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Show ORIGINAL CONTRIBUTION Visual Outcome in Eyes With Asymptomatic Optic Disc Edema Yehoshua Almog, MD, and Michaella Goldstein, MD Background: Asymptomatic optic disc edema may last for months before conversion to anterior ischemic optic neuropathy ( AION). Alternatively, the optic disc edema may resolve with preservation of normal vision. The conversion rate of asymptomatic optic disc edema to AION has not been prospectively studied. We prospectively followed patients with asymptomatic disc edema to determine this conversion rate. Methods: The cohort was followed from 1991 to 2000 at a single ophthalmology clinic in Israel. There were 23 patients aged 47- 74 years with asymptomatic disc edema and no signs of optic nerve dysfunction in whom the disc edema had been incidentally discovered on routine fundus examination performed for diabetes, hypertension, or follow- up after AION in the fellow eye. Results: In 9 ( 36%) eyes, optic disc edema progressed to overt AION with a mean latency of 16.8 weeks ( range 2- 80 weeks). In 16 ( 64%) eyes, optic disc edema resolved without loss of vision with a mean latency of 15.5 weeks ( range 4- 44 weeks). The conversion rate to AION was 40% in patients who had had AION in the fellow eye, 31 % in patients with diabetes, 43% in patients with diabetic retinopathy, and 0% in four amiodarone- treated patients. Conclusion: Asymptomatic disc edema generally resolves with no visual loss, but one third of patients progress to full- blown AION. Diabetes mellitus is common in patients with asymptomatic optic disc edema. Perhaps patients diagnosed as having diabetic papillopathy actually have an impending AION that does not progress to overt disease. ( JNeuro- Ophthalmol 2003; 23: 204- 207) Patients with anterior ischemic optic neuropathy ( AION) always manifest optic disc edema when presenting to the ophthalmologist with visual loss. In 1981, Hayreh ( 1). From the Neuro- Ophthalmology Unit, Meir Hospital Sapir Medical Center and Sackler Faculty of Medicine ( YA), Tel- Aviv University, and Department of Ophthalmology ( MG), Tel- Aviv Medical Center and Sackler Faculty of Medicine, Tel- Aviv University, Tel- Aviv, Israel. Reprints: Yehoshua Almog, MD, Neuro- Ophthalmology Unit, Meir Hospital, Tchernichovsky 59 Street, Kfar- Saba 44281, Israel. E- mail: Almogy@ clalit. org. il first described 4 visually asymptomatic patients in whom disc edema was diagnosed on a routine examination. Some of these patients, who had normal visual function, later developed typical symptomatic AION. Other patients have asymptomatic optic disc edema that resolves spontaneously. This phenomenon has been described mainly in diabetes mellitus ( 2) and has therefore been called " diabetic papillopathy." There is much confusion as to whether diabetic papillopathy and AION are the same entities. In 1997, Gordon et al ( 3) described 2 patients who had AION in 1 eye and asymptomatic optic disc edema in the fellow eye that resolved spontaneously. Spontaneous resolution of asymptomatic optic disc edema has also been described in patients treated with amiodarone ( 4,5). The conversion rate of asymptomatic optic disc edema to symptomatic AION has never been prospectively studied. It was the purpose of this study to determine this rate and to characterize the patients who undergo conversion. METHODS Included in the study are 23 patients who attended the neuro- ophthalmology unit in the Tel- Aviv Medical Center from November 1991 through December 2000 with the diagnosis of asymptomatic optic disc edema. Most patients were referred for disc edema as incidentally discovered on routine fundus examination performed for diabetes or hypertension. In most others, the asymptomatic disc edema was incidentally discovered in our clinic on follow- up after a diagnosis of AION in the fellow eye. One patient was followed because of a question of amiodarone- induced optic neuropathy. The mean age of our cohort was 63 years ( range 45- 74 years). There were 16 men and 7 women. Diabetes mellitus was present in 19 ( 83%) patients, 4 of whom were being treated with insulin. Among the 19 patients with diabetes, 11 had no evidence of diabetic retinopathy. Among the eight patients who had diabetic retinopathy, it was always nonproliferative. Systemic hypertension was present in 11 ( 48%). Four patients ( 17%) were being treated with Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 204 J Neuro- Ophthalmol, Vol. 23, No. 3, 2003 Asymptomatic Optic Disc Edema JNeuro- Ophthalmol, Vol. 23, No. 3, 2003 amiodarone for cardiac arrhythmia; 3 of them also had diabetes. Only 2 patients were free of atherosclerosis. History and findings suggesting old AION in the fellow eye were present in 10 ( 43%) patients. Bilateral asymptomatic disc edema was