Journal of Neuro-Ophthalmology, June 2002, Volume 22, Issue 2

Best Catch from NANOSNET

BEST CATCH FROM NANOSNET Section Editors: Wayne T. Cornblath, MD, and Preston C. Calvert, MD Editor's note: In this section, we have excerpted and edited some of the choice inter­changes that have transpired during the past six months on the NANOS- sponsored electronic mail discussion list known as NANOSNET. Started in 1996, NANOSNET is open to physicians and selected allied professionals who are actively working in neuro- ophthalmology. It is not restricted to NANOS members. A Web page with more information about the NANOSNET list, including instructions on subscribing, is lo­cated at: http:// www. nanosweb. org/ members/ nanosnet. htm. We have initiated this section to give neuro- ophthalmologists around the world a sense of how lively ( and sometimes silly) a free- flowing exchange can be. Wayne T. Cornblath, MD, and Pres­ton C. Calvert, MD, the section editors, have made the selections and offer a commen­tary after each exchange. The names of the participants have been deleted to protect confidentiality. Topic I. Giant Cell Arteritis Revisited Asker: I recently examined an 88- year- old woman who had developed sudden painless loss of vision in her OD. She denied symptoms of giant cell arteritis ( GCA). Visual acu­ity was OD 20/ 200, OS 20/ 50. The OS had had a stable old optic neuropathy of unknown cause. She could not cooper­ate well for visual fields. There was a relative afferent pu­pillary defect ( RAPD) OS ( not OD). The right optic disc looked minimally pale ( she was aphakic OD); the left disc was very pale ( she was phakic OS). She had been treated with prednisone 30 mg/ d for 15 days for optic neuritis. Her erythrocyte sedimentation rate ( ESR) had been 65 prior to the initiation of treatment. Temporal artery biopsy ( TAB) done two days later showed intimal hyperplasia, elastic membrane disruption, but no inflammation. The pathologist said both changes could be normal in a patient of this advanced age. I tapered her down to 5 mg prednisone/ d and 2 months later, her visual acuity was 20/ 40 OD and 20/ 50 OS. I saw her this week ( after 8 months of treatment), and she had a nerve fiber layer ( NFL) hemorrhage off the disc mar­gin without swelling. Otherwise she was unchanged, with an ESR of 61 and C- reactive protein ( CRP) of 1.2 [ normal range 0- 0.8]. What would you do next? Responder 1: In my opinion, the biopsy is positive for GCA. You may want to look at it yourself and see if the internal elastic membrane looks like mice have been chew­ing on it. If this is the case, then she has GCA, and her ste­roid dose is too low ( especially with the still elevated ESR and CRP). On the other hand, such good visual recovery is against arteritic disease. Still, I would still be very nervous about GCA. You may want to biopsy the other side, but you will probably get the same report. Responder 2: If the biopsy was of adequate size and bilat­erally negative as read by a reliable pathologist, then I think it would be hard to call this GCA. Responder 3: This sounds more like a steroid- responsive optic neuropathy than GCA. I've never seen or heard of GCA recovering from an acuity of 20/ 200 to 20/ 40. By the way, I note that the prednisone dose was given every other day. In my experience, this does not work well for optic nerve disease. I probably would not rebiopsy her, but would give her a burst of IV steroids and then restart a slow taper from 10 mg prednisone every day, while following her vi­sion and fundus exam. Responder 4: Going from 20/ 200 visual acuity to 20/ 40 can happen in GCA. It happens if one catches the phase of choroidal ischemia before disc infarction. If one blasts with steroids at that stage, one can induce reversal of the visual loss. I have had a few such cases, including one that went from about CF to 20/ 25 acuity. Responder 3: Responder 4,1 assume you mean elderly pa­tients with poor vision, no optic disc changes, small if any RAPD, positive GCA review of systems ( ROS), abnormal fluorescein angiogram ( FA) and positive TAB? I have to admit I have not seen such a case yet. Are there fundus changes or other diagnostic clues to help? Responder 4: Sometimes there are lobular choroidal changes. This may be quite subtle. A fluorescein angiogram with very early views to assess