Subfoveal Choroidal Neovascular Membrane Secondary to Idiopathic Intracranial Hypertension

Abstract

Purpose: To present a rare case of subfoveal choroidal neovascular membrane (CNVM) secondary to idiopathic intracranial hypertension. Methods: A case was evaluated. Results: A 21-year-old woman presented with a 2-week history of painless blurred vision in the right eye. She described initial metamorphopsia and intermittent bitemporal headaches lasting 30 minutes. She denied pain with eye movements and a history of trauma. Her body mass index was 49 kg/m². The visual acuity (VA) was 20/320 OD and 20/20 OS; there was no relative afferent pupillary defect. A dilated fundus examination showed bilateral optic disc edema and a subfoveal CNVM in the right eye. The patient was started on oral acetazolamide 500 mg twice daily and treated with 2 intravitreal antivascular endothelial growth factor (anti-VEGF) injections. Three months later, the VA was 20/30 in the right eye and the disc edema had improved. Conclusions: CNVMs in the setting of idiopathic intracranial hypertension–related papilledema may be subfoveal and have an excellent response to anti-VEGF agents.

Introduction

Idiopathic intracranial hypertension is characterized by signs and symptoms of raised intracranial pressure without a known etiology. Although vision loss secondary to idiopathic intracranial hypertension is primarily a result of optic neuropathy secondary to papilledema, pathologic retinal sequelae, including subretinal fluid (SRF), macular exudates, retinal arterial occlusions, venous stasis, choroidal folds, and choroidal neovascular membranes (CNVMs), can lead to decreased visual acuity (VA). ¹ CNVMs secondary to idiopathic intracranial hypertension are rare and are typically found in the peripapillary or juxtapapillary region. ² We present a rare case of a subfoveal CNVM with no peripapillary involvement in a patient with idiopathic intracranial hypertension.

Case Report

A 21-year-old woman presented to a tertiary neuro-ophthalmology clinic in Toronto, Canada, for a persistent scotoma in the right eye. The patient had no medical history or medication use; her body mass index was 49 kg/m². Two weeks before presentation, the patient described monocular metamorphopsia in the right eye, which progressed to a painless central scotoma. She denied pain with eye movements or neurological symptoms. However, in the month before presentation, the patient did note an intermittent bitemporal headache, worse when lying down and better when standing up, with episodes lasting 30 minutes. She denied photophobia, phonophobia, and tinnitus. A review of systems was otherwise negative.

The best-corrected distance VA (BCVA) was 20/320 OD and 20/20 OS. The intraocular pressure was 12 mm Hg and 13 mm Hg, respectively; there was no relative afferent pupillary defect. The slitlamp examination was within normal limits. A dilated fundus examination showed bilateral optic disc edema (Frisen score 3) with no peripapillary hemorrhages or exudates (Figure 1, A and B). Macular assessment showed a subfoveal hemorrhage and exudation in the right eye and was within normal limits in the left eye. Optical coherence tomography (OCT) imaging (Cirrus 6000, Carl Zeiss Meditec AG) of the macula in the right eye showed intraretinal fluid and SRF as well as subretinal hyperreflective material; OCT of the left-eye macula was normal (Figure 2, A and B). OCT angiography (OCTA) (Zeiss) of the right eye confirmed a subfoveal CNVM (Figure 3).

Figure 1.

(A) Fundus photograph of the right-eye posterior pole shows grade 3 optic disc edema with a yellow subfoveal lesion and normal vessels. (B) Fundus photograph of the left eye shows grade 3 optic disc edema with a normal macula and vessels.

Figure 2.

(A) Spectral-domain optical coherence tomography (SD-OCT) imaging of the right-eye macula shows subretinal fluid extending from the nerve, subretinal hyperreflective material, and intraretinal fluid. (B) SD-OCT imaging of the left eye shows a normal retina.

Figure 3.

Optical coherence tomography angiography of the right eye shows a choroidal neovascular membrane within the outer retina–choriocapillaris junction and an increased flow B-scan signal through the subfoveal retinal pigment epithelium.

Abbreviations: ETDRS, Early Treatment Diabetic Retinopathy Study; FAZ, foveal avascular zone; ILM, internal limiting membrane; IPL, inner plexiform layer; ORCC, outer retina to choriocapillaris; RPE, retinal pigment epithelium; VRI, vitreoretinal interface.

Magnetic resonance venography and magnetic resonance imaging of the brain with contrast showed sensitive and specific signs of elevated intracranial pressure secondary to idiopathic intracranial hypertension, including an empty sella and transverse sinus stenosis, respectively. Humphrey visual field testing found normal visual function. A diagnosis of CNVM in the setting of papilledema from idiopathic intracranial hypertension was made. The patient was started on oral acetazolamide 500 mg twice daily given the retinal complications. Aflibercept was injected intravitreally on the day of initial presentation.

