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Show IN OTHER JOURNALS Editor's Note: This section contains brief reviews of articles that have appeared in other journals within the past six months. From a comprehensive list of clinical and scientific medical journals, each reviewer has selected about 30 titles and reviewed the most pertinent articles. The March and September issues will include reviews from ophthalmology medicine and journals; the June and December issues will include reviews from neuroclinical and neuroscience journals. Ophthalmology Journals Reviewer: Sean P. Donahue, MD, PhD I. Automated perimetry Demirel S, Johnson CA. Incidence and prevalence of short wavelength automated perimetry deficits in ocular hypertensive patients. Am J Ophthalmol 2001; 131: 709 15. The authors evaluated 500 eyes of 250 patients with ocular hypertension in a prospective longitudinal study and followed each with both standard automated perimetry ( Humphrey 30- 2 strategy) and short wavelength automated perimetry ( SWAP). Results from visual fields of healthy patients were used to establish a normative database for both SWAP and standard automated perimetry. The baseline prevalence of visual field defects was 9.5% for SWAP and 1.4% for standard automated perimetry. However, during the 5 years of follow- up, incidence rates of new visual field loss were 6.2% ( 1.23% per year) for SWAP and 5.9% ( 1.2% per year) for standard automated perimetry. In support of previous data obtained from the ocular hypertension management study, less than 50% of automated standard perimetry field defects were present on repeated fields, whereas 80% of SWAP fields remained abnormal on the next examination. This is a very important study regarding SWAP and standard automated perimetry. The findings suggest several things: 1) both SWAP and standard automated perimetry detect the same thing, that is, visual field damage due to glaucomatous disease; 2) the higher prevalence at baseline of visual field defects with SWAP indicates that this technique likely detects defects earlier; and 3) the higher reproducibility of new visual field defects with SWAP also supports the earlier detection of field defects with this strategy. The authors are to be commended for this important study. However, for SWAP to become clinically acceptable, the reviewer feels that variability must be reduced. Although detection of new visual field defects is important, proper glaucoma management requires tests that determine which patients are having progressive visual field loss. This requires a test with low test- retest variability and represents the biggest current limitation of SWAP. Hutching N, Hosking SL, Wild JM, et al. Long- term fluctuation in short- wavelength automated perimetry in glaucoma suspects and glaucoma patients. Invest Ophthalmol Vis Sci 2001 ; 42: 2332- 7. The authors evaluated the long- term fluctuation in SWAP in glaucoma suspects and glaucoma patients. Thirty- three glaucoma suspects and 17 patients with early to moderate stable open- angle glaucoma underwent both standard automated perimetry and SWAP at each of six visits over approximately 1 year of follow- up. The long- term fluctuation ( variation in threshold estimates between examinations) was studied in two parts: a homogeneous component, which represents the amount of fluctuation that applies to all the stimulus locations, and the heterogeneous component, which represents the amount of long- term fluctuation that is due to variations within specific locations. Both components of the long- term fluctuation were compared for visual fields obtained using conventional automated perimetry and SWAP. In glaucoma patients and in glaucoma suspects, the total long- term fluctuation, the homogenous component of long- term fluctuation, and the heterogeneous component of long- term fluctuation were greater for SWAP than for standard perimetry. This result suggests that high levels of variability limit the usefulness to detect change in SWAP. The above study is highlighted by an editorial: Caprioli J. Should we use short- wavelength automated perimetry to test glaucoma patients? Am J Ophthalmol 2001; 131: 792- 4. The author noted that a visual field test that will be useful in glaucoma is not necessarily the one that is most likely to detect a defect, but the one most likely to detect change, as discussed above. Since SWAP has increased test- retest ( long- term fluctuation) variability, this essentially limits use of SWAP in standard glaucoma practice. Casson R, James B, Rubinstein A, et al. Clinical comparison of frequency doubling technology perimetry and Humphrey perimetry. Br .1 Ophthalmol 2001; 85: 360- 2. Frequency doubling perimetry has been introduced as a method for screening, particularly in patients with 58 JNeuro- Ophthalmol, Vol. 22, No. 1, 2002 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. IN OTHER JOURNALS JNeuro- Ophthalmol, Vol. 22, No. 1, 2002 glaucomatous optic neuropathy. It has been found to be relatively sensitive and specific compared with full threshold perimetry. In this prospective study, the authors compared data from 99 patients who underwent standard automated perimetry ( Humphrey 24- 2 algorithm) and frequency doubling perimetry in the screening mode. Missed