present in 2 patients. The cup- to- disc ratio exceeded 0.2 in only 1 patient. All patients underwent a complete ophthalmological examination, including visual acuity, biomicroscopy, pupillary tests, color vision tests, fundoscopy, and visual field examination ( Humphrey 30- 2 or 24- 2). Blood samples for glucose, urea, cholesterol, triglycerides, blood count, and erythrocyte sedimentation rate were drawn in all patients. Fluorescein angiography, performed in all patients to distinguish congenital optic disc elevation from acquired edema, demonstrated abnormal staining of the involved disc in every case. All patients had a corrected visual acuity of 20/ 40 or better in the eye with asymptomatic optic disc edema. Depression of visual acuity was always attributable to cataract or diabetic retinopathy. There was no relative afferent pupillary defect on the side with the disc edema. Color vision was always normal. In eyes with asymptomatic optic disc edema, there was no visual field defect other than an enlarged blind spot. Six patients underwent computed tomography of the brain when papilledema was considered, and none had pertinent abnormalities. A temporal artery biopsy in 1 patient with an erythrocyte sedimentation rate of 70 mm/ h was normal. Patients were followed on a weekly basis for the first month, then on a monthly basis until 1 of 2 endpoints was reached: 1) complete resolution of the optic disc edema with preserved visual function, or 2) development of AION, defined by subjective visual loss and visual field defect with or without decreased visual acuity, color vision, or afferent pupillary defect. RESULTS Table 1 summarizes the demographic parameters, systemic medical features, current drug therapy, and clinical endpoints of eyes with asymptomatic disc edema. In 9 ( 36%) eyes, disc edema progressed to overt AION with sudden and persistent loss of vision. In these eyes, the mean time lag between the identification of the asymptomatic disc edema and the development of AION was 16.8 weeks ( range 2- 80 weeks). If the 1 patient who developed AION after 80 weeks ( Patient 16) is excluded, the mean time lag for development of AION was 9 weeks ( range 2- 18 weeks). Optic disc edema resolved without visual loss in 16 ( 64%) of eyes. In these eyes, the mean time for resolution of the optic disc edema was 15.5 weeks ( range 4- 44 weeks). Among 10 patients ( 43%), history and ocular findings were consistent with the diagnosis of AION in the fellow eye. In this group, 4 ( 40%) demonstrated progression to overt AION, and 6 ( 60%) demonstrated resolution of the edema without visual loss. The conversion rate to AION in other subgroups was 6 ( 31%) of 19 patients with diabetes, 3( 43%) of 7 patients with diabetic retinopathy, and 0 ( 0%) of 4 patients treated with amiodarone. Among 2 patients with binocular asymptomatic disc edema, 1 patient progressed to AION in both eyes, and the other patient had 1 eye resolve without visual loss and the fellow eye develop classic AION. Among the 9 eyes that progressed to AION, the mean visual acuity was 0.63 log Mar ( range 0.2- 1.3). Among the 6 eyes who underwent threshold visual field testing after converting to AION, the mean of the mean deviation was - 15.3 dB ( range - 8.1 to - 27.7 dB). DISCUSSION Our study found that asymptomatic disc edema resolved without visual loss in 64% of eyes with a mean latency of 15.5 weeks ( range 4- 44 weeks). In 36% of eyes, optic disc edema progressed to AION with a mean latency of 16.8 weeks ( range 2- 80 weeks). Among those who progressed to AION, most had diabetes mellitus, but the rate of progression to AION was not dependent on the presence of diabetic retinopathy, nor did a history of AION in the fellow eye particularly predispose to the conversion to AION in the asymptomatic eye. Our study is the first to prospectively follow a sufficient number of patients with asymptomatic disc edema to estimate the rate of developing AION in these patients, as well as the latency of conversion. The optic disc edema in this group of patients may represent a state of disc ischemia not severe enough to cause loss of axonal function. AION is associated with systemic diseases such as hypertension, diabetes mellitus, and atherosclerotic cardiovascular and cerebrovascular disease ( 6- 9). The fact that all but two of our patients had systemic diseases that are associated with atherosclerosis suggests that asymptomatic optic disc edema may be a preinfarctive state in these patients. Almost half of our patients had past AION in the fellow eye, suggesting that their asymptomatic disc edema may be considered an impending AION. Another argument to imply that asymptomatic disc edema in these patients is related to ischemia and AION was the small cup- to- disc ratio in all but one of them ( 10). We were surprised