At the 1-month follow-up, the patient presented with 8 kg of intentional weight loss. Her BCVA improved to 20/40 OD, with a fundus examination and OCT imaging showing interval improvement of the disc edema and submacular neovascularization. A second aflibercept intravitreal injection was administered for the residual pigment epithelium detachment and SRF.

At the 3-month follow-up, with continued healthy weight loss, the BCVA was 20/30. The fundus examination showed a marked decrease in the optic disc edema (Figure 4, A and B), and OCT macula and OCTA confirmed a significant regression of the juxtafoveal CNVM (Figure 4, C and D). The patient’s VA remained stable at 20/30.

Figure 4.

(A) Fundus photograph of the right eye posterior pole shows mild blurring of the nasal optic disc margin and a focal pigment epithelial detachment at the fovea. (B) Fundus photograph of the left eye shows nasal optic disc blurring with an unremarkable macula. (C) Optical coherence tomography (OCT) imaging of the right eye 3 months after 2 intravitreal antivascular endothelial growth factor injections shows a focal fibrovascular pigment epithelial detachment at the fovea and trace adjacent subretinal fluid. (D) OCT angiography of the right eye shows a quiet choroidal neovascular membrane.

Conclusions

Based on a comprehensive review of the literature and to our knowledge, this case represents the first isolated subfoveal CNVM developing in the setting of idiopathic intracranial hypertension in a young healthy patient with no other neovascular risk factors. A 2021 review by Nichani and Micieli ¹ described 182 patients in the literature who presented with retinal manifestations associated with idiopathic intracranial hypertension, with chorioretinal folds being most prevalent sequela at 68% followed by CNVM at 15%, SRF at 9%, and macular exudates at 5%.

First described by Jamison, ³ all CNVM cases in the literature related to idiopathic intracranial hypertension have been juxtapapillary in nature, with most found in the peripapillary region. A 2019 multicenter chart review by Ozgonul et al ² described 13 eyes of 10 patients with peripapillary CNV secondary to idiopathic intracranial hypertension. All neovascular membranes resolved, whether treated with antivascular endothelial growth factor (anti-VEGF) agents or observed; however, the papilledema resolved in only 1 of these 13 cases. This is in contrast to our patient, whose papilledema had interval improvement by the 3-month mark. Similarly, a case series by Wendel et al ⁴ included 6 cases of juxtapapillary CNVM secondary to idiopathic intracranial hypertension; all membranes regressed with treatment of the idiopathic intracranial hypertension or laser therapy. A key finding by Wendel et al was that no CNVMs recurred after resolution of the papilledema.

A variety of treatment modalities have been shown to be effective in the management of juxtapapillary CNVMs in idiopathic intracranial hypertension. Fearing a poor visual prognosis, Wendel et al ⁴ elected for photodynamic therapy or argon laser therapy for 3 neovascular membranes that extended toward the fovea; these case had good visual outcomes. The authors concluded that clinical and angiographic monitoring of the neovascular network might be an indication for treatment given that the CNVMs, which remained in the juxtapapillary region, were self-limiting. In a 2009 study by Jamerson et al ⁵ and a 2013 study by Lee et al, ⁶ a single dose of intravitreal bevacizumab led to recession of the peripapillary CNVM in the setting of idiopathic intracranial hypertension. This mirrors our patient’s results. Her vision improved significantly—from 20/320 to 20/40—1 month after a single dose of treatment. Castellarin et al ⁷ became the first team to outline the histopathology results of surgical excision of CNVM in the setting of idiopathic intracranial hypertension. They noted that choriocapillaris nonperfusion and atrophy could stimulate incomplete ingrowth of the retinal pigment epithelium into the dissection bed, ultimately leading to poor visual recovery.

One of the proposed mechanisms for idiopathic intracranial hypertension–related CNVM was introduced by Morse et al. ⁸ This team postulated that peripapillary CNVMs result from pressure deformities at the border of Bruch membrane adjacent to the optic disc, leading to discontinuity in the normal chorioretinal layers. In addition, Morse et al postulated that hypoxia created from axonal swelling and poor vascular perfusion of surrounding tissue can promote subretinal angiogenesis. We postulate that in the setting of a normal choroid based on OCT, pressure-related deformities and hypoxia from poor perfusion resulting from our patient’s disc edema could have caused microscopic breaks in Bruch membrane, leading to a submacular CNVM.

In summary, this rare case of subfoveal CNVM secondary to idiopathic intracranial hypertension adds to the existing literature of retinal complications in the setting of pseudotumor cerebri. Given the good visual recovery after intravitreal anti-VEGF and poor vision at presentation based on past cases of juxtapapillary neovascularization, we elected to use intravitreal aflibercept to treat the subfoveal CNVM. OCTA helped determine the location of neovascularization, ultimately guiding the treatment decision and disease monitoring. Additional investigation is required to further elucidate the pathophysiology of subfoveal choroidal neovascularization in the setting of idiopathic intracranial hypertension.