points on the frequency doubling perimetry were correlated with both mean defect and corrected pattern standard deviation from standard automated perimetry. The number of abnormal points obtained from the frequency doubling perimetry correlated significantly with the Humphrey total deviation. If the presence of one or more missed points on the frequency doubling test was considered to be the standard for calling a field abnormal, the overall sensitivity of frequency doubling to detect a glaucomatous defect was 78%, with a specificity of 89%. These results suggest that frequency doubling technology may be appropriate for screening patients for glaucomatous optic neuropathy. Whether this technique is useful for following patients remains to be determined. n. Giant Cell Arteritis Murgatroyd H, Milne A. Positive temporal artery biopsy in a patient on therapeutic doses of steroids for six years. Eye 2001; 15: 250- 1 The authors report a case of a positive temporal artery biopsy in a patient who had been taking steroids continuously for longer than 6 years. The biopsy specimen demonstrated epithelial granulomas in the adventitial tissue and thickening of the intima. This case extends previous reports documenting much shorter time periods during which positive biopsies could be obtained. Liu NH, LaBree LD, Feldon SE, et al. The epidemiology of giant cell arteritis: a 12- year retrospective study. Ophthalmology 2001; 108: 1145- 9 One hundred twenty- one patients who underwent temporal artery biopsy at the Doheny Eye Institute and the Los Angeles County University of Southern California Hospital during the 12 years ending in 1998 were reviewed. Overall, 20 patients had positive biopsies. However, 19 of the patients with positive biopsies were white, and one was Asian. None were black or Hispanic. The ratio of positive biopsies for white patients was 29% ( 19/ 66). This decreased to 11% ( 1/ 9) for Asians. Forty biopsied patients were Hispanic, and six were black. The authors conclude that white patients might have a higher incidence of positive biopsies. The genetic predispositions by which Hispanics and blacks appear to be protected are unknown. Chan CC, Paine M, O'Day J. Steroid management in giant cell arteritis. Br J Ophthalmol W)\$ 5: V) 6\- 4. The authors evaluated the effects of intravenous steroids on visual outcome in the affected eye in patients with arteritic anterior ischemic optic neuropathy ( AION). They reviewed the records of 73 patients with biopsy- proven giant cell arteritis and vision loss. Visual acuity improved in 21 patients by a mean of two Snellen lines after commencing steroids. The authors noticed an increased likelihood of improved vision in the group who had intravenous steroids ( 40%) compared with those who had oral steroids ( 13%). The authors suggest that intravenous may help the likelihood of visual recovery in patients with arteritic AION. This intriguing study contradicts previous teaching that vision loss associated with arteritic AION is irreversible. However, it must be considered in conjunction with the optic nerve sheath fenestration study for ischemic optic neuropathy, which demonstrated similar improvement in acuity as part of the natural history of the disease. III. Myopia, its Progression, and its Association with Night Lighting and Near Work Shih YF, Hsiao CK, Chen CJ, et al. An intervention trial on efficacy of atropine and multifocal glasses in controlling myopic progression. Acta Ophthalmol Scand 2001 ; 79: 233- 6. In 1999, Quinn et al. ( Nature 399: 113^ 1) intrigued parents throughout the country by suggesting that the development of myopia is hastened by the use of nightlights during the first 2 years of childhood. This report furthered the nature- versus- nurture controversy regarding the effects of reading, near work, light and pharmacologic intervention on myopic progression. The authors performed a randomized prospective study of 227 myopic Taiwanese children 6 to 13 years old. The children were randomly assigned to one of three management groups: 1) 0.5% atropine topically with progressive bifocal spectacles; 2) progressive bifocal spectacles alone; and 3) single vision spectacles. Each patient was followed for at least 18 months. The results demonstrated that the greatest progression of myopia occurred in the single vision spectacle group ( 1.40 D) and in the multifocal group ( 1.19 D). The least progression was in the atropine plus multifocal glasses group ( 0.41 D). The progression of myopia correlated with changes in axial eye length. The authors concluded that the use of atropine with 59 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 1, 2002 Wein and Levin multifocal lenses significantly slows down the progression of myopia. Hepsen IF, Evereklioglu C, Bayramlar H. The effect of reading and near- work on the development of myopia in emmetropic boys: a prospective, controlled, three- year follow- up study. Vis . Res 2001; 41: 2511- 20. This was a prospective comparison of 114 children in two groups. Group one consisted of 67 randomly selected students, with a mean age of 13 years and a mean of 6 hours of reading and near work. This group was compared with the ODs of 47 apprentices with a similar mean age, who were working as skilled laborers in