perfusion time of the cho­roid nails it. Here is one of the original reports of this: Choroidal nonperfusion in giant cell arteritis. Quillen DA, Cantore WA, Schwartz SR, et al. Am. 1 Ophthalmol 1993; 116: 171- 5. Abstract: A 68- year- old man had visual loss second­ary to isolated choroidal nonperfusion as a clinical manifestation of giant cell arteritis. Ophthalmoscopy disclosed scattered yellow- white lesions at the level of the retinal pigment epithelium in the posterior pole of the OD. Intravenous fluorescein angiography dem­onstrated marked delay in choroidal filling of the macula in the OD. There was no ophthalmoscopic or angiographic evidence of anterior ischemic optic n. JNeuro- OvMiqlmol,. Vol. 22, No„ 2, 2002 „ . . DOI: 10.1097/ 01. WNO. 0Q00019693.06.729.7F , .123 , Copyright © Lip pincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 BEST CATCH FROM NANOSNET neuropathy or central retinal artery occlusion. After approximately 72 hours of intravenous corticosteroid therapy, the patient's visual acuity improved and re­peat intravenous fluorescein angiography showed normal choroidal circulation. Isolated choroidal ische­mia is a potential cause of reversible visual loss in patients with giant cell arteritis. Responder 5: 1 agree with Responder 4 that vision can im­prove dramatically in some cases when caught on time. I had two biopsy- positive patients with anterior ischemic op­tic neuropathy ( AION) who presented very soon after the loss of vision. ESR was 120 and 100. Treatment with ste­roids was started immediately. One improved from LP to 20/ 25 and another from CF to 20/ 20! I have never seen this kind of response in nonarteritic anterior ischemic optic neu­ropathy ( NAION). Responder 6: 1 have two GCA patients with dramatic im­provement in acuity with immediate high- dose IV steroids. One had a swollen nerve. Responder 7: Has anyone seen biopsy- proven GCA cause AION with visual acuity of 20/ 30 or better? Comment: This thread raises many issues concerning the diagnosis and management of GCA. The first issue is the diagnosis of GCA in patients on corticosteroids. This pa­tient's biopsy was done after 17 days of prednisone treat­ment and showed disruption of the internal elastic lamina, but no inflammation. This is similar to a study by Lie et al. ( 1) that showed a decrease in inflammatory response the longer the patient was on prednisone. We do not have the pathology report available, but presumably the pathologist commented on the differential diagnosis of disruption of the internal elastic lamina, which includes " healed arteritis. " Responder 2 raises the issue of the role for bilateral biopsy. Most series ( 2,3) show that biopsy of the second side pro­duces 3% more positive results, but there are still some cases diagnosed on clinical criteria with negative biopsies ( 2). Another responder questions whether dramatic visual recovery occurs in GCA. Two responders share their expe­rience of dramatic visual recovery if GCA is treated at the pre- AION stage of choroidal ischemia, which can be dem­onstrated on angiography. This is in contrast to most series in which little if any improvement in vision occurs despite treatment ( 4- 6). But perhaps the dictum that marked improvement in vision implies a disease other than GCA is incorrect. Responder 7 asks if minimal visual involvement can occur with GCA. Someone could have referred to the series of'Hayreh et al. in which 26% of eyes with arteritic AION had acuity of 20/ 40 or better ( 7). Two interesting comments about treatment are ignored. Should a persistently elevated ESR and CRP prompt a change in treatment? No one answers this one, but the treatment of elevated laboratory tests without clinical changes is not clearly needed ( 8). Responder 3 notes that alternate day corticosteroid therapy is not effective for GCA. Compari­son of alternate day and daily corticosteroid treatment shows the superior effectiveness of daily treatment ( 9). II. Monitoring For Ethambutol Optic Nerve Toxicity Asker: What would this group consider the standard of care for monitoring visual function in patients taking ethambu­tol? Responder 1: Color testing is the most sensitive test, and some advocate Farnsworth- Munsell 100 hue testing. Auto­mated perimetry is probably second, and visual acuity is third. But the simpler test is to calculate