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Show Is Intravitreal Bevacizumab an Effective Treatment Option for Nonarteritic Anterior Ischemic Optic Neuropathy? Christina Rapp Prescott, MD, PhD, Craig A. Sklar, MD, Robert L. Lesser, MD, Ron A. Adelman, MD, MPH Abstract: Nonarteritic anterior ischemic optic neuropathy (NAION) causes sudden profound loss of vision with no known cause or cure. Various treatment modalities, both surgical and pharmacologic, have been tried without suc-cess. The purpose of our retrospective study was to evaluate the effect of intravitreal bevacizumab (Avastin) as a treatment option for NAION. We evaluated demographics of 5 patients and compared visual acuity and automated visual fields prior to and following intravitreal bevacizumab injection. Visual acuity at presentation was 20/20 in 4 of 5 patients and 20/150 in 1. Visual acuity improved to 20/40 in the patient who presented with decreased acuity and decreased slowly in 3 patients and rapidly in 1. All patients presented with variable visual field defects: 1 improved slightly, 3 progressed, and 1 remained stable. One patient subsequently developed NAION in the fellow eye. These results are consistent with the natural course of the disease, and bevacizumab did not appear to have a dramatic effect on the clinical outcome in this small series of patients with NAION. Journal of Neuro-Ophthalmology 2012;32:51-53 doi: 10.1097/WNO.0b013e318240596e © 2012 by North American Neuro-Ophthalmology Society Currently, there is no accepted treatment for nonarteritic anterior ischemic optic neuropathy (NAION), altho-ugh both surgical and medical (corticosteroids) therapies have been employed (1-4). The largest clinical trial to date was the Ischemic Optic Neuropathy Decompression Trial (IONDT), which was halted, and surgical treatment was not shown to be beneficial and possibly harmful (5). In 2008, Hayreh and Zimmerman (4) performed an open clin-ical trial of 613 consecutive NAION patients (696 eyes), allowing patients to choose between observation and systemic corticosteroid treatment at the time of diagnosis (80 mg of prednisone orally for 2 weeks followed by a taper). Their results confirmed the natural history of the disease, as shown in the IONDT, and demonstrated an improvement in the steroid treated group, based on both visual field (40.1% vs 24.5%) and visual acuity (69.8% vs 40.5%). They found that visual function stabilized by approximately 6 months, although they followed the patients for an aver-age of 3.8 years. In 2007, Bennett et al (6) reported improvement of optic disc edema and vision in an 84-year-old woman diagnosed with NAION following treatment with a single intravitreal injection of bevacizumab (1.25 mg/0.05 mL), a vascular endothelial growth factor inhibitor. The patient had a history of an episode of NAION in her right eye and presented 3 weeks after noticing decreased vision in her left eye. Vision in her left eye improved from counting fingers at 1 ft to 20/100 nine days after injection and to 20/70 nineteen days after injection accompanied by improvement in the patient's left visual field. The authors proposed that by decreasing vascular permeability, bevacizumab decreased vasogenic edema and protected vulnerable open nerve tissue. METHODS We performed a retrospective study of patients seen at the Yale Eye Center and The Eye Care Group between July 1, 2007 and July 30, 2010. We searched our patient databases using NAION and bevacizumab as keywords. Eleven patients were identified in the initial screen. These patients' charts were reviewed, and 5 were identified who received bevacizumab within 3 months of onset of NAION. Each patient was examined independently by at least 2 ophthalmologists. Visual acuity and automated visual fields were compared between visits, including prior Department of Ophthalmology and Visual Science (CRP, CAS, RLL, RAA), Yale University School of Medicine, New Haven, Connecticut. Supported by Leir Foundation, Newman's Own Foundation, and Research to Prevent Blindness. The authors report no conflicts of interest. Address correspondence to Ron A. Adelman, MD, MPH, Department of Ophthalmology and Visual Science, Yale University School of Medicine, 40 Temple Street, 3rd Floor, New Haven, CT 06510; E-mail: ron.adelman@yale.edu Prescott et al: J Neuro-Ophthalmol 2012; 32: 51-53 51 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. to and following intravitreal injection of bevacizumab (1.25 mg/0.05 mL). The appearance of the optic disc was monitored with serial photographs. The Human Investigation Committee at the Yale University School of Medicine exempted this study from the Institutional Review Board approval. Case 1 A 49-year-old man with a history of tadalafil (Cialis; Eli Lilly, Indianapolis, IN) use presented with visual acuity of 20/20 and an inferior altitudinal defect in the left eye (Fig. 1). Five days later, he received an intravitreal injection of bevacizu-mab. Seven days following injection, his acuity remained 20/20, but his field loss increased in the left eye (Fig. 1). Vision in the left eye decreased to 20/30 over 3 years, but visual field remained stable (mean deviation, −23.70 dB). However, 2.5 years after his initial presentation, he developed a dense superior altitudinal defect in his right eye (mean deviation, −14.49 dB), which progressed to near-total field loss (mean deviation, −30.18 dB) 2 weeks later. Case 2 A 56-year-old man noted loss of visual field in his right eye 2 weeks previously. His vision was 20/20 bilaterally. Three weeks later, his vision remained 20/20 in the right eye, but field loss progressed (Fig. 1). Four days later, he received an intravitreal injection of bevacizumab. His visual field stabi-lized (mean deviation, −25.46 dB) (Fig. 1), but vision has gradually decreased to 20/50 in the right eye. The patient's visual function has remained unchanged over 3 years of follow-up. Case 3 A 40-year-old man was evaluated 1 week after noticing inferior visual field loss in the right eye (Fig. 1). His vision was 20/20 in each eye. Five days later, an intravitreal bev-acizumab injection was performed. Four days after treat-ment, his field loss increased (Fig. 1), and his vision decreased to 20/50. Two years later, his vision was 20/ 100 in the right eye, with slight progression of his field loss (mean deviation, −17.52 dB). FIG. 1. Visual field results in 5 patients with NAION prior to and following intravitreal bevacizumab. 