Sectoral Sparing Associated With a Cilioretinal Artery in Arteritic Anterior Ischemic Optic Neuropathy

Giant cell arteritis (GCA) is a life-threatening vasculitis occurring in older adults that can cause blindness by ischemia of the choroid, retina, and optic nerve. We report a case of a patient who presented with "occult" GCA with severe anterior ischemic optic neuropathy affecting both optic nerves, delayed choroidal filling, and a concomitant cilioretinal artery occlusion in the left eye. The retinal territory supplied by the affected cilioretinal artery was hypoperfused, yet this retinal territory at least partially corresponded to the only preserved visual field in that eye. The sector of the optic disc corresponding to the emergence of the cilioretinal artery was the only sector spared by pallid edema. This pattern of sectoral sparing associated with a cilioretinal artery has been observed in other patients with GCA and in animal models of posterior ciliary artery occlusion. This case serves as a clear example of an incompletely understood phenomenon in posterior pole circulation in vascular occlusive disease that deserves further study.

Photo and Video Essay Section Editors: Melissa W. Ko, Dean M. Cestari, Peter Quiros, Kimberly M. Winges, MD MD MD MD Sectoral Sparing Associated With a Cilioretinal Artery in Arteritic Anterior Ischemic Optic Neuropathy Eric D. Gaier, MD, PhD, Nailyn Rasool, MD, FRCPC, FRCSC, Joseph F. Rizzo III, MD FIG. 1. Fundus photographs and perimetric performance. Fundus photography of the posterior poles in the right eye (A) and in the left eye (B). Inset depicts a magnified view of the optic disc with temporal sectoral sparing indicated by the yellow arrow. C. Kinetic manual kinetic perimetry plot in the left eye using the V4e isopter. The inset depicts automated microperimeter results (MP-1, Nikon) with a corresponding area of sparing; green symbols indicate regions of perception; red symbols indicate regions without perception. Abstract: Giant cell arteritis (GCA) is a life-threatening vasculitis occurring in older adults that can cause blindness by ischemia of the choroid, retina, and optic nerve. We report a case of a patient who presented with “occult” GCA with severe anterior ischemic optic neuropathy affecting both optic nerves, delayed choroidal filling, and a concomitant cilioretinal artery occlusion in the left eye. The retinal territory supplied by the affected cilioretinal artery was hypoperfused, yet this retinal territory at least partially corresponded to the only preserved visual field in that eye. The sector of the optic disc corresponding to the emergence of the cilioretinal artery was the only sector spared by pallid edema. This pattern of sectoral sparing associated with a Department of Ophthalmology (EDG), Boston Children’s Hospital, Boston, Massachusetts; Harvard Medical School (EDG, JFR), Boston, Massachusetts; Department of Ophthalmology (EDG, JFR), Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; Picower Institute for Learning and Memory (EDG), Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts; Departments of Ophthalmology and Neurology (NR), University of California San Francisco, San Francisco, California. E. D. Gaier: NIH K08 EY030164. E. D. Gaier: Luminopia, Inc (scientific advisor, equity, patent). Stoke Therapeutics, Inc (consultant). J. F. Rizzo: Magic Leap (medical director). The remaining author report no conflicts of interest. Address correspondence to Eric D. Gaier, MD, PhD, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115; E-mail: [e-mail] e514 cilioretinal artery has been observed in other patients with GCA and in animal models of posterior ciliary artery occlusion. This case serves as a clear example of an incompletely understood phenomenon in posterior pole circulation in vascular occlusive disease that deserves further study. Journal of Neuro-Ophthalmology 2022;42:e514–e516 doi: 10.1097/WNO.0000000000001418 © 2021 by North American Neuro-Ophthalmology Society A n 85-year-old woman with a prior history of mild cognitive impairment awoke with vision loss in her right eye. Her review of systems was negative for headache, jaw claudication, scalp tenderness, arthralgias, or weight loss. Best-corrected visual acuities were hand motion in the right eye and 20/30 in the left eye. There was a relative afferent pupillary defect in the right eye. She had decreased temporal artery pulses with mild tenderness to palpation on the right side. Funduscopy revealed bilateral pallid edema of the optic nerve heads with inferotemporal sparing of the sector associated with a cilioretinal artery in the left eye (Fig. 1A,B). There was retinal edema involving