the medication dos­age in mg/ kg. At doses below 15 mg/ kg, toxicity is virtually unheard of. The risk increases as the dose increases. Responder 2: Initial screening should include color plates, to be repeated at 3 months, 6 months, and 1 year after the onset of treatment. Any changes in vision should be re­ported to the treating physician. If these changes are thought to be due to ethambutol, the drug should be replaced with an alternative. If symptoms are caught early, visual loss can be reversed. Responder 3: 1 think all that needs to be done is to warn the patient and describe the symptoms of toxicity. I have never seen toxicity be asymptomatic. The patient will be the first to know. Unless patients are not very observant, they can monitor themselves. Responder 4: 1 do an examination with visual fields every 3 months and am now including Heidelberg retinal tomog­raphy ( HRT) every 6 months. I include the HRT more for curiosity, to see what HRT will be able to detect if toxicity does occur. Responder 5: Ethambutol targets the papillomacular bundle, so I monitor color vision, contrast sensitivity ( look­ing for exclusively high spatial frequency losses), and the red- on- black Amsler grid. For research purposes, our three- dimensional Threshold Amsler Computer System works too well: The majority of patients on ethambutol have a defect. For more on that you can go to Fink's website: http:// www. wfbabcom5. com/ wG35. htm. Responder 6: The Medical Protection Society ( UK) in its 1984 report states, " It is wise to make a record of „ 124 . , „ . , „ . . © 2002 Lippincott Williams & WUkins , Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. BEST CATCH FROM NANOSNET JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 ophthalmic findings, including visual acuity in OU, before treatment starts, and at frequent ( say monthly) intervals dur­ing treatment." In line with this, the Joint Tuberculosis Committee addressed the problem of ethambutol toxicity and gave a ten- point guideline for the management of these patients. The guidelines are given in the following references: Ocular toxicity from ethambutol. Citron KM, Thomas GO. Thorax 1986; 41: 737- 9. Ethambutol- induced ocular toxicity revisited. Alvarez KL, Krop LC. The Annals of Pharmacotherapy 1993; 27: 102- 3. One of the guidelines states, " routine visual acuity tests during treatment are NOT recommended." The paper suggested, " routine tests of color vision and of peripheral and central fields might be more sensitive than visual acuity." In our clinics, where tuberculosis is a major problem, we usually do baseline a complete neuro-ophthalmic examination ( acuity, color, and visual fields) on the first visit and repeat these exams every 1- 3 months, depending on the occurrence of symp­toms, while the patient is on treatment. Concerning the comment on risk of toxicity within standard dose ranges ( 15 to 25 mg/ kg/ day), several studies have shown that toxicity can occur while patients are on so- called " safe doses". Please check out the following references: Toxic ocular effects of ethambutol. Kahana LM. Can Med Assoc J1987 ; 137': 212- 6. Optic neuropathy associated with ethambutol in Koreans. Choi SY, Hwang JM. Korean J Ophthalmol 1997; 11: 106- 10. Ocular toxicity following ethambutol in standard dosage. Chatterjee VKK, Buchanan DR, Friedmann AI, et al. BrJDis Chest 1986; 80: 288- 91. Toxic optic neuropathy secondary to ethambutol. Inocencio FP, Castillo TR. Philipp J Ophthalmol 1999; 24: 65- 8. The literature is divided on the issue of reversibility of toxicity. Some authors claim that it is when treat­ment is discontinued, while others say that it is not. In our experience, recovery is not very encouraging. Responder 7: In Istanbul, where tuberculosis is also an im­portant health threatening disease, data on recovery after stopping ethambutol are encouraging. More than 90% of the patients get their vision back after cessation of the drug. Comment: In this thread, there is considerable disagree­ment about the appropriate way to monitor for ethambutol optic nerve toxicity. The asker asks what tests and testing intervals are appropriate for monitoring patients. The first two responders suggest color vision testing and a 3- month interval for testing. While some believe that Farnsworth Munsell 100 Hue abnormalities are the