Turkey. Cycloplegic refraction was used to determine refractive error. For patients with no significant refractive error at baseline, myopic shift over 3 years occurred in 49% of the first group but in only 19% of the second group. The overall magnitude of myopic shift was 0.56 D in the first group but only 0.07 D in the second group. The difficulty with this study is that it did not control for parental myopia, and it is possible that parents of educated students had increased myopia compared with the parents of apprentices. Saw SM, Hong RZ, Zhang MZ, et al. Near- work activity and myopia in rural and urban schoolchildren in China. J Pediatr Ophthalmol Strab 2001; 38: 149- 55. These authors found results similar to Hepsen, Evereklioglu, and Bayramlar in a study of second- grade children in China. Children in city schools had an average near- work time of 2.2 hours per day and a 19.3 % prevalence of myopia, as compared with children in the countryside who had 1.6 hours of near work per day and had a 6.6%> rate of myopia. This study also did not control for parental myopia, which is likely to be more prevalent in the parents of educated students and in the Chinese who live in cities. Thus, further study to evaluate each of these conditions is necessary. Saw SM, Wu HM, Hong CY, et al. Myopia andnight lighting in children in Singapore. Br J Ophthalmol 2001 ; 85: 527- 8 The results of the original report by Quinn et al. was questioned in this report of a cross- sectional study of 1001 children in Singapore. Parents of the children filled out a detailed questionnaire regarding prevalence of nighttime lighting, near work, and education and demographic factors. In contrast to the findings of Quinn et al., there was no difference in myopia prevalence rates in children exposed to nighttime light ( 33.1%) compared with children who slept in the dark ( 31.4%) before age two. This result further supports the criticisms of the Quinn et al. study in that it did not control for parental myopia. Further details of this study are highlighted in an editorial: Fredrick DR. Myopia: was mother right about reading in the dark? Br J Ophthalmol 2001; 85: 509- 10. IV. Vigabatrin and Visual Field Loss Hardus P, Verduin WM, Berendschot TT JM, et al. The value of electrophysiology results in patients with epilepsy and vigabatrin associated visual field loss. Acta Ophthalmol Scand 2001; 79: 169- 74. Vigabatrin has been shown to be associated with peripheral visual field constriction. The electroretinogram ( ERG) abnormalities are believed to be correlated with the vision loss. These authors attempted to determine whether ERG or electrooculogram ( EOG) abnormalities could be used as screening tests to detect patients with, or at risk for, vigabatrin- associated visual field loss. Of 30 patients operated on for temporal lobe epilepsy, 26 had concentric visual field constriction, and 11 were healthy. All 30 used vigabatrin. Of these, 15 were studied with ERG and EOG. ERG abnormalities could only be found in 50% o of patients with visual field constriction due to vigabatrin. The total dose of vigabatrin and the amount of visual field loss did not correlate well with electrophysiologic results, suggesting that ERG did not appear to be an appropriate screening test for vigabatrin- associated visual field loss. V. Urine Drug Screening Following Pharmacologic Tests with Cocaine Jacobson DM, Berg R, Grinstead GF, et al. Duration of positive urine for cocaine metabolite after ophthalmic administration: implications for testing patients with suspected Homer syndrome using ophthalmic cocaine. Am J Ophthalmol 2001; 131: 742- 7. The issue of positive urine testing after pharmacologic use of cocaine for confirmation of Horner syndrome was evaluated by these authors. Two drops of 10% o cocaine were applied to OU of 50 healthy patients, and urine samples were collected at various times during the successive 4 days. Urine samples demonstrated cocaine metabolites in 94% of the patients up to 6 hours after the cocaine test, in 70% of patients 24 hours after testing, and in one of the 50 patients, 48 hours after the topical administration of cocaine. No patients tested positive 3 and 4 days after the original cocaine test. These results suggest guidelines for counseling patients regarding drug testing after the use of topical cocaine solutions. 60 © 2002 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. IN OTHER JOURNALS JNeuro- Ophthalmol, Vol. 22, No. 1, 2002 VI. Optic Nerve Gliomas in Children Parsa CF, Hoyt CS, Lesser RL, et al. Spontaneous regression of optic gliomas: thirteen cases documented by serial neuroimag-ing. Arch Ophthalmol 2001; 119: 416. The natural history of optic nerve gliomas in children, especially those associated with neurofibromatosis type 1, remains to be determined. These authors report a series of 13 patients with optic nerve gliomas, five of whom had neurofibromatosis. In 12 of the 13 patients, spontaneous regression of the gliomas was noted on neuroimaging. In ten of these patients, regression was accompanied by improvement in visual acuity. These results are important in determining the natural history of optic nerve glioma, especially when evaluating the putative effect of chemotherapy and radiation for management of these