Idiopathic intracranial hypertension is the cause of bilateral papilledema. Although not frequent, this might lead to peripapillary choroidal neovascular membrane formation. Intravitreal anti-vascular endothelial growth factor injection seems to be a reliable option in such cases.
A 13-year-old boy presented to our clinic with a 3-week history of a dark spot in the right eye that had deteriorated to blurred vision. His history included strabismus surgery at age 10 years. His refraction was +6.00 and +7.75 in the right and left eyes, respectively. On presentation, his best corrected visual acuity was counting fingers at 50 cm in the right eye and 20/100 in the left eye. His anterior segment was normal on slit-lamp examination. On fundus examination, he had bilateral obscured optic disc margins and a superotemporally located peripapillary choroidal neovascular membrane (CNVM) with subretinal hemorrhage extending the fovea (Figures 1A–1B). Optical coherence tomography showed increased thickness of the peripapillary retinal nerve fiber layer in both eyes, which was more intense in the right eye, as well as macular edema with subretinal fluid in the right eye. Central foveal thickness was 616 µm. Fundus fluorescein angiography results showed leakage from the peripapillary CNVM in addition to bilateral mild hyperfluorescence of the papillary borders in the later phases, indicating papilledema (Figure 2).
Fundus photographs. (A) Papilledema with the peripapillary choroidal neovascular membrane (CNVM) superotemporal to the optic disc, subretinal fluid involving the fovea, subretinal hemorrhage temporal and inferior to the scar, and retinal striae in the right eye on initial presentation. (B) Indistinct peripapillary border in the left eye on presentation. (C) Peripapillary choroidal scar superotemporal to optic disc and pigmentary changes in the nasal macular area in the right eye 3 months following injection. (D) Distinct peripapillary border in the left eye 3 months following injection.
Fundus fluorescein angiography. (A) The right eye at early phase shows hypofluorescence in areas due to hemorrhage, the peripapillary choroidal neovascular membrane (CNVM) superotemporal to the optic disc, and subretinal fluid, of which borders are discriminable, involving the fovea. (B) The left eye at early phase shows mild hyperfluorescence in the peripapillary border. (C) The right eye at late phase shows marked staining of the subretinal neovascular membrane superotemporal to the optic disc and hyperfluorescence of the disc. (D) The left eye at early phase shows mild increase in the hyperfluorescence of the peripapillary border.
The patient was referred to the pediatric neurology department. He had complained of headaches for several years. Results of neurologic examination were normal and cranial and orbital magnetic resonance images showed normal findings. Laboratory evaluation was normal except for a positive result on antinuclear antibodies testing and low C4 levels. Systemic evaluation revealed no other anomalies. His intracranial pressure was 260 mm H2O with normal cerebrospinal fluid analysis. Due to diagnosis of possible idiopathic intracranial hypertension, he was prescribed acetazolamide 250 mg twice a day.
Following treatment, his headache faded. However, no improvement in the peripapillary CNVM was observed. He and his parents were informed of the option of intravitreal anti-vascular endothelial growth factor injection and consents were obtained. Ranibizumab has been approved in our country for the treatment of macular degeneration and diabetic retinopathy for some time and approval from the Ministry of Health was obtained. A single dose (10 mg/mL) of intravitreal ranibizumab (Lucentis; Novartis Pharma, Stein, Switzerland) was injected 4 mm behind the limbus in the inferotemporal area of the right eye. At the time of injection, he had been taking acetazolamide for 5 weeks.
At 4 weeks following injection, his best corrected visual acuity increased to 20/30 and 20/50 in the right and left eyes, respectively. There was a marked decrease in papilledema in both eyes and macular edema in the right eye. Subfoveal thickness was 219 µm. The peripapillary CNVM had the appearance of a scar (Figures 1C–1D). Optical coherence tomography over the scar next to the papillary area showed a pigment epithelial detachment with moderate and heterogeneous reflectivity (Figure 3). After 3 months, the acetazolamide dosage was decreased to 250 mg once per day and continued for another 3 months. During the 7-month follow-up, no recurrence in either the peripapillary CNVM or papilledema was observed.
The right eye with pigment epithelial detachment with moderate and heterogeneous reflectivity on optical coherence tomography over the scar next to the papillary area 1 month following ranibizumab injection.
