Diabetic papillopathy is an uncommon hyperemic optic disc swelling that occurs in patients with long-standing diabetes and is typically self-resolving with minimal effect on vision. The differential diagnosis of bilateral disc swelling includes inflammation (e.g., sarcoidosis), infection (e.g., Lyme disease), cancerous infiltration (e.g., leukemia), elevated blood pressure (hypertension), increased intracranial pressure (papilledema), and disc ischemia.¹–³ Diabetic papillopathy is a diagnosis of exclusion, made after other causes of disc swelling have been ruled out. Likely ischemic in origin, diabetic papillopathy is considered by some authors to be a form of ischemic optic neuropathy.⁴ Diabetic papillopathy is frequently bilateral, typically has minimal signs of optic nerve dysfunction, and can be associated with diabetic macular edema or capillary nonperfusion. The etiology of diabetic papillopathy is not well understood, and there is no accepted treatment to alter its natural course. The purpose of the current report is to document the response of diabetic papillopathy to intravitreal injection of bevacizumab (Avastin, Genentech Inc, San Francisco, California, USA), a humanized monoclonal antibody to vascular endothelial growth factor (VEGF).⁵

A 42-year-old male with a 15-year history of poorly controlled adult-onset noninsulin-dependent diabetes mellitus had a 3-month history of visual loss in his right eye. The patient had been prescribed oral hypoglycemics and had no other known medical disease. Best-corrected visual acuity was 6/160 in the right eye and 20/20 in the left eye. There was no afferent pupillary defect. Anterior segment examination and intraocular pressure were unremarkable. Fundus examination was significant for bilateral optic nerve head swelling associated with disc vessel telangiectasia, peripapillary retinal hemorrhages, and clinically significant macular edema and macular hard exudates [Figures 1a and b]. The telangiectasia was radially distributed and flat, unlike neovascular vessels. Fluorescein angiography showed disc leakage (but no vessel staining of the telangiectatic vessels) [Figures 1c and d]. The patient underwent clinical neurologic examination (including brain magnetic resonance imaging), blood pressure measurement, and complete blood count and electrolyte testing, all of which were within normal limits. The diagnosis of bilateral diabetic papillopathy and clinically significant macular edema greater in the right eye was made. The patient was anxious for medical intervention to treat his macular edema and improve vision. After informed consent, the right eye was prepared and draped in a sterile manner and topical anesthetic was instilled in the eye. Subsequently, 1.25 mg/0.05 ml bevacizumab was injected through a 30-gauge needle 3.5 mm posterior to the limbus into the vitreous cavity. Two weeks following injection, there was improvement of macular edema, marked regression of the disc swelling and telangiectasia, with best-corrected visual acuity improving to 20/160. Four weeks following injection, there was complete resolution of the disc swelling and telangiectasia and best-corrected visual acuity was 20/60. The right eye remained stable 3 months following injection, whereas the untreated left eye remained unchanged from baseline [Figures 2a–d].

In this diabetic patient, the disc swelling was most consistent with diabetic papillopathy. The decreased visual acuity was due to concurrent diabetic macular edema which we treated with intravitreal bevacizumab in one eye. The marked clinical resolution of diabetic papillopathy that occurred only in the eye injected with intravitreal bevacizumab strongly suggests that the injection altered the natural course of the condition and that VEGF is involved in the pathogenesis of diabetic papillopathy. A similar recently reported case also supports this idea.⁶ In our case, the macular hard exudates may have been related to the patient's diabetic retinopathy or may have specifically been part of the papillopathy.⁷

VEGF induces a rapid and reversible increase in vascular permeability and thus could be involved in the vasogenic disc edema that occurs when an optic nerve head is ischemic.⁸ In this context, VEGF expression in the optic nerve head could result in secondary injury related to persistent edema, as has been described for animal models of brain injury.⁹ Thus bevacizumab, a VEGF inhibitor, could potentially be used to reduce the effect of this VEGF expression and alter the course of diabetic papillopathy as well as other optic nerve ischemias.^{5, 10, 11}

In addition to the recently reported case similar to ours,⁶ there are at least two other cases in the literature that support the response of ischemic optic neuropathies to bevacizumab. The first is a case of nonarteritic ischemic optic neuropathy in an 84-year-old woman who had marked clinical improvement 10 days after intravitreal bevacizumab injection.¹⁰ Nerve swelling resolved and vision improved from count fingers at 1 foot to 20/70 after treatment; this improvement was stable at 24-week follow-up.¹⁰ The second is a case of radiation-induced optic neuropathy in a 69-year-old woman whose decreased central vision (20/32) and central scotoma improved 1 week following injection (20/20).¹¹ An improved disc appearance was apparent 6 weeks following injection and following a repeat injection, the disc regained a healthy appearance.¹¹ It should be noted that at least 2 case reports^{12, 13} reported nonarteritic ischemic neuropathy after bevacizumab injection which may or may not have been related to the injections. One¹² was 1 week following injection of an eye with exudative age-related macular degeneration in a 72-year-old woman (who had had an episode of nonarteritic ischemic optic neuropathy in her contralateral eye 10 years earlier); the other¹³ was 2 weeks following injection of an eye with juxtafoveal choroidal neovascularization in a 51-year-old man with pseudoxanthoma elasticum and angioid streaks.

Although there may be a role of VEGF in the pathogenesis of ischemic optic neuropathies and thus potentially a role for bevacizumab as treatment for selected cases, larger case series and preferably prospective trials are required to properly evaluate the potential therapeutic effect in this setting.

Source of Support: Nil,

Conflict of Interest: None declared.