tumors. However, it should be noted that this was a series of cases collected from multiple institutions worldwide. VII. Radiation and Graves' Orbitopathy Gorman CA, Garrity JA, Fatourechi V, et al. A prospective, randomized, double- blind, placebo- controlled study of orbital radiotherapy for Graves' ophthalmopathy. Ophthalmology 2001; 108: 1520- 2522. The efficacy of the use of radiation for the management of Graves' orbitopathy in the absence of compressive optic neuropathy has not been definitively established. These authors used a randomized, double- blind, placebo-controlled crossover study to evaluate this issue. Forty- two patients with symptomatic Graves' orbitopathy without compressive optic neuropathy were randomized. The study design consisted of radiation of one orbit ( 20 Gy) and sham therapy ( placebo) to the contralateral side. Six months later, the managements were reversed, and the placebo orbit received radiation while the previously treated orbit was sham- treated. Outcome measures included the measurement of volume of extraocular muscle and fat, proptosis, the range of extraocular muscle motion, the area of single binocular vision fields, and lid fissure width. No significant difference in any of these outcome measures was observed between the treated and the untreated orbit at 6 months. At 12 months, there was a slight improvement in proptosis and muscle volume in the orbit that was treated first. The authors concluded that they were unable to demonstrate any significant therapeutic effect of radiation. Although the power of the study limits the ability to detect very small changes, the reviewer believes this study has definitively answered the question of the role for radiotherapy for orbital congestion with thyroid eye disease. Application of these results to clinical practice, however, demands a rigorous evaluation of study details, especially the exclusion criteria. All patients with compressive optic neuropathy were excluded. Therefore, the conclusion that radiation does not work for compressive optic neuropathy cannotbe derived from this study. In fact, many neuro- ophthalmologists, myself included, continue to recommend radiation treatment for the management of compressive optic neuropathy. The fact that the conclusions from this study do not apply to patients with compressive optic neuropathy was pointed out in an accompanying editorial: Feldon SF. Radiation therapy for Graves' ophthalmopathy: trick or treat. Ophthalmology 2001; 108: 1520- 2. Medicine Journals Reviewers: Francine Wein, MD, and Leonard A. Levin, MD, PhD I. Giant Cell Arteritis Liozon E, Herrmann F, Ly K, et al. Risk factors for visual loss in giant cell ( temporal) arteritis: a prospective study of 174 patients. Am J Med 200l; l 11: 211- 7. Liozon et al. tested the hypothesis that the thrombocytosis seen in GC A might be associated with thrombosis in the short posterior ciliary arteries. The authors studied 174 consecutive patients diagnosed with GCA for whom pre-treatment platelet counts were available. Of the 174 patients, 147 had positive temporal artery biopsies and 27 were diagnosed based on American College of Rheumatology criteria. All patients received at least 0.6 to 0.7 mg prednisone/ kg/ d until they became asymptomatic, and their C- reactive protein ( CRP) fell below 5 mg/ L. The dose was then progressively tapered to 0.35 mg/ kg within 4 to 6 weeks. They tabulated visual events that had occurred before therapy or within 2 weeks after its initiation. Permanent visual loss was present in 23 patients ( 13%), 20 before instituting management and 3 after management. The etiologies of the visual loss were AION ( 20 patients), central retinal artery occlusion ( 1) and bilateral retrobulbar optic neuropathy ( 2). Headache was noted by 21 patients before visual loss. Transient visual symptoms, mainly amaurosis fugax, heralded permanent visual loss in 10 patients ( 43%). Transient visual symptoms and thrombocytosis were risk factors for permanent visual loss, whereas a diagnosis of polymyalgia rheumatica ( PMR), constitutional symptoms and an elevated CRP level and upper limb artery involvement were associated with a reduced risk. After including only the patients who had biopsy- proven GCA, an elevated platelet count remained the only risk factor for 61 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 1, 2002 Wein and Levin permanent visual loss. The risk was especially high in patients with platelet counts higher than 600 x 109 / L. Why were extracephalic manifestations of GCA associated with a reduced risk of visual loss? The authors hypothesize that the low risk may be related to the pattern of cytokine production in affected vessels. T cells infiltrating temporal arteries produce mainly interferon ( IFN) gamma in patients with isolated cranial arteritis and mainly inter-leukin- 2 ( IL- 2) in patients with PMR or an aortic arch syndrome. They explain that IFN gamma strongly stimulates macrophages to produce platelet growth factors and metalloproteinases, resulting in thrombocytosis, intimal hyperplasia, and severe arterial wall destruction, whereas IL- 2 does not have these effects and induces less severe arterial disease. Despite the title of the article, these patients were not prospectively studied with respect