at the high prevalence of diabetes ( 83%) in our group. It could be argued that the asymptomatic disc edema was incidentally discovered in patients with diabetes because they undergo regular fundus examinations, but we have not observed this entity as frequently in other groups of patients who undergo comparable periodic Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 205 JNeuro- Ophthalmol, Vol. 23, No. 3, 2003 Almog and Goldstein TABLE 1. Clinical data in 23 patients with asymptomatic optic disc edema Pt. no./ age/ gender 1/ 67/ F 2/ 70/ M 3/ 70/ F 4/ 49/ M 5/ 74/ M 6/ 62/ M 7/ 66/ F 8/ 66/ M 9/ 73/ F 10/ 84/ M 11/ 64/ M 12/ 68/ M 13/ 53/ F 14/ 61/ M 15/ 72/ M 16/ 72/ M 17/ 65/ M 18/ 61/ M 19/ 47/ F 20/ 52/ F 21/ 54/ M 22/ 70/ M 23/ 73/ M Systemic diseases Diabetes, hypertension Diabetes, stroke, PAF, renal tumor, hypertension Diabetes Diabetes Diabetes, PAF, hypertension Diabetes, ischemic heart disease Diabetes Diabetes, arrhythmia Diabetes - Diabetes, hypercholesterolemia Hypertension, PAF Hypertension, PAF Diabetes Diabetes, hypertension Diabetes, hypertension Diabetes hypertension Diabetes, stroke, hypertension Diabetes Diabetes Diabetes hypertension - Diabetes, hypercholesterolemia, hypertension AION, anterior ischemic optic neuropathy; F, Diabetes treatment/ amiodarone Diet Oral hypoglycemics, amiodarone Oral hypoglycemics Insulin Oral hypoglycemics, amiodarone Oral hypoglycemics Oral hypoglycemics Oral hypoglycemics, amiodarone Insulin - Diet Amiodarone - Oral hypoglycemics Oral hypoglycemics Oral hypoglycemics Oral hypoglycemics Oral hypoglycemics Insulin Insulin Oral hypoglycemics - Oral hypoglycemics female; M, male; RE, right Optic disc abnormalities RE: Edema LE: Normal RE: Edema LE: Pallor RE: Pallor LE: Edema RE: Pallor LE: Edema RE: Edema LE: Normal RE: Normal LE: Edema RE: Normal LE: Edema RE: Pallor LE: Edema RE: Edema LE: Normal RE: Edema LE: Pallor RE: Edema LE: None RE: Pallor LE: Edema RE: Pallor LE: Edema RE: Normal LE: Edema RE: Pallor LE: Edema RE: Edema LE: Normal RE: Normal LE: Edema RE: Edema LE: Edema RE: Pallor LE: Edema RE: Edema LE: Pallor RE: Edema LE: Edema RE: Normal LE: Edema RE: Normal LE: Edema eye; LE, left eye; Visual acuity at presentation 20/ 30 20/ 30 20/ 800 20/ 50 20/ 40 20/ 40 20/ 25 20/ 20 20/ 25 20/ 40 20/ 400 20/ 20 20/ 20 20/ 20 20/ 100 20/ 20 20/ 25 20/ 50 20/ 25 20/ 25 20/ 50 20/ 20 20/ 20 20/ 30 20/ 20 20/ 20 20/ 70 20/ 20 20/ 30 20/ 60 20/ 20 20/ 20 20/ 20 20/ 40 PAF, paroxysmal Time to resolution or AION Resolved 9 wks Resolved 13 wks AION 6 wks Resolved 4 wks Resolved 5 wks Resolved 28 wks Resolved 9 wks Resolved 4 wks AION 4 wks AION 2 wks Resolved 9 wks Resolved 28 wks AION 4 weeks Resolved 9 wks Resolved 28 wks AION 80 wks Resolved 44 wks AION 6 wks AION 18 wks Resolved 5 wks AION 18 wks RE: Resolved 6 wks LE: AION 14 wks Resolved 28 wks Resolved 9 wks atrial fibrillation. Final visual acuity 20/ 25 20/ 30 20/ 40 20/ 25 20/ 20 20/ 25 20/ 40 20/ 25 20/ 200 20/ 40 20/ 20 20/ 25 20/ 30 20/ 20 20/ 20 20/ 400 20/ 30 20/ 400 20/ 70 20/ 20 20/ 50 20/ 20 20/ 40 20/ 25 20/ 30 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 206 © 2003 Lippincott Williams & Wilkins Asymptomatic Optic Disc Edema JNeuro- Ophthalmol, Vol. 23, No. 3, 2003 eye examinations, such as those with high myopia, previous retinal detachment, retinal artery or vein occlusion, age-related macular degeneration, or prior AION in one eye. In their case- control study, Jacobson et al ( 9) concluded that diabetes is a major risk factor for the development of non-arteritic AION. Moster ( 11) found as well that the vascular effects of diabetes contribute to nonarteritic AION. We therefore assume that the incidental finding of asymptomatic disc edema might be related, although not exclusively, to diabetes. Diabetic papiUopathy, first described in patients with juvenile- type insulin- dependent diabetes mellitus ( 12- 15), is now recognized to occur in subjects with adult- onset non-insulin- dependent diabetes as well ( 2,16). In 1995, Regillo et al ( 2) found that all patients with diabetic papiUopathy had at most only mild loss of vision, that their optic disc edema generally resolved after a few months without permanent severe visual loss, and that most had small cup- to-disc ratios. However, these authors excluded patients who developed AION, a fact that could artificially separate diabetic papiUopathy from AION. We believe there is much similarity between our group of patients and those described in the past as having diabetic papiUopathy. Perhaps such patients actually have an asymptomatic disc edema that has not evolved into full- blown AION. REFERENCES 1. Hayreh SS. Anterior ischemic optic neuropathy V. Optic disc edema as an early sign. Arch Ophthalmol. 1981; 99: 1030- 1040. 2. 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