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Show ORIGINAL CONTRIBUTION Intravitreal Triamcinolone Improves Recovery of Visual Acuity in Nonarteritic Anterior Ischemic Optic Neuropathy Berkant Kaderli, MD, Remzi Avci, MD, Ali Yucel, MD, Kazim Guler, MD and Oner Gelisken, MD Background: The visual outcome in untreated nonarteritic anterior ischemic optic neuropathy ( NAION) is dismal. Because intravitreal triamcinolone ( IVTA) has shown promise in improving edematous retinal disorders, a pilot trial of this therapy in NAION was considered reasonable. Methods: Four eyes of 4 patients with severe visual loss due to NAION were treated with 4 mg IVTA ( study group). The control group consisted of 6 consecutive patients with NAION who received no treatment. Patients were evaluated by the visual acuity and visual field measurements of the Early Treatment Diabetic Retinopathy Study ( ETDRS) and fluorescein angiography. Results: All patients completed at least 9 months of follow- up. In the study group, the mean improvement in visual acuity were 4,5.8, and 6.2 ETDRS lines at the first and third weeks and final visit, respectively. Optic disc swelling and leakage had markedly decreased at the first postinjection week and had disappeared by the third week examination in all eyes. In the control group, the mean improvements in visual acuity were 0,0.7, and 1.3 ETDRS lines at the first and third weeks and final visit, respectively. Control eyes showed resolution of the optic disc swelling between the fourth week and third month visits. No marked change in visual field defects was observed in either group. Conclusions: IVTA provided relatively improved recovery of visual acuity and relatively rapid resolution of optic disc swelling in a small sample of patients with acute NAION. It did not provide visual field improvement. A larger trial is merited by the results of this small pilot study. Department of Ophthalmology ( BK, RA, AY, OG), Uiudag University School of Medicine, Bursa, Turkey; and Focus Laser Eye Center ( KG), Bursa, Turkey. Address correspondence to Berkant Kaderli, MD, Uiudag University School of Medicine, Department of Ophthalmology, 16059 Gorukle Kampus/ Bursa/ Turkey; E- mail: kaderli@ uludag. edu. tr (/ Neuro- Ophthalmol 2007; 27: 164- 168) Nonarteritic anterior ischemic optic neuropathy ( NAION) is characterized by sudden loss of visual acuity and the visual field predominantly in individuals older than 50 years who have associated atherosclerotic diseases ( 1). There is no well- established treatment for NAION. Initial visual acuity is less than 20/ 200 in 34% of patients ( 1). At 6 months after onset, 42.7% of patients recover 3 lines of vision; however, visual acuity remains 20/ 200 or worse in 19% of patients ( 2). By using scanning laser polarimetry, Colen et al ( 3) documented progressive loss of nerve fiber layer tissue during the first 3 weeks in a patient with NAION. It has been suggested that in patients with small cup- to- disc ratios, the relative anatomic crowding within the optic disc can decrease axoplasmic flow when the optic nerve head is subjected to transient ischemia and swelling ( 4). Intravitreal triamcinolone acetonide ( IVTA) may help to resolve the optic disc edema and improve the reversible component of ischemic insult in NAION. Recently, Al- Haddad et al ( 5) reported rapid anatomic and functional recovery after IVTA in a patient with bilateral diabetic papillopathy We report our experience with IVTA in 4 patients with early stages of NAION. METHODS Study Group All patients in the study group presented to our university hospital on referral from outside ophthalmologists between June 2004 and January 2005 with unilateral painless visual acuity loss, relative afferent pupillary defect, and optic disc edema, features considered diagnostic of NAION. Exclusion criteria consisted of eyes with visual acuity better than 20/ 200, eyes that had undergone any kind of surgery, eyes with unclear optic media and ocular disease other than NAION, and patients with abnormal Westergren erythrocyte sedimentation rates, serum reactive protein levels, or pertinent neurologic findings. 