to the development of visual loss because the vast majority of patients had lost vision before entering the study. Nonetheless, these results suggest that thrombocytosis is not only a marker for GCA, but also a marker for patients at high risk of visual loss. Given that three such patients developed visual loss after the initiation of steroid therapy, patients with GCA and thrombocytosis may need to be dosed higher than 0.7 mg/ kg/ d. Turlakow A, Yeung HW, Pui J, et al. Fludeoxyglucose positron emission tomography in the diagnosis of giant cell arteritis. Arch Intern Med 2001; 161: 1003- 1. Turlakow et al. describe the novel use of positron emission tomography ( PET) to diagnose GCA in a 75- year-old woman. Though her clinical presentation ( 3- month history of fatigue, weight loss, low- grade fever, anorexia, and two episodes of transient loss of visual acuity) was typical of GCA, an initial sedimentation rate was 10 mm/ h, and the diagnosis was not considered. A chest computed tomography ( CT) scan revealed anterior mediastinal lymphadenop-athy, and the patient was eventually referred to a thoracic surgeon. Preoperative evaluation included a 18F- fludeoxyglucose PET scan. " Strikingly increased" metabolism was shown in the aorta, subclavian, carotid, vertebral, and common iliac arteries bilaterally. A large vessel vasculitis was diagnosed. Histopathologic examination of the anterior mediastinal mass confirmed giant cell vasculitis of a large muscular artery within an enlarged thymus. The patient was treated with oral prednisone, and both the patient's symptoms and PET scan normalized over the next 2 weeks. 18F- fludeoxyglucose PET scanning is based on its differential uptake by actively metabolizing cells. Clinically significant uptake has been demonstrated in numerous neoplastic, inflammatory, and infectious conditions. Increased thoracic vascular 18F- fludeoxyglucose uptake is highly specific for the diagnosis of GCA. The differential diagnosis of such uptake includes Takayasu arteritis and polymyalgia rheumatica. An advantage over gallium imaging is its ability to demonstrate vascular glucose metabolism at a higher resolution. Another advantage is that standardized uptake values can provide an objective measure of disease activity, which is useful for evaluating the response to therapy. Though PET is expensive and not available in many hospital centers, its use could be considered when there is a high clinical suspicion of GCA, but bilateral temporal artery biopsies are negative. If positive, 18F- fludeoxyglucose PET scanning can suggest the best site for performing a diagnostic biopsy. II. Stroke and Carotid Endarterectomy Alamowitch S, Eliasziw M, Algra A, et al. Risk, causes, and prevention of ischemic stroke in elderly patients with symptomatic internal- carotid- artery stenosis. Lancet 2001 ; 357: 1154- 60. Alamowitch et al. studied patients from the North American Symptomatic Carotid Endarterectomy Trial ( NASCET) with symptomatic internal carotid artery ( ICA) stenosis. They stratified by age and compared outcomes of patients treated with carotid endarterectomy to best medical therapy. Patients were classified into three age groups: 75 years or older, 65 to 74 years, and younger than 65 years. The first group was considered elderly. At baseline these patients were less likely than younger patients to have atherosclerotic risk factors and least likely to have severe ICA stenosis. Among surgically treated patients, the elderly group had the lowest risk of ipsilateral stroke, regardless of the degree of ICA stenosis. However, they had the highest risk of stroke with medical management, which depended on the degree of ICA stenosis ( 24.9% risk of stroke for 50%- 69% stenosis; 36.5% risk of stroke for 70%- 99% stenosis). Because elderly patients had the highest risk with medical management, the absolute risk reduction with surgical management was greatest ( 28.9%, P < 0.0001). In addition, among patients with 50% o to 69% o stenosis, reduction in risk was significant only for the oldest age group ( 17.3% o, P = 0.0005). No significant benefitto surgical management was seen in patients with less than 50% o stenosis in any age category. The greatest benefit of surgery in the elderly, compared with the younger patients, resulted from having a combination of the highest risk of ipsilateral ischemic stroke if managed medically and the lowest surgical risk, presumably because of their lower number of baseline atherosclerotic risk factors. These data should help guide 62 © 2002 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. IN OTHER JOURNALS JNeuro- Ophthalmol, Vol. 22, No. 1, 2002 choice of therapy for elderly patients and symptomatic ICA stenosis. Middeldorp S, Meinar di JR, Koopman MM, et al. A prospective study of asymptomatic carriers of the factor V Leiden mutation to determine the incidence of venous thromboembolism. Ann Intern Med 2001 ; 135: 322- 7. Middledorp et al. studied the incidence of venous thromboembolism ( VT) in 470 asymptomatic carriers of the factor V Leiden mutation. Carriers were identified by screening first- degree relatives of symptomatic probands. The mean age was 43 years, and 12 were homozygous carriers. Mean follow- up was 3.3 years ( range 1.5- 4.8 years). Nine heterozygotes