Presentation of High-Flow Cerebral Proliferative Angiopathy With Adie's-Like Pupil and Proptosis

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Gour Wang, MD Presentation of High-Flow Cerebral Proliferative Angiopathy With Adie’s-Like Pupil and Proptosis Tung Thanh Hoang, MD, Huy Minh Dinh Tran, MD, Ban Van Truong, MD, Prem Subramanian, MD, PhD A 32-year-old man presented because of gradual protrusion of his left eye progressing over the course of a year. He reported mild pulsatile tinnitus in the left ear. He denied any blurry vision, diplopia, eye pain, headache, dizziness, or nausea. On initial assessment, visual acuity was 20/25 in each eye, with intraocular pressures of 18 mm Hg in the right eye and 20 mm Hg in the left eye by Goldmann applanation tonometry. External examination indicated 5 mm left exophthalmos by Hertel exophthalmometry (right eye, 15 mm; left eye, 20 mm) (Fig. 1A). Extraocular movements were normal. Both pupils were round, and there was no relative afferent pupillary defect. Anisocoria was present; the left pupil was larger, demonstrated a poor light response and a slightly better near response, but constricted only slightly to an even higher than usual percentage of pilocarpine used to detect an Adie’s pupil, essentially ruling out this diagnosis (Fig. 1B, C) (1). On anterior segment examination of the left eye, although frank helicity or corkscrewing of the conjunctival blood vessels was not commented on, tortuosity was certainly present (Fig. 1D). The failure of such vessels to blanch after the administration of phenylephrine drops suggested the possibility of raised episcleral pressure as causative. Ophthalmoscopy demonstrated small cup/disc ratio and no venous stasis in the left fundus. There was no abnormality found in the right eye. The patient did not manifest any neurological deficit, and his systemic review was negative. Ultrasonography and MRI of brain and orbits (Fig. 2A, B) showed a dilated left superior ophthalmic vein with otherwise normal orbital structures. Exophthalmos can clearly be noted on the MRI axial view on the left, along with dilated vasculature in the left anterior hemisphere. Ultrasonography seems to reveal a thickened retinal/ choroidal complex. A left frontal lobe lesion was found, and cerebral angiography (Fig. 2C, D) helped to define a vascular malformation with diffuse nidus, which was FIG. 1. A. Left exophthalmos, (B, C) before and after pilocarpin test, (D) dilated episcleral vessels. Ophthalmology Department (TTH), Hanoi Medical University, Hanoi, Vietnam; Save Sight Institute (TTH), The University of Sydney School of Medicine, Camperdown, Australia; Ophthalmology Department (HMDT), University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam; Department of Research and Innovation (HMDT), Hai Yen Vision Institute, Ho Chi Minh City, Vietnam; Diagnostic Imaging Department (BVT), Vietnam National Institute of Ophthalmology, Hanoi, Vietnam; and Ophthalmology Department (PS), University of Colorado School of Medicine, Aurora, Colorado. The authors report no conflicts of interest. Address correspondence to Tung Thanh Hoang, MD, Vietnam National Institute of Ophthalmology, 85 Ba Trieu, Ha Ba Trung distr, Hanoi, Vietnam; E-mail: [e-mail] e184 surrounded by chronic generalized lesions of brain parenchyma. The cerebral cortical and subcortical structures were lost, and diffuse gliotic changes were demonstrated. The vascular lesion was supplied by branches of both the left anterior and middle cerebral arteries, and drainage flowed through the vein of Galen into anterior part of the superior sagittal sinus. There was no aneurysm or hemorrhage in the nidus. This patient was diagnosed with cerebral proliferative angiopathy and was observed without any surgical or radiological treatment. Cerebral proliferative angiopathy is differentiated from the classical cerebral arteriovenous malformation by its hallmarks Hoang et al: J Neuro-Ophthalmol 2021; 41: e184-e185 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. A, B. Different diagnostic approaches to the cerebral proliferative angiopathy; the dilated left superior ophthalmic vein in B-scan echography and MRI of brain and orbits; exophthalmos on the left side in this MRI axial view, with dilated vasculature in the left anterior hemisphere; the probable thickened retinal/choroidal complex in ultrasonography. C, D. The vascular abnormality with diffuse nidus in digital subtraction angiography. including the disparity between the large size of the nidus and the small shunting volume, the absence of flow-related aneurysm, the presence of diffuse angiogenesis, and the small caliber of a multitude of feeding arteries and draining veins (2). Because the normal brain tissue of this patient was interspersed with pathologic vascular channels, aggressive interventions can take a toll on neurological functions and lead to devastating complications (2). Hence, treatment indications are limited to those suffering from cerebral hemorrhage or neurological deficits from the lesions (3). In addition, the tortuosity of the left conjunctival blood vessels might indicate that the higher intraocular pressure in the left eye compared with the right eye was because of a chronic increase in episcleral venous pressure. Based on the left exophthalmos and dilated superior ophthalmic vein, we hypothesize that this episcleral venous pressure elevation is due to the unusual high-flow arteriovenous shunt in the abnormal vascular network. Similarly, as a consequence of the rise in the orbital venous pressure, the abnormal pupil might have arisen from the choroidal engorgement and ciliary body rotation, which might have mechanically contributed to the limitation of iris movement. This seems to be the first documentation of similar pupillary findings, with the mechanism only recently described by Todorova and Parsa in a patient with a C-C-fistula but here found due to elevated venous pressure from cerebral proliferative angiopathy (4). Hoang et al: J Neuro-Ophthalmol 2021; 41: e184-e185 In the long run, even if the patient needs no neurologic treatment, regular ocular surveillance is required to keep this patient’s intraocular pressure under control regardless of his small cup/disc ratio at that moment. In such cases with ocular hypertension, antiglaucoma drops decreasing aqueous humor secretion such as beta blocker or carbonic anhydrase inhibitor are strongly recommended because of the impeded conventional outflow. Furthermore, prostaglandin analogs have recently been described by some investigators to affect adipocyte fat metabolism (5). This potentially could help reduce some of the exophthalmos produced by the nonoperable cerebral proliferative angiopathy. 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