the superior, parafoveal, and temporal macula in the right eye and retinal edema along the path of the cilioretinal artery involving the inferior parafoveal macula in the left eye. Kinetic perimetry revealed Gaier et al: J Neuro-Ophthalmol 2022; 42: e514-e516 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay a small island of preservation superiorly in the right eye and generalized constriction with superonasal sparing in the left eye (Fig. 1C). The erythrocyte sedimentation rate was 86 mm/hr, and C-reactive protein was 20.2 mg/L. Temporal artery biopsy obtained 1 day after presentation revealed transmural inflammation with multinucleated giant cells, consistent with giant cell arteritis (GCA). Fluorescein angiography (FA) demonstrated choroidal hypoperfusion and retinal hypoperfusion in the left eye in the distribution of the cilioretinal artery (early frames were not obtained in the right eye) (Fig. 2A). Within the optic disc, only the temporal sector appeared to be perfused. Retrograde filling of the cilioretinal artery occurred in the venous phase (Fig. 2B). Choroidal hypoperfusion in the temporal macula was evident in the right eye (Fig. 2C). Late frames demonstrated that only the temporal disc sector in the left eye, which was associated with the cilioretinal artery, was perfused between the 2 eyes (Fig. 2C,D). The patient received intravenous methylprednisolone 500 mg twice daily for 5 days beginning on the day of presentation and transitioned to high dose oral prednisone. Despite an aggressive steroid regimen, her vision deteriorated to no light perception in the right eye and bare light perception in the left eye. Disc edema progressed to pallor, and the cilioretinal artery sclerosed. GCA is a vasculitis of large-diameter and mediumdiameter arteries that primarily affects elderly Caucasian females. Vascular territories of the head and neck are preferentially affected, causing many neuro-ophthalmic manifestations including arteritic anterior ischemic optic neuropathy (AAION), central retinal artery occlusion, and choroidal nonperfusion. Intimal inflammation and/or luminal thrombosis of the posterior ciliary arteries (PCAs; medium-sized, elastic arteries) results in choroidal hypoperfusion. FA performed in acute GCA often demonstrates patchy and delayed choroidal filling attributed to focal areas of impaired choroidal perfusion (1,2). Hayreh & Baines (3) experimentally occluded medial, lateral, or all PCAs in rhesus monkeys to show that PCA occlusion produces choroidal ischemia with subsequent outer retinal thinning in predictable patterns (4). They observed delayed choroidal filling on FA and hypothesized that subsequent filling was mediated through vortex veins, episcleral collaterals, or pial collaterals of the peripapillary choroid. Choroidal hypoperfusion secondary to GCA demonstrates patchy choroidal hypoperfusion reminiscent of that produced in monkeys (5), suggesting a shared mechanism. Cilioretinal arteries, found in approximately 10% of individuals, arise from a PCA directly, from the circle of Zinn–Haller or from the choroid itself (6,7). Hayreh & Baines (4) demonstrated that cilioretinal arterial hypoperfusion occurred with experimental ligation of the lateral PCA in monkeys. Late retrograde filling of the cilioretinal Gaier et al: J Neuro-Ophthalmol 2022; 42: e514-e516 FIG. 2. Fluorescein angiography images. Insets represent minutes:seconds after intravenous fluorescein injection. A. Laminar phase in the left eye. B. Completion of the arterial–venous phase in the left eye. C. First available frame in the right eye. D. Late frame in the left eye. artery was also seen, as in our patient (8). In a review of 85 patients with ocular involvement of GCA, cilioretinal arteries were found at a relatively high rate (17/85), and 14/17 eyes with cilioretinal arteries showed corresponding retinal hypoperfusion on FA (9). By contrast, concomitant cilioretinal artery occlusion is typically not observed in nonarteritic anterior ischemic optic neuropathy (8), but one case associated with sildenafil overdose has been reported (10). Hayreh & Baines (11) also observed pallid optic disc edema, a hallmark of AAION, that was more likely to occur with experimental ligation of the lateral PCA. The example FA image provided in their report includes a cilioretinal artery and demonstrates hypoperfusion in the superotemporal sector of the optic disc corresponding to the cilioretinal artery. Hayreh (8) argued that cilioretinal artery hypoperfusion associated with arteritic PCA occlusion results in ischemia of the overlying disc sector supplied by the same PCA. The overlying peripapillary filling defect seen in our case (as well as