Ciliary Body/Iris Appositioning Producing Mechanical Pupillary Defects in Carotid-Cavernous Sinus Fistula: An Overlooked Pathophysiologic Mechanism

Background: Variable pupillary responses have been described with carotid-cavernous sinus fistulas. These often are associated with a decrease in visual acuity and attributed to retinal ischemia. We propose a novel pathophysiologic mechanism for changes in pupillary reactivity involving anatomic changes secondary to choroidal effusion. Methods: To demonstrate proof-of-concept, we investigated 2 consecutive patients with carotid-cavernous sinus fistulas and pupillary disturbances using repeated refractions and anterior segment ultrasound biomicroscopy. Results: Ultrasound biomicroscopy demonstrated choroidal thickening and ciliary body effusion with forward rotation of the lens-iris diaphragm altering refraction and mechanically limiting iris movements. Conclusions: Where there are acute elevations in orbital venous pressure causing ciliary body effusion, changes in visual acuity and pupillary abnormalities can be produced by mechanical effects.

Original Contribution Ciliary Body/Iris Appositioning Producing Mechanical Pupillary Defects in Carotid-Cavernous Sinus Fistula: An Overlooked Pathophysiologic Mechanism Margarita G. Todorova, MD, Cameron F. Parsa, MD Background: Variable pupillary responses have been described with carotid-cavernous sinus fistulas. These often are associated with a decrease in visual acuity and attributed to retinal ischemia. We propose a novel pathophysiologic mechanism for changes in pupillary reactivity involving anatomic changes secondary to choroidal effusion. Methods: To demonstrate proof-of-concept, we investigated 2 consecutive patients with carotid-cavernous sinus fistulas and pupillary disturbances using repeated refractions and anterior segment ultrasound biomicroscopy. Results: Ultrasound biomicroscopy demonstrated choroidal thickening and ciliary body effusion with forward rotation of the lens-iris diaphragm altering refraction and mechanically limiting iris movements. Conclusions: Where there are acute elevations in orbital venous pressure causing ciliary body effusion, changes in visual acuity and pupillary abnormalities can be produced by mechanical effects. Journal of Neuro-Ophthalmology 2017;37:30-33 doi: 10.1097/WNO.0000000000000444 © 2016 by North American Neuro-Ophthalmology Society C arotid-cavernous sinus fistulas often present with signs of orbito-ocular venous hypertension, including proptosis, ocular motility restriction, helical and corkscrew conjunctival vessel tortuousity, elevated intraocular pressure, as well as retinal and choroidal vascular engorgement with reduced blood flow and ischemia (1-5). It has been proposed that congestive optic neuropathy also might develop (4,5). Relative afferent pupillary defects related to retinal ischemia and/or a presumed congestive optic neuropathy Department of Ophthalmology (MGT), University of Basel, Basel, Switzerland; and Quinze-Vingts National Ophthalmology Hospital (CFP), UPMC-Sorbonne Universities, Paris, France. The authors report no conflicts of interest. Address correspondence to Cameron F. Parsa, MD, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, 28 rue de Charenton, Paris 75012, France; E-mail: [e-mail] 30 have been described (4,5). Pupillary abnormalities related to Horner syndrome (6) third nerve palsy (7) also have been reported. We propose an additional, overlooked pathophysiologic mechanism for pupillary disturbances, involving anatomic changes associated with choroidal effusion, and demonstrate proof-of-concept in 2 consecutive patients with carotid-cavernous sinus fistulas with the use of ultrasound biomicroscopy. METHODS Clinical assessment of 2 patients with carotid-cavernous sinus fistulas included evaluation of best-corrected visual acuity, intraocular pressure, slit-lamp biomicroscopy, and funduscopy. In addition, anterior segment ultrasound biomicroscopy scans were obtained with a 50 MHz transducer (Model P60TM, Paradigm Medical Industries, Inc, Salt Lake City, UT). Magnetic resonance angiography (MRA) and selective digital subtraction angiography also were performed for localization and treatment of carotid-cavernous sinus fistulas in both patients. Our study and data accumulation were in conformity with institutional requirements and in accordance with the statements and principles of the Declaration of Helsinki as well as all governmental regulations. Patient 1 A 56-year-old man developed right-sided proptosis, chemosis, corkscrew conjunctival and episcleral vascular dilation, a sluggish ipsilateral pupillary reaction, and dilation of the retinal veins with numerous flame-shaped and punctuate hemorrhages in the mid-peripheral retina. Examination revealed anterior chamber shallowing without cell or flare, elevation of intraocular pressure of 24 mm Hg (left eye: 18 mm Hg), and a decrease in visual acuity from 20/20 to 20/ 40. However, with refraction, a 24.25 diopter myopic shift was discovered. Changing the patient's previous spectacle correction from +1.75 + 0.75 · 175° to 22.50 + 1.00 · 50°, Todorova and Parsa: J Neuro-Ophthalmol 2017; 37: 30-33 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Results of ultrasound bioimaging in patients with carotid-cavernous sinus fistulas UBM Findings Patient 1 Before embolization, (Fig. 1) 3 mo post-embolization (Fig. 2) Patient 2 Before embolization 3 mo post-embolization ACD, mm ACA (°), at 12 o'clock Position ACA (°), at 3 o'clock Position ACA (°), at 6 o'clock Position ACA (°), at 9 o'clock Position 2.50 3.13 13.80 24.30 12.20 26.76 12.70 27.56 19.30 29.31 1.86 2.61 Closed 8.38 6.03 30.32 19.19 30.74 11.50 28.24 ACA (°), anterior chamber angle (degrees); ACD, anterior chamber depth; UBM, ultrasound biomicroscopy. visual acuity was correctable to 20/25. Ultrasound biomicroscopy of the right anterior segment revealed an annular ciliochoroidal effusion with forward rotation of the ciliary body and of the lens-iris diaphragm, with the ciliary body in opposition to the iris (Fig. 1, Table 1). A right indirect carotid-cavernous sinus fistula (Barrow type D) was confirmed by MRA and selective digital subtraction angiography. Therapeutic embolization led