had a venous thromboembolic event, yielding an overall absolute incidence rate of 0.57%. Four events occurred spontaneously, one occurred postoperatively ( despite low- molecular- weight heparin prophylaxis), one occurred 5 months after initiation of hormone replacement therapy ( HRT), and 3 events occurred during oral contraceptive use. The incidence of VT with regard to these exogenous risk factors was therefore 3.5% o for surgery, trauma, or immobilization for longer than 7 days, 0% o for pregnancy, 2.9%> per year of use of HRT, and 1.8% per year of use of oral contraceptives. The authors conclude that the annual incidence of VT is too low to justify family screening of symptomatic patients. They point out that the spontaneous rate of VT ( 0.26% o per year) detected in their study is much lower than the reported 2% o to 10% risk of major bleeding with warfarin management. The authors acknowledge that it is unclear whether screening is indicated when a potential carrier is exposed to one of the studied risk factors. The study has several shortcomings, many noted by the authors. First, the follow- up time is short and the number of patients small. Second, family members who had histories of VT were excluded, thus biasing the results toward a lower incidence. Third, no control group was used, either from the general population or from individuals exposed to the same risk factors of immobilization, pregnancy, postpartum period, HRT, and oral contraceptive use. Fourth, knowledge of the factor V Leiden mutation may have influenced the management of these patients toward more aggressive thromboprophylaxis during high- risk situations. Indeed, seven women in the study chose to have anticoagulant prophylaxis in the postpartum period. Benavente O, Eliasziw M, Streifler JY, et al. Prognosis after transient monocular blindness associated with carotid- artery stenosis. N Engl.) Med 2001; 345: 1084- 90. Analyzing data from NASCET, Benavente et al. compared the risk of stroke in patients with transient monocular blindness ( TMB) and hemispheric transient ischemic attack ( TIA) and assessed the effectiveness of carotid endarterectomy in patients with TMB. Of the 1583 patients enrolled in the trial, 496 had episodes of TMB. Patients with TMB were more likely to have smoked in the year before entering the study, were roughly twice as likely to have ICA stenosis of at least 70% o or near- occlusion of the ICA, and were more than three times as likely to have evidence of collateral circulation. Patients with hemispheric TIA tended to be older and were more likely to have a history of hypertension, diabetes mellitus, and to have evidence of brain infarcts on imaging. After accounting for all baseline characteristics, patients with TMB were half as likely to have a stroke or die within 30 days of surgery [ adjusted hazard ratio 0.51; 95% o confidence interval ( CI) 0.21- 1.22]. The 3- year risk among the surgically managed patients with TMB and among those with hemispheric TIA was similar. However, the medically managed patients with TMB had a 3- year risk of ipsilateral stroke that was approximately half that of the medically managed patients with hemispheric TIA ( adjusted hazard ratio 0.53, 95% CI 0.30- 0.94). Among patients who had TMB and never had hemispheric TIA, neither the number nor duration of TMB episodes influenced the risk of ipsilateral stroke. The most important risk factors for subsequent ipsilateral stroke in patients who were medically managed for TMB were older than or equal to 75 years, male gender, history of hemispheric TIAs or stroke, history of intermittent claudication, ipsilateral ICA stenosis of 80% o to 94% o, and absence of collaterals on angiography. If less than two of these risk factors were present, the risk of stroke was less with medical management. If two or more risk factors were present, the risk of stroke was less with surgical management. More specifically, the number needed to treat was 20 or less with two or more risk factors, i. e., 20 patients or less would need to undergo endarterectomy to prevent one stroke or more). This article has important implications in terms of whom to refer for carotid endarterectomy. Endovascular versus surgical management in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study ( CAVATAS): a randomised trial. Lancet 2001; 357: 1729- 37. Patients with " clinically important" internal carotid stenosis were randomized to either conventional carotid endarterectomy ( 253 patients) or endovascular management ( 251 patients). No attempts were made to standardize criteria for management other than the clinical opinion of the investigator. At baseline, 25% o of patients had a history of transient monocular blindness, 38% o transient ischemic attack, 2% o retinal infarct ( presumably central or branch 63 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 1, 2002 Wein and Levin retinal occlusion), 26% hemispheric stroke, and the rest had no symptoms. The two management groups were similar in these and other baseline characteristics. Major outcomes within 30 days of management were similar, with death or stroke occurring in 10% of patients in each group. Cranial neuropathy or neck or groin hematoma was significantly more likely in the surgical group. Long-term