rebuttal is provided in the large collaborative study of Rose et al.* who concluded that “Short term, high dosage use of ACTH hastened the evidences of improvement of symptoms and signs, but it cannot be stated from the data of this study that the ultimate extent of improvement was greater than that attained by placebo . . . The results of this study provide no basis for a recommendation for the use of ACTH as a long-term treatment for MS patients.“)
4. There is much pressure to “do something,” particularly when visual impair(Rebuttal: It isn’t known that edema ment is severe, or when the second eye is inand/or inflammation play any role in the volved. The steroid agents not only provide a pathologic changes of optic neuritis. The highly visible “doing something” which imedema compression and ischemia mechanism is conjectural in the case of the optic nerves, presses the patient, but they often provide a effect which counters whatever may occur elsewhere in the central euphoria-inducing patient concern with the illness. nervous system. If edema and inflammation (Rebuttal: It is an abdication of a do play a significant role in optic neuritis, one physician’s responsibility in the scientific should reasonably expect impressive benefit practice of medicine to use medication not from steroid therapy instead of the debatable improvement observed. It is the final visual shown to benefit the disease being treated, when there are potentially acuity after one month [or more ap- particularly awesome side effects of that treatment. As to propriately, after several months] which is the euphoria, some patients respond with a important ultimately, not the speed of the imdangerous degree of euphoria, or with depresprovement.) sion severe enough to precipitate suicide soon 2. Empirical observation indicates that after initiation of therapy.) steroids work. (Rebuttal: This seems to depend upon who is making the observations.) 3. Statistical studies already published prove the beneficial effects. (Rebuttal: As indicated earlier, all such studies having to do with multiple sclerosis, and optic neuritis in particular, contain the inherent difficulties of interpretation which stem from the natural tendencies toward marked spontaneous improvement of these diseases. Probably 90% of optic neuritis patients return to visual acuity of at least 20/40. The papers of Rawson et al.7 are
5. Steroid therapy is so widespread an approach to the treatment of optic neuritis as to constitute a legally significant “standard of care in the community.” (Rebuttal: This argument is an appeal to “everyone else is doing it” and is unworthy of scientific medicine. Fortunately, while most physicians probably treat optic neuritis with steroids in one form or another, there are enough who do not do so, and enough thoughtful analysis in the literature opposing steroid therapy, to maintain a dialogue on the subject.)
354
Surv Ophthalmol 20 (5) March-April
1976
Recommended Steroid Therapy Regimens The basic aim of corticosteroid therapeutic regimens is to provide enough corticosteroid agent to influence the optic nerve lesion without inducing unacceptable side effects. These side effects are generally well known, and need not be emphasized here. It is worth mentioning, however, that the common belief that a brief trial of steroids has no serious harmful effects is not always true. There are reported instances of fatal GI bleeding, severe psychosis, aseptic necrosis of the femur, activation of latent tuberculosis, and other serious side effects which have arisen from only a few weeks’ therapy with corticosteroids. Hence, the need continues to assess the patient’s general medical status, and to balance this against the best available steroid administration program. Whatever the treatment plan, it is generally agreed that the greatest possible effect is begun by commencing therapy immediately. The following are representative recommended approaches to steroid therapy, in detail, as suggested in recent publications. ACTH given parenterally has the advantage of not suppressing the adrenal glandular output. Poskanzer, in communication with Wray, expresses the viewpoint that ACTH may be more efficacious than synthetic corticosteroids such as prednisone. The disadvantages of ACTH administration include the need for hospitalization during at least the initial phases, and the requirement for multiple percutaneous injections, to which some patients object. A representative treatment schedule, as proposed by Wray,” is as follows: ACTH 20 units/cc. 80 units IV q 6-8 hours in 500 cc of 5% Dextrose in water for three days. Then ACTH gel (40 units/cc.) IM 40 units q 12 hours for seven days, then the dose is reduced by 10 units every three days as follows: 35 units bid x three days 30 units bid x three days 50 units qd x three days 40 units qd x three days 30 units qd x three days 20 units qd x three days
