Journal of Neuro-Ophthalmology, June 2013, Volume 33, Issue 2

Intravitreal Bevacizumab in the Treatment of Peripapillary Choroidal Neovascular Membrane Secondary to Idiopathic Intracranial Hypertension

A 14 year-old Caucasian boy with idiopathic intracranial hypertension (IIH) presented with blurred vision in his left eye. Visual acuity was 20/20, right eye, and 20/80, left eye, and funduscopy revealed bilateral papilledema. In addition, there was peripapillary choroidal neovascular membrane (PPCNVM) in the left eye. Oral acetazolamide improved the symptoms and signs of IIH, but seven weeks later, acuity remained 20/80, left eye, with an increase in subretinal hemorrhage. Two weeks following an intravitreal injection of bevacizumab, visual acuity on the left had improved to 20/30 with resolution of subretinal hemorrhage and fibrosis of PPCNVM. After an additional 2 weeks, visual acuity improved to 20/20, and there has been no sign of recurrence over 3.5 years of follow-up.

Intravitreal Bevacizumab in the Treatment of Peripapillary Choroidal Neovascular Membrane Secondary to Idiopathic Intracranial Hypertension In-Jung Lee, BSc, BAppSc, MBBS, Luke J. Maccheron, BMedSc, MBBS, FRANZCO, Anthony S. Kwan, MBChB, MD, FRCOphth, FRANZCO Abstract: A 14 year-old Caucasian boy with idiopathic intracra-nial hypertension (IIH) presented with blurred vision in his left eye. Visual acuity was 20/20, right eye, and 20/80, left eye, and funduscopy revealed bilateral papilledema. In addition, there was peripapillary choroidal neovascular membrane (PPCNVM) in the left eye. Oral acetazolamide improved the symptoms and signs of IIH, but seven weeks later, acuity remained 20/80, left eye, with an increase in subretinal hemorrhage. Two weeks following an intravitreal injection of bevacizumab, visual acuity on the left had improved to 20/30 with resolution of subretinal hemorrhage and fibrosis of PPCNVM. After an additional 2 weeks, visual acuity improved to 20/20, and there has been no sign of recurrence over 3.5 years of follow-up. Journal of Neuro-Ophthalmology 2013;33:155-157 doi: 10.1097/WNO.0b013e31827c6b49 © 2012 by North American Neuro-Ophthalmology Society Peripapillary choroidal neovascularmembrane (PPCNVM) is a rare complication of long-standing papilledema (1-5). The variable prognosis of untreated PPCNVM ranges from spontaneous involution to permanent vision impairment. We present a case of successful treatment of PPCNVM with an intravitreal injection of an anti-vascu-lar endothelial growth factor (VEGF) agent in a pediatric patient. CASE REPORT A 14-year-old healthy Caucasian boy presented with a history of blurred vision for 4 months and intermittent diplopia and headaches for several weeks. He had no significant medical or ophthalmological history. Visual acuity was 20/20, right eye, and 20/80, left eye. There was a left relative afferent pupillary defect, and impaired color vision on the left eye. Extraocular move-ments were full. Automated perimetry revealed only an enlarged blind spot in the left eye. On ophthalmoscopy, there was bilateral optic disc edema and subretinal hemor-rhage extending from the temporal aspect of the left disc toward the fovea (Fig. 1). Intravenous fluorescein angiogra-phy showed leakage from a PPCNVM (Fig. 2). The patient's blood pressure was 110/60 mm Hg, and hematologic screening for causes of optic disc edema was normal. Magnetic resonance imaging of the orbits and brain and magnetic resonance venography were unremarkable. Lumbar puncture revealed an opening pressure greater than 35 cm H2O with normal cerebrospinal fluid analysis. The patient was placed on oral acetazolamide (250 mg 4 times a day, which was decreased 7 days later to 250 mg twice a day). Seven weeks later, despite an improvement in symp-toms of intracranial hypertension and papilledema, visual acuity in the left eye remained 20/80 with an increase in the area of subretinal hemorrhage. The option of intra-vitreal anti-VEGF treatment was discussed with the patient's family, and with parental consent, a single-dose intravitreal injection of 1.5 mg of bevacizumab (Avastin; Roche, Copenhagen, Denmark) was given under general anesthesia. Two weeks later, left visual acuity was 20/30, and 4 weeks after treatment, it was 20/20. At 9 weeks, ophthal-moscopy revealed a flat and fibrosed PPCNVM with Mater Adult Hospital (I-JL, LJM, ASK), South Brisbane, Queensland, Australia; and School of Medicine, Faculty of Health Sciences (ASK), University of Queensland, Queensland, Australia. The authors report no conflict of interest to disclosure. Address correspondence to Anthony S. Kwan, MBChB, MD, Queensland Eye Institute, 41 Annerley Road, South Brisbane, Queensland 4101, Australia; E-mail: [e-mail] Lee et al: J Neuro-Ophthalmol 2013; 33: 155-157 155 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. decreased subretinal hemorrhage (Fig. 3). The patient's visual acuity has remained 20/20 over 3.5 years with no sign of recurrence of idiopathic intracranial hypertension (IIH) or PPCNVM. DISCUSSION Although a recognized complication of chronic papil-ledema, PPCNVM is rare (1,2). Juxtapapillary subretinal FIG. 1. A. At presentation, there is bilateral papilledema with pigmentary change and subretinal hemorrhage temporal to the left optic disc extending toward the macula. B. Optical coherence tomography of the temporal peripapillary retina of the left eye shows subretinal and subretinal pigment epithelial fluid. FIG. 2. Fluorescein angiogram of left eye from early arterial phase (A) to late venous phase (D). There is blockage of fluorescence by subretinal blood and hyperfluorescence of the neovascular membrane in the late stages of the angiogram. 