outcomes were similar, with one exception. The mean follow- up was 2 years, and ranged from 1 month to 3 years. The risk of stroke over the subsequent 3 years was 14% in both the surgical and endovascular groups. However, the proportion of ultrasonographically measured severe ( 70%- 99%) ICA stenosis at one year was 4% in the surgical group and 14% in the endovascular group, and the proportion of occlusion was 1% in the surgical group and 4% in the endovascular group. This report is encouraging evidence that endovascular approaches to ICA stenosis may eventually rival standard extravascular approaches. However, the lack of strict inclusion and exclusion criteria for patients enrolled in the study could limit its generalizability. No data are provided for the subgroup of patients with transient monocular blindness, in whom the risk of stroke is already low. Publication of these data would be helpful in assessing the utility of the endovascular approach to ICA stenosis in these patients. Wong TY, Klein R, Couper DJ, et al. Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study. Lance? 2001 ; 358: 1134^ 10. Wong et al. obtained undilated retinal photographs in 10,358 men and women living in North Carolina, Mississippi, Minnesota, and Maryland. They followed the patients for an average of 3.5 years ( range 3- 5 years), and observed the frequency of stroke ( ischemic or hemorrhagic), stratifying it with respect to retinal vessel abnormalities, predisposing systemic diseases ( diabetes, hypertension, coronary artery disease), and other risk factors ( smoking, alcohol use, cholesterol). There were 110 patients with stroke ( 96 ischemic, 13 hemorrhagic, and one ischemic/ hemorrhagic). After adjusting for age, gender, race, and locality, each of the retinal microvascular lesions observed increased the relative risk of stroke above baseline ( microaneurysm: RR 5.0 [ 95% CI 3.0- 8.2], soft exudates: 5.6 [ 2.8- 89], blot hemorrhage: 4.9 [ 2.7- 8.8], flame hemorrhage: 4.6 [ 2.1- 9.9], arteriovenous nicking: 1.9 [ 1.3- 3.0]). Much of this could be expected because these lesions are commonly associated with hypertension, diabetes, and other vascular diseases, and these diseases are all risk factors for stroke. Surprisingly, when a multivariate analysis was done, adjusting for blood pressure, the use of antihypertensive medications, the presence of diabetes, smoking status, fasting glucose, and blood lipid measurements, each of the retinal abnormalities was still a significant risk factor for stroke, although to a lesser degree. A stratified analysis using the presence of diabetes and hypertension also showed that the retinal abnormalities were independent predictors of stroke, although the small number of patients in some of the groups meant that the confidence limits were wide. The biggest potential flaw of this study is that the confounding variables ( presence of hypertension and other vascular diseases may not have been completely eliminated in the multivariate analyses. Nonetheless, an important implication of this study is that observation of a retinal microvascular abnormality in a patient should not only prompt a work- up for vascular disease, but even if no disease is present, suggest that the patient is at an increased risk of stroke. The retinal abnormalities may be markers of small vessel disease and may be indicative of vascular pathologic processes occurring in the cerebral circulation. III. Medication Effects Yood RA, Harrold LR, Fish L, et al. Prevention of glucocorti-coid- induced osteoporosis: experience in a managed care setting. Arch Intern Med 2001 ; 161: 1322- 7. In recent years it has become apparent that even low-dose glucocorticoid management may result in bone loss. Despite information that glucocorticoid- induced osteoporosis may be prevented using calcium, vitamin D, and bis-phosphonates, many patients do not receive prophylaxis. Yood et al. analyzed osteoporosis prevention in 224 patients who were dispensed at least one prescription of oral glucocorticoid quarterly over the course of a year and who had confirmation of glucocorticoid use in the medical record. Automated databases were used to ascertain information about glucocorticoid prescriptions and prescriptions for prophylactic medication. The mean glucocorticoid dose was 8.9 ± 7.3 mg of prednisone or equivalent. Only 62% of the patients receiving glucocorticoids during the study year had any osteoporosis prophylaxis or a diagnostic intervention documented. This rate was highest among rheumatologists ( 90%), followed by pulmonologists ( 55%), internists ( 48%), and " other specialties" ( 46%). Only 31% of patients had a bone mineral density study, 40% had calcium supplementation, and 37% vitamin D supplementation. Women were more likely than men to have received education on the need for calcium and vitamin D and were also more likely to have bone- mineral density testing. There are several weaknesses in the study, most of which were recognized by the authors. They did not rely on recorded lists of medication use, but on a database of prescription use at the organization's pharmacies. Physicians 64 © 2002 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. IN OTHER JOURNALS JNeuro- Ophthalmol, Vol. 22, No. 1, 2002 may not reliably document