earliest sign of ethambutol toxicity, others believe that contrast sensitivity or visual evoked potentials are better tests for early detec­tion of toxicity ( 10- 12). Interestingly, there are no studies comparing the various types of color vision testing, auto­mated perimetry, contrast sensitivity, or evoked potentials to determine which test would be most sensitive. The next responder recommends having the patient monitor vision and return only when there are difficulties. In America's litigious climate, this approach is likely to be exceptional, but there is scientific support for it. Citron ( 13) notes " in my opinion routine visual acuity tests during ethambutol treat­ment serve no useful purpose since it appears that they fail to detect ocular toxicity before symptoms occur and may not be abnormal even when symptoms are present. " Of course Citron's comment refers to acuity testing, and while the best test for early detection is not yet clear, most would agree that acuity testing is much less sensitive than other modalities. The next responder mentions red- on- black Amslergrid testing and three- dimensional Amsler grid test­ing, two methods for testing vision that have not been for­mally assessed in this setting. Responder 6 notes a number of published recommendations on follow- up and mentions the practice in one clinic. Responder 1 was obviously not aware of the references from 1986, which show a 1% inci­dence of optic neuropathy at an ethambutol dose of 15 mg/ kg ( 14). Not mentioned in the interchange is that etham­butol is excreted via the kidneys, and decreased kidney function can increase toxicity; ethambutol blood levels are available to help monitor dosage. Responders are divided on the issue of recovery from ethambutol toxicity. Two reputable series note 40- 50% improvement ( 15,16). III. Oscillopsia in Congenital Nystagmus Asker: A 46- year- old healthy female had nystagmus noted in infancy and was told by a pediatric ophthalmologist that a " lesion in the brain caused the nystagmus." She has a null point/ zone in right gaze and no oscillopsia. In her 30s, she began having occasional oscillopsia during stress, but was able to overcome it with certain maneuvers. Gradually since her 40s, she has daily oscillopsia with moments free of it, especially when performing near tasks. It improves if she closes one eye. The null point/ zone has shifted to up and right gaze. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 BEST CATCH FROM NANOSNET Visual acuity is 20/ 20 OU, with horizontal pendular nystagmus ( appears like it might be jerk when very fast, but too fast for me to be sure). The nystagmus is variable in amplitude and frequency, and does seem to stop for a few moments here and there. It is horizontal in all positions of gaze. When it does stop, she sees double in the distance. During nystagmus, there is no diplopia. So I have four questions: 1) How common is it to develop oscillopsia later in life with congenital nystagmus ( CN)? 2) Should she be worked up? 3) Any positive experience with medications? 4) Which treatment modality would you try first, medica­tions or prisms? Responder 1: See: Onset of oscillopsia after visual maturation in patients with congenital nystagmus. HertleRW, FitzGibbon EJ, AvalloneJM, Cheeseman E, Tsilou EK. Ophthalmology 2001; 108: 2301- 7. Responder 2: She needs a scan. A paraneoplastic etiology is a consideration. Responder 3: Acquired oscillopsia does occur in CN ( 19,22), and is related to worsening of foveation period in the nystagmus cycle. You could look at the nystagmus waveform with recordings to substantiate the diagnosis of CN. Try to see if prisms for null position and/ or conver­gence help. Baclofen, clonazepam, and gabapentin have been only marginally helpful. Asker: I'm still unclear what the group's consensus is on my patient with congenital nystagmus and adult- onset os­cillopsia. I read the recent article in Ophthalmology ( 21) regarding the five or so patients. Only one patient was im­aged. Should I start with eye movement recordings to see if the pattern is consistent with congenital nystagmus? If so, would you still image? Or should she be imaged regardless? Responder 4: 1 have seen several patients who have CN [ or periodic alternating nystagmus ( PAN)] recognized since childhood with adolescent or adult onset oscillopsia. All had eye movement recordings. Many have been imaged ( all normal) and have had normal vestibular tests, too. Record­ings were all done by Larry Abel. He then started asking all patients with CN who were sent to him to record if they ever experienced oscillopsia, and several of the first patients asked reported that they had experienced it! Oscillopsia has also been reported with latent/ manifest latent nystagmus ( I have seen one of these). So: 1. Oscillopsia in CN/ PAN is probably not rare- the fre­quency may reflect the eagerness with which it is sought as a symptom. 