20 units qod x three days For patients who can’t or won’t enter the hospital, and for those to whom avoidance of multiple injections is important, orally administered agents such as prednisone are available. These have high potency, rapid and
HEPLER
total absorption, and relatively low salt retention properties. The evidence that ACTH administration provides more beneficial effect than prednisone is meager indeed, and certainly prednisone is far less costly and more convenient for patient and physician alike. A representative treatment schedule for prednisone is as follows: 100 mgm day 1 80 mgm day 2 60 mgm day 3-5 30 mgm day 6-7 At the end of the first week of therapy the response can be assessed and therapy either continued on a slowly tapering dosage, or if there has been no indication of beneficial effect, the prednisone can be simply discontinued. Lubow and Adams’ recommend intensive treatment with massive dosages of steroids (200 mgm of prednisone per day) for 36-72 hours, which they believe is effective in aborting an acute attack of optic neuritis. They believe that prolonged treatment is not indicated in this disorder. Hopefully, the patient receiving either ACTH or corticosteroids such as prednisone will be evaluated medically prior to instituting therapy, and followed during therapy by a general physician or internist. Occasionally, however, the ophthalmolpgist may have to fill at least part of the role of If this occurs, the general physician. ophthalmologist should remember the importance of: 1. Good history taking of past medical events including diabetes mellitus, peptic ulcer, tuberculosis, psychosis or depression, drugs used (aspirin, anticoagulants, digitalis). 2. Baseline chest x-ray and, possibly, skin tests. 3. Complete blood count and stool guiac. 4. Antacids (maalox or equivalent, 1 ounce two hours after meals and at bedtime). 5. Potassium supplement - eat bananas, oranges, tomatoes, and consider added potassium supplement. 6. Tapering steroid effect - if steroids are given, then discontinued within a two-week period, no significant endogenous adrenal suppression occurs. However, if steroid administration is prolonged, then the terminal phases of tapering should be carried out gradually to give the adrenal glands a chance to resume functioning. Furthermore, the
THERAPEUTIC REVIEW
355
patient and the family should be instructed that in the event of accident, surgery, or serious illness within a year of the termination of steroid therapy, physicians caring for the patient must be alerted to the past steroid therapy in order to provide supplementation. of repository Sub-Tenon’s injection steroids has obvious theoretical advantages in delivering large dosage to the region of the eye while minimizing the effects of systemic steroids. Despite the enthusiastic endorsement of persuasive advocates, proof of effectiveness is lacking. Severe side effects of this route of delivery have included perforations of the globe (several reported instances, and the number unreported can only be guessed), and severe steroid-induced glaucoma. For those who wish to utilize sub-Tenon’s injection, the following technique is recommended by Smith et al.O*lo A sterile, disposable 1 ml tuberculin syringe with a 27 gauge, l/2 inch needle is used. (One ml of triamcinolone acetonide aqueous suspension
sub-Tenon’s injection. The author prefers brief, initially intensive (100 mgm per day for two days, then taper) administration of prednisone for a one-week period in most such patients. If the indications for treatment are strong and if there are serious contraindications to systemic steroid administration, repository steroids given sub-Tenon’s injection may be offered to the patient. 5. It is a serious mistake to raise the possibility of multiple sclerosis in conversation with the patient or in medical reports. If the patient really has multiple sclerosis, this would be far better explained by a neurologist (who should evaluate the patient anyway, partitularly if there are signs or historical events to suggest disseminated disease). If the patient doesn’t go on to develop multiple sclerosis, the ophthalmologist has done an enormous disservice by even raising the issue, needlessly placing the patient under a cloud. The consulting neurologist can also advise
[Kenalog IM] is loaded into the syringe). The lower lid is gently wiped with an alcohol sponge, the patient is instructed to look up and to the opposite side, and the injection is given through the lower lid at the junction of the outer and middle thirds in the same direction as for a routine retrobulbar anesthetic. The needle is pushed snugly to its base, and the medication is injected moderately slowly. Covering the eye for about 30 minutes until the bolus of the drug is absorbed is helpful in avoiding transient diplopia. A semipressure eye patch can be applied for one to two hours if desired. The effect of the injection usually lasts for one to two weeks . . .
regarding limitation of exercise, exposure to heat, d esirability of moving to a cooler climate, and other practical aspects of care for the patient with multiple sclerosis.