use of nonprescription medications, so the results may underestimate calcium and vitamin D use. The mean daily dose of glucocorticoid was calculated but not the pattern in which it was taken ( intermittently versus continuously). The authors conclude that many patients are not receiving prevention or management of glucocorticoid-induced osteoporosis, despite publication of guidelines by the American College of Rheumatology. Explanations include a lack of knowledge about the frequency of glucocor-ticoid- induced osteoporotic fractures, lack of awareness of the existence and effectiveness of prophylactic therapy, and possibly a belief among physicians that there is a safe dose of glucocorticoids. In addition, fragmentation of care among several specialists with no primary care physician may also be a contributing factor. Ziegler DK, Mosier MC, Buenaver M, et al. How much information about adverse effects of medication do patients want from physicians? Arch Intern Med 2001; 161: 706- 13. What should we tell our patients about the side effects of the managements we give them? Ziegler et al. studied this question by surveying adult patients, their companions, medical students, and employees visiting or working at the outpatient clinics of the University of Kansas Medical Center. Patients were given the choice of wanting to hear about: 1) any side effect, no matter how rare; 2) side effects occurring in 1/ 100,000 patients; 3) side effects occurring in 1/ 100 patients; and 4) not hearing about side effects. They were also asked the same question with respect to serious side effects. They then were asked if doctors should give the same detailed information to every patient, or base it on the individual patient, and if there were occasions when a doctor would be justified in withholding information about side effects. Of the 2652 patients approached, 2500 agreed to participate in the survey, giving a response rate of 94%. Interestingly, the vast majority ( 76%) of patients preferred to be told of any side effect, no matter how rare. For serious side effects, 83% of patients wanted to be told of the possibility, no matter how rare. The less educated the patient, the more likely they wanted to be told of any side effect. Approximately 2/ 3 of patients felt that doctors should disclose the same information about side effects to all patients and should never withhold information from patients. This study clearly indicates that in the group sampled, there was a strong desire to have all of the possible adverse effects of managements disclosed. Whether these results can be extrapolated to individual patients is unknown. Given that neuro- ophthalmologists use treatments with potentially severe side effects, it may be worthwhile to ask patients how much information they would like to have, and then provide it to them. IV. Multiple Sclerosis Comi G, Filippi M, Barkhof F, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001 ; 357: 1576- 82. The CHAMPS ( Controlled High- Risk Subjects Avonex Multiple Sclerosis Prevention Study) data had previously shown that patients with an initial monosymptom-atic demyelinating event, including optic neuritis, had better clinical outcomes and lesser accumulation of MRI lesion burden when managed with intravenous methylpredniso-lone ( ONTT doses) followed by weekly intramuscular interferon beta- la than with methylprednisolone alone. The European ETOMS ( Early Treatment of Multiple Sclerosis) group performed a similar study, albeit with important differences. They enrolled patients with new onset of neurologic symptoms or signs, either unifocal or multifocal, and four white matter lesions on T2- weighted MRI scans ( three if one or more was enhancing or infratentorial). Patients were randomized to either Rebif ( subcutaneous interferon beta- la) 22 ug or placebo, injected weekly for 2 years. Of 308 patients randomized, 241 received management of the full 2 years. The endpoint of converting to clinically definite multiple sclerosis was reached by 34% of patients in the interferon group and 45% in the placebo group ( P = 0.047). The number of white matter lesions on MRI per was significantly lower in the interferon group than in the placebo group ( 2.0 [ range 0.5- 4.5] versus 3.0 [ 1.5- 6.25]; P < 0.001). There were no significant differences between groups in disability scores. As expected, there were significantly higher rates of adverse effects in the interferon group, including inflammation at the injection site ( 60% versus 12%), fever ( 28% versus 12%), and chills ( 11% versus 5%). These data largely confirm the findings of the CHAMPS study, even though there were several differences in study design. In the current study the patient population had both unifocal and multifocal clinical disease. The dose of interferon used was smaller than in the CHAMPS study, and the delivery route different. Patients were enrolled as long as 3 months after onset of clinical symptoms, as compared with the 2- week limit in CHAMPS. No stratification by type of demyelinating event was done. Nonetheless, it is encouraging that two studies of the same type of interferon both showed significant effects on preventing conversion to multiple sclerosis. 65 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. |