2. I think that a " classical" CN/ PAN recording is very re­assuring and should be done. CN really is a laboratory diagnosis [" the eye is quicker than the eye" ( Abel LA, Personal communication)]. 3. Vestibular pathology can also happen in CN patients and these patients should probably be imaged. Comment: The absence of oscillopsia in most patients with CN is a remarkable phenomenon. These patients are usu­ally unaware of ongoing retinal image slip occurring with velocities that patients with acquired nystagmus would find very uncomfortable ( 4 degrees or more). Several hypoth­eses have been advanced to explain why this is so. There is some evidence of decreased motion perception in CN pa­tients ( 17). Other proposals include use of an efference copy of the CN waveform to negate the retinal slip effects and the suppression of visual sensation except during " fo­veation periods " wherein the retinal slip velocity is below a critical velocity (< 4- 10 degrees/ sec) ( 18). The occurrence of oscillopsia in CN patients at some point after maturation of the visual system is rare, but well documented ( 19,20,21,22). Intercurrent phenomena that interfere with the mechanisms that usually suppress the perception of retinal slip have been postulated as causes of the onset of oscillopsia. The comment of Responder 3 al­ludes to the report by Dell ' Osso ( 22) of a patient who had reversal of the predominant direction of his jerk CN and onset of oscillopsia after an episode of loss of conscious­ness. While the patient had previously shown well defined foveation periods with low retinal slip velocity, his new nys­tagmus waveform produced consistently higher retinal slip. Another patient had a Chiari malformation with onset of oscillopsia following lumbar puncture, together with a changed pattern of nystagmus: horizontal/ torsional with the exponentially increasing slow phase slopes usually characteristic ofCN ( 20). The patients reported by Hertle et al. ( 21) as men­tioned by Responder 1, appear to have at least two other mechanisms for new onset of oscillopsia. One hypothesis is discussed by Reinecke ( 23) in his commentary on their pa­per. This is the increased slow phase velocity of nystagmus produced by the conversion from true latent nystagmus to manifest latent nystagmus that may follow an acquired change in ocular alignment, or visual sensory function. Three of the five patients in the series of Hertle et al. ( 21) had a latent nystagmus component on exam. The change in ocular motility could be a decompensation of a longstand­ing deviation or an acquired strabismus component. Wors­ening of a chronic visual afferent system disorder such as a n 126 . , „ . . , „ . . © 2002 Lippincott Williams & WUkins , Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. BEST CATCH FROM NANOSNET JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 retinal degeneration, as in one of the patients ofHertle et al. ( 21), may also be a trigger. As suggested by Responders 2 and 4, it is also pos­sible for CNpatients to develop any other acquired vestib­ular, cerebellar, or brainstem disorder that might be associated with a different nystagmus waveform and devel­opment of oscillopsia. This should be apparent from the his­tory and other details of the examination, and in appropri­ate cases, additional investigations such as imaging, sero­logic studies, and vestibular testing may be indicated. If the history and examination leave any doubt about the identity of the disorder as CN, a careful eye movement recording should be made by an experienced laboratory technician to look for the characteristic patterns ofCN. Efforts should be made to identify new strabismus patterns, latent nystagmus components that might be recently worsened, or