164 J Neuro- Ophthalmol, Vol. 27, No. 3, 2007 Intravitreal Triamcinolone in NAION J Neuro- Ophthalmol, Vol. 27, No. 3, 2007 The durations of visual loss before study entry were 22, 12, 10, and 10 days in Cases 1, 2, 3, and 4, respectively ( Table 1). Automated visual field examination ( Humphrey 30- 2) disclosed nerve fiber bundle defects typical of NAION in affected eyes; visual fields were normal in fellow eyes. Optic disc edema and peripapillary hemorrhages were present in all affected eyes; the cup- to- disc ratio was 0.2 in all fellow eyes. Fluorescein angiography showed leakage in all affected optic discs. Neither ophthalmoscopy nor fluorescein angiography revealed diabetic macular edema in any eyes. All patients had systemic hypertension with a duration of at least 5 years. Cases 1, 2, and 3 had type 2 diabetes mellitus with durations of 1,10, and 5 years and hemoglobin A1C levels of 6.5, 7.3, and 6.9 mg/ 100 mL, respectively. Internal consultation revealed suboptimal blood pressure and moderate metabolic control of diabetes in all patients. Only Case 2 had signs of mild diabetic retinopathy without macular edema. Westergren erythrocyte sedimentation rate and serum reactive protein levels were normal in all patients. Neurologic consultations revealed no suspicion of multiple sclerosis or intracranial pressure increase. Study group patients were informed of the natural course of NAION and of various suggested treatment modalities including periocular or systemic corticosteroids, aspirin, hyperbaric oxygen, topical brimonidine tartrate, and IVTA. After the aim of the study and the possible risks had been fully explained, they provided informed consent. An intravitreal injection of 4 mg/ 0.1 mL triamcinolone ( TA) was then performed in the affected eye of each of all 4 study group patients. The intravitreal injection was carried out in the outpatient department under sterile conditions with subconjunctival anesthesia. The injection was applied with a 27 gauge needle, 3.5 mm from the superior temporal or nasal limbus. The continuity of optic disc blood supply was confirmed with ophthalmoscopy immediately after the injection in all eyes. To prevent secondary ocular hypertension, all eyes received topical 0.2% brimonidine tartrate twice daily during the first postinjection month. Outcomes were evaluated by Early Treatment Diabetic Retinopathy Study ( ETDRS) visual acuity and automated visual field measurements and fluorescein angiography at the first and third weeks, third month, and every 3 months thereafter. We recorded potential complications such as a rise in intraocular pressure, cataract progression determined by slit- lamp biomicroscopy, and endophthalmitis. Control Group The control group consisted of 6 consecutive patients who presented to a private eye clinic from June 2004 to January 2005 and in whom NAION was diagnosed. Exclusion criteria were the same as those for the study group. The duration of visual loss before initial examination was 8, 14, 7, 18, 11, and 14 days in control Cases 1, 2, 3, 4, 5, and 6, respectively ( Table 2). The Goldmann visual field examination disclosed nerve fiber bundle defects typical of NAION in affected eyes of all 6 control patients. Optic disc swelling and peripapillary hemorrhages were present in all affected eyes. The cup- to- disc ratio was 0.2 in all affected eyes of control patients. Fluorescein angiography showed leakage in all affected optic discs without signs of macular edema. All patients had systemic arterial hypertension with a duration of at least 8 years. Cases 2 and 4 had type 2 diabetes mellitus with durations of 10 and 11 years and hemoglobin A1C levels of 7.0 and 7.2 mg/ mL, respectively. Internal consultation revealed optimal blood pressure and moderate metabolic control of diabetes in all patients. Both patients with diabetes had signs of mild diabetic retinopathy without macular edema. The Westergren erythrocyte sedimentation rates and serum reactive protein levels were normal for age in all patients. Neurologic consultations revealed no other abnormalities. All patients continued to receive their antihypertensive and antidiabetic drugs. All patients were given 150- 300 mg aspirin daily. To reduce intraocular pressure, all eyes received 0.2% topical brimonidine tartrate ( Cases 1,5, and 6) TABLE 1. Case characteristics and visual results of the study group Case 1 2 3 4 Age ( years) and gender 57/ F 67/ F 64/ M 58/ M HT/ DM +/ + +/ + +/ + +/" DM, diabetes mellitus; HT, Duration of visual loss ( days) 22 12 10 10 Type of visual field defect Inferior altitudinal Superior altitudinal Inferior altitudinal Superior altitudinal; inferotemporal arcuate systemic hypertension. Initial visual acuity 20/ 800 20/ 500 20/ 200 20/ 200 Postinj 1 st week 20/ 500 20/ 80 20/ 80 20/ 100 ection visual 3rd week 20/ 400 20/ 63 20/ 40 20/ 63 acuity Final 20/ 400 20/ 63 20/ 32 20/ 63 Follow- up ( months) 12 12 15 12 165 J Neuro- Ophthalmol, Vol. 27, No. 3, 2007 Kaderli et al TABLE 2. Case characteristics and visual results of the control group Case 1 2 3 4 5 6 Age ( years) and gender 67/ F 70/ M 74/ M 56/ F 68/ M 68/ F HT/ DM + / " + / + + / " + / + + / " + / " DM, diabetes mellitus; HT, Duration of visual loss ( days) 8 14 7 18 11 14 Type of visual field defect Inferior altitudinal Diffuse scotoma Inferior altitudinal Inferior altitudinal Inferior altitudinal Inferior altitudinal systemic hypertension. Initial 20/ 200 20/ 800 20/ 200 20/ 200 20/ 200 20/ 320 Visual acuity 1 st week 20/ 320 20/ 800 20/ 200 20/ 125 20/ 200 20/ 320 4th week 20/ 200 20/ 400 20/ 250 20/ 125 20/ 200 20/ 320 Final 20/ 200 20/ 400 20/ 200 20/ 100 20/ 100 20/ 250 Follow- up ( months) 12 12 12 12 12 9 or 0.5% timolol maleate ( Cases 2, 3, and 4) twice daily during the first 4 weeks. The control patients were evaluated by visual acuity measurement with the ETDRS chart, Goldmann perimetry, ophthalmoscopy, and color fundus photographs at the initial visit, first and fourth weeks, third month, and every 3 months thereafter. Fluorescein angiography was performed only at the initial visit. The approval of the ethics committee of our university was obtained for this study. RESULTS All study patients completed at least 12 months of follow- up. The mean improvements in visual acuity were 4, 5.8, and 6.2 ETDRS lines at the first and third weeks and final visit, respectively. Optic disc swelling and leakage markedly decreased during the first week and had disappeared by the third week examination in all cases ( Fig. 1). The visual field mean deviations at baseline were 19.13, 20.97, 30.32, and 14.89 dB in study Cases 1, 2, 3, and 4, respectively. The corresponding numbers were 19.98, 14.16, 23.22, and 13.75 dB at the first and 20.39, 13.13, 18.47, and 12.31 dB at the third postinjection week. The typical visual field defects persisted in all study eyes. None of the patients showed deterioration of visual acuity or visual field or recurrence of optic disc edema during the follow- up period. All eyes eventually developed partial optic disc pallor. None of the eyes developed intraocular pressures exceeding 21 mm Hg, worsening cataract, or endophthalmitis. All control patients completed at least 9 months of follow- up. The mean improvements in visual acuity were 0, 0.7, and 1.3 ETDRS lines at the first and third weeks and final visit, respectively ( Table 2). Two control patients ( Cases 2 and 5) showed 3 lines of visual improvement. All control eyes still had optic disc swelling at the fourth week visit. At the third month visit, only control Case 3 still had FIG. 1. Retinal fluorescein angiography of Case 3. A. Initial visit angiogram of the right eye demonstrates diffuse leakage prominent in the upper half of the optic disc. B. Third week visit angiogram shows complete resolution of optic disc swelling and leakage. Visual acuity improved from 20/ 200 to 20/ 40. 166 © 2007 Lippincott Williams & Wilkins Intravitreal Triamcinolone in NAION J Neuro- Ophthalmol, Vol. 27, No. 3, 2007 partial optic disc swelling. Goldmann perimetry revealed no change in visual field defects in the control eyes. Partial optic disc pallor was eventually observed in all affected eyes in the control group. DISCUSSION All IVTA- injected eyes in this series showed a relatively favorable recovery of visual acuity and a relatively rapid resolution of optic disc edema. Visual acuity recovery of 5 ETDRS lines was observed in all patients except Case 1, who had no improvement. The NAION in this patient had been present for 22 days before study entry, a relatively long time in this cohort. Typical visual field defects persisted in all eyes. The greatest visual improvement in our study group occurred at the first postinjection