to resolution of the clinical findings within 2 months, including normalization of the previously sluggish ipsilateral pupillary movement. Post-treatment ultrasound biomicroscopy revealed resolution of the ciliary-choroidal effusion with deepening of the anterior chamber and the absence of any ciliary body-iris appositioning (Fig. 2, Table 1). The myopic refractive shift also resolved, and visual acuity was 20/20 with the initial spectacle correction. Fundus findings, including disc appearance, also resolved. Patient 2 A 62-year-old man was referred for a second opinion for proptosis of the right eye of 2 months duration with corkscrew conjunctival and episcleral vascular dilation recent increase in intraocular pressure to 27 mm Hg (left eye: 16 mm Hg), and retinal venous dilation. Pupillary reactions were noted to be sluggish and delayed in the right eye. Visual acuity was 20/40 with the patient's usual spectacle correction of 22.25 + 0 0.50 · 67°. When refracted and corrected for a +4.00 diopter hyperopic shift, to +1.75 + 0.75 · 63°, visual acuity was 20/20. Anterior segment examination revealed a shallow anterior chamber in the right eye without cell or flare. Ultrasound biomicroscopy revealed cilio-choroidal effusion along with forward rotation of the lens-iris diaphragm, with the ciliary body appositioned against the iris (Table 1). MRA and selected digital subtraction angiography confirmed the presence of an indirect carotid-cavernous sinus fistula (Barrow type C). An embolization procedure was attempted, but was unsuccessful. Nonetheless, the fistula closed spontaneously three months later. Clinical findings including a transitory intraocular pressure elevation and the sluggish pupillary reaction resolved. Ultrasound biomicroscopy scans confirmed normalization of the ciliary body and choroid FIG. 1. Patient 1. Ultrasound biomicroscopy shows annular cilio-choroidal effusion (solid arrows), edema (solid dot) with forward rotation of the ciliary body, and iris-lens diaphragm (open arrows), leading to shallowing of the anterior chamber. Note the annular cilio-choroidal effusion with choroidal thickening (solid box) and edema of the ciliary body (solid dot), leading to mechanical appositioning of the ciliary body against the iris. Mechanically restricted iris-pupillary movements and increased friction may result in an inverted iris plateau configuration as is present at the 6 o'clock position (solid triangle). Todorova and Parsa: J Neuro-Ophthalmol 2017; 37: 30-33 31 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 2. Patient 1. Ultrasound biomicroscopy scans obtained shortly after therapeutic embolization: complete reduction of the cilio-choroidal effusion (solid arrows), widening of the anterior chamber angle in all quadrants, and normalization of the 6 o'clock inverted iris plateau configuration (solid triangle) have all occurred. (Table 1). The previously noted +4.25 diopter hyperopic shift also disappeared, with normalization of visual acuity using the patient's previous spectacle correction. DISCUSSION A unilateral decline in visual acuity, ipsilateral sluggish pupillary movements, progressive shallowing of the anterior chamber, as well as an increase of the intraocular pressure, were all noted in the proptotic eye of 2 patients with indirect carotid-cavernous sinus fistulas. Ultrasound biomicroscopy revealed not only shallowing of the anterior chamber with forward rotation of the lens-iris diaphragm but also an annular cilio-choroidal effusion. Such findings previously have been described and discussed only regarding potentiating secondary angle closure glaucoma (4,8). Annular ciliochoroidal effusion as found in our 2 patients also can lead to physical appositioning of the ciliary body with the iris, causing increased friction that mechanically restricts pupillary movements. This anatomic and mechanical possibility has been overlooked. The onset of sluggish and delayed ipsilateral pupillary reactions, in conjunction with a decrease in visual acuity with the patient's usual spectacle correction in place (potentially due mainly to acute myopic or hyperopic changes in refraction) can, unless consensual and near pupillary responses area also carefully evaluated, impart the erroneous impression of a relative afferent or other neuronal pupillary defect. Awareness of the potential for such mechanical causes for abnormal pupillary movements in the setting of high orbital venous pressure should alert the clinician to search for a mechanical as well as afferent visual pathway cause. After closure of the carotid-cavernous sinus fistula in our 2 patients, all symptoms resolved including induced changes in refraction and pupillary movements. Review of the literature reveals a number of pupillary abnormalities other than relative afferent pupillary defects associated with carotid-cavernous sinus fistulas, including 32 Horner syndrome and third nerve paresis (6,7). Changes in pupillary reactivity also have been described when orbital venous pressure becomes acutely elevated from other causes, such as cavernous sinus thrombosis (9-11), or with acute deterioration of otherwise chronically elevated venous pressure in the Sturge-Weber syndrome (12,13). As the availability of ultrasound biomicroscopy now demonstrates, sluggish pupillary abnormalities can also be present due to ciliary body effusion and expansion, mechanically restricting iris movements. Other than relative retinal ischemia potentially decreasing best-corrected acuity, a decline in visual acuities may be due to changes in refraction, which are difficult to predict. Overall, changes in refraction result from a combination of choroidal thickening advancing the retina forward producing a hyperopic component (14), along with a myopic influence due to anterior displacement of the lens-iris diaphragm as well as thickening of the ciliary body causing zonular relaxation which potentiates accommodation. In conclusion, in patients with a carotid-cavernous sinus fistula and changes in pupillary reactivity as well as decreased acuity, the possibility of a mechanical limitation of iris movements along with changes in refraction should be kept in mind. REFERENCES 1. 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