156 Lee et al: J Neuro-Ophthalmol 2013; 33: 155-157 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. neovascularization has been reported to complicate IIH in only 0.53% of cases (2). In a retrospective review of 6 patients with IIH having PPCNVM,Wendel et al (2) noted that once the papilledema is treated adequately, these neovascular membranes are unlikely to cause severe visual loss provided that they do not encroach upon or cause hemorrhage into the fovea. They concluded that argon laser therapy may not improve visual outcome in more advanced cases and that photodynamic therapy may be a less destructive treatment option. Kaeser and Borruat (5) described a 14-year-old boy with IIH. At presentation, visual acuity was 20/20, right eye, and 20/200, left eye, with bilateral papillede-ma and PPCNVM in the left eye. Following treatment with acetazolamide, the patient's vision returned to 20/30 in the left eye after 1 year, and the neovascular membrane resolved with-out treatment. However, Sathornsumetee et al (4) reported a case of IIH in which PPCNVM and reduced visual acuity persisted 9 months after a dramatic improvement in papillede-ma from optic nerve sheath fenestration. The natural history of PPCNVM is unpredictable, as it may spontaneously involute, remain stable, or expand and lead to devastating visual loss. Management options for PPCNVMs include observation alone, surgery, laser pho-tocoagulation, photodynamic therapy, or intravitreal anti- VEGF agents. Intravitreal bevacizumab has been reported as a successful management option for PPCNVM secondary to age-related macular degeneration (ARMD) (6) and peripapil-lary atrophy (7), but its use in cases of papilledema including IIH has not been described. The issue of using this agent in a pediatric patient was specifically discussed in the process of informed consent. Bevacizumab has been used in the treat-ment of retinopathy of prematurity, and there are no reports of local or systemic adverse events with follow-up of up to 10 months in this pediatric population (8). The pathophysiology of PPCNVM associated with long-standing papilledema in IIH is uncertain, but it is thought to be different from ARMD (9-11). In ARMD, it has been proposed that the accumulation of drusen between retinal pigment epithelium (RPE) and Bruch membrane initiates a cascade of inflammatory and immune reactive processes, causing RPE dysfunction and breaks in Bruch membrane. Persistent RPE dysfunction results in chronic hypoxia, thus tipping the complex balance of pro- and antiangiogenic mechanism toward angiogenesis, leading to choroidal neo-vascularization (11,12). With papilledema, it has been pos-tulated that discontinuity is formed in the peripapillary border of Bruch membrane from pressure exerted by the swollen disc. This discontinuity, in conjunction with focal hypoxia induced by axonal swelling, promotes angiogenesis and subsequent neovascular membrane formation (3). REFERENCES 1. Browning DJ, Fraser CM. Ocular conditions associated with peripapillary subretinal neovascularization, their relative frequencies, and associated outcomes. Ophthalmology. 2005;112:1054-1061. 2. Wendel L, Lee AG, Boldt HC, Kardon RH, Wall M. Subretinal neovascular membrane in idiopathic intracranial hypertension. Am J Ophthalmol. 2006;141:573-574. 3. Morse PH, Leveille AS, Antel JP, Burch JV. Bilateral juxtapapillary subretinal neovascularization associated with pseudotumor cerebri. Am J Ophthalmol. 1981;91:312-317. 4. Sathornsumetee B, Webb A, Hill DL, Newman NJ, Biousse V. Subretinal hemorrhage form a peripapillary choroidal neovascular membrane in papilledema caused by idiopathic intracranial hypertension. J Neuroophthalmol. 2006;26:197-199. 5. Kaeser P, Borruat F. Peripapillary neovascular membrane: a rare cause of acute vision loss in pediatric idiopathic intracranial hypertension. J AAPOS. 2011;15:83-86. 6. Spandau UHM, Jonas JB. Intravitreal bevacizumab for peripapillary classic subretinal neovascularization. Acta Ophthalmol Scand. 2007;85:340-341. 7. Soliman W, Lund-Andersen H, Larsen M. Resolution of subretinal hemorrhage and fluid after intravitreal bevacizumab in aggressive peripapillary subretinal neovascularization. Acta Ophthalmol Scand. 2006;84:707-708. 8. Travassos A, Teixeira S, Ferreira P, Regadas I, Travassos AS, Esperancinha FE, Prieto I, Pires G, van Velze R, Valido A, Machado Mdo C. Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging. 2007;38:233-237. 9. Castellarin AA, Sugino IK, Nasir M, Zarbin MA. Clinicopathological correlation of an excised choroidal neovascular membrane in pseudotumour cerebri. Br J Ophthalmol. 1997;81:994-1000. 10. Lopez P, Green WRC. Peripapillary subretinal neovascularization: a review. Retina. 1992;12:141-171. 11. Norwak JZ. Age-related macular degeneration (AMD): Pathogenesis and therapy. Pharmacol Rep. 2006;58:353-363. 12. Grossniklaus HE, Green WR. Choroidal neovascularization. Am J Ophthalmol. 2004;137:496-503. FIG. 3. Nine weeks following intravitreal bevacizumab. A. The area of the peripapillary choroidal neovascular mem-brane is flat and fibrosed. B. Optical coherence tomography confirming the resolution of subretinal and subretinal pig-ment epithelial fluid. Lee et al: J Neuro-Ophthalmol 2013; 33: 155-157 157 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.