visit ( mean, 4 ETDRS lines) and third post- injection visit ( mean, 5.8 ETDRS lines). By contrast, in our control group, the greatest visual improvement ( mean, 1.3 ETDRS lines) occurred at the final follow- up visit. The discordance between the visual results of our control group and that of the Ischemic Optic Neuropathy Decompression Trial Study Group ( 6), in which 31% of untreated cases had an increase in 3 lines of vision at 24 months, can be attributed to the small sample in our study. All IVTA- injected eyes showed a marked decrease in optic disc swelling and leakage during the first week after injection and disappearance of the edema by the third week visit. The optic disc edema in NAION has been reported to resolve spontaneously within 6- 8 weeks ( 7,8). Notably, all 6 control patients in our study still had optic disc edema at the fourth week and all eyes except the eye of Case 3 showed resolution at the third month visit. There is a rationale for the use of intravitreal corticosteroids in NAION. In NAION a vicious cycle of ischemia, edema, and compartment syndrome develops, leading to further tissue infarction. Neuroprotection cannot directly or solely resolve this vicious cycle ( 9), but reduction of optic disc edema could improve the reversible component of ischemic insult and blocked axoplasmic transport. Histopathologic studies performed in patients with brain infarction and ischemic optic neuropathy showed that the number of macrophages in the affected area increases over time ( 10). This response can negatively contribute to the axonal death process. Whether IVTA would work as it does in uveitic, pseudophakic, and diabetic macular edema and intraocular inflammation is unknown ( 11). The only previous study of IVTA in NAION ( 12) produced negative results. In 3 patients with NAION who were treated with 20 mg IVTA, Jonas et al ( 12) reported that after a follow- up ranging between 3 and 5 months, visual acuity changed from 0.1 to 0.2 in 1 patient, from 0.5 to 0.2 in 1 patient, and from 0.16 to 0.2 in 1 patient. No major perimetric improvement was observed in any patients. The 20 mg dose they used is much higher than the 4 mg dose we used. Moreover, they did not provide information about the duration of optic disc edema before treatment. These discrepancies make the comparison of the results of the two studies difficult. The higher the dose of IVTA, the longer it remains in the eye ( 13,14). Optic disc edema lasts for 6- 8 weeks in NAION ( 6,7), a period short enough to be covered by 4 mg IVTA, the antiedematous effect of which lasts for at least 3 months in cases of diabetic macular edema ( 11,15). Therefore, extending the duration of the effect of IVTA by using higher doses does not seem necessary. Shields et al ( 16) reported uncontrolled results of 4 mg IVTA injections in 9 patients with radiation papillopathy. In their study, signs of optic neuropathy such as hyperemia and edema resolved, often within 1 month. Visual acuity was stable or improved in 7 patients. The mean time to improvement in visual acuity by s 2 lines was 3 weeks. Over the mean of 11 months of follow- up, improvement or stabilization of visual acuity was noted in 7 of 9 patients. The authors believed that their intervention improved on the natural history of radiation papillopathy. The interpretation of our results is cautioned by the small sample size. Randomized studies with larger sample sizes are needed to show safety and efficacy. REFERENCES 1. The Ischemic Optic Neuropathy Decompression Trial Study Group. 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Graefes Arch Clin Exp Ophthalmol 2007; 245: 749- 750. 13. Jonas JB. Intraocular availability of triamcinolone acetonide after intravitreal injection. Am J Ophthalmol 2004; 137: 560- 2. 14. Mason JO 3rd, Somaiya MD, Singh RJ. Intravitreal concentration and clearance of triamcinolone acetonide in nonvitrectomized human eyes. Retina 2004; 24: 900- 4. 15. Avci R, Kaderli B, Akalp FD. Intravitreal triamcinolone injection for chronic diffuse diabetic macular oedema. Clin Experiment Ophthalmol 2006; 34: 27- 32. 16. Shields CL, Demirci H, Marr BP, et al. Intravitreal triamcinolone acetonide for acute radiation papillopathy. Retina 2006; 26: 537^ 4. 168 © 2007 Lippincott Williams & Wilkins |