the example provided in (8)) could be considered consistent with this assertion. However, the sparing of disc edema (Fig. 1B inset) and relatively preserved superonasal visual field (Fig. 1C) argue against clinically significant ischemia of retinal ganglion cell bodies and/or axons that correspond to this sector. Similar relative sectoral sparing of the optic disc associated with a cilioretinal artery is commonly seen in GCA (8,12) and can also occur with retinal vein occlusion (13). In addition to the fundus appearance, FA confirmed that this was the only perfused optic disc sector in either eye (Fig. 2). Cilioretinal arterial involvement in these conditions e515 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay is explained by the “choroidal steal hypothesis,” which asserts that cilioretinal perfusion will be preferentially delivered to the lower resistance choroidal bed in lieu of the higher resistance retinal capillary bed. The implications of the choroidal steal hypothesis is that perfusion of cilioretinal arteries, which are derived from posterior ciliary arteries or the underlying choroid but which supply the retina, will suffer in the face of reduced PCA perfusion or increase retinal capillary resistance from a central vein occlusion, which in either case will shunt blood from the cilioretinal artery to the choroid. However, the steal phenomenon does not explain the relative sparing of the overlying optic disc sector. We hypothesize that sectoral sparing of pallid disc edema associated with a cilioretinal artery may reflect the vascular anatomy of the temporal disc when a cilioretinal artery is present. This relationship may depend on the variation of origin of the cilioretinal artery (14). This case demonstrates how choroidal hypoperfusion in GCA imparts a susceptibility to retinal ischemia among patients with cilioretinal arteries. Sparing of the temporal disc in the setting of AAION and a cilioretinal artery highlights a clinically relevant gap in our understanding of the posterior circulation and the need for further experimental study using new technologies. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: E.D.G., N.R., and J.F.R.; b. Acquisition of data: E.D.G., N.R., and J.F.R.; c. Analysis and interpretation of data: E.D.G., N.R., and J.F.R. Category 2: a. Drafting the manuscript: E.D.G.; b. Revising it for intellectual content: E.D.G., N.R., and J.F.R. Category 3: a. Final approval of the completed manuscript: E.D.G., N.R., and J.F.R. e516 REFERENCES 1. Mack HG, O’Day J, Currie JN. Delayed choroidal perfusion in giant cell arteritis. J Clin Neuroophthalmol. 1991;11:221–227. 2. Siatkowski RM, Gass JD, Glaser JS, Smith JL, Schatz NJ, Schiffman J. Fluorescein angiography in the diagnosis of giant cell arteritis. Am J Ophthalmol. 1993;115:57–63. 3. Hayreh SS, Baines JA. Occlusion of the posterior ciliary artery. I. Effects on choroidal circulation. Br J Ophthalmol. 1972;56:719–735. 4. Hayreh SS, Baines JA. Occlusion of the posterior ciliary artery. II. Chorio-retinal lesions. Br J Ophthalmol. 1972;56:736–753. 5. Quillen DA, Cantore WA, Schwartz SR, Brod RD, Sassani JW. Choroidal nonperfusion in giant cell arteritis. Am J Ophthalmol. 1993;116:171–175. 6. Justice J Jr, Lehmann RP. Cilioretinal arteries. A study based on review of stereo fundus photographs and fluorescein angiographic findings. Arch Ophthalmol. 1976;94:1355–1358. 7. Hayreh SS. The cilio-retinal arteries. Br J Ophthalmol. 1963;47:71–89. 8. Hayreh SS. Anterior ischaemic optic neuropathy. Differentiation of arteritic from non-arteritic type and its management. Eye (Lond). 1990;4:25–41. 9. Hayreh SS, Podhajsky PA, Zimmerman B. Ocular manifestations of giant cell arteritis. Am J Ophthalmol. 1998;125:509–520. 10. Akash R, Hrishikesh D, Amith P, Sabah S. Case report: association of combined nonarteritic anterior ischemic optic neuropathy (NAION) and obstruction of cilioretinal artery with overdose of Viagra. J Ocul Pharmacol Ther. 2005;21:315– 317. 11. Hayreh SS, Baines JA. Occlusion of the posterior ciliary artery. 3. Effects on the optic nerve head. Br J Ophthalmol. 1972;56:754–764. 12. Galasso JM, Jay WM. An occult case of giant cell arteritis presenting with combined anterior ischemic optic neuropathy and cilioretinal artery occlusion. Semin Ophthalmol. 2004;19:75–77. 13. McLeod D. Central retinal vein occlusion with cilioretinal infarction from branch flow exclusion and choroidal arterial steal. Retina. 2009;29:1381–1395. 14. Rizzo JF III. Unraveling the enigma of nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2019;39:529– 544. Gaier et al: J Neuro-Ophthalmol 2022; 42: e514-e516 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.