Peripapillary CNVM is an uncommon finding in intracranial hypertension1 and is even less frequent in pediatric populations.2 Several modalities have been suggested for the treatment of idiopathic choroidal neovascularization, such as argon laser photocoagulation, photodynamic treatment, and intravitreal injection of anti-vascular endothelial growth factor compounds.3 Kaeser and Borruat2 described a 14-year-old boy who had intracranial hypertension and bilateral papilledema plus a peripapillary CNVM in the left eye. The patient's visual acuity in the left eye improved from 20/200 to 20/30 with acetazolamide treatment only. However, acetazolamide was not sufficient for the improvement of the peripapillary CNVM in our case, although it helped the headache.
In two previous pediatric cases, successful outcomes with intravitreal bevacizumab injection were observed. Lee et al.4 described a 14-year-old boy who presented with a peripapillary CNVM in the left eye along with bilateral papilledema. The patient responded to a single dose of intravitreal bevacizumab injection in addition to oral acetazolamide. Belliveau et al.5 described a 15-year-old boy who presented with intracranial hypertension and a peripapillary CNVM in the right eye. The patient required six doses of intravitreal bevacizumab injection to achieve a favorable result. The authors commented that lack of acetazolamide might be the reason for the necessity of multiple doses of the anti-vascular endothelial growth factor.
Similarly, acetazolamide in combination with bevacizumab was reported with a successful outcome in a young adult with pseudotumor cerebri.6 In our patient, we chose to inject the intravitreal anti-vascular endothelial growth factor agent because no improvement was observed after oral acetazolamide treatment. Our patient responded well to one dose of ranibizumab and no adverse effect was observed.
The pathophysiology of peripapillary CNVM in papilledema has been related to the discontinuity formed in the peripapillary border of Bruch's membrane due to pressure exerted by the swollen disc in conjunction with focal hypoxia induced by axonal swelling, thereby promoting angiogenesis and subsequent neovascular membrane formation.7 In our case, the high hyperopia may also have facilitated the formation of the peripapillary CNVM.
Our study supports the use of anti-vascular endothelial growth factor agents in peripapillary CNVM secondary to intracranial hypertension. A single injection of intravitreal ranibizumab was satisfactory for the treatment of the peripapillary CNVM. To our knowledge, this is the first case reporting the use of ranibizumab in peripapillary CNVM in intracranial hypertension.
- Wendel L, Lee AG, Boldt HC, Kardon RH, Wall M. Subretinal neovascular membrane in idiopathic intracranial hypertension. Am J Ophthalmol. 2006;141:573–574. doi:10.1016/j.ajo.2005.09.030 [CrossRef]
- 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. doi:10.1016/j.jaapos.2010.11.008 [CrossRef]
- Wang F, Wang W, Yu S, et al. Functional recovery after intravitreal bevacizumab treatments for idiopathic choroidal neovascularization in young adults. Retina. 2012:32;679–686. doi:10.1097/IAE.0b013e318227ab24 [CrossRef]
- Lee IJ, Maccheron LJ, Kwan AS. Intravitreal bevacizumab in the treatment of peripapillary choroidal neovascular membrane secondary to idiopathic intracranial hypertension. J Neuroophthalmol. 2013;33:155–157. doi:10.1097/WNO.0b013e31827c6b49 [CrossRef]
- Belliveau MJ, Xing L, Almeida DR, Gale JS, ten Hove MW. Peripapillary choroidal neovascular membrane in a teenage boy: presenting feature of idiopathic intracranial hypertension and resolution with intravitreal bevacizumab. J Neuroophthalmol. 2013;33:48–50. doi:10.1097/WNO.0b013e318281b7b9 [CrossRef]
- Jamerson SC, Arunagiri G, Ellis BD, Leys MJ. Intravitreal bevacizumab for the treatment of choroidal neovascularization secondary to pseudotumor cerebri. Int Ophthalmol. 2009;29:183–185. doi:10.1007/s10792-007-9186-y [CrossRef]
- Morse PH, Leveille AS, Antel JP, Burch JV. Bilateral juxtapapillary subretinal neovascularization associated with pseudotumor cerebri. Am J Ophthalmol. 1981;91:312–317. doi:10.1016/0002-9394(81)90282-8 [CrossRef]