visual sen­sory disorders that might contribute to recently increased nystagmus slow- phase velocity and oscillopsia. Treatment may then be directed to a specific disorder. Nonspecific treatment with pharmacologic agents, as mentioned by Re-sponder 3, may also be attempted, although only a few forms ofCNare readily treated ( baclofen for PAN). Con­tact lenses have been reported to suppress the oscillopsia ( 19). IV. Exercise- induced Downbeat Nystagmus Asker: I'd appreciate any thoughts on a 37- year- old healthy man on no medications who, for the past 3 years, has increasingly noticed blurred, " rolling" ( vertically) vi­sion on physical exertion or when stressed. He has had a very extensive work- up including normal MRI/ MRA. When I first saw him I could find absolutely nothing abnor­mal except for some myokymic movements of the eyelids. I asked him to return and walk around the parking lot for a couple of hours to precipitate the symptoms. He has pre­sented with and now presents with a dramatic downbeat nystagmus. Responder 1: I believe your patient may have episodic ataxia type 2 ( EA2). I had an identical young patient with symptoms induced by vigorous walking around downtown Seattle. Afterwards, I observed downbeat nystagmus in the examination chair, whereas the previous examination with­out the exercise was normal. It responded to acetazolamide therapy fairly dramatically. Comment: This fascinating patient presents a diagnostic challenge. The Asker notes that his patient has downbeat nystagmus triggered by exertion or stress, and also ob­served facial myokymia. Clinicians are often presented with patients who have combinations of clinical phenomena that can be described, but not readily attributed to a single disease process known to the examiner. One way to ap­proach such a patient is to review the literature concerning the distinctive aspects of the case and look for references to the other phenomena as a way ofrecognizing and establish­ing a potentially unifying diagnosis. This is a very time-consuming and inefficient use of the busy clinician's time, however. Fortunately, a new suite of clinical database tools has become available to make this process much more effi­cient and powerful. Genetically determined diseases are frequent in neuro- ophthalmologicpractice, and must be considered as one cause of the phenomena in the Asker's case. Apparently other categories of disease have been sought extensively, and are not apparent. Whenever a genetic disease is con­sidered as a cause of a clinical syndrome, it may be very useful to visit the Online Mendelian Inheritance in Man ( OMIM) Web site ( http:// www. ncbi. nlm. nih. gov/ entrez/ query. fcgi? db= OMIM) and query the OMIM database with the patient's findings ( 24). This database contains detailed genetic, molecular, and clinical informa­tion on 13434 entities as of March 16, 2002. Of these, 9958 have a known gene locus. If the OMIM database is queried with " nystagmus " and " myokymia, " only six disorders are returned that include these features together in the clinical descriptions of affected kindreds. They are: episodic ataxia type 1, episodic ataxia type 2, Machado Joseph disease ( spinocerebellar atrophy type 3, sca3), episodic ataxia type 4, episodic ataxia type 3, and progressive external ophthal­moplegia, and scoliosis. Responder 1 suggests the patient in question may have episodic ataxia type 2 ( EA2) and suggests a trial of acetazolamide therapy. Reviewing the OMIM article on EA2, we find that myokymia is much less frequent in EA2 than EA1 ( 25). From the associated literature reference links in OMIM, we can review the abstracts of the underly­ing citations. The two disorders are both autosomal domi­nant, butEA2 is a genetic defect in the calcium ion channel gene CACNA1A mapped to gene locus 19pl3, and allelic with the defects in the same gene that cause either spinoc­erebellar ataxia type 6 or familial hemiplegic migraine type 1 ( 25). EA2 is not associated with interictal myokymia. EA1 is caused by a genetic defect in the potassium ion channel gene KCNA1 at gene locus 12pl3. EA1 is much more likely to be triggered by body movements and is associated with interictal myokymia, including the facial muscles. How­ever, nystagmus is not seen interictally in EA1. SCA3 is a multisystem disorder with upper motor neuron