52 Prescott et al: J Neuro-Ophthalmol 2012; 32: 51-53 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Case 4 A 69-year-old woman with a history of NAION in the right eye developed NAION in the left eye 4 months later. Her vision was 20/150 in the left eye, and left visual field showed diffuse loss (Fig. 1). The next day, she received an intravitreal bevacizumab injection in the left eye and subjectively noticed an improvement within 12 hours. Four days later, her vision improved to 20/40, with improvement in her visual field (Fig. 1). Over the ensuing 10 months, visual acuity and visual field in the left eye remained stable (Fig. 1). Case 5 A 62-year-old man with a 2-year history of NAION, left eye, developed NAION in the right eye. His vision was 20/20 on presentation with right visual field loss (Fig. 1). He received an intravitreal bevacizumab injection 9 days later. One week following injection, visual acuity decreased to 20/400 with slightly increased field loss (Fig. 1) (mean deviation, −24.02 dB). Two months after his bevacizumab injection, his vision in the right eye was counting fingers at 1 ft with further decline in visual field (mean deviation, −28.97 dB). RESULTS All 5 patients presented with optic disc edema in the affected eye and subsequently developed varying degrees of optic atrophy. The only patient (Case 4) who presented with decreased visual acuity showed improvement, while 3 of the 4 patients who presented with 20/20 experienced a decline in acuity. Case 1 presented with an inferior altitudinal defect and developed field loss in the superior visual field after receiving treatment. In Case 2, the field defect progressed prior to receiving bevacizumab. Case 3 presented with a macular sparing inferior altitudinal defect that progressed to involve the macula. Only Case 4 demonstrated improve-ment in visual acuity and visual field following treatment. Case 5 also suffered progressive decline in acuity and field following intravitreal bevacizumab injections. DISCUSSION In our small retrospective case series, only 1 patient (Case 4) who presented with decreased visual acuity improved. Of the 4 with 20/20 acuity initially, all experienced a decline in vision, and 1 developed NAION in the fellow eye. Each of our patients received a single injection of bevacizumab, between 1 day and 5.5 weeks after the onset of symptoms. The only patient whose vision improved was treated within 1 day of reporting symptoms, while the others were treated between 5 days and 5.5 weeks. Perhaps earlier treatment would have had a more beneficial effect. Bennett et al (6) reported improvement in both visual acuity and visual field in a patient treated with a single dose of bevacizumab (1.25 mg/0.05 mL) 3 weeks after the onset of visual loss. For any treatment to be considered effective, it must be significantly better than observation. In the IONDT (5), 42.7% of patients in the control group experienced imp-roved visual acuity by 3 or more lines and 12.4% lost 3 or more lines at their 6-month follow-up visit. However, the patients in the trial began with vision worse than 20/40, so the only patient in our small study who would have qual-ified for the trial based on visual acuity was the patient whose vision improved. Similarly, the control group in the study by Hayreh and Zimmerman (4) had similar results to the IONDT but also started with worse vision (worse than 20/70) than our patients. We do not know whether our patient (Case 4) experienced improvement in vision due to the natural course of NAION or whether she responded to bevacizumab. There are many limitations of this study. It was retro-spective with a small sample size and no controls. Patients were not excluded based on ocular history; specifically, 2 of the patients had a history of NAION in the other eye. Bevacizumab was given at variable time points following vision loss, with no masking of who received treatment. Additionally, 4 of our 5 patients presented with isolated visual field defects and 20/20 visual acuity, so our sample is not representative of typical NAION. Bevacizumab did not appear to have a beneficial effect in our small case series and will remain a controversial treatment until a prospective randomized clinical trial is conducted. REFERENCES 1. Soheilian M, Koochek A, Yazdani S, Peyman GA. Transvitreal optic neurotomy for nonarteritic anterior ischemic optic neuropathy. Retina. 2003;23:692-697. 2. Modarres M, Sanjari MS, Falavarjani KG. Vitrectomy and release of presumed epipapillary vitreous traction of non-arteritic anterior ischemic optic neuropathy associated with posterior vitreous detachment. Ophthalmology. 2007;114:340-344. 3. Hayreh SS. Role of steroid therapy in nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2010;30:388-389. 4. Hayreh SS, Zimmerman MB. Non-arteritic anterior ischemic optic neuropathy: role of systemic corticosteroid therapy. Graefes Arch Clin Exp Ophthalmol. 2008;246:1029-1046. 5. Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful. The Ischemic Optic Neuropathy Decompression Trial Research Group. JAMA. 1995;273:625-632. 6. Bennett JL, Thomas S, Olson JL, Mandava N. Treatment of nonarteritic anterior ischemic optic neuropathy with intravitreal bevacizumab. J Neuroophthalmol. 2007;27:238-240. Prescott et al: J Neuro-Ophthalmol 2012; 32: 51-53 53 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
