Vascular endothelial growth factor (VEGF) results in a rapid and reversible increase in vascular permeability (1). Inhibition of VEGF signaling therefore provides an avenue for reducing vasogenic edema after nonarteritic ischemic optic neuropathy (NAION) and preserving viable but threatened optic nerve tissue. We report the first use of intravitreal bevacizumab (Genentech, South San Francisco, CA) for the treatment of NAION demonstrating a rapid and substantial reduction in optic nerve head edema and an unanticipated level of visual recovery. An 84-year-old woman with a history of NAION in the right eye presented with a 3-week history of visual loss in the left eye. Visual loss was acute, painless, and nonprogressive. She denied any accompanying neurologic or ophthalmologic complaints including headaches, temporal artery tenderness, jaw claudication, or polymyalgia. The initial ophthalmologic examination revealed optic disc swelling in the left eye with associated nerve fiber layer (NFL) hemorrhages. Sedimentation rate and C-reactive protein level were normal. Visual acuity was 20/400 in the right eye and count fingers (CF) at 1 foot in the left eye. Confrontation visual fields demonstrated temporal islands in both eyes. Automated perimetry was not reliably performed. The pupils measured 4 mm and reacted sluggishly to light; there was a right afferent pupillary defect. The ocular ductions were full. Ophthalmoscopic examination revealed a diffusely pale, cupless right optic nerve. The left optic nerve had marked edema and peripapillary NFL hemorrhages (Fig. 1A). The neurologic examination was normal.FIG. 1: Fundus photographs of the left eye at presentation (A) and 9 days after intravitreal injection of bevacizumab (B) show a rapid reduction in the degree of nerve fiber layer edema.Optical coherence tomography (OCT) documented marked swelling of the left optic nerve (Fig. 2). Fluorescein angiography (FA) showed capillary microangiopathy and dye leakage in the mid-phase and late-phase (Fig. 3A-B). An intravitreal injection of 1.25 mg/0.05 mL bevacizumab was administered to the left eye. Nine days later, there was marked reduction in the swelling of the left optic nerve (Figs. 1B, 2) with significant resolution of the dye leakage and microangiopathy (Figs. 3C-D). The patient noticed concurrent improvement in visual acuity to 20/1002 in the left eye.FIG. 2: Ocular coherence tomography (OCT) of the left optic nerve at presentation, 9 days after injection and 2 months after injection. The plane of imaging is through the horizontal nasotemporal axis. On initial presentation, the level of edema exceeded the available scale provided by the OCT software.FIG. 3: Fluorescein angiogram (FA) of the left fundus. A. Mid-phase FA at presentation. B. Late-phase FA at presentation. C. Mid-phase FA at 9 days after intravitreal injection. D. Late-phase FA 9 days after intravitreal injection.Ten days later, visual acuity had improved to 20/70 in the left eye, and the visual field had improved (Fig. 4). Two months after injection, there remained modest inferior and superior optic disc swelling (Fig. 2). Vision has remained stable for more than 24 weeks postinjection.FIG. 4: Automated threshold perimetry (Humphrey SITA 30-2) of the left eye 2 weeks after intravitreal injection of bevacizumab.After intravitreal bevacizumab, we observed a rapid and significant resolution of NAION-induced optic disc edema. Although visual recovery after NAION is not uncommon (2), the resolution of disc edema and visual recovery typically occur over 8 weeks (3). The rapid resolution of disc swelling and prompt improvement in visual acuity after bevacizumab administration suggest that VEGF-induced vascular permeability may play a role in tissue injury in NAION. Interestingly, cabergoline, a dopamine receptor agonist, inhibits VEGF-mediated vascular permeability (4). This feature may explain the potential benefit observed with carbidopa-levodopa therapy in recent-onset NAION (5). Although local VEGF expression after NAION may promote long-term beneficial angiogenesis, acute expression may result in deleterious edema and secondary injury. Indeed, inhibition of VEGF signaling reduces cerebral edema and tissue injury in a murine stroke model (6). Therefore, VEGF inhibition may offer a novel therapeutic approach to limit injury in NAION. A clinical trial of intravitreal bevacizumab in NAION is warranted. Jeffrey L. Bennett, MD, PhD Departments of Neurology and Ophthalmology Rocky Mountain Lions Eye Institute University of Colorado at Denver and Health Sciences Center Denver, Colorado Scott Thomas, MD Jeffrey L. Olson, MD Naresh Mandava, MD Department of Ophthalmology Rocky Mountain Lions Eye Institute University of Colorado at Denver and Health Sciences Center Denver, Colorado [email protected]
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Oct 20, 2008
Shaban Demirel + 9
Open Access