signs, ex­trapyramidal features, and many other aspects not seen in this patient. Episodic ataxia type 4 ( EA4) is not yet mapped to a specific gene locus, and is clinically similar to EA1 with myokymia and the additional features of tinnitus and ver­tigo. Episodic ataxia type 3 ( EA3) is not mapped, and not associated with myokymia. The description of the disorder Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 BEST CATCH FROM NANOSNET called Progressive External ophthalmoplegia and scoliosis is clearly different from that of our patient. In the final analysis, this patient probably has EA2 with benign eyelid fasciculations masquerading as myokymia. Acetazolamide may help patients with EA2, EA4, and less often EA1. Phe-nytoin may benefit patients with EA1 ( 26). To identify a source of genetic testing for a patient with suspected EA2, we might subscribe to the GeneTests/ GeneClinics Web site at: http:// www. genetests. org/ ( 2 7). The effective use of the online database resources can give us precise direction for further evalua­tion of the patient and suggestions for effective therapy. REFERENCES 1. Achkar AA, Lie JT, Hunder GG, et al. How does previous cortico­steroid treatment affect the biopsy findings in giant cell ( temporal) arteritis? Ann Intern Med 1994; 120: 987- 92. 2. Hall S, Hunder GG. Is temporal artery biopsy prudent?. Mayo Clin Proc 59: 793- 6, 1984. 3. Boyev LR, Miller NR, Green WR. Efficacy of unilateral versus bi­lateral temporal artery biopsies for the diagnosis of giant cell arteri­tis. AmJOphth 1999; 128: 211- 5. 4. Aiello PD, Trautmann JC, McPhee TJ, et al. Visual prognosis in giant cell arteritis. Ophth 1993; 100: 550- 5. 5. Liu GT, Glaser JS, Schatz NJ, et al. Visual morbidity in giant cell arteritis. 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De Palma P, Franco F, Bragliani G, et al. The incidence of optic neuropathy in 84 patients treated with ethambutol. Metabolic, Pe­diatric & Systemic Ophth 1989; 12: 80- 2. 13. Citron KM. Ethambutol: a review with special reference to ocular toxicity. Tubercle 1969; 50: 32- 6. 14. Kahana LM. Toxic ocular effects of ethambutol. CMAJ 1987; 137: 213- 6. 15. Kumar A, Sandramouli S, Verma L, et al. Ocular ethambutol tox­icity: is it reversible? J Clin Neuroophth 1993; 13: 15- 7. 16. Tsai RK, Lee YH. Reversibility of ethambutol optic neuropathy. J Ocular Pharm & Therap 1997; 13: 473- 7. 17. Shallo- Hoffman J, Wolsley CJ, Acheson JF, et al. Reduced duration of a visual motion aftereffect in congenital nystagmus. Doc Oph­thalmol 1998- 9; 95: 301- 14. 18. Dell'Osso LF, van der Steen J, Steinman RM, et al. Foveation dy­namics in congenital nystagmus. I: Fixation. Doc Ophthalmol 1992; 79: 1- 23. 19. Abel LA, Williams IM, Levi L. Intermittent oscillopsia in a case of congenital nystagmus. Dependence upon waveform. Invest Oph­thalmol Vis Sci 1991; 32: 3104- 8. 20. Barton JJ, Sharpe JA. Oscillopsia and horizontal nystagmus with accelerating slow phases following lumbar puncture in the Arnold- Chiari malformation. Ann Neurol 1993; 33: 418- 21. 21. Hertle RW, FitzGibbon EJ, Avallone JM, et al. Onset of oscillopsia after visual maturation in patients with congenital nystagmus. Oph­thalmology 2001; 108: 2301- 7. 22. Dell'Osso LF. Eye movements, visual acuity and spatial constancy. Acta Neurol Belg 1991; 91: 105- 13. 23. Reinecke RD. Discussion of Hertle RW, et al ( 21). Ophthalmology 2001; 108: 2307- 8. 24. Online Mendelian Inheritance in Man, OMIM. McKusick- Nathans Institute for Genetic Medicine, Johns Hopkins University ( Balti­more, MD) and National Center for Biotechnology Information, National Library of Medicine ( Bethesda, MD), 2002. Available at: http:// www. ncbi. nlm. nih. gov/ omim/ 25. Online Mendelian Inheritance in Man, OMIM. Johns Hopkins Uni­versity, Baltimore, MD MIMNumber: # 108500: 12/ 12/ 2001. Avail­able at: http:// www. ncbi. nlm. nih. gov/ omim/ 26. Online Mendelian Inheritance in Man, OMIM. Johns Hopkins Uni­versity, Baltimore, MD MIMNumber: # 160120: 12/ 12/ 2001. Avail­able at: http:// www. ncbi. nlm. nih. gov/ omim/ 27. GeneTests/ GeneClinics. University of Washington School of Medi­cine, Children's Hospital Regional Medical Center ( Seattle, WA), 2002. Available at: http:// www. genetests. org/ _ 128 . , . © 2002 Lippincott Williams & WUkins , Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.