In summary, patients with optic neuritis for whom ACTH or corticosteroid therapy is contemplated should be approached with the following realizations. 1. No physician should feel that the present evidence compels treatment of optic neuritis with ACTH or corticosteroids. 2. However, most patients with this disorder are so treated at present. 3. Because the evidence is uncertain and treatment with any form of corticosteroids or ACTH carries with it risk, the patient should participate in giving medico-legally valid informed consent. 4. Even a therapeutic conservative (such as the author of this review) will treat most patients if their opti neuritis is severe, or if it occurs in their only good eye. Individual preference and local custom can determine whether to use ACTH, corticosteroids, or
patients
with
indications
of dissemination
Treatment of Other Optic Neuropathies ISCHEMIC
OPTIC NEUROPATHY
Emboli to the circulation of the optic nerve can come from carotid atheromas, from the walls of the ventricles of the heart, particularly in the presence of cardiac arrhythmia, from infrequent sources such as cardiac myxomas, and very commonly postcardiotomy, when soft platelet emboli forming on rough surfaces along the walls of the heart break loose and are carried to the small vessels supplying the optic nerve. Nonembolic categories of ischemic optic neuropathy include carotid occlusive disease in which the pathogenesis of the optic nerve change is reduced perfusion pressure in the large vessels, (rather than emboiization from them), giant cell arteritis, and intrinsic small vessel disease adjacent to or within the optic nerve, presumed to be arteriosclerotic in nature. Neurological textbooks continue to list diabetes mellitus as a cause of optic neuritis. However, most if not all of the cases presented to support this notion are probably
356
Surv Ophtholmol 20 (5) March-April
1976
unidentified ischemic optic neuritis. Hence, the situation is not one of diabetes mellitus producing an actual optic neuritis, but rather a predisposition to small vessel occlusive disease within the optic nerve blood supply induced by the diabetes mellitus. Description of the clinical presentation of ischemic optic neuropathy is beyond the scope of the present review. These features are presented in a detailed review by Burde,’ which cites (in comparison with typical optic neuritis) the elderly age group, the abrupt onset, and the characteristic pale swelling of the optic nerve head observed in the acute phase and often misinterpreted as papilledema. Particularly helpful diagnostically is a characteristic altitudinal quality of the visual field defect, which often can be correlated with pale swelling or later atrophy of the corresponding portion of the optic nerve head. The most common source of either hard or soft embolic material in the optic nerve or retinal blood supply is from an ulcerating atheroma close to the junction of the internal and external carotid arteries. The therapeutic approach for this embolic category is to remove the source of embolism, presuming that the patient’s age and general status are such as to permit consideration of modern, safe angiography and possible endarterectomy or grafting procedures. Patients with soft platelet emboli following cardiotomy are generally anticoagulated until healing is completed to lessen the number and severity of effect of further emboli. Patients with suspected ulcerating atheromas, whose general status won’t permit consideration of endarterectomy, probably should not be anticoagulated, but they may be helped by the administration of aspirin to reduce platelet cohesiveness. When giant cell arteritis is the cause of ischemic optic neuropathy, systemic steroids are indicated, to be started as soon as a markedly elevated erythrocyte sedimentation rate and the clinical setting establish the likelihood of the diagnosis. While giant cell arteritis has been reported occasionally in younger adults, it is generally a disease of the very aged. Far more cases occur in the patient over 70 years of age than in younger persons. Proven cases under the age of 60 are rare. The sedimentation rate is usually very high, not just mildly elevated. A useful rule of thumb is to realize that the sedimentation rate is
HLPLER
generally equal to the age of the patient during active phases of giant cell arteritis. The steroids should be continued until the sedimentation rate and the clinical course indicate that the disease has become quiescent, and the patient needs to be observed for indications of recurrence for at least several years. The value of temporal artery biopsy lies not just in establishing the diagnosis for academic purposes (a negative biopsy, of course, doesn’t rule out the diagnosis in this disorder in which segmental arterial involvement is the rule). It also provides means of persuading reluctant internists that the patient has a potentially blinding or lethal disease warranting continued steroid therapy until controlled. When the diagnosis of giant cell arteritis is indicated by the history, physical findings, and elevated sedimentation rate, corticosteroid therapy should be commenced at once, even before the results of the temporal artery biopsy are received. Despite early indications that diphenylhydantoin (Dilantin@) might be helpful in treating ischemic optic neuropathy, Burde’ summarizes present consensus by pointing out that Dilantins has not proven (statistically) to be efficacious. While most patients with ischemic optic neuropathy due presumably to arteriosclerosis are treated with systemic steroids, Burde points out that neither corticosteroids nor anticoagulants have proven of benefit in this condition.’ Hayreh’” reviewed the subject of ischemic optic neuropathy recently and expressed the opinion that systemically administered steroids substantially improve the visual outcome in this disorder. His recommendation is based upon evaluation of a small group of patients whose acute optic nerve disturbance is presumed to be arteriosclerotic. His conclusion that such patients are improved by steroids given while their optic nerves are still visibly swollen is being investigated further, using larger numbers of patients subjected to a double-blind, randomized study. Hopefully, additional significant data of this sort will resolve firmly the present uncertainty which many clinicians feel about the efficacy of steroid administration in ischemic optic neuropathy not due to giant cell arteritis. TOBACCO/ALCOHOL (NUTRITIONAL, CAMP, TOXIC) OPTIC NEUROPATHY
PRISON
It is beyond the scope of this review to
THERAPEUTIC REVIEW
357
References discuss the reasons why cyanide metabolism is implicated in this CategOry of optic I. gurde RM: Ischemic optic neuropathy, in neuropathy, as well as in Leber’s hereditary Neuro-Ophthalmology Symposium of the optic atrophy. The general subject has been University of Miami and the Bascom Palmer Eye Institute, Vol VII. St. Louis, CV Mosby, reviewed by Lessell.* The traditional therapy 1973. pp 38-62 recommended in these disorders has been good nutrition, supplemental vitamins, strict la. Hayreh SS: Anterior Ischemic Optic Neuropathy, New York, Springer-Verlag, 1975, pp avoidance of tobacco and alcohol (and 101-111 perhaps a wiser choice of one’s ancestors, in the case of those who suffer from Leber’s 2. Lessell S: Toxic and deficiency optic neuropathies, in Neuro-Ophthalmology Symhereditary optic atrophy). Reports in the posium of the University of Miami and the British literature suggest that one should add Bascom Palmer Eye Institute, Vol VII, St a trial of hydroxy cobalamine, the hydroxLouis, CV Mosby, 1973. pp 21-37 ylated form of vitamin B,, which has a high 3. Lieberman TW: Use or abuse of corticosteroid degree of potency compared to ordinary therapy in acute optic neuritis, in Symposium vitamin B,,. The recommended dosage is 1 on Ocular Therapy, St Louis, CV Mosby, 1974. pp 75-82 mgm parenterally, daily for seven days, then 4. Lubow M, Adams L: The changing manageweekly for an additional three months.
ment of acute optic neuritis, in Symposium of
OPTIC
NEUROPATHY
INFILTRATIVE
the University of Miami Palmer Eye Institute, Vol
DUE TO
ent knowledge
of optic nerve disease
and its
treatment dictate humility in our therapeutic approach.
the
Bascom
Mosby, 1972. pp 44-50 Percy A, Nobrega ST, Kurland LT: Optic sclerosis. Arch and multiple neuritis
TUMOR
Optic nerve involvement with infiltrative lymphoma or metastatic tumor is often remarkably sensitive to irradiation, even when the primary tumor itself would not be expected to be responsive. Patients with optic nerve impairment due to this cause are subject to rapidly progressive decrease in vision, for instance, passing from normal acuity to bare light perception over the course of a few days. Despite their limited long term life expectancy, they are likely to be very distressed by their loss of vision which may well be reversed with externally delivered irradiation given in well tolerated dosage. Radiation therapists in major medical centers are acquainted with the recommended treatment factors. In summary, management of the optic neuropathies begins with identification of the probable etiologic/diagnostic category, followed by selection of therapy appropriate _ _. -. _. . ” to that category of disease. The limits ot pres-
and
VI, St Louis, CV
Ophthalmol
87:135-139,
1972
Rawson MD, Liversedge LA: Treatment of retrobulbar neuritis with corticotrophin. Lancet
2:222-224,
1969
Rawson MD, Liversedge LA, Goldfarb G: Treatment of acute retrobulbar neuritis with corticotrophin. Lancet 2:1044-1046, 1966 Rose AS, Kuzma JW, Kurtzke JF, et al: Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs. placebo. Neurology 9.
20: l-59,
1970
Smith JL, McCrary JA, Bird AC, et al: SubTenon steroid injection for optic neuritis.
Trans Am Acad Ophthalmol Otolaryngol 74:1249-1253, 1970 IO. Smith JL: Editor’s Note, in Symposium of the University of Miami and the Bascom Palmer Eye Institute, Vol. VI, St. Louis, CV Mosby,
1972. p 49 Il. Wray SH: The treatment of optic neuritis. Sight Saving Rev: 5-13, Spring, 1972 Reprint requests should be addressed to Dr. Robert Hepler, Jules Stein Eye Institute, University of California
California 90024.
at LOS Angeles,
LOS Angeles,